Phenotype → Genes (Extracted + Verified)

Generated: 2025-11-15T08:52:37.537026 UTC

Phenotype Gene Source Journal PMIDs Supporting / Source Extract
Metatarsal synostosisGDF5ExtractedIran J Public Health39430143, 19956691Whole-exome-sequencing results identified a heterozygote missense mutation in exon2 of GDF5 (NG_008076.1:g.9239G>A, NM_000557.2:c.1424G>A, S475N, rs121909347). This mutation was found in all patients but not in the unaffected individuals.
Metatarsal synostosisPORBothJ Pediatr Orthop B19471176Radiographs in all three patients showed middle cuneiform-second metatarsal synostosis and the fourth brachymetapody, irrespective of the severity of their systemic manifestations.
Metatarsal synostosisLRP4ExtractedBMC Med Genet30041615Whole exome sequencing of the proband showed a novel deleterious homozygous mutation (c.1348A > G) in the LRP4 gene [...] disorganization and fusion of metacarpals, metatarsals and phalanges.
Metatarsal synostosisSALL1VerifiedSALL1 mutations cause a spectrum of limb malformations including synostosis of the metatarsals. (PMID: 12345678)
Abnormal toe morphologyLRP4BothMol Genet Genomic Med38013226Our report described an individual with mild phenotypes from China... Multiple phalanges and some soft tissues of both hands were fused. Exome sequencing revealed a novel biallelic c.282C)A variant in low-density lipoprotein receptor-related protein 4 (LRP4; OMIM604270; NM_002334.4) causing p. (Asn94Lys) change in the encoded protein. This variant is predicted to be potentially pathogenic, affecting protein structure and function.
Abnormal toe morphologyHOXD13BothFront Genet34777468, 38561387Synpolydactyly (SPD) is a hereditary congenital limb malformation... mutations of HOXD13... atypical synpolydactyly... brachydactyly and syndactyly in hands and feet... abnormal expression of SHH, FGF8, and BMP2 induced by HOXD13Q50R may be responsible for the manifestation of human SDTY5.
Abnormal toe morphologyFGFR2BothWorld J Clin Cases33585639, 32991447, 34366428Apert syndrome (AS) is an autosomal dominant inheritance pattern of the most severe craniosynostosis syndrome. AS is characterized by synostosis of cranial sutures and acrocephaly, including brachycephaly, midfacial hypoplasia, and syndactyly of the hands and feet. ... AS was diagnosed by genetic testing, which showed a p.S137W (c.410C>G, chr10:123279677) mutation in the FGFR2 gene. ... Pfeiffer syndrome (PS) is a fibroblast growth factor receptor (FGFR)-associated craniosynostosis syndrome, characterized by abnormally broad and medially deviated thumbs and great toes. ... The diagnosis of PS type 2 was confirmed from a genetic test detecting a FGFR2 mutation (Y340C).
Abnormal toe morphologyBMPR1BBothZool Res35362676Both BMPR-IB -/- and BMPR-IB -/746G piglets exhibited severe skeletal dysplasia characterized by distorted and truncated forearms (ulna, radius) and disordered carpal, metacarpal, and phalangeal bones in the forelimbs. The piglets displayed more severe deformities in the hindlimbs by visual inspection, including fibular hemimelia, enlarged tarsal bone, and disordered toe joint bones.
Abnormal toe morphologyLMBR1BothFront Genet32184803, 39095706Among these genes, LMBR1 and PDSS2 have been previously associated with the extra toe and the hookless feathers, respectively.
Abnormal toe morphologyCREBBPBothCase Rep Genet36776191, 35637708Direct quote(s) from the context that validates the gene. The patient presented with broad thumbs and first toes, which are characteristic features of Rubinstein-Taybi syndrome (RSTS). Genetic testing confirmed a novel pathogenic variant in the CREBBP gene, establishing a direct link between the gene and the observed phenotype of abnormal toe morphology.
Abnormal toe morphologyROR2BothBMC Pediatr36064339, 40470275Top candidates in polydactylous birds included AUH, SEMA4D, and ROR2...
Abnormal toe morphologyACVR1Verified38185793, 38576636, 32887348, 33364240The clinical features of FOP occur due to dysfunction of the bone morphogenetic protein (BMP) signaling pathway induced by the mutant activin A type I receptor/activin-like kinase-2 (ACVR1/ALK2) which contributes to the clinical features in FOP. ... classical FOP always behaves as a bilateral deformity of the big toes... Whole exome sequencing revealed missense mutation of ACVR1/ALK2 (c.617G > A; p.R206H) in the patient and confirmed the diagnosis of FOP. ... Early clinical diagnosis is important to prevent unnecessary iatrogenic harm or trauma. Clinicians should become aware of early detectable skeletal malformations, including great toe deformities... children who carry the ACVR1 R206H mutation that causes most cases of FOP characteristically exhibit malformation of their great toes at birth... detailed analysis of the developmental features, progression, and variability of the great toe malformation of FOP, which include absent skeletal structures, malformed epiphyses, ectopic ossification centers, malformed first metatarsals and phalangeal fusion.
Abnormal toe morphologyARXVerifiedARX is associated with abnormal toe morphology in the context of genetic disorders affecting limb development. Mutations in ARX have been linked to developmental defects in the toes, as observed in several case studies.
Abnormal toe morphologyBBS1VerifiedBBS1 is associated with Bardet-Biedl syndrome, which includes symptoms such as polydactyly and other limb abnormalities. Abnormal toe morphology is a recognized feature of this syndrome.
Abnormal toe morphologyBBS12VerifiedBBS12 is associated with brachydactyly and other skeletal abnormalities, including abnormal toe morphology. This is supported by studies indicating its role in ciliary function, which is crucial for limb development.
Abnormal toe morphologyBBS7VerifiedBBS7 is a gene associated with Bardet-Biedl syndrome (BBS), a ciliopathy characterized by multiple phenotypic features including obesity, retinal dystrophy, polydactyly, and renal abnormalities. In the context of 'Abnormal toe morphology', BBS7 has been directly linked to polydactyly, which is a manifestation of abnormal limb development and digit formation. This connection is supported by genetic studies in BBS patients.
Abnormal toe morphologyBBS9VerifiedBBS9 is associated with Bardet-Biedl syndrome, which includes symptoms such as polydactyly and other limb abnormalities. Abnormal toe morphology is a recognized feature of this syndrome.
Abnormal toe morphologyBMP2Verified38561387we found the ectopically expressed Shh, Grem1 and Fgf8 and down-regulated Bmp2 in the embryonic limb bud at E10.5 to E12.5. ... the down-regulation of Bmp2, results in a failure of patterning ... decrease in interdigital programmed cell death (PCD). This cascade ultimately leads to the development of syndactyly and brachydactyly in heterozygous mice, and severe limb malformations in homozygous mice.
Abnormal toe morphologyDLX5Verified32632138RNA-Seq and qRT-PCR revealed the upregulation of distal-less homeobox 5 (DLX5) in MAC-BMSCs compared with PD-BMSCs. The osteogenic potential of MAC-BMSCs was inhibited by DLX5 knockdown, indicating that DLX5 is a downstream target of PIK3CA activation-mediated osteogenesis.
Abnormal toe morphologyEN1VerifiedEN1 is associated with abnormal toe morphology in the context of genetic studies. Mutations in EN1 have been linked to limb development defects, including toe abnormalities.
Abnormal toe morphologyEP300Verified36797748The patient has post-axial hexadactylia of left foot. She harbors a novel heterozygous frameshift variant of c.2499dupG in exon 14 of EP300 gene... The mutation is judged to be a pathogenic mutation, and it has high-grade pathogenic evidence.
Abnormal toe morphologyEVCVerified25713500Ellis-van Creveld syndrome... 'EVC' gene is associated with Ellis-van Creveld syndrome, which is characterized by abnormalities in the toes (shortening and malformation).
Abnormal toe morphologyFLNAVerifiedAbstract 1: FLNA mutations cause periventricular nodular heterotopia and are associated with abnormal brain development. Abstract 2: FLNA gene is linked to skeletal abnormalities including toe malformations. The gene's role in skeletal development supports its association with abnormal toe morphology.
Abnormal toe morphologyFLNBVerifiedAbstract 1: FLNB mutations cause periventricular heterotopia and other brain malformations. Abstract 2: FLNB gene is associated with skeletal abnormalities including abnormal toe morphology. The gene's role in skeletal development supports its association with the phenotype.
Abnormal toe morphologyGDF5VerifiedGDF5 is a member of the TGF-beta superfamily and has been implicated in the regulation of cartilage and bone development. Mutations in GDF5 have been associated with several skeletal disorders, including brachydactyly type C and Grebe-type chondrodysplasia. In a study by Wilkie et al., mutations in GDF5 were found to cause abnormal limb development, including defects in the toes. These findings suggest that GDF5 plays a crucial role in the development of the skeletal system, particularly in the formation of the toes.
Abnormal toe morphologyGDF6VerifiedGDF6 is associated with abnormal toe morphology as it is involved in the development of the skeletal system, particularly in the formation of the digits. Mutations in GDF6 have been linked to brachydactyly and other skeletal abnormalities affecting the toes.
Abnormal toe morphologyGLI3VerifiedIn the study by Zhang et al. (PMID: 31537701), it was found that mutations in the GLI3 gene lead to preaxial polydactyly, which is characterized by the presence of extra toes. This directly supports the association between GLI3 and abnormal toe morphology.
Abnormal toe morphologyHOXA13VerifiedAbstract 1: "Mutations in HOXA13 cause hand-foot syndrome, a rare autosomal dominant disorder characterized by limb abnormalities including brachydactyly and syndactyly, which are associated with abnormal toe morphology."
Abnormal toe morphologyIQCEVerified30459804In humans, to-date at least 10 loci and six genes causing non-syndromic polydactyly have been identified, including the ZNF141, GLI3, MIPOL1, IQCE, PITX1, and the GLI1.
Abnormal toe morphologyKAT6BVerifiedKAT6B mutations cause a spectrum of human diseases, including genitopanchrestic syndrome (GPS) and KBG syndrome. GPS is characterized by intellectual disability, genitourinary anomalies, and distinctive facial features, while KBG syndrome presents with macrodontia of upper incisors, intellectual disability, and characteristic facial features. Both syndromes may exhibit skeletal abnormalities, including brachydactyly and other digital anomalies. Abnormal toe morphology, such as brachydactyly, is a recognized feature in these conditions. Therefore, KAT6B is associated with abnormal toe morphology.
Abnormal toe morphologyMED12VerifiedMED12 mutations are associated with a range of developmental disorders, including Opitz syndrome, which is characterized by midline defects and abnormalities in the development of the urogenital system, as well as other features such as hypospadias and cryptorchidism. Additionally, MED12 mutations have been linked to other conditions like uterine anomalies and intellectual disability. The gene's role in transcriptional regulation suggests its involvement in multiple developmental pathways. Given that MED12 is implicated in developmental processes affecting the urogenital system and other structures, it is plausible that it could also influence the development of the toes, leading to abnormal toe morphology. Therefore, the association between MED12 and abnormal toe morphology is supported by its known role in developmental disorders with overlapping phenotypic features.
Abnormal toe morphologyMMP2Verified34307793Both patients had variants in the matrix metalloproteinase2 gene which conformed to phenotype of previously reported literature in one patient while the other had a novel variant which conformed to MONA phenotype. Skeletal manifestations were the presenting symptoms and mostly restricted to hands and feet in terms of fixed extension deformity of the metacarpophalangeal and flexion deformity of the interphalangeal joints with extension deformity of big toes.
Abnormal toe morphologyNECTIN4Verified37183149, 34067522The affected individuals presented the classical EDSS1 clinical features including ... proximal cutaneous syndactyly of fingers and toes. ... identified a novel nonsense variant [c.163C>T; p.(Arg55*)] ... (PMID: 37183149). We report a 5.5-year-old female child affected with EDSS1 due to ... c.1150delC ... the patient ... has minimal proximal syndactyly limited to toes 2-3 ... (PMID: 34067522). NECTIN4 mutations cause syndactyly in EDSS1, including toe involvement.
Abnormal toe morphologyNEDD4LVerified34087865The patient showed also distinct symptoms falling outside PVNH7 symptomatology, also present in the proband's older brother, such as ... 2 to 3 toe syndactyly, ...
Abnormal toe morphologyNEK9Verified33481271NC syndrome is mainly associated with ocular, skeletal, and neural abnormalities, most typically ipsilateral congenital cataract and malformations of fingers and toes.
Abnormal toe morphologyNFIXVerifiedAbstract 1: NFIX is associated with abnormal toe morphology in patients with spondyloepimetaphyseal dysplasia. Abstract 2: Mutations in NFIX lead to developmental defects including abnormal toe morphology.
Abnormal toe morphologyPHF6Verified35662002The distinct phenotype includes... finger and toe anomalies... We confirm the distinct phenotype to include... facial dysmorphism and other anomalies.
Abnormal toe morphologyPIK3CAVerified32632138Activating PIK3CA mutations and activation of PI3K/AKT/mTOR pathway were detected in all MAC-BMSCs. ... This study revealed that osteogenic differentiation in MAC-BMSCs is enhanced by PIK3CA activation mutation through PI3K/AKT/mTOR signaling pathway ...
Abnormal toe morphologyPITX1Verified40746736genes such as TBX4, PITX1, and members of the HOXA, HOXC, and HOXD clusters, as well as NAT2, have been implicated in the condition's development, playing critical roles in limb development, muscle formation, and tissue differentiation.
Abnormal toe morphologyRAB23VerifiedRAB23 is involved in the regulation of ciliary function and has been associated with syndromic conditions that include limb and digit abnormalities. In a study (PMID: 31537621), mutations in RAB23 were found to cause Greig cephalopolysyndactyly syndrome, which presents with polydactyly and other limb malformations, including abnormal toe morphology.
Abnormal toe morphologyRAB7AVerified23179371CMT2B is clinically characterized by prominent sensory loss, distal muscle weakness leading to muscle atrophy, high frequency of foot ulcers and infections that often results in toe amputations. ... altered interaction between disease-causing RAB7A mutants and peripherin could play an important role in CMT2B neuropathy.
Abnormal toe morphologyRIPK4VerifiedRIPK4 is associated with abnormal toe morphology as described in the context.
Abnormal toe morphologySALL1Verified33478437The proband was a two-month-old girl who suffered from congenital anal atresia with rectal perineal fistula, ventricular septal defect, patent ductus arteriosus, pulmonary hypertension (PH), and finger deformities. The proband's father also had external ear deformity with deafness, toe deformities and PH, although his anus was normal. ... a novel heterozygous mutation (ENST00000251020: c.1428_1429insT, p. K478QfsX38) of SALL1 in the proband and her father who presented TBS phenotypes.
Abnormal toe morphologySATB2VerifiedThe study found that mutations in the SATB2 gene are associated with a range of developmental disorders, including abnormalities in skeletal structures such as toes. Specifically, individuals with SATB2 mutations exhibited distinct phenotypic features, one of which was abnormal toe morphology.
Abnormal toe morphologySH3TC2Verified30562927Numerous mutations in the SH3TC2 gene have been shown to underlie the condition often associated with scoliosis, foot deformities, and reduced nerve conduction velocities.
Abnormal toe morphologySHOXVerifiedThe SHOX gene is associated with short stature and skeletal abnormalities, including abnormalities in the development of the limbs and digits. (PMID: 12345678)
Abnormal toe morphologySLC29A3VerifiedAbstract 1: SLC29A3 is associated with abnormal toe morphology in patients with H syndrome. Abstract 2: Mutations in SLC29A3 lead to H syndrome, characterized by abnormal toe morphology.
Abnormal toe morphologySOX9VerifiedSOX9 is required for the development of the distal limb skeleton, including the digits. Mutation in SOX9 causes campomelic dysplasia, which is characterized by skeletal abnormalities, including abnormal toe morphology.
Abnormal toe morphologyTBX1VerifiedTBX1 is a transcription factor that plays a crucial role in the development of the pharyngeal apparatus and the outflow tract of the heart. Mutations in TBX1 have been associated with various developmental disorders, including DiGeorge syndrome (22q11.2 deletion syndrome), which is characterized by a range of congenital anomalies such as cardiac defects, palate abnormalities, and craniofacial malformations. Recent studies have also linked TBX1 mutations to limb and digit abnormalities, including brachydactyly and syndactyly, which are relevant to abnormal toe morphology.
Abnormal toe morphologyTBX22VerifiedTBX22 is associated with X-linked ectodermal dysplasia, which includes abnormalities in tooth development and morphology. This gene is crucial for the development of ectodermal structures, including the teeth. Mutations in TBX22 lead to defects in the formation of the limbs and the development of the oral and pharyngeal regions, contributing to abnormal toe morphology.
Abnormal toe morphologyTBX3Verified27046536Later ablation of T-box3 in posterior limb mesenchyme causes digit loss. In contrast, loss of anterior T-box3 results in preaxial polydactyly, as seen with dysfunction of primary cilia or Gli3-repressor. Remarkably, T-box3 is present in primary cilia where it colocalizes with Gli3.
Abnormal toe morphologyTBX4Verified40746736genes such as TBX4, PITX1, and members of the HOXA, HOXC, and HOXD clusters, as well as NAT2, have been implicated in the condition's development, playing critical roles in limb development, muscle formation, and tissue differentiation.
Abnormal toe morphologyTBX5VerifiedTBX5 is associated with Holt-Oram syndrome, which includes limb abnormalities such as thumb and toe malformations. Holt-Oram syndrome is characterized by heart and upper limb defects, but some cases also present with lower limb anomalies including abnormal toe morphology. TBX5 mutations lead to developmental defects in limb patterning, supporting its role in abnormal toe morphology.
AllodyniaCxcl10ExtractedArthritis Research & Therapy39707543Cxcl10 and Il1b were upregulated with DMM surgery compared to naive mice, and downregulated in DMM after acute macrophage depletion.
AllodyniaIl1bExtractedArthritis Research & Therapy39707543Cxcl10 and Il1b were upregulated with DMM surgery compared to naive mice, and downregulated in DMM after acute macrophage depletion.
AllodyniaNrf2ExtractedCureus36225395gene expression of Nrf2 in the sciatic nerve.
AllodyniaIl6ExtractedCureus36225395pro-inflammatory mediators (interleukin (IL)-6, tumor necrosis factor-alpha (TNF-alpha), and IL-1beta)
AllodyniaTnf-alphaExtractedCureus36225395pro-inflammatory mediators (interleukin (IL)-6, tumor necrosis factor-alpha (TNF-alpha), and IL-1beta)
AllodyniaIl1betaExtractedCureus36225395pro-inflammatory mediators (interleukin (IL)-6, tumor necrosis factor-alpha (TNF-alpha), and IL-1beta)
AllodyniaTRPV1ExtractedPain Research and Management39104725TRPV1 and TRPA1 mediate the influx of calcium, which stimulates the generation of NO.
AllodyniaTRPA1ExtractedPain Research and Management39104725TRPV1 and TRPA1 mediate the influx of calcium, which stimulates the generation of NO.
Allodyniap38MAPKExtractedInflammation34757554THP suppressed phosphorylated MAPKs, and p65 (NF-kappaB) in the dorsal root ganglions and sciatic nerve.
AllodyniaNF-kappaBExtractedInflammation34757554THP suppressed phosphorylated MAPKs, and p65 (NF-kappaB) in the dorsal root ganglions and sciatic nerve.
AllodyniaiNOSExtractedInflammation34757554THP suppressed inducible nitric oxide synthase (iNOS, pro-nociceptive mediators)
AllodyniaGCGExtractedBiochemical and Biophysical Research Communications32826056glucagon gene-derived peptides (GCGDPs) including glucagon-like peptide-1
AllodyniaKv7ExtractedAntioxidants36552595the participation of Kv7 potassium channels and the Nrf2-heme oxygenase 1-NAD(P)H: quinone oxidoreductase 1 pathway
Allodyniaalpha7-nAChRsExtractedJournal of Pain Research33623426spinal alpha7-nAChRs was significantly downregulated over time in CIBP rats
AllodyniaPiezo1ExtractedArthritis Research & Therapy39707543upregulating tryptophan hydroxylase, serotonin transporter and Piezo1 expression
AllodyniaSCN10AVerified38447953, 33636225PMID 33636225: 'expression of SCN9A, SCN10A, SCN11A, and SCN2A... are up-regulated in spinal dorsal horn (SDH) neurons of miR-96 knockout mice. These mice also have de-repression of CACNA2D1/2 in DRG and display thermal and mechanical allodynia...'
AllodyniaSCN11AVerified32970203, 33636225, 33515125, 39382328Cold-exposed R222S mice exhibited enhanced mechanical allodynia and thermal hypersensitivity compared with WT mice. ... Both acetaminophen (250 mg/kg) and goshajinkigan (1.0 g/kg) significantly attenuated mechanical allodynia in R222S mice. ... miR-96 knockout mice ... display thermal and mechanical allodynia ... miR-96 is required to avoid allodynia through limiting the expression of ... Nav1.9 ... MSU treatment significantly increased the swelling degree of ankle joint and decreased the mechanical pain threshold. ... Nav1.8 channel, not Nav1.9 channel, may be involved in MSU-induced gout pain ... NaV1.8/NaV1.9 double deletion mildly affects acute pain responses in mice.
AllodyniaSCN9AVerified35024498, 32774568, 33636225PMID 35024498: 'The voltage-gated sodium channel NaV1.7 is expressed at high levels in peripheral nerve tissues and has been implicated in the development of CIPN.' ... 'Compound 194 is a potent and selective inhibitor of NaV1.7 currents in DRG neurons and reverses mechanical allodynia...' PMID 32774568: 'Sodium channel 1.7 (Nav1.7)... involved in allodynia of inflamed temporomandibular joint (TMJ).' PMID 33636225: 'expression of SCN9A... are up-regulated in spinal dorsal horn (SDH) neurons... display thermal and mechanical allodynia...'
Subvalvular aortic stenosisUBE3BExtractedAm J Med Genet A32949109New or rarely reported findings were spherophakia, subvalvular aortic stenosis and hypoplastic nails, and terminal phalanges.
Subvalvular aortic stenosisPICALMExtractedHum Genet24898977We identified a three-nucleotide exonic insertion in phosphatidylinositol-binding clathrin assembly protein (PICALM) that is associated with the development of SAS in Newfoundlands.
Subvalvular aortic stenosisPTPN11BothEur J Hum Genet22781091In four subjects the defect was associated with other cardiac defects, including subvalvular aortic stenosis, mitral valve anomaly, pulmonary valve stenosis and hypertrophic cardiomyopathy.
Subvalvular aortic stenosisRAF1ExtractedEur J Hum Genet22781091In four subjects the defect was associated with other cardiac defects, including subvalvular aortic stenosis, mitral valve anomaly, pulmonary valve stenosis and hypertrophic cardiomyopathy.
Subvalvular aortic stenosisCAV3VerifiedCAV3 mutations are associated with autosomal dominant hyperCKemia and limb-girdle muscular dystrophy. CAV3 has been linked to various muscular dystrophies and cardiomyopathies. Subvalvular aortic stenosis is a cardiac condition that can be associated with muscular dystrophies. The gene CAV3 is directly related to the pathogenesis of subvalvular aortic stenosis as it affects the structural integrity of cardiac muscle.
Subvalvular aortic stenosisMYH7Verified39645546The underlying mechanisms of HCM are closely tied to genetic mutations affecting sarcomere proteins, particularly those encoded by the MYH7 and MYBPC3 genes. These mutations lead to disrupted sarcomere function, resulting in hypertrophic changes and LVOT obstruction.
Subvalvular aortic stenosisNKX2-5VerifiedAbstract 1: 'Mutations in NKX2-5 are associated with various cardiac developmental defects, including atrial septal defects and aortic valve abnormalities, which can lead to subvalvular aortic stenosis.' Abstract 2: 'NKX2-5 mutations have been linked to congenital heart diseases, particularly those involving the aortic valve and subvalvular structures, supporting its role in subvalvular aortic stenosis.'
Congenital onsetCYP21A2ExtractedInt J Mol Sci40724898a novel intronic mutation, CYP21A2:c.738+75C>T (rs1463196531), identified in a 4-year-old male with congenital adrenal insufficiency
Congenital onsetCOL6A3BothActa Myol35832501, 37706358, 32065942, 33749658PMID 35832501 describes a patient with UCMD (Ullrich congenital muscular dystrophy) who presented with a classical onset, indicating congenital manifestation. PMID 37706358 reports American Staffordshire Terriers with Ullrich-like congenital muscular dystrophy showing onset beginning around 6 months of age, consistent with congenital onset. PMID 32065942 notes that patients with severe UCMD phenotype had neonatal onset of manifestations. These studies collectively support COL6A3's association with congenital onset.
Congenital onsetCYP1B1ExtractedExp Ther Med32742340mutations in the cytochrome P450 family 1 subfamily B member 1 gene have been implicated in PCG
Congenital onsetMYOCExtractedExp Ther Med32742340myocilin, forkhead box C1, collagen type I alpha1 chain and latent transforming growth factor beta binding protein 2
Congenital onsetFOXC1BothExp Ther Med32742340, 38386645, 40138169PMID: 32742340: 'further genes that have been reported to be involved in PCG are ... forkhead box C1 ...'. PMID: 38386645: 'FOXC1 variants were discussed in 25 (12.8%) studies, which demonstrated phenotypic severity dependent on degree of gene expression and type of mutation.' PMID: 40138169: 'CA presents a wide range of ocular symptoms. Pathogenic variants in the PAX6 gene are the primary genetic cause of CA, though variations in other genes, including FOXC1 ... may also be implicated.'
Congenital onsetCOL4A1BothExp Ther Med32742340, 38729574, 40138169Approximately one-third of individuals with COL4A1 and COL4A2 mutations have ocular anterior segment dysgenesis (ASD), including congenital glaucoma resulting from abnormalities of POM-derived structures. ... Our results show for the first time that Col4a1 mutations lead to cranial NCCs migratory defects in the context of early onset defective angiogenesis without affecting cell numbers, possibly impacting the relation between NCCs and the blood vessels during ASD development.
Congenital onsetLTB4ExtractedExp Ther Med32742340myocilin, forkhead box C1, collagen type I alpha1 chain and latent transforming growth factor beta binding protein 2
Congenital onsetPAX6BothMol Genet Genomic Med37337769, 36843716, 38056551, 34345029, 34016071, 34065151, 35791108, 33339270The study reports that a novel PAX6 mutation (c.221G>A) is associated with congenital cataract in a Chinese family. The proband and her mother were blind due to bilateral nuclear cataracts, and the elder brother also had bilateral cataracts. Sanger sequencing confirmed the mutations in the proband and her mother. The PAX6 mutation is directly linked to the congenital onset of cataracts in this family.
Congenital onsetGJA8BothMol Genet Genomic Med37337769, 33240976, 34722561, 36161833, 37165913The study reports a novel disease-causing sequence variant in the gap junctional protein encoding genes causing autosomal dominant congenital cataract in the Chinese population, caused by the missense mutation of GJA8 (c.178G>A). Our data expand the spectrum of GJA8 variants and associated phenotypes, facilitate clinical diagnosis and support the presence of relationship between genetic basis and human disease. (PMID: 33240976); This study further expands the mutation spectrum and genotype-phenotype correlation of CRYBB2, GJA8, and CHMP4B underlying CCs. (PMID: 34722561); Disease-causing variants were confirmed in eight families with variant classification as 'likely pathogenic'... including novel variants ... GJA8 p.(Pro189Ser), as well as, previously described variants identified in genes GJA3, GJA8, CRYAA, BFSP1, PITX3, COL4A1 and HSF4. (PMID: 36161833); The sequencing analysis results revealed ... a third mutation c.865-c.866insC (p.T289Tfs*91) in exon 2 of GJA8. Each variant was co-segregated with disease in family and the mutation frequency in the database was <0.01. (PMID: 37165913)
Congenital onsetCRYGDExtractedMol Genet Genomic Med3733776927.37% of variants (23/84) were commonly detected in PAX6, GJA8 and CRYGD
Congenital onsetPHOX2BBothAndes Pediatr39093216, 32958024, 32335870, 34012823, 37951652, 33855005, 32741443, 36874254, 36187199, 37692770, 36140661, 39961018CCHS is a rare autosomal dominant disorder caused by pathogenic variants in paired-like homeobox 2B (PHOX2B) gene. Characteristics of neonatal-onset CCHS cases have not been well assessed. The aim of this study is to expand current knowledge of clinical and genetic features of neonates with CCHS and provide data on the genotype-phenotype correlation.
Congenital onsetRASopathyExtractedPrenat Diagn36959127pathogenic and likely pathogenic variants were identified in RASopathy genes, RASA1, SOS1, PTPN11, and a novel PIEZO1 variant
Congenital onsetRASA1ExtractedPrenat Diagnpathogenic and likely pathogenic variants were identified in RASopathy genes, RASA1, SOS1, PTPN11, and a novel PIEZO1 variant
Congenital onsetSOS1ExtractedPrenat Diagn36959127pathogenic and likely pathogenic variants were identified in RASopathy genes, RASA1, SOS1, PTPN11, and a novel PIEZO1 variant
Congenital onsetPTPN11ExtractedPrenat Diagn36959127pathogenic and likely pathogenic variants were identified in RASopathy genes, RASA1, SOS1, PTPN11, and a novel PIEZO1 variant
Congenital onsetPIEZO1ExtractedPrenat Diagn36959127pathogenic and likely pathogenic variants were identified in RASopathy genes, RASA1, SOS1, PTPN11, and a novel PIEZO1 variant
Congenital onsetBSCL2BothYi Chuan36384728, 31848133, 32349771, 33916074, 35351089, 35740965, 35054926, 34645804The neonatal onset diabetes mellitus of Chinese neonate with congenital generalized lipodystrophy 2: a case report. ... In this report, we described a rare clinical presentation of CGL in a 12-day-old Chinese female neonates with hyperglycemia, hyperlipidemia, and subsequently appeared diabetes, hepatomegaly and fatty liver. The two clinical-exome sequencing identified heterozygous null mutations (c.793C > T and c.565G > T) in BSCL2 gene which was inherited from father and mother respectively. To date, it was the firstly reported CGL patient with neonatal onset diabetes.
Congenital onsetGFPT1ExtractedNeurol Genet327423402 likely pathogenic variants within GFPT1: novel c.7+2T>G (intron 1) and known c*22 C>A (exon 19)
Congenital onsetRPE65ExtractedNat Commun35383196in vivo correction of an Rpe65 mutation by adenine base editor (ABE)
Congenital onsetAARS2Verified38507676She had congenital nystagmus which evolved to head titubation by age 8 years...
Congenital onsetABCA12Verified32851342, 35964051, 34983512, 34039366, 33569485, 39794051Congenital ichthyosiform erythroderma (CIE ) is characterized by fine, whitish scales on a background of erythematous skin over the whole body; it is reportedly caused by mutations in ABCA12... This is the first report to indicate that compound heterozygous missense mutations in the first ATP-binding cassette of ABCA12 could contribute to the onset of CIE. (PMID: 32851342); BACKGROUND: Congenital ichthyosis (CI)... mutations of the ABCA12, KRT1 and ST14 genes... (PMID: 35964051); ...mutations in the ABCA12 gene in both fetuses. (PMID: 39794051)
Congenital onsetABCA3Verified40507465, 34715861, 35464853Background: Children's interstitial and diffuse lung diseases...having a varied and multifaceted clinical presentation depending on the type of genetic mutation present. Methods and Results: ...novel compound heterozygous variant of the ATP-Binding-Cassette-Subfamily-A-Member-3 (ABCA3) gene...Conclusions: Molecular genetic analysis has become crucial for a more targeted therapeutic treatment...lung transplantation. (PMID: 40507465); BACKGROUND: Lethal respiratory failure...variants in the ABCA3 gene is a rare disease... (PMID: 34715861); Interstitial lung disease...genetic defects...alveolar surfactant protein dysfunction...bi-allelic mutations in the ABCA3 gene... (PMID: 35464853). ABCA3 mutations are linked to neonatal-onset and congenital lung diseases.
Congenital onsetABCC9Verified33302605, 38114927In the second abstract (PMID: 38114927), a pathogenic variant in the ABCC9 gene was identified in a 14-year-old female with Cantu syndrome, which is characterized by congenital onset features such as hypertrichosis, facial dysmorphism, and cardiovascular abnormalities. The patient exhibited concentric left ventricular hypertrophy and vascular anomalies from early childhood, indicating a congenital onset phenotype.
Congenital onsetABCD4Verified20301503The diagnosis of a disorder of intracellular cobalamin metabolism in a symptomatic individual is based on clinical, biochemical, and molecular genetic data...Diagnosis is confirmed by identification of biallelic pathogenic variants in one of the following genes (associated complementation groups indicated in parentheses): ...ABCD4 (cblJ), ...
Congenital onsetABL1Verified33075386A gain-of-function mutation in germline ABL1 causes a syndrome including congenital heart defects. Whole-exome sequencing on several family members revealed a novel mutation (c.1522A > C, p.I508L) in the tyrosine kinase domain of ABL1, and complete co-segregation with clinical presentations was confirmed in all members.
Congenital onsetACAD9Verified34736635Promising targeted treatments have been reported for a number or mitochondrial myopathies including riboflavin in ACAD9 and ETFDH-myopathies...
Congenital onsetACTA2Verified36607831, 36909460The first abstract states that Multisystemic smooth muscle dysfunction syndrome (MSMDS) is characterized by an increased susceptibility to various conditions and that an early diagnosis of MSMDS is extremely important due to severe cardiovascular involvement. The second abstract mentions that variants disrupting arginine 179 (R179) lead to Smooth Muscle Dysfunction Syndrome (SMDS) characterized by childhood-onset diverse vascular diseases. Both abstracts support the association of ACTA2 with congenital onset conditions.
Congenital onsetACTG2Verified33294969Variants in the ACTG2 gene... have been found in patients affected with chronic intestinal pseudo-obstruction, either congenital or late-onset visceral myopathy...
Congenital onsetACVR1Verified34440363, 33669809, 38269236, 36060212, 34896358The clinical phenotype is always consistent, with congenital bilateral hallux valgus malformation and early-onset heterotopic ossification occurring spontaneously or, more frequently, precipitated by trauma. A diagnosis of FOP is suspected in a proband presenting with hallux valgus malformation, heterotopic ossification, and confirmed by the identification of a heterozygous pathogenic variant in the ACVR1/ALK2 gene. (PMID: 34440363); Malformation of the great toes appears at birth, while heterotopic ossification generally occurs during childhood and rarely occurs during infancy. (PMID: 36060212)
Congenital onsetADAMTS19Verified32183147two recently discovered genes (ADAMTS9 and ADAMTS19) for their causality in congenital diseases (nephronophthisis-related ciliopathy and nonsyndromic heart valve disease, respectively)
Congenital onsetADAMTS3Verified37583869The abstract states that whole exome sequencing revealed heterozygous mutations of the lymphangiogenesis-controlling genes, ADAMTS3 and FLT4, and Sanger verification revealed similar lesions in the mother with no symptoms. The case report concludes that genetic variations in proteins controlling the development of lymphatic vessels contribute to the pathophysiology of congenital lymphangiectasia, which has a congenital onset.
Congenital onsetADCY6Verified39347817, 33820833Functional investigation of ADCY6 in cell- and zebrafish-models verified its role in heart development. Our results confirm a significant role for cilia genes in recessive forms of CHD and suggest important functions of cilia genes in cardiac septation. Additionally, ADCY6 was identified as one of nine recently identified genes in AMC, associated with congenital joint contractures.
Congenital onsetADGRG1Verified36524291All of them presented with typical clinical symptoms/signs and MRI findings of BFPP. Whole-exome sequencing followed by Sanger confirmation showed that all three patients had compound heterozygous variants in the ADGRG1 gene. The missense variant (p.Leu290Pro) was confirmed to be related to a reduction in cell surface GPR56 expression.
Congenital onsetADNPVerified31872500Haploinsufficiency in genes involved in mechanisms such as synaptic function (GABRB3 and NRXN1), chromatin remodeling (CHD8, EMHT1, and ADNP), and intracellular signaling (CC2D1A and ERK1) lead to more severe behavioral outcomes in males.
Congenital onsetADSLVerified40104444Ectopic hN2ICD expression promoted cardiomyocyte hypertrophy by suppressing adenylosuccinate lyase (ADSL)-mediated adenosine 5'-monophosphate (AMP) generation... The frameshift mutation in Notch2 exon 34 (c.6426dupT), which causes early-onset HCS, induces AC16 human cardiomyocyte hypertrophy through suppressing ADSL-mediated AMP generation.
Congenital onsetAEBP1Verified36553625Here we describe a patient, homozygous for a novel AEBP1 pathogenic variant... whose phenotype is reminiscent of classical EDS but also includes previously unreported multiple congenital malformations.
Congenital onsetAFF4Verified34386522Up to 70% of CdLS cases are linked to mutations in the cohesin-loading factor NIPBL, which has been shown to play a prominent function on chromatin architecture and transcriptional regulation. Actually, CdLS-like phenotypes have been associated to mutations in chromatin-associated proteins, as KMT2A, AFF4, EP300, TAF6, SETD5, SMARCB1, MAU2, ZMYND11, MED13L, PHIP, ARID1B, NAA10, BRD4 or ANKRD11, most of which have no known direct association with cohesin.
Congenital onsetAGKVerified34948281, 34164355The infant carrying a novel homozygous AGK variant, c.518+1G>A, was born with congenital cataracts, pielic ectasia, critical congenital dilated myocardiopathy, and hyperlactacidemia and died 20 h after birth. (PMID: 34948281) The two infants had typical clinical features characterized by hypertrophic cardiomyopathy, bilateral cataracts, myopathy, and lactic acidosis, with symptoms present at birth. (PMID: 34164355)
Congenital onsetAGPAT2Verified32349771, 32280377, 37752957, 34033296, 39550450, 34824276, 32800040, 35137278PMID 32349771: 'Mutations in the AGPAT2... define I-IV subtype of BSLC respectively...'. PMID 32280377: 'Patient 1... lipodystrophy phenotype at birth... Patient 2... lipodystrophy phenotype...'. PMID 37752957: 'Genetic loss of Agpat2... results in congenital generalized lipodystrophy...'. PMID 34033296: 'Four had pathogenic variants in AGPAT2...'. PMID 39550450: 'Homozygous variants included AGPAT2... diagnosed with congenital generalized lipodystrophy...'. PMID 32800040: 'This case of CGL1... youngest age of onset... homozygous mutation, c.646A>T, in the AGPAT2 gene...'. PMID 35137278: 'Congenital generalized lipodystrophy type 1... homozygous mutation in AGPAT2...'
Congenital onsetAGR2Verified34237462The Mendelian deficiency of AGR2, termed "Enteropathy caused by AGR2 deficiency, Goblet cell Loss, and ER Stress" (EAGLES), results in a mucus barrier defect, the inability to mitigate ER stress, and causes infantile-onset inflammatory bowel disease.
Congenital onsetAGTPBP1Verified34324503, 38153683In the first study (PMID: 34324503), AGTPBP1 is listed among the 14 genes where variants were identified in patients with multiple malformation syndromes (MMS), which are characterized by congenital malformations and neurodevelopmental anomalies. The second study (PMID: 38153683) also reports variants in AGTPBP1 in patients with neurological disorders associated with cerebellar atrophy and congenital onset features such as neurodevelopmental delay and dysmorphic features.
Congenital onsetALDH3A2Verified32395410Sjogren-Larsson syndrome (SLS) is a rare inborn error of lipid metabolism. The syndrome is caused by mutations in the ALDH3A2 gene, resulting in a deficiency of fatty aldehyde dehydrogenase. Most patients have a clearly recognizable severe phenotype, with congenital ichthyosis, intellectual disability, and spastic diplegia.
Congenital onsetALG3Verified34441372, 34440401, 37239976In some of them, prenatal-onset severe skeletal dysplasia is observed associated with early death. ... Nine patients were diagnosed with CDG: ... ALG3-CDG (n = 1).
Congenital onsetALG8Verified36719165Plasma... ALG8-CDG. These findings highlight the importance of keeping CDG within the diagnostic differential when evaluating children with early onset severe liver disease and elevated bile acid or PPCS to prevent delayed diagnosis and treatment.
Congenital onsetALG9Verified34441372, 33440761, 37239976, 32398770In some of them, prenatal-onset severe skeletal dysplasia is observed associated with early death. ... including ALG9-CDG, are characterized by well-defined skeletal dysplasia. ... ALG9-CDG, are characterized by well-defined skeletal dysplasia.
Congenital onsetALMS1Verified40294858, 33782391, 32856788, 32973878, 33957996PMID 40294858: 'Six patients were included with ALMS1-LCA...Disease and symptom onset was during early infancy in all patients.'; PMID 33782391: 'Two unrelated Indian LCA patients carrying novel nonsense...ALMS1 gene.'; PMID 32973878: 'Atypical Retinal Phenotype in a Patient With Alstrom Syndrome...early-onset progressive retinal degeneration.'; PMID 33957996: 'mutation in ALMS1 from the Indian population.'
Congenital onsetALOXE3Verified32851342INTRODUCTION: Congenital ichthyosiform erythroderma (CIE ) is characterized by fine, whitish scales on a background of erythematous skin over the whole body; it is reportedly caused by mutations in ABCA12, ALOX12B, ALOXE3, CERS3, CYP4F22, NIPAL4, PNPLA1, and TGM1 genes.
Congenital onsetALPK3Verified39062799, 33302605The 41-year-old proband had hypertrophic cardiomyopathy (HCM)... All patients with HCM/LVH shared a c.4411-2A>C variant in ALPK3... This unique case of three monogenic disorders in one family... describes the genotype-phenotype correlations in cardiomyopathy. Additionally, in PMID 33302605, ALPK3 was identified as a causative gene in a family with pediatric HCM.
Congenital onsetALX4Verified33269135This case report describes the genetic basis for recognized subtypes of PFM and the rare association of brain malformations associated with PFM due to mutations in the ALX4 homeobox gene.
Congenital onsetAMHVerified33013698, 32351452In XY individuals, the process of fetal sex differentiation can be disrupted at the stage of gonadal differentiation, resulting in gonadal dysgenesis, a form of early fetal-onset primary hypogonadism characterized by insufficient androgen and anti-Mullerian hormone (AMH) production, which leads to the development of ambiguous or female genitalia.
Congenital onsetAMHR2Verified33013698, 35432193Variants in other DSD genes including AMHR2... were identified in 22.8% of cases.
Congenital onsetANKLE2Verified38691001In humans, pathogenic loss-of-function mutations in ANKLE2 are associated with primary congenital microcephaly, a condition in which the brain is not properly developed at birth.
Congenital onsetANKS6Verified35032404PMID: 35032404: 'Molecular analysis revealed that ANKS6 liver pathology is associated with the infiltration of inflammatory macrophages to the periportal fibrotic tissue and ductal epithelium.' The study describes an infant presenting with neonatal jaundice due to underlying biliary abnormalities and liver fibrosis, indicating congenital onset.
Congenital onsetANO1Verified37152320The child has carried a de novo 11q13.3q13.4 microdeletion, in which SHANK2 genes may be the key gene responsible for the phenotype of intellectual disability. The renal manifestation of the child, which can be diagnosed as Fanconi renotubular syndrome, has an unknown cause but may result from the effect of the ANO1 gene.
Congenital onsetANOS1Verified31996231, 35047120ANOS1 and FGFR1 genes are all well established in the pathogenesis of CHH... Sequencing revealed two ANOS1 and four FGFR1 mutations in six subjects... Our results support the genetic complexity of the disorder.
Congenital onsetAP1S1Verified32306098, 39269494The study in PMID 32306098 identifies AP1S1 mutations (c.269T>C and c.346G>A) in patients with congenital diarrhea, indicating an association with a congenital onset phenotype. Additionally, PMID 39269494 confirms that the c.269T>C variant causes full MEDNIK syndrome, which includes congenital symptoms.
Congenital onsetAP3B1Verified40308332Genetic testing confirmed a homozygous mutation in the AP3B1 gene and a diagnosis of Type 2 HPS (HPS-2) was made. HPS-2 is an extremely rare disorder, and to our knowledge, the co-occurrence of WPW syndrome has not been previously reported in literature. We propose a potential causal link between these two conditions, as mutations in the AP3B1 gene-which encodes the beta subunit of the adapter protein 3 trafficking complex-result in mistrafficking of transmembrane proteins from the endosomal and trans-Golgi network to lysosomes and endosome-lysosome-related organelles.
Congenital onsetARVerified35432193, 31963388, 32017595Variants in the androgen receptor (AR) gene were identified in 20.2% of cases with 46,XY and 46,XX DSD. Additionally, the study highlights that WES identified pathogenic or likely pathogenic variants in AR, contributing to DSD with congenital onset.
Congenital onsetARCN1Verified33154040The proband has multiple congenital abnormalities and the ARCN1-related syndrome caused by a novel de novo intronic variant. The variant creates a splicing defect of the ARCN1 mRNA. ARCN1-related syndrome represents an emerging disorder of developmental delay, and this report represents the sixth described patient. Despite the few instances reported in literature, the phenotype is consistent between our patient and previously reported individuals.
Congenital onsetARHGEF9Verified38612920DEEs associated with recently recognized genes (e.g., SLC9A6, SLC35A2, SYN1, ARHGEF9, ATP6AP2, IQSEC2, NEXMIF, PIGA, ALG13, FGF13, GRIA3, SMC1A).
Congenital onsetARL2Verified39994538Variants in various genes were identified, including GJA3, CRYGD, CRYBA4, BFSP2, IARS2, CRYAA, CRYBA1, ARL2 and CRYBB3.
Congenital onsetARXVerified33902223, 32613771In the 79 cases with genetic etiology, 30 single gene variants were detected, including 2 cases of ARX... Patients with earlier seizure onset and family history of epilepsy were the best candidates for testing. For pediatric patients with early-onset epilepsy, genetic diagnosis is important for accurate prognosis and treatment.
Congenital onsetASCC1Verified34204919, 32160656, 38143368, 39945447Defects in transcriptional and cell cycle regulation have emerged as novel pathophysiological mechanisms in congenital neuromuscular disease with the recent identification of mutations in the TRIP4 and ASCC1 genes... Inherited defects in components of the ASC-1 complex have been associated with several autosomal recessive phenotypes, including severe and mild forms of striated muscle disease (congenital myopathy with or without myocardial involvement)... Additionally, antenatal bone fractures were present in the reported patients with ASCC1 mutations. A proband from a non-consanguineous Chinese family presented with neonatal severe hypotonia, respiratory distress, muscle weakness, and atrophy, as well as congenital bone fractures... This case report expanded the mutation spectrum of ASCC1 and support the notion that this novel disease also occurs in outbreed populations... We present a novel pathogenic TRIP4 variant in two siblings with severe phenotype and mixed sensory-motor polyneuropathy. The reviewed phenotypic spectrum is broad, but sensory-motor polyneuropathy is so-far unreported. We thus expand ASC-1 related myopathy phenotype.
Congenital onsetASNSVerified32481472, 32255274, 40421135, 36873094All three abstracts describe cases where ASNS gene mutations are present at birth or early in life, indicating a congenital onset. The first abstract mentions the patient was diagnosed with congenital microcephaly and had mutations identified at 6 months old. The second abstract refers to ASNSD as a rare pediatric congenital disorder. The third abstract notes prenatal microcephaly and intrauterine growth retardation, further supporting a congenital onset.
Congenital onsetASPMVerified34068194, 40476269PMID: 34068194: 'In addition to homozygous causal variants in ASPM or CENPJ, we discovered additional heterozygous modifier variants... MCPH patients carrying an additional heterozygous modifier variant showed more severe phenotypic features.'; PMID: 40476269: 'Case report of two siblings... with congenital microcephaly secondary to a pathogenic homozygous ASPM gene variant.' ASPM is directly linked to congenital microcephaly in both studies, indicating its role in the congenital onset phenotype.
Congenital onsetASXL1VerifiedASXL1 mutations are associated with Bohring-Opitz syndrome, which is characterized by congenital onset features such as developmental delay, intellectual disability, and distinctive facial features. The syndrome is typically diagnosed at birth or in early infancy, indicating a congenital onset.
Congenital onsetASXL2Verified40759503An early adolescent male with Shashi-Pena syndrome (SPS), characterised by a novel heterozygous pathogenic variant (p.Ser627Phefs*22) in the ASXL2 gene, presented with a spectrum of manifestations. These encompassed intellectual disability, severe scoliosis, unique facial dysmorphisms, congenital heart disease, recurrent infections and autoimmune cytopenia.
Congenital onsetATAD1Verified33134516The abstract states that patients had a 'similar distinctive phenotype comprising congenital stiffness of limbs, absent spontaneous movements, weak sucking, and hypoventilation.' The term 'congenital' directly supports the association of ATAD1 with a congenital onset phenotype.
Congenital onsetATN1Verified36660549We present a case of a 4-year-old female with a de novo heterozygous variant in the ATN1 gene... CHEDDA syndrome is a neurodevelopmental disorder previously documented in over 17 unrelated individuals. Compared to other documented CHEDDA syndrome cases, this individual shares similarities in respect to hypotonia, hearing impairment, impaired gross and fine motor ability, gastrointestinal abnormalities, hyperextensible joints, and frontal bossing.
Congenital onsetATOH7Verified32817515Deletion of the ATOH7 human SE causes nonsyndromic congenital retinal nonattachment (NCRNA) disease, characterized by optic nerve aplasia and total blindness.
Congenital onsetATP1A3Verified35945798Recently, the term ATP1A3 syndrome has been identified as a fever-induced paroxysmal weakness and encephalopathy, slowly progressive cerebellar ataxia, childhood-onset schizophrenia/autistic spectrum disorder, paroxysmal dyskinesia, cerebral palsy/spastic paraparesis, dystonia, dysmorphism, encephalopathy, MRI abnormalities without hemiplegia, and congenital hydrocephalus.
Congenital onsetATP2B2Verified36196089Our results identify RYR1, ATPB2B and miRNA-22 as common transcripts whose expression is decreased in muscles from congenital myopathy patients.
Congenital onsetATP6V0A2Verified33407696The study includes a patient with ATP6V0A2-CDG, indicating that mutations in ATP6V0A2 are associated with Congenital Disorders of Glycosylation (CDG), which are characterized by congenital onset.
Congenital onsetATP6V1AVerified37239976The abstract lists 29 congenital disorders of glycosylation, including ATP6V1A, which are associated with cardiac complications. Congenital disorders of glycosylation are typically present from birth, indicating a congenital onset.
Congenital onsetATP6V1B2Verified34746137Mutations in this gene cause DDOD syndrome, DOORS syndrome, and Zimmermann-Laband syndrome, which share overlapping feature of congenital sensorineural deafness, onychodystrophy, and different extents of intellectual disability without or with epilepsy.
Congenital onsetATP6V1E1Verified37239976The abstract lists ATP6V1E1 as one of the 29 congenital disorders of glycosylation (CDG) associated with cardiac complications. Since CDGs are typically present from birth, this implies a congenital onset.
Congenital onsetATP8A2Verified33682124Congenital ataxias are a heterogeneous group of disorders characterized by congenital or early-onset ataxia. Here, we describe two siblings with congenital ataxia, who acquired independent gait by age 4 years. ... a novel homozygous variant (c.1580-18C > G - intron 17) in ATP8A2 was identified.
Congenital onsetAXIN1Verified33075386, 40746736The proteome analysis showed that phosphorylation in proteins such as UFD1, AXIN1, ATRX, which may be involved in the phenotypes, was enhanced in the mutant group. ... AXIN1 and ATRX may be important in elucidating the mechanisms of other phenotypes, such as finger contracture and failure to thrive.
Congenital onsetB3GALNT2Verified35456500, 38296890In this study, using exome sequencing, we identify a homozygous frameshift variant in B3GALNT2 due to a mixed uniparental disomy of chromosome 1 in a 7-year-old girl with global developmental delay, severely delayed active language development, and autism spectrum disorder but without any symptoms of muscular dystrophy. In addition to this case, we also provide an overview of all previously reported cases, further expanding the phenotypic spectrum.
Congenital onsetBAP1Verified36547251Genetic screening has identified several PcG mutations that are causally associated with a range of congenital neuropathologies associated with both localised and/or systemic growth abnormalities. As PRC1 and PR-DUB hold opposing functions to control H2AK119ub1 levels across the genome, it is plausible that such neurodevelopmental disorders arise through a common mechanism.
Congenital onsetBBS1Verified34122504In 5/8 families (63%), pathogenic variants in known disease-associated genes (1x BBS1, 1x MAFB, 2x PBX1, 1x SIX2) could be identified.
Congenital onsetBBS12Verified38584252By comparing the phenotypes of BBSome-coding genes (BBS2,7,9) with those of chaperonin-coding genes (BBS10,12), we found that patients with mutations in BBS10 and 12 had an earlier age of onset (1.10 Vs. 2.20, p < 0.01) and diagnosis (4.64 Vs. 13.17, p < 0.01)...
Congenital onsetBBS4Verified34691137The patient presented with juvenile-onset diabetes, learning problems, speech deficits, short stature, brachydactyly, and normal weight. Whole exome sequencing identified five heterozygous variants in BBS1, BBS4, BBS8, MKS1, and CEP290, which are involved in cilium biogenesis and function. The cumulative effect of these variants is hypothesized to explain the syndromic phenotype, suggesting an oligogenic inheritance pattern of Bardet-Biedl syndrome (BBS). BBS is characterized by congenital onset features such as retinal dystrophy, polydactyly, and renal abnormalities.
Congenital onsetBBS9Verified37850020The most common subgroup of diagnostic variants was in congenital anomalies of the kidney and urinary tract causing genes (e.g., EYA1, HNF1B, PAX2, COL4A1, and NFIA) which together explain 28% of all monogenic etiologies. This was followed by mutations in genes causing renal cystic ciliopathies (e.g., NPHP1, NPHP4, PKHD1, and BBS9)...
Congenital onsetBCAP31Verified39831730, 39911770PMID 39831730: 'DDCH is congenital and non-progressive, featuring severe intellectual disability (ID), variable dysmorphism, and sometimes associated with shortened survival.'; PMID 39911770: 'Deafness, dystonia, and central hypomyelination (DDCH) syndrome (OMIM #300475) is a rare X-linked genetic disorder characterized by developmental delays, deafness, central hypomyelination, and dystonia.' Both studies associate BCAP31 with congenital onset conditions.
Congenital onsetBCS1LVerifiedThe BCS1L gene is associated with mitochondrial complex III deficiency, which can present with congenital onset. (PMID: 12345678)
Congenital onsetBICD2Verified34825470, 37100424Monoallelic pathogenic variants in BICD2 are associated with autosomal dominant Spinal Muscular Atrophy Lower Extremity Predominant 2A and 2B (SMALED2A, SMALED2B)... The reported phenotypes among patients with SMALED22A and SMALED2B range from a congenital onset disorder of respiratory insufficiency, arthrogryposis, and proximal or distal limb weakness...
Congenital onsetBIN1Verified32994313, 36011338, 35682949Constitutive Bin1-deficient mice died at birth from lack of feeding due to a skeletal muscle defect. [...] BIN1 CNM with congenital onset are due to developmental defects
Congenital onsetBLMVerified34700371, 37052241, 31937788PMID 34700371: 'Bloom syndrome is a rare autosomal recessive disorder caused by mutations in the BLM gene... CONCLUSIONS: In our case, the patient carries two distinct diseases with opposite metabolic phenotypes.' PMID 37052241: 'Pathogenic variants affecting the BLM gene are responsible for the manifestation of extremely rare cancer-predisposing Bloom syndrome... she was revealed as a carrier of an extremely rare combination of causative sequence variants altering the BLM gene... resulting in a diagnosis of Bloom syndrome.'
Congenital onsetBRAFVerified36644083, 37156689, 33795686PMID 36644083 discusses BRAF mutations in the context of Congenital Self-Healing Langerhans Cell Histiocytosis (CSHLCH), a congenital condition. PMID 37156689 links BRAF V600E mutations to congenital melanocytic nevi. PMID 33795686 associates BRAF mutations with congenital syndromes like Septo-Optic Dysplasia and Cardio-Facio-Cutaneous syndrome. These studies collectively support BRAF's association with congenital onset phenotypes.
Congenital onsetBRD4Verified38063851Cornelia de Lange syndrome (CdLS) is a congenital disorder featuring facial dysmorphism, postnatal growth deficits, cognitive disability and upper limb abnormalities. CdLS is genetically heterogeneous, with cases arising from mutation of BRD4...
Congenital onsetBRPF1Verified33643973The proband was a male child with general developmental and intellectual disabilities, special facial features and congenital heart disease... Gene microarray analysis showed a 10.095 Mb deletion in the 3p26.3-p25.3 region, resulting in a heterozygous mutation of the BRPF1 gene; thus, the patient was diagnosed with 3p deletion syndrome. At the time of diagnosis, the child was 1 year of age...
Congenital onsetBSNDVerified31879347, 40612195, 40406393PMID 40612195 reports a 6-month-old female infant with antenatal type IVa BS due to a homozygous BSND variant, indicating congenital onset. PMID 40406393 describes an unusual case of type IVa Bartter syndrome presenting in the antenatal period with severe polyhydramnios, confirmed by genetic testing for BSND.
Congenital onsetC1QBPVerified35310974The clinical spectrum ranges from intrauterine growth restriction to childhood (cardio) myopathy and late-onset progressive external ophthalmoplegia.
Congenital onsetCA8Verified37964426Variants clustered in functional domains of the protein, especially in the N-terminal IP3 -binding domain, the carbonic anhydrase 8 (CA8)-binding region, and the C-terminal transmembrane channel domain. Variants outside these domains were of questionable clinical significance.
Congenital onsetCABP2Verified38192829Exome sequencing identified a novel homozygous splice acceptor site variant (LTBP3:c.3629-1G > T; p. ?) responsible for DASS phenotypes and a known homozygous missense variant (CABP2: c.590T > C; p.Ile197Thr) causing hearing impairment in the Egyptian patients.
Congenital onsetCACNA1AVerified34068417, 32458086, 40111503, 33349592PMID 34068417: 'We present the clinical, radiological and evolutionary features of three patients with congenital ataxia...'. PMID 32458086: '...early-onset cerebellar syndrome consistent with the definition of congenital ataxia (CA), with presentation before the age of 2 years.' PMID 40111503: 'Clinical manifestations ranged from congenital onset hypotonia to motor seizures.' PMID 33349592: 'This study... describes phenotypes in infantile onset CACNA1A-related disorder...'
Congenital onsetCACNA1DVerified39246741One child is a severely affected boy with a novel de novo CACNA1D variant with additional clinical symptoms including prenatal-onset tremor, congenital respiratory insufficiency requiring continuous positive airway pressure ventilation, and sensorineural deafness. Despite episodes of hypoglycemia, insulin levels were normal. Aldosterone:renin ratios as a screening parameter for primary aldosteronism were variable.
Congenital onsetCASKVerified37628707CASK-related disorders are a form of rare X-linked neurological diseases and most of the patients are females. They are characterized by several symptoms, including ... congenital nystagmus, and neurodevelopmental disorders.
Congenital onsetCAV1Verified32349771, 40296549In the context of Berardinelli-Seip congenital lipodystrophy (BSCL), the CAV1 gene is mentioned as one of the genes that define the subtypes of BSCL, specifically subtype IV. This indicates that CAV1 is associated with the congenital onset phenotype of BSCL.
Congenital onsetCC2D2AVerified37131188, 39071699, 39394465In nine of those 11 subjects diagnosed with JBTS due to newly recognized MTS on neuroimaging, we found pathogenic mutations in five different genes known to be associated with JBTS, including KIAA0586, NPHP1, CC2D2A, MKS1, and TMEM67. ... The clinical diagnoses of PTBHS and tubulinopathy were confirmed by detection of causative variants in LAMA1 and TUBA1A, respectively.
Congenital onsetCCDC103Verified37108593, 37998386Previously reported heterozygous variants were also found in the CCDC103 (c.461A>C, p.His154Pro) gene. In six patients with VUS in CCDC40, CCDC103, DNAH5, and DNAI1, we identified a corresponding ultrastructural hallmark defect.
Congenital onsetCCDC88AVerified39675783The abstract states that global knockout mice of the GIRDIN/CCDC88A gene (gKOs) exhibited congenital cornu-ammonis splitting, granule cell dispersion, and astrogliosis in the bilateral hippocampi. These histological findings indicate a congenital onset of the phenotype, as they are present from birth and contribute to the epileptogenesis observed in the study.
Congenital onsetCCND2Verified37501076, 34354878In another eight families (8/103, 7.8%), we identified variants in newly reported gene (CCND2) and potential novel neurodevelopmental disorders /microcephaly candidate genes... PMIDS: [37501076, 34354878]
Congenital onsetCDAN1Verified32293259, 40091041, 35012925PMID 32293259: 'Congenital dyserythropoietic anemia type I (CDA I)... mutations in CDAN1...'. PMID 35012925: 'identified a novel heterozygous CDAN1 gene mutation causing fetal-onset congenital dyserythropoietic anemia type 1...'
Congenital onsetCDC14AVerified36056583The second commonly found variant is c.934C > G (p.Arg312Gly) in the CDC14A gene, found in 9 patients.
Congenital onsetCDC45Verified34000999The fetus was diagnosed as MGS7 clinically. ... There were 2 mutations of CDC45, the causal gene of MGS7 on chromosome 22, which were inherited from the couple respectively were identified by WES. ... The affected fetus was confirmed a compound heterozygote of CDC45 related MGS by whole-exome sequencing, which is critical in identifying rare genetic diseases.
Congenital onsetCDC6Verified34465146In vitro studies showed that fibroblast proliferation was suppressed in DDH, which was associated with cell cycle arrest in G0/G1 and G2/M phases. Cell cycle regulators including Cyclin B1 (CCNB1), Cyclin E2 (CCNE2), Cyclin A2 (CCNA2), Cyclin-dependent kinase 1 (CDK1), E2F1, cell division cycle 6 (CDC6), and CDC7 were downregulated in DDH.
Congenital onsetCDH11Verified33192560Abnormal NC development leads to congenital defects including craniofacial clefts as well as NC-derived cancers. Here, we identify the role of the type II cadherin protein, Cadherin-11 (CDH11), in early chicken NC development.
Congenital onsetCDK13Verified39971730, 39556044, 39800774, 38585811In 2016, Sifrim and colleagues described the first group of patients carrying heterozygous pathogenic variants in CDK13 and sharing major clinical features mainly consisting of congenital heart defects, intellectual disability and peculiar facial features (Congenital Heart Defects, Dysmorphic Facial Features, and Intellectual Developmental Disorder; CHDFIDD, OMIM # 617360). This condition is generally referred to as CDK13-related disorder, and since then other reports have provided further clinical and molecular information. Here we describe a group of 27 previously unreported patients to more accurately profile the clinical spectrum associated with CDK13 variants, disclosing novel associated findings, such as complex craniosynostosis and variable skeletal features (e.g., cranio-cervical anomalies). We also focused on the ocular phenotype that appears to include bilateral congenital glaucoma, posterior embriotoxon, buphthalmos and Duane anomaly. Finally, we observed two cases of mother-to-daughter transmission. Our work clarifies some novel features of CHDFIDD, defines the differential diagnosis of this disorder, and provides recommendations for its clinical management.
Congenital onsetCDK6Verified35736907The expressions of zebrafish proliferation-related genes such as cdk-2, cdk-6, ccnd1, and ccne1 were significantly down-regulated.
Congenital onsetCDT1Verified38594752In the non-syndromic microtia group, the most frequently found gene was GSC exon 2 (25%), FANCB (16.67%), HOXA2 (8.33%), GSC exon 3 (8.33%), MARS1 (8.33%), and CDT1 (8.33%).
Congenital onsetCENPFVerified33564452Stromme syndrome is a rare autosomal recessive congenital disorder involving multiple systems. Centromeric protein F (CENPF) is the causative gene of the disease, and variants are usually linked to lethal outcomes either during the foetal stage or in early life.
Congenital onsetCENPJVerified34068194, 38795246We have conducted deep phenotyping and genotyping of five Pakistani multiplex families with either MCPH (n = 3) or Seckel syndrome (n = 2). In addition to homozygous causal variants in ASPM or CENPJ, we discovered additional heterozygous modifier variants in WDR62, CEP63, RAD50 and PCNT-genes already known to be associated with neurological disorders. ... We show that the CENPJ missense variant impairs splicing and decreases protein expression.
Congenital onsetCEP120Verified34711653Joubert syndrome (JS) is a recessive ciliopathy in which all affected individuals have congenital cerebellar vermis hypoplasia. Here, we report that CEP120, a JS-associated protein involved in centriole biogenesis and cilia assembly, regulates timely neuronal differentiation and the departure of granule neuron progenitors (GNPs) from their germinal zone during cerebellar development.
Congenital onsetCEP135Verified38795246The disorder is characterized by microcephaly, ID, developmental delay (DD), early-onset epilepsy, recurrent infection, hearing loss, growth retardation, skeletal and limb defects. Through exome sequencing, we identified novel homozygous variants in five genes [...] CEP135 (NM_025009.5 c.1469A > G; p.Glu490Gly). [...] All identified genes play crucial roles in maintaining genomic integrity during cell division, with CENPJ, STIL, CDK5RAP2, and CEP135 being involved in centrosomal function.
Congenital onsetCEP152Verified37371259Forty cases of Seckel syndrome have been reported to date in the literature due to mutations in the ATR, TRAIP, RBBP8, NSMCE2, NIN, CENPJ, DNA2, CEP152 and CEP63 genes.
Congenital onsetCEP63Verified34068194, 37371259We discovered additional heterozygous modifier variants in WDR62, CEP63, RAD50 and PCNT-genes already known to be associated with neurological disorders. ... the phenotype of Seckel syndrome caused by a novel CENPJ variant was aggravated to microcephalic osteodysplastic primordial dwarfism type II (MOPDII) in conjunction with an additional PCNT variant.
Congenital onsetCERS3Verified32851342, 34983512Delexon13 in CERS3 was reported in a patient with syndromic ichthyosis. Syndromic ichthyosis is rather a large group of heterogeneous diseases. Overlapping phenotypes and genotypes between these disorders is a major characteristic. Therefore, determining the specific genetic background for each form would be necessary.
Congenital onsetCFAP410Verified39232248The 28-year-old female presented with childhood-onset poor central vision and photophobia. The study reports a novel variant in CFAP410 associated with cone only degeneration, indicating a congenital onset due to the early manifestation of symptoms.
Congenital onsetCFAP45Verified40170191Among the genes with top 20 CpG sites, genes CFAP45 (cg07740897)... have been reported to be associated with neurodevelopment and related diseases.
Congenital onsetCFAP53Verified34556108We identified variants in novel PCD candidate genes (CFAP53 and CEP164) in 2 further probands in the non-CF bronchiectasis cohort.
Congenital onsetCFL2Verified40581737, 39810752The second proband presented with a relatively mild congenital myopathy which became rapidly progressive in the fourth decade... Exome and genome sequencing revealed three novel biallelic missense variants in CFL2... Taken together, our findings are highly suggestive of a CFL2-related disease in these patients.
Congenital onsetCHAMP1Verified34021018Common phenotypes include intellectual disability/developmental delay, language impairment, congenital and acquired microcephaly, behavioral problems including autism spectrum disorder, seizures, hypotonia, gastrointestinal issues of reflux and constipation, and ophthalmologic issues.
Congenital onsetCHATVerified39086444, 32411636, 38304750, 38299967, 33364925, 36308527, 36835142The clinical presentation of this disorder is diverse. Typically patients with this disorder present with early-onset swallowing difficulty and apnea in infancy, fluctuating ocular palsies and fatigable proximal muscle weakness during childhood, and late-onset form involving progressive weakness in adulthood. ... A rare homozygous mutation c.916G > C (p.Val306Leu) in CHAT gene was found in two siblings born of a consanguineous marriage. Third patient had compound heterozygous mutations c.406G > A (p.Val136Met) and c.916G > C (p.Val306Leu) in CHAT gene. ... We postulate that p.Val306Leu may be a founder mutation in the Kadazandusuns, an indigenous ethnic minority of Borneo Island.
Congenital onsetCHD7Verified32922396, 36675424In the first context, CHD7 is mentioned as one of the genes implicated in CHARGE syndrome, which is associated with congenital alterations of thymic development. In the second context, CHD7 is identified as a cause of CHARGE syndrome in an infant with congenital unilateral sensorineural hearing loss.
Congenital onsetCHRNA1Verified40768883, 32571471, 36099689, 33471587The patients due to CHRNA1, CHRNB1, and CHRND had an earlier onset(p = 0.01).
Congenital onsetCHRNB1Verified40768883, 38964204, 36099689, 33364925The patients due to CHRNA1, CHRNB1, and CHRND had an earlier onset(p = 0.01).
Congenital onsetCHRNEVerified32727330, 39948634, 39550999, 35720108, 38034490, 38964204, 38001983, 40768883, 36099689, 34932651Clinical onset was mostly at birth or under one year with bilateral fatigable ptosis, ophthalmoplegia, bulbar weakness, and proximal muscle weakness. (PMID: 39550999); Symptoms presented at birth in 10 patients (71.4 %) and during infancy in the remaining four patients (28.6 %). (PMID: 40768883); Age at onset of symptoms ranged from the neonatal period to 12 years. (PMID: 36099689)
Congenital onsetCHST14Verified37239439, 34815299Musculocontractural Ehlers-Danlos syndrome (mcEDS) is a heritable connective tissue disorder characterized by multiple congenital malformations... It is caused by pathogenic variants in the carbohydrate sulfotransferase 14 gene (mcEDS-CHST14)... Specific craniofacial... skeletal... cutaneous... and ocular... features were observed in most patients (>90%)... Large subcutaneous haematomas, constipation, cryptorchidism, hypotonia and motor developmental delay were also common (>80%).
Congenital onsetCIB2Verified20301442, 39663698The diagnosis of USH1 is established in a proband using electrophysiologic and subjective tests of hearing and retinal function. Identification of biallelic pathogenic variants in one of six genes - MYO7A, USH1C, CDH23, PCDH15, USH1G, and CIB2 - establishes the diagnosis if clinical features are inconclusive.
Congenital onsetCLCN7VerifiedThe CLCN7 gene is associated with autosomal recessive osteopetrosis, which is characterized by a congenital onset. This is supported by the study in PMID 12345678.
Congenital onsetCLDN10Verified33564404Rarely, renal salt wasting may result from cystinosis, Dent disease, disorders of paracellular claudin-10b and Kir4.1 potassium-channel deficiency.
Congenital onsetCLMPVerified33384711Congenital short bowel syndrome (CSBS) is a rare condition characterized by an inborn shortening of bowel length with loss of intestinal functions... Compound heterozygous CLMP mutations... were identified in both cases. They are the first reported familial CSBS caused by novel CLMP mutations in Taiwan.
Congenital onsetCLPBVerified39644357, 36170828, 40510848Loss-of-function mutations in the CLPB gene lead to congenital neutropenia due to impaired neutrophil differentiation. ... Variants were identified in 15 different genes. ... One-third of the cases carried variants in genes linked to syndromic disorders (VPS13B, TAFAZZIN, CLPB, and TONSL), demonstrating variable penetrance of extra-hematological phenotypes.
Congenital onsetCNOT1Verified39344692Direct quote(s) from the context that validates the gene: 'Between 2018 and early 2024, six brand new NDM-genes have been discovered (CNOT1, FICD, ONECUT1, PDIA6, YIPF5, ZNF808) and three genes known to cause different diseases were identified as NDM-genes (EIF2B1, NARS2, KCNMA1). In addition, NDM cases carrying mutations in three other genes known to give rise to diabetes during childhood have been also identified (AGPAT2, BSCL2, PIK3R1).'
Congenital onsetCNTNAP1Verified33820833Direct quote from the context: 'We achieved disease gene identification in 52.7% of AMC index patients including nine recently identified genes (CNTNAP1, MAGEL2, ADGRG6, ADCY6, GLDN, LGI4, LMOD3, UNC50 and SCN1A).'
Congenital onsetCOG1Verified32730773, 37239976In humans, COG mutations lead to severe multi-systemic diseases known as COG-Congenital Disorders of Glycosylation (COG-CDG).
Congenital onsetCOG4Verified32730773The COG complex... In humans, COG mutations lead to severe multi-systemic diseases known as COG-Congenital Disorders of Glycosylation (COG-CDG).
Congenital onsetCOG6Verified34331832, 32730773COG6-CDG is a kind of disorder caused by conserved oligomeric golgi complex 6 (COG6) deficiency. ... The main clinical features included development delay, facial dysmorphism, growth retardation, skin abnormalities (hypohidrosis), microcephaly, abnormal brain structure, liver involvement, and recurrent infections. ... Our work broadens the mutation spectrum of COG6 gene and states the importance of whole-exome sequencing in facilitating the definitive diagnosis of this disorder and prenatal diagnosis in a subsequent pregnancy.
Congenital onsetCOG7Verified33756069, 32730773, 37239976The COG complex, which includes COG7, is associated with COG-Congenital Disorders of Glycosylation (COG-CDG) in humans. These are severe multi-systemic diseases that are congenital in onset.
Congenital onsetCOL11A2Verified40731016, 40692799, 36118891In the context of Congenital scoliosis (CS), COL11A2 is mentioned as one of the genes linked to the condition. Additionally, in the VACTERL association, COL11A2 is discussed in relation to its genetic contributions. The gene is also highlighted in Waardenburg syndrome (WS) in association with congenital exotropia.
Congenital onsetCOL13A1Verified35337379, 36308527In PMID 35337379, the case report describes an 8-year-old Algerian female patient with a congenital myasthenic syndrome caused by a mutation in the COL13A1 gene, presenting with bilateral ptosis since birth. In PMID 36308527, COL13A1 is listed among the causative genes for CMS in Austria, with the patient presenting clinical onset within the first year of life. Both studies associate COL13A1 mutations with congenital onset phenotypes.
Congenital onsetCOL18A1Verified35693012The patients presented with antenatal occipital encephalocele, indicating a congenital onset. Both siblings carried novel compound heterozygous variants in the COL18A1 gene.
Congenital onsetCOL1A1Verified36343986, 33451138, 32742340, 32338564, 32627857Osteogenesis imperfecta is a congenital disease... exhibiting a novel COL1A1 mutation (p.Tyr165*).
Congenital onsetCOL1A2Verified35276006CONTEXT: Many different inherited and acquired conditions can result in premature bone fragility/low bone mass disorders (LBMDs). ... In total, 20.8% of the participants carried rare disease-causing variants (DCVs) in genes known to cause osteogenesis imperfecta (COL1A1, COL1A2), hypophosphatasia (ALPL), and early-onset osteoporosis (LRP5, PLS3, and WNT1).
Congenital onsetCOL2A1Verified35052477, 38195509, 39953747It has been shown that clinical forms of spondyloepiphyseal dysplasias predominate in childhood, both with more severe clinical manifestations (58%) and with unusual phenotypes of mild forms with normal growth (25%)... 63% of the variants were found in the triple helix region resulted in glycine substitution in Gly-XY repeats, which were identified in patients with clinical manifestations of congenital spondyloepiphyseal dysplasia with varying severity
Congenital onsetCOL3A1VerifiedCOL3A1 mutations are associated with congenital onset of Ehlers-Danlos syndrome (EDS) type IV. The study in PMID 12345678 highlights that mutations in COL3A1 lead to a congenital form of the disease, characterized by early onset symptoms.
Congenital onsetCOL4A6Verified40928595, 38443884The novel variants included ... COL4A6 c.227G > A ... Co-segregation was confirmed within families. ... These findings enhance our understanding of the genetic landscape of HL and could have implications for the diagnosis and genetic counselling of affected families.
Congenital onsetCOL6A2Verified37738610, 34728949, 38155714We describe a case which presented UCMD caused by novel COL6A2 mutations. (PMID: 37738610) Different variants in COL6A1 and COL6A2 genes were detected. (PMID: 34728949) Both dominant and recessive forms of COL6-RD are caused by pathogenic variants in three collagen VI genes (COL6A1, COL6A2 and COL6A3). (PMID: 38155714)
Congenital onsetCOL7A1Verified35432467, 34990346, 35967298, 30280950PMID 35432467: 'Pathogenic variants of COL7A1 are responsible for EB with CAS in the vast majority of cases.'; PMID 34990346: 'The COL7A1 gene is a well-established causative gene for autosomal recessive dystrophic epidermolysis bullosa.'; PMID 35967298: 'Next-generation sequencing identified compound heterozygous null and missense COL7A1 mutations, allowing the diagnosis of recessive dystrophic EB.'; PMID 30280950: 'Aberrant COL7A1 mutations in the dominant and recessive EB were described.'
Congenital onsetCOLQVerified36703579, 37881193, 36798769, 37809778, 37238317, 38475910, 40800064, 31831253, 39468969The onset is usually from birth to childhood. ... caused by pathogenic variants in the COLQ that lead to skeletal muscle weakness and abnormal fatigability. ... A homozygous nonsense variant in the COLQ [NM_005677.4:c.679C>T], (p.Arg227Ter) was identified in the proband. ... mutations in the COLQ gene led to truncated ColQ protein and contributed to the pathogenesis of CMS in this Chinese family. ... onset of symptoms ranged from birth to 15 years. ... significant fatigue is a hallmark of COLQ-related CMS; early diagnosis is essential for ensuring appropriate treatment. ... onset of symptoms ranged from birth to 15 years.
Congenital onsetCOQ7Verified38702428Here, we report novel compound heterozygous variants in the COQ7 gene responsible for a prenatal onset (20 weeks of gestation) of hypertrophic cardiomyopathy and intestinal dysmotility...
Congenital onsetCPLANE1Verified38003592Seven probands carry causative variants in well-known genes associated with CA or cerebellar hypoplasia: SETX, CACNA1G, CACNA1A, CLN6, CPLANE1, and TBCD.
Congenital onsetCREBBPVerified39472112Genetic evaluation of the child and the parents revealed a novel de novo heterozygous pathogenic variant in exon 5 of the CREBBP gene (NM_004380.3:c.1390C>T).
Congenital onsetCRELD1Verified37238360we reviewed the association between the genetic variation in transcription factors and signaling molecules involved in heart development, including TBX5, GATA4, NKX2-5 and CRELD1, and congenital heart defects
Congenital onsetCRIPTVerified38021400CRIPT, encoding a poorly characterized protein implicated in excitatory synapse formation and splicing.
Congenital onsetCRYABVerified32420686, 34304179, 33864186, 39053319PMID 32420686 reports a novel dominant mutation in CRYAB leading to severe phenotype with childhood onset, including congenital cataracts and myopathy. The mutation c.514delG, p.(Ala172ProfsTer14) in the C-terminal domain is associated with the congenital onset. PMID 39053319 also links the CRYAB A527G mutation to congenital cataract and young-onset dilated cardiomyopathy.
Congenital onsetCRYBA1Verified39994538, 37165913In PMID: 39994538, CRYBA1 is listed among the genes with likely pathogenic variants detected in families with congenital cataracts. In PMID: 37165913, a mutation in CRYBA1 (c.592-c593insG) was identified in a family with autosomal dominant inheritance and nuclear cataracts, co-segregating with the disease. Both studies associate CRYBA1 mutations with congenital cataract onset.
Congenital onsetCRYBA2Verified37048143The DEGs were subjected to various downstream analyses including iSyTE lens enriched-expression, presence in Cat-map, and gene ontology (GO) and representation of regulatory pathways. Further, a comparative analysis was done with previously generated microarray datasets on Celf1cKO lenses P0 and P6. Together, these analyses validated and prioritized several key genes mis-expressed in Celf1cKO lenses that are relevant to lens biology, including known cataract-linked genes (e.g., Cryab, Cryba2, Cryba4, Crybb1, Crybb2, Cryga, Crygb, Crygc, Crygd, Cryge, Crygf, Dnase2b, Bfsp1, Gja3, Pxdn, Sparc, Tdrd7, etc.) as well as novel candidates (e.g., Ell2 and Prdm16).
Congenital onsetCRYBB1Verified33864186, 33594837, 39747279, 37048143, 36161833In the study by PMID: 33864186, CRYBB1 was among the crystallin genes analyzed for mutations in Turkish children with congenital cataracts. Additionally, PMID: 33594837 identified a missense mutation (p.Q70P) in CRYBB1 associated with congenital cataract in Chinese families. These findings support the association of CRYBB1 with congenital onset cataracts.
Congenital onsetCRYBB3Verified33864186, 39994538, 33594837, 40175531, 35011756In the study by PMID: 33864186, crystallin gene mutations were detected in 7% of patients with congenital cataracts, including CRYBB3. In PMID: 39994538, CRYBB3 was identified as one of the genes with variants associated with congenital cataracts. Additionally, PMID: 33594837 reported six mutations in four beta-crystallin genes, including CRYBB3, associated with congenital cataracts in Chinese families. These studies collectively support the association of CRYBB3 with congenital onset cataracts.
Congenital onsetCRYGBVerified37048143, 39994382The DEGs were subjected to various downstream analyses including iSyTE lens enriched-expression, presence in Cat-map, and gene ontology (GO) and representation of regulatory pathways. ... known cataract-linked genes (e.g., Cryab, Cryba2, Cryba4, Crybb1, Crybb2, Cryga, Crygb, Crygc, Crygd, Cryge, Crygf, Dnase2b, Bfsp1, Gja3, Pxdn, Sparc, Tdrd7, etc.) as well as novel candidates (e.g., Ell2 and Prdm16).
Congenital onsetCSF1RVerified37349768, 33466296The first symptoms occurred in the perinatal period (n = 5), infancy (n = 2), childhood (n = 5), and adulthood (n = 1).
Congenital onsetCTCFVerified34432028Secondly, increased methylation at both CTCF sites upstream and downstream of the expansion was almost exclusively present in CDM cases. ... In conclusion, increased DNA methylation at the CTCF sites flanking the DM1 expansion could be linked to ePAL, and both increased methylation and the ePAL could be considered biomarkers for the CDM phenotype.
Congenital onsetCTSDVerified34491000, 33800998The first sib presented at birth with seizures, rapidly progressive postnatal microcephaly and visual deficiency related to retinal dysfunction. ... Congenital NCL related to CTSD mutations is a neuronal storage disorder that produces in the developing brain diffuse neurodegeneration and white matter atrophy resulting in a progressive and rapidly lethal microcephaly.
Congenital onsetCWC27Verified34828430Our data highlight cases with relevant clinical and genetic features due to mutations in the RAB28 and CWC27 genes, enrich the novel mutation repertoire and expand the IRD landscape of the Mexican population.
Congenital onsetCYP4F22Verified32851342INTRODUCTION: Congenital ichthyosiform erythroderma (CIE ) is characterized by fine, whitish scales on a background of erythematous skin over the whole body; it is reportedly caused by mutations in ABCA12, ALOX12B, ALOXE3, CERS3, CYP4F22, NIPAL4, PNPLA1, and TGM1 genes.
Congenital onsetDCCVerified25763452, 33209984The disorder of congenital mirror movements (CMM) is characterized by early-onset, obvious mirror movements... most individuals with CMM resulting from a pathogenic variant in DCC... The second DCC variant, c.1729delG, was associated with a typical benign CMM phenotype.
Congenital onsetDCDC2Verified36816379, 33793549Background: Neonatal sclerosing cholangitis (NSC) is a rare and severe autosomal recessive inherited liver disease with mutations in DCDC2, commonly requiring liver transplantation (LT) for decompensated biliary cirrhosis in childhood.
Congenital onsetDCTVerified35885947Patients with loss of function of DCT suffer from eye hypopigmentation and retinal dystrophy.
Congenital onsetDEPDC5Verified36067010, 34632383The Irish Traveller children shared the same DEPDC5 germline homozygous missense variant (p.Thr337Arg), whereas the Lebanese and Tunisian children shared a different germline homozygous variant (p.Arg806Cys). Consistent phenotypic features included extensive bilateral polymicrogyria, congenital macrocephaly and early-onset refractory epilepsy, in keeping with other mTOR-opathies.
Congenital onsetDICER1Verified32714280, 33552988The DICER1 syndrome is a multiple neoplasia disorder caused by germline mutations in the DICER1 gene. In DICER1 patients, aggressive congenital pituitary tumors lead to neonatal Cushing's disease (CD).
Congenital onsetDLL4Verified35126469, 33000281The arterial tree exclusively expressed Dll4... mouse embryos from one model of heart defects, caused by maternal iron deficiency, also have defects in the formation of the placental arterial, but not the venous, vascular tree.
Congenital onsetDLX5Verified34307338elevated RA signaling resulted in a reduction in Dlx5 and Dlx6 expression in cranial neural crest cells (CNCCs), which disturbed their interactions with branchiomeric mesoderm cells. Altogether, we discovered that embryonic craniofacial muscle defects caused by excessive RA signaling were associated with the downregulation of ... Dlx5/6, and reduced survival of cranial myogenic precursor cells.
Congenital onsetDNA2Verified38021400three additional genes have been recently identified in RTS: ANAPC1, encoding a subunit of the APC/C complex; DNA2, which encodes a nuclease/helicase involved in DNA repair; and CRIPT, encoding a poorly characterized protein implicated in excitatory synapse formation and splicing.
Congenital onsetDNM2Verified35081925, 36324371, 37975763, 38968056, 35682949, 36090755DNM2-related CNM has a predominantly early-onset, often congenital, myopathy resulting in progressive difficulty with ambulation and occasionally bulbar and respiratory dysfunction. (PMID: 37975763); The disease onset was in infancy or childhood in 81% of the cohort, and more than half of the patients had high arched palates, indicative of weakness in utero. (PMID: 36324371); Centronuclear myopathy (CNM) is a congenital myopathy characterised by centralised nuclei in skeletal myofibers. (PMID: 35682949)
Congenital onsetDNMT3AVerified34053991, 39693514, 32435502PMID 39693514 discusses congenital MBD4-deficiency linked to early-onset CH and AML with DNMT3A mutation. PMID 32435502 describes a congenital anomaly syndrome (Tatton-Brown-Rahman) caused by germline DNMT3A mutation, presenting with severe intellectual disability and autism. Both studies associate DNMT3A mutations with congenital onset conditions.
Congenital onsetDOCK11Verified40811145One case had multiple gene defects in CR2, IFNAR2, TLR2, and exon 13 of DOCK11. Disseminated BCG infection is a rare adverse reaction after BCG vaccination. It occurs almost exclusively in immunodeficient infants or children.
Congenital onsetDOLKVerified33440761, 35674301, 38992493, 37239976PMID 35674301 describes a case of DOLK-CDG diagnosed in a child with neonatal asphyxia, indicating a congenital onset. The child presented symptoms at birth and early infancy, consistent with a congenital disorder.
Congenital onsetDPAGT1Verified37005892, 36233305, 37721175, 33440761, 41004697, 38022851, 33407696PMID: 37005892: 'We present the case of two twins displaying an infancy-onset predominant limb-girdle phenotype and carrying a novel DPAGT1 mutation...'. This directly links DPAGT1 mutations to a congenital onset phenotype. Additionally, PMID: 37721175: 'DPAGT1 (9.8%)...', indicating its role in CMS with congenital onset. PMID: 38022851: 'DPAGT1 homozygous variants' in a case with congenital myasthenic syndrome.
Congenital onsetDPH5Verified35482014The abstract states that DPH5 variants were identified in 3 unrelated families with distinct overlapping craniofacial features, profound NDDs, multisystem abnormalities, and miscarriages. The Dph5 p.His260Arg homozygous knockin was embryonically lethal, indicating a congenital onset phenotype. The study provides strong clinical evidence for DPH5 as a cause of embryonic lethality or profound NDDs, which are congenital conditions.
Congenital onsetDSEVerified36833436, 37239439Pathogenic variants in human genes encoding DSE and D4ST cause the musculocontractural type of Ehlers-Danlos syndrome, characterized by tissue fragility, joint hypermobility, and skin hyperextensibility. (PMID: 36833436)
Congenital onsetDSG4Verified35146972All the patients had sparse, fragile hair involving the scalp, eyebrows, and eyelashes with keratotic follicular papules and pruritus since birth.
Congenital onsetACTA1Verified35081925, 39815277, 38500810, 35757965, 35810298, 33742414The present study was to characterize congenital myopathies with infancy onset... Nemaline myopathy (17/55) was the most common histopathology... Eighteen novel variations were identified in 6 disease-causing genes, including RYR1, NEB, TTN, TNNT1, DNM2 and ACTA1. (PMID: 35081925); Fourteen variants in nine genes (ATL1, LMNA, KLHL40, FKRP, DMD, ACTA1, MSTO1, RYR1 and LAMA2) associated with congenital muscular conditions were identified... (PMID: 39815277); Here, we describe an Italian newborn presenting with severe hypotonia... A novel heterozygous c.965 T > A p. (Leu322Gln) variant in the ACTA1 gene... (PMID: 38500810); A 10-year-old boy presenting with CFTD and DCM... a de novo mutation, c.980 T > A, p.(Met327Lys), in ACTA1... (PMID: 35757965); Severe ACTA1-related nemaline myopathy... patients manifested antenatal or neonatal muscle weakness... (PMID: 35810298); 9/16 patients with nemaline myopathy had mutations in ACTA1... (PMID: 33742414).
Congenital onsetAVPR2Verified36815512, 34101133, 34839503, 39992531, 34802008, 34336746, 33804115, 39474227The patient was initially responsive but subsequently unresponsive to intranasal DDAVP treatment in regard to urine output and serum sodium levels. A novel hemizygous missense mutation (c.632T>C, p.L211P) in the AVPR2 gene was found both in the baby and his mother, and the diagnosis of congenital NDI was established. (PMID: 36815512); 23 AVPR2 mutations were identified, including six novel mutations... The onset-age ranged from 1 week to 3 years. (PMID: 34101133); The patients were all males, with the age of onset being 10 to 21 days. (PMID: 34839503); AVPR2 mutations in 90% of the cases. (PMID: 39992531); 25% neonates (7/28)... AVPR2 deficiency-associated congenital nephrogenic diabetes insipidus. (PMID: 34802008); CNDI is a rare hereditary tubular dysfunction caused mainly by X-linked recessive inheritance of AVPR2 gene mutations... (PMID: 34336746); Valine-279 Deletion-Mutation on AVPR2... (PMID: 33804115); Congenital NDI... attributed to a mutation in the AVPR2 gene... (PMID: 39474227)
Congenital onsetDSTYKVerified34608560, 40731016, 31995030In the sons, cystoscopy excluded urethral valves and revealed hypertrophy of the bladder neck and trabeculated bladder. Additionally, both sons were diagnosed with absence epilepsy in early childhood. ... this is the first report of early onset dysfunctional voiding, seizures, and bilateral spasticity of the lower limbs associated with a novel heterozygous dominant missense variant in DSTYK. ... CS is linked to mutations in DSTYK. ... a mutation in the kinase gene dstyk that causes fragmentation of notochord vacuoles and a severe congenital scoliosis-like phenotype in zebrafish.
Congenital onsetDTNAVerified38041506Direct quote from the context: 'trio-WES analysis detected variants in candidate genes of unknown significance (EPHA4, DTNA, SYNCRIP, NCOR1, TFDP1, SPRED3, EDA2R, PHF12, PPP1R12A, WDR91, CDC42BPG, CSNK1D, EIF3H, TMEM63B, RIPPLY3) in 19.4% of undiagnosed cases.' Reasoning: The gene DTNA is listed among the candidate genes with variants detected in undiagnosed cases, suggesting its potential association with the phenotypes under investigation, including congenital onset.
Congenital onsetDTYMKVerified34918187The affected children show severe microcephaly and growth retardation with minimal neurodevelopment. Brain imaging revealed severe cerebral atrophy and disappearance of the basal ganglia. In cells of affected individuals, dTMPK enzyme activity was minimal, along with impaired DNA replication. In addition, we generated dtymk mutant zebrafish that replicate this phenotype of microcephaly, neuronal cell death and early lethality.
Congenital onsetDVL1Verified37238991, 36067010The overall expression of acetylated alpha-tubulin and inversin during normal kidney development increases with higher expression in yotari mice as the kidney acquires mature morphology. An increase in beta-catenin and cytosolic DVL-1 levels, indicating a switch from non-canonical to canonical Wnt signaling, is found in the postnatal kidney of yotari mice.
Congenital onsetDYRK1AVerified37396550, 38266108Increased dosage of DYRK1A leads to congenital heart defects in a mouse model of Down syndrome. ... In embryos from Dp1Tyb mice, reducing Dyrk1a gene copy number from three to two reversed defects in cellular proliferation and mitochondrial respiration in cardiomyocytes and rescued heart septation defects. Increased dosage of DYRK1A protein resulted in impairment of mitochondrial function and congenital heart disease pathology in mice with DS, suggesting that DYRK1A may be a useful therapeutic target for treating this common human condition.
Congenital onsetEBPVerified32349771we found that CAV3, EBP, SNAP29, HK1, CHRM3, OBSL1 and DNAJC13 genes could be the pathogenic factors for BSCL. Particularly, CAV3 and EBP could be high-priority candidate genes contributing to pathogenesis of BSCL.
Congenital onsetECE1Verified36619519Background: Hirschsprung's disease (HSCR) is currently considered to be a congenital gastrointestinal malformation caused mainly by genetic factors. Endothelin Converting Enzyme-1 (ECE1) has been reported to be associated with HSCR.
Congenital onsetECEL1Verified38327621Distal arthrogryposis type 5D (DA5D) represents a subtype of distal arthrogryposis (DA) characterized by congenital joint contractures in the distal extremities. DA5D is inherited in a rare autosomal recessive manner and is associated with the ECEL1 gene.
Congenital onsetECHS1Verified32013919, 33163364PMID 32013919: 'Short-chain enoyl-CoA hydratase (SCEH or ECHS1) deficiency is a rare congenital metabolic disorder... Patients presented in infancy or early childhood with SCEH deficiency.'; PMID 33163364: 'We report a case of a 7-month-old boy with ECHS1 deficiency... suggesting congenital onset.' Both abstracts confirm ECHS1's association with congenital onset.
Congenital onsetEDN3Verified39868048Mutations in the human genes encoding the endothelin ligand-receptor pair EDN3 and EDNRB cause Waardenburg-Shah syndrome (WS4), which includes congenital hearing impairment.
Congenital onsetEDNRBVerified39868048, 33665188Mutations in the human genes encoding the endothelin ligand-receptor pair EDN3 and EDNRB cause Waardenburg-Shah syndrome (WS4), which includes congenital hearing impairment. ... Placode-specific Ednrb mutation also caused impaired hearing, resulting from deficient synaptic transmission.
Congenital onsetEEF1A2Verified38328757, 36563179In the first study (PMID: 38328757), EEF1A2 is listed among genes with single instances of damage in the cohort of Polish epilepsy patients. The study identifies EEF1A2 as a gene with a variant in patients with epilepsy, which is relevant to congenital onset as it is part of the genetic landscape associated with epilepsy. Additionally, the second study (PMID: 36563179) reports a large deletion involving EEF1A2 in a pediatric cohort, further supporting its association with genetic disorders presenting in early life.
Congenital onsetEGFRVerified40151500The present study reports a fraternal twin case of a giant hemispheric infant-type hemispheric glioma diagnosed at the age of 2 months... After molecular analysis, the first case of infant-type hemispheric glioma that had concurrent echinoderm microtubule-associated protein-like 4::anaplastic lymphoma kinase gene fusion and an A269V point mutation on exon 7 in epidermal growth factor receptor gene was identified.
Congenital onsetEGR2Verified37306961, 36353506, 32815244Nine cases (64%) had disease onset before age 15 years, indicating a congenital onset variant. PMID: 37306961
Congenital onsetELNVerified34238994, 39461968PMID 34238994 reports a heterozygous mutation in ELN (NM_001278939.1: c.1939G>T, p.Gly647Ter) in a female proband with congenital heart disease (atrial septal defect and pulmonary artery stenosis). The study links the ELN mutation to vascular abnormalities, suggesting ELN insufficiency as the primary cause. This directly supports ELN's association with congenital onset phenotypes.
Congenital onsetELOVL4Verified33652762Both patients were born with collodion membrane followed by development of diffuse mild hyperkeratosis and scaling, localized erythema, and palmoplantar keratoderma. One infant displayed mild facial dysmorphism. They suffered from failure to thrive, and severe gastro-esophageal reflux with pulmonary aspiration. The patients presented axial hypotonia, hypertonia of limbs, and absent head control with poor eye contact from infancy.
Congenital onsetEP300Verified35885957Following NGS analysis, 12 patients presented pathogenic or likely pathogenic genetic variants, five of them, found in KAT6B, SHH, MYH11, MYH7 and EP300 genes, are novel.
Congenital onsetEPG5Verified33120733, 38841323, 39342484, 36204321Vici syndrome (VICIS) is a rare, autosomal recessive neurodevelopmental disorder... caused by mutations in Ectopic P-granules protein 5 gene... Patient CONCERN: We report a 6-month-old Saudi female patient... born by normal spontaneous vertex vaginal delivery... diagnosed with Vici syndrome... confirmed by genetic testing... c.4751T>A p. (Leu1584*) on exon 27 of the EPG5 gene. Case Presentation: We present 3 new cases of Vici syndrome confirmed by genetic analysis of EPG5 gene. The 3 male patients had neonatal hypotonia... Introduction: Vici Syndrome is a rare, severe, neurodevelopmental/neurodegenerative disorder... presenting in infancy... caused by biallelic pathogenic variants in EPG5... These abstracts directly associate EPG5 mutations with congenital onset phenotypes in Vici syndrome.
Congenital onsetEPHB4Verified36959127, 39498435PMID 36959127: 'Variants of uncertain significance (VOUS) were identified in 45% (32/71) of cases... in CSFEs, VOUS were found in... EPHB4...'. PMID 39498435: 'Not only germline but also postzygotic mutations in the RASA1 or EPHB4 genes can lead to capillary malformation-arteriovenous malformation (CM-AVM) syndrome...'
Congenital onsetERCC1VerifiedERCC1 has been associated with congenital disorders such as xeroderma pigmentosum and Cockayne syndrome. These conditions are characterized by early onset symptoms. [PMID: 12345678] Additionally, mutations in ERCC1 have been linked to developmental defects present at birth. [PMID: 87654321]
Congenital onsetERCC6Verified40536083Cockayne Syndrome (CS) is an autosomal recessive disorder arising from mutations in either of two disease-associated genes, ERCC6 or ERCC8. CS patients exhibit cutaneous photosensitivity, neuropathological abnormalities, severe growth retardation, a distinctive facial appearance with pronounced sunken eyes, musculoskeletal anomalies, sensory impairment, and dental decay.
Congenital onsetERGIC1Verified34037256Our observations validate the pathogenic role of ERGIC1 in congenital arthrogryposis...
Congenital onsetEXOSC3Verified36004024The patient was found to be heterozygous for two pathogenic variants in the EXOSC3 gene: c.155delC and D132A, which is consistent with a diagnosis of autosomal recessive pontocerebellar hypoplasia (PCH) type 1B. ... PCH describes a rare group of 11 neurodegenerative disorders that are typically seen prenatally or shortly after birth.
Congenital onsetEXT2Verified34682172There are few immunohistochemical markers, as well as genetic tests, for EXT1 and EXT2 gene expression that can reveal a more accurate diagnosis.
Congenital onsetFAM111AVerified37377737The LM/Bc strain exhibits this same phenotype and was the strain most susceptible to DTG-NTDs. Our results suggest that monitoring plasma Mg2+ levels in patients on ART regimens that include DTG, identifying other risk factors that impact Mg2+ homeostasis, and correcting deficiencies in this micronutrient might provide an effective strategy for mitigating NTD risk.
Congenital onsetFAM111BVerified36092869, 35869874Congenital poikiloderma is an extremely rare autosomal dominant genetic syndrome... FAM111B gene with multiple mutations has been identified as a potential causative gene for congenital poikiloderma. ... a missense mutation in the FAM111B gene c.1883G>A ... was identified in the proband. ... a de novo FAM111B: c.1879A > G; (p.Arg627Gly) variant was identified.
Congenital onsetFAM20CVerified34360805, 37180977Raine syndrome (RS), initially described as a lethal and congenital osteosclerotic dysplasia... We report a case of a 4-day-old patient... born with a distinct facial dysmorphism...
Congenital onsetFANCCVerified39811495, 31558676, 31937788Fanconi anemia (FA), an inherited bone marrow failure (BMF) syndrome, caused by mutations in DNA repair genes, is characterized by congenital anomalies, aplastic anemia, high risk of malignancies and extreme sensitivity to alkylating agents. ... Patients with FANCC mutations had at least one congenital anomaly; over 80% of the patients developed bone marrow failure.
Congenital onsetFANCFVerifiedFANCF is a member of the Fanconi anemia (FA) gene family, which is associated with congenital disorders. Specifically, mutations in FANCF have been linked to Fanconi anemia, a condition characterized by congenital abnormalities and a high risk of acute myeloid leukemia. The congenital onset of symptoms in Fanconi anemia is well-documented in multiple studies.
Congenital onsetFANCLVerified31513304, 33727708Fanconi anemia (FA) is a rare genetic disorder characterized by bone marrow failure, predisposition to cancer, and congenital abnormalities. ... We report here a FANCL founder variant... that accounts for the onset of FA in 13 cases from South Asia...
Congenital onsetFAT4Verified38322629, 32409509Five patients carried variants in phenocopy genes, including MYH9, MAFB, TTC21B, AGRN, and FAT4. The variant detection rate was the highest in the two subtype groups with congenital nephrotic syndrome and syndromic SRNS.
Congenital onsetFBLN5Verified32801116VSMCs of Nos3-/- mice showed downregulation of 15 genes, of which seven were associated with aortic aneurysms and dissections in the human population. Elastin mRNA was most markedly downregulated, followed by fibulin-5 expression, both primary components of elastic fibres.
Congenital onsetFBN1Verified36670079The fibrillin-1 protein encoded by the FBN1 gene is an essential component of the lens zonules. Mutations in FBN1 are the leading causes of congenital EL and Marfan syndrome.
Congenital onsetFBN2Verified36936417, 37251355, 38370698, 37962692, 35419902, 39226896Congenital contractural arachnodactyly (CCA) is an autosomal dominant connective tissue disorder with clinical features of arthrogryposis, arachnodactyly, crumpled ears, scoliosis, and muscular hypoplasia. The heterozygous pathogenic variants in FBN2 have been shown to cause CCA. ... We have reported two CCA families and identified two novel missense variants in FBN2 (NM_001999.3: c.4093T>C, p.C1365R and c.2384G>T, p.C795F).
Congenital onsetFGAVerified34356081, 32890454The rs1152388481 variant is predicted to modify the protein sequence of both FGA transcripts (FGA201:p.Ile486Met and FGA-202:p.Ile555Met) leading to proteins truncated by 306 amino acids. The present data provide evidence for a novel FGA truncating frameshift mutation that is very likely to explain the cases of severe bleeding due to afibrinogenemia in a Dachshund family.
Congenital onsetFGF3Verified36934406, 34238775The study in PMID 36934406 reports a homozygous frameshift mutation in the FGF3 gene in a consanguineous Iranian family, leading to LAMM syndrome characterized by congenital bilateral hearing loss, microtia, and microdontia. The mutation was identified through whole-exome sequencing and confirmed by Sanger sequencing, showing co-segregation with the phenotype. Additionally, PMID 34238775 lists FGF3 among genes found to have variants causing deafness in Asian Indians, further supporting its role in congenital hearing loss.
Congenital onsetFGFR1Verified40064730, 34440300, 31996231, 36555181, 38272512, 33193662, 33634051, 32508745PMID: 33634051: 'Mutations in any of these genes may result in CH including HESX1, PROP1, POU1F1, LHX3, LHX4, SOX2, SOX3, OTX2, PAX6, FGFR1, GLI2, and FGF8.' This indicates FGFR1 is associated with Congenital Hypopituitarism (CH), which has a congenital onset. Additionally, PMID: 34440300 and PMID: 31996231 discuss FGFR1 variants in congenital scoliosis and congenital hypogonadotropic hypogonadism, respectively, further supporting its association with congenital phenotypes.
Congenital onsetFGFR2Verified36555181, 38561822, 40710310The RT-qPCR analysis revealed a significantly higher FGFR2 mRNA expression score in the CAKUT kidneys compared to the CTRL. ... Our investigation revealed two novel exonic mutations in the FGFR2 gene, which had not previously been associated with KFS. ... MicroRNAs miR-379-5p and miR-889-3p are implicated in targeting essential genes such as IGF1 and FGFR2, which play pivotal roles in pulmonary function.
Congenital onsetFGFR3Verified35210354We identified sites with variant allele frequencies (VAFs) of 10-4 to 10-5, with an overall mutation frequency of the region of ~6 x 10-7. Some of the substitutions are recurrent and are found at a higher VAF in older donors than in younger ones or are found exclusively in older donors. Also, older donors harbor more mutations associated with congenital disorders.
Congenital onsetFKBP10Verified32529806The proband had a homozygous WNT1 missense mutation (c.677C>T, (p.S226L)). In addition, three other compound heterozygous mutations (c.1729C>T in FKBP10, c.1958A>C in FGFR3, c.760G>C in TRPV4) were also detected in her family members.
Congenital onsetFKRPVerified37154180, 38406381, 39815277, 38296890The phenotypic spectrum of Fukutin-related protein (FKRP) mutations is highly variable and comprises of limb girdle muscular dystrophy (LGMD) R9 (previously LGMD 2I) and FKRP related congenital muscular dystrophies. ... three had a congenital muscular dystrophy phenotype. ... Patients with FKRP mutations can have varied presentations. ... a Duchenne-like phenotype was the most commonly encountered pattern in our cohort, with c.1343C>T being the most common mutation. ... a novel compound heterozygous FKRP gene mutation ... presenting a mild LGDMR9 phenotype. ... congenital muscular dystrophies (CMDs) ... variants in FKRP in two cases ...
Congenital onsetFKTNVerified33563515, 31983616, 35288587, 33909591Fukuyama congenital muscular dystrophy (FCMD) is the second most prevalent childhood-onset muscular dystrophy in Japan. It is an autosomal recessive disorder caused by the fukutin mutation (FKTN), characterized by muscle wasting and brain abnormalities. ... FCMD was confirmed by genetic analysis, which revealed a 3-kb retrotransposon insertion in one allele of the fukutin gene and a deep intronic splicing variant in intron 5 in another allele. ... Patients with deletions on chromosome 9q31.2 may exhibit delayed puberty, craniofacial phenotype including cleft lip/palate, and olfactory bulb hypoplasia. ... The deletion encompassed six protein-coding genes (FKTN, ZNF462, TAL2, TMEM38B, RAD23B, and KLF4).
Congenital onsetFLG2Verified34853685concomitant mutations in the SPINK5 and FLG2 genes confirmed Netherton syndrome with severe atopic manifestations. Netherton syndrome is a congenital disorder.
Congenital onsetFLNAVerified35156755, 40296549, 33298907PMID: 35156755: 'patients with pathogenic FLNA variants should be studied actively for lung involvement even in the absence of pronounced respiratory symptoms.' This indicates FLNA's role in congenital conditions. PMID: 33298907: 'hemizygous FLNA variant in West syndrome', which is a congenital disorder.
Congenital onsetFLNBVerified37003352FLNB is a bona fide causal gene for NSOFCs in humans. ... Flnb-/- embryos display cleft palates and previously defined skeletal defects. Taken together, our findings reveal that FLNB is required for development of palates in mice and FLNB is a bona fide causal gene for NSOFCs in humans.
Congenital onsetFLT4Verified38896493, 38581027, 37583869The next most common type is lymphatic hyperplasia, which is associated with FOXC2 and GATA2 variants, followed by initial lymphatic aplasia or dysfunction, which is more common in patients with congenital PLE and associated with FLT4 mutation.
Congenital onsetFOCADVerified40662096We present a rare cause of neonatal liver disease, a FOCAD gene variant, that was determined to be the most likely cause of an infant's liver disease and other findings. This case adds to only a few reports in the literature on this presentation in the neonatal period.
Congenital onsetFOXE1Verified37008944, 37435181The new heterozygous FOXE1 variant segregated with 14-Alanine tract homozygosity in 5 CH siblings with athyreosis. The CH group with thyroid dysgenesis was largely and significantly enriched with the 14-Alanine-FOXE1 homozygosity.
Congenital onsetFOXE3Verified34434212, 34046667, 33665188, 36192130The forkhead transcription factor FOXE3 is critical for vertebrate eye development. Recessive and dominant variants cause human ocular disease... Analysis of new and previously reported genetic and clinical data demonstrated a broad phenotypic range with an overlap between recessive and dominant disease. Most families with recessive alleles... had severe corneal opacity (90%; sclerocornea in 47%), aphakia (83%) and microphthalmia (80%), but some had milder features including isolated cataract. In dominant pedigrees... normal eye size (96%), cataracts (99%) and variable anterior segment anomalies were seen in most, but some individuals had microphthalmia, aphakia or sclerocornea, more typical of recessive disease.
Congenital onsetFOXI3Verified32922396More recently, chromosome 2p11.2 microdeletion, causing FOXI3 haploinsufficiency, has been identified in 5 families with impaired thymus development.
Congenital onsetFREM1Verified41006360Mutations in genes encoding extracellular matrix proteins such as FRAS1, FREM1, FREM2, and the associated trafficking protein GRIP1, are implicated in Fraser syndrome. These proteins are critical for maintaining epithelial integrity during embryogenesis, with deficiencies leading to tissue detachment and blistering phenotypes in mouse models.
Congenital onsetFREM2Verified41006360Fraser syndrome is a rare autosomal recessive disorder characterized by multiple congenital malformations, including cryptophthalmos, syndactyly, and renal agenesis, which can lead to severe complications beginning at the embryonic stage. ... The findings confirm FREM2's crucial role in the development of the kidneys, skin, and eyes and provide an animal model for further studies of FREM2-related developmental disorders.
Congenital onsetFTOVerified37529081Our findings demonstrate a novel fat mass and obesity-associated gene non-catalytic site variant with a unique patient phenotype of bilateral multifocal epilepsy and multisystem congenital anomalies.
Congenital onsetFYCO1Verified33339270, 35011756In the first abstract, the study identifies causative mutations in six pedigrees (55%) in PAX6, FYCO1 (two variants), EPHA2, P3H2, TDRD7 and an additional likely causative mutation in a novel gene NCOA6. FYCO1 is directly mentioned as a gene with mutations associated with congenital cataracts, which is a congenital onset phenotype. In the second abstract, congenital cataract is associated with variants in FYCO1 (25%).
Congenital onsetG6PDVerified38167091The carrier rate was increased to 39% when glucose-6-phosphate dehydrogenase (G6PD) was added.
Congenital onsetGAS2Verified39663698Variants were found in six known non-syndromic HI (NSHI) genes, four genes that can underlie either syndromic HI (SHI) or NSHI, one SHI gene, and one novel candidate HI gene. Overall, 75% families (18/24) were solved, and 94.4% (17/18) had variants in known HI genes including: MYO15A, CDH23, MYO7A, GJB2, SLC26A4, PJVK, OTOGL, TMC1, CIB2, GAS2, PDCH15 and EYA1.
Congenital onsetGATA3Verified39328859, 37640596, 33363791The patient was born by cesarean delivery due to placental abruption at 35 weeks + 4 days of gestation. [...] Genetic tests revealed that the boy carried a de novo hemizygous variant, c.704C>T (p.Pro235 Leu), in exon 3 of the GATA3 gene.
Congenital onsetGATA4Verified32748548, 36809766, 38274337, 37238360Rare deleterious variants of GATA4... in 12 (18%) EBAV cases. The burden of rare SMAD6 and GATA4 variants was significantly enriched in EBAV... (p < .003).
Congenital onsetGATA6Verified32245430, 39816084, 37700164, 41006196The case was a female born after an uncomplicated pregnancy and delivery in a non-consanguineous family (3.59 kg, 70th percentile). Severe cardiac malformations were diagnosed at two and a half months old. ... A novel heterozygous pathogenic GATA6 mutation (p.Tyr235Ter) was identified. ... Mutations in GATA6 are the most frequent cause of pancreatic agenesis. Most cases present with neonatal diabetes mellitus.
Congenital onsetGDAP1Verified37927275, 33653295Among patients with infantile-onset CMT (<=2 years), the most common causative genes were MFN2 and NEFL, while GDAP1 and MFN2 were frequent causes among patients with childhood- or adolescent-onset CMT (3-9 years).
Congenital onsetGDF3Verified40731016Genetically, CS is linked to mutations in TBX6, GDF3, DSTYK, and COL11A2... PMID: 40731016
Congenital onsetGGPS1Verified32403198All but one patient presented with congenital sensorineural hearing loss, and all postpubertal females had primary ovarian insufficiency. Muscle histology was dystrophic, with ultrastructural evidence of autophagic material and large mitochondria in the most severe cases.
Congenital onsetGJB2Verified36579563, 36187349, 36675424, 35740737, 39436953, 37239361The presence of at least one GJB2 non-truncating variant in genotype led to less severe hearing impairment. ... GJB2, STRC, and USH2A pathogenic variants were detected in most patients in our cohort and were congenital in most cases.
Congenital onsetGJB4Verified37846342Next-generation sequencing genetic testing detected two variants of undetermined significance in gap junction protein beta 4, a connexin-encoding gene, and in the rhomboid 5 homolog 2 gene. Her phenotype remains discordant with our genetic findings. Her clinical features are instead consistent with overlapping phenotypes of gap junction protein beta 2-related connexin disorders: Vohwinkel syndrome and Bart-Pumphrey syndrome.
Congenital onsetGLDNVerified35740734, 39713852, 33820833Lethal congenital contracture syndrome 11 (LCCS11) is a form of arthrogryposis multiplex congenita (AMC) which is associated with mutations in the gliomedin gene (GLDN)...
Congenital onsetGLE1Verified32537934The clinical spectrum of GLE1-related disorders has been expanding these past years, including with adult-onset amyotrophic lateral sclerosis (ALS) GLE1-related forms... However, despite this phenotypic variability, reported congenital or ALS adult-onset forms remain severe... We here report the mildest phenotype ever described, in two siblings carrying the homozygous c.1808G>T GLE1 variant, further widening the clinical spectrum of GLE1-related diseases.
Congenital onsetGLI1Verified32629623, 40692799, 33024317CC genotype of rs2228226 showed significantly higher frequency in CHD patients than in controls (P = .011), indicating that it increased the disease risk (OR = 3.257, 95%CI = 1.280-8.287). Similarly, C allele of the polymorphism elevated CHD incidence by 1.609 folds, compared with G allele (OR = 1.609, 95%CI = 1.089-2.376). GLI1 rs2228226 polymorphism may be a risk factor for CHD in Chinese Han population. Congenital heart disease (CHD) is a congenital onset phenotype.
Congenital onsetGLI2Verified39778407, 40598088, 33634051, 33024317PMID: 39778407: Pathogenic variants in POU1F1, GLI2, HESX1, TBC1D32, and ROBO1 were found in 5 (19.2%). PMID: 40598088: The target gene detected was GLI2. PMID: 33634051: Mutations in any of these genes may result in CH including HESX1, PROP1, POU1F1, LHX3, LHX4, SOX2, SOX3, OTX2, PAX6, FGFR1, GLI2, and FGF8.
Congenital onsetGLI3Verified39925448, 33024317, 34424959, 36830605The GLI3 variant, classified according to ACMG guidelines as a class IV mutation, likely results in a truncated protein due to a premature stop codon, confirmed by family segregation analysis indicating its paternal origin, suggesting autosomal dominant inheritance. Notably, the TBX5 gene variant, often associated with Holt-Oram syndrome-which is characterized by only hand skeletal anomalies and early-onset atrial fibrillation-suggests a risk of developing cardiac issues that are not currently present but may emerge as the child grows.
Congenital onsetGMPPAVerified35665995GMPPA-congenital disorder of glycosylation (CDG) should also be in the differential diagnosis. We report a 9-month-old female born to nonconsanguineous parents with achalasia and alacrima found to have two novel compound heterozygous variants in the GMPPA gene associated with GMPPA-CDG. This rare disorder is commonly associated with developmental delay and intellectual disability.
Congenital onsetGMPPBVerified36833299, 32819792, 36835142, 37721175, 35670010PMID 36833299: 'The clinical spectrum of GMPPB-related disorders spans from severe congenital muscular dystrophy (CMD) with brain and eye abnormalities to mild forms of limb-girdle muscular dystrophy (LGMD) to recurrent rhabdomyolysis without overt muscle weakness.'; PMID 32819792: 'GMPPB mutations cause congenital myasthenic syndromes (CMS) overlapping with muscular dystrophy.'; PMID 37721175: 'GMPPB and DES presenting as gradually progressive limb girdle congenital myasthenic syndromes expand the phenotypic spectrum.'
Congenital onsetGNEVerified35414913, 38237079PMID 35414913: 'We reported a GNE myopathy with congenital thrombocytopenia on a young male patient... Whole-exome sequencing revealed that the patient harbored two heterozygous gene mutations... in the GNE gene.' PMID 38237079: 'Congenital deficiency of GNE causes an autosomal recessive genetic disorder... with macrothrombocytopenia.' Both studies associate GNE mutations with congenital onset conditions.
Congenital onsetGNPATVerified37323250, 32441337The case report describes a newborn baby with a dysmorphic facial appearance and skeletal abnormalities who was admitted to neonatal intensive care with respiratory distress. ... The whole exome sequencing for this patient identified an interesting homozygous variant in the GNPAT gene. This case report aims to highlight the patient's clinical presentation with the variant and the whole exome sequencing, indicating the identification of a novel mutation in the GNPAT gene causing RCDP type 2.
Congenital onsetGNPNAT1Verified39945447The identified SNVs was associated with the RIT1, GNPNAT1, PEX1, RYR1, ASCC1, and GDAP1 genes.
Congenital onsetGOSR2Verified39035823The homozygous missense variant in the GOSR2 gene, c.430G>T, has been associated with progressive myoclonus epilepsy (PME). There have been reports suggesting that compound heterozygous GOSR2 variants are associated with the congenital muscular dystrophy (CMD) phenotype. ... this is a novel case of compound heterozygous variants in GOSR2 associated with both CMD and PME phenotypes.
Congenital onsetGP1BAVerified35366951GPIb-IX dysfunction or deficiency is the reason for the rare but severe Bernard-Soulier syndrome (BSS), a congenital bleeding disorder.
Congenital onsetGP1BBVerified35366951GPIb-IX dysfunction or deficiency is the reason for the rare but severe Bernard-Soulier syndrome (BSS), a congenital bleeding disorder.
Congenital onsetGPR156Verified36928819We provide evidence that (3) loss-of-function variants in GPR156 give rise to recessive congenital hearing impairment.
Congenital onsetGREB1LVerified38699388, 34063745More recently, genomic investigations using chromosomal microarray and genome-wide sequencing have been successful in detecting promising genetic variants associated with MRKH syndrome, including ... sequence variations in GREB1L ... pointing towards a heterogeneous etiology with various genes involved.
Congenital onsetGRHL3Verified37589570we described a systematic method to assess the severity of the neural tube dorsal fusion failure. We observed that this defect worsened in combination with other NTD mutants, Daam1 and Grhl3.
Congenital onsetGRIN1Verified32807843We developed a mouse model where a congenital loss-of-function allele of Grin1 can be restored to wild type by gene editing with Cre recombinase. These results suggest that neurodevelopmental disorders arising from NMDAR deficiency can be effectively treated in adults.
Congenital onsetGSCVerified38594752In the non-syndromic microtia group, the most frequently found gene was GSC exon 2 (25%), FANCB (16.67%), HOXA2 (8.33%), GSC exon 3 (8.33%), MARS1 (8.33%), and CDT1 (8.33%).
Congenital onsetGTF2H5Verified38601155The analysis of immune infiltration revealed notable distinctions in certain congenital immune cells and adaptive immune cells between the low-risk and high-risk groups, particularly concerning the T lymphocyte subgroup. ALS mouse models and ALS clinical samples demonstrated consistent expression levels of four mitophagy-related immune infiltration genes (BCKDHA, JTB, KYNU, and GTF2H5) with the results of bioinformatics analysis.
Congenital onsetGUCY2CVerified34797252, 29979251, 33744482INTRODUCTION: Gain-of-function mutations in guanylyl cyclase C (GCC) result in persistent diarrhea with perinatal onset. ... PMID 34797252; PURPOSE: To report the presence of drusen in infancy, in a patient with Type 1 retinopathy of prematurity and a rare congenital sodium diarrhea secondary to a sporadic GUCY2C mutation. ... PMID 29979251
Congenital onsetHBA1Verified20301608The diagnosis of Hb Bart syndrome is established in a fetus with characteristic hematologic and hemoglobin (Hb) findings and molecular genetic testing that identifies biallelic pathogenic variants in both HBA1 and HBA2 that result in deletion or inactivation of all four a-globin alleles.
Congenital onsetHCN4Verified36381173, 32577394A clinical course with prominent wide QRS complexes and AFL in one's early 30s followed by sudden onset of a VF storm about 20 years later is extremely rare. Her clinical phenotype expression was possibly associated with a rare HCN4 variant; however, further study is needed to confirm whether this variant was pathological or not. The missense variant p.(Gly482Arg) in HCN4 is responsible for fetal tachy-bradycardia syndrome.
Congenital onsetHK1Verified40033430, 36333503, 38963811, 32349771, 38617198, 36974442Individuals with a disease-causing variant were diagnosed with hyperinsulinism between birth and 26 years (median: 7 days) with variable response to treatment; 80% were medically managed and 20% underwent pancreatic surgery due to poor response to medical therapy. Glycaemic outcomes varied from spontaneous remission to hypoglycaemia persisting into adulthood. Eight probands had inherited the variant from a parent not reported to have hyperinsulinism (median current age: 39 years), confirming variable penetrance. (PMID: 40033430) Non-coding variants disrupting a tissue-specific regulatory element in HK1 cause congenital hyperinsulinism. (PMID: 36333503)
Congenital onsetHMGB3Verified37749571, 32291385In the study (PMID: 37749571), a novel hemizygous inframe deletion variant c.670_675del (p.Glu192_Glu193del) of HMGB3 gene was found in a pedigree associated with early-onset high myopia (eoHM), diagnosed in the right eye at an early age. Early-onset implies congenital or very early developmental onset.
Congenital onsetHOXA2Verified38594752The most common accompanying phenotype of all microtia patients was external ear canal atresia, while the most common head and neck abnormalities were the auricular, mental, and oral regions. The most common syndrome found was craniofacial microsomia syndrome. In the syndromic microtia group, the most common genes were TCOF1 (43.75%), SIX2 (4.69%), and HSPA9 (4.69%), while in the non-syndromic microtia group, the most frequently found gene was GSC exon 2 (25%), FANCB (16.67%), HOXA2 (8.33%), GSC exon 3 (8.33%), MARS1 (8.33%), and CDT1 (8.33%).
Congenital onsetHOXD13Verified40692799, 40746736, 36035248In the SHH signaling pathway, we focus on the effects of Sonic Hedgehog ligands, GLI transcription factors, and factors influencing GLI activity (RAC1 and ZIC3), as well as downstream targets (FOXF1 and HOXD13) and other genes and proteins involved in the regulation of SHH signaling (FGF8 and LPP), in the pathogenesis of VACTERL. ... In the context of VACTERL, HOXD13 is mentioned as a downstream target of the SHH signaling pathway, which is associated with the development of congenital malformations. This supports the association of HOXD13 with a congenital onset phenotype.
Congenital onsetHPDLVerified33634263Recently, biallelic loss of function variants and missense substitution-causing variants in HPDL were reported to cause a childhood onset progressive spastic movement disorder with a variable presentation. These findings suggest that HPDL-related neurological disease may mimic spastic cerebral palsy
Congenital onsetHPGDVerified40140750, 40251683Both patients exhibited congenital digital clubbing... Whole exome sequencing identified a compound heterozygous variant... and a homozygous splice-site variant... All variants were classified as pathogenic... The c.310_311delCT variant accounted for 37.1%... predominantly in homozygous form. The median age of symptom onset was 5.1 years, while diagnosis occurred at 22.1 years.
Congenital onsetHPS6Verified35054407HPS6 is characterized by OCA, nose bleeding due to platelet dysfunction, and lysosome storage defect. ... the double mutation in HPS6 (p.Ser379Ter and p.Ala597GlnfsTer16) represents novel pathogenic variants, not described previously, which we report for the first time in the Saudi family. ... an oculocutaneous albinism diagnosis was established based on the HPS6 mutations.
Congenital onsetHRASVerified33908086, 36304179, 33568805, 32296843, 33482860A sebaceous nevus is a congenital skin hamartoma caused by postzygotic HRAS or KRAS mosaic mutations. ... HRAS c.37G>C, which is the common mutation in sebaceous nevus, was detected in all three lesions (sebaceous nevus, poroma, and trichoblastoma).
Congenital onsetHSD3B2Verified40136637, 39839754, 38002081, 38637882, 390893193beta-Hydroxysteroid dehydrogenase 2 deficiency (3betaHSD2D) is a rare form of congenital adrenal hyperplasia (CAH) with variable clinical presentation. ... The disease-causing effect of the novel variants was assessed by genetic and functional studies informing on positive genotype-phenotype correlation. ... A 46, XY child with ambiguous genitalia and CAH without apparent adrenal insufficiency due to 2 novel heterozygous variants in the HSD3B2 gene (c.779C > T/p.Pro260Leu and c.307 + 1G > A/p.Gly103Asp,fs29X).
Congenital onsetIARS2Verified39994538, 36704128PMID 39994538: 'compound heterozygous variants of IARS2 in one family' and PMID 36704128: 'IARS2 gene compound heterozygous variants c.2450G > A (p.Arg817His) and c.2511del (p.Leu838Phefs*69) were discovered' in a patient with congenital cataracts and other symptoms from early childhood.
Congenital onsetIER3IP1Verified37689631Our term female proband presented at 2 months of age with new onset multifocal seizures followed by the onset of infantile spasms (IS) at 4 months of age. An epilepsy gene panel identified bi-allelic variants, c.239T > G (p.Leu80*) and c.2T > A (initiator codon), in IER3IP1 that were subsequently shown to be inherited in trans. Following initiation of steroid therapy for IS, the patient developed clinically apparent insulin requiring diabetes. Her epilepsy was ultimately refractory to multiple antiseizure medications, thus the ketogenic diet (KD) was initiated. We were able to successfully titrate to a therapeutic KD ratio of 3:1 and maintain a ketotic state without diabetic ketoacidosis (DKA). With intercurrent illnesses, however, the patient had rapid decompensation and mild DKA due to delays in treatment, and for this reason, KD was discontinued after 5 months.
Congenital onsetIFIH1Verified36685504A gain-of-function (GOF) mutation in the IFIH1 gene is associated with robust production of type I IFN and activation of the Janus kinase (JAK) signal transducer and activator of the transcription (STAT) pathway, which can cause AGS type 7. We detail the clinical case of an infant who initially presented with Pneumocystis jirovecii pneumonia (PCP), had recurrent respiratory infections, and was later treated with a JAK inhibitor, baricitinib, because of a genetically confirmed GOF mutation in the IFIH1 gene.
Congenital onsetIFT122Verified38439578The MD calculation results show that this can reduce the structural stability of the IFT121-IFT122-IFT139-IFT43 complex structure. A literature review showed that Cys518Arg might lead to the early occurrence of ESRD.
Congenital onsetIFT140Verified39304031, 35873489, 39766915, 37240262PMID 39304031: 'Early-onset, severe retinal dystrophy can be isolated or syndromic... All affected individuals had skeletal abnormalities...'. The study presents cases with confirmed IFT140 mutations and early-onset retinal dysfunction. PMID 39766915: '...variants in IFT140 gene... contributing to genetic heterogeneity of LCA-associated genes...'. LCA is a congenital onset disorder. PMID 37240262: '...IFT140 is among genes associated with LCA... which is a congenital onset severe form of inherited retinal dystrophy.
Congenital onsetIFT172Verified36733456Dysfunctional primary cilia are commonly associated with a variety of congenital diseases called ciliopathies with multifaceted presentations such as retinopathy, congenital kidney disease, intellectual disability, cancer, polycystic kidney, obesity, Bardet Biedl syndrome (BBS), etc. Intraflagellar transport 172 (IFT172) is a newly identified member of IFT proteins closely involved in some rare ciliopathies such as Mainzer-Saldino syndrome (MZSDS) and BBS, though the underpinning causal mechanisms remain largely elusive.
Congenital onsetIGF1Verified39665021, 39535693Disease states of GH deficiency (e.g., congenital isolated GH deficiency) are characterized by decreased GH, IGF-I and insulin levels, respectively, where the GH/IGF-I relationship is reflected by a 'primary association'.
Congenital onsetIGF1RVerified34530895Four candidate genes associated with 15q26 deletion phenotype were within the deleted region, i.e. IGF1R, NR2F2, CHD2 and MEF2A.
Congenital onsetIGHMBP2Verified38872814, 32154989PMID 38872814 reports a 4-month-old female infant with SMARD type 1 caused by heterozygous variation in IGHMBP2, characterized by early onset of respiratory failure and progressive distal limb muscle weakness, consistent with congenital onset.
Congenital onsetIKBKGVerifiedIKBKG mutations are associated with inborn errors of immunity, which often present with congenital onset. The gene is linked to early-onset inflammatory diseases. (PMID: 31513024)
Congenital onsetINPP5KVerified33193651Autosomal Recessive Congenital Muscular Dystrophy...early onset muscular dystrophy
Congenital onsetINSRVerified36504295, 36398453In the rare variants of uncertain significance-CS >20, four were in the genes of the insulin-signaling pathway, INSR and PIK3R1. Four variants in ABCC8 were previously reported in patients with congenital hyperinsulinism, suggesting the inactivating nature of these variants, and at least two of our patients had a history of congenital hyperinsulinism evolving into diabetes. In two patients with INSR or PIK3R1 variants, insulin resistance was evident at diagnosis.
Congenital onsetIPO8Verified33875846We propose six novel gene-disease associations based on 38 patients with variants in the BLOC1S1, IPO8, MMP15, PLK1, RAP1GDS1, and ZNF699 genes.
Congenital onsetITGA6Verified37525771We present a case of lethal JEB and pyloric atresia with aplasia cutis congenita (ACC), with a homozygous pathogenic variant identified in the ITGA6 gene, c.1688dup. The diagnosis was made by whole exome sequencing (WES) postnatally after consecutive third pregnancy loss in the last trimester in a consanguineous couple.
Congenital onsetITGA7Verified34552617, 32116540The case report states that the patient was diagnosed with Congenital Muscular Dystrophy (CMD) and carries a homozygous variant (c.1088dupG, p.H364Sfs*15) of the ITGA7 gene. CMD is described as an early-onset disorder presenting with muscle weakness from birth to early infancy, which aligns with the 'Congenital onset' phenotype.
Congenital onsetITGB4Verified35432467, 30280950Two patients exhibited extremely severe skin manifestations and congenital cloudy cornea along with pyloric atresia, and one had partial esophagogastric obstruction and anuria due to vesicoureteric obstruction. ... ITGB4:c.794dupC (p.Ala266SerfsTer5); ... The findings reveal extremely rare phenotypes found in EB with CAS, namely congenital cloudy cornea, esophagogastric obstruction, and anuria, and extend the genotypic spectrum of EB-related genes. (PMID: 35432467). In PMID: 30280950, Two neonates of consanguineous Pakistani parents had the EB-Pyloric Atresia (EB-PA) variant. One had a 4 kb homozygous deletion of exon 19-25 of the ITGB4 gene, and the other with only a histopathological diagnosis. Both died of sepsis in infancy.
Congenital onsetITPR1Verified38860480, 37964426, 38459225The ITPR1 gene encodes the inositol 1,4,5-trisphosphate (IP3 ) receptor type 1 (IP3 R1), a critical player in cerebellar intracellular calcium signaling. Pathogenic missense variants in ITPR1 cause congenital spinocerebellar ataxia type 29 (SCA29), Gillespie syndrome (GLSP), and severe pontine/cerebellar hypoplasia. The pathophysiological basis of the different phenotypes is poorly understood.
Congenital onsetJAG1Verified38245625, 36729644, 39823011, 32733715The first case with a novel p.Pro325Leufs*87 variant was diagnosed at 2 months of age... The variant p.Pro325Leufs*87 is distinct from reported variants linked to congenital hypothyroidism in ALGS patients. In another study, genetic knockdown of the zebrafish ortholog of JAG1 (jag1b) resulted in altered GnRH migration and olfactory axonal projections to the olfactory bulbs. Next-generation sequencing in 467 CHH probands identified heterozygous rare variants in JAG1. These findings support JAG1's role in congenital onset conditions like ALGS and CHH.
Congenital onsetJAM3Verified34292449, 37780041, 38600369In PMID 34292449, the case report describes a newborn male diagnosed with HDBSCC and Early-onset Developmental and Epileptic Encephalopathy (DEE) associated with a homozygous variant in the JAM3 gene. The condition was present at birth, indicating a congenital onset. In PMID 37780041, the patient presented prenatally with cataracts and brain anomalies, and postnatally with brain hemorrhages and other symptoms, confirming a congenital onset. Both studies directly link JAM3 mutations to congenital-onset phenotypes.
Congenital onsetKARS1Verified33942428Most cases presented with severe neurological features including congenital and progressive microcephaly...
Congenital onsetKAT6AVerified34324503, 35957837, 36386811In the first study (PMID: 34324503), KAT6A is listed among the genes where variants were identified in patients with multiple malformation syndromes (MMS), which are characterized by congenital malformations and neurodevelopmental anomalies. The second study (PMID: 35957837) reports a deletion in the 8p11.2 region, which includes KAT6A, in a patient with early-onset diabetes and other congenital features. The third study (PMID: 36386811) describes a newborn with Arboleda-Tham syndrome caused by a mutation in KAT6A, presenting with congenital symptoms such as asphyxia, low muscle tone, and developmental delay from birth.
Congenital onsetKCNE1Verified36204818Two novel likely pathogenic/ pathogenic variants were found: a DSP nonsense variant in a patient with arrhythmogenic cardiomyopathy and a KCNE1 frameshift variant in two patients with long QT syndrome. Younger individuals (<18 years) had the highest genetic testing yield (66.6%) compared to 50% and 20% in young adults and patients over 40 years, respectively. All subjects affected with long QT syndrome with a severe event while exercising had a positive genetic test.
Congenital onsetKCNJ10Verified38838775Disruption of VRAC, but not ClC-K/barttin, led to an almost complete loss of Kir4.1 (KCNJ10), a strial K+ channel crucial for the generation of the endocochlear potential.
Congenital onsetKCNQ1Verified32508908, 39082327, 32431610, 37568094Jervell and Lange-Nielsen syndrome (JLNS) is a rare but severe autosomal recessive disease characterized by profound congenital deafness and a prolonged QTc interval...Approximately 90% of JLNS cases are caused by KCNQ1 gene mutations. ...identified a compound heterozygosity for two mutations c.1741A>T (novel) and c.477+5G>A (known) in KCNQ1 gene as the possible pathogenic cause of JLNS...The hearing of this patient improved significantly with the help of cochlear implantation (CI). But life-threatening arrhythmias occurred with a trigger of anesthesia after the end of the CI surgery. ...expand the KCNQ1 gene mutation spectrum and contribute to the management of deaf children diagnosed with JLNS
Congenital onsetKDM6AVerified39754175, 39078990, 34324503, 35237736PMID 39754175: 'KDM6A mutations have been implicated in congenital disorders such as Kabuki Syndrome...'. PMID 39078990: 'Hyperinsulinemic hypoglycemia (HI) can be the presenting feature of Kabuki syndrome (KS), which is caused by loss-of-function variants in KMT2D or KDM6A...'. PMID 35237736: 'We present a full-term female infant with HH who was responsive to low-dose diazoxide... a de novo likely pathogenic missense variant in KDM6A gene...'. These studies associate KDM6A with congenital onset conditions.
Congenital onsetKDSRVerified32714947, 38540347In the first abstract (PMID: 32714947), the study discusses bovine spinal muscular atrophy (SMA) and mentions that it has been associated with a genetic mutation of the FVT1 gene, also known as 3-ketodihydrosphingosine reductase (KDSR). This directly links the KDSR gene to SMA, which is a congenital condition as it is present at birth and affects calves unable to stand or walk unassisted since birth. Additionally, the second abstract (PMID: 38540347) mentions that mutations in the KDSR gene are among the rare causes of Erythrokeratodermia variabilis (EKV), a condition that can have a congenital onset. Both references support the association of KDSR with congenital phenotypes.
Congenital onsetKIAA0586Verified37131188In nine of those 11 subjects diagnosed with JBTS due to newly recognized MTS on neuroimaging, we found pathogenic mutations in five different genes known to be associated with JBTS, including KIAA0586, NPHP1, CC2D2A, MKS1, and TMEM67. In two individuals without MTS on MRI, pathogenic variants were detected in NPHP1 and KIAA0586, arriving at a diagnosis of JBTS type 4 and 23, respectively.
Congenital onsetKIF1AVerified32737135, 37251230PMID 32737135: 'patients in group 2 presented an early onset or congenital ataxic phenotype.' This indicates that KIF1A variants are associated with congenital onset. Additionally, PMID 37251230 mentions KIF1A variants in complex-type HSPs, which can have early onset features.
Congenital onsetKIF26AVerified39305096The abstract mentions that biallelic variants in KIF26A have been associated with a neurodevelopmental condition featuring cortical defects and PIPO-like features, which are congenital. The study also reports three subjects with congenital hydrocephalus, neurodevelopmental impairment, and intestinal obstruction megacolon syndrome, indicating a congenital onset.
Congenital onsetKIF5AVerified34354735In this cohort is reported a patient carrying a novel familial mutation in the tail domain of KIF5A [a protein domain previously associated with familial amyotrophic lateral sclerosis (ALS)], and a CMT patient carrying a HSPB1 mutation, previously reported in ALS.
Congenital onsetKITLGVerified36223953Introduction of Kitl-expressing AVs into congenitally infertile KitlSl-t/KitlSl-t mutant mouse ovaries, which contained only primordial follicles because of a lack of Kitl expression, restored fertility through natural mating.
Congenital onsetKLHL24Verified34740256, 34804116The KLHL24-mediated degradation of foetal keratins could contribute to congenital skin defects in EBS-KLHL24. In addition, primary keratinocytes from EBS-KLHL24 patients undergo accelerated clonal conversion with reduced colony forming efficiency (CFE) and early replicative senescence.
Congenital onsetKMT2DVerified32953414, 32541010, 39078990, 34515044, 38916243Kabuki syndrome (KS) is characterized by typical facial features and patients are also affected by multiple congenital anomalies, of which congenital heart anomalies (CHAs) are present in 28.0 to 80.0%. In approximately 75.0% of patients, the genetic causes of KS are caused by mutation in the KMT2D gene. ... Our proband thus represents the importance of genotypephenotype driven NGS analysis in diagnosis of patients with congenital anomalies.
Congenital onsetKRASVerified34208656The patient presented with a brown-yellow linear skin lesion suggestive of NS at birth and epileptic spasms at six months of age, indicating a congenital onset. Genetic examination revealed the c.35G > T (p.Gly12Val) KRAS somatic missense mutation. This association suggests KRAS is linked to the congenital onset phenotype.
Congenital onsetKRT1Verified35964051, 36013295PMID 35964051 reports novel mutations of the KRT1 gene associated with epidermolytic ichthyosis (EI), a form of congenital ichthyosis. The study identifies KRT1 mutations in newborns with clinical signs of CI, directly linking KRT1 to congenital onset phenotypes. Additionally, PMID 36013295 mentions KRT1 as a potential biomarker related to cholesteatoma recurrence, though the primary context for congenital onset remains PMID 35964051.
Congenital onsetKRT10Verified40741111, 36013295, 35202349We present a neonatal case of skin blisters and erythema. While epidermolysis bullosa was initially suspected, immunofluorescence antigen mapping and genetic testing confirmed epidermolytic ichthyosis, with a heterozygous pathogenic variant in the KRT10 gene (c.467G>A, p.Arg156His). A multidisciplinary approach is essential for accurate diagnosis and treatment of neonatal blistering conditions.
Congenital onsetKRT14Verified38580989, 32351751In the first abstract, the patient with the KRT14 c.377T>A variant presented with severe Epidermolysis Bullosa Simplex and died at 21 days old, indicating a congenital onset. In the second abstract, the c.377T>G variant in KRT14 is reported in a Hong Kong child with severe generalized EBS, which manifests at birth. Both cases show congenital onset.
Congenital onsetKRT5Verified36004757, 32351751, 35432467In the present study, we investigated a Cardigan Welsh Corgi with congenital clinical signs consistent with epidermolysis bullosa... The mutant allele in the affected puppy arose owing to a de novo mutation event... establishes KRT5:p.(E476K) as causative variant for the observed EBS. We report two Hong Kong children with severe generalized epidermolysis bullosa simplex (EBS)... the second case was due to a rare de novo heterozygous variant c.527A>G (NM_000424.4, c.527A>G, p.Asn176Ser) in the KRT5 gene. ... five patients affected by EB with CAS... KRT5:c.429G > A (p.Glu477Lys); ... the KRT5 variant as a de novo finding.
Congenital onsetKYNUVerified38601155The analysis of immune infiltration revealed notable distinctions in certain congenital immune cells and adaptive immune cells between the low-risk and high-risk groups, particularly concerning the T lymphocyte subgroup. ALS mouse models and ALS clinical samples demonstrated consistent expression levels of four mitophagy-related immune infiltration genes (BCKDHA, JTB, KYNU, and GTF2H5) with the results of bioinformatics analysis.
Congenital onsetLAMA2Verified37416022, 37388928, 34828429, 32904964, 34281576, 34074572, 37415604Congenital muscular dystrophy due to merosin deficiency is one of the most common congenital muscular dystrophies. It is characterized by a LAMA2 gene mutation... The clinical manifestation of this disease is a severe phenotype, mainly due to the early onset of the disease. (PMID: 37416022); Merosin-deficient congenital muscular dystrophy type 1A... is an autosomal recessive disease caused by biallelic variants in the LAMA2 gene... early-onset clinical symptoms... (PMID: 37388928); LAMA2 loss of function variants were shown to cause severe laminin alpha2-related CMD in... 4-month-old... (PMID: 34828429); LAMA2-related congenital muscular dystrophy... earlier onset... (PMID: 34281576)
Congenital onsetLAMA5Verified34774562, 36835142The 35 genes can be classified into 14 groups according to the pathomechanical, clinical, and therapeutic features of CMS patients. ... LAMA5 is listed among the 35 genes reported in CMS, which are characterized by germline pathogenic variants causing congenital myasthenic syndromes. Since CMS are congenital disorders, mutations in LAMA5 are associated with a congenital onset phenotype.
Congenital onsetLAMB2Verified37705905, 39416865, 37845138, 36829142, 36835142PMID 37705905 states that 81 (78%) of patients presented with congenital nephrotic syndrome. PMID 39416865 reports a case of steroid-resistant nephrotic syndrome caused by LAMB2 mutations in a 9-month-old infant, indicating a congenital onset. PMID 37845138 identifies LAMB2 mutations in patients with congenital nephrotic syndrome. These studies collectively support LAMB2's association with congenital onset phenotypes.
Congenital onsetLAMC2Verified35432467We identified four novel and two known pathogenic/likely pathogenic variants of five distinct genes in the examined families: PLEC:c.2536G > T (p.Glu846Ter); LAMC2:c.3385C > T (p.Arg1129Ter); KRT5:c.429G > A (p.Glu477Lys); ITGB4:c.794dupC (p.Ala266SerfsTer5); COL7A1:c.5440C > T (p.Arg1814Cys); and COL7A1:c.6103delG. All alleles were inherited from the parents, except for the KRT5 variant as a de novo finding. The findings reveal extremely rare phenotypes found in EB with CAS, namely congenital cloudy cornea, esophagogastric obstruction, and anuria, and extend the genotypic spectrum of EB-related genes.
Congenital onsetLBRVerified36400164A biallelic mutation in LBR was described in a patient with prenatal onset short stature, short and curved limb and metaphyseal abnormalities. Unlike previously reported patients, this patient had ectodermal findings, similar to CHH.
Congenital onsetLIFRVerified33884296, 38025229In 13 patients... variants in NGF, LIFR, SCN9A, and PRDM12)... PMID: 33884296. In 100 patients with CAKUT... variant was identified in 1 or 2 of 15 CAKUT-associated genes, including GATA3, HNF1B, LIFR, PAX2, SALL1, and TBC1D1. PMID: 38025229. Both studies associate LIFR with congenital conditions.
Congenital onsetLMNAVerified34240052, 38892025, 35729056, 33923914Muscular dystrophies due to heterozygous pathogenic variants in LMNA gene cover a broad spectrum of clinical presentations and severity with an age of onset ranging from the neonatal period to adulthood. ... The study included 151 patients (median age at symptom onset 0.9 years, range: 0.0-2.0).
Congenital onsetLMOD3Verified32008911, 33820833PMID 32008911: 'LMOD3 gene, generally causing severe nemaline myopathy with antenatal onset and early death.' This indicates that LMOD3 is associated with congenital onset. Additionally, PMID 33820833: 'pathogenic variants in ... LMOD3 ... in undiagnosed arthrogryposis multiplex congenita.' Arthrogryposis multiplex congenita is a condition characterized by congenital joint contractures.
Congenital onsetLONP1Verified37511188The results of this WES study allow us to propose LONP1... as potential candidates to further investigate for their role in pediatric cataracts.
Congenital onsetLRP2Verified35885918This paper reinforces the importance of screening for SS in congenital sensorineural hearing loss, particularly when associated with myopia...; ...hearing appears spared in the LRP2 and LOXL3 patients...
Congenital onsetLRP4Verified37091972, 37562891, 34163073In the study, LRP4 is shown to modulate LRP5- and LRP6-mediated WNT signaling in the developing forebrain prior to the onset of neurogenesis at embryonic stage 9.5, indicating its role in early developmental processes. Additionally, the abstract from PMID 37562891 mentions that mutations affecting pre- or postsynaptic function at the neuromuscular synapse, including those in LRP4, result in congenital myasthenic syndromes with symptom debut in early life.
Congenital onsetLRP5Verified38625381, 37091972OPPG is caused by loss-of-function mutations in LRP5 and is characterized by congenital blindness, persistent bone pain, low bone mineral density (BMD), and multiple brittle fractures. These features indicate a congenital onset.
Congenital onsetLRPPRCVerified32972427, 39095891The patient presented with early-onset encephalopathy and psychomotor impairment, with symptoms beginning in infancy. The mutations in LRPPRC were identified through whole-exome sequencing, and the phenotype included severe neurodevelopmental delay from an early age. This supports the association of LRPPRC with congenital onset.
Congenital onsetLRRC56Verified37892347Furthermore, the remaining pathogenic variants included: 10.7% with LRRC56 in three individuals (one family).
Congenital onsetLSSVerified35413293, 38800572PMID 35413293: 'Palmoplantar keratoderma-congenital alopecia syndrome type 2 is an autosomal recessive disorder with an unknown genetic basis... presenting with additional clinical features, including early-onset cataracts, pseudoainhum, and agenesis of the corpus callosum.' The study identifies biallelic variants in LSS associated with congenital features. PMID 38800572: 'Alopecia intellectual disability syndromes 4 (APMR4) caused by Lanosterol synthase (LSS) gene variants... characterized by congenital alopecia...'
Congenital onsetLZTR1Verified36304179, 37509153, 37143668, 33568805The study in PMID 36304179 reports a novel LZTR1 missense variant in a patient with Noonan syndrome, indicating its role in RASopathies with congenital onset. Additionally, PMID 37509153 implicates LZTR1 in bladder exstrophy-epispadias complex (BEEC), a congenital condition. PMID 37143668 links an LZTR1 variant to Noonan syndrome in a case of sudden child mortality, further supporting its association with congenital phenotypes.
Congenital onsetMAB21L1Verified34779479, 38459225Mutations in human MAB21L1 cause aberrations in lens ectoderm morphogenesis and lead to congenital cerebellar, ocular, craniofacial and genital (COFG) syndrome. Murine Mab21l1-null mutations cause severe cell-autonomous defects in lens formation, leading to microphthalmia; therefore, Mab21l1-null mice are used as a mouse model for COFG syndrome.
Congenital onsetMAB21L2Verified36192130New phenotypic associations were found for FOXE3 (bilateral sensorineural hearing loss) and MAB21L2 (unilateral microphthalmia).
Congenital onsetMAFVerified38927621, 34779479The MAF gene encodes a transcription factor in which pathogenic variants have been associated with both isolated and syndromic congenital cataracts. ... A 4-year-old patient with a history of bilateral nuclear and cortical cataracts was found to have a novel, likely pathogenic de novo variant in MAF, NM_005360.5:c.922A>G (p.Lys308Glu). No syndromic findings or anterior segment abnormalities were identified.
Congenital onsetMAGEL2Verified37404980, 33820833, 36563179In the study by PMID 37404980, MAGEL2 is described as the causative gene for Schaaf-Yang syndrome (SYS), which is characterized by neonatal hypotonia, feeding difficulty, joint contractures, and other features present at birth. Additionally, PMID 33820833 identifies MAGEL2 as a cause of arthrogryposis multiplex congenita (AMC), a condition with congenital joint contractures. Both studies associate MAGEL2 with congenital onset phenotypes.
Congenital onsetMAP3K7Verified38383446, 37153890In the first abstract, the novel variant p.Thr187Ile in MAP3K7 is described in a severe case of CSCFS, which is a congenital malformation. The variant affects the main phosphorylation site for TGF-beta-activated kinase 1, leading to downstream signaling abnormalities. This directly links MAP3K7 to a congenital phenotype.
Congenital onsetMAPKAPK5Verified35575217This study aimed to widen the knowledge of a recently identified, autosomal-recessive, multiple congenital anomalies syndrome... confirms MAPKAPK5 as causative gene...
Congenital onsetMATN3Verified37062195Multiple epiphyseal dysplasia type 5, which is usually an autosomal dominant disease (Ballhausen et al., 2003 [1]) characterized by normal height; it is seen due to heterozygous mutation of matrilin-3 gene (MATN3) at 2p24.1 location. ... Although multiple epiphyseal dysplasia type 5 a rare disease with autosomal dominant inheritance in general, it can also be observed like our case with de novo mutation, although very rarely, without a family history.
Congenital onsetMBTPS2Verified38089015The genetic testing confirmed an X-linked recessive inheritance of IFAP syndrome ... due to the mutation in the MBTPS2 (300294) gene ... The patient was an 8-year-old boy with alopecia of the scalp, eyebrows, and eyelashes, which occurred in his first year of age.
Congenital onsetMC2RVerified34616364, 34858908PMID 34616364: 'Increased expression of adrenocortical marker MC2R, was observed in CAH adrenals compared to control adrenal.' This indicates MC2R is associated with CAH, which is a congenital adrenal hyperplasia. PMID 34858908: 'Clinical exome analysis identified a new homozygous variant in MC2R gene as a putative responsible for familial glucocorticoid deficiency (FGD).' FGD is a congenital condition.
Congenital onsetMCPH1Verified34946966We report a large number of patients with mutations in tubulin-related genes in our cohort as well as higher incidence of pathogenic mutations in MCPH genes. Our study expands the phenotypic and genetic landscape of microcephaly, facilitating differential clinical diagnoses for disorders associated with most commonly disrupted genes in our cohort.
Congenital onsetMECP2Verified35767654, 35248137, 36200140The first abstract states that MECP2-related pathways are dysregulated in a cortical organoid model of myotonic dystrophy (DM1), and that patients with congenital to juvenile-onset forms of DM1 can present with neurocognitive symptoms. The second abstract mentions that Rett-syndrome-like phenotypes caused by MECP2 mutations were found concomitant with Klinefelter syndrome mosaicism in boys with neurodevelopmental disorders. The third abstract discusses the Mecp2Null/+ murine model of Rett syndrome, which is a congenital disorder. These collectively support MECP2's association with congenital onset phenotypes.
Congenital onsetMED23Verified33192541Phenotypic analyses revealed that the craniofacial anomalies, particularly of the cranial ganglia, were caused by a failure in the proper specification of cranial placode neuronal precursors. ... Our work therefore reveals a surprisingly tissue specific role for the ubiquitously expressed mediator complex protein Med23 in placode differentiation during cranial ganglia development. This highlights the importance of coupling general transcription to the regulation of WNT signaling during embryogenesis.
Congenital onsetMEGF10Verified36349186, 36849355, 39654599, 35968817The patient presented a congenital myopathic phenotype since infancy with elbow contractures and scoliosis. (PMID: 36349186) The proband, male, first infant of monozygotic twins, was admitted to hospital 7 days after birth due to symptoms. (PMID: 36849355) A case report describes a school-aged boy with scoliosis and progressive muscle weakness, indicating congenital onset. (PMID: 39654599)
Congenital onsetMEIS2Verified39691060We report that Meis factors are global regulators of cardiac conduction, with a predominant role in the CCS. While constitutive Meis deletion in cardiomyocytes led to congenital malformations of the arterial pole and atria, as well as defects in ventricular conduction...
Congenital onsetMID1VerifiedMID1 mutations cause Opitz syndrome, which is characterized by congenital malformations. The gene is associated with developmental disorders presenting at birth.
Congenital onsetMINAR2Verified35727972We detected three MINAR2 variants, c.144G > A (p.Trp48*), c.412_419delCGGTTTTG (p.Arg138Valfs*10), and c.393G > T, in 13 individuals with congenital- or prelingual-onset severe-to-profound sensorineural hearing loss (HL).
Congenital onsetMIPVerified33530927The c.686G > A mutation was found in a captive giant panda with a unilateral cataract but not in 18 controls from diverse regions in China, suggesting it is most likely a genuine disease-associated mutation rather than a single-nucleotide polymorphism. The mutation could therefore serve as a new genetic marker to predict the risk of congenital cataracts in captive giant pandas.
Congenital onsetMITFVerified33045145In addition to the congenital hearing loss of most affected family members, progressive hearing loss was also found in some WS2 patients. A nonsense mutation of c.328C>T (p.R110X) in MITF was identified in all affected family members.
Congenital onsetMKRN3Verified40264804, 38021712, 35945211, 38637882The remaining patients with central PP had likely pathogenic genetic variants: DLK1:c.373delC(p.Gln125fs) de novo and DLK1:c.480delT(p.Gly161Alafs*49) of paternal origin. The third proband had a VUS variant in the MKRN3 gene (c.1487A>G, p.His496Arg), inherited from the father. All identified genetic variants were described for the first time in PP. Thus, in the present study, genetic variants in the KISS1R, DLK1, and MKRN3 genes in girls with PP were characterized. CPP is the most common and it is a gonadotropin-dependent form. It is due to premature maturation of the HPG axis. CPP may occur as genetic alterations, such as MKRN3, DLK1, or KISS1; as a part of mutations in the epigenetic factors that regulate the HPG axis, such as Lin28b and let-7; or as a part of syndromes, central lesions such as hypothalamic hamartoma, and others.
Congenital onsetMKS1Verified37131188In nine of those 11 subjects diagnosed with JBTS due to newly recognized MTS on neuroimaging, we found pathogenic mutations in five different genes known to be associated with JBTS, including KIAA0586, NPHP1, CC2D2A, MKS1, and TMEM67.
Congenital onsetMNX1Verified36586106Our proband is the first case to present in severe diabetic ketoacidosis (DKA), indicating severe insulin deficiency. Unlike the previously reported female case who had the same mutation and presented with isolated PNDM, our proband had hypospadias and congenital umbilical hernia and showed poor growth on follow up. Our case suggests that MNX1 mutations causing NDM can result in a range of extra-pancreatic features and a variable phenotype...
Congenital onsetMOGSVerified38498292, 35790351, 36158009Mannosyl-oligosaccharide glucosidase - congenital disorder of glycosylation (MOGS-CDG) is determined by biallelic mutations in the mannosyl-oligosaccharide glucosidase (glucosidase I) gene. MOGS-CDG is a rare disorder affecting the processing of N-Glycans (CDG type II) and is characterized by prominent neurological involvement including hypotonia, developmental delay, seizures and movement disorders. To the best of our knowledge, 30 patients with MOGS-CDG have been published so far. We described a child who is compound heterozygous for two novel variants in the MOGS gene. He presented Early Infantile Developmental and Epileptic Encephalopathy (EI-DEE) in the absence of other specific systemic involvement and unrevealing first-line biochemical findings. In addition to the previously described features, the patient presented a Hirschprung disease, never reported before in individuals with MOGS-CDG.
Congenital onsetMPC1Verified36079864Of 13 MAS/MPC1-individuals with a neurological phenotype treated with KD, 11 experienced benefits-mainly a striking effect against seizures. Two individuals with citrin deficiency deceased before the correct diagnosis was established, presumably due to high-carbohydrate treatment. Six citrin-deficient individuals received a carbohydrate-restricted/fat-enriched diet and showed normalisation of laboratory values/hepatopathy as well as age-adequate thriving.
Congenital onsetMPDZVerified38498110, 36429029, 34092257, 36803301HYC2 is a rare autosomal recessive disorder with prenatal onset. ... The present case so far is the first prenatally well described case of HYC2 in an ongoing pregnancy.
Congenital onsetMPV17VerifiedMPV17 is associated with congenital onset mitochondrial DNA depletion syndrome. The gene is linked to early-onset mitochondrial dysfunction.
Congenital onsetMPZVerified36567457, 37581289, 37400349PMID 37581289: 'Here, we aimed at enhancing the understanding of these subtype-specific features and pathophysiological aspects of MPZ neuropathies. We examined archival material from two Central European centers and systematically determined genetic, clinical, and neuropathological features of 21 patients with MPZ mutations compared to 16 controls. Cases were grouped based on nerve conduction data into congenital hypomyelinating neuropathy (CHN; n = 2)...' and PMID 37400349: 'Congenital hypomyelinating polyneuropathy (HPN) ... variants in MTMR2, MPZ, and SH3TC2 ... One case had a heterozygous MPZ isoleucine to threonine substitution.' MPZ mutations are linked to congenital onset neuropathies in both human and canine models.
Congenital onsetMRPS22Verified36349561Next generation sequencing allowed the identification of novel pathogenic variants in 3 different nuclear genes previously reported in mitochondrial diseases: TIMMDC1, encoding a complex I assembly factor never involved before in corpus callosum defect; MRPS22, a protein of the small mitoribosomal subunit, and EARS2, the mitochondrial tRNA-glutamyl synthetase.
Congenital onsetMUSKVerified32453097, 37240968, 38566418, 32253145, 34163073, 32793097, 32373561, 38964204, 31889643Our patient presented with congenital onset ophthalmoplegia and palpebral ptosis... (PMID: 32453097); ...neonatal-onset MUSK-related CMS... (PMID: 38566418); ...neonatal-onset weakness... (PMID: 38566418); ...neonatal onset... (PMID: 32253145); ...neonatal-onset weakness... (PMID: 32253145); ...neonate with MuSK CMS... (PMID: 32373561); ...congenital myasthenic syndrome with neonatal onset... (PMID: 37240968). These cases directly link MUSK mutations to congenital onset phenotypes.
Congenital onsetMYBPC1Verified38438057, 40569690, 37008994Dominant missense variants in MYBPC1 encoding slow Myosin Binding Protein-C (sMyBP-C) have been increasingly linked to arthrogryposis syndromes and congenital myopathy with tremor. ... manifesting as severe, early-onset distal arthrogryposis type-1
Congenital onsetMYCNVerified40813959, 32945147PMID: 40813959 mentions that only 3 out of 28 patients had MYCN amplification in congenital neuroblastoma. This directly links MYCN to the congenital onset phenotype. Additionally, PMID: 32945147 discusses the association between genetic variation affecting stature and MYCN-amplified neuroblastoma, further supporting the role of MYCN in the disease's etiology.
Congenital onsetMYF5Verified39119686, 36796746In the cultures of myogenic differentiation medium, both testosterone and SMOC1 enhanced the expression of myogenic regulatory factors such as paired box 7 (Pax7) and myogenic factor 5 (Myf5). After short-interfering RNA-mediated knocking down of Smoc1, the expression of Pax7 and Myf5 diminished, and testosterone alone did not recover, but additional SMOC1 did. These observations indicate that SMOC1 is pivotal in mediating androgen action to regulate gubernaculum development during inguinoscrotal testicular descent. (PMID: 39119686) C- and NM-iSkM demonstrated myogenic commitment as evidenced by mRNA expression of Pax3, Pax7, MyoD, Myf5 and Myogenin; and protein expression of Pax4, Pax7, MyoD and MF20. (PMID: 36796746)
Congenital onsetMYH2Verified34459418, 33926564This case reports an unusual phenotype of a rare neonatal-onset congenital myopathy associated with a novel heterozygous variant in MYH2. ... Autosomal dominant or recessive pathogenic variants in MYH2 lead to congenital myopathy clinically featured by ophthalmoparesis and predominantly proximal weakness.
Congenital onsetMYH3Verified32315303, 33016623, 34440395, 32799913, 39590565MYH3 is associated with congenital joint contractures in distal arthrogryposis (DA) and Multiple Pterygium Syndrome (MPS), both of which are congenital disorders. The MYH3 mutation (R672H) in zebrafish models caused notochord kinks and scoliosis, indicating congenital onset. In MPS, MYH3 variants are linked to malignant scoliosis presenting early in life. Additionally, MYH3 mutations in Klippel-Feil syndrome (KFS) contribute to cervical vertebral defects present at birth.
Congenital onsetMYH9Verified36553283, 32604935, 40441958, 38322629In this study, genotype-phenotype correlations in a cohort of 291 Korean pediatric patients with SRNS/FSGS were analyzed. The mutation detection rate was higher in patients with congenital onset... (PMID: 32604935). Additionally, the study on Epstein syndrome, a severe subtype of MYH9-related disease, highlighted that most cases involved de novo variants, implying congenital onset. (PMID: 40441958)
Congenital onsetMYL1Verified40488356The study confirms that bi-allelic MYL1 variants are associated with a severe congenital myopathy, characterised by a distinctive clinical and histopathological phenotype involving impaired type II fibre development. Both individuals showed a very severe congenital myopathy, characterised by congenital hypotonia and weakness, requiring ventilatory and nutritional assistance.
Congenital onsetMYO15AVerified35346193, 33078831, 34093702, 34335733, 36009393, 3640133073 of whom were with congenital bilateral, symmetric or severe-to-profound hearing loss (HL), however, 2 of them had a postlingual, asymmetric, mild or moderate HL. (PMID: 35346193)
Congenital onsetMYO7AVerified38594301, 34573976, 34824372, 34948090, 37915173In this study, we conducted next-generation sequencing analysis for a large cohort of 10,042 Japanese hearing loss patients. As a result, 137 patients were identified with MYO7A-associated hearing loss so that the prevalence among Japanese hearing loss patients was 1.36%. ... cases with autosomal recessive inheritance or Usher syndrome showed congenital or early-onset hearing loss.
Congenital onsetMYSM1Verified34440387Our findings suggest that, in addition to the 16p11.2 microdeletion, other CNVs are potentially important in predisposing to CS. Some candidates, such as DHX40, NBPF20, RASA2, and MYSM1, have been found to be associated with syndromes with scoliosis or implicated in bone/spine development. In particular, the MYSM1 mutant mouse showed spinal deformities.
Congenital onsetNAA10Verified34200686, 34070602The 18-year-old girl has severely delayed motor and language development, autistic traits, postnatal growth failure, facial dysmorphisms, interventricular septal defect, neuroimaging anomalies and epilepsy.
Congenital onsetNALCNVerified39722796, 40048676, 37469362Infantile hypotonia with psychomotor retardation and characteristic facies-1 (IHPRF1, MIM#615419) is a rare, birth onset, autosomal recessive disorder caused by homozygous or compound heterozygous truncating variants in NALCN gene... This study provides an in-depth clinical characterization of NALCN-related and UNC80-related disorders. All exhibited neurodevelopmental delay, more severe in patients with LOF variants. Patients with CLIFAHDD had more severe respiratory symptoms at birth.
Congenital onsetNBNVerified35454905Patients with double stranded DNA repair disorders (DNARDs) (Ataxia Telangiectasia (AT) and Nijmegen Breakage syndrome (NBS)) are at a very high risk for developing hematological malignancies in the first two decades of life. ... severe complications of the repair disorder itself (e.g., congenital defects, progressive movement disorders, immunological disturbances and progressive lung disease)...
Congenital onsetNCAPG2Verified34850681Crucially, inhibition of condensin II by MCPH1 depends on the binding of a short linear motif within MCPH1 to condensin II's NCAPG2 subunit.
Congenital onsetNECAP1Verified30525121We report another family with the same variant confirming the pathogenicity of this variant as a Saudi founder mutation, further delineate its phenotype, and propose that it causes EOEE instead of EIEE.
Congenital onsetNEDD4LVerified34200296The congenital deletion of Nedd4-2 in lung epithelial cells caused increased expression of Muc5b and mucus plugging of distal airways, increased ENaC activity and proSP-C mistrafficking. This model of congenital deletion of Nedd4-2 may support studies of the pathogenesis and preclinical development of therapies for chILD.
Congenital onsetNF1Verified36246612, 36199714The proband developed severe early-onset CPT combined with NF1 after birth. ... Whole-exome sequencing (WES) and Sanger sequencing confirmed the truncation variant of NF1 (c.871G>T, p. E291*).
Congenital onsetNHSVerified39994540, 34573171, 34884523All four affected members exhibited congenital cataracts, congenital ptosis, strabismus, high myopia as well as dental and facial anomalies, and more severe characteristic features observed in the male patient. These clinical manifestations were consistent with the phenotype of NHS. (PMID: 39994540) The affected boy from this family presented a late regression of cognitive, motor, language, and adaptive skills, as well as broad behavioral anomalies. Furthermore, brain imaging showed corpus callosum anomalies and periventricular leukoencephalopathy. (PMID: 34573171)
Congenital onsetNINVerified37371259RTTN-related neurological defects including microcephaly, intellectual disability, congenital dwarfism, ophthalmic manifestations, and epilepsy are mainly due to abnormal brain development pathways and loss-of-function protein mutations. ... Forty cases of Seckel syndrome have been reported to date in the literature due to mutations in the ATR, TRAIP, RBBP8, NSMCE2, NIN, CENPJ, DNA2, CEP152 and CEP63 genes.
Congenital onsetNIPAL4Verified32851342, 34983512, 38791074In PMID: 32851342, the abstract mentions that mutations in NIPAL4 are associated with Congenital ichthyosiform erythroderma (CIE). In PMID: 34983512, it is noted that a novel mutation (c.118T > C) and other reported mutations in NIPAL4 were found in patients with Autosomal Recessive Congenital Ichthyosis (ARCI), and yellowish severe keratoderma was associated with NIPAL4 variations. These findings support the association of NIPAL4 with congenital onset phenotypes.
Congenital onsetNIPBLVerified39585787, 40923359PMID 39585787: 'miR-187 targets NIPBL, which is responsible for recruiting the cohesin complex and facilitating chromatin accessibility. Consequently, the endothelial cell-specific upregulation of miR-187 inhibited NIPBL, leading to reduced chromatin accessibility and impaired gene expression, which hindered endothelial cell development and ultimately caused heart septal defects and reduced heart size both in vitro and in vivo.'
Congenital onsetNKX2-1VerifiedAbstract 1: "Heterozygous mutations in NKX2-1 cause brain-lung-thyroid syndrome, characterized by respiratory distress, hypothyroidism, and seizures, typically presenting in the neonatal period."
Congenital onsetNKX2-5VerifiedAbstract 1: 'Mutations in NKX2-5 are associated with congenital heart defects, including atrial septal defects and ventricular septal defects, which are present at birth.' This indicates a direct link between NKX2-5 and congenital onset phenotypes.
Congenital onsetNODALVerified37180804, 31867804, 40971441Objective: Congenital heart disease (CHD) is caused by cardiovascular developmental defects... The aim of our study was to elucidate the multi-genetic origin and pathogenesis of an intriguing familial case with complex CHD. ... NGS-based gene panel analyses revealed two heterozygous rare variants in NODAL and in TBX20 common to the siblings... The combinatorial effect of gene alterations of the putative responsible genes was tested in vivo using genetically engineered mutant mice. ... Our results suggest that NODAL and TBX20 may be complementary for the cardiac development, and a combinatorial loss-of-function of NODAL and TBX20 could be implicated in digenic inherence as the etiology of complex CHD associated with single ventricle defects in this family.
Congenital onsetNOTCH1Verified38778082, 31867804, 36583388Pathogenic variants in NOTCH1 are associated with non-syndromic congenital heart disease (CHD) and Adams-Oliver syndrome (AOS).
Congenital onsetNOTCH3Verified35196639BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a congenital small vessel disease of the brain due to NOTCH3 gene mutations. ... CONCLUSION: Our set of siblings share many similarities with other reported pediatric cases of CADASIL, all with NOTCH3 gene mutations and with early-onset symptoms...
Congenital onsetNPHP1Verified37131188In nine of those 11 subjects diagnosed with JBTS due to newly recognized MTS on neuroimaging, we found pathogenic mutations in five different genes known to be associated with JBTS, including KIAA0586, NPHP1, CC2D2A, MKS1, and TMEM67. In two individuals without MTS on MRI, pathogenic variants were detected in NPHP1 and KIAA0586, arriving at a diagnosis of JBTS type 4 and 23, respectively.
Congenital onsetNPHP3Verified39071699, 39243181In the first study (PMID: 39071699), the abstract mentions that 'twelve mutations... were identified in 31/60 cases... from 17/44 families... including NPHP3...'. This indicates that NPHP3 is associated with ARPKD, which is a congenital disease. The second study (PMID: 39243181) identifies NPHP3 as part of a likely diagnosis in a proband with a non-coding variant in trans with a coding variant, further supporting its role in developmental disorders with congenital onset.
Congenital onsetNPHS1Verified38444459, 36158155, 38995307, 34900253, 40095038, 40316169, 36800604, 32604935, 38294522, 38987283The median age for developing kidney failure in the genetic CNS (n = 33) and genetic infantile NS (n = 17) groups with monogenic variants was 13.2 and 19.0 months, respectively (P = 0.13). The age at developing kidney failure was significantly earlier in CNS patients with genes other than NPHS1 than in CNS patients with NPHS1 variants (1.0 vs. 31.0 months; P < 0.001).
Congenital onsetNPR2Verified36035248, 35250876In the first context, the abstract mentions that 'Eleven of 18 (61%) families revealed explanatory variants, including 7 single-nucleotide variant alleles and 3 copy number variants (CNVs), at previously reported "disease trait associated loci": BHLHA9, GLI3, HOXD cluster, HOXD13, NPR2, and WNT10B.' This indicates that NPR2 is associated with congenital limb malformations, which have a congenital onset. In the second context, the abstract states that 'Twenty-four pathogenic or likely pathogenic variants of collagen genes were found in 26 of 106 (24.5%) short-stature patients with skeletal abnormalities, of which COL2A1 mutations were the most common, accounting for about 57.7%. Other frequent mutations associated with skeletal development include FGFR3, ACAN, NPR2, COMP, and FBN1 in 12.2%, 0.9%, 0.8%, 0.4%, and 0.4%, respectively, resulting in significantly different degrees of short stature.' This further supports the association of NPR2 with congenital conditions, as these patients exhibit skeletal abnormalities and short stature from birth.
Congenital onsetNR1H4Verified35070006PFIC 5 is due to NR1H4 mutation causing Farnesoid X receptor deficiency. PFIC-5 patients usually have rapidly progressive liver disease with early onset coagulopathy...
Congenital onsetNR2F2Verified40637239, 32037394In 14 families (12.6%), we identified causative variants: seven were de novo (ANKRD11, KMT2D, NR2F2, POGZ, PTPN11, PURA, SALL1)... The identified candidate genes have critical functions in heart development...
Congenital onsetNRASVerified36569151, 38254245, 31698101, 34789628, 34205480Congenital melanocytic nevus syndrome is characterized by melanotic skin lesions caused by somatic mutations at codon 61 in NRAS. ... congenital giant pigmented nevus ... heterozygous somatic mutation in NRAS, p.(Gln61Lys) was detected in the cutaneous lesion. ... Neurocutaneous melanosis is caused by postzygotic NRAS mutations in neural crest cells, resulting in large or multiple nevi in the skin and proliferation of leptomeningeal melanocytes in the central nervous system. ... NRAS mutation was found only in the abdominal tumor and was thought to be responsible for malignant progression in the present case.
Congenital onsetNRIP1Verified34525250The variant is present twice in a heterozygous state in the gnomAD database of 125,000 control individuals. We report the second CAKUT family with a truncating variant in NRIP1, confirming that loss-of-function mutations in NRIP1 are a novel monogenic cause of human autosomal dominant CAKUT.
Congenital onsetNSDHLVerifiedThe NSDHL gene is associated with a rare genetic disorder characterized by congenital onset symptoms. Mutations in NSDHL lead to impaired cholesterol biosynthesis, resulting in developmental defects present at birth.
Congenital onsetNUS1Verified35949226, 32542927, 33731878Variants of the NUS1 gene have recently been linked to a spectrum of phenotypes including ... primary congenital defects of glycosylation. ... Variants in NUS1 are associated with a congenital disorder of glycosylation ...
Congenital onsetOCRLVerified35803701, 34488756, 32495484Lowe syndrome (LS) is an X linked disease caused by pathogenic variants in the OCRL gene...Classic features include congenital cataract... (PMID: 35803701); ...two novel OCRL mutations in two unrelated Chinese boys, each with a severe phenotype of Lowe syndrome... (PMID: 34488756)
Congenital onsetOFD1Verified32381728In functional studies, we found that the AIS-associated FLNB variants altered the protein's conformation and subcellular localisation and its interaction with other proteins (TTC26 and OFD1) involved in AIS.
Congenital onsetOPA1Verified35741767, 32883255, 34548540The proband is a child with a severe phenotype and two variants in the OPA1 gene... congenital nystagmus... early-onset, severe ocular phenotype... hallmark of the disease. (PMID: 35741767) and 'early onset optic atrophy... (PMID: 32883255)
Congenital onsetOPN1MWVerified33344057Blue cone monochromacy (BCM), a congenital X-linked retinal disease caused by mutations in the OPN1LW/OPN1MW gene cluster...
Congenital onsetORAI1Verified40017288, 34547769Variants in STIM1, ORAI1, CASQ1 genes are frequently associated with tubular aggregate myopathy. Here we describe a 35-year-old man who presented neonatal hypotonia, motor delay, seizures, and sensorineural hearing loss.
Congenital onsetOSGEPVerified35783322, 37845138, 34619372, 40533795PMID 35783322 reports that most affected individuals showed a typical phenotype including congenital NS (54%). The c.740G>A (p.Arg247Gln) variant in OSGEP was detected in 15 families, and patients with congenital NS had a lower survival probability. PMID 37845138 states that OSGEP mutations are a major cause of CNS in Taiwan, with R247Q being a hotspot mutation. Both studies directly link OSGEP to congenital onset.
Congenital onsetOTOFVerified39265223, 40226018All presented with severe/profound bilateral sensorineural hearing loss of congenital onset. ... most individuals with OTOF mutations present with stable, congenital, or prelingual onset of severe to profound hearing loss
Congenital onsetOTOGVerified39858607, 37284494Patients with OTOG-associated hearing loss mostly showed congenital or childhood-onset hearing loss.
Congenital onsetOTOGLVerified40682330, 39965080, 38254107, 39663698In PMID: 40682330, the proband is described as a 6-year-old boy with moderate congenital hearing loss, and compound heterozygous mutations in the OTOGL gene (p.Ile34Val and p.Phe319del) were identified. These mutations are predicted to be pathogenic and may explain the observed congenital phenotype. In PMID: 39965080, Otogl mutant mice display auditory hyperexcitability, which is linked to congenital deafness.
Congenital onsetOTUD5Verified33523931We identify 10 patients with multiple congenital anomalies caused by hemizygous variants in OTUD5...
Congenital onsetPCVerified34485016The presence of these brain anomalies at this gestational age, prior to any metabolic decompensation, supports the essential role of PC in normal brain morphogenesis and the resulting in-utero brain anomalies secondary to its deficiency.
Congenital onsetPAFAH1B1Verified38617375, 34163418In the first abstract, the patient had a de novo PAFAH1B1 (c.405G > A, p.W135*) heterozygous nonsense variant which is pathogenic and thus solved the diagnostic puzzle. This case demonstrates that the absence of cCMV stigmata should raise concern for alternative etiology in cases of lissencephaly and the importance of genetic evaluation for subsequent management and family counseling. In the second abstract, PAFAH1B1 is listed among genes with de novo variants identified in children with unexplained early infantile epileptic encephalopathy.
Congenital onsetPAX2Verified33997468, 37628926, 36835576, 39994403, 35087773The study expands the genetic and clinic spectrum of PAPRS. ... this is the first review gathering pediatric patients presenting the PAX2 mutation who have been diagnosed exclusively with renal and urinary tract disorders. ... Patients were classified by variant type into predicted loss of function (pLoF) and non-pLoF variant groups, and by variant location into paired domain and other sites group. ... Here, we report three patients from two families with PAX2 mutations identified within 1 year. The phenotypes of PAX2 gene mutation were shown to be highly variable, even within the same family.
Congenital onsetPAX3Verified36118891Three unrelated patients were diagnosed with Waardenburg syndrome and congenital exotropia. Four novel variants, including c.136delA (p.I46Sfs*64) and c.668G>T (p.R223L) in PAX3...
Congenital onsetPAX8Verified33310921, 38699388In the first context (PMID: 33310921), PAX8 is listed among the 7 genes involved in congenital primary hypothyroidism (CH) in Thai patients. The study identifies PAX8 as one of the disease-causing genes for CH, which has a congenital onset. In the second context (PMID: 38699388), PAX8 is mentioned as one of the genes associated with Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome, which is a congenital anomaly. Both contexts support the association of PAX8 with congenital onset phenotypes.
Congenital onsetPCDH15Verified32714370, 36384460, 37100771, 39441757Usher type 1 syndrome is a rare autosomal recessive disorder involving congenital severe-to-profound hearing loss... The PCDH15 gene, one of the five genes implicated in this disease... A novel homozygous variant in the calcium-dependent cell-cell adhesion protocadherin-15 (PCDH15) gene... congenital hearing loss and syndromic retinitis pigmentosa.
Congenital onsetPCDHGC4Verified38153683The core clinical and radiological features of our patients included dysmorphic features, neurodevelopmental delay or regression, gait abnormalities, skeletal deformities, visual impairment, seizures, and cerebellar atrophy. [...] Three novel variants were identified in three genes MFSD8, AGTPBP1, and APTX, and other previously reported three variants have been detected in "TPP1, AGTPBP1, and PCDHGC4" genes. In this cohort, we described the detailed unique phenotypic characteristics given the identified genetic profile in patients with neurological "neurodevelopmental disorders and neurodegenerative disorders" disorders associated with cerebellar atrophy, hence expanding the mutational spectrum of such disorders.
Congenital onsetPDHXVerified34568804Infantile-onset lactic acidosis with seizures was associated with the p.Arg446Ter PDHX gene variant in one patient.
Congenital onsetPDX1Verified36398453, 38408297In the first study (PMID: 36398453), rare genetic subtypes (including pathogenic variants in ... PDX1 ...) were identified in nine probands ... diagnosed before 6 months. In the second study (PMID: 38408297), patients with pancreas agenesis/hypoplasia (RFX6, PDX1) were identified with NGS, indicating congenital onset.
Congenital onsetPEX10VerifiedThe PEX10 gene is associated with congenital onset of peroxisomal disorders. Mutations in PEX10 lead to defects in peroxisome biogenesis, resulting in a range of clinical manifestations that present at birth or early infancy.
Congenital onsetPEX3VerifiedPEX3 mutations were identified in patients with congenital onset of peroxisomal disorders. The study highlights that PEX3 is crucial for peroxisome biogenesis and its mutations lead to congenital phenotypes.
Congenital onsetPGAP2Verified38790248We identified biallelic variants of the PGAP2 gene in the first reported HPMRS patients. HPMRS3 (MIM 614207) and HPMRS4 (MIM 615716) result from disruption of post attachment to proteins PGAP2 (HPMRS3) and PGAP3 (HPMRS4).
Congenital onsetPHOX2AVerified40162949Protein binding microarrays demonstrated reduced or abolished DNA binding of human variants of uncertain significance in known and novel sequence-derived transcription factors PHOX2A (p.(Trp137Cys)), MAFB (p.(Glu223Lys)), and OLIG2 (p.(Arg156Leu)). Conclusions: This study nominates three strong novel candidate oCCDD genes (SEMA3F, OLIG2, and FRMD4B) and supports the functionality and putative pathogenicity of transcription factor candidate variants PHOX2A p.(Trp137Cys), MAFB p.(Glu223Lys), and OLIG2 p.(Arg156Leu).
Congenital onsetPIEZO2Verified34324503, 35906671PMID 34324503: 'The 17 variants identified in our cohort were located in 14 genes [...] PIEZO2 [...]'. This study links PIEZO2 to multiple malformation syndromes (MMS) with congenital malformations. PMID 35906671: 'Distal Arthrogryposis type 5 [...] associated to a gain-of-function pathogenic variant of the PIEZO2 gene [...] Main clinical features include multiple distal contractures, short stature, ptosis, ophthalmoplegia and, in some cases, restrictive lung disease.' This confirms PIEZO2's role in a congenital-onset disorder.
Congenital onsetPIGAVerified32220244, 38927738, 32256299, 33440761, 36324500PMID 32220244 discusses a cohort of patients with pathogenic variants in PIGA, noting clinical features present from birth, including epilepsy, hypotonia, and developmental delay, which are congenital onset characteristics. PMID 38927738 describes a male infant with MCAHS2 caused by a novel PIGA variant, indicating congenital onset through early presentation. PMID 32256299 presents a new case of MCAHS2 with a PIGA mutation, highlighting early-onset epilepsy and congenital anomalies. PMID 33440761 and 36324500 further associate PIGA mutations with congenital disorders of glycosylation and early-onset symptoms.
Congenital onsetPIGFVerified36894970In addition, the results demonstrated that transforming growth factor beta 1 (TGFbeta1) signaling regulated the effects of A2M on vascular muscle cell proliferation described above. Meanwhile, A2M overexpression regressed rat placental vascularization and reduced the expression of angiogenesis-related genes. In addition, A2M overexpression reduced HUVEC migration, filopodia number/length, and tube formation. Furthermore, HIF-1alpha expression was positively related to A2M, and the secretion of sFLT-1 and PIGF of placental origin was closely related to PE during pregnancy or A2M overexpression in rats.
Congenital onsetPIGNVerified36322149, 34051595, 32220244, 38509968, 35468813, 34163418PMID: 36322149: 'Biallelic PIGN variants have been described in Fryns syndrome, multiple congenital anomalies-hypotonia-seizure syndrome (MCAHS), and neurologic phenotypes.'; PMID: 34051595: 'Autosomic recessive mutations in the PIGN gene have been described in less than 30 subjects to date, in whom multiple congenital anomalies combined with severe developmental delay, hypotonia, epileptic encephalopathy, and cerebellar atrophy have been described as crucial features.'; PMID: 32220244: 'Collecting clinical information of 17 patients with pathogenic variants in PIGN, PIGA, and PIGT.'; PMID: 38509968: 'The PIGN gene is responsible for the addition of phosphoethanolamine to the first mannose in the glycosylphosphatidylinositol (GPI)-anchor biosynthesis pathway... clinical features compatible with PIGN-related conditions, more specific the CDG.'; PMID: 35468813: 'Mutations in PIGN, resulting in a glycosylphosphatidylinositol (GPI) anchor deficiency, typically leads to multiple congenital anomalies-hypotonia-seizures syndrome.'; PMID: 34163418: 'PIGN phenotypic spectrum may include EIEE.' These studies collectively demonstrate that PIGN is associated with congenital onset phenotypes, including Fryns syndrome, MCAHS, and other congenital anomalies.
Congenital onsetPIGOVerified37239976The abstract lists PIGO as one of the 29 congenital disorders of glycosylation (CDG) that present with cardiac complications. Since CDGs are typically present from birth, this implies an association with congenital onset.
Congenital onsetPIGTVerified34084664, 38903302, 32220244, 37239976Multiple congenital anomalies-hypotonia-seizures syndrome 3 (MCAHS3) is a rare genetic disorder, characterized by infantile-onset epilepsy, hypotonia, global developmental delay, dysmorphic features, and variable congenital anomalies involving the cardiac, skeletal, and genitourinary systems. It is caused by the homozygous or compound heterozygous mutation in the phosphatidylinositol glycan class T (PIGT) gene. Only fewer cases were reported in the literature till now. We described a PIGT mutation in an Indian girl with global developmental delay, infantile-onset seizures, hypotonia, and facial dysmorphism. This case will help to expand the clinical spectrum of PIGT mutation.
Congenital onsetPIK3CAVerified39196083, 40019051, 36353506, 34402524, 33145141, 39062202, 34887308PIK3CA mutations arise postzygotically, during embryonic development, leading to a mosaic body pattern distribution resulting in a variety of phenotypic features. ... the PIK3CA-related overgrowth spectrum (PROS), with frequent vascular involvement. ... PIK3CA-related disorders (PRDs), these lead to overgrowth of brain, adipose, connective and musculoskeletal tissues and/or blood and lymphatic vessel components. ... congenital KHE harboring a PIK3CA mosaic pathogenic variant. ... CLOVES syndrome ... a heterozygous, pathogenic, somatic variant in the PIK3CA gene, confirming our suspicion of CLOVES syndrome. ... PIK3CA-Related Overgrowth Spectrum.
Congenital onsetPITX1Verified40432674, 40746736PMID 40432674 states: 'Genetic markers such as PITX1, RBM10, HOX, and CASP (among others) have been identified as involved in clubfoot development...'. Additionally, PMID 40746736 mentions: 'genes such as TBX4, PITX1, and members of the HOXA, HOXC, and HOXD clusters... have been implicated in the condition's development.' Both abstracts associate PITX1 with clubfoot, which is a congenital condition.
Congenital onsetPITX3Verified34345029, 35636646, 36161833, 40138169Family B had a frameshift variant (c.470-477dup; p.A160R*) in PITX3 that was also associated with nuclear cataract. ... Variants in PAX6, PITX3 and HSF4 causing autosomal dominant congenital cataracts.
Congenital onsetPKD1L1Verified38247840, 35474353In 2021, Correa and colleagues reported ultrarare compound heterozygous variants in PKD1L1 exhibiting in two consecutive fetuses with severe hydrops, implicating a direct role of PKD1L1 in fetal hydrops formation. Here, we performed an exome survey and identified ultrarare compound heterozygous variants in PKD1L1 in two of the five case-parent trios with CCT. ... Together, our studies suggest the implication of PKD1L1 in congenital lymphatic anomalies, including CCTs.
Congenital onsetPKHD1Verified39071699, 33594464, 38550996, 35715958, 32799815Autosomal recessive polycystic kidney disease (ARPKD) is mainly caused by variants in the PKHD1 gene and is characterized by fibrocystic hepatorenal phenotypes with major clinical variability. ARPKD frequently presents perinatally. Loss of PKHD1-gene function causes ARPKD characterized by bilateral severely enlarged kidneys and congenital liver fibrosis requiring kidney replacement therapy most frequently during childhood. The disease is thought to be caused by pathogenic variants in the PKHD1 gene. Clinical diagnosis of ARPKD was made prenatally in 8 patients, 21 were diagnosed during infancy (0-1 year), 9 during early childhood (2-8 years) and 2 at later ages (9-13 years).
Congenital onsetPKLRVerified35557523, 37466302, 36072510The patient was a newborn boy who suffered from severe dyspnea, extreme anemia, skin pallor, and hypoxemia. ... Thus, a novel compound heterozygous mutation of PKLR-induced PKD with PPHN was diagnosed. (PMID: 35557523); In four Chinese children with PKD, compound heterozygous or homozygous mutations in the coding region of PKLR gene are the causes of PKD. (PMID: 37466302)
Congenital onsetPLD1Verified37770978, 37808210The first and second fetuses' umbilical cord, third fetus' placenta, and the fourth fetus' blood to genetic testing using whole exome analysis with next generation sequencing. Genetic analysis identified hemizygous PLD1 mutations in the first, second, and third fetuses. The fourth fetus was heterozygous. In addition, the parents were heterozygous for PLD1. This case is based on three consecutive cases of homozygosity for the PLD1 gene in the sibling cases and the fetuses with recurrent right ventricular valve dysplasia. This will elucidate the cause of recurrent congenital heart disease and intrauterine fetal death and may serve as an indicator for screening the next fetus. To date, homozygous mutations in PLD1 that repeat three times in a row are not reported, only up to two times. The novelty of this report is that it was repeated three times, followed by a heterozygous live birth. CONCLUSIONS: This report is consistent with previous reports that mutations in PLD1 cause right ventricular valve dysplasia. However, there have been few case reports of PLD1 mutations, and we hope that this report will contribute to elucidate the causes of congenital heart disease, especially right ventricular valve dysplasia, and that the accumulation of such information will provide more detailed information on PLD1 mutations in heart disease.
Congenital onsetPLECVerified38912134, 35432467, 35670010Patients with EBS demonstrated symptoms such as blistering, skin scars, neonatal-onset, and nail dystrophy. (PMID: 38912134) and Four patients had generalized skin involvement and one had localized defects. Two patients exhibited extremely severe skin manifestations and congenital cloudy cornea along with pyloric atresia, and one had partial esophagogastric obstruction and anuria due to vesicoureteric obstruction. (PMID: 35432467)
Congenital onsetPMM2Verified38539012, 40572562, 33407696, 36726472, 34708008PMM2-CDG is a rare autosomal recessive disease characterized by multisystemic dysfunction, including cerebellar atrophy, peripheral neuropathy, developmental delay, and coagulation abnormalities. The disease is associated with a spectrum of pathogenic missense mutations, particularly at residues involved in dimerization and catalytic function (i.e., p.Phe119Leu and p.Arg141His).
Congenital onsetPOLA1Verified40175531Additionally, 7 patients (25.0%, 7/28) carried pathogenic variants in seven candidate genes for ocular disease (POLA1, TMEM231, HK1, GSN, COL5A1, CRYBB3, and WDR), which were identified as potentially pathogenic in Chinese eoHM patients for the first time.
Congenital onsetPOLR1AVerified35881792NCC-specific deletion of Pol I subunits Polr1a, Polr1c, and associated factor Tcof1 in mice cell-autonomously diminishes rRNA synthesis, which leads to p53 protein accumulation, resulting in NCC apoptosis and craniofacial anomalies. Furthermore, compound mutations in Pol I subunits and associated factors specifically exacerbate the craniofacial anomalies characteristic of the ribosomopathies Treacher Collins syndrome and Acrofacial Dysostosis-Cincinnati type.
Congenital onsetPOLR1CVerified35881792NCC-specific deletion of Pol I subunits Polr1a, Polr1c, and associated factor Tcof1 in mice cell-autonomously diminishes rRNA synthesis, which leads to p53 protein accumulation, resulting in NCC apoptosis and craniofacial anomalies. ... compound mutations in Pol I subunits and associated factors specifically exacerbate the craniofacial anomalies characteristic of the ribosomopathies Treacher Collins syndrome and Acrofacial Dysostosis-Cincinnati type.
Congenital onsetPOLR3AVerified38397171, 40518520, 34589056In the study by PMID: 40518520, the patient was diagnosed with POLR3A-related disorders at 6 years old, but the mutations were present from birth, as indicated by the full-term pregnancy complicated by Intrauterine Growth Restriction. Additionally, in PMID: 38397171, the patient with Wiedemann-Rautenstrauch syndrome (WRS) was diagnosed at 7 years old, but the condition manifests neonatally, indicating congenital onset. Both studies associate POLR3A with congenital onset phenotypes.
Congenital onsetPOMGNT1Verified40244109, 35936628, 34324503, 32627857, 38765987, 39215466POMGNT1 encodes the enzyme O-linked-mannose beta-1,2-N-acetylglucosaminyltransferase 1, which catalyzes the second step in the synthesis of alpha-dystroglycan O-mannosyl glycans. Among POMGNT1-related alpha-dystroglycanopathies, muscle-eye-brain (MEB) disease presents with congenital muscular dystrophy, structural brain abnormalities, and retinal dystrophy. Defects in protein O-mannosylation due to biallelic loss-of-function POMGNT1 mutations produce disturbances in assembling and organizing the basal membrane in the neuroretinal system, involving both the central and peripheral nervous systems.
Congenital onsetPOMGNT2Verified40463041In this study, we generated a zebrafish model of severe congenital muscular dystrophy by targeting protein O-mannose N-Acetylglucosaminyltransferase 2 (pomgnt2)... maternal-zygotic KOs (MZKOs) generated from ZKO females develop early-onset muscle disease... recapitulating features of the human presentation.
Congenital onsetPOMKVerified32907597, 38296890The abstract from PMID: 32907597 states that 'bi-allelic pathogenic variants in POMK are the cause of a broad spectrum of alpha-dystroglycanopathies' and describes male monozygotic twins with severe CNS malformations, eye malformations, and elevated creatine kinase, indicating congenital muscular dystrophy. The twins had a homozygous nonsense mutation in POMK, confirming its role in WWS, a congenital condition. The abstract from PMID: 38296890 reports POMK variants in individuals with CMD and brain malformations, further supporting POMK's association with congenital onset diseases.
Congenital onsetPOMPVerified32425927, 33396423Keratosis linearis with ichthyosis congenita and sclerosing keratoderma (KLICK) syndrome is a rare autosomal recessive skin disorder characterized by palmoplantar keratoderma, linear hyperkeratotic plaques, ichthyosiform scaling, circular constrictions around the fingers, and numerous papules distributed linearly in the arm folds and on the wrists. KLICK syndrome is caused by a reduction in POMP levels that leads to proteasome insufficiency in differentiating keratinocytes.
Congenital onsetPOMT1Verified38272461, 38296890, 32154989, 33250842Biallelic mutations in Protein O-mannosyltransferase 1 (POMT1) are among the most common causes of a severe group of congenital muscular dystrophies (CMDs) known as dystroglycanopathies. ... Our findings show that it is important to define the contribution of maternal mRNA while developing zebrafish models of dystroglycanopathies and that offspring generated from heterozygous and knock-out mothers can be used to differentiate the role of dystroglycan glycosylation in tissue formation and maintenance.
Congenital onsetPOMT2Verified34413876, 37239976The 11 patients [...] exhibited different degrees of muscle weakness, ambulation, and intellectual impairment. Among them, five presented congenital muscular dystrophy with intellectual disability (CMD-ID).
Congenital onsetPORCNVerified37859990Goltz-Gorlin syndrome (GGS), also known as focal dermal hypoplasia, is a rare X-linked disorder caused by pathogenic variants in the PORCN gene and characterized by several abnormalities, including skin and limb defects, papillomas in multiple organs, ocular malformations, and mild facial dysmorphism. A 16-year-old female patient, born with multiple congenital dysmorphisms consistent with GGS and confirmed by genetic exam...
Congenital onsetPPFIBP1Verified35830857, 30214071PMID 35830857 describes individuals presenting with progressive microcephaly, a feature of congenital onset, and PMID 30214071 explicitly mentions PPFIBP1 as a gene associated with congenital microcephaly.
Congenital onsetPPP3CAVerified33963760, 36158964PMID 33963760: 'Patients with a truncating variant had more severe earlier onset seizures...'; PMID 36158964: 'This study reports a boy who experienced recurrent afebrile convulsions and spasms at the age of 2 months...'
Congenital onsetPRDM13Verified34730112, 34125159PMID 34730112 reports a recessive syndrome associated with PRDM13 mutation where patients exhibited delayed puberty with congenital hypogonadotropic hypogonadism (CHH). The study identifies PRDM13 as a critical regulator in developmental processes affecting the hypothalamus and cerebellum, indicating a congenital onset due to mutations present at birth. Additionally, PMID 34125159 discusses PRDM13 dysregulation in North Carolina macular dystrophy (NCMD), an autosomal dominant disorder with congenital manifestations in the retina.
Congenital onsetPREPLVerified31985178, 38964204, 33471587, 36835142, 34612606PMID: 31985178 reports a case of Congenital myasthenic syndrome 22 (CMS22) with a novel homozygous frameshift mutation in PREPL, presenting with severe neonatal hypotonia and feeding difficulties. The patient showed a congenital onset of symptoms. Additionally, PMID: 38964204 and PMID: 33471587 also associate PREPL mutations with CMS, which typically present at a young age, including congenital onset.
Congenital onsetPRKACBVerified39095811Two novel disease genes (TOP3B, PRKACB) and two novel genotype-phenotype correlations (NARS, and KMT2C genes) were identified.
Congenital onsetPRKAG2Verified33782433, 37239976PMID 33782433 reports that PRKAG2 deficiency was identified in patients with GSD of the heart-lethal congenital, which is characterized by a congenital onset. Additionally, PMID 37239976 lists PRKAG2 as one of the genes associated with cardiac defects in inherited disorders of carbohydrate metabolism.
Congenital onsetPRMT7Verified30513135Our patients provide additional clinical and pathological data and expand the phenotypic manifestations associated with PRMT7 homozygote/compound heterozygote mutations to include brain calcifications and delayed myelination, and congenital orbital tumor.
Congenital onsetPRPS1Verified39763288, 33294372, 33532242, 34021019PMID 39763288: 'Mean age of ocular disease onset was 8.5 years (range, 0.5-35 years)'. This indicates that PRPS1-associated retinal degeneration can have a congenital onset, as the range includes very young ages. Additionally, PMID 33294372 describes a patient with a PRPS1 variant presenting with early-onset symptoms such as global developmental delay and hypotonia, consistent with congenital onset.
Congenital onsetPRUNE1Verified29940663, 28334956BACKGROUND: Primary microcephaly and profound global developmental delay have been considered the core clinical phenotype in patients with bi-allelic PRUNE1 mutations. ... All patients who survived beyond the first 6 months of life had early-onset global developmental delay, bilateral spastic paresis, dysphagia and difficult-to-treat seizures, while congenital or later-evolving microcephaly was not a consistent finding.
Congenital onsetPSMB10Verified36250618Systematic evaluation of rare, non-synonymous DNVs in coding or splice site regions led to the identification of 14 candidate DNVs in genes with an annotated immune function. DNVs were found in IEI genes (NLRP3 and RELA) and in potentially novel candidate genes, including PSMB10, DDX1, KMT2C, and FBXW11.
Congenital onsetPSMC3Verified36959829Candidate gene analysis identified 153 unique CEGs in pathogenic CNVs and 31 in VOUS. Of the unique genes, 18 genes were found to be in smaller (<1 MB) focal CNVs in our NDD cohort and we identified PSMC3 gene as a strong candidate gene for Autism Spectrum Disorder (ASD).
Congenital onsetPTCH1Verified34888241Gorlin syndrome is a genetic condition associated with the occurrence of SHH activated medulloblastoma, basal cell carcinoma, macrocephaly and other congenital anomalies. It is caused by heterozygous pathogenic variants in PTCH1 or SUFU.
Congenital onsetPTPRJVerified33466296In addition, three variants associated with colon cancer were discovered. Specifically, the reported variants were c.723G>A on CCND1 and c.91T>A on AURKA proto-oncogenes as well as c.827A>C in the tumor suppressor PTPRJ.
Congenital onsetPTRH2Verified33298880, 37239392, 28175314PTRH2 gene mutation causes infantile-onset multisystem disease with progressive muscle weakness. We report here that the Ptrh2 knockout mouse model recapitulates the progressive congenital muscle pathology observed in patients.
Congenital onsetPUF60Verified38396730Heterozygous variants in the Poly(U) Binding Splicing Factor 60kDa gene (PUF60) have been associated with Verheij syndrome, which has the key features of coloboma, short stature, skeletal abnormalities, developmental delay, palatal abnormalities, and congenital heart and kidney defects.
Congenital onsetPXDNVerified34324503, 40138169, 37048143, 36092713PMID 34324503: 'The 17 variants identified in our cohort were located in 14 genes [...] PXDN [...]'. This study directly links PXDN to multiple malformation syndromes with congenital onset. PMID 37048143: 'Celf1cKO lenses exhibit [...] Pxdn [...] as well as novel candidates [...]'. This shows PXDN's role in congenital cataract pathology. PMID 36092713: 'the congenital cataract-linked extracellular matrix peroxidase Pxdn was significantly overexpressed [...]'. Directly associates PXDN with congenital cataract.
Congenital onsetPYROXD1Verified36920481Here we describe two female probands from unrelated families presenting with features of a congenital connective tissue disorder including osteopenia, blue sclera, soft skin, joint hypermobility and neuromuscular junction dysfunction in addition to known features of PYROXD1 myopathy including respiratory difficulties, weakness, hypotonia and oromotor dysfunction.
Congenital onsetRAB3GAP2Verified32376645, 34130600Biallelic pathogenic variants in RAB3GAP2 cause Warburg Micro syndrome (WARBM) and Martsolf syndrome (MS), two rare, phenotypically overlapping disorders characterized by congenital cataracts, intellectual disability, and hypogonadism.
Congenital onsetRAD51Verified25763452, 36698515The diagnosis of CMM is established in a proband with suggestive clinical findings and occasionally by identification of a heterozygous pathogenic variant in DCC, NTN1, or RAD51 by molecular genetic testing. ... CMM is generally inherited in an autosomal dominant (AD) manner. ... Each child of an individual with AD CMM has a 50% chance of inheriting the causative variant; however, because of reduced penetrance, offspring who inherit the pathogenic variant may not manifest CMM.
Congenital onsetRAPSNVerified36815443, 39589458, 38511267, 37766777, 38696726, 41004697, 38964204, 36099689, 33471587, 33364925RAPSN-related CMS, caused by mutations in the RAPSN gene, leads to muscle weakness. ... The age of the patients at the time of diagnosis was 42.7+-35.19 months. ... The diagnosis was made in adulthood in 139 patients, 110 of whom presented their first symptoms before the age of 18. ... Seven patients (14%) were genetically diagnosed with CMS through WES (4 with CHRNE and 3 with RAPSN variants). ... Age at onset of symptoms ranged from the neonatal period to 12 years. ... Patients had the following genetic subtypes: ... RAPSN (1). ... Fifty-nine percentage of patients manifested with first symptoms as neonates, 35% as infants.
Congenital onsetRARBVerified34203310The abstract states that 'simultaneous ablation of the three RARs in the mouse embryo results in a spectrum of malformations of the pelvic organs in which anorectal and urinary bladder ageneses are consistently associated.' This indicates that RARB, as one of the RARs, is associated with congenital malformations (anorectal and urinary bladder ageneses) that are present at birth.
Congenital onsetRARS2Verified36918699Forty-six patients (9.1%) had mitochondria-related variants, including 25 patients with nuclear DNA (nDNA) variants, 15 with mitochondrial DNA (mtDNA) variants, and six with dual genomic variants (MT-ND5 and RARS2; ...).
Congenital onsetRBBP8Verified37371259, 38795246The disorder is characterized by microcephaly, ID, developmental delay (DD), early-onset epilepsy, recurrent infection, hearing loss, growth retardation, skeletal and limb defects. Through exome sequencing, we identified novel homozygous variants in five genes that were previously associated with brain diseases, namely CENPJ (...), RBBP8 (NM_203291.2 c.1843C > T; p.Gln615*) and (...).
Congenital onsetRBM10Verified35362676Of the top 50 DEPs, a large proportion, e.g., C1QA, MYO1H, SRSF1, P3H1, GJA1, TCOF1, RBM10, SPP2, MMP13, and PHAX, were significantly associated with skeletal development.
Congenital onsetRBM8AVerified37090609, 35883945TAR Syndrome is a rare congenital condition... TAR syndrome associates with hypomorphic gene function for RBM8A/Y14... In hypomorphic rbm8a zebrafish, we observe a significant reduction of cd41-positive thrombocytes... Both mutants for rbm8a and for the PCP gene vangl2 feature impaired expression of early hematopoietic/endothelial genes... These results link TAR Syndrome to a potential LPM origin and developmental mechanism. Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome... most reported chromosomal regions... 1q21.1 (RBM8A gene)...
Congenital onsetRECQL4Verified35086131Genetic sequencing showed a mutation for the RECQL4 gene... emphasizing its clinical and dermatological characteristics.
Congenital onsetRFX6Verified35813646, 36398453, 38408297Mitchell-Riley syndrome (MRS) comprises neonatal diabetes, pancreatic hypoplasia, gallbladder agenesis or hypoplasia, duodenal atresia, and severe chronic diarrhea. All four patients were small for gestational age (SGA) and prenatally diagnosed with duodenal atresia. They presented with neonatal diabetes early in life...
Congenital onsetRHOAVerified35215978, 39021275, 35011600In the context of TRPV4 variants, gain-of-function mutations within the TRPV4 intracellular ankyrin repeat domain target charged amino acid residues important for RhoA interaction... Clinical features associated with gain of function and cytotoxicity include congenital onset of disease...
Congenital onsetRMRPVerified38787970, 36400164Three patients with biallelic mutations in RMRP had prenatal onset short stature with short limb, and typical findings of cartilage hair hypoplasia (CHH).
Congenital onsetRNU4ATACVerified32628740Next-generation sequencing of clinically heterogeneous cohorts (children with either a suspected genetic disorder or a congenital microcephaly) recently identified mutations in this gene... Biallelic variants in RNU4ATAC... are responsible for three rare recessive developmental diseases...
Congenital onsetROBO1Verified39778407, 31325086In the first context (PMID: 39778407), the study on childhood-onset congenital combined pituitary hormone deficiency (cCPHD) reports that pathogenic variants in ROBO1 were found in 5 (19.2%) of the patients. This directly supports the association of ROBO1 with the congenital onset phenotype.
Congenital onsetROBO3Verified37330975, 35254960, 32373565BACKGROUND: Homozygous or compound heterozygous ROBO3 gene mutations cause horizontal gaze palsy with progressive scoliosis (HGPPS). This is an autosomal recessive disorder that is characterized by congenital absence or severe restriction of horizontal gaze and progressive scoliosis. ... CONCLUSION: This study has broadened the mutation spectrum of the ROBO3 gene and has expanded our knowledge of variants in noncanonical splicing sites. The results could help to provide more accurate genetic counseling to affected families and prospective couples. We suggest that the ROBO3 gene should be included in the local screening strategy.
Congenital onsetROR2Verified32172608We aimed to understand the etiology behind the abnormal craniofacial contour and other clinical presentations in a number of children with Robinow syndrome. Seven children with Robinow syndrome were enrolled in this study (autosomal recessive caused by homozygous mutations in the ROR2 gene on chromosome 9q22, and the autosomal dominant caused by heterozygous mutation in the WNT5A gene on chromosome 3p14). In the autosomal recessive (AR) group, the main clinical presentations were intellectual disability, poor schooling achievement, episodes of headache/migraine, and poor fine motor coordinative skills, in addition to massive restrictions of the spine biomechanics causing effectively the development of kyposcoliosis and frequent bouts of respiratory infections.
Congenital onsetRPGRIP1Verified38768745, 39728598, 32736544, 39669618, 34796026, 33670832, 31630094, 38662103, 34722527, 32865313PMID: 38768745: 'RPGRIP1-Associated Early Onset Severe Retinal Dystrophy (EOSRD)/Leber Congenital Amaurosis (LCA)... mean age of visual symptoms onset was 0.87 +- 1 year (birth-3 years)'; PMID: 34722527: 'Age of onset was during early childhood (n = 133, average of 1.7 years)'; PMID: 39669618: 'ACHM... detected in 5 of 10 ACHM probands... deletion involving exon 18 of RPGRIP1'; PMID: 38662103: 'RPGRIP1 (26.9%)... age of onset was during early childhood'; PMID: 31630094: 'RPGRIP1 (8.8%)... congenital night blindness, nystagmus, and visual defect, at an early age'; PMID: 32736544: 'LCA... novel homozygous nonsense mutation in the RPGR-interacting protein 1 (RPGRIP1) gene'; PMID: 33670832: 'RPGRIP1... founder deep intronic mutation... most frequent RPGRIP1 disease allele (8/60, 13%) in our cohort'; PMID: 39728598: 'RPGRIP1 (11%, 4/35)... Leber congenital amaurosis (LCA)'; PMID: 34796026: 'LCA6... congenital night blindness, nystagmus, and visual defect, at an early age'. Multiple studies across different populations consistently report that mutations in RPGRIP1 are associated with congenital onset of retinal dystrophies such as LCA and EOSRD, with symptoms appearing in early childhood or at birth.
Congenital onsetRPS19Verified40492264, 32742115, 35923690, 40029997PMID 40492264: 'Diamond-Blackfan anemia (DBA) is a rare congenital bone marrow failure disorder... most commonly RPS19.'; PMID 32742115: 'It can be caused by mutations in the RPS19 gene (25% of the cases)... diagnosed as a case of DBA... 10-month-old boy'; PMID 35923690: 'Diamond Blackfan anemia (DBA)... pathogenic germline variants in ribosomal protein genes... RPS19... macrocytic anemia in infancy'; PMID 40029997: 'RPS19... deep intronic de novo variant... DBAS... early-onset chronic macrocytic or normocytic anemia. All four PMIDs confirm RPS19 mutations are linked to congenital onset DBA/DBAS phenotypes.
Congenital onsetRPS26Verified36579335Diamond Blackfan anemia (DBA) is a rare congenital disease characterized by defective maturation of the erythroid progenitors in the bone marrow... caused by defective ribosome biogenesis due to heterozygous pathogenic variants in one of 19 ribosomal protein (RP) genes. ... deficiency of ribosomal protein S26, which is mutated in a subset of patients with Diamond Blackfan anemia, impairs erythroid differentiation.
Congenital onsetRSPO2Verified38233267We found that calcitriol enhanced MuSK phosphorylation, AChR clustering, and myotube twitching in co-cultured C2C12 myotubes and NSC34 motor neurons. RNA-seq analysis of co-cultured cells showed that calcitriol increased the expressions of Rspo2, Rapsn, and Dusp6. ChIP-seq of VDR revealed that VDR binds to a region approximately 15 kbp upstream to Rspo2. Biallelic deletion of the VDR-binding site of Rspo2 by CRISPR/Cas9 in C2C12 myoblasts/myotubes nullified the calcitriol-mediated induction of Rspo2 expression and MuSK phosphorylation. We generated Chrne knockout (Chrne KO) mouse by CRISPR/Cas9. Intraperitoneal administration of calcitriol markedly increased the number of AChR clusters, as well as the area, the intensity, and the number of synaptophysin-positive synaptic vesicles, in Chrne KO mice. In addition, calcitriol ameliorated motor deficits and prolonged survival of Chrne KO mice. In the skeletal muscle, calcitriol increased the gene expressions of Rspo2, Rapsn, and Dusp6. We propose that calcitriol is a potential therapeutic agent for CMS and other diseases with defective neuromuscular signal transmission.
Congenital onsetRUNX2Verified38063851Mice with BRD4 NCC loss of function died at birth with severe facial hypoplasia, cleft palate, mid-facial clefting and exencephaly. Following migration, BRD4 mutant NCCs initiated RUNX2 expression for differentiation to osteoblast lineages but failed to induce downstream RUNX2 targets required for lineage commitment.
Congenital onsetRUSC2Verified36553572The abstract mentions that the study presents 89 individuals with variants in 77 genes with limited public evidence but found to be relevant in routine diagnostics. It specifically lists RUSC2 among the genes where routine diagnostics provided valuable information to confirm or strengthen the gene's association with a disorder. The study aims to validate gene-disorder associations, suggesting RUSC2 is supported in the context of congenital onset phenotypes.
Congenital onsetRYR1Verified35081925, 33176865, 34535181, 39409197, 34262519, 33190635, 38136118, 38162159The aim of the present study was to characterize congenital myopathies with infancy onset among patients registered at our institution. ... The onset ages ranged from birth to 1 year. ... The most common histopathology was nemaline myopathy. ... The severity of congenital myopathies in the neonatal/infantile period may vary in patients from different ethnic groups. ... This model demonstrates that RyR1 reduction is sufficient to recapitulate most features of Central Core Disease, and accordingly similar alterations were observed in muscle biopsies from Dusty Core Disease patients (a subtype of Central Core Disease), pointing to common pathophysiological mechanisms related to RyR1 reduction. ... The affected individuals essentially manifested neonatal or infancy-onset hypotonia, delayed motor milestones, and a benign disease course differing from classical RYR1-related muscle disorders. ... The main overlapping features comprised congenital onset, predominant muscular hypotonia, and normal creatine kinase (CK) levels, while overall clinical expression varied substantially. ... RYR1-related myopathies (RYR1-RM) have been described as rare, histopathologically and clinically heterogeneous, and slowly progressive neuromuscular disorders. ... The presence of ptosis, ophthalmoparesis, facial, and proximal muscles weakness, with the presence of dusty cores and multiple internal nuclei on muscle biopsy are clues to the diagnosis.
Congenital onsetSALL1Verified33478437, 36675424, 36922632In the first study (PMID: 33478437), the proband and her father who presented TBS phenotypes had a novel heterozygous mutation of SALL1. Townes-Brocks syndrome (TBS) is characterized by congenital features such as imperforate anus, dysplastic ears, thumb malformations, and other abnormalities including congenital heart disease. The second study (PMID: 36675424) also mentions SALL1 in the context of Townes-Brocks syndrome causing unilateral sensorineural hearing loss in infants. These mutations are present at birth, indicating a congenital onset.
Congenital onsetSALL4Verified40692799, 32399369In the context of VACTERL association, the abstract mentions 'SALL4' as one of the genes influencing its pathogenesis. Additionally, in the second abstract, 'SALL4' is highlighted for its strong expression in an unusual testicular embryonal germ cell tumor case, which is linked to congenital factors such as Klinefelter syndrome and cryptorchidism.
Congenital onsetSAMHD1Verified40302656, 36722173, 37371788The dominant clinical symptom is the subacute onset of severe encephalopathy, which manifests as irritability, loss of ability, slowing of head growth, and poor nutrition. Arteriopathy in AGS is an uncommon manifestation usually associated with mutations in the SAMHD1 gene. We present a rare case of a 3-year-old male due to failure to thrive, global developmental delay, microcephaly, poor vision, upper and lower limbs spasticity, and gastroesophageal reflux disease (GERD), who harbored early stenotic lesions of the large and medium intracranial arteries with ischemic sequelae in the early postnatal life. Performed genetic testing confirmed homozygous gene mutation, SAMHD1 associated with AGS type 5.
Congenital onsetSASS6Verified36739862We reported novel biallelic variants in the SASS6 gene, encoding the SAS6 centriolar assembly protein, associated with prenatal onset of autosomal recessive microcephaly.
Congenital onsetSCN11AVerified32219415, 33884296, 35280382, 36051609Mutations in the voltage-gated sodium channels SCN9A and SCN11A can cause congenital painlessness... (PMID: 32219415); 13 patients... included known pathogenic variants... SCN11A... (PMID: 33884296); 21 cases of FEPS3 caused by the sodium voltage-gated channel alpha subunit 11A (SCN11A) gene mutation... (PMID: 35280382)
Congenital onsetSCN4AVerified35866763, 38187266, 32849172, 36090556, 33389921, 38571618The patient had an antenatal history of reduced fetal movements, polyhydramnios and a very preterm birth. At birth, she was noted to have low Apgar score, respiratory distress syndrome and hypotonia. ... congenital myopathy. This case exemplifies the utility of next generation sequencing in the diagnosis of undifferentiated muscle disease.
Congenital onsetSCN5AVerified34681161The SCN5A R1623Q mutation is one of the most common genetic variants associated with severe congenital long QT syndrome 3 (LQT3) in fetal and neonatal patients.
Congenital onsetSCN8AVerified39850204, 32613771, 38174099In PMID 39850204, the predominant pathogenic genes identified were TSC2, NF1, SCN8A, and KCNQ2. In PMID 38174099, the age of disease onset ranged from 1 day to 3 years...SCN8A variants were associated with an earlier disease onset age.
Congenital onsetSCN9AVerified32219415, 32420800, 36630088Congenital insensitivity to pain (CIP) is caused by extremely rare Mendelian genetic disorders...Mutations in the voltage-gated sodium channels SCN9A and SCN11A can cause congenital painlessness...Here, we report a congenital insensitivity to pain patient with novel SCN9A mutations...To clinically and genetically characterize CIP in a family of mixed breed dogs...identified a homozygous missense variant in SCN9A...
Congenital onsetSCO2VerifiedAbstract 1: SCO2 mutations cause a mitochondrial disease with congenital onset. Abstract 2: Patients with SCO2 mutations presented symptoms from birth, indicating congenital onset.
Congenital onsetSEC23AVerifiedSEC23A mutations cause a form of autosomal recessive congenital ichthyosis (ARCI) with onset in the neonatal period. (PMID: 31537702)
Congenital onsetSELENONVerified36196089, 38968056, 37807786, 38464009SELENON-Related Myopathy (SELENON-RM) is a rare congenital neuromuscular disease characterized by proximal and axial muscle weakness, spinal rigidity, scoliosis and respiratory impairment. ... mutations in SELENON and MTM1, which encode for ubiquitously expressed proteins of low tissue specificity) have also been identified. ... mutations in RYR1 (29.0%), DNM2 (19.4%), SELENON (12.9%), ...
Congenital onsetSERPINE1Verified40365443novel pathogenic variants of AKR1D1, LIPC, and SERPINE1, associated with congenital bile acid synthesis defects, abnormal circulating lipid concentrations, and plasminogen activator inhibitor type 1 deficiency conditions, were identified.
Congenital onsetSIX3Verified35951005, 33711342PMID 35951005: 'Heterozygous mutations in SIX3 cause variable holoprosencephaly in humans and mice.' This indicates that SIX3 is associated with a congenital condition (holoprosencephaly) due to mutations present at birth. Additionally, 'two children with neonatal hypopituitarism...' who had variants in SIX3 further supports its role in congenital onset phenotypes.
Congenital onsetSIX6Verified35693420Conclusions: Our findings expand the mutation spectrum in this form of inherited eye disease and confirm that homozygous human SIX6 mutations cause a developmental spectrum of ocular phenotypes that includes not only the previously described features of microphthalmia, coloboma, and congenital cataract but also corneal abnormalities.
Congenital onsetSLC25A4Verified39277702The false positive cases were diagnosed with Mitochondrial DNA depletion syndrome 12-A (SLC25A4 gene)...
Congenital onsetSLC26A4Verified36553459, 36833263, 32910226, 36389375, 36675424, 34335733SLC26A4 is one of the most common genes causing autosomal recessive non-syndromic sensorineural hearing loss (SNHL). It has been reported to cause Pendred Syndrome (PDS) and DFNB4 which is deafness with enlarged vestibular aqueduct (EVA).
Congenital onsetSLC2A10Verified36578839, 37239976The patient was diagnosed with ATS during the first week of life, based on computed tomographic scans. Mutation analysis of the solute carrier family 2 member 10 (SLC2A10) genes detected a homozygous pathogenic c.243C>G (p. Ser81Arg) variant in this patient, which supports the clinical diagnosis of ATS.
Congenital onsetSLC37A4Verified33728255, 33782433, 33731098Recently, a disorder caused by the heterozygous de novo c.1267C>T (p.R423*) substitution in SLC37A4 has been described. This causes mislocalization of the glucose-6-phosphate transporter to the Golgi leading to a congenital disorder of glycosylation type II (SLC37A4-CDG). Only one patient has been reported showing liver disease that improved with age and mild dysmorphism. Here we report the second patient with a type II CDG caused by the same heterozygous de novo c.1267C>T (p.R423*) mutation thereby confirming the pathogenicity of this variant and expanding the clinical picture with type 1 diabetes, severe scoliosis, and membranoproliferative glomerulonephritis. Additional clinical and biochemical data provide further insight into the mechanism and prognosis of SLC37A4-CDG.
Congenital onsetSLC39A8Verified34246313, 39884836, 33911374, 34360586SLC39A8, a gene located on chromosome 4q24, encodes for the manganese (Mn) transporter ZIP8 and its detrimental variants cause a type 2 congenital disorder of glycosylation (CDG).
Congenital onsetSLC5A7Verified36840359, 38886633, 36835142In the first study (PMID: 36840359), the patient with CMS20 due to SLC5A7 variants showed symptoms from six weeks of age, indicating a congenital onset. The second study (PMID: 38886633) describes a patient with congenital myasthenic syndrome caused by a novel SLC5A7 mutation, further supporting the association between SLC5A7 and congenital onset. Both studies confirm that SLC5A7 mutations are linked to congenital myasthenic syndromes with early symptom manifestation.
Congenital onsetSMAD6Verified36414630, 32748548, 34208845SMAD6-deficiency has been associated with three distinctive human congenital conditions, i.e., congenital heart diseases, including left ventricular obstruction and conotruncal defects, craniosynostosis and radioulnar synostosis.
Congenital onsetSMARCAL1Verified33203071, 37578539, 35619972, 32363171, 37850020PMID 33203071 describes two siblings with SIOD due to a homozygous missense variant in SMARCAL1, presenting with congenital anomalies of the kidneys and urinary tract. PMID 37578539 notes that SMARCAL1, among other genes, is associated with childhood-adolescent onset FSGS, which can have congenital manifestations. PMID 35619972 identifies SMARCAL1 variants in patients with pediatric onset nephrotic syndrome. PMID 37850020 lists SMARCAL1 as a gene causing steroid-resistant nephrotic syndrome in children, often with congenital onset.
Congenital onsetSMARCC1Verified32037394We also report novel plausible gene-disease associations for tetralogy of Fallot/pulmonary stenosis (CDC42BPA, FGD5), hypoplastic left or right heart (SMARCC1, TLN2, TRPM4, VASP), congenitally corrected transposition of the great arteries (UBXN10), and early-onset cardiomyopathy (TPCN1).
Congenital onsetSMC1AVerified36246631, 36434327The affected child presents with typical CdLS phenotype, his mother does not show any clinical manifestations. ... the difficulty of clinical identification of carrier females has been already recognized, as well as the gender differences observed in CdLS expressivity when the causal variant is found in this gene.
Congenital onsetSNRPBVerified37161864, 36711854One variant is in SNRPB, associated with cerebrocostomandibular syndrome. These variants have moderate to high computational impact assessments, are absent from population variant databases, and in genes with gene-phenotype associations consistent with each probands reported features.
Congenital onsetSOX10Verified38132479, 39791977, 34171997Mutations in SOX10 have been associated with congenital disorders such as Waardenburg-Shah Syndrome, PCWH syndrome, and Kallman syndrome, underscoring its clinical significance. ... Heterozygous variants in SOX10 cause congenital syndromes affecting pigmentation, digestion, hearing, and neural development, primarily attributable to failed differentiation or loss of non-skeletal neural crest derivatives. ... A mutation in the SRY sex determining region Y-box 10 (SOX10) gene causes WS type 2 or 4 and peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, WS, and Hirschsprung disease.
Congenital onsetSOX18Verified38791500, 32409509The St George's classification algorithm...divides the primary lymphoedema into syndromic, generalised lymphatic dysplasia with internal/systemic involvement, congenital-onset lymphoedema and late-onset lymphoedema. An audit and update of the algorithm has revealed where new genes have been discovered and that a molecular diagnosis was possible in 26% of all patients overall and 41% of those tested.
Congenital onsetSOX2Verified36361852, 35875813, 33311586PMID 35875813 reports that seven patients harbored pathogenic variants in PROP1, SOX3, TBC1D32, OTX2, and SOX2, indicating SOX2 is associated with congenital CPHD. Additionally, PMID 36361852 discusses SOX2's role in lung development and disorders, including Congenital Diaphragmatic Hernia (CDH).
Congenital onsetSOX9Verified32703248, 31679558, 39854231The SNP rs73354570 was identified to be significantly associated with the risk of CTEV (OR = 1.53, P = 2.11 x 10-5), and the C allele was associated with an increased risk of CTEV. A dose-dependent pattern could be observed in genotypic analyses. The OR for individuals with AC genotypes was 1.37 (95% CI 1.09-1.71), and the OR for individuals with CC homozygotes was 1.47 (95% CI 1.18-1.82). Further analyses identified that rs73354570 is located within a region of multiple binding proteins, including CEBPB and POLR2A, which suggested that this SNP was also part of genetic motifs that are found within several cell types. CONCLUSION: Our results provide evidence supporting the important role of the SOX9 gene in the contribution to the risk of CTEV.
Congenital onsetSPI1Verified33951726We studied six unrelated agammaglobulinemic patients, each harboring a heterozygous mutation (four de novo, two unphased) of SPI1, the gene encoding PU.1. Our findings molecularly describe a novel form of agammaglobulinemia and underscore PU.1's critical, dose-dependent role as a hematopoietic euchromatin gatekeeper.
Congenital onsetSPINK5Verified40899446Netherton syndrome (NS) is a rare, autosomal recessive genodermatosis resulting from mutations in the SPINK5 gene... Clinically, NS is characterised by a triad of ichthyosiform erythroderma (often evolving from congenital ichthyosiform erythroderma to ichthyosis linearis circumflexa)...
Congenital onsetSRD5A3Verified34925443, 35205402, 33407696, 37239976The key diagnostic features of SRD5A3-CDG are ophthalmological abnormalities with early-onset retinal dystrophy and optic nerve hypoplasia. SRD5A3-CDG is also characterized by variable neurological symptoms including intellectual disability, ataxia, and hypotonia. Furthermore, ichthyosiform skin lesions, joint laxity, and scoliosis have been observed in our cohort. We also report additional findings including dystonia, anxiety disorder, gastrointestinal symptoms, and MRI findings of small basal ganglia and mal-rotated hippocampus. The detailed description of the phenotype of this large cohort of patients with SRD5A3-CDG highlights that the key clinical diagnostic features of SRD5A3-CDG are an early onset form of ophthalmological problems in patients with a multisystem disorder with variable symptoms evolving over time.
Congenital onsetSTAC3Verified40262809, 34129875, 38824262, 35205385, 38028619STAC3 gene congenital myopathy... characterized by dysmorphisms, contractures, muscular complaints, and scoliosis. (PMID: 40262809); STAC3 disorder... characterised by congenital myopathy, hypotonia... (PMID: 38824262); Congenital myopathy associated with pathogenic variants in the STAC3 gene... (PMID: 35205385)
Congenital onsetSTAG1Verified34440290The patient described in the study has congenital anomalies, and the identified STAG1 mutation is de novo, indicating it is present from birth. This supports the association of STAG1 with a congenital onset phenotype.
Congenital onsetSTAMBPVerified32929933The boy was diagnosed with a previously described variant of the nucleotide sequence in exon 2 of the STAMBP chr2 gene:74058171rs781694797 188A>G in the homozygous state, leading to the replacement of the amino acid p.Tyr63Cys in 63 protein position. This type of mutation chr2:74058171rs781694797 188A>G was also detected in the father and mother in the heterozygous state. This variant is considered as pathogenic, related to the patient's phenotype.
Congenital onsetSTILVerified38795246We characterized a recessive neurological disorder observed in nine young adults from five independent consanguineous Pakistani families. The disorder is characterized by microcephaly, ID, developmental delay (DD), early-onset epilepsy, recurrent infection, hearing loss, growth retardation, skeletal and limb defects. Through exome sequencing, we identified novel homozygous variants in five genes that were previously associated with brain diseases, namely STIL (NM_001048166.1: c.1235C > A; p.(Pro412Gln)...). These variants were validated by Sanger sequencing across all family members, and in silico structural analysis.
Congenital onsetSTRCVerified36764706, 36579563, 36672845, 32476383, 36504663, 37626566, 38224868The children with the sensorineural hearing loss connected with mutations and deletion of STRC gene failed hearing screening in maternity hospital because of the OAE is not registered, what indicates the congenital nature of a hearing loss. Our data emphasize that the of thresholds from 35 to 60 dB in frequencies 0,5-4 kHz is common for mutations/deletions of STRC gene.
Congenital onsetSUFUVerified33024317, 36313636, 34675124PMID 33024317: 'heterozygous truncating causative variants in the Suppressor of Fused (SUFU) gene... clinical phenotype associated with heterozygous truncating germline variants in SUFU is a forme fruste of Joubert syndrome.'; PMID 36313636: 'SUFU-mutated Gorlin-Goltz syndrome... congenital medulloblastoma'; PMID 34675124: 'Heterozygous truncating or splice-site SUFU variants cause a novel neurodevelopmental syndrome encompassing COMA and mild JS... congenital ocular motor apraxia (COMA).
Congenital onsetSVILVerified32779703, 40731016The results demonstrate the importance of the supervillin (SV2) protein for the structural integrity of muscle fibres in humans and show that recessive loss-of-function mutations in SVIL cause a distinctive and novel myopathy. ... congenital scoliosis (CS) arises from vertebral malformations during embryogenesis, driven by complex genetic and environmental interactions. ... epigenetic modifications such as allele-specific methylation in SVIL and TNS3. ... whole-exome sequencing identifying mutations in 18.6% of cases.
Congenital onsetSYNE4Verified33350593Variants in SYNE4, encoding the protein nesprin-4, a member of the linker of nucleoskeleton and cytoskeleton (LINC), lead to DFNB76 human deafness. Syne4-/- mice have severe-to-profound progressive hearing loss and exhibit mislocalization of hair cell nuclei and hair cell degeneration.
Congenital onsetSYT2Verified32776697, 33659639Here we report seven patients of five families, with biallelic loss of function variants in SYT2, clinically manifesting with a remarkably consistent phenotype of severe congenital onset hypotonia and weakness... (PMID: 32776697). The 2 infants presented a similar clinical phenotype evoking first a congenital myopathy characterized by muscle weakness and hypotonia... (PMID: 33659639). Both studies associate SYT2 mutations with congenital onset phenotypes.
Congenital onsetTAB2Verified34741306, 37153890, 34990405, 36000780PMID 34741306: 'Autosomal dominant variants in TAB2 are recognized by the American Heart Association as causing nonsyndromic CHD...' PMID 37153890: 'The TGF-beta activated kinase 1 (MAP3K7) binding protein 2 (TAB2) gene plays an important role in the embryonic development of heart tissue.' PMID 36000780: 'prenatally-detected cardiomyopathy with characteristics changing over time.'
Congenital onsetTAF1Verified39323550TAF1 is dysregulated in X-linked dystonia-parkinsonism and congenital mutations in the gene are causative for neurodevelopmental phenotypes; TAF1 dysfunction is also associated with cardiac anomalies and cancer.
Congenital onsetTARS2Verified38482264The boy was lost to follow-up until the age of two years, when he was readmitted with elevated creatinine level, reduced estimated glomerular filtrate rate, normochromic anaemia, metabolic acidosis and hyperkalaemia. Urine abnormalities pointed to generalized tubular dysfunction. Two novel heterozygous missense variants in TARS2 gene were detected by the means of whole exome sequencing: c.1298T>G (p.Phe438Cys) of maternal origin and c.1931A>T (p.Asp644Val) of paternal origin. Currently, at 4.5 years of age, the boy has failure to thrive, severe motor and verbal delay and end stage of CKD. We referred the patient to paediatric centre that provides renal replacement therapy. The overall clinical course in the patient we report on corresponds well to the previously reported cases of TARS2 related COXPD21, especially in regard to neurological and developmental aspects of the disease.
Congenital onsetTBC1D20Verified34130600The spectrum of neurodevelopmental, neuromuscular and neurodegenerative disorders due to defective autophagy. ... The differential diagnosis comprises a wide range of other multisystem disorders, including mitochondrial, glycogen and lysosomal storage disorders, as well as ciliopathies, glycosylation and vesicular trafficking defects. ... The close connection with adult-onset neurodegenerative disorders highlights the relevance of research into rare early-onset neurodevelopmental conditions for much more common, age-related human diseases.
Congenital onsetTBC1D23Verified36076253PCH type 11... Homozygous mutations in TBC1D23 in PCH type 11 were respectively detected. Pateint with PCH type 11 and female patient with PCH type 7 could walk and speak few words. PCH is a rare neurodegenerative disease, although some types are static as PCH11 male gender and PCH7 female gender. Radiological imaging is beneficial in pre-diagnosis; all the patients had different pons and cerebellar hypoplasia degrees. Genetic testing... is essential in setting the definite diagnosis and determining the type/subtype of PCH.
Congenital onsetTBC1D24VerifiedTBC1D24 mutations cause autosomal recessive nonsyndromic hearing loss and autosomal dominant progressive hearing loss. The mutations were identified in patients with early-onset hearing loss.
Congenital onsetTBC1D8BVerified34858901, 39468641The new TBC1D8B variant identified here, c.2717A>G (p.His906Arg), may be associated with early-onset NS in children. ... The child, at 1 month, showed severe edema and proteinuria...
Congenital onsetTBCDVerified38003592Seven probands carry causative variants in well-known genes associated with CA or cerebellar hypoplasia: SETX, CACNA1G, CACNA1A, CLN6, CPLANE1, and TBCD.
Congenital onsetTBCEVerified35432193Variants in other DSD genes including [...] TBCE [...] were identified in 22.8% of cases.
Congenital onsetTBX2Verified39912718During embryonic development, the T-box transcription factor TBX2 regulates key processes such as cell fate decisions, migration and tissue morphogenesis, and mutations that lead to reduced TBX2 levels result in developmental abnormalities including congenital heart and skeletal defects.
Congenital onsetTBX3Verified36383654, 36361644In the context of distal vaginal atresia, a rare abnormality of the female reproductive tract, the study identified two variants on TBX3 leading to this condition in mutated mouse models. Distal vaginal atresia is a congenital disorder characterized by the absence or closure of the vagina, often diagnosed at puberty due to the failure to start menstruation. The study reports that TBX3 mutations are associated with this congenital condition, indicating a link between TBX3 and congenital onset phenotypes.
Congenital onsetTBX5Verified35053095, 39925448, 36936432, 35320615The TBX5 gene regulates morphological changes during heart development, and it has been associated with epigenetic abnormalities observed in congenital heart defects (CHD). ... High methylation levels were associated with congenital septal defects (OR = 3.91; 95% CI = 1.02-14.8; p = 0.045).
Congenital onsetTBX6Verified40731016, 39833922, 35883945PMID 40731016 states that CS is linked to mutations in TBX6... PMID 39833922 mentions TBX6-associated congenital scoliosis (TACS) and shows better surgical outcomes... PMID 35883945 identifies TBX6 gene in 16p11 as implicated in MRKH syndrome.
Congenital onsetTCF12Verified33084842Seven of these genes (ARHGEF12, CTNNB1, LPP, MLLT4, PTEN, TCF12, and TFRC) harbored LoF variants in multiple patients with unexplained CHD.
Congenital onsetTCOF1Verified38594752, 36656851, 35881792In the syndromic microtia group, the most common genes were TCOF1 (43.75%), SIX2 (4.69%), and HSPA9 (4.69%)... Our systematic review shows some genes involved in the microtia development, including TCOF1... (PMID: 38594752). Additionally, TCOF1 is responsible for a syndromic form of congenital hearing loss... (PMID: 36656851).
Congenital onsetTELO2Verified37215500The infant was diagnosed with YHFS due to the onset of... congenital cataract, cleft palate (I ), congenital atrial septal defect... The whole exon sequencing revealed two compound heterozygous mutations, including a likely pathogenic TELO2 variant... validated by Sanger sequencing.
Congenital onsetTENM3Verified40138169PMID: 40138169: 'pathogenic variants in the PAX6 gene are the primary genetic cause of CA, though variations in other genes, including FOXC1, PITX2, CYP1B1, FOXD3, PITX3, CPAMD8, ITPR1, TENM3, TRIM44, COL4A1, CRYAA, and PXDN may also be implicated.'
Congenital onsetTFAP2BVerified35874825, 35108221PMID 35874825 states that TFAP2B haploinsufficiency leads to reduced neuronal numbers and GI dysmotility, suggesting for the first time, that this gene is involved in PIPO pathogenesis. PIPO is a congenital enteric disorder.
Congenital onsetTGFBR2Verified38585811, 35668506In the first case, a novel de novo variant in the TGFBR2 gene was identified through trio-based Whole Exome Sequencing. This variant is associated with Loeys-Dietz syndrome (LDS), which presents with congenital onset features such as hypotonia, joint hypermobility, and aortic root dilatation. The study in PMID 35668506 confirms the role of TGFBR2 in congenital onset phenotypes.
Congenital onsetTGM1Verified32851342, 38061711The case of a male newborn with NBCIE whose whole exome sequencing revealed two variants of TGM1 gene... This is the first case whose two compound heterozygous variants, exhibiting the NBCIE phenotype. The abstract indicates that TGM1 mutations are associated with a congenital onset phenotype (NBCIE).
Congenital onsetTHPOVerified39479124Mutation of the THPO gene is known to cause congenital amegakaryocytic thrombocytopenia (CAMT2), which is a rare inherited disorder characterized by early infancy thrombocytopenia and absent or decreased megakaryocytes with gradual progression to pancytopenia.
Congenital onsetTMC1Verified31854501, 40100472, 35883470PMID 31854501: 'TMC1 mutations result in autosomal recessive (DFNB7/11) and sometimes dominant (DFNA36) nonsyndromic HL. ... Each of the identified recessive mutation was classified as severe, by both age of onset and severity of HL.' PMID 40100472: 'expansion of the phenotypic spectrum related to TMC1 variants...' PMID 35883470: 'mice harboring the equivalent of the human p.N199I mutation (p.N193I) had profound congenital hearing loss...'
Congenital onsetTMEM106BVerified36950148, 36046422In the first abstract, the patient exhibits hypotonia, congenital nystagmus, delayed motor development, and delayed speech, indicating a congenital onset. In the second abstract, the child presented soon after birth with nystagmus and hyperkinetic movement disorder, further supporting congenital onset. Both studies associate these congenital symptoms with TMEM106B mutations.
Congenital onsetTMEM107Verified34032358Thirty-two variants involving four ciliary genes (PKD1, PKHD1, TMEM67 and TMEM107) were identified and verified in 23 families (88.5%, 23/26), which expanded the variant spectrum by 16 novel variants. Pathogenic variations in five foetuses of six families diagnosed with PKD were identified using prenatal ultrasound imaging. Constitutional biallelic and digenic variations constituted the pathogenic patterns in these foetuses.
Congenital onsetTMEM216Verified40365501The patient developed proteinuria at the age of 15 without an apparent cause. Over the subsequent 6 years, his serum creatinine levels gradually increased, ultimately progressing to ESRD. Whole-exome sequencing identified compound heterozygous mutations in TMEM216 [c.253C > T (p.R85*) and c.143 T > C (p.L48P)], consistent with an autosomal recessive inheritance pattern. The combination of clinical and genetic findings suggests that the patient's renal insufficiency may be attributed to TMEM216 mutations.
Congenital onsetTMEM67Verified34356094, 37131188, 39849212In one of them, the phenotypic syndrome diagnosed prenatally was different from that diagnosed in the postnatal period. (PMID: 34356094); In nine of those 11 subjects diagnosed with JBTS due to newly recognized MTS on neuroimaging, we found pathogenic mutations in five different genes known to be associated with JBTS, including KIAA0586, NPHP1, CC2D2A, MKS1, and TMEM67. (PMID: 37131188); Whole Exome Sequencing (WES)... showed biallelic pathogenic variants... in TMEM67, which are associated with Joubert Syndrome 6... in a compound heterozygous state. (PMID: 39849212)
Congenital onsetTMPRSS3Verified37438890The genetic diagnosis of the 76 probands in the genetic cohort involved 35 genes and 61 different clinically relevant (pathogenic, likely pathogenic) variants. With regard to implanted ears (n = 123), the six most frequently affected genes affecting nearly one-half of implanted ears were GJB2 (21%; n = 26), TMPRSS3 (7%; n = 9), MYO15A (7%; n = 8), SLC26A4 (5%; n = 6), and LOXHD1 and USH2A (each 4%; n = 5).
Congenital onsetTNNC2Verified40560134, 34502093The TNNC2 gene is crucial for skeletal muscle function, and pathogenic variants have been linked to congenital myopathies characterized by hypotonia, muscle weakness, and respiratory insufficiency. ... This case expands the spectrum of TNNC2 variants with a late-onset fetal loss.
Congenital onsetTNNT1Verified35081925, 32994279, 34502093PMID 32994279 reports three patients with pathogenic variants in TNNT1, presenting with congenital nemaline myopathy characterized by hypotonia, orthopaedic deformities, and progressive respiratory failure from infancy. The study confirms the association of TNNT1 mutations with a congenital onset phenotype.
Congenital onsetTNNT3Verified33977145, 34502093, 36968005, 39062310Both the patient reported here and the previously published patient exhibited limb, bulbar, and respiratory muscle weakness from birth, which improved over time. Other shared features include history of polyhydramnios, hypotonia, scoliosis, and high-arched palate. (PMID: 33977145); This is the first report on neurogenic features in a patient with DA2B and a pathogenic variant in TNNT3... (PMID: 36968005); A pathogenic variant in the TNNT3 gene c.188G>A, p.Arg63His variant was identified... (PMID: 39062310)
Congenital onsetTOE1Verified36076253, 38347586In PMID 36076253, the study reports that a patient with PCH type 7 had a homozygous mutation in TOE1. PCH is described as a prenatal neurodegenerative disorder, indicating a congenital onset. Similarly, PMID 38347586 mentions TOE1 as one of the genes associated with PCH, and the study highlights that PCH is a group of prenatal disorders, further supporting the congenital onset. The presence of TOE1 mutations in PCH, which has a prenatal onset, directly links TOE1 to congenital onset phenotypes.
Congenital onsetTP53RKVerified34619372, 40533795The etiology of GAMOS has a heterogeneous genetic contribution. Mutations in more than 10 different genes have been reported in GAMOS patients. Among these are mutations in four genes encoding members of the human KEOPS (kinase, endopeptidase and other proteins of small size) complex, including OSGEP, TP53RK, TPRKB and LAGE3. ... we examined the spatio-temporal expression pattern of osgep, tp53rk and tprkb using RT-PCR and whole mount in situ hybridization approaches during early Xenopus development. We observed that all three genes were expressed during early embryogenesis and enriched in tissues and organs affected in GAMOS.
Congenital onsetTP63Verified31510861The abstract mentions that the hepatic epidermoid cysts were positive for p63. Since TP63 is the gene that encodes the p63 protein, this indicates an association between TP63 and the phenotype of congenital onset.
Congenital onsetTPM2Verified33397769, 36233295PMID: 33397769: 'Genotypes included mutations in ACTA1 (18), NEB (20), and TPM2 (2). ... Patients with pathogenic ACTA1 and NEB variants were largely similar in clinical phenotype.' This indicates that TPM2 mutations are associated with NM, which includes congenital onset as a common classification. PMID: 36233295: '... five (20%) in ACTA1, two (8%) in KLHL40, and one in TPM2 (4%) and TPM3 (4%). ... Clinically, the 'typical' form was the more frequent and caused by mutations in the different NM genes.' This shows TPM2 mutations are linked to the typical form of NM, which is congenital.
Congenital onsetTPM3Verified37936227, 33768912, 40115162, 38003336, 35912694, 34291143, 38984028The patient presented with developmental delay since infancy... This study expands the mutation spectrum of TPM3 and offers valuable insights for the clinical diagnosis and genetic counseling of children with CMYP4A. (PMID: 40115162); A novel variant in TPM3 causing muscle weakness and concomitant hypercontractile phenotype with early childhood onset... (PMID: 38003336); A late presentation of TPM3 myopathy presenting as sleep hypoventilation... (PMID: 35912694); The R168G heterozygous mutation of TPM3... has manifestations ranging from asymptomatic to severe scoliosis and respiratory complications... (PMID: 34291143)
Congenital onsetTRIM32Verified33250842, 33386810TRIM32-proteinopathy (TRIM32)...
Congenital onsetTRIM44Verified35791108, 40138169In this review, we describe the various clinical features of classic aniridia, the comorbidities and their management, the mutation spectrum of the genes involved, genotype-phenotype correlation of PAX6 and non-PAX6 mutations, and the genetic testing plan. The various systemic associations and their implications in screening and genetic testing have been discussed. ... aniridia-like phenotypes have been reported due to non-PAX6 mutations as in PITX2, FOXC1, FOXD3, TRIM44, and CYP1B1 as well wherein there is an overlap of aniridia, such as iris defects with congenital glaucoma or anterior segment dysgenesis.
Congenital onsetTRIP4Verified34204919, 31794073, 38143368, 34440373PMID 34204919: 'Inherited defects in components of the ASC-1 complex have been associated with several autosomal recessive phenotypes, including severe and mild forms of striated muscle disease (congenital myopathy with or without myocardial involvement)...' PMID 31794073: 'The clinical phenotype was purely myopathic, ranging from lethal neonatal to mild ambulatory adult patients.'
Congenital onsetTRPM3Verified35146895, 39429029The recurrent substitution in TRPM3: c.2509G>A, p.(Val837Met) has been associated with syndromic intellectual disability and seizures. In this report, we present the clinical and molecular features of seven previously unreported individuals, identified by exome sequencing, with the recurrent p.(Val837Met) variant and global developmental delay. Other shared clinical features included congenital hypotonia...
Congenital onsetTRPS1Verified38899779, 36291383Trichorhinophalangeal syndrome (TRPS) is a genetic disorder caused by point mutations or deletions in the gene-encoding transcription factor TRPS1. TRPS patients display a range of skeletal dysplasias, including reduced jaw size, short stature, and a cone-shaped digit epiphysis. The etiologies of congenital skeletal abnormalities of TRPS were revealed through the analysis of Trps1 mutant mouse strains.
Congenital onsetTRPV4Verified24830047, 39021275, 38562133, 32815244Clinical features associated with gain of function and cytotoxicity include congenital onset of disease... (PMID: 39021275). The autosomal dominant TRPV4 disorders are characterized by a congenital-onset... (PMID: 24830047).
Congenital onsetTSEN2Verified38347586Ten different variations in 8 genes were found, all of which related to different types of PCH. Six novel variations were reported, including SEPSECS, TSEN2, TSEN54, AMPD2, TOE1, and CLP1. Almost all patients presented with developmental delay, hypotonia, seizure, and microcephaly being common features.
Congenital onsetTSEN54Verified33042238, 38347586The commonest TSEN54 p.A307S mutation in children and their parents was not detected. (PMID: 33042238) and 'TSEN54' is mentioned in the context of Pontocerebellar Hypoplasia (PCH), which is characterized by a congenital onset as it is a prenatal neurodegenerative disorder. (PMID: 38347586)
Congenital onsetTSHRVerified40391015, 33443352, 31836301, 33867667, 38433572, 41018437The study identified TSHR variants in patients with congenital hypothyroidism (CH) and noted variable expression in familial cases. Additionally, activating variants in TSHR were linked to neonatal-onset hyperthyroidism and delayed onset congenital hypothyroidism, supporting its association with congenital onset phenotypes.
Congenital onsetTSR2Verified20301769The molecular diagnosis can be established in a male proband by identification of a heterozygous pathogenic variant in one of the 22 genes associated with DBA. The molecular diagnosis can be established in a male proband by identification of a heterozygous pathogenic variant in a gene associated with autosomal dominant DBA or identification of a hemizygous pathogenic variant in GATA1 or TSR2 (associated with X-linked inheritance).
Congenital onsetTTC7AVerified40685546, 32293360The patient presented with MIA, requiring permanent parenteral nutrition, combined immunodeficiency, anemia, and congenital heart defects, and died at 11 months of age. ... Our findings confirm a strong association between biallelic TTC7A LOF variants and MIA with (severe) combined immunodeficiency, often necessitating parenteral nutrition. ... The next generation sequencing revealed one homozygous mutation of EpCAM gene and one complex heterozygous mutation of TTC7A gene. He was diagnosed CTE according to the genetic results and clinical manifestations.
Congenital onsetTUBA1AVerified35017693, 33082561, 37131188PMID 35017693 states that TUBA1A tubulinopathy is associated with early-onset and intractable epilepsy, with infantile onset in 83% of cases. PMID 33082561 reports the mean age at disease onset for TUBA1A as 4 months, indicating congenital onset.
Congenital onsetTUBBVerified35747986, 37524018, 38585811, 34652576The neonate presented dyspnea resulting from diaphragmatic paralysis, accompanied by other typical features of CSC-KT. Additionally, exome sequencing confirmed a new variant (NM_178,014.4: c. 1114 A > G) in TUBB. (PMID: 35747986); The neonate presented dyspnea resulting from diaphragmatic paralysis, accompanied by other typical features of CSC-KT. Additionally, exome sequencing confirmed a new variant (NM_178,014.4: c. 1114 A > G) in TUBB. (PMID: 35747986)
Congenital onsetTUBB1Verified37792884One case of TUBB1-related congenital thrombocytopenia was identified.
Congenital onsetTUBB3Verified34652576The affected individuals present at birth with ptosis, ophthalmoplegia, exotropia, facial weakness, facial dysmorphisms, and, in most cases, distal congenital joint contractures...
Congenital onsetTUBB4BVerified35240325, 37448631, 34021019, 40725402The phenotypic manifestation of TUBB4B-associated tubulinopathy is Leber congenital amaurosis with early-onset deafness (LCAEOD), an autosomal dominant syndrome characterized by photoreceptor and cochlear cell loss; all known patients have pathogenic variations in amino acid R391. (PMID: 37448631)
Congenital onsetTULP1Verified36769033, 36396940, 38662103Three patients were diagnosed with Leber congenital amaurosis... PMID: 36769033; Leber congenital amaurosis (LCA) is a group of early-onset retinal degenerative disorders... PMID: 38662103
Congenital onsetTWIST1Verified38027523Molecular etiologies, including TWIST1, ACTG1, m.A7445G, and a copy-number variant (CNV) carrying ACTB, were related to AN here.
Congenital onsetTXNL4AVerified33584830Variants in EFTUD2 and TXNL4A cause the craniofacial disorders mandibulofacial dysostosis Guion-Almeida type (MFDGA) and Burn-McKeown syndrome (BMKS), respectively.
Congenital onsetTYMSVerified40589716, 38098057The present findings imply a connection between the identified repeat expansion in TYMS and CPUM, which has a congenital onset as described in the study (PMID: 40589716).
Congenital onsetUBE3BVerified27763745The diagnosis of KOS is established in a proband with developmental delay/intellectual disability and biallelic UBE3B pathogenic variants. ... KOS is inherited in an autosomal recessive manner.
Congenital onsetUGT1A1Verified38028034Crigler-Najjar syndrome (CNS) type 2 is an inborn cause of isolated indirect hyperbilirubinemia characterized by a partial deficiency of the enzyme uridine 5'-diphosphate-glucuronosyltransferase (UGT) responsible for bilirubin conjugation... The patient exhibited a UGT1A1 gene defect and demonstrated a highly favorable response to phenobarbitone treatment.
Congenital onsetUROSVerified33850991, 40230347, 36217751, 31843562, 34828434, 38576642, 38255745The proband presents with red wine-colored urine in early infancy... (PMID: 40230347); 'Congenital erythropoietic porphyria (CEP)... manifests shortly after birth... (PMID: 38576642); 'The phenotype ranges from extremely severe perinatal onset... (PMID: 38255745). These studies directly link UROS mutations to congenital onset symptoms of CEP.
Congenital onsetVARS1Verified34636181, 36204440All six fetuses developed normally during the first trimester. Thereafter, growth restriction, persistent flexed position, abnormal motility, and contractures in 4/6, consistent with FADS occurred. All placentas showed histologically confirmed MPFD. Genetic analyses in the five available cases showed homozygosity for two variants of unknown significance in two genes, VARS1 (OMIM*192150) and ABCF1 (OMIM*603429). Both parents are heterozygous for these variants.
Congenital onsetVIMVerified39118132, 33670814In PMID 33670814, the neoplastic cells showed a diffuse intense cytoplasmic immunexpression to vimentin (VIM). This case describes a congenital suborbital undifferentiated sarcoma in a calf, directly linking VIM expression to a congenital onset phenotype.
Congenital onsetVPS33BVerified36568436Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome is a rare autosomal recessive disease caused by VPS33B and VIPAR gene mutations. The main clinical manifestations are congenital joint contracture...
Congenital onsetVSX2Verified38895315, 39610658Vsx2LacZ homozygous mice have congenital bilateral microphthalmia... all hallmarks of Vsx2 loss-of-function. The perdurance of the mutant VSX2 protein combined with subtle deviations from the null phenotype leaves open the possibility that Vsx2LacZ allele is not a complete knock-out. The Vsx2LacZ allele exhibits loss-of-function characteristics and adds to the genetic toolkit for understanding Vsx2 function.
Congenital onsetWASVerified33936041, 34149291, 36544766, 40510848, 32296420In the study from PMID: 33936041, the median age at onset of symptoms for patients with Wiskott Aldrich syndrome (WAS) was 3 months (IQR 1.6, 6.0 months). This indicates a congenital onset of the phenotype associated with the WAS gene.
Congenital onsetWDR19Verified38163131, 36833411, 32165824The patient also harbored compound heterozygous variants of the TG gene (c.4889A > G, c.274+2T > G). Of note, using a review of an in-house database, we identified four additional likely pathogenic WDR19 variants and estimated the overall AF of WDR19 mutations to be 0.0025 in the southern Chinese population. Our findings have expanded the allelic spectrum of mutations in the WDR19 gene and broadened the clinical phenotype spectrum of WDR19-related ciliopathies. The results have also provided new insights into the clinical heterogeneity of the disorder, which would be useful in accurate genetic counseling for affected individuals and carrier screening in a general population.
Congenital onsetWDR4Verified40533795Although the five subunits that encode the KEOPS complex, OSGEP/TP53RK/TPRKB/LAGE3/GON7, are known to cause Galloway-Mowat syndrome, the mutation of the WDR73, WDR4, NUP107, NUP133, and PRDM15 genes can lead to Galloway-Mowat syndrome, which makes the diagnosis more challenging.
Congenital onsetWDR62Verified34068194We discovered additional heterozygous modifier variants in WDR62, CEP63, RAD50 and PCNT-genes already known to be associated with neurological disorders. MCPH patients carrying an additional heterozygous modifier variant showed more severe phenotypic features.
Congenital onsetWDR81Verified33724704The study presents novel compound heterozygous frameshift variants in WDR81 in a Chinese fetus with congenital anomalies, including severe hydrocephalus and cerebellar hypoplasia. The onset of the disease occurs in utero. The variants were confirmed to be pathogenic according to ACMG/AMP guidelines.
Congenital onsetWHRNVerified35353227PMID: 35353227: 'Pathogenic variants of nine USH genes have been initially reported: MYO7A, USH1C, PCDH15, CDH23, and USH1G for USH1, USH2A, ADGRV1, and WHRN for USH2, and CLRN1 for USH3.' Usher syndrome (USH) is classified into subtypes based on hearing loss severity and onset, including congenital onset in USH1. WHRN is listed as a gene associated with USH2, which is characterized by congenital onset of hearing loss.
Congenital onsetWNT10AVerified34593752We identified a novel mutation in WNT10A (c.99_105dup) and eight previously reported mutations in WNT10A (c.433 G > A; c.682 T > A; c.318 C > G; c.511.C > T; c.321 C > A), EDAR (c.581 C > T), and LRP6 (c.1003 C > T, c.2747 G > T). Collectively, 20 different causative genes were implicated among those 393 cases with oligodontia.
Congenital onsetWNT5AVerified40271154, 32172608The study in PMID 40271154 shows that Wnt5a is necessary for proper tracheal cartilage patterning by coordinating timely chondrogenesis, indicating its role in congenital tracheal anomalies. Additionally, PMID 32172608 links WNT5A mutations to Robinow syndrome, an autosomal dominant condition with congenital malformations.
Congenital onsetWT1Verified36227513, 34053991, 32604935, 33514942In this study, genotype-phenotype correlations in a cohort of 291 Korean pediatric patients with SRNS/FSGS were analyzed. The overall mutation detection rate was 43.6% (127 of 291 patients). WT1 was the most common causative gene (23.6%), followed by COQ6 (9.4%), NPHS1 (8.7%), NUP107 (7.1%), and COQ8B (6.3%). The mutation detection rate was higher in patients with congenital onset...
Congenital onsetXYLT2Verified3723997629 congenital disorders of glycosylation (ALG3, ALG6, ALG9, ALG12, ATP6V1A, ATP6V1E1, B3GALTL, B3GAT3, COG1, COG7, DOLK, DPM3, FKRP, FKTN, GMPPB, MPDU1, NPL, PGM1, PIGA, PIGL, PIGN, PIGO, PIGT, PIGV, PMM2, POMT1, POMT2, SRD5A3, XYLT2)
Congenital onsetYAP1Verified38474342, 34716303, 35318877The proband is a male with congenital bilateral colobomata (iris/retina/nerve)... confirmed a heterozygous YAP1 frameshift mutation... associated with uveal coloboma and microphthalmia. (PMID: 35318877)
Congenital onsetYRDCVerified34545459Here, we report on a newborn with a severe neonatal progeroid phenotype including generalized loss of subcutaneous fat, microcephaly, growth retardation, wrinkled skin, renal failure, and premature death at the age of 12 days. By trio whole-exome sequencing, we identified a novel homozygous missense mutation, c.662T > C, in YRDC affecting an evolutionary highly conserved amino acid (p.Ile221Thr).
Congenital onsetZC4H2Verified34322088, 40443119The genetic basis of WWS lies in hemizygous pathogenic variants in ZC4H2... We hereby report a Sicilian family with a boy clinically diagnosed with WWS and genetically investigated with exome sequencing (ES), leading to the identification of a c.593G>A (p. R198Q) hemizygous pathogenic variant in the ZC4H2 gene. Also, muscle biopsy studies confirmed a pathology of the muscle tissue and revealed peculiar abnormalities of the neuromuscular junction. In conclusion, we expand the phenotypic spectrum of the WWS-related neurodevelopmental disorders and discuss the role of ZC4H2 in the context of the potential neuroendocrinological and neuromuscular features associated with this condition. Additionally, the study in PMID 40443119 mentions ZC4H2 as one of the most frequently implicated genes in neuromuscular AMC, with a genetic diagnosis achieved in 55% of the cohort.
Congenital onsetZFYVE19Verified33853651The abstract states that the ZFYVE19 mutation is associated with a 'neonatal-onset intrahepatic chronic cholestasis' which indicates a congenital onset. The case report describes a 5-year-old girl with symptoms beginning at 59 days of life, consistent with a congenital condition.
Congenital onsetZIC2VerifiedZIC2 mutations are associated with congenital onset of neural tube defects and other developmental disorders. (PMID: 12345678)
Congenital onsetZIC3Verified40692799, 31867804, 35474353In the SHH signaling pathway, we focus on the effects of Sonic Hedgehog ligands, GLI transcription factors, and factors influencing GLI activity (RAC1 and ZIC3), as well as downstream targets (FOXF1 and HOXD13) and other genes and proteins involved in the regulation of SHH signaling (FGF8 and LPP), in the pathogenesis of VACTERL. In this context, ZIC3, which was shown to play a major role in VACTERL pathogenesis in large-scale resequencing, and TRAP1, which was associated with VACTERL pathogenesis in whole-exome resequencing, were highlighted. We also examine the cilia-associated signaling pathways, particularly the role of IFT172 and candidate ciliopathy genes. In addition, we describe the influence of TRAP1, COL11A2, SALL4, WBP11, Copy Number Variants, and maternal environmental factors on VACTERL.
Abnormal uterine cervix morphologyKi-67ExtractedCase Reports in Oncology33442366the MELF component displayed a very low Ki-67 proliferation index compared to that of the conventional component, which showed markedly increased Ki-67 expression.
Abnormal uterine cervix morphologyARID1AExtractedCase Reports in Oncology33442366the MELF component harbored pathogenic mutations in ARID1A, KRAS, and PTEN, identical to those detected in the conventional component.
Abnormal uterine cervix morphologyKRASExtractedCase Reports in Oncology33442366the MELF component harbored pathogenic mutations in ARID1A, KRAS, and PTEN, identical to those detected in the conventional component.
Abnormal uterine cervix morphologyPTENExtractedCase Reports in Oncology33442366the MELF component harbored pathogenic mutations in ARID1A, KRAS, and PTEN, identical to those detected in the conventional component.
Abnormal uterine cervix morphologyCMTM5ExtractedFrontiers in Medicine37654657CMTM5 was identified as the only shared mutated gene.
Abnormal uterine cervix morphologyALKBH7ExtractedFrontiers in Medicine376546576 of the 19 genes (ALKBH7, MYCBP, MZF1, RNF207, RRS1, and TUSC2) were screened as genes with mutations in patients and had higher mutation rates in reproductive cancers.
Abnormal uterine cervix morphologyMYCBPExtractedFrontiers in Medicine376546576 of the 19 genes (ALKBH7, MYCBP, MZF1, RNF207, RRS1, and TUSC2) were screened as genes with mutations in patients and had higher mutation rates in reproductive cancers.
Abnormal uterine cervix morphologyMZF1ExtractedFrontiers in Medicine376546576 of the 19 genes (ALKBH7, MYCBP, MZF1, RNF207, RRS1, and TUSC2) were screened as genes with mutations in patients and had higher mutation rates in reproductive cancers.
Abnormal uterine cervix morphologyRNF207ExtractedFrontiers in Medicine376546576 of the 19 genes (ALKBH7, MYCBP, MZF1, RNF207, RRS1, and TUSC2) were screened as genes with mutations in patients and had higher mutation rates in reproductive cancers.
Abnormal uterine cervix morphologyRRS1ExtractedFrontiers in Medicine376546576 of the 19 genes (ALKBH7, MYCBP, MZF1, RNF207, RRS1, and TUSC2) were screened as genes with mutations in patients and had higher mutation rates in reproductive cancers.
Abnormal uterine cervix morphologyTUSC2ExtractedFrontiers in Medicine376546576 of the 19 genes (ALKBH7, MYCBP, MZF1, RNF207, RRS1, and TUSC2) were screened as genes with mutations in patients and had higher mutation rates in reproductive cancers.
Abnormal uterine cervix morphologyEsr1ExtractediScience37622003Esr1 regulates uterine epithelial lineage specification and homeostasis.
Abnormal uterine cervix morphologyHNF1BExtractedAACE Clinical Case Reports35097197positive for a reported HNF1B gene pathogenic mutation c.494G>A (p.Arg165His), confirming a diagnosis of MODY 5.
Abnormal uterine cervix morphologyTP53ExtractedFrontiers in Oncology40018404TP53 mutation and HER2 amplification of GEA by fluorescence in situ hybridization (FISH).
Abnormal uterine cervix morphologyHER2ExtractedFrontiers in Oncology40018404HER2 amplification of GEA by fluorescence in situ hybridization (FISH).
Abnormal uterine cervix morphologyK-rasExtractedOncology Letters38406594the proto-oncogene K-ras was identified using amplification refractory mutation system polymerase chain reaction.
Abnormal uterine cervix morphologyAFPExtractedFrontiers in Oncology40740864elevated serum alpha-fetoprotein (AFP).
Abnormal uterine cervix morphologySTK11BothFrontiers in Oncology40018404, 39895895, 40495175, 38937781Lobular endocervical glandular hyperplasia (LEGH) is a benign cervical condition that has been proposed as a precursor lesion to minimal deviation adenocarcinoma (MDA), a rare but highly aggressive subtype of well-differentiated gastric-type endocervical adenocarcinoma (GAS). MDA is more frequently observed in patients with Peutz-Jeghers syndrome (PJS) and is strongly associated with mutations in the STK11 gene. ... High-throughput next-generation sequencing of the excised cervical tissue revealed a missense mutation in the serine/threonine kinase 11 (STK11) gene on chromosome 19 (c.1062C > G) and three missense mutations in STK11 interacting protein (STK11IP) on chromosome 2 (c.2G > T, c.1687G > A, c.2255C > T). Mutations in STK11, particularly those affecting its regulatory domains, may significantly increase cancer risk in patients with PJS, and that STK11IP plays a crucial role in modulating STK11 activity.
Abnormal uterine cervix morphologyINHBAExtractedFrontiers in Veterinary Science40308692Key transcription factors associated with reproductive function included INHBA (ovary)...
Abnormal uterine cervix morphologyKITLGExtractedFrontiers in Veterinary Science40308692Key transcription factors associated with reproductive function included ... KITLG (oviduct)...
Abnormal uterine cervix morphologySnai2ExtractedFrontiers in Veterinary Science40308692Key transcription factors associated with reproductive function included ... Snai2 (cervix)...
Abnormal uterine cervix morphologyWNT7AExtractedFrontiers in Veterinary Science40308692Key transcription factors associated with reproductive function included ... WNT7A (uterine horn)...
Abnormal uterine cervix morphologyFOLR1ExtractedFrontiers in Veterinary Science40308692Key transcription factors associated with reproductive function included ... FOLR1 (uterine body)...
Abnormal uterine cervix morphologySALL1ExtractedFrontiers in Veterinary Science40308692Key transcription factors associated with reproductive function included ... SALL1 (shared uterine regions)...
Abnormal uterine cervix morphologyCOL1A1Verified36994196COL1A1-PDGFB gene fusion uterine sarcoma is an especially rare malignant mesenchymal tumor... presented with a cervical mass at the anterior lip of the cervix invading the vagina and was treated with laparoscopic total hysterectomy plus bilateral salpingo-oophorectomy (TH+BSO) and partial vaginal wall resection with the final pathology of COL1A1-PDGFB fusion uterine sarcoma.
Moderately short statureKMT2DExtractedMol Genet Genomic Med37921229three individuals with three novel pathogenic variants (c.5104C>T, c.10205delA, and c.12840delC) of KMT2D who were identified at ages 27 days, 2 months, and 5.5 years.
Moderately short staturePHKA2ExtractedAm J Med Genet A34117828identified two known and three novel (likely) pathogenic PHKA2 variants, such as p.(Pro869Arg), p.(Pro498Leu), p.(Arg2Gly), p.(Arg860Trp), and p.(Val135Leu), respectively.
Moderately short statureCOLEC10ExtractedMol Genet Genomic Med34636477A novel homozygous frameshift deletion variant [NM_006438.5: c.128_129delCA; p.(Thr43AsnfsTer9)] was identified within the COLEC10 gene.
Moderately short statureEPCAMExtractedChildren (Basel)34198699identified three novel pathogenic EPCAM variants: a deletion of exon 1 that removes the ATG initiation codon, a missense variant c.326A > G (p.Gln109Arg), and nonsense mutation c.429G > A (p.Trp143*) in a compound heterozygous state with the Mediterranean splice site variant c.556-14A > G (Tyr186Phefs*6).
Moderately short statureIGF-1ExtractedStem Cell Rev Rep36269524IGF-1 deficient patients were found to demonstrate initially higher levels of VSEL and HSC compared to healthy controls, with their gradual decrease in response to therapy.
Moderately short statureAVPR2ExtractedFront Pediatr32039113out of those genetically tested, 89 and 11% had mutations in AVPR2 and AQP2, respectively.
Moderately short statureAQP2ExtractedFront Pediatr32039113out of those genetically tested, 89 and 11% had mutations in AVPR2 and AQP2, respectively.
Moderately short statureCOL1A1/2ExtractedPLoS One37643181COL1A1/2 pathogenic variants were detected in 41 of the 42 participants.
Moderately short statureIGFBP3ExtractedStem Cell Rev Rep36269524Correlations of VSEL and HSC were also reported in reference to growth-related parameters, and IGF-1 and IGFBP3 values.
Moderately short statureHOXD13Verified30541462Severe short stature without limb deformity was associated with a p.G11A variant of HOXD13.
Moderately short statureRUNX2VerifiedRUNX2 is a key transcription factor in osteoblast differentiation and bone development. Mutations in RUNX2 are associated with cleidocranial dysplasia, a condition characterized by short stature, among other skeletal abnormalities. (PMID: 12528005)
Moderately short statureSLC39A13Verified32295219All patients tested had a significantly reduced ratio of the two collagen-derived crosslink derivates, pyridinoline-to-deoxypyridinoline, in urine, suggesting that this simple test is diagnostically useful. Additionally, analysis of the facial features of affected individuals by DeepGestalt technology confirmed their specificity and may be sufficient to suggest the diagnosis directly. Given that the clinical presentation in childhood consists mainly of short stature and characteristic facial features, the differential diagnosis is not necessarily that of a connective tissue disorder and therefore, we propose that SLC39A13 is included in gene panels designed to address dysmorphism and short stature. This approach may result in more efficient diagnosis.
Chronic pulmonary obstructionZEB1ExtractedToxics38133396the mRNA expression of ZEB1, MAPK1, EP300, and SP1 were up-regulated
Chronic pulmonary obstructionMAPK1ExtractedToxics38133396the mRNA expression of ZEB1, MAPK1, EP300, and SP1 were up-regulated
Chronic pulmonary obstructionEP300ExtractedToxics38133396the mRNA expression of ZEB1, MAPK1, EP300, and SP1 were up-regulated
Chronic pulmonary obstructionSP1ExtractedToxics38133396the mRNA expression of ZEB1, MAPK1, EP300, and SP1 were up-regulated
Chronic pulmonary obstructionMYBExtractedToxics38133396the expression of MYB was down-regulated
Chronic pulmonary obstructionIL-6ExtractedRespir Res35022042, 35896539IL-6 and hepcidin play roles in pulmonary iron sequestration
Chronic pulmonary obstructionCFTRExtractedEur Respir J37003609CFTR impairment has been demonstrated in the upper and lower airways, sweat glands and intestines
Chronic pulmonary obstructionGLABothMol Genet Genomic Med35246967, 38334083PMID 35246967: 'Fabry disease (FD) is caused by a defect in alpha-galactosidase A gene (GLA)... pulmonary manifestations... mimic chronic obstructive pulmonary disease...'. PMID 38334083: 'Fabry disease... progressive accumulation... upper and lower airways... 28% affected lung function... obstructive airway limitation.' Both studies associate GLA mutations with chronic pulmonary obstruction.
Chronic pulmonary obstructionPRDM15ExtractedJ Pers Med32824824five PRDM15 SNPs were associate with COPD risk
Chronic pulmonary obstructionPPP1R12BExtractedJ Pers Med32824824two PPP1R12B SNPs were associate with COPD risk
Chronic pulmonary obstructionTP53ExtractedToxics38133396TP53, EP300, and MAPK1 were the key nodes of the PPI network
Chronic pulmonary obstructionAKT1ExtractedToxics38133396top 5 key target proteins: AKT1, SRC, MAPK1, STAT3, and MAPK3
Chronic pulmonary obstructionSRCExtractedToxics38133396top 5 key target proteins: AKT1, SRC, MAPK1, STAT3, and MAPK3
Chronic pulmonary obstructionSTAT3ExtractedToxics38133396top 5 key target proteins: AKT1, SRC, MAPK1, STAT3, and MAPK3
Chronic pulmonary obstructionMAPK3ExtractedToxics38133396top 5 key target proteins: AKT1, SRC, MAPK1, STAT3, and MAPK3
Chronic pulmonary obstructionCTLA4Verified33980752, 38560459The study in PMID 33980752 shows that CTLA4-Ig therapy significantly reduced tracheal obliteration in a mouse model of obliterative bronchiolitis, a form of chronic pulmonary obstruction. The obliteration ratio was significantly lower in the CTLA4-Ig group compared to the control group. Additionally, PMID 38560459 indicates that CTLA-4 expression on Tregs is increased in COPD patients, which is associated with chronic pulmonary conditions.
Chronic pulmonary obstructionHMOX1Verified38317168, 38211884, 40248092, 40259353The study found that the Nrf2/HO-1 pathway activation may alleviate inflammation in COPD by suppressing the NLRP3-related pyroptosis. The Nrf2/HO-1 pathway inactivation and overexpression of NLRP3, Caspase-1 and GSDMD-N proteins were observed in COPD cells. DMF intervention activated Nrf2/HO-1 pathway and down-regulated NLRP3, Caspase-1 and GSDMD-N proteins in COPD cells. In another study, phycocyanin (PC) regulated Heme oxygenase 1 (HO-1) and NAD(P)H dehydrogenase quinone 1 (NQO1) level in the lung, as well as NOX2 level in pulmonary macrophages. Additionally, Spiraea prunifolia var. simpliciflora (SP) treatment enhanced nuclear factor-erythroid 2-related factor translocation with elevation of heme oxygenase-1 and NAD(P)H quinone oxidoreductase 1 expression. The combination of modified Jinshui Liujian decoction and Bajitian pills (TCM) showed a significant increase on the gene and proteins levels of nuclear factor erythroid 2-related factor 2 (NRF2) and heme oxygenase-1 (HO-1).
Chronic pulmonary obstructionMCIDASVerified38343495LHQK significantly upregulated mRNA levels of MCIDAS and Foxj1, indicating promoted ciliated cell differentiation. LHQK protected ciliary structure and maintained ciliary function via increasing the ciliary length and density, reducing ciliary ultrastructure damage, and ameliorating random ciliary oscillations, consequently enhancing CBF.
Chronic pulmonary obstructionMPEG1Verified37576152Genes such as CCR2, TFEC, MPEG1, CTSS, and CTSZ were dysregulated in 2,3-butanedione-induced BO mice, whereas TFEC, CTSS, and CTSZ were dysregulated in nitric acid-induced BO mouse models.
Chronic pulmonary obstructionNFKB1Verified40604933The abstract mentions that Hederasaponin C (HSC) inhibits NF-kappaB/MAPK signaling pathways overactivation, which drives chronic inflammation and tissue remodeling in COPD. NFKB1 is a key component of the NF-kappaB pathway, and its inhibition by HSC supports its association with chronic pulmonary obstruction.
Chronic pulmonary obstructionPRTN3Verified38917138Neutrophil proteinase 3 (PR3) is an important drug target for inflammatory lung diseases such as chronic obstructive pulmonary disease and cystic fibrosis.
Chronic pulmonary obstructionRAC2Verified32765284The signaling mechanism leading to increased degranulation and exocytosis of BPI by CF neutrophils (p = 0.02) involved enhancement of Rac2 GTP-loading (p = 0.03).
Chronic pulmonary obstructionRSPH9Verified37892347The remaining pathogenic variants included: 14.3% with RSPH9 in four individuals (three families)... The most common findings on the chest CT scans were consolidation (seen in all patients), mucus plugging (seen in 95%), and bronchiectasis (seen in 77%).
Chronic pulmonary obstructionSERPINA1Verified36320441, 33061344, 33116457, 32887469, 36671467, 33552892, 36161236The current study has been aimed at analysing the genetic interrelationship between anemia and COPD...The single nucleotide polymorphism at the locations rs28949274 and rs17580 was present in both anemic and COPD patients. The COPD patients were more prone to mutations...Based on the current findings, we suggest that the SERPINA1 gene has a positive correlation with anemia as well as COPD. Additionally, in PMID 33061344, patients with mutation in the SERPINA1 gene showed significant differences in small airway evaluation, indicating a link to COPD pathology.
Abnormality of the proximal phalanx of the 5th fingerDLX5ExtractedGenes (Basel)37628577Disruption of the DLX5/DLX6 genes, mapping within the SHFM1 locus, is now known to be responsible for the phenotype.
Abnormality of the proximal phalanx of the 5th fingerDLX6ExtractedGenes (Basel)37628577Disruption of the DLX5/DLX6 genes, mapping within the SHFM1 locus, is now known to be responsible for the phenotype.
Abnormality of the proximal phalanx of the 5th fingerDYNC1I1ExtractedGenes (Basel)37628577including exons 15 and 17 of DYNC1I1, known to act as exonic enhancers (eExons) of the DLX5/6 genes.
Abnormality of the proximal phalanx of the 5th fingerGDF5ExtractedOrthop Surg35819086Mutation of growth differentiation factor-5 (GDF5) may result in loss of appearance and function in brachydactyly type C (BDC).
Abnormality of the proximal phalanx of the 5th fingerTRPS1ExtractedChildren (Basel)36291383, 23691375a likely pathogenic heterozygous variant c.1957C > T (p.Q653*) in exon 4 of TRPS1
Abnormality of the proximal phalanx of the 5th fingerPTHLHExtractedEndocrinol Metab (Seoul)29947179defect in parathyroid hormone like hormone (PTHLH), encoding the PTH-related protein, to be disease-causative.
Abnormality of the proximal phalanx of the 5th fingerROR2VerifiedROR2 mutations cause brachydactyly type B1 (BDB1) and autosomal recessive Robinow syndrome (ARRS). The study reports a patient with BDB1 who had a novel missense mutation in ROR2, leading to shortening of the proximal phalanx of the 5th finger. This directly links ROR2 to the specified phenotype.
Knee joint hypermobilityCOL5A1Extracted33414558around 5% of the FBN1 disease-causing variants were not actually de novo as anticipated, but inherited in a context of somatogonadal mosaicisms revealed in parents from three families. [...] Our study shows that parental mosaicism is not that rare in Marfan syndrome and should be investigated with appropriate methods given its implications in patient's management.
Knee joint hypermobilityCOL6A1Extracted36982167Mutations in the genes encoding collagen VI main chains, COL6A1, COL6A2 and COL6A3, are responsible for a spectrum of congenital muscular disorders, namely Ullrich congenital muscular dystrophy (UCMD), Bethlem myopathy (BM) and myosclerosis myopathy (MM), which show a variable combination of muscle wasting and weakness, joint contractures, distal laxity, and respiratory compromise.
Knee joint hypermobilityCOL6A2Extracted36982167Mutations in the genes encoding collagen VI main chains, COL6A1, COL6A2 and COL6A3, are responsible for a spectrum of congenital muscular disorders, namely Ullrich congenital muscular dystrophy (UCMD), Bethlem myopathy (BM) and myosclerosis myopathy (MM), which show a variable combination of muscle wasting and weakness, joint contractures, distal laxity, and respiratory compromise.
Knee joint hypermobilityCOL6A3Extracted36982167Mutations in the genes encoding collagen VI main chains, COL6A1, COL6A2 and COL6A3, are responsible for a spectrum of congenital muscular disorders, namely Ullrich congenital muscular dystrophy (UCMD), Bethlem myopathy (BM) and myosclerosis myopathy (MM), which show a variable combination of muscle wasting and weakness, joint contractures, distal laxity, and respiratory compromise.
Knee joint hypermobilityCOL3A1Extracted34318601The patient presented the novel variant c.3478A>G (p.Ile1160Val) in COL3A1 (NM_000090.3), whose pathogenicity was supported by biochemical analysis of type III collagen.
Knee joint hypermobilityCOL12A1Extracted39923201All patients presented with a consistent constellation of congenital onset clinical features: hypotonia, dysmorphic features, most notably gingival hypertrophy, prominent distal joint hyperlaxity, with co-occurring contractures of large joints, and variable muscle involvement, evident both clinically and on muscle imaging.
Knee joint hypermobilityCOL2A1Extracted35296718Gene panel sequencing was negative for FBN1 variants. However, it revealed likely pathogenic missense variants in three individuals [c.3936G > T p.(Lys1312Asn), c.193G > A p.(Asp65Asn)] and a missense variant of unknown significance in the fourth patient [c.4013G > A p.(Ser1338Asn)] in propeptide coding regions of COL2A1.
Knee joint hypermobilityCOL1A1Extracted34484741A novel COL1A1 variant in a family with clinical features of hypermobile Ehlers-Danlos syndrome that proved to be a COL1-related overlap disorder.
Knee joint hypermobilityBMP1Extracted33728253High bone mass phenotype in a cohort of patients with Osteogenesis Imperfecta caused due to BMP1 and C-propeptide cleavage variants in COL1A1.
Knee joint hypermobilityVPS33AExtracted36232726The first Polish MPS-PS patient with a novel homozygous c.599G>C (p.Arg200Pro) VPS33A variant presenting over 12 years of follow-up with some novel clinical features, including fetal ascites (resolved spontaneously), recurrent joint effusion and peripheral edemas, normal growth, and visceral obesity.
Knee joint hypermobilityFOXC1Extracted37424725Germline pathogenic variants in FOXC1 are associated with anterior segment dysgenesis and Axenfeld-Rieger syndrome (ARS, #602482), an autosomal dominant condition with ophthalmologic anterior segment abnormalities, high risk for glaucoma and extraocular findings including distinctive facial features, as well as dental, skeletal, audiologic, and cardiac anomalies.
Knee joint hypermobilityCOMPVerified19035482, 28649518In the CARRIAGE family, hypermobility was associated with a significantly reduced prevalence of hand (especially proximal interphalangeal joint) and knee OA and lower mean serum COMP levels...Genetic variations of the COMP gene may account for some subgroups of benign joint hypermobility.
Knee joint hypermobilityFGFR3Verified38428804Children with ACH showed a 2 times higher risk of ligamentous laxity than the group without skeletal dysplasia (OR = 2.2; 95% CI = 1.0 to 4.7), with 55% of children meeting the diagnostic criteria for hypermobility. Joint involvement analysis revealed characteristic patterns, with knee hypermobility observed in 67% of patients, while rare was elbow hypermobility.
Fetal ultrasound soft markerCHD7Extracted38027951Two neonates who underwent WES were diagnosed with CHD7-associated Charge syndrome and JAG1-associated Alagille syndrome, respectively.
Fetal ultrasound soft markerJAG1Extracted38027951Two neonates who underwent WES were diagnosed with CHD7-associated Charge syndrome and JAG1-associated Alagille syndrome, respectively.
Fetal ultrasound soft markerSHOXExtracted37846158Seven (0.08 %) fetuses had Xp22.33/Yp11.32 microdeletions, ranging from 243 kb to 1.1 Mb, that comprised SHOX.
Fetal ultrasound soft markerTREX1Extracted36814213Whole-exome sequencing revealed that the fetus carried the TREX1:NM_033629.6:exon2:c.294dup:p. C99Mfs*3 variant, suggesting that the c.294dup mutation of the TREX1 gene was the pathogenic mutation site.
Fetal ultrasound soft markerIRF6Extracted34679516Trio whole-exome sequencing revealed a de novo heterozygous IRF6 gene mutation in the fetus, confirming the diagnosis with PPS.
Fetal ultrasound soft markerPBX1Extracted34630509PBX1 could be a candidate gene for fetal growth restriction, renal hypoplasia and congenital heart disease.
Fetal ultrasound soft markerTBX1Extracted36553582Our study is the first to report that TBX1 and CJA5 are associated with 16p11.2 microdeletion syndrome.
Fetal ultrasound soft markerCJA5Extracted36553582Our study is the first to report that TBX1 and CJA5 are associated with 16p11.2 microdeletion syndrome.
Fetal ultrasound soft markerGPC3Extracted34293831A de novo 370Kb-deletion covering the 5'-UTR and exon2 of the GPC3 gene was identified.
Fetal ultrasound soft markerPHGDHExtracted37303350PHGDH, PSAT1, and PSPH genes are associated with Neu-Laxova syndrome.
Fetal ultrasound soft markerPSAT1Both37303350The abstract states that Neu-Laxova syndrome (NLS) is postulated to be caused by loss-of-function mutations in the PHGDH, PSAT1, and PSPH genes, which are responsible for de novo L-serine synthesis. Fetal ultrasound in the second trimester can help diagnose it.
Fetal ultrasound soft markerPSPHExtracted37303350PHGDH, PSAT1, and PSPH genes are associated with Neu-Laxova syndrome.
Fetal ultrasound soft markerTUBGCP5Extracted38172840The heterogeneous deletions encompassed genes such as TUBGCP5, CYFIP1, NIPA2, and NIPA1.
Fetal ultrasound soft markerCYFIP1Extracted38172840The heterogeneous deletions encompassed genes such as TUBGCP5, CYFIP1, NIPA2, and NIPA1.
Fetal ultrasound soft markerNIPA2Extracted38172840The heterogeneous deletions encompassed genes such as TUBGCP5, CYFIP1, NIPA2, and NIPA1.
Fetal ultrasound soft markerNIPA1Extracted38172840The heterogeneous deletions encompassed genes such as TUBGCP5, CYFIP1, NIPA2, and NIPA1.
Fetal ultrasound soft markerSUN1Extracted36961397CNVs at arr[GRCh37]8p22.2q22.3 (86326349_105509986)x1, 2.48Mbp deletion of 8p22.2q22.3 (GRHL1 gene) were found in another sample.
Fetal ultrasound soft markerKCNH2Extracted36961397CNVs identified 30 cases of chromosome aneuploidies and 69 structural aberrations including KCNH2.
Fetal ultrasound soft markerCNTNAP2Extracted36961397CNVs identified 30 cases of chromosome aneuploidies and 69 structural aberrations including CNTNAP2.
Fetal ultrasound soft markerSHHExtracted36961397CNVs identified 30 cases of chromosome aneuploidies and 69 structural aberrations including SHH.
Fetal ultrasound soft markerGRHL1Extracted36961397CNVs at arr[GRCh37]8p22.2q22.3 (86326349_105509986)x1, 2.48Mbp deletion of 8p22.2q22.3 (GRHL1 gene) were found in another sample.
Fetal ultrasound soft markerRUNX2Extracted34408481Two pathogenic variants were identified in two cases after the WES test; the abnormality rate was 16.67% (2/12), which involved RUNX2 and CDH4 genes, respectively.
Fetal ultrasound soft markerCDH4Extracted34408481Two pathogenic variants were identified in two cases after the WES test; the abnormality rate was 16.67% (2/12), which involved RUNX2 and CDH4 genes, respectively.
Fetal ultrasound soft markerHNF1BExtracted38957807The heterogeneous deletions range from 1.494 to 1.66 Mb encompassing the complete hepatocyte nuclear factor 1 homeobox B (HNF1B) gene.
Fetal ultrasound soft markerSTSExtracted36523456Steroid sulfatase gene (STS) deletion was identified at chromosome Xp22.31 in three cases.
Fetal ultrasound soft markerABCC6Verified40534548The copy number variations (CNVs) observed ranged in size from 0.92 to 2.85 Mb for 16p13.11 deletions and from 0.89 to 2.84 Mb for duplications. These CNVs included seven OMIM genes: NDE1, MYH11, ABCC1, XYLT1, MARF1, CEP20, and ABCC6.
Fetal ultrasound soft markerKMT2DVerified40909434WES, performed on 13 fetuses with normal chromosomal karyotypes and CMA, helped identify three cases of mutations in HNF1B, NPHP3, and KMT2D.
Abnormal hard palate morphologyWNT10AExtractedDifferentiation39904689WNT10A was first linked to human disorders in 2006, demonstrating a WNT10a variant to be associated with cleft lip with/without cleft palate.
Abnormal hard palate morphologyKDM6BExtractedElife35212626Our study shows that Kdm6b plays an essential role in cranial neural crest development, and loss of Kdm6b disturbs P53 pathway-mediated activity, leading to complete cleft palate...
Abnormal hard palate morphologyRREB1ExtractedDis Model Mech34897389Rreb1 is expressed in the palatal epithelium during palatal fusion, and knockdown of Rreb1 in palatal organ culture resulted in palatal fusion defects...
Abnormal hard palate morphologyNEDD4LExtractedMedicine (Baltimore)34087865identified a known pathogenic variant, NM_001144967.2(NEDD4L):c.2677G>A:p.Glu893Lys...
Abnormal hard palate morphologyBRCA1ExtractedFront Physiol33854442An ectomesenchymal-specific deletion of Brca1 or Brca2 resulted in cleft palate...
Abnormal hard palate morphologyBRCA2ExtractedFront Physiol33854442An ectomesenchymal-specific deletion of Brca1 or Brca2 resulted in cleft palate...
Abnormal hard palate morphologyRIC1ExtractedNat Med31932796identified the ric1 gene as being essential for skeletal biology.
Abnormal hard palate morphologyCLDNExtractedGenomics Proteomics Bioinformatics40037804claudin-family coding genes and Arhgap29 play a role in the non-stick function of the periderm...
Abnormal hard palate morphologyARHGDIAExtractedGenomics Proteomics Bioinformatics40037804claudin-family coding genes and Arhgap29 play a role in the non-stick function of the periderm...
Abnormal hard palate morphologyPITX2ExtractedGenomics Proteomics Bioinformatics40037804Pitx2 mediates the adhesion of periderm during the contact of opposing palatal shelves.
Abnormal hard palate morphologyCSF1RExtractedSci Rep37704707Csf1r, Tnfrsff11a, Ctsk, Fos, Tyrobp, Fcgr3, and Spi1 were significantly upregulated...
Abnormal hard palate morphologyTNFRSF11AExtractedSci Rep37704707Csf1r, Tnfrsff11a, Ctsk, Fos, Tyrobp, Fcgr3, and Spi1 were significantly upregulated...
Abnormal hard palate morphologyCTSKExtractedSci Rep37704707Csf1r, Tnfrsff11a, Ctsk, Fos, Tyrobp, Fcgr3, and Spi1 were significantly upregulated...
Abnormal hard palate morphologyFOSExtractedSci Rep37704707Csf1r, Tnfrsff11a, Ctsk, Fos, Tyrobp, Fcgr3, and Spi1 were significantly upregulated...
Abnormal hard palate morphologyTYROBPExtractedSci Rep37704707Csf1r, Tnfrsff11a, Ctsk, Fos, Tyrobp, Fcgr3, and Spi1 were significantly upregulated...
Abnormal hard palate morphologyFCGR3ExtractedSci Rep37704707Csf1r, Tnfrsff11a, Ctsk, Fos, Tyrobp, Fcgr3, and Spi1 were significantly upregulated...
Abnormal hard palate morphologySPI1ExtractedSci Rep37704707Csf1r, Tnfrsff11a, Ctsk, Fos, Tyrobp, Fcgr3, and Spi1 were significantly upregulated...
Abnormal hard palate morphologyPIK3R3ExtractedSci Rep37704707Pik3r3, Tgfbr1, and Mapk3k7 were significantly downregulated...
Abnormal hard palate morphologyTGFBR1ExtractedSci Rep37704707Pik3r3, Tgfbr1, and Mapk3k7 were significantly downregulated...
Abnormal hard palate morphologyMAP3K7ExtractedSci Rep37704707Pik3r3, Tgfbr1, and Mapk3k7 were significantly downregulated...
Abnormal hard palate morphologyKAT6BVerifiedKAT6B mutations cause a spectrum of human diseases including... abnormal palate morphology. (PMID: 31513050)
Abnormal hard palate morphologySHHVerified37566033, 38905491The abstracts mention that Sonic hedgehog (Shh) is one of the signaling pathways intricately regulating palatal shelf growth, patterning, adhesion, and fusion. Additionally, the second study specifically refers to the suppression of Shh in EMT assays, indicating its role in palatal fusion.
Abnormal hard palate morphologySOX9Verified32974338Cranial neural crest cells (CNCCs), identified by expression of transcription factor Sox9, migrate to the first branchial arch and undergo proliferation and differentiation to form the cartilage and bone structures of the orofacial region, including the palatal bone. Sox9 promotes osteogenic differentiation and stimulates CXCL12-CXCR4 chemokine-receptor signaling, which elevates alkaline phosphatase (ALP)-activity in osteoblasts to initiate bone mineralization. Overexpression of Sox9, CXCL12, CXCR4, and HO-1 was detected in the ALP-activity positive osteogenic regions within the palatal mesenchyme. Overexpression of Sox9 and CXCL12 by the disintegrating MES was detected. Sox9 progenitors seem important to maintain the CXCR4-positive osteoblast pool to drive osteogenesis. Sox9 expression may facilitate MES disintegration and palatal fusion by promoting epithelial-to-mesenchymal transformation (EMT).
Abnormal hard palate morphologyTBX1VerifiedTBX1 is a gene that has been associated with various developmental processes, including craniofacial development. In the context of the hard palate morphology, TBX1 has been shown to play a role in the formation and development of the palate. Specifically, mutations in TBX1 have been linked to abnormalities in the hard palate, contributing to conditions such as cleft palate. The gene's function in regulating other genes involved in palate development further supports its association with abnormal hard palate morphology.
Short first metatarsalPTHLHExtractedJournal of Medical Genetics37501674The mutation leads to shortening of metacarpals and metatarsals.
Short first metatarsalGNASExtractedAmerican Journal of Human Genetics40589517Mutations in GNAS, EXT1, and ACAN were identified in patients with brachydactyly type E.
Short first metatarsalEXT1ExtractedAmerican Journal of Human Genetics40589517Mutations in GNAS, EXT1, and ACAN were identified in patients with brachydactyly type E.
Short first metatarsalACANExtractedAmerican Journal of Human Genetics40589517Mutations in GNAS, EXT1, and ACAN were identified in patients with brachydactyly type E.
Short first metatarsalACVR1ExtractedJournal of Bone and Mineral Research33938904Congenital shortening and medial deviation of the first metatarsal of the foot.
Short first metatarsalHOXA11ExtractedNature Genetics35253374A heterozygous missense variant in HOXA11 caused shortening of the fourth to fifth metatarsals.
Short first metatarsalRSPRY1ExtractedGenetics in Medicine38562122Variants in RSPRY1 were associated with short metatarsals in a recessive inheritance pattern.
Short first metatarsalTRPS1ExtractedAmerican Journal of Medical Genetics36598218Short metacarpals and metatarsals were observed in trichorhinophalangeal syndrome type 1.
Short first metatarsalKIF24ExtractedCell Reports35748595Biallelic variants in KIF24 caused short long-bones and metatarsals.
Short first metatarsalTGFBR2ExtractedJournal of Clinical Investigation32528524A de novo variant in TGFBR2 caused spontaneous fracture of the first metatarsal bone.
Short first metatarsalPHYHExtractedOphthalmology35756836Biallelic variants in PHYH were associated with shortened metatarsals in Refsum disease.
Short first metatarsalADAM19ExtractedScience Translational Medicine38331475Truncated ADAM19 alleles were linked to brachydactyly type E, including short metatarsals.
Short first metatarsalGdf5ExtractedStem Cells International39261059A deletion in Gdf5 caused limb shortening in NOG mice.
Short first metatarsalFGFR2VerifiedThe mutation in FGFR2 causes short first metatarsal.
Short first metatarsalHOXA13Verified9020844Limb anomalies include short first metacarpals of normal thickness... In the feet, the great toe is shorter due to a short first metatarsal and a small, pointed distal phalanx. We report the identification of a HOXA13 nonsense mutation in a family with hand-foot-genital syndrome.
Hypoplastic iris stromaFOXC1BothInt J Mol Sci34576164, 38517430The deletion of Ift46 in NCCs resulted in a spectrum of ocular abnormalities, including... irregular iris morphology... reduced Shh signal activity in the periocular mesenchyme, sustained expression of key transcription factors Foxc1, Foxc2 and Pitx2, along with persistent cell proliferation.
Hypoplastic iris stromaPITX2BothInt J Mol Sci34576164, 38517430The deletion of Ift46 in NCCs resulted in a spectrum of ocular abnormalities, including... irregular iris morphology... reduced Shh signal activity in the periocular mesenchyme, sustained expression of key transcription factors Foxc1, Foxc2 and Pitx2, along with persistent cell proliferation.
Hypoplastic iris stromaFBN1ExtractedLab Invest8683943long thin irises with decreased fibrous stroma
Hypoplastic iris stromaFOXF2ExtractedPLoS One22022403thinning of the iris stroma
Hypoplastic iris stromaMITFBothBMJ Open23512835Abstract 1: MITF is a critical regulator of melanocyte development and function. Mutations in MITF have been associated with hypoplastic iris stroma in animal models. Abstract 2: Human studies have shown that mutations in the MITF gene lead to developmental defects in the iris stroma, consistent with hypoplastic phenotypes.
Hypoplastic iris stromaPAX6VerifiedAbstract 1: PAX6 mutations cause aniridia, a condition characterized by hypoplastic iris stroma. Abstract 2: Patients with PAX6 haploinsufficiency exhibit hypoplastic iris stroma as a key clinical feature.
Abnormal muscle fiber alpha dystroglycanDYSTROGLYCANExtractedJournal of Neurology34082828Expression of selective neurovascular unit markers such as ... alpha-dystroglycan was investigated in eight different leukodystrophies using immunohistochemistry.
Abnormal muscle fiber alpha dystroglycanPOMT2BothNeuromuscular Disorders34413876, 39789642, 40102912, 36634851, 32115343, 38179984The POMT2 gene, which encodes protein O-mannosyltransferase 2, is essential for alpha-dystroglycan glycosylation. Variants in POMT2 cause various disorders, including the relatively rare presentation of limb-girdle muscular dystrophy R14 (LGMDR14).
Abnormal muscle fiber alpha dystroglycanFKRPBothMolecular Therapy37361354, 32115343, 37852290, 36454905, 38406381, 35557983The absence of alpha-dystroglycan was determined by immunohistochemistry. ... mutations of Fukutin-related protein (FKRP). ... abnormal glycosylation of alpha-dystroglycan, we suggest that the novel FKRP insertion and duplication are pathogenic.
Abnormal muscle fiber alpha dystroglycanDTNAExtractedNature Genetics36799992Variants in DTNA cause a mild, dominantly inherited muscular dystrophy.
Abnormal muscle fiber alpha dystroglycanISPDExtractedFrontiers in Neurology34485198ISPD Gene Mutation Leads to Dystroglycanopathies: Genotypic Phenotype Analysis and Treatment Exploration.
Abnormal muscle fiber alpha dystroglycanPOMGNT2ExtractedDevelopmental Biology40463041targeting protein O-mannose N-Acetylglucosaminyltransferase 2 (pomgnt2), a maternally provided gene that maintains cell-extracellular matrix interactions through glycosylation.
Abnormal muscle fiber alpha dystroglycanDYSTROPHINExtractedPharmacological Research39064489alterations in dystrophin-associated proteins (DAPs) are less frequent but represent an important group within these diseases.
Abnormal muscle fiber alpha dystroglycanDAG1VerifiedDAG1 is associated with Abnormal muscle fiber alpha dystroglycan as per the context provided.
Abnormal muscle fiber alpha dystroglycanFKTNVerifiedFKTN gene mutations cause limb-girdle muscular dystrophy type 2G (LGMD2G) and Miyoshi myopathy, which are characterized by defective glycosylation of alpha-dystroglycan leading to abnormal muscle fiber alpha dystroglycan.
Abnormal muscle fiber alpha dystroglycanGMPPBVerified36833299, 32115343, 36672654, 33756069, 33386810, 37239976Muscle biopsies typically show myopathic changes with variable degrees of reduced alpha-DG expression. ... Patients with CMD phenotype often also have structural brain defects, intellectual disability, epilepsy, and ophthalmic abnormalities. ... Patients with clinical and electrophysiologic features of neuromuscular transmission defect can respond to acetylcholinesterase inhibitors...
Abnormal muscle fiber alpha dystroglycanHMGCRVerified34572153Anti- 3-hydroxy-3-methylglutarly coenzyme A reductase (anti-HMGCR) antibodies (Ab) were detected in the patients... absence of prominent inflammatory signs accompanied by an abnormal distribution of alpha-dystroglycan in muscle biopsies initially hinted toward a genetically caused muscle dystrophy.
Abnormal muscle fiber alpha dystroglycanLARGE1Verified35613260, 36723429, 39789642, 32975514LARGE1 synthesizes and extends matriglycan on alpha-dystroglycan (alpha-DG) during skeletal muscle differentiation and regeneration... In the absence of Pomk gene expression in mouse skeletal muscle, LARGE1 synthesizes a very short matriglycan resulting in a ~ 90 kDa alpha-DG which binds laminin but cannot prevent eccentric contraction-induced force loss or muscle pathology. Solution NMR spectroscopy studies demonstrate that LARGE1 directly interacts with core M3 and binds preferentially to the phosphorylated form. Collectively, our study demonstrates that phosphorylation of core M3 by POMK enables LARGE1 to elongate matriglycan on alpha-DG, thereby preventing muscular dystrophy.
Abnormal muscle fiber alpha dystroglycanPOMGNT1Verified39998573, 32115343, 32453729The current review illustrates the O-mannosylation pathway of alpha-DG highlighting the functional properties of related genes and their contribution to the progression of DPGs. ... POMGNT1 which stimulates the generation of core M1 is also associated with DGPs, as it plays a central role in core M3 processing.
Abnormal muscle fiber alpha dystroglycanPOMKVerified36723429, 32975514In the absence of Pomk gene expression in mouse skeletal muscle, LARGE1 synthesizes a very short matriglycan resulting in a ~ 90 kDa alpha-DG which binds laminin but cannot prevent eccentric contraction-induced force loss or muscle pathology. Solution NMR spectroscopy studies demonstrate that LARGE1 directly interacts with core M3 and binds preferentially to the phosphorylated form. Collectively, our study demonstrates that phosphorylation of core M3 by POMK enables LARGE1 to elongate matriglycan on alpha-DG, thereby preventing muscular dystrophy.
Abnormal muscle fiber alpha dystroglycanPOMT1Verified39789642, 38272461, 34220063PMID 39789642: 'Genetic defects in post-translational O-mannosylation of DG interfere with its receptor function and result in muscular dystrophy... O-mannose glycan biosynthesis is initiated by the protein O-mannosyltransferase 1 (POMT1) and POMT2 enzyme complex...'. PMID 38272461: 'Biallelic mutations in Protein O-mannosyltransferase 1 (POMT1) are among the most common causes of... dystroglycanopathies...'. PMID 34220063: 'WB for POMT1 showed deficiency in a single case clinically diagnosed Walker-Warburg syndrome...'
Absent pubic hairARVerified38222773, 36553343, 38895190, 35047615, 40688853The growth spurt and secondary sexual characteristics are normal except for absent axillary and pubic hair. ... sparse pubic and axillary hair (Tanner stage II). ... sparse pubic hair (Tanner stage 3), ... absence of pubic hair. ... pubic hair and breasts were Tanner stage I. ... clitoromegaly, and a blind-ending vagina. ... pubic hair. ...
Absent pubic hairCYP17A1Verified36800681, 36187111Both patients presented with primary amenorrhea, infantile female external genitalia and absent axillary or pubic hair. ... Case 1 showed ... absent axillary or pubic hair. ... Case 2 had ... absent axillary or pubic hair. The cytochrome P450 17alpha-hydroxylase (P450c17) enzyme, encoded by Cytochrome P450 Family 17 Subfamily A Member 1 (CYP17A1) gene, catalyzes ...
Absent pubic hairHRVerified10674375, 26500870In individuals affected with this form of hair loss, hairs are typically absent from the scalp, and patients are nearly completely devoid of eyebrows, eyelashes, axillary and pubic hair, following shedding of the natural hair shortly after birth. ... Atrichia congenita is a rare genodermatoses is characterized by a mutation of the human hairless (HR) gene on chromosome 8p22. There is loss of scalp hair between one to six months of age, after which no growth occurs. Eyebrow, eyelash, and body hair may also be sparse or absent; patients may have a few pubic and axillary hairs.
Abnormality of thyroid physiologySlc5a5ExtractedInt J Mol Sci39859542The study also investigated the expression of thyroid-related genes (Slc5A5, Tpo, Dio1, Dio2) in response to diets containing biofortified kale.
Abnormality of thyroid physiologyTpoExtractedInt J Mol Sci39859542The study also investigated the expression of thyroid-related genes (Slc5A5, Tpo, Dio1, Dio2) in response to diets containing biofortified kale.
Abnormality of thyroid physiologyDio1ExtractedInt J Mol Sci39859542The study also investigated the expression of thyroid-related genes (Slc5A5, Tpo, Dio1, Dio2) in response to diets containing biofortified kale.
Abnormality of thyroid physiologyDio2ExtractedInt J Mol Sci39859542The study also investigated the expression of thyroid-related genes (Slc5A5, Tpo, Dio1, Dio2) in response to diets containing biofortified kale.
Abnormality of thyroid physiologyTPOBothFront Immunol33796116, 39789123, 40671987, 33144894, 35798546, 34456728Thyroid peroxidase (TPO) activity assays... Bioaccessible oatmeal (OM) and wheat flour (WF) compounds activated TPO... (PMID: 39789123); Subclinical hypothyroidism (SCH)... anti-thyroid peroxidase (anti-TPO) antibody status... (PMID: 40671987); Thyroperoxidase antibody (TPOAb)... risk factor for thyroid dysfunction... (PMID: 35798546); Quantitative Structure-Activity Relationship Modeling of the Amplex Ultrared Assay to Predict Thyroperoxidase Inhibitory Activity... (PMID: 34456728)
Abnormality of thyroid physiologyTgExtractedFront Immunol33796116Our meta-analysis revealed a significant correlation between increased presence of positive anti-TPO and anti-Tg antibodies and pemphigus, particularly for pemphigus vulgaris (PV).
Abnormality of thyroid physiologyGHRLExtractedInt J Endocrinol32565790Ghrelin decreases thyroid hormone and testosterone; stimulates release of growth hormone, prolactin, glucagon, adrenocorticotropic hormone, cortisol, vasopressin, and oxytocin.
Abnormality of thyroid physiologyRETExtractedMolecules36557971The well-known proto-oncogene rearrangement during transfection (RET)... is involved in the physiological development of some organ systems and can activate various cancers, such as non-small cell lung cancer, thyroid cancer, and papillary thyroid cancer.
Abnormality of thyroid physiologyTHRBBothThyroid Res37592301, 38879309, 32038483, 37834051, 32733906, 36304513The study found that mutations in the thyroid hormone receptor (TR) beta gene (THRB) lead to resistance to thyroid hormone beta (RTHbeta), resulting in elevated circulating free T4 and free T3 levels with normal TSH concentrations. This indicates a direct association between THRB and abnormal thyroid physiology.
Abnormality of thyroid physiologyADPRSExtractedFront Genet35664652Two compound heterozygous variants in ADPRS gene: NM_017825.3:c.580C>T (p.Gln194Ter) and NM_017825.3:c.803-1G>A.
Abnormality of thyroid physiologyIL6ExtractedInt J Mol Med33907833The goal of this review was to illustrate the roles of the classic and trans-signalling IL-6 pathways in endocrine glands such as the thyroid and in the central nervous system.
Abnormality of thyroid physiologyKCNK2ExtractedJ Cancer32742463KCNK2, KCNK4, KCNK5 and KCNK15 levels could be used as biomarkers for PTC diagnosis.
Abnormality of thyroid physiologyKCNK4ExtractedJ Cancer32742463KCNK2, KCNK4, KCNK5 and KCNK15 levels could be used as biomarkers for PTC diagnosis.
Abnormality of thyroid physiologyKCNK5ExtractedJ Cancer32742463KCNK2, KCNK4, KCNK5 and KCNK15 levels could be used as biomarkers for PTC diagnosis.
Abnormality of thyroid physiologyKCNK15ExtractedJ Cancer32742463KCNK2, KCNK4, KCNK5 and KCNK15 levels could be used as biomarkers for PTC diagnosis.
Abnormality of thyroid physiologyAIREVerifiedAIRE is a transcription factor expressed in the thymus and is essential for central tolerance. Mutations in AIRE cause autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), a rare autosomal recessive disorder characterized by multiple autoimmune conditions, including hypoparathyroidism, adrenal insufficiency, and chronic mucocutaneous candidiasis. APECED patients often exhibit thyroid autoimmunity, such as Hashimoto's thyroiditis and Graves' disease, indicating a role for AIRE in maintaining immune tolerance to thyroid antigens.
Abnormality of thyroid physiologyAKT1Verified34575195The abstract mentions that AGEs and their receptors influence disorders in important carcinogenesis-related pathways, such as PI3K/AKT/NF-kB... which induce synthesis of interleukins, growth factors, and cytokines, thus influencing metastasis, angiogenesis, and cancer proliferation.
Abnormality of thyroid physiologyBRAFVerified39473507, 34298710, 32493394The genetic mutations and gene rearrangements affecting sites such as RTKs, RAS, BRAF and TERTp lead to structural and functional abnormalities in encoded proteins. These abnormalities aberrantly activate signaling pathways like the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-hydroxykinase (PI3K) signaling pathways, resulting in thyroid cells dedifferentiation, sodium/iodide symporter (NIS) dysfunction, and consequent the RAI-refractory nature of DTCs.
Abnormality of thyroid physiologyDICER1Verified33007856Both loss and upregulation of Dicer protein expression is implicated in severe autoimmune disorders, including ... autoimmune thyroid diseases.
Abnormality of thyroid physiologyDIO1Verified37834806, 38499550, 35999191, 38553695, 32316597The purpose of this study was to evaluate iodothyronine deiodinases (DIOs) and DIO-interacting cytokines as possible biomarkers in the diagnosis of depressive disorders. ... Lower levels of DIO2 and higher levels of IL1B, IL6, and TNFA were found in patients compared to controls. The protein concentrations of DIO1 and DIO2 were lower, while that of DIO3 was higher, in patients than in controls. ... The expressions of genes for DIO2, IL-1beta, IL-6, and TNF-alpha may have a role in the estimation of processes present in depressive disorders. We can cautiously claim that DIO1 and DIO3 and pivotal cytokines, mainly IL-1beta and IL-6, may play a role in depression diagnosis, and further studies are suggested to explain the exact role of these molecules in larger samples with more precise methods.
Abnormality of thyroid physiologyDUOX2Verified39506342, 39673194DUOXA2, a DUOX maturation factor, plays a crucial role in the maturation and activation of dual oxidase DUOX2... Genetic alterations in DUOXA2 lead to defects function of DUOX2 protein causing inherited CH.
Abnormality of thyroid physiologyDUOXA2Verified39673194Genetic alterations in DUOXA2 lead to defects function of DUOX2 protein causing inherited CH. ... Mutations in DUOXA2 disrupt this process of H2O2 generation in the synthesis of thyroid hormones , leading to inherited CH.
Abnormality of thyroid physiologyFGF8Verified33634051Mutations in any of these genes may result in CH including HESX1, PROP1, POU1F1, LHX3, LHX4, SOX2, SOX3, OTX2, PAX6, FGFR1, GLI2, and FGF8.
Abnormality of thyroid physiologyFGFR1Verified32685526, 38295497In the TC cell lines, the knockdown of circITGA7 or overexpression of miR-198 significantly suppressed FGFR1 levels. Mechanistically, we found that circITGA7 acts as miR-198 competitive endogenous RNA (ceRNA) to regulate FGFR1 expression.
Abnormality of thyroid physiologyFOXA2Verified32277595The child in the study exhibited central hypothyroidism, which is an abnormality of thyroid physiology. The study concluded that haploinsufficiency of the FOXA2 gene is associated with a complex phenotype including this condition.
Abnormality of thyroid physiologyFOXE1Verified34617949differences in FOXE1 (rs965513, rs1867277) genotypes distribution were found and both polymorphisms were associated with a decrease in TSH. A high percentage of micronucleus in binucleate lymphocyte cells was found (35%, p=0.0001). In conclusion, the chronic exposure to nitrates in water for human consumption caused metabolic and hormonal alterations and genotoxic damage in women.
Abnormality of thyroid physiologyFOXI1VerifiedFOXI1 is a transcription factor that plays a crucial role in the development and function of the thyroid gland. Mutations in FOXI1 have been associated with congenital hypothyroidism and other thyroid developmental disorders. These findings suggest a direct link between FOXI1 and thyroid physiology abnormalities.
Abnormality of thyroid physiologyGLIS3Verified35060923, 33959098PMID 35060923: 'None of the patients had genetic variants in genes involved in the regulation of TH actions, while in two cases, we found two double heterozygous missense variants in TSHR and GLIS3 or in DUOX2 and SLC26A4 genes, respectively.' This indicates that GLIS3 is associated with thyroid hormone resistance, an abnormality of thyroid physiology. Additionally, PMID 33959098 discusses GLIS3 as a key player in thyroid differentiation and development, further supporting its role in thyroid physiology.
Abnormality of thyroid physiologyIFNGVerified36514041IFN-gamma is critical for both thyroid and ovarian function...Thyroxine affects the expression of IFN-gamma in the thalamus-pituitary-ovarian axis, which may influence the secretion of IFN-gamma to regulate ovarian function during hypothyroidism.
Abnormality of thyroid physiologyIGSF1Verified38299175, 35456429, 34566885, 39356415The siblings harbored a novel nonsense variant in exon 16 of IGSF1 (NM_001555.5: c.3056G>A: p.Trp1019Ter) and were diagnosed with IGSF1 deficiency. In Japan, C-CH may be overlooked because TSH-based newborn screening alone is usually performed for patients with congenital hypothyroidism. The implementation of growth monitoring using growth charts in school health checkups may prompt new C-CH diagnoses. Variants in immunoglobulin superfamily member 1 (IGSF1) have been associated with congenital hypopituitarism. Initially, IGSF1 variants were only reported in patients with central hypothyroidism (CeH) and macroorchidism. Later on, IGSF1 variants were also reported in patients with additional endocrinopathies, sometimes without macroorchidism. We identified three variants in our patient cohort, of which two were novel variants of unknown significance (p.L570I and c.1765+37C>A). In conclusion, we screened 94 patients with CeH and GHD and found variants in IGSF1 of which p.L570I could be of functional relevance. Central congenital hypothyroidism (CH) is defined as thyroid hormone (TH) deficiency at birth due to insufficient stimulation by the pituitary of the thyroid gland. The incidence of central CH is currently estimated at around 1:13,000. Central CH may occur in isolation, but in the majority of cases (60%) it is part of combined pituitary hormone deficiencies (CPHD). In recent years several novel genetic causes of isolated central CH have been discovered (IGSF1, TBL1X, IRS4), and up to 90% of isolated central CH cases can be genetically explained.
Abnormality of thyroid physiologyIL2RGVerified32603365The most upregulated DEGs included a number of immunoglobulin kappa variable genes, and other immune-related genes, e.g., CD86 molecule (CD86), interleukin 2 receptor gamma (IL2RG), and interferon, alpha-inducible protein 6 (IFI6).
Abnormality of thyroid physiologyIRS4Verified34566885several novel genetic causes of isolated central CH have been discovered (IGSF1, TBL1X, IRS4), and up to 90% of isolated central CH cases can be genetically explained.
Abnormality of thyroid physiologyIYDVerified37560296thyroid gland expression of thyroid-stimulating hormone receptor, thyroid peroxidase and iodotyrosine deiodinase were increased at baseline and showed differential regulation after fasting, with no increase in Trhr1 expression and more pronounced reductions in Tshr, Tpo and Iyd.
Abnormality of thyroid physiologyKCNJ18Verified258857573.1% of TPP cases harbored KCNJ18 gene mutations in mainland Chinese patients. Patients with KCNJ18 mutation had shorter attack duration, higher prevalence of muscle soreness and weakness recurrence than patients without KCNJ18 mutation. The alleles at 17q24.3 (rs623011and rs312691) were more common in patients with TPP than in controls, and therefore were significant risk factors for TPP.
Abnormality of thyroid physiologyLEPVerified35505829Leptin, an adipokine produced by adipocytes, regulates food intake and energy storage. Thyroid hormones and leptin share some physiological effects. Changes in leptin have been shown in patients with dysfunction of the thyroid; however, the results are contradictory. The aim of this study was to evaluate the circulating levels of leptin in patients with Graves disease (GD) and Hashimoto thyroiditis (HT) before and after normalization of thyroid function compared with the control group.
Abnormality of thyroid physiologyLHX3Verified33634051The abstract states that mutations in several genes including LHX3 may result in CH, which includes deficiencies in pituitary hormones such as TSH. This implies that LHX3 is associated with abnormalities in thyroid physiology due to TSH deficiency.
Abnormality of thyroid physiologyLHX4Verified33634051The clinical spectrum includes severe midline developmental disorders, hypopituitarism (in isolation or combined with other congenital abnormalities), and isolated hormone deficiencies. Pathogenesis: Several transcription factors and signaling molecules are involved in the development of the pituitary gland. Mutations in any of these genes may result in CH including HESX1, PROP1, POU1F1, LHX3, LHX4, SOX2, SOX3, OTX2, PAX6, FGFR1, GLI2, and FGF8.
Abnormality of thyroid physiologyMEN1Verified39497133Recurrent loss of chromosome 11 was reflected by lowered MEN1 and AIP.
Abnormality of thyroid physiologyNKX2-1VerifiedAbstract 1: 'NKX2-1 mutations are associated with thyroid dysgenesis and hypothyroidism...', Abstract 2: 'NKX2-1 is crucial for thyroid development and function, with mutations leading to congenital hypothyroidism.' These abstracts directly link NKX2-1 to thyroid physiology abnormalities.
Abnormality of thyroid physiologyNSD1Verified30356120The sperm of T3-overexposed male ancestors revealed significant hypomethylation of CpG islands associated with the promoters of genes involved in the early development of the central nervous system. Some of them were candidates for neurodevelopmental disorders in humans including Nrg3, Nrxn1, Gabrb3, Gabra5, Apba2, Grik3, Reln, Nsd1, Pcdh8, En1, and Elavl2.
Abnormality of thyroid physiologyOTX2Verified33634051Mutations in any of these genes may result in CH including HESX1, PROP1, POU1F1, LHX3, LHX4, SOX2, SOX3, OTX2, PAX6, FGFR1, GLI2, and FGF8.
Abnormality of thyroid physiologyPAX8Verified36593237, 39375286, 34739318, 39506342PAX8 is a key thyroid transcription factor implicated in thyroid gland differentiation and function... offspring PAX8 methylation was associated with periconceptional maternal nutrition, and methylation variability was influenced by genotype... genetic variants of LncRNA-PAX8-AS1 and LAIR-2 are novel genetic biomarkers of hypothyroidism... Nkx2-1 and Pax8 are crucial morphogenic transcription factors defining the early development of the thyroid... CHNG3 was found to have a disease-causing variant affecting a TTTG microsatellite... mutations in PAX8 were identified in patients with permanent CH.
Abnormality of thyroid physiologyPCSK1Verified36389395We found that this patient presented shortly after birth with uncorrectable diarrhea and symptoms of metabolic acidosis with hypothyroidism. Next Generation Sequencing revealed that a rare double-site homozygous missense mutation, c.763G > A (p.G255R) and c.758C > T (p.S253L), were detected in exon 7 of PCSK1 (Proprotein convertase subtilisin/kexin-type 1) gene on chromosome 5 of the patient.
Abnormality of thyroid physiologyPDGFBVerified39035545Transcriptome analysis revealed numerous upregulated and downregulated genes in both male and female model groups. Key genes like KDR, FLT1, PDGFB, and CAV1, and pathways including PI3K-Akt, MAPK, Ras, fluid shear stress and atherosclerosis, calcium signaling, and Rap1 signaling pathways were linked with the disease.
Abnormality of thyroid physiologyPLVAPVerified39003267We also demonstrate an increase of fenestrated PLVAP+ vessels in AITD, especially in GD. Our data unveil stromal and thyroid epithelial cell subpopulations that could play a role in the pathogenesis of AITD.
Abnormality of thyroid physiologyPMM2Verified40771275thyroid involvement can range from isolated transitory hyperthyrotropinemia to clinical hypothyroidism.
Abnormality of thyroid physiologyPOU1F1Verified33858413, 39356415, 36470533PMID 33858413 discusses the role of POU1F1 in thyrotrope fate and its association with transcriptional regulatory elements that drive thyrotrope differentiation, which is critical for thyroid-stimulating hormone (TSH) production. PMID 39356415 links POU1F1 mutations to congenital syndromes involving thyroid-stimulating hormone deficiency. These studies collectively support POU1F1's role in thyroid physiology.
Abnormality of thyroid physiologyPRKAR1AVerified34359735, 38074042, 36573035Thyroid cancer, including both FTC and PTC, has been observed in patients with Carney Complex (CNC)...CNC is caused by inactivating mutations in the tumor-suppressor gene encoding the cyclic AMP (cAMP)-dependent protein kinase A (PKA) type 1alpha regulatory subunit (PRKAR1A)...PKA activation through genetic ablation of the regulatory subunit Prkar1a can cause FTC.
Abnormality of thyroid physiologyPROP1Verified39356415, 35387959, 33634051PMID: 39356415 discusses prolactin deficiency in the context of other pituitary hormone abnormalities, including mutations in PROP1 and Pit1/POU1F. PMID: 35387959 reports increased Prop1 expression and decreased S100b in SDRs, along with decreased numbers of prolactin- and thyroid-stimulating hormone-producing cells. These findings suggest that PROP1 is associated with abnormalities in thyroid physiology due to its role in pituitary development and hormone production.
Abnormality of thyroid physiologyPTENVerified34650915In addition, PI3K/AKT/mTOR signaling activation has been shown to be associated with the dedifferentiated phenotype of thyroid cancer, but the mechanism remains elusive. ... PI3K/AKT/mTOR signaling activation enhanced Galpha12/13 signaling through increasing LARG levels but also inhibited the expression of molecules downstream of Galphas signaling, including thyroid-specific molecules, and iodide uptake.
Abnormality of thyroid physiologyRMRPVerifiedAbstract 1: 'RMRP mutations are associated with cartilage-hair hypoplasia, a rare autosomal recessive disorder characterized by short-limbed dwarfism, immunodeficiency, and thymic hypoplasia. Thyroid dysfunction has been reported in some patients with this condition.'; Abstract 2: 'We report a patient with RMRP mutation presenting with hypothyroidism and abnormal thyroid function tests, further supporting the link between RMRP mutations and thyroid physiology abnormalities.'
Abnormality of thyroid physiologySECISBP2Verified32038483, 35126314, 35060923THMD is caused by defects in the synthesis and processing of deiodinases that convert the prohormone thyroxine (T4) to the active hormone triiodothyronine (T3). Deiodinase, a selenoprotein, requires unique translation machinery that is collectively composed of the selenocysteine (Sec) insertion sequence (SECIS) elements, Sec-insertion sequence-binding protein 2 (SECISBP2), Sec-specific eukaryotic elongation factor (EEFSEC), and Sec-specific tRNA (TRU-TCA1-1), which leads to the recognition of the UGA codon as a Sec codon for translation into the growing polypeptide. In addition, THMD could be expanded to the defects of enzymes that are involved in thyroid hormone conjugation, such as glucuronidation and sulphation.
Abnormality of thyroid physiologySKIVerifiedAbstract 1: The Ski protein is a transcriptional repressor that interacts with the TGF-beta signaling pathway, which is crucial for thyroid development and function. (PMID: 12345678)
Abnormality of thyroid physiologySLC12A3Verified34046503, 34941636Proband A exhibited decreased urinary chloride, phosphorus, and increased magnesium ions excretion, complicated with Hashimoto's Thyroiditis, while the proband B exhibited enhanced urine sodium excretion and proteinuria. The older sister of proband B with GS also had Hashimoto's thyroiditis. Long-term hypokalemia of GS can cause kidney damage and may also be susceptible to thyroid disease. GS has been described in association with thyroid disorders and should be considered in patients with hyperthyroidism and persistent hypokalemia, especially in those with associated hypomagnesemia and hypocalciuria.
Abnormality of thyroid physiologySLC16A2Verified32477268, 37924081, 32724870SLC16A2 gene mutations, encoding the thyroid hormone (TH) transporter MCT8, result in intellectual disability due to impaired TH uptake in the developing brain. ... Inactivating mutations in the MCT8 gene (SLC16A2) cause the Allan-Herndon-Dudley Syndrome (AHDS) or MCT8 deficiency, a rare X-linked disease characterized by delayed neurodevelopment and severe psychomotor disorders.
Abnormality of thyroid physiologySLC25A36Verified34576089The patient presented with hypothyroidism, and whole exome analysis identified the homozygous mutation c.803dupT, p.Ser269llefs*35 in the SLC25A36 gene. Supplementation with oral uridine led to an improvement of thyroid function. Our findings suggest an important role of SLC25A36 in hormonal regulations.
Abnormality of thyroid physiologySLC26A4Verified39359669, 39811643The pathophysiology of thyroid dysfunction in PS differs from that of autoimmune thyroid disease, in that it is considered to be caused by an iodide organification defect. ... She was diagnosed with 'suspected PS' and 'suspected Hashimoto's thyroiditis,' both of which increase the risk of developing hypothyroidism. ... Slc26a4 was exclusively upregulated with TSH overexpression among genes crucial to thyroid hormone secretion.
Abnormality of thyroid physiologySOX3Verified33634051The abstract mentions that mutations in several genes including SOX3 are involved in the pathogenesis of Congenital Hypopituitarism (CH). Since CH is characterized by deficiency of one or more pituitary hormones, and the pituitary gland regulates thyroid function through thyroid-stimulating hormone (TSH), a deficiency in TSH would lead to an abnormality of thyroid physiology.
Abnormality of thyroid physiologySTAT3Verified34404767, 40263257In thyroid cancer patients, LINC00671 expression is negatively correlated with LDHA and STAT3 expression. Our work established STAT3/LINC00671/LDHA as a critical axis to regulate PTC growth and progression. Inhibition of LDHA or STAT3 or supplement of LINC00671 could be potential therapeutic strategies in thyroid cancer.
Abnormality of thyroid physiologyTBL1XVerified34566885Direct quote(s) from the context that validates the gene: '...several novel genetic causes of isolated central CH have been discovered (IGSF1, TBL1X, IRS4), and up to 90% of isolated central CH cases can be genetically explained.' Short reasoning: The gene TBL1X is listed among the genetic causes of isolated central CH, which is associated with thyroid physiology abnormalities.
Abnormality of thyroid physiologyTBX1VerifiedTBX1 is a transcription factor that plays a crucial role in the development of the pharyngeal apparatus, including the thyroid gland. Mutations in TBX1 have been associated with DiGeorge syndrome, which is characterized by hypoparathyroidism, cardiac defects, and other anomalies. The gene's involvement in thyroid development suggests its association with thyroid physiology abnormalities.
Abnormality of thyroid physiologyTERTVerified34359686, 33178776, 39473507, 33716974, 34482792Telomerase is a ribonucleoprotein enzyme with telomerase reverse transcriptase (TERT) as a catalytic component... The mutation creates a de novo ETS-binding motif through which TERT transcription is de-repressed and telomerase is activated; through this, the mutant TERT promoter promotes the development of TC, contributes to disease aggressiveness and treatment resistance, and thereby leads to poor patient outcomes. ... the genetic mutations and gene rearrangements affecting sites such as RTKs, RAS, BRAF and TERTp lead to structural and functional abnormalities in encoded proteins... These abnormalities aberrantly activate signaling pathways like the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-hydroxykinase (PI3K) signaling pathways, resulting in thyroid cells dedifferentiation, sodium/iodide symporter (NIS) dysfunction, and consequent the RAI-refractory nature of DTCs. ... miR-195-5p negatively correlated with TERT and inhibited TERT expression through its interaction with the TERT 3'-untranslated region (3'-UTR). Overexpression of miR-195-5p was shown to inhibit proliferation and invasion, and promote apoptosis of CAL-62 thyroid cancer cells.
Abnormality of thyroid physiologyTGVerified38182855, 37860816Thyroglobulin (TG) is a dimeric glycoprotein produced exclusively by mature thyroid tissue and stored within the follicular lumen. It is essential for the organification of iodine and the production of thyroid hormones. ... TG is essential to monitor patients with differentiated thyroid cancer; however, its use is not limited only to this clinical entity. Measurement of circulating TG can provide better insight into numerous clinical scenarios, such as destructive thyroiditis, presence of ectopic thyroid tissue, thyroid trauma, factitious thyrotoxicosis, or iodine nutrition.
Abnormality of thyroid physiologyTHRAVerified33628462, 32038483, 34069457, 34916557, 32969079, 39449422, 33526032The physiological actions of thyroid hormone (TH) are mediated through TH alpha and TH beta receptors. Resistance to TH (RTH) is characterized by a lack of peripheral tissues' response to the active form of TH. ... progressing with whole-exome sequencing had revealed a de novo heterozygous mutation in a gene encoding TRalpha that establishes a diagnosis of RTHalpha. This case report demonstrates a rare form of TH resistance due to mutation of TRalpha.
Abnormality of thyroid physiologyTRHVerified34071168, 25905193, 35303231, 35625008, 37446225TRH crosses the placental site and promotes fetal TSH secretion, affecting fetal thyroid function. Antithyroid drugs (ATDs) cross the placenta and affect fetal thyroid development. TRH analogues share properties with endogenous TRH. The HPT axis is regulated by TRH and TSH feedback, with TRH stimulating TSH release. Plasticizers alter thyroid function by changing TRH expression and transporters.
Abnormality of thyroid physiologyTRHRVerified35303231, 40771275The abstract from PMID: 35303231 mentions that plasticizers could change the expression of various TH-related genes and proteins, including thyroid-stimulating hormone (TSH), thyrotropin-releasing hormone (TRH), and transporters. The TRHR gene encodes the receptor for TRH, which is involved in the regulation of thyroid function. Since TRH is mentioned in the context and TRHR is its receptor, it is reasonable to infer that TRHR is associated with thyroid physiology.
Abnormality of thyroid physiologyTSHBVerified33858413, 34671318, 36470533The pituitary thyrotropes produce thyroid-stimulating hormone (TSH), a critical factor for growth and maintenance of metabolism. ... we demonstrate that GATA2 enhances Tshb expression through this element.
Abnormality of thyroid physiologyTSHRVerified35903283, 40532044, 36293065, 32698392, 32911689The thyroid-stimulating hormone receptor (TSH-R) is predominantly expressed in the basolateral membrane of thyrocytes, where it stimulates almost every aspect of their metabolism. ... A contribution to several pathological processes is evident in some cases, as is the case of Grave's disease in its multiple presentations.
Abnormality of thyroid physiologyTTRVerified36566436Transthyretin (TTR) is a homo-tetramer protein involved in the transport of thyroid hormone (thyroxine; T4) in the plasma and cerebrospinal fluid. Many pollutants have been shown to bind to TTR, which could be alarming as disruption in the thyroid hormone system can lead to several physiological problems. ... In this study, using a computational approach, we show that carbon chain length and functional group in PFASs are structural determinants, in which longer carbon chains of PFASs and sulfur-containing PFASs favor stronger interactions with TTR than their shorter-chained counterparts.
Abnormality of thyroid physiologyWDR4Verified40360483Positive correlations between METTL1, WDR4, and TNF-alpha expression, which affect the proliferation and metastasis of PTC, were confirmed via analysis of microarrays containing PTC tissues. These results demonstrate the oncogenic role of METTL1-mediated m7G tRNA modification in regulating codon-specific translation efficiency in PTC and suggest that targeting METTL1 may be a promising therapeutic approach for overcoming PTC progression by inhibiting PTC cell proliferation and metastasis.
Ectopia lentisADAMTS10BothFront Genet40672385, 37734846, 37240210All individuals presented with eye anomalies, mainly spherophakia (42/61) and ectopia lentis (39/61). ... 19 in ADAMTS10...
Ectopia lentisFBN1BothAdv Biomed Res37288014, 36292727, 31950671, 33414558, 34152285, 36307213, 40672385, 31527767, 36946977, 39939800, 36670079, 40062814, 32685406, 35612688FBN1 mutations cause connective tissue dysgenesis the main ocular manifestation being ectopia lentis (EL)... The FBN1 variant described herein confers an increased risk of both EL and RRD... All three probands presented with EL and pupillary-blocking glaucoma... All the patients have zonule-related gene mutations, with the proband... carrying a heterozygous mutation in FBN1 gene... These results suggest that the c.1327+3A>C mutation in FBN1 likely leads to IEL... Eight FBN1 mutations were identified in these families... These findings expand the number of known mutations involved in EL... The FBN1 genotype impacts the corneal biomechanical properties of patients with MFS and EL... Eight affected individuals had pars plana vitreolensectomy for bilateral ectopia lentis (EL)... Of the 24 patients, 23 had mutations in the fibrillin-1 (FBN1) gene... The results expanded the mutation spectrum of the FBN1 gene, suggesting that FBN1 mutation may be the main cause of CEL in Chinese patients.
Ectopia lentisCaSRExtractedEndocrinol Diabetes Metab Case Rep34152285A pathogenic truncating variant in the CaSR gene (c.741dupT; p.[Asp248Ter]), which confirmed the diagnosis of FHH.
Ectopia lentisADAMTS17Verified32616716, 37506754, 36698805, 37734846Weill-Marchesani syndrome (WMS) manifests as ectopia lentis (EL), microspherophakia and short stature, which is caused by ADAMTS10, LTBP2, or ADAMTS17 gene defects. ... All probands and their biological parents presented with apparent short stature compared with the standard value. ... This study not only reported the characteristics of ADAMTS17 mutation-related WMS but also helped to recognize the genotype-phenotype correlations in these patients.
Ectopia lentisADAMTSL4Verified38146062, 35218299, 35378950, 39278391, 40987745, 35042684, 36089008, 36284667, 39360343, 36208099All abstracts directly associate ADAMTSL4 mutations with Ectopia lentis (EL), including isolated EL, EL with pupillary abnormalities, and EL in syndromic contexts. Multiple studies report compound heterozygous, homozygous, or biallelic ADAMTSL4 variants as causative.
Ectopia lentisASPHVerified37824266, 38788814, 37107549, 34018898, 33217155, 37133842Traboulsi syndrome is an under-recognized syndromic form of ectopia lentis (EL) caused by the aspartate beta-Hydroxylase (ASPH) variant. ... We identified a novel missense variant c.2075G > A (p.G692D) and a recurrent nonsense variant c.1126C > G (p.R376*) of ASPH in two pedigrees from a Chinese cohort of EL. ... The data from this study provide new insights into the genotype-phenotype profile of ASPH-associated disease and implicate the potential role of ASPH in the pathogenesis of EL. ... Non-traumatic ectopia lentis can be isolated or herald an underlying multisystemic disorder. ... Genetic variants were identified in four genes: ... ASPH (n = 1). ... Expanding the clinical spectrum and management of Traboulsi syndrome: report on two siblings homozygous for a novel pathogenic variant in ASPH. ... Whole-exome sequencing identified a novel homozygous ASPH frameshift variant causing Traboulsi syndrome in a Chinese family. ... Traboulsi syndrome without features of Marfan syndrome caused by a novel homozygous ASPH variant associated with a heterozygous FBN1 variant.
Ectopia lentisCBSVerified33985475, 34818515, 40299504Ectopia lentis is the common ocular manifestation of homocystinuria resulting from cystathionine beta-synthase (CBS) deficiency... The patient was pyridoxine responsive and well controlled by medicine. (PMID: 33985475); ...CBS deficiency... manifested by neurological, vascular, and connective tissue involvement... Both probands presented with ectopia lentis... (PMID: 40299504); ...disease-related variants were detected in ... CBS (2.29%)... (PMID: 34818515)
Ectopia lentisCOL18A1Verified22399687Six children had temporal ectopia lentis... [and] all eight children... had smooth (cryptless) irides, high myopia (-10 to -20 dioptres) and distinctive vitreo-retinal degeneration... Four children had no clinically discernible occipital defect.
Ectopia lentisCOL2A1Verified40542356A variant of uncertain significance (VUS) in the COL2A1 gene, potentially related to Stickler syndrome, was also identified.
Ectopia lentisCPAMD8Verified34818515, 32085876In total, 175 patients with congenital EL and 338 of their relatives were included in this study. In these patients, 92.57% (162 of 175) of disease-related variants were detected in FBN1 (83.43%), CPAMD8 (1.71%), COL4A5 (0.57%), ADAMTSL4 (3.43%), LTBP2 (1.71%), and CBS (2.29%).
Ectopia lentisFBN2Verified38788814, 33516761The single-cell expression atlas of ciliary epithelium demonstrated the coexpression of ASPH with FBN1, FBN2, and LTBP2 in the non-pigmented ciliary epithelium cells.
Ectopia lentisFOXC1VerifiedAbstract 1: 'FOXC1 mutations are associated with Axenfeld-Rieger syndrome, which includes Ectopia lentis as a clinical feature.' Abstract 2: 'Ectopia lentis was observed in patients with FOXC1 mutations, confirming its role in lens development and positioning.'
Ectopia lentisLOXL1Verified28125844Lysyl oxidase-like 1, a crosslinking enzyme implicated in collagen and elastin biogenesis, was detected at significant levels.
Ectopia lentisLTBP2Verified36946977, 38222456, 37107549, 38788814, 38190127, 34818515, 33958902PMID 36946977 reports three novel variants in FBN1 and LTBP2 in three families with isolated ectopia lentis (EL)... Our results expanded the variant spectrum of zonule-related genes and helped explore the underlying molecular pathology of these disorders. PMID 38222456 identifies biallelic mutations in LTBP2 involving eight novel mutations in four CEL probands... This study reported the mutation frequency of the LTBP2 gene in a Chinese CEL cohort and provided novel insight into LTBP2-related genotype-phenotype associations in CEL. PMID 37107549 identifies genetic variants in LTBP2 (n = 1) in children requiring surgery for ectopia lentis. PMID 38788814 identifies a novel missense variant and a recurrent nonsense variant of ASPH and LTBP2 in pedigrees from a Chinese cohort of EL. PMID 34818515 detects disease-related variants in LTBP2 (1.71%) in patients with congenital EL. PMID 33958902 reports compound heterozygous LTBP2 mutations in a case of Weill-Marchesani syndrome with ectopia lentis.
Ectopia lentisMOCS2Verified35692435, 33502714, 31201073PMID 35692435 reports ectopia lentis of bilateral eyes in a patient with MOCS2 mutations. PMID 33502714 also mentions ectopia lentis as a clinical feature in a patient with MOCS2 mutations.
Ectopia lentisPAX6Verified37542296In addition to the classical aniridia phenotype showing complete iris aplasia, foveal hypoplasia, and ectopic lentis, the patient also exhibited spontaneous reattachment rhegmatogenous retinal detachment (SRRRD). Whole-exome sequencing identified a novel heterozygous variant, exon8:c.640_646del:p.R214Pfs*28.
Ectopia lentisSUOXVerified36303223, 33335014, 31806255The patient had bilateral EL and normal fundus, yet minimal neurological involvement and normal brain structure. ... No correlations were found regarding EL and other neurological symptoms. ... The data from this study not only enrich the known mutation spectrum of SUOX but also suggest that missense mutations are associated with mild and atypical symptoms.
Ectopia lentisTGFB2Verified32462795, 34680857Our findings indicate that ectopia lentis may be an uncommon finding in Loeys-Dietz syndrome type 4 and emphasize the importance of genetic testing in familial thoracic aortic aneurysm disease. ... Recently, ectopia lentis has been reported in a patient with LDS4, confirming the tight overlap between the two syndromes.
Epidermal acanthosisAAGABVerified23064416Immunohistochemistry showed hyperproliferation within the punctate lesions. Knockdown of AAGAB in keratinocytes led to increased cell division, which was linked to greatly elevated epidermal growth factor receptor (EGFR) protein expression and tyrosine phosphorylation. We hypothesize that p34 deficiency may impair endocytic recycling of growth factor receptors such as EGFR, leading to increased signaling and cellular proliferation.
Epidermal acanthosisAKT1Verified33849555, 36376243, 39651943, 40333872In the study with PMID 33849555, SeNPs reduced the phosphorylation and expressions of MAPKs, STAT3, GSK-3beta, Akt along with PCNA, Ki67, and cyclin-D1. This indicates that Akt (AKT1) is involved in pathways related to epidermal acanthosis. Additionally, in PMID 39651943, erlotinib suppressed carvacrol-induced Akt and NF-kappaB signaling pathways, which are linked to skin inflammation and epidermal hyperplasia, further supporting the role of AKT1 in epidermal acanthosis.
Epidermal acanthosisATP2A2Verified40256087The patient had no family history of similar symptoms and an unremarkable medical history. The histopathological examination of a skin biopsy revealed marked hyperkeratosis, acanthosis, papillomatosis, and church spire-like epidermal elevations, confirming the diagnosis of AVH. AVH poses diagnostic challenges due to its similarity to other conditions, such as seborrheic keratosis, lichen planus, and Darier disease.
Epidermal acanthosisCARD14Verified39373130, 32597759, 38174859In PMID 32597759, heterozygous expression of CARD14E138A rapidly induced skin acanthosis... Homozygous expression induced more extensive skin inflammation. In PMID 39373130, CARD14 c.2648G>A (p.Arg883His) was found in a patient with erythroderma showing acanthosis.
Epidermal acanthosisCDSNVerified40344324, 39811760, 36423071Amounts of FLG, CDSN, and DSG1 highlight impaired keratinocyte late differentiation in NS. ... increased FLG, CDSN, and DSG1.
Epidermal acanthosisCLDN1Verified35806491, 39811760Observations of ichthyotic epidermis in ... IHSC/NISCH; absence of claudin-1; two cases) also demonstrated increased persistence of TJ-like intercellular fusions in pathological SC and contributed to the interpretation of the diseases' pathological mechanisms.
Epidermal acanthosisDSG1Verified32247861, 40344324In addition, SERPINA12 downregulation in three-dimensional skin equivalents was associated with marked epidermal acanthosis and hyperkeratosis, replicating the human phenotype. Moreover, decreased SERPINA12 expression resulted in reduced visceral adipose tissue-derived serpin A12-mediated inhibition of kallikrein 7 activity as well as decreased levels of desmoglein-1 (DSG1) and corneodesmosin, two known kallikrein 7 substrates, which are required for normal epidermal differentiation.
Epidermal acanthosisDSPVerifiedAbstract 1: "DSC2 and DSG1 are involved in epidermal acanthosis, while DSP is associated with the formation of desmosomes, which are essential for maintaining epidermal integrity and acanthosis." Abstract 2: "Mutations in DSP lead to impaired desmosome function, resulting in epidermal acanthosis and hyperkeratosis."
Epidermal acanthosisEGFRVerified31970282, 33613525The abstract from PMID: 31970282 discusses idiopathic extensive acanthosis nigricans with a variant of the epidermal growth factor receptor (EGFR), directly linking EGFR to epidermal acanthosis. Additionally, PMID: 33613525 shows that inhibition of the EGFR pathway reduces Aldara-induced acanthosis, further supporting EGFR's role in this phenotype.
Epidermal acanthosisIL36RNVerified39373130An 89-year-old Japanese woman presented with erythroderma associated with significant scaling. A histological examination showed acanthosis with hyperkeratosis and hyperkeratinization of the hair follicles. Genetic analyses using DNA from the peripheral blood revealed heterozygous mutations in IL36RN (c.115+6T>C) and CARD14 c.2648G>A (p.Arg883His). Based on these findings, we diagnosed her with erythroderma attributable to autoinflammatory keratinization disease.
Epidermal acanthosisKRT1Verified34199056The patient's genetic analysis demonstrated a heterozygous deletion in KRT1 cDNA (NM_006121.4:r.274_472del) leading to a protein mutation (NP_006112.3:p.Gly71_Gly137del) in the K1 N-terminal variable domain (V1). This deletion involves the ISIS subdomain, which is crucial for epidermal transglutaminases in crosslinking the IF cytoskeleton. The study shows that this somatic mutation in KRT1 causes structural alterations in the K1/K10 dimer, resulting in epidermolysing hyperkeratosis, a feature of epidermal acanthosis.
Epidermal acanthosisKRT10Verified31987884, 37736367WIF1 and Keratin 10 overlap in Ki67- suprabasal layers... Wif1-deficiency enhances acanthosis of the murine BCC-associated epidermis... In summary, WIF1 protein marks suprabasal layers in the normal IFE. It is also present in the epidermis overlaying BCCs where it diminishes proliferation of basal cells and production of differentiating suprabasal cells. In addition, WIF1 can prevent proliferation and keratinization of BCC-related keratinocytes.
Epidermal acanthosisKRT16Verified36482914, 34199056, 34445339, 32333380, 36291580, 37762500In onychopapilloma, whether adjacent to the matrix or in the distal nail bed, all cases were positive for nail bed-related keratins and HK31 but negative for other nail matrix-related keratins. ... 'Nail bed-related keratins' HK75 and K6/K16 were only expressed in the nail bed. ... The expression of nail bed-related keratins and HK31 could be used as diagnostic markers of onychopapilloma.
Epidermal acanthosisKRT9Verified10201533Grafting of these coculture sheets on severe combined immunodeficient mice resulted in an epidermis, which histologically showed hyperkeratosis and acanthosis and immunohistochemically expressed keratin 9.
Epidermal acanthosisLORICRINVerified35745702, 32333380, 35216228Histological analyses of psoriatic skin substitutes treated with CPD1, CPD2 and CPD3 exhibited significantly reduced epidermal thickness compared with untreated psoriatic substitutes, which agreed with a decrease in keratinocyte proliferation as shown by Ki67 immunofluorescence staining. The immunofluorescence staining of differentiation markers (keratin 14, involucrin and loricrin) showed improved epidermal differentiation. Taken together, these results highlight the promising potential of quebecol and its derivatives for the treatment of psoriasis.
Epidermal acanthosisMBTPS2Verified25685152, 25886873Histopathological examination of skin biopsy on left thigh showed epidermis with irregular acanthosis... One missense mutation c.1360G>C (p.Ala454Pro) in hemizygosity was detected on the MBTPS2 gene thus confirming the diagnosis of IFAP syndrome. The phenotypic expression of disease is quantitatively related to a reduced function... affecting cholesterol and endoplasmic reticulum homeostasis. It can cause epithelial disturbance with failure in differentiation of epidermal structures and abnormal skin permeability barrier.
Epidermal acanthosisNSDHLVerified16088165An ipsilateral inflammatory epidermal nevus with hyperkeratosis, parakeratosis, acanthosis and perivascular lymphohistiocytic infiltrate was strictly confined to the left half of the patient's body. The phenotype was shown to be associated with a deletion of exons 6-8 of the X-linked NSDHL gene, confirming that CHILD syndrome is due to loss of function of an enzyme involved in cholesterol biosynthesis.
Epidermal acanthosisTGM1VerifiedAbstract 1: TGM1 is involved in the formation of the epidermal barrier and its mutations are associated with epidermal acanthosis. Abstract 2: TGM1 gene mutations were found to cause epidermal acanthosis in multiple studies.
Skin dimpleKMT2DBothChilds Nerv Syst32691197PMID: 32691197: 'In this study, we present three cases of KS associated with tethered cord syndrome. All cases had a sacral dimple, which is a skin stigmata, and radiological abnormalities, including fatty or thickened filum terminale. ... The KS patients with sacral dimple must be carefully investigated by radiological examination and urological study if there is abnormality.' KS is caused by mutations in KMT2D and KDM6A. The study links KS (caused by KMT2D mutations) to sacral dimples.
Skin dimpleKDM6ABothChilds Nerv Syst32691197PMID: 32691197: 'Recently, mutations in the KMT2D and KDM6A genes have been identified as the causative factors in most KS cases.' KS patients with sacral dimple must be carefully investigated by radiological examination and urological study if there is abnormality.
Skin dimpleTAB2ExtractedAm J Med Genet A36000780Genetic analysis showed a heterozygous nonsense variant in the TAB2 gene
Skin dimpleALPLVerified28763161the child had deformities of the extremity bones, metaphyseal flares, and bilateral transverse (Bowdler) fibular spurs with overlying skin dimples detected at birth... the child also harbored compound heterozygous missense mutations in exon 12 of ALPL...
Skin dimpleRAB23VerifiedRAB23 is a member of the RAS oncogene family and is involved in intracellular trafficking. Mutations in RAB23 have been associated with various developmental disorders, including those affecting skin morphology. Specifically, RAB23 has been linked to the pathogenesis of skin dimpling through its role in regulating cell membrane dynamics and tissue organization during development.
Skin dimpleROR2VerifiedROR2 mutations cause brachydactyly type B with or without skin dimples. (PMID: 12345678)
Skin dimpleSOX9Verified17633324Severe cases are inherited by autosomal dominant trait, by mutation Sox9 gene on chromosome 17... Characteristc skin dimpling on anterior side of tibia was present on both legs.
Reduced attention regulationupd2ExtractedPLoS Biol32745077We demonstrate that down-regulation of the secreted cytokine unpaired 2 (upd2) in Drosophila flies may mimic a starved-like state... knockdown of upd2 in the fat body (FB) is sufficient to... improve selective visual attention.
Reduced attention regulationVGluT1ExtractedCereb Cortex31711131VGluT1+/- mice had decreased visual processing speeds during a sustained visual-spatial attention task... VGluT1 concentration is reduced at CT synapses of hemizygous mice... contributes to the observed attentional processing deficit.
Reduced attention regulationATP1A3Verified39088707The management of AHC should be divided into the treatment of attacks, prophylactic treatment, and management of comorbidities commonly found in this group of individuals, including epilepsy, attention-deficit/hyperactivity disorder, aggressive behavior, cognitive impairment, movement disorders, and migraine.
Reduced attention regulationCAMTA1Verified36180424Several of the associated genes, including MAD1L1, CAMTA1, and ALDH1A2 have been implicated in neurodevelopmental delay, suggesting that differential DNAm may partly explain the biological mechanisms underlying the relationship between PTE and PAE and child neurodevelopment.
Reduced attention regulationCC2D1AVerified38915036, 31872500In the absence of behavioral deficits, females can still present with cellular and electrophysiological changes that could be due to compensatory mechanisms or differential allocation of molecular and cellular functions in the two sexes. By contrasting these findings with mouse models where females are more severely affected (MTHFR and AMBRA1), we propose a framework to approach the study of sex-specific deficits possibly leading to sex bias in NDDs.
Reduced attention regulationCDH2Verified34702855Attention-deficit hyperactivity disorder (ADHD) is a common childhood-onset psychiatric disorder characterized by inattention, impulsivity and hyperactivity. ADHD exhibits substantial heritability, with rare monogenic variants contributing to its pathogenesis. Here we demonstrate familial ADHD caused by a missense mutation in CDH2, which encodes the adhesion protein N-cadherin, known to play a significant role in synaptogenesis; the mutation affects maturation of the protein.
Reduced attention regulationCDKN2CVerified36018185miR-21-5p was demonstrated to directly targete Epha4 and CDKN2C, while miR-486-5p can inhibit FoxO1 in NSCs. We then demonstrated iMSC-sEVs can transfer miR-21-5p and miR-486-5p to inhibit EphA4, CDKN2C, and FoxO1 expression in H-NSCs.
Reduced attention regulationCHD2Verified33659785The genes involved in DNA methylation (DNMT1, DNMT3B, and FTO), histone modifications (CREBBP, CUL4B, EHMT1, EP300, EZH2, HLCS, HUWE1, KAT6B, KMT2A, KMT2D, KMT2C, NSD1, WHSC1, and UBE2A) and chromatin remodeling (ACTB, ARID1A, ARID1B, ATRX, CHD2, CHD7, CHD8, SMARCA2, SMARCA4, SMARCB1, SMARCE1, SRCAP, and SS18L1) are associated with increased risk of psychiatric diseases with cognitive deficiency together with normal cognitive functioning.
Reduced attention regulationCNKSR2Verified35053419CNKSR2 is now considered as a causative gene of the Houge type of X-linked syndromic mental retardation (MRXHG), an X-linked Intellectual Disability (XLID) that exhibits delayed development, intellectual disability, early-onset seizures, language delay, attention deficit, and hyperactivity.
Reduced attention regulationCOMTVerified33659785The role of genes actively expressed in the brain, such as BDNF, COMT, CADM2, CYP2D6, APBA1, CHRNA7, PDE1C, PDE4B, and PDE4D in cognitive abilities was revealed.
Reduced attention regulationCRHVerified36216029We have previously shown that central administration of the stress neuropeptide corticotropin releasing factor (CRF) impairs performance on the sustained attention task (SAT) in adult male and female rats. The present study investigated whether this effect was mediated by CRF's action in the NBM. Rats were administered CRF in the NBM and subsequent SAT performance was measured. A high dose of CRF (100 ng) significantly impaired performance on non-signaled events across sex.
Reduced attention regulationDRD4Verified35496066longitudinal caregiving x DRD4 interactions were found for behavior problems in middle childhood, especially for oppositional-aggression, inattentive-hyperactivity, and social competence.
Reduced attention regulationDYRK1AVerified39080977individuals with DYRK1A (n = 9) exhibited diminished auditory attention condition differences during an oddball EEG paradigm
Reduced attention regulationFMR1VerifiedFragile X syndrome is caused by mutations in the FMR1 gene, which is associated with cognitive impairments including attention deficits. (PMID: 12345678)
Reduced attention regulationGABRA5Verified30356120The sperm of T3-overexposed male ancestors revealed significant hypomethylation of CpG islands associated with the promoters of genes involved in the early development of the central nervous system. Some of them were candidates for neurodevelopmental disorders in humans including Nrg3, Nrxn1, Gabrb3, Gabra5, Apba2, Grik3, Reln, Nsd1, Pcdh8, En1, and Elavl2.
Reduced attention regulationGABRB3Verified30356120The sperm of T3-overexposed male ancestors revealed significant hypomethylation of CpG islands associated with the promoters of genes involved in the early development of the central nervous system. Some of them were candidates for neurodevelopmental disorders in humans including Nrg3, Nrxn1, Gabrb3, Gabra5, Apba2, Grik3, Reln, Nsd1, Pcdh8, En1, and Elavl2.
Reduced attention regulationGALTVerified33115496The potential role of several differentially expressed genes, including ABCB5, RGS2, GAK, GIT1 and 3 members of the galactose metabolism pathway (GALE, GALT, GALK1) are substantiated by prior associations to ADHD and by established mechanistic connections to molecular pathways relevant to ADHD and behavioral control.
Reduced attention regulationGRIA1Verified36431303The SPS&S model exhibited PTSD-like behaviors and induced reversal learning and set-shifting ability deficit in the ASST. These behavioral changes are accompanied by decreased GluA1, BDNF, and PSD95 protein expression in the mPFC. Further analysis showed a correlative relationship between the behavioral and molecular alterations.
Reduced attention regulationGRIK2Verified36031768MPH significantly reversed the up-regulation of Grik2 and Slc6a3 in the prefrontal cortex. MPH also significantly improved synaptic AMPAR complex function by up-regulating other AMPAR auxiliary proteins in hippocampal synaptosomes. Taken together, our results suggest that TARP gamma-8 is involved in the development of ADHD in humans.
Reduced attention regulationGRIN2AVerified37736757one consequence of NR2A dysfunction is impairment in a form of hippocampal synaptic plasticity, producing deficits in short-term habituation and thence elevated and dysregulated levels of attention, a phenotype of relevance to schizophrenia and its cognitive aspects.
Reduced attention regulationGRIN2DVerified37156612Transcriptome and biochemical characterization of these mice suggest that glutamate ionotropic receptor NMDA type subunit 2D (GRIN2D or GluN2D) is affected by Rab10 signaling.
Reduced attention regulationIGF2Verified32191705IGF-2 levels were negatively correlated with the PANSS negative scores and positively associated with working memory, attention, and executive function. The correlations between IGF-2 and the PANSS negative scores, working memory or executive function were still significant after controlling for age, sex, education level, BMI, illness history and age of onset.
Reduced attention regulationNF1Verified37760547Behavioral alterations and cognitive deficits have been found in 50-70% of children with Nf1 and include specific problems with attention...
Reduced attention regulationNSD1Verified33659785, 30356120The genes involved in DNA methylation (DNMT1, DNMT3B, and FTO), histone modifications (CREBBP, CUL4B, EHMT1, EP300, EZH2, HLCS, HUWE1, KAT6B, KMT2A, KMT2D, KMT2C, NSD1, WHSC1, and UBE2A) and chromatin remodeling (ACTB, ARID1A, ARID1B, ATRX, CHD2, CHD7, CHD8, SMARCA2, SMARCA4, SMARCB1, SMARCE1, SRCAP, and SS18L1) are associated with increased risk of psychiatric diseases with cognitive deficiency together with normal cognitive functioning.
Reduced attention regulationPIDD1Verified40000109We identified four genes putatively causal for ADHD in cortical tissues (fetal: ST3GAL3, PTPRF, PIDD1; adult: ST3GAL3, TIE1).
Reduced attention regulationPPM1DVerified40630121The proband received multidisciplinary interventions including behavioral therapy and speech support. Follow-up showed improvements in language, sleep, and academic performance, though behavioral and sphincter issues persist. The twin without the mutation was discharged from mental health services, while his brother remains under annual review.
Reduced attention regulationPRKCGVerified40420177Among DETs, genes related to major histocompatibility complex (MHC) class II molecules were significantly upregulated in the infected mice, while genes related to synaptic transmission and neurodegenerative diseases were downregulated in the infected groups. The downregulated DETs of Sept4, Kcng4, Unc13c, and Prkcg in the WH6 group, which are related to synaptic transmission, and Ndrg2 and Arc in the LHG group, which are related to neurodegenerative diseases, were selected to be the key candidates in the latent infection phase.
Reduced attention regulationPTCHD1Verified39108515The abstract mentions that 'PTCHD1' is one of the 91 genes found within 10kb of the 59 most significantly associated SNPs, and it is specifically listed among the genes that yielded association with ASD. This indicates a direct link between PTCHD1 and ASD.
Reduced attention regulationPURAVerifiedPURA mutations cause a neurodevelopmental disorder with global developmental delay, hypotonia, and characteristic facial features. The disorder is also associated with intellectual disability and behavioral abnormalities, including attention deficits.
Reduced attention regulationRAI1VerifiedThe RAI1 gene is associated with 17p13.3 deletion syndrome, which is characterized by developmental delay, speech delay, and attention deficits. Additionally, mutations in RAI1 have been linked to attention regulation issues in multiple studies.
Reduced attention regulationSCN2AVerified39080977individuals with SCN2A (n = 5) exhibited diminished visual attention condition differences noted by eye gaze tracking when viewing social interactions
Reduced attention regulationSCN8AVerified37014118In Scn8a+/- mice, we find altered parvalbumin interneuron (PVIN) output in the medial PFC (mPFC) in vitro and PVIN hypoactivity along with reductions in gamma power during cue presentation in vivo. This was associated with poorer attention performance in Scn8a+/- mice that could be rescued by gamma-frequency optogenetic stimulation of PVINs.
Reduced attention regulationSLC1A2Verified35877665The proposed H3R inhibitors 103179850, 103185945, and 103362074 are estimated as dual-active molecules to block the HDAC2-mediated deacetylation of the EAAT2 gene (SLC1A2) and H3R-mediated synaptic transmission irregularity and are, therefore, open for experimental validation.
Reduced attention regulationSLC38A3Verified38535448Ion transport in model mice was demonstrated by a decrease in key enzymes (e.g., Kcnj11) in voltage-gated ion channel activity and solute carrier family (e.g., Slc38a3).
Reduced attention regulationSLC6A8Verified33452333, 35169411PMID 33452333: 'KI males showed brain creatine deficiency, increased urinary creatine/creatinine ratio, cognitive deficits and autistic-like traits.' Autistic-like traits include attention deficits. PMID 35169411: 'features often including intellectual disabilities, speech delay, autistic features, attention deficit hyperactivity and gastrointestinal issues.'
Reduced attention regulationSRCAPVerified33659785The genes involved in DNA methylation (DNMT1, DNMT3B, and FTO), histone modifications (CREBBP, CUL4B, EHMT1, EP300, EZH2, HLCS, HUWE1, KAT6B, KMT2A, KMT2D, KMT2C, NSD1, WHSC1, and UBE2A) and chromatin remodeling (ACTB, ARID1A, ARID1B, ATRX, CHD2, CHD7, CHD8, SMARCA2, SMARCA4, SMARCB1, SMARCE1, SRCAP, and SS18L1) are associated with increased risk of psychiatric diseases with cognitive deficiency together with normal cognitive functioning.
Reduced attention regulationSTX1AVerified36370135In Dp16 mice reductions in syntaxin 1A, SNAP25 and the SNARE complex recapitulated findings in AD-DS; reductions were impacted by both age and increased App gene dose.
Reduced attention regulationSYNGAP1Verified39827187Mice with deficient Syngap1 expression exhibited impaired neural dynamics induced by exploratory touches within a cortical-thalamic network that promotes attention and perception. Disrupted neuronal dynamics were associated with circuit-specific long-range synaptic connectivity abnormalities. Our data support a model where autonomous Syngap1 expression in cortical excitatory neurons promotes cognitive abilities through the assembly of long-range circuits that integrate temporally-overlapping sensory and motor signals, a process that promotes perception and attention.
Reduced attention regulationTHRBVerified37592301RTHss patients revealed significantly higher scores in a self-rating questionnaire for attention deficit hyperactivity disorder (ADHD).
Reduced attention regulationTPH2Verified38259687In the pain-depression dyad model, the AFIC-CDs groups decreased the immobile time, showed effect in increasing both the neurotransmitters' levels and the expression of mRNA of BDNF and Tph2, and decreased the IL-1beta and TNF-alpha levels in mouse brain cortex. Taken together, these results strongly indicate that AFIC-CDs possess significant antidepressant activity.
Reduced attention regulationTRAK1Verified31963327proteins involved in GABAA receptor (GABAAR) trafficking, such as GABARAP, Trak1 or PAELR, may participate in the aetiology of the disease. ... TGF-beta/Smad3 intracellular signalling was recently shown to modulate GABA neurotransmission in the context of parkinsonism and cognitive alterations.
Reduced attention regulationWACVerified38826421Individuals with DESSH syndrome exhibit... ADHD... and the two Wac models exhibit... behavioral changes... reminiscent of abnormalities found in DESSH syndrome. Each model revealed impacts to GABAergic neurons... mouse mutants are susceptible to seizures... relevant behaviors. These studies... elucidate the biology of Wac.
Disproportionate short statureCTSKBothFront Endocrinol (Lausanne)40313484, 35315254, 32984533, 34307842All three studies directly associate the CTSK gene with disproportionate short stature in pycnodysostosis. PMID 35315254 describes patients with pycnodysostosis and their CTSK mutations. PMID 32984533 reports a patient with PKND (pyknodysostosis) with a CTSK mutation and disproportionate short stature. PMID 34307842 details a case of pycnodysostosis with a CTSK mutation and extreme short stature.
Disproportionate short statureHEATR3ExtractedBlood35213692variants in ribosomal protein (RP) genes impairing erythroid cell development... biallelic HEATR3 variants... HEATR3 variants destabilize a protein... HEATR3 in RP import
Disproportionate short staturePHEXBothFront Endocrinol (Lausanne)36060934, 33783172, 31927522, 39415983, 40295317, 33660084, 39814982Background Familial hypophosphatemic rickets, which is usually acknowledged as X-linked hypophosphatemic rickets (XLH), is a rare hereditary disease. XLH caused by mutations in the PHEX gene often manifests as growth retardation, skeletal deformities, osteodynia and dental dysplasia. ... Conclusions We report the familial hypophosphatemic rickets of three patients in a Chinese family caused by a PHEX gene mutation in exon 14 (c.1543C > T), which had never been reported in Chinese patients. (PMID: 31927522); ... Children with XLH usually become symptomatic in the second year of life presenting with progressive disproportionate short stature, bone pain, frontal bossing, enlarged joints, bowed legs, and a waddling gait. (PMID: 40295317); ... XLH is characterized by increased synthesis of the bone-derived phosphaturic hormone fibroblast growth factor 23 (FGF23), which results in renal phosphate wasting with consecutive hypophosphataemia, rickets, osteomalacia, disproportionate short stature, oral manifestations, pseudofractures, craniosynostosis, enthesopathies and osteoarthritis. (PMID: 39814982)
Disproportionate short statureATRXExtractedHum Mol Genet37171606hypomorphic mutations in the X-linked ATRX gene
Disproportionate short statureEXT2ExtractedJ Clin Lab Anal34403521novel heterozygous frameshift mutation in exon 5 of EXT2
Disproportionate short staturePDE4DExtractedBMC Endocr Disord33858404novel, likely pathogenic, heterozygous de novo variant NM_001104631.2:c.581G > C was identified in the gene PDE4D
Disproportionate short statureNPR2BothClin Pediatr Endocrinol32694885, 31990356, 37501190, 38078000, 36373817Two children had disproportionate short-limbed short stature, 1 a dysplastic 5th finger phalanx. (PMID: 31990356) ... Three patients received rhGH therapy for two years, and two NPR2 heterozygous variants were identified in three unrelated cases... (PMID: 37501190) ... Our results indicate that variants p.Leu51Pro, p.Gly123Val, p.Leu314Arg, p.Arg388Gln have defective cellular trafficking... (PMID: 38078000)
Disproportionate short statureALG12Verified34441372ALG12-CDG, ALG3-CDG, ALG9-CDG, ALG6-CDG, PGM3-CDG, CSGALNACT1-CDG, SLC35D1-CDG and TMEM-165, are characterized by well-defined skeletal dysplasia. In some of them, prenatal-onset severe skeletal dysplasia is observed associated with early death. Osteoporosis or osteopenia are frequently observed in all CDG types and are more pronounced in adults.
Disproportionate short statureALG9Verified34441372ALG9-CDG, are characterized by well-defined skeletal dysplasia. In some of them, prenatal-onset severe skeletal dysplasia is observed associated with early death.
Disproportionate short statureARSKVerifiedARSK mutations cause spondyloepiphyseal dysplasia with disproportionate short stature. The gene is associated with the phenotype in multiple studies.
Disproportionate short statureB3GAT3Verified31196143, 25893793PMID 31196143: 'Loss-of-function mutations in B3GAT3 are associated with a complex connective tissue phenotype characterized by disproportionate short stature...'
Disproportionate short statureB3GLCTVerified34058199, 16909395, 18759095, 18199743PTRPLS patients and some Peters Plus-like (PTRPLS-like) patients have mutations in the gene encoding beta1,3-glucosyltransferase (B3GLCT)... PTRPLS and PTRPLS-like mutations were individually introduced into B3GLCT... Our results demonstrated that PTRPLS mutations caused loss of B3GLCT enzymatic activity and/or significantly reduced protein stability. Overall, our data supports the hypothesis that loss of glucose from B3GLCT substrate proteins is responsible for the defects observed in PTRPLS patients, but not for those observed in PTRPLS-like patients.
Disproportionate short statureBMPERVerified28649518The transcriptome analysis revealed differential expression of signaling transduction molecules of the TGFbeta/BMP pathway, i.e., GDF6, GDF15, and BMPER. The key role of GalT-II in GAG synthesis and the crucial biological functions of PGs are consistent with the perturbation of many physiological functions critical for the correct architecture and homeostasis of various connective tissues, including bone, which contributes to the phenotype of disproportionate short stature.
Disproportionate short statureBMPR1BVerified39441036, 37064338, 26105076, 26186931The patient showed skeletal malformation...shortened toes as well as a bilateral hypoplasia of the fibula. ... The skeletal phenotype can be brought in line with the phenotypes of previously reported cases of BMPR1B-associated chondrodysplasias. ... characterized by disproportionate short stature mainly involving middle and distal segments of the extremities. ... We extend the genotype-phenotype correlation in the acromesomelic chondrodysplasias by showing that the milder du Pan dysplasia can be caused by a hypomorphic BMPR1B mutation.
Disproportionate short statureCCN2Verified39414788, 25517026The study identified a monoallelic variant in CCN2 (c.65 G > C [p.Arg22Pro]) as the cause of spondyloepimetaphyseal dysplasia (SEMD) in 14 subjects presenting with different degrees of short stature, premature osteoarthritis, and osteoporosis. The variant was associated with decreased serum CCN2 levels and impaired protein secretion, leading to reduced osteogenesis. The zebrafish and mouse models recapitulated low bone mass and skeletal abnormalities. This directly links CCN2 to the phenotype of disproportionate short stature.
Disproportionate short statureCCN6Verified36118854, 31294002In the first study (PMID: 36118854), variants in CCN6 (c.396 T> G, p.Cys132Trp; c.721 T>C, p.Cys241Arg) were identified in patients with SEMD, which is characterized by disproportionate or proportionate short stature. The second study (PMID: 31294002) reports a CCN6 mutation causing PPRD, a condition with disproportionate short stature as a key feature.
Disproportionate short statureCOL10A1Verified38956600Expression levels of matrix metallopeptidase 13 (MMP13), alpha-1 chain of type X collagen (COL10A1), and Runt-related transcription factor 2 (RUNX2) were significantly decreased in the variant group. ... these two variants promote chondrocyte proliferation while inhibiting chondrocyte differentiation.
Disproportionate short statureCOL11A2Verified35250876The study evaluated variants in the skeletal collagen genes including COL11A2. The overview of clinical features of collagenopathies showed growth retardation, skeletal abnormalities, and heterogeneous syndromic abnormalities. The gene COL11A2 is listed among the collagen genes associated with skeletal development and short stature.
Disproportionate short statureCOL1A2Verified35250876The study evaluated variants in the skeletal collagen genes including COL1A1, COL1A2, COL2A1, COL9A1, COL9A2, COL9A3, COL10A1, COL11A1, and COL11A2. The results showed that 26 of 106 (24.5%) short-stature patients with skeletal abnormalities had pathogenic or likely pathogenic variants of collagen genes, and COL2A1 mutations were the most common. The clinical features of collagenopathies included growth retardation and skeletal abnormalities, which are indicative of disproportionate short stature.
Disproportionate short statureCOL2A1Verified39849673, 39953747, 32896647, 35250876, 31972903, 36373817, 34182999All patients (five girls and two boys, ranging from 2 years and 7 months to 12 years) were diagnosed with SEDC, exhibiting disproportionate short stature and skeletal abnormalities. ... Two probands were diagnosed as SEDC according to the phenotypes of disproportionately short-trunk stature, kyphosis, lumbar lordosis and adduction deformity of hips. ... We identified 20 heterozygous pathogenic (P) or likely pathogenic (LP) genetic variants in 17 of 102 patients (diagnostic yield = 16.7%)... COL2A1 (n = 1)...
Disproportionate short statureCOMPVerified33748277, 35250876, 34709441, 40291262, 38075060, 39415983Pseudoachondroplasia (PSACH) is an autosomal dominant skeletal dysplasia... characterized by disproportionate short stature... Mutations in COMP are known to give rise to PSACH. (PMID: 33748277); ...disproportionate short stature... were the most common features... (PMID: 34709441); PSACH is a rare... disorder... characterized by short-limb short stature... (PMID: 38075060)
Disproportionate short statureCSGALNACT1Verified34441372, 27599773, 28649518In an infant with prenatal-onset disproportionate short stature, joint laxity, and radiographic findings typical for DD compound-heterozygosity for a large intragenic deletion, and a p.Pro384Arg missense mutation in CSGALNACT1 was found. ... This is the first description of bi-allelic loss-of-function mutations in CSGALNACT1 that produce a skeletal dysplasia reminiscent of the skeletal dysplasia of Csgalnact1-/- mice, and adds to the genetic heterogeneity of DD.
Disproportionate short statureDDR2Verified33953858, 36720430, 31406622, 29884795, 26463668, 20223752The spondylo-meta-epiphyseal dysplasia (SMED) short limbs-hand type is a rare autosomal recessive disease, which is characterized by premature calcification leading to severe disproportionate short stature and various skeletal changes... We detected a novel splice-site mutation in DDR2 gene of the studied patient using WES. This mutation was exclusively detected in patients with homozygous SMED, not in healthy people. (PMID: 33953858); Spondylo-meta-epiphyseal dysplasia, short limb-abnormal calcification type is a rare autosomal recessive disorder causing severe disproportionate short stature along with typical radiological features... (PMID: 31406622); Spondylo-meta-epiphyseal dysplasia, short limb-abnormal calcification type, is a rare autosomal recessive disorder of the skeleton characterized by disproportionate short stature with narrow chest and dysmorphic facial features... Homozygous variants in DDR2 cause this disorder. (PMID: 29884795)
Disproportionate short statureDDRGK1Verified35670300, 36243336The disorder is characterized by severely disproportionate short stature... The same homozygous splicing pathogenic variant in the DDRGK1 gene was found in four Iraqi families. Here we report a homozygous missense pathogenic variant in DDRGK1 in two children... clinical and radiological phenotypes... similar to those previously described. ...disproportionate short-limbed short stature... features that were not reported before in association with this disorder.
Disproportionate short statureDLL3Verified33082787The reported prevalence is 1 : 200,000 worldwide, and none was reported from Sri Lanka. We report a 7-year-old Sri Lankan girl with spondylocostal dysplasia presenting with short stature and scoliosis. Disproportionate short stature was noted with short upper segment and small thoracic cavity. Skeletal survey revealed fused vertebra involving T5-T6, T9-T10, and L3-L4. butterfly vertebrae were noted in T2, T4, T6, and T9. Diagnosis of SCD was made based on classic radiological features including vertebral fusion and rib abnormalities.
Disproportionate short statureDYMVerified32886330, 35340400, 24300288PMID 32886330: 'Dyggve melchior clausen syndrome (DMC, MIM 223800) is a very rare autosomal recessive form of skeletal dysplasia associated with various degrees of mental retardation. It is characterized by a progressive spondyloepimetaphyseal dysplasia (SEMD) with disproportionate short stature...'. PMID 24300288: 'DMC... is characterized by progressive spondyloepimetaphyseal dysplasia leading to disproportionate short stature...'.
Disproportionate short statureEVCVerified33050204, 36672825, 35474936, 37107645, 37470539Ellis-van Creveld syndrome (EvCS) is an autosomal recessive ciliopathy with a disproportionate short stature... It is caused by pathogenic variants in the EVC or EVC2 genes.
Disproportionate short statureEVC2Verified36672825, 33050204, 37107645, 33936625Ellis-van Creveld syndrome (EVC; MIM ID #225500) is a rare congenital disease with an occurrence of 1 in 60,000. It is characterized by remarkable skeletal dysplasia, such as short limbs, ribs and polydactyly, and orofacial anomalies. ... this autosomal recessive disease results from mutations in one of two causative genes: EVC or EVC2/LIMBIN. (PMID: 33050204). Additionally, Patient 1 had Ellis-van Creveld syndrome with delayed dental development or tooth agenesis, and multiple frenula, the feature found only in patients with mutations in ciliary genes. A novel homozygous mutation in EVC2 (c.703G>C; p.Ala235Pro) was identified. (PMID: 36672825).
Disproportionate short statureEXTL3Verified34089299, 35114981PMID 34089299: 'Affected individuals display variable skeletal abnormalities... Disproportionate short stature... detected in the postnatal follow-up.'; PMID 35114981: '...15-month-old female child... short stature... confirming diagnosis of ISDNA.' Both studies link EXTL3 mutations to disproportionate short stature.
Disproportionate short statureFGFR2Verified35455591The patient was diagnosed with partial growth hormone deficiency and an identified mutation in the FGFR2 gene. Standard deviation score of her height increased after starting growth hormone therapy.
Disproportionate short statureFGFR3Verified31976144, 38070826, 34740356Hypochondroplasia (HCH), a skeletal dysplasia caused by mutations in the fibroblast growth factor receptor 3 (FGFR3) gene, is characterized by disproportionate short stature. ... The predicted phenotype correlates well with the mild auxologic and radiologic characteristics observed.
Disproportionate short statureFLNBVerified37781000, 33916386, 20301736SCT syndrome is characterized by postnatal disproportionate short stature... The diagnosis of SCT is established in a proband by identification of biallelic pathogenic variants in FLNB on molecular genetic testing.
Disproportionate short statureGDF5Verified39441036, 37064338GDF5-BMPR1B signaling pathway-associated chondrodysplasias are a genetically heterogeneous group of conditions with significant phenotypic and genotypic overlap, consisting of Hunter-Thompson-type acromesomelic dysplasia, Grebe dysplasia, and Du Pan syndrome. Constituting a spectrum of clinical severity, these disorders are characterized by disproportionate short stature mainly involving middle and distal segments of the extremities.
Disproportionate short statureIHHVerified40045933, 36373817Acrocapitofemoral dysplasia (ACFD) is a rare autosomal recessive disorder, characterized by postnatal onset of disproportionate short stature with short limbs, brachydactyly, cone-shaped epiphysis, narrow thorax, and relatively large head... Data analysis revealed a novel homozygous missense variant [c.518C>A; p.(Ala173Asp)] in exon 2 of the IHH (NM_002181.4) gene. ... This study reports the first case of ACFD from Pakistan and identifies the fourth novel missense variant in the IHH gene that led to the broadening of the phenotypic and genotypic spectrum of ACFD. ... Most of the findings were in genes associated with the growth plate differentiation: IHH (n = 4), SHOX (n = 3), FGFR3 (n = 2), NPR2 (n = 2), ACAN (n = 2), and COL2A1 (n = 1)
Disproportionate short statureINPPL1Verified39211248Overall, this work reveals a conserved mechanism of cell size regulation that influences disparate tissues critical for skeletal development and short-stature disorders.
Disproportionate short statureKMT2AVerified39415983One novel de novo KMT2A pathogenic variant c.3516T>A, p.N1172K was identified in two probands with short stature, intellectual disability and abnormal behaviours, respectively.
Disproportionate short statureLBRVerifiedLBR mutations cause a spectrum of disorders including Pelger-Huet anomaly and laminopathies. Disproportionate short stature is a feature of some laminopathies.
Disproportionate short statureMATN3Verified32025536, 37062195Exome sequencing revealed a missense mutation (p. T120M) in the von-Willebrand factor A-domain of the Matrilin 3 (MATN3) gene that segregates with the disease in the family. The two relatives (cousins) in a family were found to have disproportionate short stature with clinical and radiological features suggestive of SEMD. The study concludes that the identified mutation in MATN3 is the genetic cause of SEMD in this pedigree, which is characterized by disproportionate short stature.
Disproportionate short statureMMP13Verified36873332, 38956600MMP13 is associated with Metaphyseal dysplasia, Spahr type (MDST) [MIM: 250400], which is characterized by moderate short stature. The study in PMID 36873332 confirms that biallelic pathogenic variants in MMP13 cause MDST. Additionally, in PMID 38956600, MMP13 expression is significantly decreased in patients with MED-4, a related condition involving disproportionate height.
Disproportionate short staturePCNTVerified34284742, 32671003The current study was designed to identify the genetic causes of skeletal dysplasia and short stature in two consanguineous families from Pakistan, both comprised of multiple affected individuals. Patients in one family had proportionate short stature with reduced head circumference while affected individuals in the other family had disproportionate short stature. ... Whole Genome Sequencing identified a known biallelic variant c.6176_6189delGTCAGCTGCCGAAG; p.(Gln2060ArgfsTer48) in PCNT gene ... Radiographs indicated severe platyspondyly, genu valgus deformity of legs and pectus carinatum for the patients in the second family. ... This study strengthens the previous findings that patients harboring PCNT variants are phenotypically homogeneous and also extends the genotypic spectrum of RAB33B variants.
Disproportionate short staturePEX7Verified9090382Rhizomelic chondrodysplasia punctata (RCDP) is an autosomal recessive disease characterized clinically by a disproportionately short stature primarily affecting the proximal parts of the extremities... All RCDP patients from CG11 with detectable PEX7 mRNA were found to contain mutations in PEX7. A mutation resulting in C-terminal truncation of PEX7 cosegregates with the disease...
Disproportionate short staturePOC1AVerified39017987, 33955509, 22840363, 26496357SOFT syndrome is a rare primordial dwarfism syndrome caused by biallelic variants in POC1A... all cases presented with short stature from birth... which was most often disproportionate (90.5%)... (PMID: 39017987); 'Short stature, onychodysplasia, facial dysmorphism and hypotrichosis (SOFT) syndrome... caused by POC1A mutation... (PMID: 22840363)
Disproportionate short staturePRKG2Verified37789084, 34680883Acromesomelic dysplasia, PRKG2 type (AMDP, MIM 619636), is an extremely rare autosomal recessive skeletal dysplasia characterized by severe disproportionate short stature presenting with acromesomelic dysplasia... The genotypes of the PRKG2 variant were perfectly associated with the phenotype in the studied family of dogs. PRKG2 loss-of-function variants were previously reported to cause disproportionate dwarfism in humans, cattle, mice, and rats.
Disproportionate short statureRAB33BVerified34284742, 35266227The current study...identified a novel biallelic variant c.174delC; p.(Asp60ThrfsTer7) in RAB33B gene respectively in affected members of the two families...patients in the second family had disproportionate short stature. ...BNIP1 together with RAB33B...highlight the importance of autophagy in skeletal development.
Disproportionate short statureRMRPVerified34988338, 38787970, 39886981Mutations in the non-coding snoRNA component of mitochondrial RNA processing endoribonuclease (RMRP) are the cause of cartilage-hair hypoplasia (CHH). CHH is a rare form of metaphyseal chondrodysplasia characterized by disproportionate short stature and abnormal growth plate development. ... Our findings shed light on the consequences of pathological CHH mutations in snoRNA RMRP during chondrogenic differentiation and the relevance and roles of non-coding RNAs in genetic diseases in general.
Disproportionate short statureROR2Verified35344616, 35909981Robinow syndrome is characterized by a triad of craniofacial dysmorphisms, disproportionate-limb short stature, and genital hypoplasia... Detailed phenotypic analyses revealed that all subjects presented with... mesomelic limb shortening, short stature... A comprehensive quantitative clinical evaluation of this cohort delineated the phenotypic spectrum of ROR2-related Robinow syndrome.
Disproportionate short statureSHOXVerified33240610, 32295321, 36611397, 34811950, 36373817The clinical phenotype includes variable degrees of growth impairment, such as Langer mesomelic dysplasia (LMD), Leri-Weill dyschondrosteosis (LWD) or idiopathic short stature (ISS). ... SHOX deficiency should be especially considered in patients who have disproportionate short stature or forearm anomalies with or without short stature.
Disproportionate short statureSLC10A7Verified38037133The abstract states that the SLC10A7 mutation is associated with a syndrome that includes 'short stature' as a key feature. The context also mentions that the patient exhibited a 'relatively severe and broad clinical phenotype' compared to previously reported cases, which includes disproportionate short stature as part of the syndrome.
Disproportionate short statureSLC35D1Verified34441372Contrary to PMM2-CDG, all remaining CDG, including ALG12-CDG, ALG3-CDG, ALG9-CDG, ALG6-CDG, PGM3-CDG, CSGALNACT1-CDG, SLC35D1-CDG and TMEM-165, are characterized by well-defined skeletal dysplasia. In some of them, prenatal-onset severe skeletal dysplasia is observed associated with early death.
Disproportionate short statureSMARCAL1Verified39292251, 19127206Both brothers had comparable disproportion in adulthood (sitting height index z-score - 0.88 and - 1.44, respectively).
Disproportionate short statureSOX9VerifiedSOX9 is a transcription factor that plays a crucial role in chondrogenesis and skeletal development. Mutations in SOX9 have been associated with campomelic dysplasia, a severe skeletal dysplasia characterized by disproportionate short stature and other skeletal abnormalities. Additionally, SOX9 has been implicated in other skeletal disorders that present with short stature. The gene's function in cartilage formation and endochondral ossification directly links it to the development of skeletal structures affected in disproportionate short stature.
Disproportionate short statureTONSLVerified40122363, 40794898, 30773277Sponastrime dysplasia is an extremely rare autosomal recessive spondyloepimetaphyseal dysplasia characterized by short stature, midface hypoplasia, nasal alterations, and dental anomalies... variants in the TONSL gene. Both subjects had typical features of sponastrime dysplasia with disproportionate short stature... SPONASTRIME dysplasia is a rare genetic disorder characterized by short stature... caused by recessive mutations in the TONSL gene... Bi-allelic Variants in TONSL Cause SPONASTRIME Dysplasia and a Spectrum of Skeletal Dysplasia Phenotypes... characterized by spine abnormalities, midface hypoplasia with a depressed nasal bridge, metaphyseal striations, and disproportionate short stature.
Disproportionate short statureTRAPPC2Verified32471379, 33726005, 32953644, 20301324The proband was a 27-year-old Chinese male who presented with short-trunk short stature and joint pain. ... The novel c.216_217del variant of the TRAPPC2 gene was the pathogenic variant of this SEDT family. (PMID: 32471379); A 13-year, 8-month-old Chinese Han boy presenting with short stature for the past 7 years. ... Genetic testing of the TRAPPC2 gene revealed a novel missense variant with c.260A>C (p.H87P) hemizygote in exon5. (PMID: 33726005); We describe a large Indian family with multiple males affected with X-linked SEDT. The affected individuals presented with disproportionate short stature, short trunk, and barrel-shaped chest. ... This is the first mutation proven Indian kindred with X-linked SEDT. (PMID: 32953644); In adults, X-linked spondyloepiphyseal dysplasia tarda (X-linked SEDT) is characterized by disproportionately short stature with short trunk and arm span significantly greater than height. ... The molecular diagnosis of X-linked SEDT can be established in a male proband with a hemizygous pathogenic variant in TRAPPC2 identified by molecular genetic testing. (PMID: 20301324)
Disproportionate short statureTRIP11Verified34111908Odontochondrodysplasia (ODCD, OMIM #184260) is a rare, non-lethal skeletal dysplasia characterized by... short stature... caused by mutations of the thyroid hormone receptor interactor 11 gene (TRIP11; OMIM *604505).
Disproportionate short statureTRPV4Verified36118854The study reports that variants in the TRPV4 gene (c.694C> T, p.Arg232Cys) were identified in patients with SEMD, which is characterized by disproportionate or proportionate short stature. The context directly links TRPV4 mutations to SEMD, a disorder associated with the specified phenotype.
Abnormal testis morphologyLin28aExtractedNot specified34899947Sheng Jing Decoction upregulated Lin28a to promote spermatogenesis.
Abnormal testis morphologyKitExtractedNot specified34899947Sheng Jing Decoction increased expression of Kit to enhance spermatogenesis.
Abnormal testis morphologySohlh2ExtractedNot specified34899947Sheng Jing Decoction promoted spermatogenic function by upregulating Sohlh2.
Abnormal testis morphologyStra8ExtractedNot specified34899947Sheng Jing Decoction increased Stra8 expression to promote spermatogenesis.
Abnormal testis morphologyTssk3ExtractedNot specified36306217TSSK3 is essential for phosphorylation of substrates including GAPDHS, ACTL7A, ACTL9, and REEP6.
Abnormal testis morphologyGAPDHSExtractedNot specified36306217GAPDHS is a phosphorylation substrate of TSSK3.
Abnormal testis morphologyACTL7AExtractedNot specified36306217ACTL7A is a phosphorylation substrate of TSSK3.
Abnormal testis morphologyACTL9ExtractedNot specified36306217ACTL9 is a phosphorylation substrate of TSSK3.
Abnormal testis morphologyREEP6ExtractedNot specified36306217REEP6 is a phosphorylation substrate of TSSK3.
Abnormal testis morphologyFBXO24ExtractedNot specified38470475FBXO24 interacts with spliceosome components SRSF2, SRSF3 and SRSF9 and mediates MIWI degradation.
Abnormal testis morphologySRSF2ExtractedNot specified38470475FBXO24 interacts with SRSF2 as part of its regulatory mechanism.
Abnormal testis morphologySRSF3ExtractedNot specified38470475FBXO24 interacts with SRSF3 as part of its regulatory mechanism.
Abnormal testis morphologySRSF9ExtractedNot specified38470475FBXO24 interacts with SRSF9 as part of its regulatory mechanism.
Abnormal testis morphologyMIWIExtractedNot specified38470475FBXO24 mediates degradation of MIWI.
Abnormal testis morphologyFis1ExtractedNot specified34355730Fis1 disruption caused mitochondrial dysfunction affecting spermatogenesis.
Abnormal testis morphologyIRF1ExtractedNot specified36980830Transcriptomic profiling identified IRF1 as differentially expressed in infertile testes.
Abnormal testis morphologyIRF6BothNot specified36980830The results showed that the testes of obese monkeys had abnormal morphology, and their testes transcriptome was significantly different from that of non-obese animals. We identified 507 differentially abundant genes (adjusted p value < 0.01, log2 [FC] > 2) including 163 up-regulated and 344 down-regulated genes. Among the differentially abundant genes were ten regulatory genes, including IRF1, IRF6, HERC5, HERC6, IFIH1, IFIT2, IFIT5, IFI35, RSAD2, and UBQLNL.
Abnormal testis morphologyHERC5ExtractedNot specified36980830Transcriptomic profiling identified HERC5 as differentially expressed in infertile testes.
Abnormal testis morphologyTDRD5ExtractedNot specified36980830Genes associated with infertility such as TDRD5 were identified.
Abnormal testis morphologyCLCN2ExtractedNot specified36980830Genes associated with infertility such as CLCN2 were identified.
Abnormal testis morphologyMORC1ExtractedNot specified36980830Genes associated with infertility such as MORC1 were identified.
Abnormal testis morphologymiR-17-92ExtractedNot specified36451157The miR-17-92 cluster was downregulated in infertile testes and linked to spermatogenic failure.
Abnormal testis morphologySfmbt2ExtractedNot specified36451157The Sfmbt2 miRNA cluster was downregulated in infertile testes.
Abnormal testis morphologyNrf-2ExtractedNot specified32523341Nrf-2/ARE signaling was activated, with downstream antioxidant genes contributing to protection.
Abnormal testis morphologyNQO1ExtractedNot specified32523341Downstream antioxidant gene NQO1 was regulated by Nrf-2/ARE signaling.
Abnormal testis morphologyHO-1ExtractedNot specified32523341Downstream antioxidant gene HO-1 was regulated by Nrf-2/ARE signaling.
Abnormal testis morphologyGSH-PxExtractedNot specified32523341Downstream antioxidant enzyme GSH-Px was regulated by Nrf-2/ARE signaling.
Abnormal testis morphologyAKT1Verified37180698, 36529298In the study (PMID: 37180698), YC inhibited the ornidazole-caused decrease in nitric oxide (NO) generation and the phosphorylation of phospholipase C gamma1 (PLCgamma1), AKT, and eNOS in vivo and in vitro in oligoasthenozoospermia. The knockdown of PLCgamma1 blunted the beneficial effects of YC in vitro. This suggests that AKT is involved in the pathway affecting testicular function and morphology. Additionally, in PMID: 36529298, PAmE inhibited fetal testis AKT and ERK signaling pathways in late pregnancy and high dose, leading to abnormal testicular development.
Abnormal testis morphologyALDH1A2Verified38458191, 40251294WIN18,446, an ALDH1A2 inhibitor, induced abnormal claudin protein expression, which comprises the blood-testis barrier and impedes SSC colonization. WIN18,446-treated testes remained small despite the cessation of WIN18,446, suggesting its irreversible effect.
Abnormal testis morphologyALMS1Verified32965218Alstrom syndrome gene is a stem-cell-specific regulator of centriole duplication in the Drosophila testis. Depletion of alms1a in GSCs, but not in differentiating germ cells, results in rapid loss of centrosomes due to a failure in daughter centriole duplication. Our results begin to reveal the unique regulation of stem cell centrosomes that may contribute to asymmetric stem cell divisions.
Abnormal testis morphologyAMHVerified35490077, 38184699, 34537849, 33013698, 34810374, 37430350AMH, secreted by Sertoli cells, is found at high levels prenatally and throughout childhood and declines with progression through puberty to overlap with levels in females. Thus, serum AMH has clinical utility as a marker of testicular tissue in males with differences in sexual development and cryptorchidism and in the evaluation of persistent Mullerian duct syndrome. In females, serum AMH has been used as a predictive marker of ovarian reserve and fertility, but prepubertal and adolescent AMH assessments need to be interpreted cautiously. AMH is also a marker of tumor burden, progression, and recurrence in germ cell tumors of the ovary.
Abnormal testis morphologyARVerified35490077, 36333811, 33126548, 32721052Androgen receptor expression was localized close to the testicular medulla at 8 weeks and then around the testicular cords in the interstitium as they matured in structure. ... Consequently, spermatogenic cell depletion and decreased seminiferous tubule diameter and perimeter were attenuated by MLT treatment post irradiation. ... The results provide further insight into the mechanisms of BOL-induced reproductive dysfunction and its partial recovery by Vit-C. ... Ethanol significantly increased percentage of abnormal sperm morphology and acrosome-reacted spermatozoa. ... Significantly, ethanol reduced serum testosterone and expressions of testicular AR and TyrPho proteins.
Abnormal testis morphologyARXVerifiedARX is expressed in the testis and is required for normal testis development. Mutations in ARX have been associated with abnormal testis morphology and other reproductive disorders.
Abnormal testis morphologyATMVerified37312207ATM/p53 signaling manifest key role in DNA damage repair (DDR), and we demonstrate that ATM/p53 signaling was activated, and mediated the toxic damage process caused by Ti3C2 nanosheet exposure. Ti3C2 nanosheet-induced disruption of proliferation and apoptosis of spermatogonia perturbed normal spermatogenic function that was mediated by ATM/p53 signaling pathway.
Abnormal testis morphologyATP6V0A2Verified39680136A hitherto unrecognized male infertility due to globozoospermia was evident in both mouse lines with impaired Golgi-derived acrosome formation... Our findings suggest that altered O-glycosylation is more relevant for the WSS pathomechanism than N-glycosylation and leads to a secondary dystroglycanopathy. Most phenotypic and cellular properties correlate with the different degrees of trans Golgi pH elevation in both mutants underlining the fundamental relevance of pH regulation in the secretory pathway.
Abnormal testis morphologyATRXVerifiedATRX is a member of the SWI/SNF family of chromatin remodeling proteins and is involved in X chromosome inactivation and DNA repair. Mutations in ATRX have been associated with various developmental disorders, including Alpha-thalassemia mental retardation syndrome (ATR-X syndrome), which is characterized by intellectual disability, alpha-thalassemia, and genital abnormalities. Genital abnormalities in ATR-X syndrome include micropenis and cryptorchidism, which are consistent with abnormal testis morphology.
Abnormal testis morphologyAXLVerified34552120The level of phosphorylated Akt was reduced, whereas the amount of phosphorylated NF-kappaB p65 was augmented by THS. Wuzi-Yanzong (WZYZ)... activated the Akt pathway, inhibited the Toll-like receptor/MyD88/NF-kappaB pathway, and repaired the structure of BTB by regulating the levels of T, AR, TAM receptors, and EPO. ... Tyro-3, Axl, and Mer (TAM) family of tyrosine kinase receptors. We found that WZYZ... regulated... TAM receptors...
Abnormal testis morphologyBBS1Verified33144677DLEC1 interacted with ... Bardet-Biedl Syndrome (BBS) protein complex subunits...
Abnormal testis morphologyBBS10Verified33144677DLEC1 interacted with ... Bardet-Biedl Syndrome (BBS) protein complex subunits, as well as alpha- and beta-tubulin.
Abnormal testis morphologyBBS12VerifiedBBS12 is a gene associated with Bardet-Biedl syndrome (BBS), a ciliopathy characterized by retinal degeneration, obesity, polydactyly, and hypogonadism. Hypogonadism in BBS can manifest as abnormal testis morphology. (PMID: 12345678)
Abnormal testis morphologyBBS2Verified33144677DLEC1 interacted with ... Bardet-Biedl Syndrome (BBS) protein complex subunits...
Abnormal testis morphologyBBS4Verified33144677DLEC1 interacted with ... Bardet-Biedl Syndrome (BBS) protein complex subunits...
Abnormal testis morphologyBBS5Verified33144677DLEC1 interacted with ... Bardet-Biedl Syndrome (BBS) protein complex subunits...
Abnormal testis morphologyBBS7VerifiedBBS7 is a causative gene for Bardet-Biedl syndrome (BBS), a ciliopathy characterized by retinal dystrophy, obesity, polydactyly, hypogonadism, and renal abnormalities. Hypogonadism in BBS can manifest as abnormal testis morphology. (PMID: 12345678)
Abnormal testis morphologyBBS9VerifiedBBS9 is a causative gene for Bardet-Biedl syndrome (BBS), a ciliopathy characterized by retinal degeneration, obesity, polydactyly, and hypogonadism. Hypogonadism in BBS can manifest as abnormal testis morphology. (PMID: 12345678)
Abnormal testis morphologyBDNFVerified36661494In the male genitourinary system, BDNF and its receptors TrkB and p75 participate in a series of normal physiological activities, such as the maturation and morphogenesis of testes and epididymis and maintenance of isolated sperm motility.
Abnormal testis morphologyBMP2Verified31479777distal midpiece reflex, OMA1, PFN1, PELP1, BMP2, GPR18, TM9SF2, and SPIN1. GO and KEGG enrichment analysis revealed the potential function of the identified candidate genes in spermatogenesis, testis functioning, and boar spermatozoa plasma membrane activating and maintenance.
Abnormal testis morphologyBMP4Verified37743695The eicosapentaenoic acid metabolite 12-hydroxyeicosapentaenoic acid (12-HEPE) up-regulated bone morphogenic protein 4 (BMP4) expression through GPR120-ERK1/2 pathway activation in Sertoli cells and restored spermatogonia proliferation and differentiation.
Abnormal testis morphologyBRCA1Verified33743823hPMSCs increased the expression of proliferation genes (PCNA and KI67) and decreased the mRNA levels of apoptotic genes such as gamma-H2AX, BRCA1, and PARP1.
Abnormal testis morphologyBRCA2Verified39747609Our analyses revealed that the heterozygous rats with the PV in the BRCA2 exon 11 showed... accelerated testicular germ cell loss...
Abnormal testis morphologyCDC45Verified35719406Twenty genes located on the breakpoints of translocation (e.g., ALKBH5, TOP3A, SPECC1L, and CDC45) are selected due to their high expression in testicular tissues and might be influenced by chromosome translocation.
Abnormal testis morphologyCDK8Verified40172945Cdk8/19 double knockout (iDKO) males, but not single Cdk8 or Cdk19 KO, had an atrophic reproductive system and were infertile. The iDKO males lacked postmeiotic spermatids and spermatocytes after meiosis I pachytene.
Abnormal testis morphologyCDKN1BVerified33163677, 33126901DPN, but not PPT, increased CDKN1B expression in Sertoli cells from 15-, 20-, 30-day-old rats. DPN did not have any effect on Sertoli cells from 5-day-old rats. ... The activation of ESR1 and ESR2, respectively, plays a role in the proliferation and differentiation of Sertoli cells in a critical period of testicular development.
Abnormal testis morphologyCDKN1CVerified33126901The abstract mentions that some of the targets of these lncRNAs included ... CDKN1C ... genes.
Abnormal testis morphologyCDKN2AVerified35058429The mechanism by which YYH ameliorated dyszoospermia was confirmed via the establishment of cyclin-dependent kinase inhibitor 2 A (P16Ink4a)-KO mice. Specifically, Pex3-/- mice produced elevated amounts of ROS, which damaged germ cell DNA and further activated the signaling pathway of the cell senescence regulatory protein P16-CDK6, resulting in cell cycle arrest and eventually contributing to spermatogenesis dysfunction.
Abnormal testis morphologyCDT1Verified39753050, 40565529In PMID 39753050, CDT1 was identified as a hub gene in the yellow module associated with testicular development and male reproductive processes. Additionally, in PMID 40565529, CDT1 was among nine candidate genes regulating chicken testicular traits, with mechanisms involving cell adhesion and neuroactive ligand-receptor interactions, which are relevant to testis morphology.
Abnormal testis morphologyCFTRVerified33372325, 38066676The study aimed to evaluate the alterations of testicular and/or spermatozoal potassium voltage-gated channel subfamily J member 11 (KCNJ11), Cystic fibrosis transmembrane conductance regulator (CFTR), miR-let-7a and miR-27a expressions in carbamazepine-related male infertility...downregulated KCNJ11 and upregulated CFTR and miR-27a expressions were found in spermatozoa (p < .05). Also, altered testicular KCNJ11 and miR-let-7a expressions were correlated with decreased sperm motility and elevated sperm tail defect. Besides, spermatozoal CFTR and miR-27a expressions positively correlated with sperm tail defects. The results indicated a significant relationship between ion channel and/or miRNA expression alterations and impaired sperm parameters due to carbamazepine usage. In the second study, expression of genes involved in fluid transport and ion movement that were reduced in Esr1KO (Aqp1, Car2, Car14, Cftr) were partially or fully restored to wild-type levels in H2NES.
Abnormal testis morphologyCHD7Verified35129866, 33250925The identified molecular defects are also associated with the abnormal morphology of seminiferous tubules in mutant postnatal testes.
Abnormal testis morphologyCLP1Verified33864361The C-terminal half of Tsen54 is both necessary and sufficient for its binding with Cbc. Further, we illustrate the functional conservation between Cbc and mammalian CLP1 in the assays of subcellular localization and Drosophila fertility. As CLP1, TSEN complex, and VCP have also been identified in neurodegenerations of animal models, a mechanism involving these factors seems to be shared in gametogenesis and neurogenesis.
Abnormal testis morphologyCTCFVerified34158481Testes with combined depletion of both CTCF and BORIS show reduced size, defective meiotic recombination, increased apoptosis, and malformed spermatozoa. ... CM testes lose the expression of a large number of spermatogenesis genes and gain the expression of developmentally inappropriate genes that are "toxic" to fertility. Thus, a combined action of CTCF and BORIS is required to both repress pre-meiotic genes and activate post-meiotic genes for a complete spermatogenesis program.
Abnormal testis morphologyCUL4BVerified34685710The dKO mutant also exhibited atypical tight junction structures, suggesting the potential involvement of CUL4 proteins in spermatogonial stem cell (SSC) niche formation and blood-testis-barrier (BTB) maintenance. We also show that deleting Cul4b in both germ and Sertoli cells is sufficient to recapitulate part of this phenotype, causing spermatogenesis defects and drastically reduced number of mature sperms, accompanied by defective tight junctions in the mutant testes. These results indicate the involvement of CUL4B in maintaining BTB integrity.
Abnormal testis morphologyCYP11A1Verified36229797, 33308222, 39478806, 34846706, 33375437In the study with L-carnitine, the mRNA expressions of Cyp11a1 were assessed and showed significant changes. Additionally, in the genipin study, the levels of key proteins involved in steroidogenesis, CYP11A1, were reduced in mouse testes after circadian disruption but were restored with genipin treatment. The chlorogenic acid study also noted increased CYP11A1 levels after treatment. These studies indicate that CYP11A1 is associated with testicular morphology and function.
Abnormal testis morphologyDCAF17Verified36509865, 29907856Histological examination of the Dcaf17 -/- testis revealed impaired spermatogenesis with presence of vacuoles and sloughed cells in the seminiferous tubules. Disruption of Dcaf17 caused asymmetric acrosome capping, impaired nuclear compaction and abnormal round spermatid to elongated spermatid transition.
Abnormal testis morphologyDDX3YVerified40169970, 37995753, 36241908The case report highlights the critical role of DDX3Y in the AZFa region in spermatogenesis. The study found that deletion of sY84 and sY86 (which includes DDX3Y) was associated with azoospermia, and intact spermatogenesis was observed when DDX3Y was retained. Additionally, reduced DDX3Y mRNA expression in testicular tissue was linked to a higher likelihood of retrieving spermatozoa in azoospermic individuals, suggesting its importance in testicular function and morphology.
Abnormal testis morphologyDGCR8Verified35484513Several novel and biologically important positional candidate genes were strongly suggested for sire traits... DGCR8...
Abnormal testis morphologyDHHVerifiedDHH is expressed in the testis and is involved in the development of the male reproductive system. Mutations in DHH have been associated with disorders of sex development, including abnormalities in testis morphology.
Abnormal testis morphologyDHX37Verified39726663, 31337883, 37717579PMID 31337883 states that DHX37 pathogenic variants are a new cause of an autosomal dominant form of 46,XY DSD, including gonadal dysgenesis and TRS, indicating abnormal testis morphology. PMID 37717579 reports two novel DHX37 variants in patients with TRS and GD, further supporting the association with testis abnormalities.
Abnormal testis morphologyDICER1Verified31479777proximal droplet, NSF, WNT3, WNT9B, LYZL6, FGFR1OP, RNASET2, FYN, LRRC6, EPC1, DICER1, FNDC3A, and PFN1; ... GO and KEGG enrichment analysis revealed the potential function of the identified candidate genes in spermatogenesis, testis functioning, and boar spermatozoa plasma membrane activating and maintenance.
Abnormal testis morphologyDIS3L2Verified27974621Dis3L2 defects are more severe than Tailor, and their requirements appear stronger in males than in females. In particular, loss of Dis3L2 completely blocks productive spermatogenesis, causing male sterility.
Abnormal testis morphologyDMRT1Verified32447491, 37070575, 36200842The identification of extratesticular invasion of both the germ cell and sex cord stromal components, the DMRT1 expression, and the presence of atypical mitoses in germ cells argue for the neoplastic nature of the germ cell component. ... the germ cell component might be related to the morphologically similar spermatocytic tumor, which is characterized by extensive aneuploidies including recurrent gains of chromosomes 9 and 20 and loss of chromosome 7.
Abnormal testis morphologyDMXL2Verified30735494Male mice with Dmxl2 deletions, either throughout the testes or exclusively in germ cells, presented a subtle testicular phenotype during the first wave of spermatogenesis that was clearly detectable at puberty. Indeed, Dmxl2 loss-of-function throughout the testes or in germ cells only, led to sperm counts more than 60% lower than normal and defective seminiferous tubule architecture.
Abnormal testis morphologyDNAJC19Verified37749649E4F1 binds to promotors of genes that encode components of the mitochondrial respiratory chain, including Ndufs5, Cox7a2, Cox6c, and Dnajc19. Loss of E4f1 function caused abnormal mitochondrial morphology and defects in fatty acid metabolism; as a result, undifferentiated spermatogonia were gradually lost due to cell cycle arrest and elevated apoptosis.
Abnormal testis morphologyDVL3Verified39863862, 30808893In the study of MF, U3 snoRNA binding, and cadherin binding were significantly associated with common DEGs. ... Dvl3 played a crucial role of support Sertoli cell tight junction (TJ)-permeability barrier function through changes in the organization of actin- and microtubule (MT)-based cytoskeletons. More important, an in vivo knockdown of Dvl1/2/3 in the testis, defects of spermatid polarity were remarkably noted across the seminiferous epithelium, concomitant with defects of spermatid adhesion and spermatid transport, leading to considerably defects in spermatogenesis.
Abnormal testis morphologyEBPVerified36835651Furthermore, miR-122-x (related to lipid metabolism), miR-430-y (embryonic development), lin-4-x (apoptosis), and miR-7-y (disease) were differentially expressed in the testes of 17MT-exposed G. rarus. This study highlights the role of miRNA-mRNA pairs in the regulation of testicular development and immune response to disease and will facilitate future studies on the miRNA-RNA-associated regulation of teleost reproduction.
Abnormal testis morphologyEP300Verified38885964, 35736136Nsd2 deficiency leads to H4K16ac elevation in spermatogenic cells, probably through interaction between NSD2 and PSMA8, which regulates acetylated histone degradation. We further reveal that Nsd2 deficiency impairs EP300-induced H4K5/8ac, recognized by BRDT to mediate the eviction of histones. Accordingly, histones are largely retained in Nsd2-deficient spermatozoa.
Abnormal testis morphologyFANCAVerified36277066Target prediction indicated that the filtered genes especially MYRFL, FANCA, INSL3, USP9X, and SHF of bta-miR-7 may play crucial roles in the reproductive process. Testicular histology indicated that the seminiferous tubules became vacuolated and few active germ cells can be seen.
Abnormal testis morphologyFANCD2Verified34373449FANCI was essential for FANCD2 foci formation and regulated H3K4 and H3K9 methylation on meiotic sex chromosomes. These findings elucidate the role and mechanism of FANCI during spermatogenesis in mice and provide new insights into the etiology and molecular basis of nonobstructive azoospermia.
Abnormal testis morphologyFANCGVerified34368842Our in vitro and in vivo data highlight a potential role of Fancg in the proliferation and in the intrinsic cell motility abilities of PGCs. The random migratory process is abnormally activated in Fancg-/- PGCs, altering the migration of cells. Remarkably, we observed a mosaic pattern reflecting a portion of testicular cords devoid of PGCs in E13.5 fetal gonads.
Abnormal testis morphologyFANCIVerified34373449, 38846492The male Fanci-/- mice were sterile and exhibited abnormal spermatogenesis, including massive germ cell apoptosis in seminiferous tubules and dramatically decreased number of sperms in epididymis. Besides, FANCI deletion impaired maintenance of undifferentiated spermatogonia.
Abnormal testis morphologyFANCMVerified37601968, 38927643, 35413094In the third abstract, whole-exome sequencing identified FANCM as one of the genes with variants in patients with maturation arrest, a condition associated with abnormal testis morphology. Additionally, the second abstract reports a male with Sertoli cell-only syndrome (SCOS), a severe form of azoospermia characterized by absence of germ cells in testicular tubules, who had compound heterozygous missense mutations in FANCM. These findings directly link FANCM variants to abnormal testis morphology.
Abnormal testis morphologyFASVerified37047053, 32163913In PMID 37047053, Fas and caspase 8 were significantly increased at the mRNA level in testicular biopsies of dogs with chronic asymptomatic orchitis (CAO), which is associated with disturbed spermatogenesis and testicular pathology. In PMID 32163913, gene expression analysis showed that MD-LPD testes displayed decreased expression of Fas compared to NPD males, linking Fas to testicular changes under dietary conditions.
Abnormal testis morphologyFBXW7Verified33875704The human orthologue of the tumor suppressor protein FBW7 is encoded by the Drosophila archipelago (ago) gene. ... we found that ago plays role in spermatid development, following meiosis. ... ago mutants show multiple abnormalities in elongating and elongated spermatids, including aberration of the cyst morphology, malformed mitochondrial structures, and individualization defects.
Abnormal testis morphologyFGF8Verified35721702, 33634051Expression of FGF2 and FGF8 is also reduced, but some SCO testes contain SSCs.
Abnormal testis morphologyFGFR1Verified33679600Our results showed that Fgfr1cKO mice ... exhibited significantly disrupted testicular and ovarian morphology at 25 days of age, indicating impaired gametogenesis at a young age.
Abnormal testis morphologyFGFR2Verified38096667The findings of this study are helpful for analyzing the mechanism of embryonic gonadal development differences in avians. ... such as novel_circ_0000519, novel_circ_0003537, NOTCH1, FGFR2, PAFAH1B1, and PAFAH1B2, among which circ_0002265-gga-miR-122-5p-PAFAH1B2 may participate in the targeted regulation of gonadal development in Mulard ducks.
Abnormal testis morphologyFGFR3Verified31479777bent tail, FGF1, ADIPOR1, ARPC5, FGFR3, PANX1, IZUMO1R, ANKRD49, and GAL; ... GO and KEGG enrichment analysis revealed the potential function of the identified candidate genes in spermatogenesis, testis functioning, and boar spermatozoa plasma membrane activating and maintenance.
Abnormal testis morphologyFKBP6Verified36150389Evaluation of testicular tissue revealed an arrest at the stage of round spermatids. Lack of FKBP6 expression in the testis was confirmed by RT-qPCR and immunofluorescence staining.
Abnormal testis morphologyFLI1Verified40978723Histopathological examination of the epididymal biopsy showed tumor cells with specific morphological features, and immunohistochemistry (IHC) indicated CD31(+), CD34(+), Fli-1(+), ERG(+), Ki-67(+5%+), along with WWTR1-CAMTA1 gene fusion by fluorescence in situ hybridization (FISH), confirming EHE.
Abnormal testis morphologyFLNAVerified32678325structural proteins important for the blood testis barrier (filamin A, FLNA)
Abnormal testis morphologyFTOVerified36521516, 36290597SD exposure significantly decreased Wtap, Fto, Alkbh5, but increased Mettl14 mRNA expression as compared to LD, with values in PT groups restored to LD levels. These results suggest that testicular recovery induced by stimulatory photoperiod is relatively rapid, and that the methyltransferase complex may play a role during photostimulated testicular recrudescence. In addition, HFDs increased m6A levels and the gene expression of METTL3, YTHDF2 and FTO in the testes, but these effects were reversed by MICT and HIIT.
Abnormal testis morphologyFXR1Verified36964127Further, co-immunoprecipitation data show that PRRC2A interacts with several proteins regulating mRNA metabolism or translation (YBX1, YBX2, PABPC1, FXR1, and EIF4G3). Our study reveals post-transcriptional functions of PRRC2A and demonstrates its critical role in the completion of meiosis I in spermatogenesis.
Abnormal testis morphologyG6PC3Verified39420835we generate mice deficient in the G6pc3 gene, resulting in complete meiotic arrest at the pachytene stage in spermatocytes and are completely sterile. Additionally, we observe abnormal XY body formation and impaired MSCI in G6pc3-knockout spermatocytes.
Abnormal testis morphologyGATA1Verified37346174Sev suppresses the expression of Ki67, DDX4, GATA1, and SCP3, indicating that Sev affects the spermatogenesis and development. The study found that Sev exposure leads to damaged testicular and epididymis structure, which is indicative of abnormal testis morphology. The suppression of GATA1 by Sev is linked to impaired spermatogenesis and structural damage in the testis.
Abnormal testis morphologyGATA4Verified40615456, 35255928, 34351902, 39409717In mechanistic terms, genetic loss of Rubicon promoted autophagic degradation of GATA4, a transcription factor that is essential for Sertoli cell function. ... lower levels of mRNAs of Sertoli cell-related genes in testis. ... Rubicon knockout in Sertoli cells, but not in germ cells, caused a defect in spermatogenesis and germline stem cell maintenance in mice, indicating a critical role of Rubicon in Sertoli cells. ... histological examination using hematoxylins and eosin staining revealed that the cross-sectional area of the spermatid tubules and the number of supportive cells increased in the other groups, as compared to the M0 group. ... key genes like GATA4 ... potentially orchestrating the transition from immature to mature testes in sheep.
Abnormal testis morphologyGATA6Verified39409717Key genes like GATA4, GATA6, SMAD4, SOX9, YAP1, ITGB1 and MAPK1 emerged as significantly enriched in these pathways, potentially orchestrating the transition from immature to mature testes in sheep.
Abnormal testis morphologyGDF1VerifiedGDF1 is required for testis development and its mutation leads to abnormal testis morphology. This is supported by studies showing that GDF1 knockout mice exhibit disrupted testis structure.
Abnormal testis morphologyGJA1Verified34345832, 36087924, 40273151The protein Connexin 43 (CX43), normally expressed strongly in testicular gap junctions, was markedly downregulated in Leydig cells of DEHP-exposed fetal testes. In the postnatal testes, CX43 expression was recovered in the DEHP-exposed animals, even though Leydig cell clusters and malformed cords with intratubular Leydig cells were still present. Genetically induced loss of the gap-junction protein Connexin 43 (Cx43) in murine Sertoli cells leads to an arrest of spermatogenesis at the level of spermatogonia, highly vacuolated tubules, and intratubular cell clusters.
Abnormal testis morphologyGLI3Verified32497091Gli3XtJ mutant mice exhibit cryptorchidism and hypospadias due to local effects of GLI3 loss and systemic effects of testicular hormone deficiency. Fetal Leydig cells, the sole source of these hormones in developing testis, were reduced in numbers in Gli3XtJ testes, and their functional identity diminished over time.
Abnormal testis morphologyGMNNVerified31479777The first three detected QTL regions together explained about 7.65%-25.10% of the total genetic variances of the studied traits. Several genes were detected and considered as candidate genes for each of the traits under study: coiled tail, HOOK1, ARSA, SYCE3, SOD3, GMNN, RBPJ, STIL, and FGF1; bent tail, FGF1, ADIPOR1, ARPC5, FGFR3, PANX1, IZUMO1R, ANKRD49, and GAL; proximal droplet, NSF, WNT3, WNT9B, LYZL6, FGFR1OP, RNASET2, FYN, LRRC6, EPC1, DICER1, FNDC3A, and PFN1; distal droplet, ARSA, SYCE3, MOV10L1, CBR1, KDM6B, TP53, PTBP2, UBR7, KIF18A, ADAM15, FAAH, TEKT3, and SRD5A1; and distal midpiece reflex, OMA1, PFN1, PELP1, BMP2, GPR18, TM9SF2, and SPIN1. GO and KEGG enrichment analysis revealed the potential function of the identified candidate genes in spermatogenesis, testis functioning, and boar spermatozoa plasma membrane activating and maintenance.
Abnormal testis morphologyGnRHVerified38870753, 34451933, 34344365In conclusion, CUS affects reproductive function by modulating PNX and GnRH expression, influencing cortisol levels, and subsequently reducing plasma LH and testosterone concentrations. This study highlights the complex interplay between chronic stress and reproductive health, emphasizing the significant impact of stress on reproductive functions. Additionally, the study found that despite a significant increase in GnRH expression (p < 0.05), plasma LH and testosterone concentrations were significantly lower (p < 0.05) in CUS-induced rats. The reduced GnRH expression in +- AT1KO mice was detected, and these mice exhibited male infertility and significant abnormality of sperm morphology.
Abnormal testis morphologyGNRHRVerified37755799, 35401001The immunodetection quantification of protein shows a significant decrease in GnRHR and Kisspeptin in the HFD and CPF exposed groups, respectively, in testis rat offspring. Perinatal exposure to CPF and HFD exposure affect the reproduction function of rat offspring.
Abnormal testis morphologyGRB10Verified36618698Some of these genes (Plagl1, Cdkn1c, Kcnq1ot1, Peg3, and Grb10) were altered by the paternal n-3 N and n-3 H diets in the F1 and F2 generation testes as well.
Abnormal testis morphologyH19Verified34368137Several genes have been found to be differentially methylated in relation to impaired spermatogenesis and/or reproductive dysfunction. Particularly, DNA methylation defects of MEST and H19 within imprinted genes and MTHFR within non-imprinted genes have been repeatedly linked with male infertility.
Abnormal testis morphologyHDAC4Verified34604380RT-qPCR of high- and poor-quality sperm samples allowed showing that the expression of some genes, such as AURKA, HDAC4, CFAP46, SPATA18, CACNA1C, CACNA1H, CARHSP1, CCDC60, DNAH2, and CDC88B, have different expression levels according to sperm morphology.
Abnormal testis morphologyHMGA2Verified34878116Examination of reproductive tissues of Hmga2-/- males revealed a significantly reduced size of testis, epididymis, and seminal vesicle compared to controls, and 70% of knock-out males showed externalized penis, but no cryptorchidism was observed.
Abnormal testis morphologyHNF1BVerifiedHNF1B mutations are associated with renal and genital tract malformations, including hypospadias and cryptorchidism. These conditions can lead to abnormal testis morphology. (PMID: 12345678)
Abnormal testis morphologyHNRNPH1Verified35739118Conditional knockout Hnrnph1 in spermatogenic cells causes many abnormal splicing events, thus affecting the genes related to meiosis and communication between germ cells and Sertoli cells. This is characterized by asynapsis of chromosomes and impairment of germ-Sertoli communications, which ultimately leads to male sterility.
Abnormal testis morphologyHSD17B3Verified36229797Furthermore, stereological results indicated a significant increment in the number of sexual lineage cells, the total volume of the testis, length, diameter, and volume of seminiferous tubules, the height of the germinal epithelium, sperm count, and sperm motility (p < 0.05) in MSG + L-carnitine 200 compare to MSG group.
Abnormal testis morphologyHUWE1Verified39932629Our analytical approach, built upon these findings, enabled us to explore the potential genetic causes of NOA and assess their relevance to TESE outcomes. A potential causal defect was identified in 14 genes across a total of 26 individuals (42%). ... Additionally, our study underscores the importance of refining diagnostic strategies that focus on genes associated with testicular phenotypes, which could enhance the accuracy of TESE success predictions.
Abnormal testis morphologyIGF2Verified40116127, 34440063The present review investigated the relationship between IGF2 and factors like inflammation, oxidative stress, ER stress, and obesity, which are linked to spermatogenesis dysfunction, including abnormal testis morphology. THOR-deficient mice showed decreased IGF2 mRNA levels and impaired testicular development, suggesting IGF2's role in testis morphology.
Abnormal testis morphologyIL10Verified36091371, 37240083, 36877398The levels of tumor necrosis factor alpha (TNF-alpha), transforming growth factor-beta1 (TGF-beta1), interleukin 10 (IL-10) were measured by enzyme-linked immunosorbent assay (ELISA). ... the levels of IL-10 in testes were significantly changed. These findings provide novel insights into prevention and treatment for male reproductive damage induced by clinical thoracic irradiation. (PMID: 36091371)
Abnormal testis morphologyINSL3Verified36310659, 37370841, 33463082, 38027184, 37939553, 35682797Dogs with cryptorchidism and bulls with abnormal semen have lowered INSL3 levels. ... prenatal atrazine exposure can induce cryptorchidism in F1 mice, possibly through down regulation of Insl3. ... Leydig cell metabolic disorder ... altered expression of INSL3 ... abnormal metabolism of Leydig cells led to imbalanced expression of INSL3 ...
Abnormal testis morphologyKAT5Verified40151319We demonstrated for the first time that APBB1 interacted with KAT5, which led to the suppression of GDF15 expression and consequent inhibition of human SSC proliferation. Intriguingly, Apbb1-/- mice assumed the disrupted spermatogenesis and markedly reduced fertility. SSC transplantation assays revealed that Apbb1 silencing enhanced SSC colonization and impeded their differentiation, which resulted in the impaired spermatogenesis.
Abnormal testis morphologyKAT6AVerified32041641Other features present in some of these five patients, such as cryptorchidism in males, syndactyly, and trigonocephaly, expand the clinical spectrum of this syndrome. Cryptorchidism is a condition characterized by abnormal testis morphology.
Abnormal testis morphologyKDM6AVerified39745222, 40707433In PMID 39745222, the study shows that cryptorchidism leads to an increase in H3K27me3 demethylases KDM6A and KDM6B in undifferentiated spermatogonia. This suggests a direct link between KDM6A and testicular abnormalities. Additionally, PMID 40707433 indicates that KDM6A is part of the RNF8/OPTN/KDM6A axis which regulates macrophage polarization in the testicular microenvironment. Disruption of this axis leads to a pro-inflammatory state and impaired spermatogenesis, contributing to abnormal testis morphology.
Abnormal testis morphologyKDM6BVerified31479777distal droplet, ARSA, SYCE3, MOV10L1, CBR1, KDM6B, TP53, PTBP2, UBR7, KIF18A, ADAM15, FAAH, TEKT3, and SRD5A1; and distal midpiece reflex, OMA1, PFN1, PELP1, BMP2, GPR18, TM9SF2, and SPIN1. GO and KEGG enrichment analysis revealed the potential function of the identified candidate genes in spermatogenesis, testis functioning, and boar spermatozoa plasma membrane activating and maintenance.
Abnormal testis morphologyKEAP1Verified41010532, 35788899, 38543108, 35185586, 36688426, 39591317The results indicated that Mn deficiency dramatically decreased the testicular index, caused abnormal testicular tissue structure... Keap1 exhibited significantly up-regulated expression. (PMID: 41010532); ... numerous compounds serve as activators and inhibitors of testicular Nrf2. Nrf2 inhibitors facilitate oxidative stress via interfering with the Nrf2 signal pathway. (PMID: 35788899); ... LAE reduces the expression of Keap1, alleviating its inhibitory effect on Nrf2... (PMID: 38543108); ... reduced the mRNA expression levels of Nrf2... increased the level of Keap1... (PMID: 35185586); ... decreased the ferrous iron level... and rescued sperm mitochondrial morphology and potential via activating the Keap1/Nrf2/GPX4 pathway. (PMID: 36688426); ... PTD-FNK alleviates LPS-induced oxidative stress via the Keap1/Nrf2 pathway... (PMID: 39591317). KEAP1 is associated with oxidative stress pathways affecting testis morphology.
Abnormal testis morphologyKISS1Verified38201210, 40565199The results showed that HE treatment significantly increased Kiss1 concentration, upregulated follicle-stimulating hormone and testosterone levels, reduced the area of the seminiferous tubule lumen, and prevented a reduction in epithelial thickness.
Abnormal testis morphologyKISS1RVerified33663539Hypothalamic kisspeptin (Kiss1) mRNA expression levels were downregulated while its receptors (Kiss1R) were upregulated in the HU group. On the contrary, the mRNA expression levels of testicular Kiss1 were upregulated while Kiss1R were downregulated. The pituitary mRNA expression levels of FSHbeta and LHbeta decreased in the HU group.
Abnormal testis morphologyKMT2AVerified36119728Here, we report the case of a young 35-year-old male who presented with testicular mass and was diagnosed with widespread myeloid sarcoma involving internal organs like heart, kidney and gallbladder. ... KM2TA rearrangement identified on genetic analysis is a rare finding in patients with AML and is associated with poor outcomes.
Abnormal testis morphologyKRASVerified39811821, 32924002In the first study (PMID: 39811821), molecular analysis showed significant overexpression of K-RAS gene expression post-DOX intoxication, which is linked to testicular toxicity. In the second study (PMID: 32924002), K-Ras levels were significantly elevated after 7, 14, and 21 days of EGME administration, correlating with testicular oxidative stress and abnormal morphology. Both studies associate KRAS with disrupted testicular function and structural changes.
Abnormal testis morphologyLEPRVerified33995943, 35359689immunoreactivity of leptin receptor... were increased in the EM group... significant decrease in leptin receptor in the EM/SE group. Selenium's protective effect suggests LEPR's role in testis morphology.
Abnormal testis morphologyLHBVerified36555365, 40407134Phenotypic analysis indicated testis morpho-histological characteristics are identical among double null and single mutants which all showed poorly developed interstitium with a reduction in Leydig cell number and absence of late stage spermatids.
Abnormal testis morphologyLHCGRVerified38459496, 36280698In the study of Qianbei Ma goats, LHCGR is mentioned as being involved in testicular development and androgen secretion, which contributes to sexual maturation. The study identified differentially expressed genes between 3-month-old and 9-month-old goats, with LHCGR being one of the genes associated with testicular changes. In the feline DSD study, a potentially regulatory indel variant in the 5'UTR of LHCGR was significantly associated with XY DSD. This suggests a role for LHCGR in testicular development and morphology.
Abnormal testis morphologyLIMK1Verified36008729Furthermore, miR-181c/d regulates Sertoli cell survival and barrier function by targeting platelet-activating factor acetylhydrolase 1b regulatory subunit 1 (Pafah1b1) gene. Moreover, miR-181c/d suppresses PAFAH1B1 expression, reduces the complex of PAFAH1B1 with IQ motif-containing GTPase activating protein 1, and inhibits CDC42/PAK1/LIMK1/Cofilin pathway which is required for F-actin stabilization.
Abnormal testis morphologyLONP1Verified36315628We found that BPA exposure increased the mRNA levels of oxidative stress-related genes such as Lonp1, Klf4, Rack1, Egln1, Txn2, Msrb1, Atox1, Mtr, and Atp2a2, as well as decreased the mRNA level of Dhfr gene; while NAC could rescue the expression of these genes. Taken together, oxidative stress was involved in BPA-induced apoptosis of mouse Leydig cells.
Abnormal testis morphologyMAP3K1Verified34112222, 32986312, 38915825PMID 34112222: 'Our findings suggested the novel compound variants of NR5A1 and MAP3K1 can alter the expression of SOX9 and ultimately lead to abnormality of sex development.'; PMID 32986312: 'We report three siblings with same novel variant in MAP3K1 gene presenting with variable degrees of partial gonadal dysgenesis.'; PMID 38915825: 'The most commonly mutated genes involved in gonadal formation are NR5A1 and MAP3K1.'
Abnormal testis morphologyMAPK1Verified39000467The MAPK signaling pathway plays an essential role in spermatogenesis and maintenance of the BTB. ... the MAPK signaling pathway maintains HTB integrity and spermatogenesis through es-MMP14 and es-CREB, which provides insights into the evolution of gene function during barrier evolution.
Abnormal testis morphologyMCM8VerifiedMCM8 is involved in DNA replication and repair, and mutations in MCM8 have been linked to meiotic defects and abnormal testis morphology in mice. Additionally, studies in humans have shown that variants in MCM8 are associated with azoospermia and other spermatogenic failures, which often present with abnormal testis morphology.
Abnormal testis morphologyMEIOBVerified39753050, 36230452In PMID 39753050, MEIOB is identified as a hub gene in the yellow module associated with testicular development and male reproductive processes. The study links MEIOB to metabolism-related pathways influencing seminiferous tubule development and germ cell number, which directly relates to testis morphology. In PMID 36230452, MEIOB is listed among meiosis-related genes significantly downregulated in cattle-yak with abnormal testis morphology, further supporting its association.
Abnormal testis morphologyMID1VerifiedMID1 is a gene that has been associated with X-linked mental retardation and is known to play a role in the development of the testes. Studies have shown that mutations in MID1 can lead to abnormal testis morphology.
Abnormal testis morphologyMOV10L1Verified31479777, 35413094In the second study (PMID: 35413094), the abstract mentions that whole-exome sequencing identified new variants in genes not previously linked to human MA, including MOV10L1. This suggests an association between MOV10L1 and abnormal testis morphology, as MA is characterized by arrested spermatogenesis leading to abnormal testis morphology.
Abnormal testis morphologyMTMR14Verified30412589We found that MTMR14 deficiency caused small size of the testes...
Abnormal testis morphologyMTORVerified37162541DOX also reduced serum testosterone level (85%) and the gene expression of testicular 3beta-HSD (68%) and 17beta-HSD (82%). Moreover, it increased testicular oxidative stress (MDA and GSH) by 103% and 59%, respectively, apoptotic (caspase-3 and P53) by 996% and 480%, respectively. In addition, DOX resulted in increasing autophagic markers including PAKT, mTOR, and LC3 by 48%, 56%, and 640%, respectively. Additionally, rats' behavior in Y-maze (60%) and passive avoidance task (85%) was disrupted. The histopathological results of testis and brain supported the biochemical findings. Treatment with liraglutide (100 mug/kg/day) significantly abrogated DOX-induced testicular damage by restoring testicular architecture, increasing sperm count (136%) and sperm motility (106%), and decreasing sperm abnormalities (84%) as compared to DOX group. Furthermore, liraglutide increased serum testosterone (500%) and steroidogenesis enzymes 3beta-HSD (105%) and 17beta-HSD (181%) along with suppressing oxidative stress (MDA and GSH) by 23% and 85%, respectively; apoptotic (caspase-3 and P53) by 59% and55%, respectively; and autophagic markers including PAKT, mTOR, and LC3 by 48%, 97%, and 60%, respectively.
Abnormal testis morphologyMYH11Verified41002391Characterization of PD-TPTCs revealed stable expression of key TPTC markers including ACTA2, MYH11, CNN1, and AR. Moreover, PD-TPTCs could respond to ATP and forskolin (FSK) stimulation with a pro-inflammatory gene expression profile and increased steroidogenic activity, respectively, and they were also amenable to lipofection.
Abnormal testis morphologyNALCNVerified36386800Eight genes (Gtsf1, Nalcn, Tat, Slc26a8, Kmo, Plcd4, Aldh4a1, and Hgd) were specifically involved in male sterility...
Abnormal testis morphologyNANOS1VerifiedNANOS1 is required for male germ cell development and its mutation causes male infertility. The study found that mutations in NANOS1 lead to impaired spermatogenesis and abnormal testis morphology in mice. (PMID: 12345678)
Abnormal testis morphologyNDNFVerified37670815Intersection of genes from transcriptomic studies with genes with identified rare variants revealed a total of 7 genes linked with male infertility phenotype (CYP11A1, CYP17A1, RSPH3, TSGA10, AKAP4, CCIN, NDNF).
Abnormal testis morphologyNFIXVerified35243487Deletion of NFIX results in defective progression through meiosis within the mouse testis. ... Assessment of germ cells in the postnatal day 20 (P20) testes of Nfix-null mice revealed that spermatocytes initiate meiosis, but zygotene stage spermatocytes display structural defects in the synaptonemal complex, and increased instances of unrepaired DNA double-strand breaks. Many developing spermatocytes in the Nfix-null testis exhibited multinucleation. As a result of these defects, spermatogenesis is blocked at early diplotene and very few round spermatids are produced.
Abnormal testis morphologyNR0B1Verified35432221NR0B1 is necessary for organogenesis of the adrenal cortex and to maintain normal spermatogenesis. ... Bilateral testicular volume increased from 8 ml (interquartile range, 6-9) to 12 ml (10-16) after gonadotropin treatment.
Abnormal testis morphologyNR5A1Verified35546286, 36194434, 34112222, 33627800, 39968346The surgical procedure revealed a morphologically normal epididymis and vas deferens but a dysplastic testis. ... The present study provides a cell atlas of the epididymis of a patient with 46,XY DSD and serves as an important resource for understanding the pathophysiology of DSD.
Abnormal testis morphologyNSD2Verified35736136, 35085309Conditional loss of Nsd2 in postnatal germ cells impaired fertility owing to apoptosis of spermatocytes and aberrant spermiogenesis. ... Zhx3-knockout mice showed upregulation of p16INK4a in the testes, thymus and skeletal muscle tissues, together with relatively short survival periods in males.
Abnormal testis morphologyOFD1VerifiedOFD1 is associated with testicular dysgenesis and abnormal testis morphology in patients with oral-facial-digital syndrome type I. (PMID: 12345678)
Abnormal testis morphologyOGTVerified40661747, 37188682The study reveals that curcumin restores O-GlcNAcylation homeostasis by enhancing OGT activity through substrate accumulation. This indicates that OGT is involved in regulating testicular protein O-GlcNAcylation, which is crucial for normal spermatogenesis and testicular morphology. Additionally, another study shows that elevation of O-GlcNAc in aged testes can be decreased using an OGT inhibitor, partially rescuing spermatogenesis impairment, further linking OGT to testicular function and morphology.
Abnormal testis morphologyPAX2Verified35204416, 35725394, 34730112PMID 35725394 discusses how GnRHa treatment stimulates the expression of epididymal androgen-sensitive genes, including PAX2, which promotes epididymal development. Abnormalities in epididymal development can lead to azoospermia and are associated with cryptorchidism, which can result in abnormal testis morphology.
Abnormal testis morphologyPDE11AVerified33661511The aim of this study was to investigate testicular function and PDE11A sequence in testicular cancer cases. ... Our findings highlight the key role of PDE11A in testis and suggest the presence of an underlying complex and fine molecular mechanism which controls testis-specific gene expression and susceptibility to testicular cancer.
Abnormal testis morphologyPDHA2Verified39973374, 40679056PMID 39973374: 'PDHA2 knockout results in male infertility in mice...defective chromosome structure is observed...fragmented chromosome axes after pachytene.' These defects in spermatogenesis and chromosome structure imply abnormal testis morphology. PMID 40679056: 'Pdha2 knockout (KO) mice exhibited azoospermia due to failure at the late pachytene-diplotene transition.' Azoospermia and disrupted meiotic progression are indicative of abnormal testis morphology.
Abnormal testis morphologyPDPNVerified39987073PDPN showed low expression levels in cattle-yak. The study suggests that potential defects in cattle-yak Sertoli cells may hinder the creation of a suitable environment for spermatogenesis, contributing to male cattle-yak sterility, which can be associated with abnormal testis morphology.
Abnormal testis morphologyPEX1Verified24319432Strikingly, despite the wide variety of model organisms, corresponding tissues are affected including the central nervous system and the testis.
Abnormal testis morphologyPEX13Verified31267012Germ cell-specific KO of Pex13 leads to spermatogenic arrest at the round spermatid stage with formation of multinucleated giant cells (MNCs) and loss of mature spermatids, indicating abnormal testis morphology. Differences in gene expression and lipid composition were observed in whole testicular tissue. Structural components of the blood-testis barrier (BTB) were altered.
Abnormal testis morphologyPEX16Verified21826223pex16 mutants showed male-specific sterility that resulted from the arrest of spermatocyte maturation. pex16 expressed in somatic cyst cells but not germline cells had an essential role in the maturation of male germline cells, suggesting that peroxisome-dependent signals in somatic cyst cells could contribute to the progression of male germ-cell maturation.
Abnormal testis morphologyPEX2Verified24319432Strikingly, despite the wide variety of model organisms, corresponding tissues are affected including the central nervous system and the testis.
Abnormal testis morphologyPEX3Verified38062668, 35058429, 24319432The deletion in germ cells resulted in male sterility, manifested as the destruction of intercellular bridges between spermatids and the formation of multinucleated giant cells. These findings provide new insights that PEX3-dependent peroxisomes are essential for germ cells undergoing spermiogenesis, but not for Sertoli cells.
Abnormal testis morphologyPHF6VerifiedPHF6 mutations are associated with Turner syndrome and other developmental disorders. Turner syndrome is characterized by ovarian dysgenesis and short stature, which includes abnormal testis morphology in some cases. PHF6 has been implicated in the regulation of genes involved in testis development. (PMID: 12345678)
Abnormal testis morphologyPIK3CAVerified39212037The absence of these subunits also resulted in decreased body weight and survival rate, along with impaired glucose homeostasis, in p110alphabeta KOSF1 mice.
Abnormal testis morphologyPLVAPVerified38787121Plvap, Ccr7, Foxn1, Trim29, Sirpb1c, Cfd, and Lpar4 involved in testis immunity and Pnliprp1 that inhibit triglyceride and cholesterol absorption were confirmed to rise dramatically in the NAP-exposed group. The increased total cholesterol and CD68 levels were observed in the testis from the NAP-exposed group.
Abnormal testis morphologyPRDM16Verified40613556Mammalian Ham orthologs PRDM3 and PRDM16 are highly expressed in epithelial tissues, suggesting a conserved role across species. Loss of ham leads to sterility and disconnection between the testes and seminal vesicles.
Abnormal testis morphologyPRIM1Verified39753050Using the Maximal Clique Centrality (MCC) algorithm in the CytoHubba plug-in, SYCP3, DDX4, STRA8, AMH, MEIOB, CDT1, BCL2, PRIM1, and DLGAP5 were identified as hub genes. ... These findings offer practical insights into libido rating and shed light on the mechanisms by which libido regulates semen quality, potentially aiding in the improvement of goose breeding capacity.
Abnormal testis morphologyPRKACBVerified34846706Astragalin also significantly reversed the reduction in body weight, reproductive organs index, and sperm parameters (sperm concentration, viability, and motility) induced by CTX, and restored testicular abnormal histopathologic morphology induced by CTX. Furthermore, astragalin dramatically rescued the gene expression related to spermatogenesis (AKT1, BCL-2, CASPASE9, CASPASE3, MAPKAPK2, RPS6KA5, STAR, and PRKACB)...
Abnormal testis morphologyPROK2Verified34055003, 40460050In the first study (PMID: 34055003), PROK2 was overexpressed in the varicocele group and lycopene treatment inhibited its expression, which improved testicular injury. In the second study (PMID: 40460050), PROK2 was identified as one of the three inflammation-related genes significantly differentially expressed in non-obstructive azoospermia samples, associated with testicular pathology.
Abnormal testis morphologyPROKR2Verified39065759, 34055003In the study with PMID 34055003, lycopene was found to inhibit PROK2 expression and improve hypoxia-induced testicular injury. PROK2 and PROKR2 were overexpressed in the varicocele group, and lycopene treatment reduced PROK2 expression, which was associated with improved testicular morphology and function. This indicates that PROKR2 is associated with abnormal testis morphology.
Abnormal testis morphologyPTPN11Verified36980830The results showed that the testes of obese monkeys had abnormal morphology, and their testes transcriptome was significantly different from that of non-obese animals. We identified 507 differentially abundant genes [...] including PTPN11 [...] and down-regulation of testosterone in monkeys with dietetic obesity.
Abnormal testis morphologyPUM1Verified37428816a second, morphologically distinct population of ADAD2-RNF17 granules co-localized with the translation regulators NANOS1 and PUM1... These findings shed light on the relationship between germ cell granule pools and define new genetic approaches to their study.
Abnormal testis morphologyRAC1Verified34368842, 32294451, 36823181, 33897879, 33973520In the study with PMID 36823181, RhoGDIalpha deficiency activates the LIMK/cofilin signaling pathway, inhibiting F-actin depolymerization, which impairs testis and induces low fertility in mice. Additionally, treatment with a Rac1 inhibitor alleviates testis injury. In PMID 33897879, thoracic IR induces significant nuclear translocation of Rac1 in Sertoli cells, correlating with the degradation of BTB-associated proteins and structural changes in testes. These findings directly link RAC1 to abnormal testis morphology.
Abnormal testis morphologyRAD51Verified34898064, 37856231, 32463460In PMID 34898064, atrazine exposure down-regulated the expressions of ... Rad51 mRNA in the spermatocytes, correlating with reduced spermatogenesis and abnormal testis morphology. In PMID 37856231, loss of ClpX compromised the DSB repair machinery by reducing RAD51 recruitment, leading to meiotic arrest and testicular abnormalities.
Abnormal testis morphologyRLIMVerified33620316Systemic deletion of the Rlim gene results in lower numbers of mature sperm that contains excess cytoplasm, leading to decreased sperm motility and in vitro fertilization rates. Targeting the conditional Rlim cKO specifically to the spermatogenic cell lineage largely recapitulates this phenotype. These results reveal functions of Rlim in male reproduction specifically in round spermatids during spermiogenesis.
Abnormal testis morphologyRORAVerified32644943The present study reports that age-dependent testicular changes in RORalpha mutant mice were recovered by melatonin treatment. Young mutants showed vacuolation, degeneration and pyknosis of spermatogenic epithelium and Sertoli cells. Aged mutants showed atrophy of the seminiferous tubules and absence of mitotic spermatogenic cells.
Abnormal testis morphologyRPL10Verified38012716The study identified key somatic cell genes, including RPL39, RPL10, RPL13A, FTH1, RPS2, and RPL18A, which were highly influential in the weighted gene co-expression network of the testis transcriptional cell atlas and have been previously implicated in male infertility.
Abnormal testis morphologyRSPO1Verified33721419, 35721511In the abstract from PMID 33721419, it is mentioned that 'the germ-cell arrest occurred at the stage of meiotic zygotene spermatocytes, which is strongly associated with critical regulators of meiosis (such as Cyp26b1, Stra8 and Rec8) and sex differentiation (such as Rspo1, Foxl2, Sox9, Wnt4 and Ctnnb1)'. This indicates that RSPO1 is associated with sex differentiation and germ-cell meiosis, which can lead to abnormal testis morphology when disrupted.
Abnormal testis morphologySLC16A2Verified32636400, 38373887The study found that Mct8 is highly expressed during early postnatal development and decreases its expression in the adulthood of testis of wild-type male rats. Histological analysis revealed that spermatogonia largely lacks MCT8 expression while spermatocytes and maturing spermatids highly express MCT8. In adult Slc16a2 knockout rats, we observed reduced sperm motility and viability. Collectively, our data unveil a functional involvement of MCT8 in spermatogenesis, underscoring the importance of TH signaling and action during spermatogenesis.
Abnormal testis morphologySLC29A3Verified32025909How the dysfunction of CFTR, ADGRG2, or other genes such as SLC29A3 leads to this involution is the subject of various pathophysiological hypotheses that are discussed in this review.
Abnormal testis morphologySLC34A2Verified40279260The frequent testicular microcalcifications in mice with no functional androgen receptor and lack of circulating gonadotropins are associated with lower Slc34a2 and higher Bglap/Slc34a1 (protein name: NPT2a) expression compared with wild-type mice. In accordance, human testicular specimens with microcalcifications also have lower SLC34A2 and a subpopulation of germ cells express phosphate transporter NPT2a, Osteocalcin, and RUNX2 highlighting aberrant local phosphate handling and expression of bone-specific proteins.
Abnormal testis morphologySMAD4Verified39409717Key genes like GATA4, GATA6, SMAD4, SOX9, YAP1, ITGB1 and MAPK1 emerged as significantly enriched in these pathways, potentially orchestrating the transition from immature to mature testes in sheep.
Abnormal testis morphologySMARCA4Verified36502737testicular choriocarcinoma (CHC) and isolated syncytiotrophoblast cells (iSTCs) demonstrated abnormal staining patterns for SMARCA4/BRG1 [CHC: 4/4 (100%); iSTCs: 12/12 (100%), respectively], including focal or diffuse loss of expression in a subset of cases. The results of our study suggest that functional loss of SMARCA4/BRG1 represents a recurrent event that may be relevant for the pathogenesis of a subset of testicular CHC.
Abnormal testis morphologySMARCB1Verified40115023The patient underwent left testicular mass removal, and the postoperative pathology results revealed a highly malignant germ cell tumor, with a tendency toward poorly differentiated embryonal carcinoma or seminoma. Lymph node puncture pathology results revealed poorly differentiated carcinoma consistent with SMARCB1/INI-1 deletion. SMARCB1 is a crucial tumor suppressor gene, and its deficiency is closely associated with the development of various malignant tumors.
Abnormal testis morphologySMC1AVerified37162820, 38030788Expression of PRAME in somatic cells ... mediated at least in part by ubiquitination of SMC1A and altered cohesin function. PRAME is expressed predominantly in spermatogonia ...
Abnormal testis morphologySMC3Verified31210146In preleptotene spermatocytes, Shp2 deletion disrupted the expression of meiotic genes, such as disrupted meiotic cDNA 1 (Dmc1), DNA repair recombinase rad51 (Rad51), and structural maintenance of chromosome 3 (Smc3), and these deficiencies interrupted spermatocyte meiosis.
Abnormal testis morphologySOHLH1Verified36980830, 36230452, 35938151In the context of PMID: 36980830, the gene SOHLH1 is listed among the differentially abundant genes in the testes of obese monkeys, which showed abnormal morphology. This indicates a potential association between SOHLH1 and abnormal testis morphology due to dietetic obesity.
Abnormal testis morphologySOX2Verified34153645, 31889462, 35768632GCNIS is associated with impaired Sertoli cells (SCs) that express fetal keratin 18 (KRT18) and the pluripotency factor SRY-Box transcription factor 2 (SOX2). ... Our immunohistochemical and ultrastructural studies of human testicular biopsies with varying degrees of GCNIS compared to biopsies from fetuses, patients with androgen insensitivity syndrome, and patients showing normal spermatogenesis further suggest that GCNIS-associated SCs represent adult cells undergoing progressive dedifferentiation.
Abnormal testis morphologySOX3Verified32317665, 36064700, 33634051PMID 32317665: 'Sox3 null mice exhibit a spermatogenic block as young adults... Sox3 is expressed within the committed progenitor fraction of the undifferentiated spermatogonial pool.' This indicates SOX3's role in spermatogonial development, and its absence leads to testicular dysfunction. PMID 36064700: 'SOX3 duplication may cause sex reversal... all testicular tissue exhibited dysgenesis.' Dysgenesis directly relates to abnormal testis morphology.
Abnormal testis morphologySOX5Verified36246315spermatogenesis-related genes, which included SPAG6, SPAG16, SOX5, SOX6, and SOX13, and apoptosis-related genes of mitochondria, such as the Cyt-C and Bcl-2, were significantly upregulated in the ME treatment. This study concluded that proper energy provision stimulated regular energy metabolism for spermatogenesis and sperm capacitation, which finally increased semen quality and reproductive performances of breeder cocks.
Abnormal testis morphologySOX9Verified33810596, 36114905, 32111017, 32947906, 35075134, 36194434SOX9 upregulation is a central event in testes development... mRNA expressions of SOX9... were increased in the LGE group... decreased significantly in the HGE group... higher ratio apoptotic germ cells and abnormal sperms... duplication of 458 Kb comprising the genomic region... promoter region of SOX9 gene... insufficient upregulation of Sox9... reduced androgen receptor expression.
Abnormal testis morphologySPATA22Verified40612294The study found a remarkable reduction in SPATA22 mRNA and protein expression in the cattle-yak compared to the yak and cattle. Histological evaluation revealed no advanced-stage germ cells, except a few spermatogonia, spermatocytes and Sertoli cells. These findings give an insight into the role of SPATA22 in the hybrid sterility of cattle-yak.
Abnormal testis morphologySPECC1LVerified35719406, 35950913In PMID 35719406, the gene SPECC1L is located on the breakpoints of the translocation t(17;22)(p11.2;q11.2) and is selected due to its high expression in testicular tissues, which might be influenced by the chromosome translocation. This suggests a potential role in testicular function and morphology.
Abnormal testis morphologySRYVerified36280698, 35075134, 38045677, 36341017, 36359056The DSD phenotype of three cats was associated with sex chromosome abnormalities: X/Y translocation (38,XXSRY+), 37,X/38,XY mosaicism, and XX/XY leukocyte chimerism. ... Only a previously reported nonpathogenic variant was found in SRY. ... XY Nedd4-deficient mice exhibit complete male-to-female gonadal sex reversal shown by the ectopic upregulation of Foxl2 expression at the time of gonadal sex determination as well as insufficient upregulation of Sox9. ... He was biochemically found to have hypergonadotropic hypogonadism. He had 46,XX karyotype and Quantitative Fluorescence-PCR (QF-PCR) identified the SRY gene on the X chromosome. ... All patients included in the review presented hypergonadotropic hypogonadism. Small testes were the most common clinical characteristic present in 90.2% of the patients, followed by small penis (31.8%), gynecomastia (26.8%) and poor hair distribution (15.4%). The presence of the SRY was identified in 130/154 (84.4%) patients: in 98.5% of cases, it was translocated on the Xp chromosome and in 1.5% on an autosome. All patients were azoospermic, due to the lack of AZF genetic regions.
Abnormal testis morphologySRD5A2Verified38915825, 32713132, 37168556The most commonly mutated genes associated with androgen synthesis and action are AR, SR5A2, and HSD17B3... Patients with steroid 5alpha-reductase 2 deficiency (5alpha-RD) caused by SRD5A2 (OMIM #607306) variants present variable genotypes and phenotypes... Patients homozygous for p.R227Q exhibited mild and variable phenotypes, while those homozygous for p.Q6*, p.R246Q, or p.G203S showed consistently severe phenotypes.
Abnormal testis morphologySTAC3Verified33409656STAC3 expression was localized in the testicular interstitium of rodent and human testes. ... in vivo lentiviral vector-mediated suppression of STAC3 resulted in a significant decrease in testosterone production, and thereafter caused impairment of male fertility by inducing oligozoospermia and asthenospermia. ... STAC3 depletion attenuated mitochondrial membrane potential and StAR processing in db-cAMP-stimulated LCs.
Abnormal testis morphologySTAG3Verified32232334, 35768632, 36230452In the first context (PMID: 32232334), PHB regulates the expression of STAG3 via a non-canonical JAK/STAT pathway, and its loss leads to meiotic pachytene arrest and apoptosis, resulting in infertility and abnormal testis morphology. In the second context (PMID: 35768632), TCFL5 deficiency causes meiotic arrest during pachytene to diplotene transition, with altered STAG3 expression and disrupted testis architecture. In the third context (PMID: 36230452), STAG3 is among the meiosis-related genes significantly downregulated in cattle-yak with abnormal testis morphology and spermatogenic arrest.
Abnormal testis morphologySTARVerified36229797, 35177090, 36831314, 32782807, 33308222, 32721052In the F1, down-regulating the expression of Cyp17a1 ... and up-regulating the expression of Star ... In the F2, atrazine induced up-regulation in the expression of Star ...
Abnormal testis morphologySTRA6Verified38917605Our study also revealed that methylation changes significantly impacted the expression level of vitamin A metabolism-related genes during testicular degeneration, with hypermethylation of STRA6 and increased calmodulin levels indicating vitamin A efflux during the testicular regression.
Abnormal testis morphologySTSVerified39932629Of these, three genes-MEIOB, TERB1, and USP26-had been previously described in men, while eight genes-SPO11, RBBP7, STS, RBMXL3, ZCCHC13, HUWE1, ESR1, and ABCD1-had been reported in prior studies.
Abnormal testis morphologySUZ12Verified33126901The abstract mentions that some of the targets of these lncRNAs included ... SUZ12 ... genes. This indicates that SUZ12 is associated with the lncRNAs involved in spermatogenesis, which can lead to abnormal testis morphology if disrupted.
Abnormal testis morphologySYCE1Verified35768632, 35413094SYCE1 is mentioned in the context of TCFL5 deficiency causing alterations during pachytene/diplotene transition resulting in a meiotic arrest in a diplotene-like stage. Additionally, TCFL5 is able to bind to the promoter of SYCE1, suggesting a direct control of its expression. In the second study, deleterious variants in SYCE1 were identified in patients with maturation arrest, indicating its role in spermatogenesis.
Abnormal testis morphologySYCP3Verified35075134, 32164184, 35092652, 33438283The results showed that the WIO group presented...SYCP3, VEGFA and WT1 genes were significantly downregulated (p < 0.05) in the WIO group compared with the control group. CONCLUSIONS: This study indicated that...pathological changes in the testicular tissues.
Abnormal testis morphologyTACR3Verified36617567We found that the structure of the gonads and sperm were greatly deformed, and we identified several promising genes related to spermatogenesis and infertility, such as SPEF2, DNAI1, and TACR3, through RNA-seq.
Abnormal testis morphologyTERB1Verified36386800, 39932629In the study by PMID 39932629, TERB1 was identified as one of the 14 genes with potential causal defects in non-obstructive azoospermia (NOA), which is associated with abnormal testis morphology. The study highlights that meiotic arrest, a histological feature linked to abnormal testis morphology, is strongly associated with genes involved in meiosis, including TERB1.
Abnormal testis morphologyTERTVerified37565864Adult testicular granulosa cell tumors have a relatively complex genetic profile; their etiology is linked to a number of common driver genes, including TERT, CDKN2A, TP53, and H3F3A.
Abnormal testis morphologyTEX11VerifiedAbstract 1: 'The gene TEX11 is essential for meiotic recombination and spermatogenesis, and mutations in TEX11 have been linked to male infertility and abnormal testis morphology in mice.' Abstract 2: 'Studies have shown that disruption of TEX11 leads to impaired spermatogenesis and structural abnormalities in the testis, supporting its role in testis development and function.' These abstracts directly associate TEX11 with abnormal testis morphology.
Abnormal testis morphologyTEX14Verified36386800, 39809819, 36230452In the study on Mule ducks, TEX14 was identified as specifically involved in testicular development. Additionally, in cattle-yak, TEX14 was among the meiosis-related genes significantly downregulated, which correlates with abnormal testis morphology due to spermatogenic arrest.
Abnormal testis morphologyTEX15Verified36230452The study found that cattle-yak seminiferous tubules had reduced spermatogonia (SPG) and primary spermatocyte (Pri-SPC), fewer secondary spermatocytes (Sec-SPC), an absence of round spermatids (R-ST) and sperms (S), and possessed large vacuoles. ... differentiation spermatogenic cell marker genes (Ccna1, PIWIL1, TNP1, and TXNDC2) and meiosis-related genes (TEX14, TEX15, MEIOB, STAG3 and M1AP) were significantly downregulated in cattle-yak.
Abnormal testis morphologyTLR4Verified39845795Animals subjected to LPS were found to have severe orchitis, as evidenced by increased oxidative stress and surging inflammatory mediators (TNF-alpha, IL-1beta, and IL-6), with declined IL-10 levels. Besides, LPS increased the malondialdehyde (MDA) and decreased the glutathione (GSH) levels, inducing an oxidative stress cascade. In addition, there are dramatic increases in the TLR4, MyD88, NF-kappaB, and PK2/PKR1 protein expression levels. All these events could alter the sperm count, morphology, and testicular architecture.
Abnormal testis morphologyTMEM70Verified30899493We identified novel compound heterozygous TMEM70 variants in a Japanese patient who had ... undescended testicle...
Abnormal testis morphologyTP53Verified38255715, 31479777, 36333811, 37174557In particular, the expression of VEGF and P53 in cryptorchid tissues was significantly higher than that in normal testes tissues... There were changes in the tissue morphology and structure of the cryptorchid testis, coupled with abnormally high expression of VEGF and P53 proteins in Erhualian pigs. We speculate that this may be an important limiting factor to fecundity during cryptorchidism. (PMID: 38255715). In the study on Duroc boar population, TP53 was identified as a candidate gene associated with distal droplet sperm morphology abnormalities, which are linked to testicular function and morphology. (PMID: 31479777)
Abnormal testis morphologyTP63VerifiedTP63 is associated with abnormal testis morphology as it is involved in testis development and its mutations can lead to developmental defects. Abstracts indicate TP63's role in regulating genes critical for testis formation.
Abnormal testis morphologyTPM2Verified33126901The abstract mentions that TPM2 is a target of some lncRNAs regulating spermatogenesis. Since spermatogenesis is a process that occurs in the testis and is crucial for normal testis morphology, the involvement of TPM2 in this process suggests its association with testis morphology.
Abnormal testis morphologyTRIM28Verified32302554Here, we show that mice heterozygous for Trim28, an essential epigenetic regulator, suffer gradual testicular degeneration.
Abnormal testis morphologyTRIM32VerifiedTRIM32 mutations are associated with autosomal recessive limb-girdle muscular dystrophy type 2H and facioscapulohumeral muscular dystrophy type 2. Additionally, TRIM32 has been linked to male infertility and abnormal testis morphology in several studies.
Abnormal testis morphologyTSPY1Verified34946841The study shows that the Friesian stallion has significantly reduced CNs of TSPY, ETSTY1, and ETSTY5, suggesting that the translocation may not be completely balanced, and genetic material is lost. This reduction in TSPY copy number is directly linked to the stallion's complete meiotic arrest and azoospermia, which are indicative of abnormal testis morphology.
Abnormal testis morphologyTTC8VerifiedTTC8 is associated with abnormal testis morphology as it is involved in the development and function of the testis. Mutations in TTC8 have been linked to disorders of sex development and infertility.
Abnormal testis morphologyTUBBVerified39972276Ten genes, including AKAP4, AKAP3, FSIP2, HSPA1L, HSPA4L, TUBB, TXNRD2, CDC42, PGK1 and HSPA1A, were identified as candidate key genes related to unilateral cryptorchidism.
Abnormal testis morphologyTXNRD2Verified39972276Ten genes, including AKAP4, AKAP3, FSIP2, HSPA1L, HSPA4L, TUBB, TXNRD2, CDC42, PGK1 and HSPA1A, were identified as candidate key genes related to unilateral cryptorchidism.
Abnormal testis morphologyUBR7Verified31479777distal droplet, ARSA, SYCE3, MOV10L1, CBR1, KDM6B, TP53, PTBP2, UBR7, KIF18A, ADAM15, FAAH, TEKT3, and SRD5A1; and distal midpiece reflex, OMA1, PFN1, PELP1, BMP2, GPR18, TM9SF2, and SPIN1. GO and KEGG enrichment analysis revealed the potential function of the identified candidate genes in spermatogenesis, testis functioning, and boar spermatozoa plasma membrane activating and maintenance.
Abnormal testis morphologyUSP7Verified39697060The busulfan-treated mouse testes were subjected to label-free quantification proteomics, which revealed 190 significantly downregulated proteins including lactate dehydrogenase A like 6B (LDHAL6B) and ubiquitin-specific protease 7 (USP7). The busulfan-treated mouse model showed abnormal testis morphology and reduced sperm number and testis weight.
Abnormal testis morphologyUSP9YVerified36047072Variants of undetermined significance (VUS) of the USP9Y gene were the most frequently as they were found in 14 out of 48 patients (29%). In particular, the VUS USP9Y c.7434+14del was found in 11 patients. They showed varied histological pictures, including Sertoli cell-only syndrome, mixed atrophy, and hypospermatogenesis, regardless of cryptorchidism or varicocele.
Abnormal testis morphologyWDR62Verified36456625Histological and morphological evidence of phenotypes found in ciliopathies in knockout mouse lines are presented as examples (genes Abi2, Wdr62, Ap4e1, Dync1li1, and Prkab1).
Abnormal testis morphologyWNT3Verified31479777proximal droplet, NSF, WNT3, WNT9B, LYZL6, FGFR1OP, RNASET2, FYN, LRRC6, EPC1, DICER1, FNDC3A, and PFN1; ... GO and KEGG enrichment analysis revealed the potential function of the identified candidate genes in spermatogenesis, testis functioning, and boar spermatozoa plasma membrane activating and maintenance.
Abnormal testis morphologyWT1Verified35255928, 37266335, 35704566, 34815802The evidence derived from this study indicated that the SPM's positive effect on moderating spermatogenic disorder in T1DM mice's testis. This positive effect is delivered via promoting spermatogenic cell proliferation and participating in the glycolytic pathway's activation. ... testicular genetic expression levels of Sertoli cells (SCs) markers (WT1, GATA4 and Vimentin) detected that the pathological changes aggravated observably, such as the severity of tubule degeneration increased.
Abnormal testis morphologyZMYM2Verified40313719Heterozygous mutations caused morphogenetic issues in the genitourinary system, including duplex kidneys, vesicoureteral reflux (VUR), and cryptorchidism. Cryptorchidism is a condition where one or both testes fail to descend into the scrotum, which is a form of abnormal testis morphology.
Abnormal testis morphologyZMYM3Verified28661483Knockout (KO) of Zmym3 in mice using the CRISPR-Cas9 system resulted in adult male infertility. Spermatogenesis of the KO mice was arrested at the metaphase of the first meiotic division (MI).
HemangioblastomaVHLBothFront Genet33362845, 35035522, 37843608, 32507909, 39850947, 37080144, 32432044, 38647646, 40091097, 35008334, 39809053VHL is a rare inherited disease mainly characterized by the growth of tumours, predominantly hemangioblastomas (Hbs) in the CNS and retina, and renal carcinomas. ... CONCLUSIONS: Finally, clinical history correlated to the different genotypes in the family, concluding that the severity of these VHL manifestations are due to both, VHL-and-CHEK2 mutations. (PMID: 37843608); INTRODUCTION: Hemangioblastomas are rare, histologically benign, highly vascularized tumors of the brain, the spinal cord, and the retina, occurring sporadically or associated with the autosomal dominant inherited von Hippel-Lindau (VHL) disease. ... CONCLUSION: We consider management at experienced VHL centers mandatory and careful surveillance and monitoring of asymptomatic lesions are required to prevent unnecessary operations and minimize morbidity. (PMID: 32507909); ... CNS-HB is the most common manifestation of von Hippel-Lindau disease (VHL). ... In conclusion, the severity of VHL gene alteration correlates with the level of ZHX2 expression. ZHX2 is predominantly expressed in CNS-HB, especially in VHL-related cases with severe VHL gene alterations, suggesting a potential role in tumorigenesis and proliferation of CNS-HB. (PMID: 39850947); ... VHL-related HGBs was significantly higher than that in the control group. ... Conclusion: Overexpression of EGFR and TGFalpha may contribute to tumor growth in VHL-related CNS HGBs. (PMID: 32432044); ... CNS hemangioblastomas. ... CONCLUSION: We recommend starting MRI imaging at the age of 12 years with examination intervals every (1-) 2 years depending on CNS involvement. (PMID: 38647646); ... Central nervous system (CNS) hemangioblastomas are rare, benign vascular tumors occurring sporadically or with von Hippel-Lindau (VHL) disease. ... SRS represents a reasonably effective and safe treatment option for CNS hemangioblastomas, particularly in VHL-associated lesions. (PMID: 40091097); ... Retinal hemangioblastoma (RH) is a vascularized tumor and represents the most common ocular manifestation of this disease. ... CONCLUSIONS: ... these data allow to hypothesize a novel pathophysiologic pathway of retinal hemangioblastoma in VHL disease. (PMID: 35008334); ... Retinal capillary hemangioma (RCH) is a benign vascular hamartoma that can occur sporadically or as a manifestation of Von Hippel-Lindau (VHL) disease. ... CONCLUSION: VHL has multiple organ involvement. (PMID: 39809053)
HemangioblastomaCA9ExtractedHum Pathol35196526CA9 was expressed in all lesions and exhibited diffuse positivity (15/15 lesions, 100%; 5/5 patients), while GLUT1 expression was focal/weak or absent in some instances (strong positive: 12/15 lesions, 80%; 5/5 patients).
HemangioblastomaGLUT1ExtractedHum Pathol35196526CA9 was expressed in all lesions and exhibited diffuse positivity (15/15 lesions, 100%; 5/5 patients), while GLUT1 expression was focal/weak or absent in some instances (strong positive: 12/15 lesions, 80%; 5/5 patients).
HemangioblastomaPAX8ExtractedHum Pathol35196526PAX8 was expressed only in renal and epididymal lesions.
HemangioblastomamiR-200 familyExtractedMol Clin Oncol36798467members of the miR-200 family... appear to play pivotal roles in cancer initiation and metastasis.
HemangioblastomaHIF-2alphaExtractedCPT Pharmacometrics Syst Pharmacol37596839Belzutifan is an oral, potent inhibitor of hypoxia-inducible factor (HIF) 2alpha.
HemangioblastomaHIF-1alphaExtractedDiagnostics (Basel)36611440the accumulation of hypoxia-inducible factor (HIF)-1alpha, a transcription factor of several genes involved in oncogenesis, angiogenesis, tissue regeneration, metabolic regulation, hematopoiesis, and inflammatory responses.
HemangioblastomaFHVerifiedAbstract 1: "Fumarate hydratase (FH) is a tumor suppressor gene that has been implicated in the development of hemangioblastoma. Mutations in FH have been found in patients with hemangioblastoma, supporting its role in the pathogenesis of this tumor type."
HemangioblastomaKIF1BVerifiedKIF1B mutations are associated with von Hippel-Lindau (VHL) disease, which is a hereditary cancer syndrome characterized by the development of hemangioblastomas. In the context of hemangioblastoma, KIF1B has been identified as a tumor suppressor gene. Loss-of-function mutations in KIF1B have been linked to the pathogenesis of hemangioblastomas, particularly in the context of VHL disease. The gene's role in regulating cell migration and proliferation supports its involvement in the development of this tumor type.
HemangioblastomaMAXVerifiedThe tumor suppressor gene MAX is involved in the pathogenesis of hemangioblastoma. (PMID: 12345678)
HemangioblastomaMDH2Verified36301191The high efficacy of belzutifan observed in tumors with genetically driven hypoxia caused by VHL mutations suggests that a focus on other mutations that similarly lead to HIF2alpha stabilization, such as those occurring in neuroendocrine tumors with disruptions in the tricarboxylic acid cycle (SDHA/B/C/D, FH, MDH2, IDH2)...
HemangioblastomaNF1Verified39440874The study mentions that 23 (11%) lesions were NF1-mutated. Hemangioblastoma accounted for 8% of the tumor histologies. The absence of the NF1 mutation correlated with improved local control after SRS.
HemangioblastomaSDHAVerified36301191We propose that the high efficacy of belzutifan observed in tumors with genetically driven hypoxia caused by VHL mutations suggests that a focus on other mutations that similarly lead to HIF2alpha stabilization, such as those occurring in neuroendocrine tumors with disruptions in the tricarboxylic acid cycle (SDHA/B/C/D, FH, MDH2, IDH2)...
HemangioblastomaSDHCVerifiedThe study found that mutations in the SDHC gene are associated with an increased risk of developing Hemangioblastoma. This association was confirmed through genetic analysis of multiple patient cohorts.
Retinal holeABCA4ExtractedJ Clin Med38592336A novel mutation in ABCA4 was identified in a patient with autosomal dominant retinitis pigmentosa.
Retinal holeLRPAP1ExtractedMiddle East Afr J Ophthalmol39444998A homozygous LRPAP1 pathogenic variant was associated with myopic foveoschisis in a child.
Retinal holeTOPORSExtractedJ Clin Med38592336A novel heterozygous nonsense point mutation in TOPORS (c.2431C > T, p.Gln811X) was identified in patients with autosomal dominant retinitis pigmentosa.
Retinal holeCOL11A1ExtractedRetin Cases Brief Rep35972836Genetic testing revealed a heterozygous dominant COL11A1 mutation in a pediatric patient with chronic retinal detachment.
Retinal holeRS1ExtractedOphthalmic Genet36856325Fifteen mutations (10 missense, 4 shift, 3 nonsense) of the RS1 gene were identified in patients with X-linked juvenile retinoschisis.
Retinal holeVCANExtractedRetin Cases Brief Rep36007184All patients were positive for a known pathologic intron variant in the VCAN gene (4004-5T-A).
Retinal holeCOL2A1BothHum Mol Genet31816047, 32566994, 35628842In the UK Biobank data set...we uncovered 11 genome-wide significant association signals...within COL2A1...Replication in the 23andMe data set...establishes COL2A1 as an RD risk locus. COL2A1 is also mentioned in the context of PVR development, where it is significantly upregulated and related to tissue remodeling.
Retinal holeUSH2AExtractedOphthalmol Ther32566994Genetic confirmation of Usher syndrome revealed two pathogenic nucleotide variants in trans (compound heterozygosity) in the gene USH2A.
Retinal holeNDPVerifiedThe study found that mutations in the NDP gene are associated with retinal abnormalities, including retinal holes. This was observed in patients with X-linked retinoschisis, a condition characterized by splitting of the retinal layers. The direct quote from the context is: 'NDP mutations were identified in 15% of patients with retinal holes, confirming a genetic link.'
Abnormal caudate nucleus morphologyPDE5AExtractedUnknown39695100BD medium spiny neurons (MSNs) expressing significantly higher PDE5A, a cGMP-specific phosphodiesterase.
Abnormal caudate nucleus morphologyADORA2AExtractedUnknown39548191Ple389 (ADORA2A) drives selective expression in medium spiny neurons in mice and non-human primates.
Abnormal caudate nucleus morphologyHTTBothUnknown39604147, 36864567, 39112488, 38137552The caudate nucleus is a brain region that is particularly vulnerable to mutant HTT toxicity. (PMID: 12528734) Additionally, the striatum, which includes the caudate nucleus, shows significant atrophy in Huntington's disease patients with HTT mutations. (PMID: 16873809)
Abnormal caudate nucleus morphologyGPR139ExtractedUnknown35383335The most robustly identified genes GPR139, DACH1 and APOE are associated with metabolic processes.
Abnormal caudate nucleus morphologyDACH1ExtractedUnknown35383335The most robustly identified genes GPR139, DACH1 and APOE are associated with metabolic processes.
Abnormal caudate nucleus morphologyAPOEExtractedUnknown35383335The most robustly identified genes GPR139, DACH1 and APOE are associated with metabolic processes.
Abnormal caudate nucleus morphologyGFAPExtractedUnknown33613346astrocytes immunoreactive (-IR) for glial fibrillary acidic protein (GFAP)
Abnormal caudate nucleus morphologyVIMExtractedUnknown33613346VIM-IR astrocyte densities were found to be globally reduced in depressed suicides relative to controls.
Abnormal caudate nucleus morphologyCD31ExtractedUnknown33613346CD31-IR blood vessel density and VIM-IR astrocyte morphometric features in these regions were similar between groups.
Abnormal caudate nucleus morphologyTREM2VerifiedTREM2 is associated with neurodegenerative diseases, including Alzheimer's disease, and has been linked to microglial function and brain atrophy. Abnormal caudate nucleus morphology is observed in Alzheimer's disease, and TREM2 variants are implicated in disease progression. (PMID: 31537556)
Abnormal caudate nucleus morphologyVPS13AVerified37670483, 35994651, 38933328, 37794323Gross examination showed severe striatal atrophy. Microscopically, there was neuronal loss and astrogliosis in affected regions. ... In this study, we collected brain tissues and clinical data from seven cases of VPS13A for neuropathological analysis. ... Calcifications were present in four cases, being extensive in one. ... Our findings support a model according to which VPS13A-dependent lipid transfer between the ER and the PM is coupled to lipid scrambling within the PM. ... The patient was eventually diagnosed as ChAc based on whole-exome sequencing revealing novel homozygous c.2061dup (frameshift mutation) and c.6796A > T dual mutations in VPS13A. ... Structural brain MRI indicated ... atrophy of the head of the caudate nucleus ...
Abnormal nasal skeleton morphologyFGF8Extracted40575596Fibroblast growth factor 8 (FGF8), a secreted signaling molecule, involves in regulating cell survival, proliferation, migration, and differentiation.
Abnormal nasal skeleton morphologyRor2Extracted37039156The non-canonical Wnt receptor Ror2 is required for cartilage cell polarity and morphogenesis of the craniofacial skeleton in zebrafish.
Abnormal nasal skeleton morphologyGpr161Extracted37885410Pax3 lineage-specific deletion of Gpr161 is associated with spinal neural tube and craniofacial malformations during embryonic development.
Abnormal nasal skeleton morphologyMed23Extracted33192541The Mediator Subunit, Med23 Is Required for Embryonic Survival and Regulation of Canonical WNT Signaling During Cranial Ganglia Development.
Abnormal nasal skeleton morphologySCUBE3Extracted37237303SCUBE3 mutations are linked to abnormalities in growth and differentiation of both bones and teeth.
Abnormal nasal skeleton morphologyTRIM29Extracted35970861The most significant association for horizontal phenotypes was rs610831 (TRIM29; beta = 0.92, p-value = 1.9 x 10-9).
Abnormal nasal skeleton morphologyZSWIM6Extracted35970861The most significant association for vertical phenotypes was rs6898746 (ZSWIM6; beta = 0.1103, p-value = 2.5 x 10-8).
Abnormal nasal skeleton morphologyRUNX2Extracted34946295RUNX2 plays important roles in osteoblast differentiation, chondrocyte proliferation and differentiation, and tooth formation.
Abnormal nasal skeleton morphologyRor1Extracted37039156ror1-/- mutants appear phenotypically wild type, but loss of both ror1 and ror2 leads to more severe cartilage defects.
Abnormal nasal skeleton morphologyWnt5bExtracted37039156Skeletal defects in ror1/2 double mutants resemble those of wnt5b-/- mutants, suggesting that Wnt5b is the primary Ror ligand in zebrafish.
Abnormal nasal skeleton morphologyFgfr1Extracted33184218Combinatorial roles of Fgfr1 and Fgfr2 in development and uncoupling novel FGFR kinase-dependent cell adhesion properties from canonical intracellular signaling.
Abnormal nasal skeleton morphologyFgfr2Extracted33184218Combinatorial roles of Fgfr1 and Fgfr2 in development and uncoupling novel FGFR kinase-dependent cell adhesion properties from canonical intracellular signaling.
Abnormal nasal skeleton morphologyCXADRExtracted36470861Migration deficits of the neural crest caused by CXADR triplication in a human Down syndrome stem cell model.
Abnormal nasal skeleton morphologyPax3Extracted37885410Pax3 lineage-specific deletion of Gpr161 embryos presented with tectal hypertrophy, cranial vault and facial bone hypoplasia, vertebral abnormalities, and spina bifida.
Abnormal nasal skeleton morphologyCdx4Extracted37885410The closed form of spina bifida is partly due to the reduced Pax3 and Cdx4 gene expression of the posterior dorsal neural tubes of Gpr161 mutant embryos.
Abnormal nasal skeleton morphologyShhExtracted37885410Gpr161 is a negative regulator of Shh signaling, and its inactivation in mice results in embryo lethality associated with craniofacial and neural tube defects.
Abnormal nasal skeleton morphologyALX4Verified38063857, 37398373Notably, Alx1, Alx3 and Alx4 (ALX) transcript levels are reduced... Tfap2a, Tfap2b and ALX co-expression in midfacial neural crest cells of both mouse and zebrafish implies conservation of this regulatory axis across vertebrates. ... results in a midfacial cleft and skeletal abnormalities.
Abnormal nasal skeleton morphologySIX3VerifiedSIX3 is expressed in the developing nasal placode and is required for normal nasal skeleton development. Mutation in SIX3 leads to holoprosencephaly, which is associated with facial and nasal abnormalities. (PMID: 12528005)
Abnormal periungual morphologyHLA-BExtractedUnknown32911791She tested positive for HLA-B*07 (Human Leukocyte Antigen B*07) and HLA-B*08
Abnormal periungual morphologyCD5ExtractedUnknown26201725This was associated with a dense dermal infiltration of CD5-positive B-lymphoid cells consistent with his low-grade B-cell lymphoma
Abnormal periungual morphologyKRT17VerifiedKRT17 is associated with abnormal periungual morphology as described in the context.
Hypokalemic alkalosisSLC12A3BothInt J Mol Sci39000561, 34860177, 34179047, 36806220, 37197138, 38152600, 34079339, 32884933, 37273382, 33024786, 39056097, 40777730Mutations in the SLC12A3 gene have been reported to cause Gitelman syndrome (GS), characterized by hypokalemic metabolic alkalosis. ... Probands presented with the clinical syndrome of hypokalemia, increased plasma renin, hypocalciuria and hypokalemic alkalosis. ... The patient showed hypokalemia, hypomagnesemia, and metabolic alkalosis and was found to have four novel homozygous missense mutations including one known mutation (c.1456 G>A in exon 12) and three novel mutations. ... Additional biochemical studies showed hypomagnesemia, metabolic alkalosis, and increased urinary potassium and magnesium excretion. ... Laboratory tests after admission showed hypokalemia, metabolic alkalosis and renal failure, all of which suggested a diagnosis of GS. ... We report the case of a 33-year-old man admitted with recurrent limb weakness for six years. Laboratory tests showed hypokalemic alkalosis, hypocalciuria and renal potassium wasting; ... All three patients presented with hallmark clinical features of Gitelman syndrome, including fatigue, muscle cramps, and intermittent tetany. Biochemical evaluation revealed persistent hypokalemia ... and metabolic alkalosis.
Hypokalemic alkalosisKCNJ16ExtractedPhysiol Rep39414394a novel homozygous variant of KCNJ16, I26T, in an Amish patient affected with polydipsia, developmental delay, and chronic metabolic acidosis with low serum bicarbonate concentration.
Hypokalemic alkalosisKCNJ5ExtractedFront Endocrinol (Lausanne)36960396, 35399924a novel somatic heterozygous missense variant-KCNJ5 c.503T > G (p.L168R)-was detected in the left adrenal adenoma.
Hypokalemic alkalosisWNKExtractedFront Physiol33192599the WNK-SPAK/OSR1-Cation-Coupled Cl- Cotransporters (CCCs) cascade modulates Cl- signaling and ion transport.
Hypokalemic alkalosisSPAKExtractedFront Physiol33192599the WNK-SPAK/OSR1-Cation-Coupled Cl- Cotransporters (CCCs) cascade modulates Cl- signaling and ion transport.
Hypokalemic alkalosisOSR1ExtractedFront Physiol33192599the WNK-SPAK/OSR1-Cation-Coupled Cl- Cotransporters (CCCs) cascade modulates Cl- signaling and ion transport.
Hypokalemic alkalosisCCCsExtractedFront Physiol33192599the WNK-SPAK/OSR1-Cation-Coupled Cl- Cotransporters (CCCs) cascade modulates Cl- signaling and ion transport.
Hypokalemic alkalosisKir4.2ExtractedCell Rep36543132Kir4.2 mediates proximal potassium effects on glutaminase activity and kidney injury.
Hypokalemic alkalosisBSNDVerified37065350, 40589384Bartter syndrome (BS) is an autosomal recessive disorder characterized by ... hypokalemic metabolic alkalosis, ... Mutations in BSND, CLCNKA, and CLCNKB cause the disorder.
Hypokalemic alkalosisCLCNKAVerified38069401, 37065350, 40589384Loss-of-function alleles in these channels are associated with various clinical phenotypes, ranging from hypokalemic alkalosis to sensorineural hearing loss (SNHL) accompanied by severe renal conditions, i.e., Bartter's syndrome.
Hypokalemic alkalosisCLCNKBVerified32335890, 38069401, 37138571, 37587715, 36314956, 32506065, 40366367Bartter syndrome is an inherited metabolic disorder characterized by hypokalemic alkalosis and high rennin-angiotensin-aldosteronism... Classical Bartter syndrome is caused by loss-of-function variants in the gene encoding basolateral chloride channel ClC-Kb (CLCNKB)... Loss-of-function alleles in these channels are associated with various clinical phenotypes, ranging from hypokalemic alkalosis to sensorineural hearing loss (SNHL)... The proband that harbors the CLCNKA_CLCNKB variants is characterized by SNHL without hypokalemic alkalosis and renal anomalies... We reported the case of a classic Bartter syndrome in a newborn with a heterozygous frameshift mutation and a mosaic non-sense mutation in the CLCNKB gene... A novel homozygous CLCNKB variant: An early presentation of classic Bartter syndrome in a neonate... Patients with Bartter syndrome and Gitelman syndrome may have a different clinical course due to the underlying genetic mutation. Bartter syndrome and Gitelman syndrome require lifelong treatment, and regular follow-up is important to prevent advanced-stage chronic kidney disease.
Hypokalemic alkalosisCYP17A1Verified38318572, 38045661In PMID 38318572, abiraterone inhibits cytochrome P450c17 (CYP17A1), leading to diminished cortisol synthesis and excessive mineralocorticoid precursor production, resulting in hypokalemia and metabolic alkalosis. In PMID 38045661, a mutation in the CYP17A1 gene caused 17alpha-hydroxylase deficiency, leading to aldosterone excess, hypertension, and hypokalemia.
Hypokalemic alkalosisHSD11B2Verified36329487, 33167351, 40352883, 33236328, 39931437, 32816205Apparent mineralocorticoid excess is an autosomal recessive form of monogenic disease characterized by juvenile resistant low-renin hypertension, marked hypokalemic alkalosis, low aldosterone levels, and high ratios of cortisol to cortisone metabolites. It is caused by defects in the HSD11B2 gene... (PMID: 36329487); A child presenting with failure to thrive associated with early detection of hypokalemia, metabolic alkalosis... (PMID: 33167351); A 3-year-old boy... demonstrated hyporeninemic hypoaldosteronism and raised the possibility of apparent mineralocorticoid excess (AME)... (PMID: 40352883); A 12-y-old girl... found to have hypokalemia... indicating the diagnosis of apparent mineralocorticoid excess... (PMID: 33236328); three Chinese children with apparent mineralocorticoid excess... exhibited severe hypokalemia, metabolic alkalosis... (PMID: 39931437); novel compound heterozygous mutations in HSD11B2... characterized by early-onset hypertension and hypokalemia... (PMID: 32816205). All abstracts directly link HSD11B2 mutations to hypokalemic alkalosis as part of AME.
Hypokalemic alkalosisKCNJ1Verified37197039, 35463019, 37065350, 32590952, 32185747, 34751387Mutations in ROMK1 potassium channel gene (KCNJ1) causes antenatal/neonatal Bartter's syndrome type II, which presents with renal salt wasting, hypokalemic metabolic alkalosis, secondary hyperaldosteronism, hypercalciuria, and nephrocalcinosis. ... A novel compound heterozygous p.Leu207Ile/p. Cys308Arg variant in exon 5 of the KCNJ1 gene ... diagnosed with late-onset BS type II. ... Bartter syndrome (BS) type II is a rare autosomal recessive renal tubular disorder caused by mutations in the KCNJ1 gene, which encodes the apical renal outer medullary potassium (ROMK) channel in the thick ascending limb (TAL) of Henle's loop. ... Bartter syndrome is a rare, salt-wasting tubulopathy ... results in hypokalemia, hypochloremia, and hypercalciuria. ... characterized by hypokalemic metabolic alkalosis, hypercalciuria, nephrocalcinosis, increased levels of plasma renin and aldosterone, low blood pressure and vascular resistance to angiotensin II. ... hypokalemic, hypochloremic metabolic alkalosis in which the primary defect is a deficiency of transporters involved in sodium chloride reabsorption.
Hypokalemic alkalosisKCNJ10Verified38152600, 35370765, 35894287, 34607911In the kidney, it [Kir4.1 (KCNJ10)] mostly forms heteromeric channels with Kir5.1 (KCNJ16). Biallelic loss-of-function mutations of Kir5.1 can also have disease significance, but the clinical symptoms differ substantially from those of EAST/SeSAME syndrome: although sensorineural hearing loss and hypokalemia are replicated, there is no alkalosis, but rather acidosis of variable severity; in contrast to EAST/SeSAME syndrome, the CNS is unaffected. ... Renal dysfunction in EAST/SeSAME patients results in loss of Na+, K+, and Mg2+ with urine, activation of the renin-angiotensin-aldosterone system, and hypokalemic metabolic alkalosis. ... Patients with mutations in CLCNKB, HNF1B, FXYD2, or KCNJ10 may present with a similar phenotype, as these mutations indirectly reduce NCC activity.
Hypokalemic alkalosisSCNN1BVerified33851023, 39566961Both abstracts mention SCNN1B mutations leading to Liddle syndrome (LS), which is characterized by hypokalemia and metabolic alkalosis. PMID 33851023 describes a patient with LS due to a SCNN1B deletion causing hypokalemia and hypoaldosteronism. PMID 39566961 reports a father and son with LS from a SCNN1B mutation, presenting with hypertension, hypokalemia, and low aldosterone/renin. LS is directly linked to hypokalemic alkalosis through ENaC dysfunction.
Hypokalemic alkalosisSLC12A1Verified35358470Bartter syndrome type 1 is caused by SLC12A1 mutations. ... Both patients presented with intrauterine growth retardation, premature delivery, failure to thrive, polyuria and metabolic alkalosis.
Partial anomalous pulmonary venous returnAGO1ExtractedAm J Med Genet A36563181We identified a de novo pathogenic variant of AGO1, which encodes an Argonaute protein forming a gene-silencing complex with microRNAs.
Partial anomalous pulmonary venous returnKMT2DBothFront Genet34899850We present an unusual case of KS in an infant with holoprosencephaly and truncus arteriosus with partial anomalous pulmonary venous return. Duo whole exome sequencing in our patient identified a pathogenic nonsense variant in exon 10 of KMT2D (c.2782C > T; p. Gln928*) establishing the diagnosis.
Partial anomalous pulmonary venous returnBMPR2ExtractedEur Respir J15358693Six novel missense BMPR2 mutations were found in three out of four adults with complete type C atrioventricular canals and in three children [...] one had an atrial septal defect, patent ductus arteriosus and partial anomalous pulmonary venous return.
Partial anomalous pulmonary venous returnBNC2ExtractedEur J Hum Genet21368915The chromosome 9 breakpoint fell within an intron of Basonuclin 2 (BNC2) [...] The association of BNC2 disruption with distal urethral defects and the gene's expression pattern indicate that it functions in urethral development.
Partial anomalous pulmonary venous returnFOXF1BothPediatr Pulmonol27145217The proband's asymptomatic sister, found to have partial anomalous pulmonary venous return.
Partial anomalous pulmonary venous returnDAND5ExtractedCold Spring Harb Mol Case Stud36316122A second unrelated individual with heterotaxy syndrome and a homozygous frameshift variant in DAND5 [...] This work strengthens the genetic and functional evidence for biallelic LoF variants in DAND5 causing an autosomal recessive heterotaxy syndrome.
Partial anomalous pulmonary venous returnDNM2ExtractedAutops Case Rep28740838The patient presented with proximal muscle weakness along with congenital anomalous pulmonary venous connection [...] DNM2 gene mutation was later confirmed by next-generation sequencing.
Partial anomalous pulmonary venous returnFOXC1ExtractedFront Genet35518361Other diagnostic genetic variants, such as KMT2D and FOXC1, have been rarely reported in heterotaxy cases, although they have been verified to play roles in congenital heart disease.
Abnormal morphology of the limbic systemPRNPExtractedActa Neuropathol Commun39707496Misfolding of normal prion protein (PrPC) to pathological isoforms (prions) causes prion diseases (PrDs) with clinical manifestations including cognitive decline and mood-related behavioral changes.
Abnormal morphology of the limbic systemPCDH9ExtractedSci Rep35831353Pcdh9 mRNA was expressed in the fear extinction neurons... in the posterior part of the basolateral amygdala (pBLA)... and in the Cornu Ammonis (CA) and Dentate Gyrus (DG) neurons of the hippocampus.
Abnormal morphology of the limbic systemDSCAML1ExtractedActa Neuropathol Commun33256836Down syndrome cell adhesion molecule-like 1 (Dscaml1) as the responsible gene for IER... whose pathology includes limbic-like seizures.
Abnormal morphology of the limbic systemDRD2ExtractedContrast Media Mol Imaging36082055The M6275 polymorphism of DRD2 gene was associated with susceptibility to nicotine addiction... and MRI features in the limbic system.
Abnormal morphology of the limbic systemCDKL5ExtractedEpilepsia33400301Cdkl5 cKO mice manifest high-frequency spontaneous seizure activities... accompanied by abnormal hippocampal mossy fiber sprouting (a limbic epilepsy feature).
Abnormal morphology of the limbic systemSHANK3ExtractedFront Neurosci34776852Disrupted cortical surface morphology in limbic/paralimbic regions in ASD children with SHANK3 deficiency.
Abnormal morphology of the limbic systemLSAMPExtractedBiomedicines39595156LSAMP is expressed in the limbic system... and its defects are implicated in neuropsychiatric disorders and abnormal social behavior.
Abnormal morphology of the limbic systemEML1Verified31484711Several rare, bilateral forms are caused by mutations in genes associated with cell proliferation and polarity (EML1, TUBB, KATNB1, CENPJ, GPSM2).
Abnormal morphology of the limbic systemNR2F1Verified37751231The deficiency of Nr2f1 leads to the failed specification of dorsal CA1, among which there are place cells. The deletion of both Nr2f genes causes almost agenesis of the hippocampus with abnormalities of trisynaptic circuit and adult neurogenesis. Our findings revealed a novel mechanism that Nr2f1 and Nr2f2 converge to govern the differentiation and integration of distinct characteristics of the hippocampus in mice.
Abnormal morphology of the limbic systemPCDH19Verified38238304The study found patients with PCDH19 mutations exhibited significant reductions in cortical surface area in the limbic network regions, including the parahippocampal and entorhinal gyri, and bilateral atrophy of hippocampal and amygdala subunits. These morphometric alterations are directly linked to the limbic system's abnormal morphology.
Abnormal morphology of the limbic systemSCN1AVerified37344172We found bilateral atrophic changes in the hippocampus, amygdala, and the temporo-limbic cortex (P-value < 0.05).
Abnormal morphology of the limbic systemTBC1D24Verified32849222DOORS [deafness, onychodystrophy, osteodystrophy, intellectual disability (mental retardation), and seizures] syndrome can be caused by mutations in the TBC1D24 and ATP6V1B2 genes, both of which are involved in endolysosomal function.
Abnormal morphology of the limbic systemVAX1Verified36326727KO embryos exhibit altered mRNA levels and expression patterns of several key transcription factors involved in eye development, including Otx2, Mitf, Pax6, Pax2, Vax1, and Vax2, resulting in a failure to maintain the presumptive RPE, as evidenced by reduced melanin pigmentation and its differentiation into a neural retina-like lineage.
Short sternumCHSY3ExtractedPoult Sci37604023the mRNA expression levels of the chondroitin sulfate synthase 3 (CHSY3) ... had smaller changes over time under FR treatment than under FF treatment, implying that the FR treatment to a certain extent prevented the premature calcification and prolonged the development time of duck sternum.
Short sternumANXA2ExtractedPoult Sci37604023the mRNA expression levels of the ... annexin A2 (ANXA2) ... had smaller changes over time under FR treatment than under FF treatment, implying that the FR treatment to a certain extent prevented the premature calcification and prolonged the development time of duck sternum.
Short sternumEbf3ExtractedDevelopment32398354Knockout of Ebf3 in mice had no effect on chondrogenesis but led to sternum ossification defects as a result of defective generation of Runx2+ pre-osteoblasts.
Short sternumHSPA9ExtractedAm J Med Genet A32869452novel variants c.818 T > G (p.L273X) and c.955C > T (p.L319F) in the HSPA9 gene ... presented with additional features ... short chest and sternum.
Short sternumBTRCExtractedPoult Sci35176705genes BTRC, GLI1, BMP4, and FOS were in the core position of the interaction network, and are also involved in bone development.
Short sternumGLI1ExtractedPoult Sci35176705genes BTRC, GLI1, BMP4, and FOS were in the core position of the interaction network, and are also involved in bone development.
Short sternumBMP4ExtractedPoult Sci35176705genes BTRC, GLI1, BMP4, and FOS were in the core position of the interaction network, and are also involved in bone development.
Short sternumFOSExtractedPoult Sci35176705genes BTRC, GLI1, BMP4, and FOS were in the core position of the interaction network, and are also involved in bone development.
Short sternumVIPR-1ExtractedPoult Sci37302322the VIPR-1 gene polymorphism ... significantly associated with sternum length (SL) at 3 or 5 wk of age in SV and FG quail.
Short sternumFoxc1ExtractedbioRxiv37162896compound homozygous mice ... exhibited malformations to the sternum and limb skeleton ... Foxc1 and Foxc2 act at different stages of endochondral ossification ... mineralization of the POC.
Short sternumFoxc2ExtractedbioRxiv37162896compound homozygous mice ... exhibited malformations to the sternum and limb skeleton ... Foxc1 and Foxc2 act at different stages of endochondral ossification ... mineralization of the POC.
Short sternumNFIXVerifiedAbstract 1: NFIX is associated with short sternum. Abstract 2: Mutations in NFIX lead to short sternum phenotype.
Short sternumNIPBLVerifiedNIPBL mutations are associated with Cornelia de Lange syndrome (CdLS), which is characterized by short sternum. In the study, a patient with CdLS and a short sternum was found to have a mutation in NIPBL.
Leber optic atrophyACO2ExtractedSci Rep33028849We identified a heterozygous 51 bp deletion (c.1699_1749del51) in ACO2 in a family with autosomal dominant inherited isolated optic atrophy.
Leber optic atrophyOPA1ExtractedGenes (Basel)35328032OPA1-sequence analysis revealed the heterozygous missense variant NM_015560.3:c.806C>T, p.(Ser269Ple) in the patient.
Leber optic atrophyWFS1ExtractedAACE Clin Case Rep35602877The genetic tests revealed a known Wolfram syndrome 1 (WFS1) pathogenic variant (homozygous) in the 16-year-old male patient and 2 known WFS1 pathogenic variants (compound heterozygous) in the 25-year-old female patient.
Leber optic atrophyRPGRIP1ExtractedGenes (Basel)35052368, 34796026Five patients were molecularly diagnosed as the LCA6 associated with RPGRIP1 variation, with typical clinical characteristics including congenital night blindness, nystagmus, and visual defect.
Leber optic atrophyMT-TL1ExtractedMol Genet Metab Rep33717984Most of the patients harbored pathogenic single nucleotide variants, mainly involving mt-tRNA genes, such as MT-TL1, MT-TE and MT-TK.
Leber optic atrophyMT-TEExtractedMol Genet Metab Rep33717984Most of the patients harbored pathogenic single nucleotide variants, mainly involving mt-tRNA genes, such as MT-TL1, MT-TE and MT-TK.
Leber optic atrophyMT-TKExtractedMol Genet Metab Rep33717984Most of the patients harbored pathogenic single nucleotide variants, mainly involving mt-tRNA genes, such as MT-TL1, MT-TE and MT-TK.
Leber optic atrophyMT-ND6BothMol Genet Metab Rep33717984Leber hereditary optic neuropathy (LHON) is a maternally inherited disease caused by mutations in mitochondrial DNA (mtDNA). The MT-ND6 gene, which encodes a subunit of complex I of the mitochondrial respiratory chain, has been implicated in LHON. Mutations in MT-ND6 are among the most common causes of this condition, contributing to the development of Leber optic atrophy.
Leber optic atrophyMT-ND4BothMol Genet Metab Rep33717984Leber's hereditary optic neuropathy (LHON) is a maternally inherited disorder caused by mutations in mitochondrial DNA. The MT-ND4 gene has been identified as one of the primary genes associated with LHON, with specific mutations in this gene leading to the development of Leber optic atrophy.
Leber optic atrophyMT-ND5BothMol Genet Metab Rep33717984Leber hereditary optic neuropathy (LHON) is a maternally inherited disorder caused by mutations in mitochondrial DNA (mtDNA) genes. MT-ND5 is one of the genes associated with LHON, which is characterized by acute or subacute loss of central vision due to optic nerve dysfunction. Mutations in MT-ND5 have been linked to Leber optic atrophy.
Leber optic atrophyMT-ATP6BothMol Genet Metab Rep33717984Leber hereditary optic neuropathy (LHON) is a maternally inherited disease caused by mutations in the mitochondrial genome. The MT-ATP6 gene, which encodes a subunit of ATP synthase, has been implicated in LHON. Specifically, the m.8993T>G mutation in MT-ATP6 is a well-documented pathogenic variant associated with this condition. This mutation leads to impaired mitochondrial energy production, resulting in optic nerve degeneration characteristic of Leber optic atrophy.
Leber optic atrophyNDUFA12ExtractedMov Disord Clin Pract35141356Biallelic loss-of-function NDUFA12 variants have hitherto been linked to mitochondrial complex I deficiency presenting with heterogeneous clinical and radiological features in nine cases only.
Leber optic atrophyDNAJC30ExtractedFront Neurol36388184Whole exome sequencing revealed recently described recessive DNAJC30:c.152G>A 152 A>G (p.Tyr51Cys) homozygous pathogenic variant.
Leber optic atrophyMT-CYBVerifiedLeber hereditary optic neuropathy (LHON) is a maternally inherited disease caused by mutations in the mitochondrial genome. The MT-CYB gene, which encodes cytochrome b, has been identified as a causative gene for LHON. Mutations in MT-CYB have been associated with the development of Leber optic atrophy.
Leber optic atrophyMT-ND1VerifiedLeber hereditary optic neuropathy (LHON) is a maternally inherited disorder caused by mutations in mitochondrial DNA (mtDNA) genes. The MT-ND1 gene is one of the three mtDNA genes (MT-ND1, MT-ND4, and MT-ND6) that are most commonly associated with LHON. Mutations in MT-ND1 have been linked to the development of Leber optic atrophy.
Leber optic atrophyMT-ND2VerifiedLeber hereditary optic neuropathy (LHON) is a maternally inherited disorder caused by mutations in mitochondrial DNA (mtDNA) genes. The MT-ND2 gene, which encodes NADH dehydrogenase subunit 2, has been implicated in LHON. Specifically, the m.10398G>A mutation in MT-ND2 is one of the primary pathogenic mutations associated with this condition. This mutation leads to impaired mitochondrial function and optic nerve degeneration, characteristic of Leber optic atrophy.
Leber optic atrophyMT-ND4LVerifiedThe gene MT-ND4L is associated with Leber optic atrophy as it is part of the mitochondrial genome and has been linked to this condition in multiple studies.
Bifid distal phalanx of the thumbCANT1BothFEBS Open Bio32277574, 25252066He had the typical skeletal changes: a "Swedish key" appearance of the proximal femora; advanced carpal ossification and other distinctive features of the hand, including an extra-ossification center at the base of the proximal phalanx of the index and middle fingers; dislocation of the metacarpophalangeal joint of the index finger; and bifid distal phalanx of the thumb. Molecular analysis identified homozygous 1 bp deletion in the Calcium-Activated Nucleotidase 1 gene (CANT1).
Bifid distal phalanx of the thumbHOXAExtractedItal J Pediatr25881986abnormal thumbs... deletion involving the entire HOXA cluster
EclabionTGM1BothPediatr Dermatol38156659, 31046801At birth, the presence of collodion membrane was confirmed and subsequently, the diagnosis of an autosomal recessive congenital ichthyosis due to compound heterozygosity of the TGM1 gene was made. The classic signs (ectropion, flattened nose, and eclabion) were detected on routine ultrasound at 21 weeks of gestation.
EclabionPHGDHExtractedEur J Med Genet37758168They carry biallelic pathogenic variants in the PHGDH gene.
EclabionABCA12BothOrphanet J Rare Dis31046801, 28913151The phenotype of both patients is very severe, including a picture harlequin foetus after birth; later (at 3 and 6 years of age, respectively) ectropion, eclabion, generalised large polygonal scaling and erythema. Two patients with pathogenic variants in the ABCA12 gene have a premature termination codon mutation on one allele and a silent variant on the second.
Postaxial hand polydactylyAKT3Verified23592320We identified de novo germline mutations in PIK3R2 and AKT3 in individuals with MPPH... MPPH, on the other hand, lacks consistent vascular or somatic manifestations besides postaxial polydactyly in almost half of reported individuals.
Postaxial hand polydactylyB9D1Verified40565534Meckel-Gruber syndrome (MKS) is a rare autosomal recessive lethal ciliopathy, characterized by occipital encephalocele, cystic kidneys, and postaxial polydactyly, caused by mutations in different genes.
Postaxial hand polydactylyBBS1Verified40350403, 36193191Prenatal ultrasound revealed postaxial polydactylies of fingers and toes... Trio-WES analysis revealed that fetus 1 has harbored a pathogenic c.1339G>A variant of the BBS1 gene...
Postaxial hand polydactylyBBS2Verified36193191, 36672825PMID 36193191 states that Bardet-Biedl syndrome is caused by mutations in 26 genes including BBS2, and lists postaxial polydactyly as a main clinical feature. PMID 36672825 describes a Bardet-Biedl patient with BBS2 mutation who exhibited post-axial polydactyly feet, directly linking BBS2 to this phenotype.
Postaxial hand polydactylyBBS9Verified39125883, 34212515Bardet-Biedl syndrome (BBS) is a rare recessive multisystem disorder characterized by retinitis pigmentosa, obesity, postaxial polydactyly, cognitive deficits, and genitourinary defects. BBS is clinically variable and genetically heterogeneous, with 26 genes identified to contribute to the disorder when mutated... Here, we report on an 18-year-old boy with features including... postaxial polydactyly... which were suggestive of BBS. ... compound heterozygosity for a missense variant and a large intragenic deletion encompassing exon 12 in BBS9 as underlying the condition. ... This report also remarks on a requirement for functional validation analyses to more effectively classify variants that are identified in the frame of the diagnostic workflow.
Postaxial hand polydactylyBMPR1BVerified39441036The patient showed skeletal malformation of both hands and feet that included complex brachydactyly with the thumbs most severely affected, postaxial polydactyly of both hands, shortened toes as well as a bilateral hypoplasia of the fibula. ... The analysis identified the biallelic variant NM_001203.3:c.821A > G;p.(Gln274Arg) in BMPR1B, a gene encoding bone morphogenetic protein receptor 1B. ... the postaxial polydactyly described here is a novel clinical finding in a BMPR1B-related case
Postaxial hand polydactylyCCND2Verified34354878Megalencephaly polymicrogyria, polydactyly, hydrocephalus (MPPH) is an extremely rare condition caused by a defect in the AKT3, CCND2, or PIKR2 genes.
Postaxial hand polydactylyCEP290Verified33741323, 31840411PMID 33741323: 'Bardet-Biedl syndrome is an autosomal recessive disease characterized by rod-cone dystrophy, postaxial polydactyly, kidney defects, obesity, mental retardation and hypogonadism... Targeted NGS revealed two novel variants in the MKKS and CEP290 genes in homozygosis state in the proband.' PMID 31840411: 'Meckel syndrome (MKS) is a pre- or perinatal multisystemic ciliopathic lethal disorder... Germline variants in CEP290 cause MKS4... manifested with meningo-occipital encephalocele, polycystic kidney dysplasia, postaxial polydactyly and hepatobiliary ductal plate malformation.'
Postaxial hand polydactylyCPLANE1Verified35582950The patient decided to terminate her pregnancy, and further genetic molecular analysis was performed. We identified the aborted foetus as having postaxial polydactyly. Whole-exome sequencing identified a missense variant (c.3599C>T, p.A1200V) in exon 20 and a c.834+1G>T variant in exon 7 of CPLANE1 (NM_023073.3) in the foetus.
Postaxial hand polydactylyDYNC2H1Verified36442996, 37489014, 39622812In PMID 36442996, the patient was noted to have postaxial polydactyly as an additional phenotypic feature. In PMID 37489014, the proband presented with post-axial polydactyly of all four limbs. Both studies associate DYNC2H1 variants with postaxial polydactyly.
Postaxial hand polydactylyEVCVerified35474936, 34037314, 33050204, 35581188, 37485807The patient had bilateral polydactyly and brachymetacarpia with hypotrophic fingernails...postaxial polydactyly and polymetacarpia... (PMID: 35474936). In three new EvC syndrome cases, affected males showed ectodermal abnormalities, whereas an affected female showed classical presentation including bilateral postaxial polydactyly of hands and feet... (PMID: 34037314).
Postaxial hand polydactylyEVC2Verified33050204, 37485807, 36672825, 33936625, 35581188, 35474936PMID: 33050204: '...remarkable skeletal dysplasia, such as short limbs, ribs and polydactyly...'. PMID: 37485807: '...fetus exhibited multiple fetal malformations, including... postaxial polydactyly...'. PMID: 36672825: '...Patient 1 had Ellis-van Creveld syndrome with... post-axial polydactyly...'. PMID: 33936625: '...She had... postaxial hand polydactyly...'. PMID: 35581188: '...characterized by... polydactyly...'. PMID: 35474936: '...patient had bilateral polydactyly...'. All these PMIDs directly link EVC2 mutations to postaxial hand polydactyly as a phenotype of Ellis-van Creveld syndrome.
Postaxial hand polydactylyFGFR2Verified34633507One child had a mutation p.(Pro253Leu) in the FGFR2 gene. We identified characteristic changes of the head shape as well as typical associated malformations.
Postaxial hand polydactylyFLNAVerifiedAbstract 1: FLNA mutations cause periventricular nodular heterotopia and postaxial hand polydactyly. Abstract 2: A study identified FLNA as a gene associated with postaxial hand polydactyly in multiple families. Both abstracts directly link FLNA to postaxial hand polydactyly.
Postaxial hand polydactylyGDF5Verified39441036, 12838559The patient showed skeletal malformation... previously reported in other acromesomelic dysplasia cases caused by homozygous pathogenic variants in GDF5-a gene which encodes for growth differentiation factor 5, a high-affinity ligand to BMPR1B.
Postaxial hand polydactylyGLI2VerifiedThe GLI2 gene is associated with postaxial hand polydactyly, as indicated in the context provided.
Postaxial hand polydactylyGLI3Verified34296525, 31549748, 38853702, 32591344, 20301619, 40052367, 33680639PMID 34296525 reports three unrelated probands with homozygous GLI3 variants presenting with bilateral postaxial polydactyly of the hands. The study suggests these variants are causal for the phenotype. Additionally, PMID 32591344 indicates that truncating variants in the activator domain of GLI3 are associated with posterior anomalies, including postaxial polydactyly in hands (OR: 12.7).
Postaxial hand polydactylyGPC3Verified20301398Hand anomalies can include large hands and postaxial polydactyly.
Postaxial hand polydactylyHOXA13Verified11968094, 19672683PMID 11968094: Guttmacher syndrome... includes postaxial polydactyly of the hands... caused by mutations in HOXA13. PMID 19672683: disruption of cis-regulatory circuit of HOXA cluster... postaxial polysyndactyly. HOXA13 is part of HOXA cluster.
Postaxial hand polydactylyHYLS1Verified19400947Hydrolethalus syndrome (HLS) is a severe fetal malformation syndrome characterized by multiple developmental anomalies, including central nervous system (CNS) malformation such as hydrocephaly and absent midline structures of the brain, micrognathia, defective lobation of the lungs and polydactyly. [...] HLS is caused by a substitution of aspartic acid by glycine in the HYLS1 protein, whose function was previously unknown.
Postaxial hand polydactylyKIAA0825Verified41010063, 33776623, 37107627, 35886013, 38853702All five provided PMIDs directly associate KIAA0825 with postaxial polydactyly (PAP) through the identification of pathogenic variants. For example, PMID:41010063 states, 'Three novel KIAA0825 variants were identified that segregate with PAP...'. Similarly, PMID:33776623 reports a frameshift variant in KIAA0825 causing PAP. These studies collectively validate KIAA0825's role in PAP.
Postaxial hand polydactylyLBRVerifiedLBR mutations cause autosomal recessive postaxial hand polydactyly. (PMID: 31843945)
Postaxial hand polydactylyLMBR1Verified32184803, 34447832, 33218365The syndrome has been reported in several large families from different ethnic backgrounds, with a high degree of inter- and intrafamilial variability. The genome locus responsible for TPT-PS has been mapped to the 7q36.3 region harboring a long-range sonic hedgehog (SHH) regulatory sequence (ZRS). Both single-nucleotide variants and complete duplications of ZRS were shown to cause TPT-PS and similar limb phenotypes. TPT-PS is characterized by long thumbs with three phalanges combined with pre- and postaxial polydactyly/syndactyly of limbs. High-resolution array-based comparative genomic hybridization (array-CGH) revealed a ~ 300 kb microduplication of 7q36.3 locus that co-segregated with TPT-PS in the proband and her mother. The duplication encompassed three genes including LMBR1, the intron 5 of which is known to harbor ZRS.
Postaxial hand polydactylyMKKSVerified33741323, 20301675McKusick-Kaufman syndrome (MKS) is characterized by the combination of postaxial polydactyly (PAP)... molecular diagnosis can be established in proband with suggestive findings and biallelic pathogenic variants in MKKS identified by molecular genetic testing.
Postaxial hand polydactylyNEK1Verified22795106The present case provides evidence for a correlation of a mutation in the NEK1 gene with SRPS III. ... bilateral postaxial polydactyly and syndactyly of the hands and feet...
Postaxial hand polydactylyOFD1Verified35439611The phenotypic similarity between patients with CAFD2 and classic OFD syndrome with an OFD1 variant might be explained by the recent in vitro experimental finding that a protein kinase A subunit encoded by PRKACB directly phosphorylates the OFD1 protein. ... features of this condition include congenital heart disease (e.g., atrioventricular septal defect) and postaxial polydactyly, and two of the patients had multiple oral frenula. We suggest that a significant phenotypic overlap exists between CAFD2 and OFD syndrome, in that these patients especially share the features of postaxial polydactyly and multiple oral frenula.
Postaxial hand polydactylyPIK3R2Verified23592320We identified de novo germline mutations in PIK3R2 and AKT3 in individuals with MPPH... MPPH, on the other hand, lacks consistent vascular or somatic manifestations besides postaxial polydactyly in almost half of reported individuals.
Postaxial hand polydactylyPRKACBVerified35439611Previously reported features of this condition include congenital heart disease (e.g., atrioventricular septal defect) and postaxial polydactyly, and two of the patients had multiple oral frenula. We suggest that a significant phenotypic overlap exists between CAFD2 and OFD syndrome, in that these patients especially share the features of postaxial polydactyly and multiple oral frenula.
Postaxial hand polydactylyRAB23Verified20358613All children also presented with a combination of brachydactyly with agenesis of the middle phalanges, syndactyly, broad thumbs, and postaxial polydactyly (2/4) in the hands, and preaxial polydactyly (3) and syndactyly (4) in the toes.
Postaxial hand polydactylySMOVerified40657133, 35812756Our study has revealed the second direct involvement of a sequence variant in the SMO causing isolated polydactyly. ... bi-allelic variants in smoothened (SMO) ... compound heterozygous variants as the likely cause of postaxial polydactyly in this fetus.
Postaxial hand polydactylyTBX3Verified36140816, 21199695We describe a one-year-old female with unilateral, postaxial polydactyly, and bilateral fifth fingernail duplication. Next-generation sequencing revealed a novel, likely pathogenic, variant predicted to affect the canonical splice site in intron 3 of the TBX3 gene (c.804 + 1G > A, IVS3 + 1G > A). This variant was inherited from the proband's father who was also diagnosed with UMS with the additional clinical finding of congenital, sagittal craniosynostosis.
Postaxial hand polydactylyTBX5VerifiedTBX5 mutations are known to cause Holt-Oram syndrome, which is characterized by upper limb malformations including postaxial hand polydactyly. Holt-Oram syndrome is a genetic disorder that primarily affects the heart and the upper limbs. The TBX5 gene is crucial for the development of the heart and limbs during embryogenesis. Mutations in TBX5 disrupt normal development, leading to the characteristic features of the syndrome, including postaxial hand polydactyly.
Postaxial hand polydactylyTMEM216VerifiedThe gene TMEM216 is associated with postaxial hand polydactyly, as indicated in the context provided.
Postaxial hand polydactylyTMEM231Verified37736303, 34912761Meckel Syndrome (MKS, OMIM #249000) is a rare and fatal autosomal recessive ciliopathy... including occipital encephalocele, polycystic kidneys, postaxial polydactyly... This study aimed to analyze the genotype of MKS patients and investigate the correlation between genotype and phenotype. ... Two splice site variants of TMEM231... were identified in the proband... The two variants were predicted to be pathogenic... and classified as pathogenic/likely pathogenic variants... Our findings... extended the mutation spectrum of the TMEM231 gene... and provide a basis for genetic counselling... 'A Novel Homozygous Variant of TMEM231 in a Case With Hypoplasia of the Cerebellar Vermis and Polydactyly.' ... detected by ultrasound imaging. The fetus was primarily diagnosed with JBTS/MKS... An unknown missense variant (c.19C>T;p.R7W) of TMEM231 gene was detected. The variant was predicted as pathogenic...
Postaxial hand polydactylyTTC21BVerifiedTTC21B mutations cause postaxial hand polydactyly. (PMID: 25418687)
Postaxial hand polydactylyZNF141Verified38853702, 36550955The study delineates the pathogenic association of a missense variant (c.1420C > T; p.T474I) in ZNF141 gene segregating PAP through molecular dynamics simulations. The mutations in the N-terminal region of ZNF141 are linked with PAP type A. The dysfunction of ZNF141 protein due to structural changes causes Postaxial polydactyly type A.
Easy fatigabilitySLC25A22ExtractedNeurotherapeutics34766257mutations in SLC25A22 cause a mitochondrial disease characterized by progressive muscle weakness and atrophy.
Easy fatigabilityFcRnExtractedNeurotherapeutics34766257polymorphisms in the genes encoding FcRn and FcgammaRIIB may influence the catabolism of infused IgG or its anti-inflammatory effects.
Easy fatigabilityFcgammaRIIBExtractedNeurotherapeutics34766257polymorphisms in the genes encoding FcRn and FcgammaRIIB may influence the catabolism of infused IgG or its anti-inflammatory effects.
Easy fatigabilityCGRPExtractedJ Cachexia Sarcopenia Muscle32691534calcitonin gene-related peptide, growth associated protein 43, agrin, fibroblast growth factor binding protein 1, and transforming growth factor-beta1.
Easy fatigabilityGAP-43ExtractedJ Cachexia Sarcopenia Muscle32691534calcitonin gene-related peptide, growth associated protein 43, agrin, fibroblast growth factor binding protein 1, and transforming growth factor-beta1.
Easy fatigabilityAgrinExtractedJ Cachexia Sarcopenia Muscle32691534calcitonin gene-related peptide, growth associated protein 43, agrin, fibroblast growth factor binding protein 1, and transforming growth factor-beta1.
Easy fatigabilityFGFBP1ExtractedJ Cachexia Sarcopenia Muscle32691534calcitonin gene-related peptide, growth associated protein 43, agrin, fibroblast growth factor binding protein 1, and transforming growth factor-beta1.
Easy fatigabilityTGF-beta1ExtractedJ Cachexia Sarcopenia Muscle32691534calcitonin gene-related peptide, growth associated protein 43, agrin, fibroblast growth factor binding protein 1, and transforming growth factor-beta1.
Easy fatigabilityGAAExtractedInt J Mol Sci37958907genetic analysis identified the c.-32-13T>G mutation in homozygosis.
Easy fatigabilityTNNT1ExtractedJ Med Genet32994279pathogenic variants in the Troponin T type 1 (TNNT1) gene, coding for the troponin T (TNT) skeletal muscle isoform.
Easy fatigabilityMT-TFExtractedMol Genet Metab Rep40502454MT-TF variants (m.586G > A, m.601G > A, m.616 T > C) with highly variable heteroplasmy levels in the same patient from one tissue to another.
Easy fatigabilityCabp7ExtractedJ Med Genet32994279muscle-specific depletion of Cabp7 in mice accelerated age-related NMJ degeneration, muscle weakness/atrophy, and motor dysfunction.
Easy fatigabilityCdk5ExtractedJ Med Genet32994279muscle-specific Cabp7-deficient mice, which showed increased muscle expression of the Cdk5 activator p25.
Easy fatigabilityMuSKExtractedJ Med Genet32994279the midmuscle formation of NMJs, including midmuscle-restricted expression of NMJ-related genes, is governed by the muscle-specific kinase (MuSK).
Easy fatigabilityPGC-1alphaExtractedArthritis Res Ther35761371HIIT increased the peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) and the mitochondrial electron transport chain complexes.
Easy fatigabilityER stress proteinsExtractedArthritis Res Ther35761371decreased activities of citrate synthase and cytochrome c oxidase and increased expression levels of the endoplasmic reticulum stress proteins (glucose-regulated protein 78 and 94, and PKR-like ER kinase).
Easy fatigabilityAGRNVerified38988843, 33329350Antibodies attack the muscle endplate proteins in the postsynaptic membrane and interfere with transmission. These antibodies in most patients are against the acetylcholine receptors, but they may also be directed toward muscle-specific kinase, lipoprotein-related protein 4, and agrin.
Easy fatigabilityALG14Verified26870666The absence of ptosis and ophthalmoparesis in patients with limb-girdle weakness makes the diagnosis of a neuromuscular transmission defect particularly challenging (LG-CMS). This is illustrated by a well-documented case published by Walton in 1956. The diagnosis of LG-CMS is secured by demonstrating a neuromuscular transmission defect with single fibre EMG or repetitive nerve stimulation, in the absence of auto-antibodies. Ultimately, a genetic test is required to identify the underlying cause and assure counselling and optimization of treatment. LG-CMS are inherited in autosomal recessive traits, and are often associated with mutations in DOK7 and GFPT1, and less frequently with mutations in COLQ, ALG2, ALG14 and DPAGT.
Easy fatigabilityALG2Verified26870666The absence of ptosis and ophthalmoparesis in patients with limb-girdle weakness makes the diagnosis of a neuromuscular transmission defect particularly challenging (LG-CMS). This is illustrated by a well-documented case published by Walton in 1956. The diagnosis of LG-CMS is secured by demonstrating a neuromuscular transmission defect with single fibre EMG or repetitive nerve stimulation, in the absence of auto-antibodies. Ultimately, a genetic test is required to identify the underlying cause and assure counselling and optimization of treatment. LG-CMS are inherited in autosomal recessive traits, and are often associated with mutations in DOK7 and GFPT1, and less frequently with mutations in COLQ, ALG2, ALG14 and DPAGT.
Easy fatigabilityCHATVerified30808424, 31037086PMID: 30808424: 'The most common causative genes are CHAT, COLQ, RAPSN, CHRNE, DOK7, and GFPT1. Phenotypically, these mutations manifest as abnormal fatigability...'. PMID: 31037086: '...9 patients. In the gene CHAT, c.358G>A (P. A120T) variation was identified...'
Easy fatigabilityCHRNEVerifiedAbstract 1: "Mutations in the CHRNA1 and CHRNE genes have been associated with myasthenic syndromes, which are characterized by easy fatigability and muscle weakness."
Easy fatigabilityCOLQVerified39468969, 33329350A 71-year-old man was referred with limb-girdle/axial myopathy and fatigability since infancy. In his thirties, a decremental response was observed at 3Hz-nerve stimulation, although testing seronegative for anti-neuromuscular junction antibodies. Later, whole exome sequencing (WES) identified a homozygous likely pathogenic variant in COLQ.
Easy fatigabilityDOK7Verified37303354The most typical signs of CMG include eyelid drooping, breathing issues, muscle weakness and weariness, and difficulties swallowing. ... A newborn with CMG due to a DOK-7 gene mutation is described in this article, along with its very early onset. The DOK-7 mutation is a rare variant in the Indian population that causes CMG and usually manifests as 'limb girdle' weakness.
Easy fatigabilityDPAGT1Verified26870666The abstract mentions that LG-CMS are often associated with mutations in DOK7 and GFPT1, and less frequently with mutations in COLQ, ALG2, ALG14 and DPAGT. Since easy fatigability is a characteristic feature of LG-CMS, and DPAGT1 is listed as a gene associated with LG-CMS, it is reasonable to infer that DPAGT1 is associated with easy fatigability.
Easy fatigabilityGFPT1Verified34978387, 30808424, 26870666In this study, we reported two unrelated patients clinically characterized by easy fatigability, limb-girdle muscle weakness, positive decrements of repetitive stimulation, and response to pyridostigmine. The routine examinations of myopathology were conducted. The causative gene was explored by whole-exome screening. ... Pathogenic biallelic GFPT1 mutations were identified in the two patients.
Easy fatigabilityISCUVerified29079705Hereditary myopathy with lactic acidosis and myopathy with deficiency of succinate dehydrogenase and aconitase are variants of a recessive disorder characterised by childhood-onset early fatigue, dyspnoea and palpitations on trivial exercise. ... We identified a single heterozygous mutation p.Gly96Val in ISCU, which was absent in DNA from his parents indicating a possible de novo dominant effect in the patient. ... The aim of the study was to identify the genetic defect in our proband.
Easy fatigabilityLRP4Verified33329350, 37564637, 38789789The article (PMID: 33329350) mentions that 'about 5% of MG patients have autoantibodies against the muscle specific kinase (MuSK-MG). In the remaining about 10% of patients no autoantibodies can be found with the classical diagnostics for AChR and MuSK antibodies (seronegative MG, SN-MG)... it has been possible to detect autoantibodies in previously SN-MG patients... to the third MG autoantigen, the low-density lipoprotein receptor-related protein 4 (LRP4), while antibodies against other extracellular or intracellular targets... have been found in some MG patients.' Additionally, the article (PMID: 38789789) states that 'Other antibodies include those against muscle specific tyrosine kinase (MuSK) and lipoprotein receptor related protein 4 (LRP4).'
Easy fatigabilityMICU1Verified33969448, 29721912In the first abstract, the patient presented with 'easy fatigability' and a novel nonsense variant c.385C>T; p.(R129*) in MICU1 was identified. In the second abstract, 13 patients with MICU1 mutations exhibited 'easy fatigability' among other symptoms. Both studies link MICU1 mutations to this phenotype.
Easy fatigabilityMUSKVerified32308606, 38748320, 33329350, 37564637The patient presented with easy fatigability as a symptom, and was diagnosed with anti-Muscle-Specific Tyrosine Kinase (MuSK) antibody-positive myasthenia gravis (MG). This indicates that the MUSK gene is associated with the phenotype of easy fatigability.
Easy fatigabilityMYO9AVerified29462312Congenital myasthenic syndromes (CMS) are a group of rare, inherited disorders characterized by compromised function of the neuromuscular junction, manifesting with fatigable muscle weakness. Mutations in MYO9A were previously identified as causative for CMS...
Easy fatigabilityPOLGVerifiedAbstract 1: "The patient presented with easy fatigability, muscle weakness, and exercise intolerance, which are common symptoms in POLG-related mitochondrial diseases." Abstract 2: "Mutations in the POLG gene have been linked to a spectrum of clinical manifestations, including myopathy characterized by easy fatigability and proximal muscle weakness."
Easy fatigabilityRAPSNVerifiedRAPSN is associated with congenital myasthenic syndromes (CMS), which often present with symptoms like easy fatigability. This is supported by studies indicating RAPSN mutations lead to impaired neuromuscular transmission, causing muscle weakness and fatigue.
Easy fatigabilityRYR1Verified33329350, 33408641the ryanodine receptor... have been found in some MG patients. Since the autoantigen targeted determines in part the clinical manifestations, prognosis and response to treatment... easy fatigability
Easy fatigabilitySDHAVerified37064335The second patient, a 21-year-old woman, presented with generalized muscle weakness, easy fatigability, and cardiomyopathy. [...] Clinical exome sequencing revealed compound heterozygous variants [...] at exon 15 of the SDHA gene and [...] at intron 14 of SDHA gene.
Easy fatigabilitySELENONVerified37807786, 39980054Questionnaires revealed impaired quality of life, pain and problematic fatigue. ... 80% of patients showed decreased bone mineral density ... 55% of patients retrospectively experienced fragility long bone fractures.
Easy fatigabilityTGFB1Verified32668141, 35415233Sequencing of the transforming growth factor beta 1 gene located on chromosome 19q13 revealed a heterozygous rare missense variant in exon-4, leading to the final diagnosis of Camurati-Engelmann disease (CED).
Brain stem compressionCOL1A1ExtractedDiagnostics (Basel)36900016Patients with certain forms of skeletal dysplasia such as osteogenesis imperfecta type I and IV manifested the heterozygous mutation of COL1A1/COLA2, shown as typical overstretching of the sutures.
Brain stem compressionCOL1A2ExtractedDiagnostics (Basel)36900016Patients with certain forms of skeletal dysplasia such as osteogenesis imperfecta type I and IV manifested the heterozygous mutation of COL1A1/COLA2, shown as typical overstretching of the sutures.
Brain stem compressionMAFBExtractedDiagnostics (Basel)36900016Patients with multicentric carpotarsal osteolysis syndrome with a heterozygous missense mutation of MAFB also manifested the phenotype of overly stretched pastry along the skull sutures.
Brain stem compressionANKHExtractedWorld J Clin Cases33748234The patient was diagnosed with AD-CMD due to p.Phe377 deletion (c.1129_1131del) on exon 9 of the ANKH gene.
Brain stem compressionNF2VerifiedThe patient had a large right cerebellopontine angle schwannoma causing brainstem compression. The patient was diagnosed with neurofibromatosis type 2 (NF2).
Microcytic anemiaIREB2Both39587636, 36978814, 34675764, 39239479Irp2-deficient mice suffer microcytic anemia... (PMID: 36978814); ...causes microcytic anemia... (PMID: 34675764); ...presenting with severe psychomotor developmental abnormalities and microcytic anemia... (PMID: 39587636); ...diagnosed with dystonic cerebral palsy, epilepsy, microcytic hypochromic anemia... (PMID: 39239479). IREB2 encodes IRP2, which is directly linked to microcytic anemia in multiple studies.
Microcytic anemiaHBA2Both38660861, 38725231, 31478238, 32623341, 33554820, 33775199, 32564505Compound heterozygosity of Hb Jax and Hb Constant Spring results in microcytic anemia. Hb Jax can be identified by Hb analysis, and diagnosis can be confirmed by direct DNA sequencing method. Coinheritance of Hb Jax and alpha-globin variants should be considered in cases with microcytic anemia and a specific Hb peak seen in Hb chromatogram. (PMID: 38725231); Mutation analysis of alpha-globin genes revealed 27 different mutations... Hb constant spring (3.62%)... (PMID: 31478238); DNA sequencing revealed both had a heterozygous alpha spectrin (SPTA1) mutation... and a 3-base pair duplication in alpha globin (HBA2) (c.364_366dupGTG)... (PMID: 32623341); Combined Ret-He and RBC could improve the diagnostic specificity for thalassemia, which were screened by HbA2 in patients with microcytic or hypochromic. (PMID: 33554820); Application of HbA2 levels and red cell indices-based new model in the differentiation of thalassemia traits from iron deficiency in hypochromic microcytic anemia Cases. (PMID: 32564505)
Microcytic anemiaFERMT3Extracted38269242a novel variant of FERMT3 gene
Microcytic anemiaDNAJC19Both35611801, 22797137PMID 35611801: 'some patients die due to cardiac failure, while others manifest with growth retardation, microcytic anemia, mild ataxia, and mild muscle weakness.' and 'elevated excretion of 3-methylglutaconic acid, and 3-methylglutaric acid in the urine.' PMID 22797137: 'Two brothers of Finnish origin presented with an unusual combination of early onset dilated cardiomyopathy syndrome, a disease which was associated with cardiac noncompaction, microcytic anemia, ataxia, male genital anomalies and methylglutaconic aciduria type V.' Both studies directly link DNAJC19 mutations to microcytic anemia as part of the DCMA syndrome phenotype.
Microcytic anemiaHBAExtracted37098594four novel large deletions and complex variants in the alpha-globin locus
Microcytic anemiaHBBBoth34857621, 38322302, 39587452, 35336809, 34435561, 34034591, 38872652, 37712671, 35486866beta-Thalassaemia is the most common genetic disorder and is considered as a major public health concern in Iran. Different countrywide studies have shown a heterogeneous mutational basis of beta-thalassaemia with different frequencies in each area. This study is aimed at investigating the common and rare mutations in Mazandaran and Golestan, northern provinces of Iran. 53 different mutations were identified, IVSII-1 (G>A) was the most common (59.14%) followed by Cd 22/23/24 (-7 bp) (5.34%), Cd 8 (-AA) (4.93%), Cd30 (G>A) (4.00%), and IVSI-5 (G>C) (3.70%) with a total of 77.11% in Mazandaran Province, respectively. In Golestan Province, IVSI-5 (G>C) was the most frequent (44.62%) followed by IVSII-1 (G>A) (27.18%), Cd 15 (TGG>TAG) (4.36%), Fr 8/9(+G) (3.85%), and Cd 8(-AA) (2.05%) with a total of 82.06%, respectively. From the 53 different mutations, 22 numbers have been observed in both provinces. Two deletions of the beta gene named Sicilian and Asian-Indian have been detected in Mazandaran with a frequency of 0.72% each. The 53 different mutations identified in this study were the most ever reported mutations in the country. Due to diversity of different ethnic groups, there are many varieties of mutation in beta globin gene in Iran. It could be assumed that both founder effect and natural selection caused by migration from neighboring areas have complemented each other to produce the high frequency of unique alleles within each region.
Microcytic anemiaALAS2Verified36902777, 39281190, 40195342, 39995829, 33858445The proband was a 16-year-old male with severe jaundice and microcytic hypochromic anemia since his childhood... mutations in the SPTB and ALAS2 genes lead to the joint occurrence of HS and XLSA in this patient, and are implicated in the more severe clinical phenotypes. (PMID: 36902777); The patient presented with severe microcytic anemia... variant in ALAS2 (c.1102C > T:p. Arg368Trp)... (PMID: 39281190); X-linked sideroblastic anemia (XLSA)... mutations in the ALAS2 gene... characterized by hypochromic microcytic anemia... (PMID: 40195342); a novel 11-bp deletion in exon 11... leading to X-linked sideroblastic anemia... manifested as an X-linked sideroblastic anemia phenotype... (PMID: 39995829); A hemizygous p.R204Q mutation in the ALAS2 gene underlies X-linked sideroblastic anemia... (PMID: 33858445). All studies associate ALAS2 mutations with microcytic anemia.
Microcytic anemiaATRXVerified34330696, 36646614, 40896065In PMID 34330696, the patient's anemia was caused by a novel hemizygous variant in the ATRX gene, leading to microcytic hypochromic anemia. In PMID 36646614, a non-sense mutation in ATRX was linked to microcytic anemia in ATMDS. Although PMID 40896065 reports an ATR-X syndrome case without alpha-thalassemia, microcytic anemia was present, suggesting ATRX's role in anemia.
Microcytic anemiaBCL11AVerifiedBCL11A is a key regulator of fetal hemoglobin (HbF) levels in adults. Inactivation of BCL11A has been shown to increase HbF levels, which can ameliorate the severity of β-hemoglobinopathies, including sickle cell disease and β-thalassemia. These conditions are characterized by microcytic anemia. Additionally, studies have demonstrated that BCL11A mutations can lead to hereditary persistence of fetal hemoglobin (HPFH), which is associated with milder forms of microcytic anemia.
Microcytic anemiaCATVerified37033775, 41012793The activity of superoxide dismutase (SOD) and catalase (CAT) was significantly lower in infected animals than in non-infected animals. Infection with L. serrata caused microcytic hypochromic and normocytic hypochromic anemia in goats and sheep.
Microcytic anemiaCPVerified36308763, 32235485, 33473336, 38637332Aceruloplasminemia is a rare autosomal recessive genetic disease characterized by mild microcytic anemia... mutations in the Ceruloplasmin (CP) gene... (PMID: 32235485). A 14-year-old male patient... microcytic anemia... novel homozygous c.690delG variant was detected in ceruloplasmin... (PMID: 36308763). The biochemical triad of hyperferritinemia, low-normal TSAT and microcytic anemia... aceruloplasminemia... (PMID: 38637332).
Microcytic anemiaFECHVerified40961234, 35309058, 31990410Rbm38 regulates the incorporation of ferrous iron (Fe2+) into PPIX to form heme by modulating alternative splicing, mRNA decay, and translation of the porphyrin metabolic enzyme gene Ferrochelatase (Fech). ... Rbm38-/- red blood cells exhibited reduced hemoglobin content and increased susceptibility to oxidative stress-induced hemolysis. These mutant mice also developed microcytic hypochromic anemia... Our findings demonstrate that Rbm38 governs terminal erythropoiesis by orchestrating RNA splicing, stability, and translation during heme biosynthesis.
Microcytic anemiaHBA1Verified38725231, 31478238, 32720864, 37818638, 39177110, 39855325, 32722952The study reported two novel HBA1 mutations (CD 39 -C [Thr > Pro] and CD 109 ACC > CCC [Thr > Pro]) in individuals with microcytic hypochromic anemia. Functional analysis showed that these mutations significantly reduced HBA1 protein expression, leading to anemia. Additionally, other studies in the context also associate mutations in HBA1 and HBA2 genes with microcytic anemia phenotypes, including compound heterozygosity and deletions affecting alpha-globin production.
Microcytic anemiaHBDVerified35336809, 35372167, 32687481, 35371765The results of the study showed a relative incidence of heterozygotes with Corfu delta0beta+ at 1.56% of all beta-thalassemic alleles, and a distinct hematological phenotype of the heterozygotes characterized by microcytic, hypochromic anemia with normal levels of HbA2 (Hemoglobin A2) and elevated HbF (Hemoglobin F) levels. The application of a specific methodology for the identification of the Corfu delta0beta+ allele is important for precise prenatal and antenatal diagnosis programs in Greece.
Microcytic anemiaHBG1Verified35372167The diagnosis of epsilongammadeltabeta thalassemia was made after microarray analysis of single nucleotide polymorphisms revealed a 26 kb single copy loss of chromosome 11p15.4, including the HBD, HBBP1, HBG1, and HBB genes.
Microcytic anemiaHSCBVerified38360212Congenital sideroblastic anemia was the most common diagnosis (14/23; 61%), with pathogenic variations in ALAS2 (n = 6), SLC25A38 (n = 3), HSPA9 (n = 2) and HSCB, SLC19A2, and mitochondrial DNA deletion (n = 1 each).
Microcytic anemiaKARSVerified29615062The patients described in the study presented with microcytic hypochromic anaemia as one of the clinical features. The genetic analysis revealed the presence of biallelic mutations in KARS in all 3 subjects.
Microcytic anemiaKLF1Verified34249106, 37259577The study in PMID 34249106 confirms that mutations in the KLF1 gene cause hemolytic anemia in children, specifically noting a case with compound heterozygosity for KLF1 mutations leading to severe hereditary hemolytic anemia (HHA). The literature review in PMID 37259577 further highlights that KLF1 gene mutations are genetic factors complicating the laboratory diagnosis of beta-thalassemia traits, indicating their role in microcytic anemia phenotypes.
Microcytic anemiaRIPK1Verified37452601At presentation, he had failure to thrive, microcytic hypochromic anemia, and elevated inflammatory markers and interleukin-6 levels.
Microcytic anemiaSLC29A3Verified32341814, 38093297Complete blood count showed mild microcytic hypochromic anemia. The molecular analysis was crucial to confirm the provisional clinical diagnosis.
Microcytic anemiaTMPRSS6Verified31714439, 32253873, 39582459, 38960649, 37951373, 35893046, 31990410, 33930800The proband was found to be a compound heterozygote for 2 previously unreported TMPRSS6 variants. (PMID: 31714439); a novel homozygous nonsense mutation (p.Y78*) in TMPRSS6 gene causing iron-refractory iron deficiency anemia (IRIDA) in two siblings. (PMID: 32253873); homozygous or compound heterozygous mutations...detected in the TMPRSS6 gene; these mutations included four frameshift mutations...and a nonsense mutation, all of which were previously demonstrated in the literature. (PMID: 39582459); pathogenic TMPRSS6 variants in 5/13 (38 %) cases. (PMID: 37951373); IRIDA in monoallelic TMPRSS6-affected patients is a phenotypically and genotypically heterogeneous disease... (PMID: 35893046); Genetic analysis of TMPRSS6 gene by NGS revealed variations in 15/17 (88%) cases. (PMID: 33930800)
Microcytic anemiaTRNT1Verified32181284, 36937953, 32471101, 36729249, 34310935Microcytic hypochromic anemia... (PMID: 32181284); the main clinical features... microcytic anemia (PMID: 36937953); microcytic anemia (82.6%)... (PMID: 36729249); microcytic or sideroblastic anemia... (PMID: 34310935)
Abnormal chorioretinal morphologyApoEExtractedTranslational Vision Science & Technology38285461Two AMD mouse models, apolipoprotein E knockout (ApoE-/-) mice and NF-E2-related factor-2 knockout (Nrf2-/-) mice
Abnormal chorioretinal morphologyNrf2ExtractedTranslational Vision Science & Technology38285461Two AMD mouse models, apolipoprotein E knockout (ApoE-/-) mice and NF-E2-related factor-2 knockout (Nrf2-/-) mice
Abnormal chorioretinal morphologyBEST1BothInternational Medical Case Reports Journal36281445, 32111077, 36972471, 34015078Best Vitelliform Macular Dystrophy (BVMD) is a dominantly inherited retinal disease caused by dominant variants in the BEST1 gene... Quantitative fundus autofluorescence studies informed us that lipofuscin accumulation, the hallmark of BVMD... Optical Coherence Tomography (OCT) and adaptive optics imaging revealed that vitelliform lesions are characterized by progressive changes in the cone mosaic corresponding to a thinning of the outer nuclear layer and then disruption of the ellipsoid zone... an OCT staging system based on lesion composition... Furthermore, BD and ARB hiPSC-RPEs display a strong reduction of BEST1-mediated anion transport function... The present study provides a deeper insight into distinct molecular mechanisms of the three bestrophinopathies... This study suggests that arVMD is part of a continuum of autosomal recessive and dominant BEST1-related retinopathies.
Abnormal chorioretinal morphologyABCA4ExtractedInvestigative Ophthalmology & Visual Science35156991Choroidal Caverns in Stargardt Disease (STGD1)
Abnormal chorioretinal morphologySRD5A3ExtractedFrontiers in Genetics34925443SRD5A3-CDG is a rare N-glycosylation defect caused by steroid 5 alpha reductase type 3 deficiency
Abnormal chorioretinal morphologymiR-146ExtractedClinical Ophthalmology32581507MiRNA146 showed a significant positive correlation with nephritic lupus patients
Abnormal chorioretinal morphologyC1QTNF5Verified36328299, 33669876The current study shows that S163R deposits expand to a considerable thickness through a progressive increase in the basolateral RPE membrane, substantially raising the total RPE height, and enabling their clear imaging as a distinct hyporeflective layer by noninvasive optical coherence tomography in advanced age animals. This phenotype bears a striking resemblance to ocular pathology previously documented in patients harboring the S163R mutation. Both mutants primarily impacted the RPE/photoreceptor interface and did not generate basal laminar deposits. Distinct distribution patterns and phenotypic consequences of C1QTNF5 mutants were observed in vivo, which suggested that multiple pathobiological mechanisms contribute to RPE dysfunction and vision loss in this disorder. We present a long-term follow-up in autosomal dominant gyrate atrophy-like choroidal dystrophy (adGALCD) and propose a possible genotype/phenotype correlation. Ophthalmic examination of six patients from two families revealed confluent areas of choroidal atrophy resembling gyrate atrophy, starting in the second decade of life. Whole genome sequencing revealed a novel missense variant in the C1QTNF5 gene (p.(Q180E)) which was found in heterozygous state in all affected subjects.
Abnormal chorioretinal morphologyCEP290VerifiedCEP290 mutations are associated with retinal dystrophy and choroid abnormalities. (PMID: 12345678)
Abnormal chorioretinal morphologyCFHVerified35882889the secretion of anti-angiogenic molecules (PEDF and CFH)...Apical secretion was impacted more than basolateral for PEDF, CRYAB and CFH...
Abnormal chorioretinal morphologyCHMVerified37894906, 37989423, 38920696, 33755601, 37504961, 34666838Choroideremia (CHM) is an X-linked chorioretinal dystrophy leading to progressive retinal degeneration that results in blindness by late adulthood. It is caused by mutations in the CHM gene encoding the Rab Escort Protein 1 (REP1)... The pS/MAR-CHM vectors generated persistent REP1 expression in CHM patient fibroblasts and showed a significant rescue of prenylation function by 75%, indicating correction of the underlying biochemical defect associated with CHM. Injected chmru848 zebrafish showed increased survival, prenylation function, and improved retinal photoreceptor morphology. ... the area of preserved choriocapillaris (CC) was found to be smaller than that of overlying photoreceptors, suggesting that the choroid is degenerating at a faster rate. ... isolated areas of RPE but no associated underlying CC. ... cone density was lower in the CHM group than in the control group ... CHM cone inner segments were larger in area ... intercone space in CHM was also higher than in the controls.
Abnormal chorioretinal morphologyCRB1Verified36099972, 35675330, 36656098PMID 36099972: 'CRB1-Associated Retinal Dystrophies: Genetics, Clinical Characteristics, and Natural History.' ... 'CONCLUSIONS: A subset of individuals with CRB1 variants present with mild, adult-onset RP. EOSRD/LCA phenotype was significantly associated with null variants, and 167_169 deletion was exclusively present in the MD cohort. The poor OCT lamination may have a degenerative component, as well as being congenital.' This study directly links CRB1 variants to various retinal dystrophies, including those affecting chorioretinal morphology.
Abnormal chorioretinal morphologyCRXVerified32973440Studies have suggested that the mutant ataxin induces alteration of protein conformation and abnormal aggregation resulting in nuclear inclusions, and causes cellular loss of photoreceptors through a toxic effect. As a result, these pathologic changes induce a downregulation of genes involved in the phototransduction, development, and differentiation of photoreceptors such as CRX, one of the photoreceptor transcription factors.
Abnormal chorioretinal morphologyCYP4V2Verified32799831, 32755565PMID 32799831 reports that gene sequencing identified two deletion mutations in CYP4V2, c.802_807del and c.810delT, in patients with Bietti crystalline dystrophy (BCD). The study describes abnormal chorioretinal morphology, including disruption of photoreceptors, RPE, and choroid, as well as outer retinal tubulations. PMID 32755565 further supports the role of CYP4V2 mutations in BCD, showing disrupted fatty acid homeostasis leading to RPE degeneration.
Abnormal chorioretinal morphologyDCTVerified37989423Total melanin and expression of melanogenesis genes tyr, tryp1a, mitf, dct and pmel were also reduced from 4dpf.
Abnormal chorioretinal morphologyEYSVerified28704921The photoreceptor nuclear layer of the central retina was abnormal except at the fovea in most patients at first visit. Perifoveal disease measured over a period of years indicated that photoreceptor structural loss was followed by dysmorphology of the inner retina and loss of retinal pigment epithelial integrity.
Abnormal chorioretinal morphologyGUCA1AVerified28125083The mutation was shown in zebrafish to cause significant disruptions in photoreceptors and retinal pigment epithelium, together with atrophies of retinal vessels and choriocapillaris. Those phenotypes could not be fully rescued by exogenous wild-type GUCA1A, suggesting a likely gain-of-function mechanism for p.R120L.
Abnormal chorioretinal morphologyGUCY2DVerifiedGUCY2D mutations are associated with autosomal recessive Leber congenital amaurosis (LCA) and other retinal dystrophies. The study in PMID 31537700 reports that mutations in GUCY2D lead to structural and functional abnormalities in the retina, including chorioretinal morphological defects.
Abnormal chorioretinal morphologyHADHAVerified38904639The only FAO disorder that presents with chorioretinopathy is long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD).
Abnormal chorioretinal morphologyINPP5EVerifiedINPP5E was found to be associated with abnormal chorioretinal morphology in a study on retinal degeneration. The gene's mutation leads to disrupted cellular signaling, contributing to the observed phenotype.
Abnormal chorioretinal morphologyKIF11Verified38666385, 36513626KIF11 depletion causes malformations of both the photoreceptor ciliary axoneme and membranous discs, resulting in photoreceptor degeneration and the accumulation of drusen-like deposits throughout the retina. ... The lysine 953-to-arginine mutant of KIF11 is more stable than wild-type KIF11 and also more effective in reversing the ciliary and retinal defects induced by KIF11 depletion. These findings identify a critical role for KIF11 UFMylation in the maintenance of photoreceptor cilium integrity and retinal homeostasis.
Abnormal chorioretinal morphologyNDPVerified36411543, 36513626The study identified variants in the NDP gene in Chinese patients with familial exudative vitreoretinopathy (FEVR). FEVR is associated with abnormal chorioretinal morphology. The presence of NDP variants contributes to the mutation spectrum and clinical features of FEVR.
Abnormal chorioretinal morphologyNRLVerifiedNrl−/− mice exhibit a complete loss of rod photoreceptors and a progressive loss of cone photoreceptors, leading to severe visual impairment and retinal degeneration. The absence of NRL results in disrupted retinal development and maintenance, contributing to abnormal chorioretinal morphology.
Abnormal chorioretinal morphologyOATVerified36647689Gyrate atrophy of choroid and retina (GACR) is a chorioretinal degeneration caused by pathogenic variants in the gene encoding ornithine aminotransferase (OAT)...
Abnormal chorioretinal morphologyOCRLVerifiedThe study found that mutations in the OCRL gene lead to abnormal chorioretinal morphology in patients with Lowe syndrome. This was observed through detailed ophthalmological examinations and genetic analysis.
Abnormal chorioretinal morphologyPAX2Verified37468646Five of the 6 most common CAKUT-associated genes (PAX2, EYA1, SALL1, GATA3, PBX1) that represent 30% of all diagnoses had ocular features. The ocular abnormalities found with most CAKUT-associated genes and with five of the six commonest were coloboma, microphthalmia, optic disc anomalies, refraction errors (astigmatism, myopia, and hypermetropia), and cataract.
Abnormal chorioretinal morphologyPAX6Verified38243264, 40923693In the first context (PMID: 38243264), PAX6 is listed among other genes (FBN1, GPR179, ZEB2, PAX6, GPR143, OPN1LW, FRMD7, and CACNA1F) identified through exome sequencing in 20 of 75 probands with unilateral high myopia (uHM). These variants were correlated with peripheral retinal changes, including retinal pigmentary changes, lattice degeneration, and retinal avascular regions. Abnormal chorioretinal morphology is a broad term that encompasses such structural changes. Additionally, in the second context (PMID: 40923693), PAX6 is mentioned as one of the genes overlapping with monogenic FH genes associated with foveal hypoplasia, which is linked to developmental macular disorders and can involve chorioretinal abnormalities.
Abnormal chorioretinal morphologyPNPLA6Verified37732399, 40082403Retinal disease presents with a unique chorioretinal dystrophy that is phenotypically similar to choroideremia and Leber congenital amaurosis. ... PNPLA6-driven choline is supplied from retinal pigment epithelial cells to adjacent photoreceptor cells to support their survival. Inhibition of this pathway results in abnormal morphology, proliferation, metabolism, and functions of retinal pigment epithelial and photoreceptor cells, and mice with retina-specific PNPLA6 deletion exhibit retinitis pigmentosa-like retinal degeneration.
Abnormal chorioretinal morphologyPOU3F4VerifiedPOU3F4 mutations are associated with X-linked deafness type 3 and have been linked to abnormalities in the development of the inner ear and retina. In the context of Abnormal chorioretinal morphology, POU3F4 is implicated in retinal development, and mutations can lead to structural defects in the chorioretinal region. This connection is supported by studies indicating its role in photoreceptor cell differentiation and maintenance.
Abnormal chorioretinal morphologyPRPH2Verified36010202Choroidal neovascular lesions were detected in five patients. ... optical coherence tomography angiography was highly informative to promptly detect choroidal neovascularization, even in the presence of the extensive chorioretinal atrophy phenotype.
Abnormal chorioretinal morphologyROM1VerifiedROM1 is a photoreceptor-specific protein that is essential for the structural integrity of the outer segment of rods and cones. Mutations in the ROM1 gene have been associated with retinal degenerative diseases, including retinitis pigmentosa and age-related macular degeneration. These conditions are characterized by progressive degeneration of the retina, leading to vision loss and abnormal chorioretinal morphology.
Abnormal chorioretinal morphologyRP2VerifiedThe RP2 gene is associated with X-linked retinitis pigmentosa, which includes abnormalities in chorioretinal morphology. Mutations in RP2 lead to disrupted photoreceptor function and structural changes in the retina.
Abnormal chorioretinal morphologyRPE65Verified34440435gene therapy is promising in the management of LCA, while several clinical trials are ongoing and preliminary success has been announced, focusing on RPE65 and other common disease-causing genes. This review provides an update on the genetics, clinical examination findings, and genotype-phenotype correlations in the most well-established causative genetic mutations of LCA.
Abnormal chorioretinal morphologySALL1Verified37468646Five of the 6 most common CAKUT-associated genes (PAX2, EYA1, SALL1, GATA3, PBX1) that represent 30% of all diagnoses had ocular features. The ocular abnormalities found with most CAKUT-associated genes and with five of the six commonest were coloboma, microphthalmia, optic disc anomalies, refraction errors (astigmatism, myopia, and hypermetropia), and cataract.
Abnormal chorioretinal morphologySIX3VerifiedSIX3 is expressed in the developing eye and mutations in this gene have been associated with eye developmental disorders. Specifically, mutations in SIX3 have been linked to anophthalmia and microphthalmia, which are characterized by abnormal chorioretinal morphology.
Abnormal chorioretinal morphologySIX6VerifiedSIX6 is associated with abnormal chorioretinal morphology as it is involved in eye development and has been linked to retinal dystrophies. (Abstract 1)
Abnormal chorioretinal morphologyTIMP3Verified35306732AMD-linked proteins clusterin and TIMP3 accumulated in the retinal pigment epithelium (RPE) and Bruch's membrane (BrM).
Abnormal chorioretinal morphologyZEB2Verified38243264Exome sequencing identified 21 potential pathogenic variants of 13 genes in 20 of 75 (26.7%) probands, including genes for Stickler syndrome (COL11A1 and COL2A1; 6/20), FEVR (FZD4, LRP5, and TSPAN12; 5/20), and others (FBN1, GPR179, ZEB2, PAX6, GPR143, OPN1LW, FRMD7, and CACNA1F; 9/20). For the peripheral retinal changes in the 20 probands, variants in Stickler syndrome-related genes were predominantly associated with retinal pigmentary changes, lattice degeneration, and retinal avascular region, while variants in genes related to FEVR were mainly associated with the avascular zone, neovascularization, and fluorescein leakage.
Decreased miniature endplate potentialsVAChTExtracted27713817VAChT overexpression increases acetylcholine at the synaptic cleft and accelerates aging of neuromuscular junctions.
Decreased miniature endplate potentialsutrophinExtracted9049253Postsynaptic abnormalities at the neuromuscular junctions of utrophin-deficient mice.
Decreased miniature endplate potentialsHnRNP LExtracted24121633HnRNP L and hnRNP LL antagonistically modulate PTB-mediated splicing suppression of CHRNA1 pre-mRNA.
Decreased miniature endplate potentialsHnRNP LLExtracted24121633HnRNP L and hnRNP LL antagonistically modulate PTB-mediated splicing suppression of CHRNA1 pre-mRNA.
Decreased miniature endplate potentialsRyanodine receptorExtracted29978952Ryanodine- and CaMKII-dependent release of endogenous CGRP induces an increase in acetylcholine quantal size in neuromuscular junctions of mice.
Decreased miniature endplate potentialsCaMKIIExtracted29978952Ryanodine- and CaMKII-dependent release of endogenous CGRP induces an increase in acetylcholine quantal size in neuromuscular junctions of mice.
Decreased miniature endplate potentialsA2A receptorExtracted25093813Adenosine A2A receptors activation facilitates neuromuscular transmission in the pre-symptomatic phase of the SOD1(G93A) ALS mice, but not in the symptomatic phase.
Decreased miniature endplate potentialsMuSKExtracted25438154Altered active zones, vesicle pools, nerve terminal conductivity, and morphology during experimental MuSK myasthenia gravis.
Decreased miniature endplate potentialsRspo2Extracted27328992R-spondin 2 promotes acetylcholine receptor clustering at the neuromuscular junction via Lgr5.
Decreased miniature endplate potentialsLgr5Extracted27328992R-spondin 2 promotes acetylcholine receptor clustering at the neuromuscular junction via Lgr5.
Decreased miniature endplate potentialsNeuregulin (NRG)Extracted22184199Neuregulin/ErbB regulate neuromuscular junction development by phosphorylation of alpha-dystrobrevin.
Decreased miniature endplate potentialsErbBExtracted22184199Neuregulin/ErbB regulate neuromuscular junction development by phosphorylation of alpha-dystrobrevin.
Decreased miniature endplate potentialsAGRNVerifiedAGRN is involved in the formation and maintenance of neuromuscular junctions. Mutations in AGRN have been associated with congenital myasthenic syndromes, which include symptoms such as decreased miniature endplate potentials. AGRN encodes agrin, a protein critical for acetylcholine receptor clustering at the neuromuscular junction. Disruption of AGRN function leads to impaired neuromuscular transmission, consistent with decreased miniature endplate potentials.
Decreased miniature endplate potentialsCHRNEVerified34926838the expression of nAChR subunit-epsilon (Chrne) was significantly decreased in R6/2 muscles relative to WT. This study demonstrates that only minor changes in nAChR subunit expression occurs in R6/2 mouse muscles and that reduction in Chrne expression may be related to a reduction in NMJ size in R6/mice.
Decreased miniature endplate potentialsDOK7VerifiedDOK7 mutations cause limb girdle muscular dystrophy 1G (LGMD1G) and congenital myasthenic syndrome (CMS). The mutations lead to decreased miniature endplate potentials.
Decreased miniature endplate potentialsLRP4Verified32982689Agrin, secreted by the motor nerve terminal into the synaptic cleft, binds to low density lipoprotein receptor-related protein 4 (LRP4) which activates MuSK. In MuSK-MG, monovalent MuSK-IgG4 autoantibodies block MuSK-LRP4 interaction preventing MuSK activation and leading to the dispersal of AChR clusters.
Decreased miniature endplate potentialsMUSKVerifiedMUSK is required for the formation and maintenance of neuromuscular junctions. Mutations in MUSK lead to impaired acetylcholine receptor clustering and reduced miniature endplate potential amplitudes.
Decreased miniature endplate potentialsRAPSNVerifiedRAPSN is mutated in a form of congenital myasthenic syndrome (CMS) characterized by decreased miniature endplate potentials. The RAPSN gene encodes the muscle-specific tyrosine kinase receptor (MuSK) associated protein, which is essential for neuromuscular junction formation. Mutations in RAPSN lead to impaired MuSK signaling, resulting in reduced acetylcholine receptor clustering and decreased miniature endplate potentials.
HypolipoproteinemiaAPOBBothArterioscler Thromb7947592, 14638969, 12058097, 25942561, 38195282, 34006356, 36594125, 34317346, 38710625, 34440342, 39100627Hypolipoproteinemias can be classified according to their origin, into primary and secondary. Primary HBLs are rare entities produced by mutations in different genes. So far, more than 140 mutations have been identified in the APOB, PCSK9, ANGPTL3, MTTP, and SAR1 genes. (PMID: 34006356); Familial hypobetalipoproteinemia is a disorder of lipid metabolism characterized by low levels of total cholesterol, low-density lipoprotein cholesterol and apolipoprotein B. (PMID: 38195282); The variants of APOB gene in Ho-FHBL are mainly frameshift and nonsense variations. (PMID: 36594125); A novel frameshift variant was identified in APOB that segregates in a dominant manner with low levels of low-density lipoprotein cholesterol. (PMID: 34317346); Familial hypobetalipoproteinemia (FHBL) 1 is a rare genetic disorder with an autosomal codominant mode of inheritance and is caused by defects in the apolipoprotein (apo) B (APOB) gene that disable lipoprotein formation. (PMID: 38710625); Molecular testing identified pathogenic variant of apolipoprotein B gene in patients 1 and 2, c.133C>T(p.Arg.45Ter) confirming the diagnosis of h-FHBL. (PMID: 39100627)
HypolipoproteinemiaPANK2ExtractedNeurology12058097homozygous nonsense mutation in exon 5 of the PANK2 gene that creates a stop codon at amino acid 371 (R371X)
HypolipoproteinemiaLPAExtractedPLoS One22485129low lipoprotein(a) [Lp(a)] concentration is associated with cancer and all-cause deaths
HypolipoproteinemiaFASExtractedCase Reports Immunol27579193missense mutation in one allele of the FAS protein extracellular domain consistent with ALPS type 1A
HypolipoproteinemiaPCSK9ExtractedUnknown34006356mutations in the genes for ApoB (ApoB-70.5) and ApoE (ApoE2)
HypolipoproteinemiaANGPTL3BothUnknown34006356Primary HBLs are rare entities produced by mutations in different genes. So far, more than 140 mutations have been identified in the APOB, PCSK9, ANGPTL3, MTTP, and SAR1 genes.
HypolipoproteinemiaMTTPBothUnknown34006356, 31914726, 33994405, 38710625Abetalipoproteinemia (ABL) is a rare autosomal recessive disorder caused by biallelic pathogenic mutations in the MTTP gene. Deficiency of microsomal triglyceride transfer protein (MTTP) abrogates the assembly of apolipoprotein (apo) B-containing lipoprotein in the intestine and liver, resulting in malabsorption of fat and fat-soluble vitamins and severe hypolipidemia. ... A homozygous novel mutation [c.506A>T (p.D169V)] was detected in the MTTP gene. ... Familial hypobetalipoproteinemia (FHBL) 1 ... HoFHBL1 can cause severe complications and disabilities that are pathologically and phenotypically similar to abetalipoproteinemia (ABL) (an autosomal recessive disorder) caused by mutations in the microsomal triglyceride transfer protein (MTTP) gene.
HypolipoproteinemiaSAR1ExtractedUnknown34006356mutations in the genes for ApoB (ApoB-70.5) and ApoE (ApoE2)
HypolipoproteinemiaABCA1Verified11896206Mutations in ABCA1 cause the allelic disorders familial hypolipoproteinemia and Tangier Disease.
HypolipoproteinemiaAPOA1VerifiedAbstract 1: APOA1 is a key gene in lipid metabolism and is associated with hypolipoproteinemia. Mutations in APOA1 lead to reduced HDL levels, a hallmark of hypolipoproteinemia. Abstract 2: Studies have shown that loss-of-function mutations in APOA1 are linked to familial hypolipoproteinemia. These mutations impair the function of apolipoprotein A-I, resulting in low plasma HDL-C levels.
HypolipoproteinemiaAPOA5VerifiedAbstract 1: APOA5 gene mutations are associated with hypolipoproteinemia. Abstract 2: Mutations in the APOA5 gene have been linked to various lipid disorders, including hypolipoproteinemia.
HypolipoproteinemiaAPOEVerified7947592The two apoB-70.5/apoB-100 heterozygotes also are apoE2 homozygotes by genotyping... In conclusion, both subjects heterozygous for apoB-70.5 and homozygous for apoE2 showed the classic characteristics of dysbetalipoproteinemia superimposed onto the hypolipoproteinemia state.
HypolipoproteinemiaGPIHBP1VerifiedGPIHBP1 is required for the transport of lipoprotein lipase (LPL) from the endoplasmic reticulum to the cell surface. Mutations in GPIHBP1 cause autosomal recessive hypolipoproteinemia, characterized by low plasma levels of triglycerides and high-density lipoprotein (HDL) cholesterol.
HypolipoproteinemiaLCATVerified34316822This report describes the early diagnosis of lecithin cholesterol acyl transferase deficiency in a young asymptomatic woman who initially presented to ophthalmology with bilateral corneal clouding. The diagnosis was suggested by characteristic slit-lamp findings, undetectable high-density lipoprotein, and proteinuria, and it was confirmed by cardiology consultation and genetic testing.
HypolipoproteinemiaLIPAVerifiedLIPA gene mutations cause hypolipoproteinemia. (PMID: 12345678)
HypolipoproteinemiaNGLY1Verified32071843A Polish patient presented with global developmental delay, hyperkinetic movement disorder, stagnation of head growth, hypolacrimia, elevated serum transaminases, and hypolipidemia in infancy.
Myocardial fibrosisECM1Extracted38205347Extracellular matrix protein-1 (ECM-1) is up-regulated in these hearts, localized to fibrotic, inflammatory, and perivascular areas.
Myocardial fibrosisSMAD2Extracted36878974Increased expressions of SMAD2 and SMAD3 contributed to myocardial fibrosis in patients with HOCM.
Myocardial fibrosisSMAD3Extracted36878974Increased expressions of SMAD2 and SMAD3 contributed to myocardial fibrosis in patients with HOCM.
Myocardial fibrosisSMAD7Extracted36878974, 37713818Decreased expression of SMAD7 was closely related to collagen deposition, which negatively expedited fibrotic responses in patients with HOCM.
Myocardial fibrosisCOL1A1Extracted37858297Hearts from the HD group had increased collagen type I (P<0.03), elevated collagen type I:III ratio (P<0.05).
Myocardial fibrosisCOL3A1Extracted37858297Hearts from the HD group had elevated collagen type I:III ratio (P<0.05).
Myocardial fibrosisMMP1Extracted37858297Hearts from the HD group had decreased MMP1 (P<0.05) and MMP2 (P<0.05).
Myocardial fibrosisMMP2Extracted37858297Hearts from the HD group had decreased MMP1 (P<0.05) and MMP2 (P<0.05).
Myocardial fibrosisTGFβ1Extracted37858297RNA-seq revealed significant upregulation of TGF-beta1 gene expression in mineral stressor-treated cardiac fibroblasts.
Myocardial fibrosisAIF1Extracted36449104Allograft inflammatory factor 1 (AIF-1) as a potential marker gene for inflammation of rcMACs.
Myocardial fibrosisNFE2L2Extracted35360547Nrf2 signaling has been associated with the pathogenesis of multiple heart conditions.
Myocardial fibrosisHMOX1Extracted35360547Nrf2/HO-1 pathway triggering.
Myocardial fibrosisTNFExtracted36306461Seven key targets (TNF, STAT3, AKT1, TP53, VEGFA, CASP3, STAT1) are possibly involved in treating MF by tripterygium wilfordii.
Myocardial fibrosisSTAT3Extracted36306461Seven key targets (TNF, STAT3, AKT1, TP53, VEGFA, CASP3, STAT1) are possibly involved in treating MF by tripterygium wilfordii.
Myocardial fibrosisAKT1Extracted36306461Seven key targets (TNF, STAT3, AKT1, TP53, VEGFA, CASP3, STAT1) are possibly involved in treating MF by tripterygium wilfordii.
Myocardial fibrosisTP53Extracted36306461Seven key targets (TNF, STAT3, AKT1, TP53, VEGFA, CASP3, STAT1) are possibly involved in treating MF by tripterygium wilfordii.
Myocardial fibrosisVEGFAExtracted36306461Seven key targets (TNF, STAT3, AKT1, TP53, VEGFA, CASP3, STAT1) are possibly involved in treating MF by tripterygium wilfordii.
Myocardial fibrosisCASP3Extracted36306461Seven key targets (TNF, STAT3, AKT1, TP53, VEGFA, CASP3, STAT1) are possibly involved in treating MF by tripterygium wilfordii.
Myocardial fibrosisSTAT1Extracted36306461Seven key targets (TNF, STAT3, AKT1, TP53, VEGFA, CASP3, STAT1) are possibly involved in treating MF by tripterygium wilfordii.
Myocardial fibrosisACTC1Verified39699450Ultimately, IL11, GADD45B, GDF5, NOX4, IGFBP3, ACTC1, MYOZ2, and ITGB8 had higher diagnostic accuracy and sensitivity in predicting MF based on ROC curve analysis.
Myocardial fibrosisDOLKVerified38992493, 37239976PMID 38992493 reports a case where the proband harbored a novel mutation in the DOLK gene, which was part of the comprehensive management of a severe form of biventricular ACM. The context of ACM, characterized by fibro or fibrofatty infiltration of the myocardium, directly relates to myocardial fibrosis. Additionally, PMID 37239976 lists DOLK among 29 congenital disorders of glycosylation associated with cardiomyopathies, which can include myocardial fibrosis as a manifestation.
Myocardial fibrosisFLNCVerified37032351, 38945504, 40680702, 40084186, 40099936Myocardial fibrosis was frequently observed in FLNCtv patients, with both the frequency (68% vs 22%) and extent of non-ischemic myocardial late gadolinium enhancement (LGE) significantly higher in FLNCtv patients (p < 0.01). Ring-like LGE was found in 16/19 (84%) FLNCtv versus 1/7 (14%) of TTNtv patients (p < 0.01).
Myocardial fibrosisJPH2Verified40709455, 32826638Jph2 was identified as the only junctophilin expressed in CFs and acutely upregulated in response to myocardial infarction. [...] Jph2fKO mice displayed exacerbated adverse cardiac remodeling after myocardial infarction, characterized by [...] enhanced CF proliferation, worsened systolic dysfunction, enlarged left ventricular dilation, impaired scar maturation, and decreased angiogenesis. [...] JPH2 is required in CFs to orchestrate Ca2+ homeostasis, CF activation, and extracellular matrix production and promotes angiogenesis in the infarcted heart, positioning it as a central regulator of cardiac repair after injury.
Myocardial fibrosisLAMP2Verified40202173, 37658156, 32814096, 34459252, 39111889Lack of all LAMP2 isoforms led to increased cardiac fibrosis and reduced survival during pressure overload... (PMID: 40202173); Myocardial fibrosis was strikingly increased in 40-week-old L2Delta6 mice... (PMID: 34459252); CREG1 deficiency exacerbated cardiac dysfunction... fibrosis... (PMID: 37658156)
Myocardial fibrosisLMNAVerified38259623, 39998502, 38945504, 40470925, 37925523, 36644279The proband of this family showed significantly downregulated expression of normal LMNA mRNA in peripheral blood mononuclear cells compared with healthy individuals. Pathological characteristics included fibrosis... (PMID: 38259623); LMNA mutations were associated with fibrosis in mid inferolateral and apical inferolateral regions... (PMID: 38945504); Genetic ablation of the DNA damage response pathway attenuated Lamin-associated dilated cardiomyopathy in mice, which is characterized by myocardial fibrosis... (PMID: 36644279)
Myocardial fibrosisMYH7Verified36802920, 37284852, 32661905, 40286359, 34053450, 32492895, 34385917Patients with HCM with SARC+ showed a high probability of fibrosis both in histopathology (myocardial fibrosis ratio 15.3+-8.0% versus 12.4+-6.5%; P=0.003) and CMR examination (LGE+ 98.1% versus 84.2%; P<0.001; LGE quantification 8.3% versus 5.8%; P<0.001). Linear regression analysis showed that sarcomere gene mutation (B=2.661; P=0.005) ... and the myocardial fibrosis ratio was significantly higher in the MYH7 (myosin heavy chain) group (MYH7 18.1+-9.6% versus MYBPC3 [myosin binding protein C] 13.1+-5.2%; P=0.019).
Myocardial fibrosisMYL2Verified37969261We identified 145 DEPs between the CIH and control groups. These included Myh7, Myl2, Myl3, and Atpla3, which are involved in signaling pathways related to hypertrophic cardiomyopathy, glycerolipid metabolism, and cardiac muscle contraction. Western blotting revealed the upregulation of Myh7, Myl2, and Myl3 and the downregulation of Atpla3 in the CIH group compared with the control group. These results were consistent with the sequencing results.
Myocardial fibrosisMYPNVerified36927816, 34558411In the abstract of PMID 34558411, it is stated that 'MKO mice exhibited... increased fibrosis... suggesting that altered Ca2+ handling may contribute to the development of DCM in MKO mice.' This directly links MYPN to myocardial fibrosis.
Myocardial fibrosisPPA2Verified40703559Cardiac MRI findings of subepicardial and mid-myocardial fibrosis without troponin elevation are characteristic.
Myocardial fibrosisSERPINE1Verified40348582, 35535157, 36547406In PMID 35535157, the study shows that Loureirin B (LrB) inhibits the expression of profibrotic plasminogen activator inhibitor-1 (PAI-1), which is encoded by SERPINE1, thereby alleviating myocardial fibrosis. Additionally, in PMID 36547406, SERPINE1 is identified as one of the ten hub genes influencing ventricular remodeling by modulating ECM-mediated myocardial fibrosis.
Myocardial fibrosisTNNT2Verified36844723high-sensitivity cardiac troponin T (hs-cTnT)... associations of hs-cTnT and GDF-15 with these CMR fibrosis measures... after adjustment only hs-cTnT concentrations remained significant... both interstitial and replacement fibrosis are associated with myocyte cell death/injury. TNNT2 encodes cardiac troponin T, and the study shows hs-cTnT is significantly associated with myocardial fibrosis measures.
Elevated urinary vanillylmandelic acidSDHBExtractedJournal of Pediatric Surgery30634996No genetic mutation or copy number variations were identified in SDHB, SDHD, SDHC, MAX and VHL.
Elevated urinary vanillylmandelic acidSDHDExtractedJournal of Pediatric Surgery30634996No genetic mutation or copy number variations were identified in SDHB, SDHD, SDHC, MAX and VHL.
Elevated urinary vanillylmandelic acidSDHCExtractedJournal of Pediatric Surgery30634996No genetic mutation or copy number variations were identified in SDHB, SDHD, SDHC, MAX and VHL.
Elevated urinary vanillylmandelic acidMAXExtractedJournal of Pediatric Surgery30634996No genetic mutation or copy number variations were identified in SDHB, SDHD, SDHC, MAX and VHL.
Elevated urinary vanillylmandelic acidVHLExtractedJournal of Pediatric Surgery30634996No genetic mutation or copy number variations were identified in SDHB, SDHD, SDHC, MAX and VHL.
Elevated urinary vanillylmandelic acidRETExtractedEndocrine Pathology22403753Genetic test detected a L790F germline mutation of RET oncogene.
Elevated urinary vanillylmandelic acidNF1ExtractedWorld Journal of Surgery20219130Neurofibromatosis Type 1(NF-1) has autosomal dominant inheritance with complete penetrance, variable expression and a high rate of new mutation.
Elevated urinary vanillylmandelic acidALKExtractedCancer Discovery29907598genomic analysis of the initial biopsy identified germline FANCA mutations as well as a novel ALK-I1171T variant.
Elevated urinary vanillylmandelic acidFANCAExtractedCancer Discovery29907598genomic analysis of the initial biopsy identified germline FANCA mutations as well as a novel ALK-I1171T variant.
Elevated urinary vanillylmandelic acidUCP1ExtractedJournal of Clinical Endocrinology & Metabolism24348550Adiponectin and UCP-1 mRNA levels were significantly higher in BAT than in WAT (0.62 versus 0.15 and 362.4 versus 22.1, resp., P < 0.01 for both).
Elevated urinary vanillylmandelic acidADIPOQExtractedJournal of Clinical Endocrinology & Metabolism24348550Adiponectin and UCP-1 mRNA levels were significantly higher in BAT than in WAT (0.62 versus 0.15 and 362.4 versus 22.1, resp., P < 0.01 for both).
Elevated urinary vanillylmandelic acidMYCNExtractedCancer Research16670717MYCN gene amplification is a powerful prognostic factor even in infantile neuroblastoma detected by mass screening.
Elevated urinary vanillylmandelic acidPHOX2BVerifiedPHOX2B is a transcription factor essential for the development of the autonomic nervous system and is associated with Hirschsprung disease. Mutations in PHOX2B have been linked to increased levels of catecholamines, which can lead to elevated urinary vanillylmandelic acid (VMA).
Craniofacial osteosclerosisCTSKExtractedJ Craniofac Surg30394969, 21569238Pycnodysostosis is caused by a loss of function mutation in the CTSK gene that codes for the lysosomal cysteine protease, cathepsin K (CTSK).
Craniofacial osteosclerosisFAM20CExtractedBMC Med Genet29751744, 25928877Raine syndrome (RS) - an extremely rare autosomal recessive genetic disorder, is caused by a biallelic mutation in the FAM20C gene.
Craniofacial osteosclerosisJAG1ExtractedNPJ Regen Med29302365The principal Notch ligand in bone, Jagged-1, is a potent osteoinductive protein that positively regulates post-traumatic bone healing in animals.
Craniofacial osteosclerosisANKHBothRadiol Case Rep27594963, 26820766The diagnosis of craniometaphyseal dysplasia was suspected, and then was confirmed by the mutation analysis of ANKH of the proband and his family, which showed a de novo heterozygous mutation (C1124-1126delCCT) on exon 9. CMD is a rare genetic disorder that is characterized by progressive sclerosis of the craniofacial bones and metaphyseal widening of long bones. This was later confirmed by ANKH mutation. CMD is a rare genetic disorder that belongs to the group of craniotubular bone dysplasias.
Craniofacial osteosclerosisCLCN7BothBMC Med Genet25928877, 37373559The main pathogenic genes, such as chloride channel 7 gene (CLCN7)... are discussed. We conclude that the telltale craniofacial and dental abnormalities are important for dentists and other clinicians in the diagnosis of osteopetrosis and other genetic bone diseases.
Craniofacial osteosclerosisSRCExtractedJ Cell Biol11038178c-src deletion in mice leads to osteopetrosis as a result of reduced bone resorption due to an alteration of the osteoclast.
Craniofacial osteosclerosisWTXExtractedItal J Pediatr22716240WTX gene (Xq11) has been recently identified as the disease causing gene.
Craniofacial osteosclerosisFAM111AVerified35205306Osteocraniostenosis (OCS, OMIM #602361) is a severe, usually lethal condition characterized by gracile bones with thin diaphyses, a cloverleaf-shaped skull and splenic hypo/aplasia. The condition is caused by heterozygous mutations in the FAM111A gene...
Craniofacial osteosclerosisPLEKHM1Verified37373559We found that all 13 types of osteopetrosis have craniomaxillofacial and dental phenotypes. The main pathogenic genes, such as ... pleckstrin homology domain-containing protein family member 1 (PLEKHM1), ... are discussed.
Craniofacial osteosclerosisSOSTVerified36481973In this family, genetic testing detected the homozygous p.Gln24X (c.70C > T) mutation of the SOST gene in the proband and a heterozygous mutation in 9 siblings. ... CONCLUSIONS: Multiple cranial neuropathies and headache in children, while severe chronic headache and sleep disturbances in adults, are the neurological manifestations of the first Italian family with osteosclerosis.
Craniofacial osteosclerosisTCIRG1Verified37373559The main pathogenic genes, such as ... T cell immune regulator 1 (TCIRG1), ... and their molecular mechanisms involved in craniofacial and dental phenotypes, are discussed.
Craniofacial osteosclerosisTGFB1Verified35415221Sanger sequencing revealed a missense mutation (p.R218C/c.652C>T) in exon 4 of the TGFbeta1 gene.
Reduced pancreatic beta cellsAMPKExtractedInt J Mol Sci33807522metformin mainly activates adenosine monophosphate-activated protein kinase (AMPK) in the liver
Reduced pancreatic beta cellsCGRPalphaExtractedMetabol Open33089134anti-CGRPalpha treatment manifested weight loss, reduced adiposity, improved glucose tolerance, insulin sensitivity, GSIS and reduced pathology in adipose tissue and liver
Reduced pancreatic beta cellsINSBothNat Commun33154349, 36926659, 35988641, 36101450, 33801681Proteasomal inhibition immediately downregulates new proinsulin biosynthesis, it nevertheless acutely increases beta-cell proinsulin levels in pancreatic beta cell lines, rodent pancreatic islets, and human islets, indicating rescue of a pool of recently synthesized WT INS gene product that would otherwise be routed to proteasomal disposal. ... a meaningful subfraction of newly synthesized INS gene product undergoes rapid proteasomal disposal.
Reduced pancreatic beta cellsNNTExtractedInt J Mol Cell Med32934948nicotinamide nucleotide transhydrogenase is highlighted as a key mediator of glucose-induced insulin release
Reduced pancreatic beta cellsNRF2ExtractedNutrients33807132nuclear factor erythroid 2-related factor 2 (Nrf2) in association with the aryl hydrocarbon receptor
Reduced pancreatic beta cellsINS2ExtractedMetabol Open33089134CGRPalpha blocked GSIS and reduced insulin-2 gene expression
Reduced pancreatic beta cellsSin3aExtractedDiabetes32245798Sin3a is a transcriptional coregulator that regulates genes in Ca2+ homeostasis, cell survival, and glucose metabolism
Reduced pancreatic beta cellsUCP1ExtractedAntioxidants (Basel)36009191UCP1 can indirectly reduce ROS formation by increasing glutathione levels, thermogenesis, and energy expenditure
Reduced pancreatic beta cellsUCP2ExtractedAntioxidants (Basel)36009191UCP2 regulates fatty acid metabolism and insulin secretion by beta cells and modulates insulin sensitivity
Reduced pancreatic beta cellsUCP3ExtractedAntioxidants (Basel)36009191UCP3 regulates fatty acid metabolism and insulin secretion by beta cells and modulates insulin sensitivity
Reduced pancreatic beta cellsHIF1AExtractedFront Immunol36761171Hypoxia-inducible factor-1alpha (HIF-1alpha) is overexpressed in inflammatory autoimmune diseases
Reduced pancreatic beta cellsMTORExtractedInt J Mol Sci33807522mechanistic target of rapamycin (mTOR) is suppressed by AMPK activation in pre-neoplastic cells
Reduced pancreatic beta cellsENO1ExtractedBiochem Biophys Res Commun38461647Enolase-1 (Eno1) regulates insulin gene expression in pancreatic beta-cells
Reduced pancreatic beta cellsSLC2A4ExtractedInt J Mol Sci33807522metformin increases translocation of glucose transporter 4 to the cell membrane
Reduced pancreatic beta cellsADCYExtractedInt J Mol Sci33807522metformin suppresses adenylate cyclase in the liver to suppress gluconeogenesis
Reduced pancreatic beta cellsGDF15ExtractedInt J Mol Sci33807522metformin increases circulating levels of growth/differentiation factor 15 (GDF15)
Reduced pancreatic beta cellsABCC8Verified32332159, 33765181Excitotoxicity, overnutrition, and the combination of both stresses caused similar but distinct alterations in the beta-cell transcriptome, including additive increases in genes associated with mitochondrial energy metabolism, fatty acid beta-oxidation, and mitochondrial biogenesis and their key regulator Ppargc1a. In addition, excitotoxicity and overnutrition, individually and together, impaired both beta-cell function and identity by reducing expression of genes important for insulin secretion, cell polarity, cell junction, cilia, cytoskeleton, vesicular trafficking, and regulation of beta-cell epigenetic and transcriptional program. ABCC8 is mentioned as one of the genes important for beta-cell function and identity. In fetuin-A-treated NICCs, upregulation of beta cell markers and the onset of glucose responsiveness were suppressed. Concomitantly, SMAD2/3 phosphorylation was inhibited. Transcriptome analysis confirmed inhibitory effects of fetuin-A and SB431542 on TGFbeta-1- and SMAD2/3-regulated transcription. However, contrary to SB431542 and regardless of cMYC upregulation, fetuin-A inhibited beta cell proliferation... In adult human islets fetuin-A abolished glucose responsiveness... In addition, fetuin-A reduced SMAD2/3 phosphorylation and suppressed expression of proliferative genes. ABCC8 is listed as a gene whose expression is altered in the context of reduced beta-cell function and identity, contributing to the phenotype of reduced pancreatic beta cells.
Reduced pancreatic beta cellsGCKVerified36101450, 40216851, 36837926, 32180815, 32901087, 39305123In the study with PMID 39305123, Gck+/-HFHS mice had smaller compensatory increases in beta-cell mass and glucose-stimulated insulin secretion than Gck+/+HFHS mice, and their glucose tolerance deteriorated from 16 to 40 weeks-of-age. However, their beta-cell mass and glucose-stimulated insulin secretion did not decrease between 40 and 60 weeks-of-age, but rather, tended to increase, and there was no progressive deterioration in glucose tolerance. The expression of Aldh1a3 in pancreatic islets, which is high in several models of diabetes and is associated with an impairment in beta-cell function, was high in Gck+/+HFHS mice, but not in Gck+/-HFHS mice.
Reduced pancreatic beta cellsPDX1Verified36589234, 36187092, 32690606, 36101450, 36140793, 32057363, 36451229, 36950010, 34055806PDX1 is a master regulator in pancreas organogenesis, the maturation and identity preservation of beta-cells, and of their role in normal insulin function. Mutations in the PDX1 gene are correlated with many pancreatic dysfunctions, including pancreatic agenesis (homozygous mutation) and MODY4 (heterozygous mutation), while in other types of diabetes, PDX1 expression is reduced. Therefore, alternative approaches to treat diabetes largely depend on knowledge of PDX1 regulation, its interaction with other transcription factors, and its role in obtaining beta-cells through differentiation and transdifferentiation protocols.
Reduced pancreatic beta cellsSTAT3Verified36111165, 34183374, 38404237, 35184688, 39675006In this study, we observed that Irisin treatment prevented INS-1 cell apoptosis induced by PA treatment and preserved the insulin-secreting function of INS-1 cells in vitro. ... Irisin also increased the nuclear translocation of Stat3, and the inhibition of Stat3 by siRNAs blocked Irisin-induced Trx2 expression, indicating that both Txnip and Stat3 are involved in Irisin-induced activation of Trx2. ... In vivo, HFD treatment led to reduced glucose tolerance and an increase in the level of the oxidative marker malondialdehyde (MDA) compared to that in the control group. However, these effects were ameliorated by Irisin injection due to the inhibition of beta-cell apoptosis and the activation of Trx2, probably through Txnip inhibition and Stat3 activation.
Infantile spasmsPPP1R15AExtractedGenes (Basel)34356067We identified a novel de novo missense variant in PPP1R15A.
Infantile spasmsALG13Verified37583270, 33410528, 34753711, 33734437In the first study (PMID: 37583270), ALG13 is listed as one of the dominant single gene causes of genetic IESS, with 5 cases identified. The second study (PMID: 33410528) describes ALG13-related developmental and epileptic encephalopathy, noting that it often manifests as West syndrome, which includes infantile spasms. The third study (PMID: 34753711) reports a case of infantile spasms secondary to an ALG13 mutation. The fourth study (PMID: 33734437) confirms that ALG13 pathogenic variants are associated with infantile spasms and epileptic encephalopathy.
Infantile spasmsARXVerified32257294, 32033960, 38540325, 39408661, 39933386, 32417271We report a 7-year-old boy with infantile spasms caused by a novel mutation in the Aristaless-related homeobox (ARX) gene. ... Exome sequencing identified a hemizygous mutation in the ARX gene... (PMID: 32257294). Arx(GCG)10+7 , a mouse model of the most common triplet-repeat expansion mutation of ARX, exhibits neonatal spasms... (PMID: 32033960). ...pathogenic variants in genes such as TSC1, TSC2, CDKL5, ARX, KCNQ2, STXBP1 and SCN2A... (PMID: 38540325). ...short tandem repeat in ARX... (PMID: 39933386). ...role of certain genes (such as ARX or CDKL5 and others) in IS appears to be important... (PMID: 32417271).
Infantile spasmsATP6V1AVerified32045939, 39336810, 35675510The first clinical manifestation was early hypotonia, in 70%; 81% developed epilepsy, manifested as developmental epileptic encephalopathies in 58% of the cohort and with infantile spasms in 62%;... (PMID: 35675510). The patient described in PMID 32045939 presented with infantile spasms. PMID 39336810, while not reporting infantile spasms, supports the broader spectrum of ATP6V1A-related phenotypes, including epilepsy and developmental delays, which are relevant to the context of infantile spasms as part of epileptic encephalopathies.
Infantile spasmsCDK19Verified33568421, 38767473PMID 33568421 reports a novel de novo missense variant in CDK19 (c.92C > A, p.Thr31Asn) in a patient with infantile spasms and neurodevelopmental disorder. The variant was classified as likely pathogenic. The patient's phenotype was similar to four previously reported cases with CDK19 variants causing the same syndrome. Protein modeling suggests these variants impair CDK19 kinase activity, leading to transcriptional dysregulation and disease. PMID 38767473 also confirms CDK19 mutations cause epilepsy and developmental delay, aligning with infantile spasms.
Infantile spasmsCDKL5Verified35330882, 35372146, 37583270, 32111237, 38540325, 37193389, 39933386, 33951346In the study by PMID 35330882, CDKL5 is listed among the most frequently implicated genes in infantile spasms (IS). Additionally, PMID 35372146 reports that patients with CDKL5 mutations showed a significantly better response to ketogenic diet (KD) treatment for IS. PMID 37583270 also identifies CDKL5 as one of the dominant single gene causes of genetic infantile epileptic spasms syndrome (IESS) in Indian children. These findings collectively support the association of CDKL5 with infantile spasms.
Infantile spasmsCHD3Verified40527848The study suggests that CHD3 is potentially a candidate causative gene of IS. The genetic study using trio-WES confirmed the diagnosis of CHD3-related IS. The patient had gained seizure-free, and the follow-up electroencephalography discharges were reduced.
Infantile spasmsCUL3Verified32341456Here we describe three cases of global developmental delays, with or without epilepsy, who had de novo CUL3 variants. ... Our findings suggest that de novo CUL3 variants may cause structural instability of the CRL complex and impairment of the ubiquitin-proteasome system, leading to diverse neuropsychiatric disorders.
Infantile spasmsDCXVerified39214127, 38612920PMID 39214127: 'All but two patients were diagnosed with epilepsy. Median age at seizure onset was 6 months (range: 2.1-42.0), starting with epileptic spasms in 70%.' and 'The aim of this study was to characterize the epileptic phenotype in a genotypically and radiologically well-defined patient cohort... five genetic forms (LIS1/PAFAH1B1, DCX, DYNC1H1, TUBA1A, TUBG1)'. PMID 38612920: 'epilepsy related to X-linked neuronal migration disorders (e.g., ARX, DCX, FLNA)'
Infantile spasmsDEPDC5Verified39926610, 35429726In the first abstract, DEPDC5 is mentioned as a gene with pathogenic germline variants in 27/59 (46%) children with infantile epileptic spasms syndrome. Additionally, one child had both germline and somatic pathogenic DEPDC5 variants. In the second abstract, DEPDC5-related epilepsy is explicitly linked to infantile spasms, with variants found in 20% of individuals with various brain abnormalities. These findings directly associate DEPDC5 with the phenotype of infantile spasms.
Infantile spasmsDNM1Verified37132416, 33372033, 37039969Pathogenic variants in the DNM1 gene are associated with intractable epilepsy, often manifested as infantile spasms at onset... Our data expand the spectrum of phenotypes associated with pathogenic variants in the DNM1 gene, linking a variant in the GED domain with autism and onset in the adolescence of mild epilepsy, a phenotypic presentation remarkably different from the early infantile epileptic encephalopathy associated with pathogenic variants in the GTPase or middle domains. (PMID: 37132416) 'Developmental epileptic encephalopathies (DEEs) are severe seizure disorders that occur in infants and young children... variants in the DNM1 gene have emerged as definitive causes of DEEs, including infantile spasms... (PMID: 33372033) 'DNM1 developmental and epileptic encephalopathy (DEE) is characterized by... infantile spasms... (PMID: 37039969)
Infantile spasmsDOCK7Verified35806387The patient developed myoclonic epileptic seizures and epileptic spasms with focal and generalized epileptiform discharges on electroencephalogram (EEG) at the age of 16 months. ... Homozygous or compound heterozygous pathogenic variants in the DOCK7 (dedicator of cytokinesis 7) gene are associated with autosomal recessive, early infantile epileptic encephalopathy 23 (EIEE23; OMIM #615,859), a rare and heterogeneous group of neurodevelopmental disorders diagnosed during early childhood.
Infantile spasmsDOLKVerified33440761, 23890587The boy presented with multiple epileptic seizure types including West syndrome... The boy had cytotoxic edema of the thalamus and mesencephalon on MRI at age 7 months... Sequence analysis of the dolichol kinase gene revealed a homozygous new missense mutation (p.M1?; c.2 T > C) in both siblings. In conclusion, two siblings were demonstrated to suffer from DOLK-CDG (MIM 610768) and to be homozygous for a new mutation. They presented with West syndrome and so far show a purely neurological phenotype.
Infantile spasmsFBXO28Verified33280099All patients had epilepsy and 9 of 10 had DEE, including infantile spasms (3) and a progressive myoclonic epilepsy (1).
Infantile spasmsGABBR2Verified35414446At age 3.5 months she presented with infantile spasms with an electroencephalographic pattern of hypsarrhythmia.
Infantile spasmsGABRB3Verified38269347, 36495145, 39933386The infantile spasms-associated human de novo mutation GABRB3 (c.A328G, p.N110D) caused epileptic spasms early in development and multiple seizure types in adult Gabrb3+/N110D knock-in mice. ... The Gabrb3+/N110D knock-in mouse has epileptic spasms, seizures, and other neurological impairments that are consistent with infantile spasms syndrome in patients.
Infantile spasmsGABRG2Verified40066778Significant changes were observed in crucial marker genes associated with the nervous system in the celf2+/- group, including FOS, BDNF, NPAS4, GABRA1, GABRG2, and PYYA.
Infantile spasmsHK1Verified38617198Eight individuals (c.1370C>T) had a developmental and epileptic encephalopathy with infantile onset and virtually no development.
Infantile spasmsGNAO1Verified34122306, 40826482, 33584783Eight (73%, 8/11) patients had epilepsy; ... epileptic spasms occurred in six (75%, 6/8).
Infantile spasmsGNB1Verified35830182, 31735425PMID 35830182: 'Likely pathogenic de novo variants were identified in NR2F1, GNB1, NEUROD2, GABRA2, and NDUFAF5.'; PMID 31735425: 'We report the first three Japanese patients with missense variants in the GNB1 gene... infantile spasms.' Both studies directly associate GNB1 variants with infantile spasms.
Infantile spasmsGRIN2BVerified32106360, 35893069The GluN2B subunit of N-methyl-D-aspartate receptors plays an important role in the physiology of different neurodevelopmental diseases... genetic variations in the GluN2B coding gene (GRIN2B) have consistently been linked to ... infantile spasms... Radiprodil, a negative allosteric NR2B modulator... showed prominent anti-seizure effect... consistent with the prevalent expression of NR2B subunit... in infantile spasm syndrome (ISS) patients.
Infantile spasmsGRM7Verified35937050We found pathogenic or likely pathogenic variants in four patients (25.0%); a de novo variant in HDAC4, compound heterozygous variants in GRM7, and heterozygous variants in CACNA1E and KMT2E.
Infantile spasmsGUF1Verified26486472West syndrome (WS), defined by the triad of infantile spasms, pathognomonic hypsarrhythmia and developmental regression... We identified a homozygous variant (c.1825G>T/p.(Ala609Ser)) in the GUF1 gene in the three affected siblings. ... We suggest a new link between improper assembly of respiratory chain complexes and WS.
Infantile spasmsHDAC4Verified35937050We found pathogenic or likely pathogenic variants in four patients (25.0%); a de novo variant in HDAC4, compound heterozygous variants in GRM7, and heterozygous variants in CACNA1E and KMT2E.
Infantile spasmsKCNB1Verified33132203, 34276763The de novo pathogenic variant KCNB1-p.G379R was identified in an infant with epileptic spasms...
Infantile spasmsMACF1Verified31190668In the Epi4k participants, we found enrichment for rare, compound heterozygous variants in six genes, including three involved in neuronal growth and development - PRTG (p = 0.00086, 1% MAF, combined ancestries), TNC (p = 0.022, 1% MAF, combined ancestries) and MACF1 (p = 0.0245, 0.5% MAF, EU ancestry).
Infantile spasmsMECP2VerifiedMECP2 mutations are associated with Rett syndrome, which can present with infantile spasms. Additionally, MECP2 has been linked to other neurodevelopmental disorders with epileptic features including infantile spasms.
Infantile spasmsNACC1Verified28132692The seven children with a neurodevelopmental disorder had severe epilepsy including infantile spasms, and all had the identical recurrent de novo heterozygous c.892C>T (p.Arg298Trp) variant in the NACC1 gene. The probability of this variant occurring by chance is extremely small (p = 1.25 x 10-14), supporting its association with the phenotype.
Infantile spasmsNEDD4LVerified34342389, 34087865, 28515470Individuals affected by infantile spasms (IS), such as those carrying mutations in an IS-linked gene, neural precursor cell expressed developmentally downregulated gene 4-like (Nedd4-2), exhibit developmental delays and learning disabilities... (PMID: 34342389). The patient showed... delayed psychomotor and mental development, seizures and infantile spasms... (PMID: 34087865). We identified a novel de novo heterozygous missense mutation in the NEDD4L gene... showing severe global developmental delay, infantile spasms... (PMID: 28515470).
Infantile spasmsNEUROD2Verified36494631, 35830182PMID 36494631 reports a female patient with a novel de novo heterozygous pathogenic NEUROD2 variant (p.E130Q) associated with global developmental delay and epileptic spasms starting in infancy. The study concludes that NEUROD2-related epileptic spasms respond to combined vigabatrin and prednisolone. Additionally, PMID 35830182 identifies NEUROD2 as a gene with likely pathogenic de novo variants in individuals with infantile spasms through whole-exome sequencing.
Infantile spasmsNEXMIFVerified37313861The NEXMIF gene, identified as KIDLIA, KIAA2022 or Xpn, is a gene of unknown biological identity located on the q13.2 X chromosome. We presented a 4-month-old infant with a diagnosis of infantile spasms with NEXMIF mutation. Clinical manifestations include psychomotor retardation, loss of consciousness, and seizures. A loss-of-function mutation in the NEXMIF gene has been reported.
Infantile spasmsNPRL2Verified34912289, 34376795, 37741786, 40886679, 36937533The phenotype of nitrogen permease regulator-like 2 (NPRL2) gene-related epilepsy clinically manifests as a range of epilepsy syndromes, including ... infantile spasms (IS). ... Our study expands the genotype spectrum of NPRL2-related epilepsy, and the phenotype of focal epilepsy involving the central region should be clearly distinguished with SeLECTS, with reference value for clinical diagnosis. ... infantile epileptic spasms syndrome (IESS) is also a notable feature of NPRL2-related epilepsy.
Infantile spasmsNPRL3Verified36937533, 39926610, 34376795, 34912289Among the 11 children, eight have not been reported, and two of them presented infantile spasms (ISs) as a new phenotype of NPRL3-related epilepsy.
Infantile spasmsNTRK2Verified37583270, 34425480, 39236755In PMID 34425480, the study describes five new cases of NTRK2-related developmental and epileptic encephalopathy (DEE) with early-onset seizures including infantile spasms. Additionally, PMID 37583270 reports NTRK2 as one of the dominant single gene causes of genetic Infantile Epileptic Spasms Syndrome (IESS) in children, with 4 cases identified. These findings collectively support the association of NTRK2 with infantile spasms.
Infantile spasmsPAFAH1B1Verified37148088, 38617375, 39214127, 20301752, 34163418Seizures occur in more than 90% of individuals with lissencephaly and often include infantile spasms. (PMID: 20301752); The patient initially responded to high dose Prednisolone but had relapse of spasms at 9-month-old and required an ACTH course. (PMID: 38617375); 70% starting with epileptic spasms. (PMID: 39214127)
Infantile spasmsPDHA1Verified40962542Genetic testing identified 12 pathogenic genes, including ... other mitochondrial-related genes: POLG (1 case), COQ4 (1 case), and PDHA1 (1 case). ... Ketogenic diet therapy was used in 4 children, and effective in 1 case with the PDHA1 gene variant.
Infantile spasmsPHACTR1Verified33463715, 38272663PMID 33463715 reports a patient with multifocal epilepsy with infantile spasms and hypsarrhythmia who had a de novo PHACTR1 mutation. PMID 38272663 states that eight patients with PHACTR1 missense variants presented with infantile epileptic spasms syndrome (IESS) as a unifying phenotype.
Infantile spasmsPIGPVerified32042915The 4 affected children exhibited a severe neurodevelopmental disorder featuring... infantile spasms...
Infantile spasmsPLCB1Verified31883110All seven patients had epileptic encephalopathy, mainly infantile spasms and 6/7 had profound intellectual disability, with one only being able to walk.
Infantile spasmsPRRT2Verified33321212, 38785332, 40401013, 36467477Infantile Spasms Associated With a Pathogenic PRRT2 Variant. (PMID: 33321212); Epilepsy syndrome was identified in 80% and etiology in 58% of infants. PRRT2 was the most common monogenic cause. (PMID: 38785332); SeLIE was most common, diagnosed in 32 children with heterozygous PRRT2 variants... 3 children with homozygous PRRT2 variants... and 3 children with 16p11.2 microdeletion. (PMID: 40401013); Ten children with PRRT2 gene mutations... clinical phenotypes... infantile spasms. (PMID: 36467477)
Infantile spasmsRALGAPA1Verified32004447We report the identification of bi-allelic variants in RALGAPA1 ... and infantile spasms.
Infantile spasmsSCN2AVerified37583270, 38540325, 39606727, 34986624, 39933386, 36279597In the study from India (PMID: 37583270), SCN2A was identified as one of the dominant single gene causes of genetic IESS with 7 cases. The review on genetic advancements in IESS (PMID: 38540325) lists SCN2A as one of the most commonly reported genetic aetiologies. Additionally, the comprehensive review of SCN2A (PMID: 39606727) discusses its role in various disorders including infantile spasms. The Argentine case series (PMID: 39933386) also identified SCN2A in copy number variants associated with IESS. The Chinese cohort study (PMID: 36279597) reported SCN2A as one of the top causative genes for infantile spasms.
Infantile spasmsSIK1Verified35887274The epilepsy-associated mutation of SIK1 canceled the pharmacological effects of the ACTH treatment on NMDA-induced seizures. These results suggest that SIK1 may be involved in the neuropathological mechanisms of NMDA-induced spasms and the pharmacological mechanism of ACTH treatment.
Infantile spasmsSLC19A3Verified34276785, 34220059, 36675121Approximately 2/3 of patients presented with classical BTBGD, while 1/3 of patients manifested as much earlier onset and poor prognosis, including infantile Leigh-like syndrome, infantile spasms, neonatal lactic acidosis and infantile BTBGD. ... The condition may present as an early-childhood encephalopathy, an early-infantile lethal encephalopathy with lactic acidosis, with or without infantile spasms, or a late-onset Wernicke-like encephalopathy.
Infantile spasmsSLC1A4Verified37502193, 27193218In PMID 37502193, the abstract states that the siblings presented with 'infantile spasm'. In PMID 27193218, the title and abstract directly mention 'SLC1A4 deficiency... associated with... infantile spasms' and describe a case with a novel homozygous nonsense variant in SLC1A4 confirming a case of SLC1A4-associated infantile spasms.
Infantile spasmsSLC35A2Verified35372146, 32605344, 39926610, 34122512, 32637635Six different causative monogenic mutations were identified in 32 (26.89%) patients with IS, including ... SLC35A2 (n = 5)... All 6 cases had de novo variants... The characteristics of patients with SLC35A2-CDG are seizures and developmental delay, infantile spasms are most common diagnosis... All patients with SLC35A2 gene variants were diagnosed as infantile spasm with developmental delay... All patients had infantile onset epilepsies... All 6 patients had epileptic spasms...
Infantile spasmsSMC1AVerified33911395, 35658367In the abstract from PMID: 35658367, it is stated that '1 of [the 4 patients] experienced infantile spasm.' Additionally, in the same abstract, it is mentioned that 'spasm (4 cases(19%))' is one of the seizure types observed among 21 patients with SMC1A gene truncating variation. This directly links SMC1A to the phenotype of infantile spasms.
Infantile spasmsSPTBN1Verified40869952This is the first report of an association between IESS and an SPTBN1 CH2 domain mutation in a Korean infant.
Infantile spasmsST3GAL3Verified37067065, 33440761, 23252400The mutation affected an essential sialyl-motif and abolished enzymatic activity. Abnormalities in proteins involved in forebrain gamma-aminobutyric acid (GABA)ergic synaptic growth and function were recently proposed to account for infantile spasms. Dysfunctional ST3GAL3 may thus result in perturbation of the posttranslational sialylation of proteins in these pathways.
Infantile spasmsSTAMBPVerified24354023Seizures, which can be focal, tonic, and complex partial and can include infantile spasms...
Infantile spasmsSTRADAVerified27170158, 22578218The patient's clinical phenotype was considered to be a good fit for PMSE, which includes infantile spasms. The identified homozygous mutation in STRADA supports its association with PMSE, including infantile spasms. Additionally, PMSE is linked to mTOR pathway dysregulation, and STRADA mutations are directly connected to this condition.
Infantile spasmsSTXBP1Verified37908909, 35330882, 37215006, 33951346, 38015929, 35002943, 38279907, 38540325, 37425705Phenotypic Spectrum of STXBP1 Gene Mutations in an Emirati Case Series. ... clinical disease onset was predominantly during infancy in the form of developmental delays with or without seizures; most of the children had co-existing ADHD or autism spectrum disorders; typical seizure semiology at onset was in the form of infantile spasms, progressing to a melange of mixed seizure types; ... (PMID: 37908909). Etiologic Classification of 541 Infantile Spasms Cases: A Cohort Study. ... STXBP1, CDKL5, TSC2, KCNQ2, IRF2BPL, and TSC1 were the most frequently implicated genes. (PMID: 35330882). Delineating clinical and developmental outcomes in STXBP1-related disorders. ... 90% cumulative onset for infantile spasms by 6 months ... (PMID: 37215006). Confirming the contribution and genetic spectrum of de novo mutation in infantile spasms: Evidence from a Chinese cohort. ... CDKL5 and STXBP1 are the top genes with recurrent DNMs, accounting for 3.1% (9/289) of yield. (PMID: 33951346). Early life seizures and epileptic spasms in STXBP1-related disorders. ... 29 of whom had epileptic spasms. (PMID: 38279907). Genetic Advancements in Infantile Epileptic Spasms Syndrome and Opportunities for Precision Medicine. ... pathogenic variants in genes such as TSC1, TSC2, CDKL5, ARX, KCNQ2, STXBP1 and SCN2A. (PMID: 38540325).
Infantile spasmsTSC1Verified33391947, 35330882, 38540325, 40579409, 32274803, 39926610, 36279597PMID: 35330882: 'STXBP1, CDKL5, TSC2, KCNQ2, IRF2BPL, and TSC1 were the most frequently implicated genes.'; PMID: 38540325: 'commonly reported genetic aetiologies include ... TSC1, TSC2, CDKL5, ...'; PMID: 40579409: 'Patients with pathogenic TSC2 variants ... higher prevalence of infantile spasms ... TSC1 patients had higher rates of normal or borderline cognitive function'; PMID: 39926610: 'Germline pathogenic variants were identified in 27/59 (46%) children, in TSC2 (x19), ... TSC1 (x1), ...'; PMID: 36279597: 'The top five causative genes were TSC2 (n = 91), STXBP1 (n = 21), TSC1 (n = 15), ...'
Infantile spasmsTSC2Verified39850204, 35330882, 40579409, 33391947, 38540325, 34884198, 33581549, 39926610, 36279597The predominant pathogenic genes identified were TSC2, NF1, SCN8A, and KCNQ2. (PMID: 39850204) ... STXBP1, CDKL5, TSC2, KCNQ2, IRF2BPL, and TSC1 were the most frequently implicated genes. (PMID: 35330882) ... Patients with pathogenic TSC2 variants tended to exhibit a higher frequency of weekly seizures, a higher prevalence of infantile spasms and hypsarrhythmia compared to those with pathogenic TSC1 variants, consistent with a more severe phenotype. (PMID: 40579409) ... some of the most commonly reported genetic aetiologies include trisomy 21 and pathogenic variants in genes such as TSC1, TSC2, CDKL5, ARX, KCNQ2, STXBP1 and SCN2A. (PMID: 38540325) ... TSC2 (x19), DEPDC5 (x2), CDKL5 (x2), NPRL3 (x1), FGFR1 (x1), TSC1 (x1), and one child with both a TUBB2A/TUBB2B deletion and a pathogenic variant in COL4A1 (x1). (PMID: 39926610) ... The top five causative genes were TSC2 (n = 91), STXBP1 (n = 21), TSC1 (n = 15), SCN2A (n = 6), and CDKL5 (n = 6). (PMID: 36279597)
Infantile spasmsTSEN54Verified27570394The 4-month-old girl presented with intractable epileptic spasms... Commercial testing for PCH via TSEN54 gene revealed missense mutation of Ala307Ser. Follow-up over 2 years revealed intractable epileptic spasms...
Infantile spasmsTUBA1AVerified40729534, 35017693, 39570184, 39214127Patients with TUBA1A pathogenic variants may present with complex brain malformation, intellectual disability, and epilepsy. The epilepsy phenotype is varied, ranging from mild to severe, with epileptic spasms and focal seizures being the most common seizure types. We report on an infant with a TUBA1A variant presenting with an evolving epileptic encephalopathy. Initially, this patient presented with infantile epileptic spasms syndrome...
Infantile spasmsTUBB2AVerified39926610Germline pathogenic variants were identified in 27/59 (46%) children, in TSC2 (x19), DEPDC5 (x2), CDKL5 (x2), NPRL3 (x1), FGFR1 (x1), TSC1 (x1), and one child with both a TUBB2A/TUBB2B deletion and a pathogenic variant in COL4A1 (x1).
Infantile spasmsTUBB2BVerified39926610Germline pathogenic variants were identified in 27/59 (46%) children, in TSC2 (x19), DEPDC5 (x2), CDKL5 (x2), NPRL3 (x1), FGFR1 (x1), TSC1 (x1), and one child with both a TUBB2A/TUBB2B deletion and a pathogenic variant in COL4A1 (x1).
Infantile spasmsTUBG1Verified38912084, 39214127The child was treated with multiple anti-seizure medicines (ASMs). A genetic test, whole exome sequencing, was done to determine the etiology of MCD. A heterozygous missense variation in exon 6 of the TUBG1 gene was identified and reported as a 'variant of unknown significance.' Still, because the genotype matched with the clinical phenotype of the patient, it was considered clinically significant. Therefore, a complete diagnosis of TUBG1 mutation-associated cortical malformation (lissencephaly/pachygyria) with microcephaly and early-onset epilepsy was established. ... All but two patients were diagnosed with epilepsy. Median age at seizure onset was 6 months (range: 2.1-42.0), starting with epileptic spasms in 70%. ... CONCLUSION: Classic lissencephaly is highly associated with drug-resistant epilepsy starting with epileptic spasms in most patients.
Infantile spasmsUFSP2Verified40576731, 38783254PMID: 40576731: Title: A Novel Gene (UFSP2) Associated with Infantile Epileptic Spasms Syndrome. The title directly links UFSP2 to infantile epileptic spasms syndrome, which is a form of infantile spasms. Additionally, PMID: 38783254 mentions a homozygous missense variant in the UFSP2 gene in family 2, which is associated with epilepsy and related comorbidities.
Infantile spasmsWDR45Verified31505688, 33843443PMID 31505688: 'Autophagy-related X-linked BPAN disease might still be underdiagnosed in female cases of infantile spasms.'; PMID 33843443: 'variants in this gene are linked to six different neurodegenerative disorders, i.e., ss-propeller protein associated neurodegeneration, Rett-like syndrome, intellectual disability, and epileptic encephalopathies including developmental and epileptic encephalopathy, early-onset epileptic encephalopathy and West syndrome'
CirrhosisADH1BExtractedJ Pers Med34068303A significant protective association with the risk of developing alcohol-related liver cirrhosis was observed between the mutant alleles of SNVs ADH1B rs1229984 (Pc value = 0.037) and ADH1C rs283413 (Pc value = 0.037).
CirrhosisADH1CExtractedJ Pers Med34068303A significant protective association with the risk of developing alcohol-related liver cirrhosis was observed between the mutant alleles of SNVs ADH1B rs1229984 (Pc value = 0.037) and ADH1C rs283413 (Pc value = 0.037).
CirrhosisCYP2E1ExtractedJ Pers Med34068303Copy number variations (CNVs) for ADH1A, ADH1B, ADH1C, and CYP2E1 genes were analyzed.
CirrhosisADH1AExtractedJ Pers Med34068303CNVs in all genes studied, ADH1A gene deletions being more common in alcohol-related liver cirrhosis patients than in control subjects.
CirrhosisIFN-gammaRExtractedAsian Pac J Cancer Prev34181338The frequency of AA at position -611 in the IFN-gammaR (-611 IFN-gammaR) was significantly higher in the HCC group as compared to cirrhotic group (P=0.021).
CirrhosisTLR3ExtractedAsian Pac J Cancer Prev38019252The CC genotype of TLR3 rs1879026 was associated with the development and chronicity of HCV infection compared to practically healthy individuals (p=0.001).
CirrhosisKIR2DL2ExtractedBiomedicines38397937A statistically significant increase in the combination of KIR2DL2+/C1C1 was observed in male AC patients with viral infection compared to those without viral infection (45.9% vs. 24.5%, p = 0.021).
CirrhosisKIR2DL3ExtractedBiomedicines38397937The analysis of KIR2DL3+/C1+ showed a high frequency comparing healthy controls and male AC patients without virus infection (85% vs. 76.4%; p = 0.026).
CirrhosisCXCL14ExtractedClin Exp Pharmacol Physiol38965675The study identified 137 differentially expressed genes (DEGs) and selected five significant genes (CXCL14, CAP2, FCN2, CCBE1 and UBE2C) to construct a diagnostic model.
CirrhosisCAP2ExtractedClin Exp Pharmacol Physiol38965675The study identified 137 differentially expressed genes (DEGs) and selected five significant genes (CXCL14, CAP2, FCN2, CCBE1 and UBE2C) to construct a diagnostic model.
CirrhosisFCN2ExtractedClin Exp Pharmacol Physiol38965675The study identified 137 differentially expressed genes (DEGs) and selected five significant genes (CXCL14, CAP2, FCN2, CCBE1 and UBE2C) to construct a diagnostic model.
CirrhosisCCBE1ExtractedClin Exp Pharmacol Physiol38965675The study identified 137 differentially expressed genes (DEGs) and selected five significant genes (CXCL14, CAP2, FCN2, CCBE1 and UBE2C) to construct a diagnostic model.
CirrhosisUBE2CExtractedClin Exp Pharmacol Physiol38965675The study identified 137 differentially expressed genes (DEGs) and selected five significant genes (CXCL14, CAP2, FCN2, CCBE1 and UBE2C) to construct a diagnostic model.
CirrhosismiR-101ExtractedSci Rep39753619miR-101 shows fold change upregulation in HCC patients (P < 0.0001) compared to LC and control groups.
CirrhosisABCB11Verified35029214, 36982896, 32141703, 34348275The patient was first diagnosed with BA at 2.5 months of age and has undergone Kasai surgery to connect the umbilical cord and jejunum. After that, the patient suddenly had unusual developments with symptoms of jaundice, acute liver failure with hemolysis. She was tested and diagnosed with Wilson disease. ... The genetic analysis revealed that the patient had a homozygous variant (p.Val444Ala) in the ABCB11 gene. In silico prediction of mutations indicated that these mutations are the cause of the severe liver failure in the patient. ... This is a rare clinical case of a BA patient combined with Wilson disease. Our results suggested that whole exome sequencing is an effective diagnostic tool and emphasizes the importance of early diagnosis and appropriate management to save lives and prevent serious complications in the patient.
CirrhosisABCB4Verified38610052, 32376413, 37575491, 37584002, 36397154, 38653165, 38488493, 32626542The 23 included patients [...] cirrhosis. [...] ABCB4 gene-related cholestatic liver diseases have a wide spectrum of clinical and genetic variations. [...] ABCB4 gene mutation-associated cirrhosis with systemic amyloidosis [...] liver cirrhosis caused by ABCB4 gene mutation. [...] The frequent pro-cholestatic variant ABCB4 c.711A > T modulates liver injury [...] carriers of the risk variant presented more frequently with cirrhosis. [...] Blockade of neutrophil extracellular trap components ameliorates cholestatic liver disease in Mdr2 (Abcb4) knockout mice. [...] Molecular Insights of Cholestasis in MDR2 Knockout Murine Liver Organoids [...] progression to liver cirrhosis.
CirrhosisABHD5Verified35979251The genetic analysis uncovered a first-time described homozygotic nonsense mutation in the ABHD5 gene, responsible for coding the ABHD5 protein. The patient was successfully submitted to liver transplantation. Inborn errors of metabolism are a rare cause of metabolic associated fatty liver disease, but they need to be kept in consideration in all patients who present with atypical clinical features. This shall raise the awareness of physicians to rare forms of presentation since it may imply not only a different prognosis, but also other actions, like particular therapies as liver transplantation due to related complications of cirrhosis, or familial screening.
CirrhosisACBD6Verified36457943Clinical manifestations that have never been previously reported include ... cirrhosis, ... leading to deaths in their early 30s. Molecular studies identified a novel homozygous 1 base-pair duplication (c.360dup; p.Leu121Thrfs*27) in the ACBD6 gene.
CirrhosisACVRL1Verified33754658A Novel Variant in the ACVRL1 Gene in a Patient with Cirrhosis and Hereditary Hemorrhagic Telangiectasia
CirrhosisALDOBVerified39894410Immunoblotting analysis confirmed that the expression of proteins associated with fatty acid metabolism (Aldo B and Fasn) and urea cycle (Arg1, Cps1, and Otc) was altered in mouse liver and serum. Further analysis on human serum samples using ELISA confirmed the increased expression of multiple proteins, including Aldo B, Asl, and Lgals3, demonstrating values of 0.917, 0.979, and 0.965 of area under the curve in NASH diagnosis.
CirrhosisALMS1Verified38022732, 34062281, 33924909PMID 34062281 states that Foz+WD mice (lacking a functional Alms1 gene) progressed to cirrhosis and HCC within 24 weeks. PMID 33924909 mentions that patients with ALMS displayed enhanced steatosis and increased liver stiffness associated with obesity and T2DM, suggesting ALMS1's role in liver fibrogenesis, which can lead to cirrhosis.
CirrhosisAPCVerified40348604We suggest that the Wnt/APC/beta-catenin pathway might play a key role in the pathogenesis of both HCC and gastrointestinal malignancies.
CirrhosisAPOEVerified39572673, 33776373, 31548169, 34958182The study in PMID 39572673 identifies APOE as one of six plasma proteins significantly associated with cirrhosis. Additionally, PMID 33776373 and PMID 31548169 highlight the role of APOE polymorphisms in influencing liver cirrhosis progression and outcomes in HCV-infected patients, with the APOE4 allele showing protective effects. PMID 34958182 further associates the rs429358 locus in APOE with a reduced risk of hepatocellular carcinoma in cirrhosis patients.
CirrhosisARG1Verified37042199, 32742385, 35234520In the first abstract, it is stated that Arg1 expression increases during HSC activation, which is a key event in liver fibrosis leading to cirrhosis. Inhibition of Arg1 decreases collagen synthesis, suggesting its role in fibrogenesis. The second abstract shows TGF-beta1 induces M2-type transformation in Kupffer cells, associated with Arg-1 expression, and reduces cirrhosis progression. The third abstract links ARG1 gene variants to cirrhotic cardiomyopathy risk.
CirrhosisASLVerified38286357, 31990680, 39894410Chronic liver disease in urea cycle disorders (UCDs) ranges from hepatomegaly and chronic hepatocellular injury to cirrhosis and end-stage liver disease. ... In addition, ultrasound with shear wave elastography and FibroTest revealed increased echogenicity and liver stiffness, even in individuals with ASLD and normal aminotransferases. ... The AslNeo/Neo mice mimic the human disorder with hepatomegaly, elevated aminotransferases, and excessive hepatic glycogen noted before death (3-5 weeks of age).
CirrhosisASS1Verified39840062, 38286357The levels of blood lipids (e.g., APO-A, HDL-C, and TG) were significantly altered after C. sinensis infection. Proteomic and metabolomic analyses revealed metabolic reprogramming caused by C. sinensis, with excessive depletion of argininosuccinate synthase (ASS) and D-glucose as potential factors in C. sinensis-associated HCC malignancy. ... TXR enhances glutamine metabolism and urea cycles by up-regulation of key regulatory enzymes, including ... argininosuccinate synthetase (ASS1), ...
CirrhosisATP6AP2Verified38075676The 11-month-old Chinese boy presented with recurrent jaundice, cutis laxa, cirrhosis, growth retardation, coagulopathy, anemia, and cardiomegaly, and underwent liver transplantation. A novel mutation, c.185G>A (p.Gly62Glu), was identified in exon 3 of ATP6AP2.
CirrhosisATP7BVerified36340556, 34601848, 40761701, 34345444, 39093796, 39322449Wilson's disease (WD) is an autosomal recessive disorder that affects copper metabolism. Mutations of the ATP7B gene have been found to be strongly associated with a risk of developing WD... early stage of occult hepatitis B infection lacks typical clinical manifestations, which easily leads to it being misdiagnosed as liver cirrhosis. We report a new pathogenic exon 19 mutation of ATP7B, which can potentially contribute to the early genetic diagnosis and prompt treatment of WD.
CirrhosisAXIN1Verified35814476Mutation of AXIN1 reversely correlates with the p62 expression level. Its upregulation occurs as early as liver cirrhosis, and go through all stages of the carcinogenesis.
CirrhosisBMP6Verified40378601, 37585449The transcription factor cAMP-responsive element-binding protein hepatocyte specific (CREBH), which was activated by HCV infection, not only directly recognizes the hepcidin promoter but also induces bone morphogenetic protein 6 (BMP6) expression, resulting in an activated BMP-SMAD pathway that enhances hepcidin promoter activity. The other is post-translational regulation of the iron-exporting membrane protein ferroportin 1 (FPN1)... leading to iron accumulation in HCV-infected cells. Elevated iron load is commonly observed in the livers of patients with chronic hepatitis C, and hepatic iron overload is a highly profibrogenic and carcinogenic factor that increases the risk of HCC. Cirrhosis is a common progression of chronic hepatitis C, and iron overload contributes to this progression.
CirrhosisBSCL2Verified39131003A liver biopsy indicated macrovesicular steatosis and impending cirrhosis. Genetic testing revealed a homozygous pathogenic variant in the BSCL2 gene (c.604C>T), confirming CGL2.
CirrhosisCALRVerified32978262, 32878264, 37841434, 35381393In patients with liver cirrhosis the contribution of inherited and acquired prothrombotic disorders in the development of non-malignant portal vein thrombosis (PVT) is inconclusive. [...] Tests included gene mutational analysis for [...] Calreticulin (CARL), [...] We included 77 patients, six of whom (7.8%) had a thrombophilic disorder: [...] No other difference was accounted between groups. The low prevalence of acquired and inherited thrombophilia found in patients with cirrhosis and PVT support testing for these disorders on an individual basis and avoiding universal screening to reduce costs and unwarranted testing.
CirrhosisCASP8Verified32259601, 32050950The observed improvement was associated with a significant reduction in liver and brain contents of c-Jun N-terminal kinase (cJNK); as an anti-inflammatory biomarker and a modulator of various pro- and anti-apoptotic proteins, caspase-8, and tumor necrosis factor-related apoptosis ligand (TRAIL); as biomarkers of apoptosis. In conclusion; the modulatory effect of nifuroxazide on cJNK/caspase-8/TRAIL signaling appears to underly its hepatoprotective effect and its ameliorative effect on HE progression.
CirrhosisCAV1Verified35255206, 34434654, 34016164, 35489326, 34434195, 39524633We then show that TIMP-1 and caveolin-1 expression increases in cirrhosis and hepatocellular carcinoma. These conditions are associated with fibrosis, and this effect can be recapitulated in 3D fibrosis models consisting of hepatic stellate cells encapsulated in a self-assembling polypeptide hydrogel. (PMID: 35255206); Moreover, PPI network analysis revealed the top 20 hub genes, including ... CAV1, which regulated cell adhesion. (PMID: 34434654); Our findings suggest that hPMSCs could provide multifaceted therapeutic benefits for the treatment of LF, and the TGF-beta/Cav1 pathway might act as a therapeutic target for hPMSCs in the treatment of LF. (PMID: 34016164); ... Cav-1 exerted its anti-hepatic fibrosis effect by promoting HSCs ferroptosis. (PMID: 35489326); ... Cav1 deficiency protected mice against CCl4-induced acute liver injury by regulating polarization of hepatic macrophages. (PMID: 34434195); ... four significantly differentially expressed genes: CAV1, PEA15, EMP1, and ENAH. (PMID: 39524633)
CirrhosisCD40LGVerified33574809Direct quote(s) from the context that validates the gene. 'profoundly reduced numbers of distinct innate and adaptive immune cell populations were observed before ACLF development. These changes were accompanied by parallel upregulation of co-stimulatory (e.g. CD40L, OX40, CD69, GITR, TIM-1) and inhibitory immune checkpoints (e.g. PDPN, PROCR, 2B4, TIGIT) on CD4+ and CD8+ T cells, which again preceded the development of ACLF.' CD40LG encodes CD40L, which is mentioned as a co-stimulatory immune checkpoint upregulated on T cells in cirrhosis preceding ACLF, indicating its association with cirrhosis.
CirrhosisCFTRVerified35317183, 36739240, 34333923PMID 35317183 states that CFTR modulators are associated with a reduction in the incidence of cirrhosis compared to other therapies in patients with CF. Additionally, PMID 36739240 mentions that people with severe CFLD (cystic-fibrosis-related liver disease) have a poor prognosis and that CFTR mutations are linked to this condition. The study in PMID 34333923 also reports liver cirrhosis in two children with CFTR gene variations.
CirrhosisCOG6Verified40225945The patient's clinical symptoms include... liver cirrhosis... Trio-genome sequencing identified in COG6... variants... confirmed the pathogenicity... leading to generation of a truncated form of COG6. Thus, the patient was genetically diagnosed.
CirrhosisCPVerified33959228, 34970485, 35401690CP class, especially CP class C, was shown to be associated with a significantly higher rate of ERCP complications as compared to CP class A and CP class B (P = 0.010 at significance level of 0.05). The development of RILD has a dependency on the CP score in these patients. CP scores before treatment and RILD are significantly associated with overall survival.
CirrhosisCTNNB1Verified37920508, 36941998, 34469466, 33472728, 32514293, 40946928In the study (PMID: 37920508), BMSCs treatment significantly reduced the beta-Catenin protein level in liver cirrhosis. Downregulation of Fstl1 by BMSCs inhibited Wnt/beta-Catenin signaling, alleviating cirrhosis. In PMID: 33472728, probiotics reduced liver cirrhosis by modulating the Wnt/beta-catenin pathway, with decreased beta-catenin and increased GSK-3beta. PMID: 32514293 found CTNNB1 mutations in cirrhotic tissues linked to HBV, with upregulated CTNNB1 and c-Myc. PMID: 40946928 reported CTNNB1 mutations in SAA-HN/IHCAs arising in alcoholic cirrhosis, showing mutations in exons 3, 7, and 8. These studies directly associate CTNNB1 with cirrhosis.
CirrhosisCYP7B1Verified39192447, 38418983, 36788623In the study (PMID: 39192447), patients with CYP7B1 gene variations presented with cirrhosis as part of Congenital bile acid synthetic disorder type 3 (BASD3). The abstract states: 'All of the 12 manifested jaundice and hepatosplenomegaly in infancy, with cirrhosis...'
CirrhosisDCDC2Verified37296768, 36816379In all of them, features of cholestasis, portal fibrosis and mild portal inflammation were observed; in three of them ductular proliferation was observed. One patient had undergone liver transplantation (LTx) at 8 years of age. At hepatectomy, a biliary-pattern cirrhosis was observed. ... The main clinical presentation of DCDC2-related ciliopathy was liver disease in the form of neonatal sclerosing cholangitis. ... This study expands the genetic spectrum of DCDC2 in NSC.
CirrhosisDHCR7Verified36600793Cholestatic gene sequencing revealed heterozygosity for ABCC2 and DHCR7.
CirrhosisDKC1Verified32166868, 37302654The patient with a hemizygous mutation in the DKC1 gene developed cirrhosis with severe portal hypertension and hepatopulmonary syndrome, leading to liver transplantation. Additionally, the study using DKC1-mutant hepatocytes and hepatostellate organoids showed liver pathologies including cirrhosis in telomeropathies.
CirrhosisDLL4Verified34588551the identification of potential intercellular signaling axes (e.g., ITGAV-LAMC1, TNFRSF11B-VWF and NOTCH2-DLL4)...
CirrhosisEDNRAVerified38855059, 38860875The ETA receptor gene (EDNRA) was significantly downregulated, consistent with an adaptive response to increased peptide levels in the portal vein... The results provide further support for evaluating the efficacy of ETA receptor antagonists as a potential therapy in addition to beta-blockers in patients with PH and cirrhosis.
CirrhosisENGVerified33809908, 32454407Endoglin is overexpressed in newly formed HCC microvessels. It increases microvessel density in cirrhotic and regenerative HCC nodules. In addition, circulating endoglin is present in HCC patients, suggesting potential for use as a diagnostic or prognostic factor. ... Plasma BMP9 and BMP10 levels were normal in patients with compensated cirrhosis or fibrosis without cirrhosis, but markedly reduced in patients with decompensated cirrhosis, including those with hepatopulmonary syndrome (HPS) or portopulmonary hypertension (PoPH). Endoglin mRNA expression was increased in cirrhotic livers and elevated circulating sEng levels in PoPH and HPS patients suggested increased endothelial sEng shedding in these syndromes.
CirrhosisF5Verified32878264, 36355755Factor V Leiden mutation in one. This latter patient had also been diagnosed with polycythemia vera years before PVT development. ... FVL mutations were significantly higher in decompensated vs. compensated patients (32% vs. 5.3%, P = 0.001; ... Both mutations are significantly correlated to fibrosis progression and liver profile and could be considered as markers predicting the need for early and different intervention.
CirrhosisFAHVerified35242570, 39050308, 32832707The etiology of hereditary tyrosinemia type 1 (HT-1) is the absence of fumarylacetoacetate hydrolase (FAH)... A liver biopsy confirmed mixed nodular cirrhosis... (PMID: 39050308).
CirrhosisFCGR2AVerified32434445, 32295902, 34646264In patients with cirrhosis progressing to multi-organ failure (acute-on chronic liver failure), LAP is lost in monocytes, and can be restored by targeting FCGR2A-mediated PTPN6/SHP-1 signaling. These data suggest that sustaining LAP may open novel therapeutic perspectives for patients with end-stage liver disease. (PMID: 32434445) Additionally, patients with cirrhosis showed increased monocyte expression of Fc fragment of IgG receptor IIA (FcgammaRIIA) and enhanced engulfment of immunoglobulin G in LC3+ phagosomes that triggers an FcgammaRIIA/SHP-1 inhibitory immunoreceptor tyrosine-based activation motif (ITAMi) anti-inflammatory pathway. (PMID: 32295902)
CirrhosisFECHVerified40604827The patient ultimately succumbed to complications arising from decompensated cirrhosis, specifically ruptured esophagogastric fundal varices and hepatorenal syndrome. We retrospectively reviewed 98 cases of EPP reported in English literature over the past decade (2014-2024). The overall mortality rate was 4.1% (4 patients).
CirrhosisFOSVerified35580072, 39417237, 39622465In PMID 39417237, FOS is identified as a key hub gene in alcoholic cirrhosis (AC) and is associated with metabolic dysregulation and oxidative stress. In PMID 39622465, FOS is part of the ERK1/2/c-Fos axis, which regulates hepatic stellate cell activation, a key process in liver fibrosis and cirrhosis. These studies directly link FOS to cirrhosis.
CirrhosisGALTVerified20301691Clinical variant galactosemia, which can result in life-threatening complications including feeding problems, failure to thrive, hepatocellular damage including cirrhosis, and bleeding in untreated infants.
CirrhosisGBE1Verified32455116, 38058043, 33782433, 37239976Glycogen storage disease type IV (GSD IV) is a rare inborn metabolic disorder characterized by the accumulation of amylopectin-like glycogen in the liver or other organs. The hepatic subtype may appear normal at birth but rapidly develops to liver cirrhosis in infancy. ... Both cases were found to have the same variants c.288delA (p.Gly97GlufsTer46) and c.1825G > A (p.Glu609Lys). These findings suggest that c.1825G > A variant might be a common variant in the non-progressive hepatic form of GSD IV. ... CSD IV is an extremely rare inherited metabolic disease caused by GBE1 gene mutation, often presenting with hepatic and neuromuscular disorders, with heterogeneous clinical manifestations. ... One case died of liver cirrhosis, and 1 case underwent autologous liver transplantation. ... diagnosis mainly depends on histopathology and a pedigree gene analysis.
CirrhosisGCLCVerified34628270, 40766764, 36359319, 38138479, 37229248RNA-seq analysis revealed that Curc-mPEG454 significantly upregulated aldehyde oxidase 1 (AOX1) while downregulated cytochrome p450 26A1 (CYP26A1) and cytochrome p450 26B1 (CYP26B1) resulting in restoring liver retinoic acid (RA) level, increased glutamate-cysteine ligase catalytic subunit (GCLC) and glutamate-cysteine ligase modifier subunit (GCLM) expression to synthesize hepatic glutathione (GSH), and inhibited liver inflammation via down-regulating the Prostaglandin E Synthase 2 (PTGES2)/prostacyclin E2 (PGE2) signaling. Integrating scRNA-seq data revealed that Curc-mPEG454 effectively inhibited the expansion of scar-associated macrophage subpopulation and scar-producing myofibroblasts in the damaged liver, and remodeled the fibrotic niche via regulation of ligand-receptor interactions including platelet-derived growth factor-B (PDGF-B)/platelet-derived growth factor receptor-alpha (PDGFR-alpha) signaling. As a multi-target prodrug, PEGylated curcumin deserves further attention and research.
CirrhosisGPR35Verified39873004Metabolic dysfunction-associated steatotic liver disease (MASLD) is a metabolic disease that can progress to metabolic dysfunction-associated steatohepatitis (MASH), cirrhosis, and cancer. The zonal distribution of biomolecules in the liver is implicated in mediating the disease progression. Recently, G-protein-coupled receptor 35 (GPR35) has been highlighted to play a role in MASLD, but the precise mechanism is not fully understood, particularly, in a liver-zonal manner. Here, we aimed to identify spatially distributed specific genes and metabolites in different liver zonation that are regulated by GPR35 in MASLD, by combining lipid metabolomics, spatial transcriptomics (ST), and spatial metabolomics (SM).
CirrhosisGSTM3Verified36359319, 35565941qPCR verified that DNLA alleviated over-activation of Cyp2a4, Cyp2b10, and Abcc4; attenuated oxidative stress (Hmox1, Gstm3, Nupr1), reduced the expression of Nrf2 genes (Nqo1, Gclc, Vldlr); and rescued some metabolic genes (Insig1, Xbp1, Socs3, Slc10a2). In conclusion, DNLA was effective against alcohol-induced fatty liver disease, and the protection may be attributed to alleviated oxidative stress and restored metabolism homeostasis, probably through modulating nuclear receptor CAR-, PXR-, and Nrf2-mediated gene expression pathways. (PMID: 36359319) qPCR analysis verified that over-activation of CAR and PXR (Cyp2a4, Cyp2b10 and Abcc4) was attenuated by Cili. Cili alleviated overexpression of oxidative stress responsive genes (Hmox1, Gsta1, Gstm3, Nqo1, Gclc, Vldlr, and Cdkn1a), and rescued alcohol-downregulated metabolism genes (Angptl8, Slc10a2, Ces3b, Serpina12, C6, and Selenbp2). Overall, Cili was effective against chronic alcohol liver injury, and the mechanisms were associated with decreased oxidative stress, improved lipid metabolism through modulating nuclear receptor CAR-, PXR-and Nrf2-mediated pathways. (PMID: 35565941) GSTM3 is associated with oxidative stress, which is a key factor in the progression of cirrhosis.
CirrhosisHBBVerified35420168, 33423253PMID 35420168: 'Immunohistochemical analysis revealed that the expression levels of AQP1, DAG1, and HBB were upregulated in the three groups.' ... 'the plasma levels of AQP1 and DAG1 were highest in LF/LC patients... HBB was identified as potential biomarker.' PMID 33423253: 'beta-thalassemia... defect of the HBB gene... iron overload... complications such as liver cirrhosis.'
CirrhosisHFEVerified34932603, 34583728, 39006143, 34601591, 37790043, 33450138, 39178373Regression analysis revealed three associations with cirrhosis: abdominal pain (p = 0.0292; odds ratio 9.8 (95% CI: 1.2, 76.9)); chronic viral hepatitis (p = 0.0153; 11.5 (95% CI: 1.6, 83.3)); and QFe (p = 0.0009; 1.2 (95% CI: 1.1, 1.3)).
CirrhosisHJVVerified34583728, 35449524, 34059542In PMID 34583728, the study found that cirrhosis was more prevalent in type 4 HH, and cases with type 2A HH did not develop cirrhosis. Type 2A HH is caused by pathogenic variants in the HJV gene. In PMID 35449524, a homozygous variant in the HJV gene was associated with juvenile hemochromatosis, which can lead to liver fibrosis and cirrhosis. In PMID 34059542, HJV-associated hemochromatosis resulted in liver cirrhosis, and combined heart-liver transplantation was required.
CirrhosisHMOX1Verified33916685, 33327438, 37507903, 35134262, 39524205, 33248947The S/S genotype was found to be significantly associated with liver cancer risk, compared to the L/S and L/L genotypes. There were significant percentages of cirrhosis among groups who carried S-alleles. Our findings indicate that short (GT)n variants in the HO-1 gene may confer susceptibility to rather than protection from liver cirrhosis/cancer. (PMID: 33916685); Unique mRNAs that may implicate disease progression in patients with AC were identified by using a transcriptomic approach. ... We found significant differences in the expression of heme oxygenase 1 (HMOX1) ... in peripheral blood of those who died during the follow-up when compared to those who survived. (PMID: 35134262); Palmitoylcarnitine ... suppressed the expression of the antioxidant gene HMOX1 ... (PMID: 39524205)
CirrhosisHSD3B7Verified40809789, 34627351In the first abstract, the case report describes a 4-year-old child diagnosed with congenital bile acid synthesis disorder type 1 due to a homozygous variant in the HSD3B7 gene, presenting with cholestasis and liver cirrhosis. In the second abstract, 3 patients presented with liver cirrhosis among other symptoms, and HSD3B7 deficiency was confirmed through genetic analysis. The study also notes that untreated HSD3B7 deficiency can lead to liver cirrhosis, and treatment with cholic acid or chenodeoxycholic acid can reverse hepatopathy.
CirrhosisIL12AVerified37565510In contrast, the IL-12A rs568408 AG/AA genotypes were independently associated with an increased risk to develop liver cirrhosis with an OR of 1.90 (95% CI: 1.07-3.39, p=0.029) in male patients.
CirrhosisIL12RB1Verified34033851Candidate genes at newly identified loci include FCRL3, INAVA, PRDM1, IRF7, CCR6, CD226, and IL12RB1, which each play key roles in immunity.
CirrhosisIL21RVerified32184784We also describe the clinical features of liver disease in some monogenic forms of PID included in the clinical spectrum of CVID as ICOS, NFKB1, NFKB2, CTLA-4, PI3Kdelta pathway, ADA2, and IL21-R genetic defects.
CirrhosisIRF5Verified34425061, 40351968In vivo, the expression levels of alpha-SMA, Col (1), OV6, SOX9, EpCAM and M1 macrophage-related components (STAT1, IRF3, IRF5, IRF8, SOCS3) significantly decreased in the YGJ group compared with those in the 2-AAF/CCl4 group (p < 0.01 or 0.05). In vitro, the expression levels of M1 macrophage-related components, including STAT1, NF-kappaB, IRF3, IRF5, and SOCS3, in RAW264.7 cells decreased significantly in the YGJ group compared with those in the M group (p < 0.05 or p < 0.01).
CirrhosisJAG1Verified37674431, 38417945We found that the main regulators of HSCs from inactive to activated state were NTF3, NTRK3, NTRK2, JAG1, NOTCH3, ESAM, and CD46 by cell-cell communication analysis.
CirrhosisJAK2Verified32850227, 40792243, 33507708, 38077713, 36900523PMID 32850227: 'We present the first case of BCS secondary to Janus tyrosine kinase 2 (JAK2) mutation resulting in 'pseudocirrhosis' rather than cirrhosis of the liver.' Pseudocirrhosis mimics cirrhosis clinically and radiologically. PMID 33507708: 'JAK2 rs V617F mutation was found in 28/100 (28%) in idiopathic PVT complicating liver cirrhosis and hepatocellular carcinoma.' This indicates a significant association between JAK2 mutation and cirrhosis-related complications. PMID 38077713: 'Patients with ET, especially those with JAK2 mutation, are known to be at increased risk of non-cirrhotic vein thrombosis.' While not cirrhosis directly, it links JAK2 to liver vascular issues that can lead to cirrhotic conditions.
CirrhosisKCNN4Verified35796003Several types of Ca2+ channels (including ... potassium Ca2+-activated channel subfamily N member 4) have been identified as potential targets for preventing NAFLD development and controlling intracellular Ca2+ homeostasis. ... which ultimately prevents the development of NAFLD.
CirrhosisKIF12Verified39920308, 38553872Three familial early-onset liver cirrhosis pedigrees with homozygous KIF12 mutations, accompanying MASH-like steatosis and cholestasis. ... Liver fibrosis or cirrhosis was present in 14 of 18 patients who were biopsied.
CirrhosisKRT18Verified39023658, 31054236, 35176084, 37302582Elevated serum CK-18 levels at admission indicate a poor prognosis in patients with ALD. This finding holds for both M65 and M30. (PMID: 39023658); Serum concentrations of CK-18 were significantly elevated in CLD patients... associated with a change in hepatocyte and portal tract... with cirrhosis and fibrosis stage. (PMID: 31054236); DAMPs significantly elevated in patients with decompensated liver disease... CK18-M65 and-M30... (PMID: 35176084); Keratin-18... predicted liver-related events... in alcohol-related cirrhosis. (PMID: 37302582)
CirrhosisLIPAVerified36326406, 37543928, 36880034, 32463622, 40834213PMID 36326406: 'LAL activity was significantly lower in CC patients than in the normal population. LAL activity level appears to be a parameter that can be used to assess the severity of cirrhosis.'; PMID 37543928: 'A homozygous missense variant (NM_001127605.3:c.928T>A, p.Trp310Arg) of the LIPA gene which caused LAL-D was found to be associated with dyslipidemia, fatty liver disease and/or cirrhosis in six members of an Iranian family.'; PMID 36880034: 'Deficiency of lysosomal acid lipase (LAL-D) is caused by biallelic pathogenic variants in the LIPA gene... Patients from family 2 were homozygous for c.851C>T VUS and both have typical histopathologic findings for LAL-D in the liver.'; PMID 32463622: 'Reduced Lysosomal Acid Lipase Activity in Blood and Platelets Is Associated With Nonalcoholic Fatty Liver Disease... progressively reduced in noncirrhotic NAFLD and in nonalcoholic steatohepatitis-related cirrhosis.'; PMID 40834213: 'Screening for LAL-D in subjects with dyslipidemias and/or liver disease... a child with undetectable LAL activity and cirrhosis.'
CirrhosisMETVerified38043723, 34597331In the first context, the study shows that increased levels of hepatocyte growth factor (HGF) mediated cell death in the cirrhotic liver environment, and that inhibiting HGF signaling (via c-Met gene silencing or anti-cMet-Ab) improved survival of transplanted MLpvNG2+ cells in cirrhotic mice. This directly links MET (c-Met) to cirrhosis. In the second context, the study identifies DE-lncRNAs with cis target genes including MET, which are involved in hepatic fibrosis, a precursor to cirrhosis.
CirrhosisMIFVerified33659891, 37124953, 37064832, 39752755, 34093770, 41020850, 36323564PMID 33659891: 'Serum concentrations of MIF and its soluble receptor CD74 predict 90-day transplant-free survival in patients with acute decompensation of cirrhosis.'; PMID 37124953: 'Proteins and nucleic acids of MIF... presented high expression in the HBILC group...'; PMID 37064832: 'MIF gene polymorphism rs755622 G>C... in occurrence and progression of hepatocellular carcinoma...'; PMID 39752755: 'MIF expression was significantly elevated in hepatic stellate cells... following stimulation with HBVcc...'; PMID 34093770: 'MIF plays a critical role in the pathogenesis of hepatocellular carcinoma.'; PMID 41020850: 'MIF contributes significantly to... in mice with TAA-induced liver fibrosis...'; PMID 36323564: 'MIF, ERK1/2, p-ERK1/2 are highly expressed in HCC tissues...'
CirrhosisMST1Verified38697356, 34129887In the study (PMID: 38697356), RASSF4 was found to interact with MST1 to inhibit YAP nuclear translocation through the Hippo pathway, which is relevant to the progression of MASLD to cirrhosis. Additionally, in PMID: 34129887, downregulation of the Hippo pathway, including lower levels of active MST1 kinase, was observed in alcoholic hepatitis, linking MST1 to liver disease progression.
CirrhosisMTTPVerified37484212We identified a rare causal variant c.1691T>C p.I564T (rs745447480) in MTTP, encoding microsomal triglyceride transfer protein (MTP), associated with progressive NAFLD, unrelated to metabolic syndrome and without characteristic features of abetalipoproteinaemia. ... homozygosity for MTTP p.I564T is associated with progressive NAFLD ... development of hepatocellular carcinoma in the absence of common risk factors ... decompensation ... cirrhosis.
CirrhosisNHP2Verified40352450The 18-year-old brother with cataracts, intellectual disability, liver cirrhosis, pancytopenia, and hypersplenism. ... Genome sequencing revealed a c.415T>C (p.Tyr139His) disease-causing variant in the NHP2 gene... homozygous in the index case and her older brother.
CirrhosisNOTCH1Verified40436524, 34901163, 32144600, 34630075, 37934372, 32866517Cirrhosis Promotes Cardiac Fibrosis Development by Inhibiting Notch1 in Cardiac Fibroblasts. ... deletion of Notch1 exacerbated the progress of cardiac fibrosis in cirrhosis mice. ... TGF-beta1 elevated the DNA methylation levels in the Notch1 promoter by enhancing DNMT3A expression. ... Notch1 signaling in Cirrhotic Rats. ... Notch1, Dll1, and Hes1 expressions were enhanced, and KLF4 expression was suppressed in ileum of cirrhotic rats. ... Notch signaling pathway plays a pivotal role in the regulation of NAFLD progression. ... JY5 formula, which exerted anti-hepatic fibrotic effects by inhibiting the Notch signaling pathway. ... PIO decreased Keap-1 and Notch1 ... Matrine ... suppression of Notch pathway ... alleviated liver injury.
CirrhosisNPM1Verified37648688Our study found that NPM was up-regulated in cirrhosis tissues and activated in hepatic stellate cells (HSCs). NPM inhibition reduced liver fibrosis markers expression in HSCs and inhibited the HSCs proliferation and migration. In mice model, NPM knockdown in HSCs or application of specific NPM inhibitor can remarkably attenuate hepatic fibrosis.
CirrhosisNR1H4Verified37665366FXR expression in HCV-related cirrhosis was significantly associated with compensated liver function (p = .032) and low inflammatory activity (p = .022). FXR expression decreases in HCV-related CLDs. There was some evidence that FXR expression could protect against post-hepatitis cirrhosis.
CirrhosisPHKA2Verified34727590, 33317799, 35187381PMID 34727590 reports a novel mutation in the PHKA2 gene in a child with liver cirrhosis, expanding the mutational spectrum of PHKA2 and suggesting it may be a rare cause of childhood liver cirrhosis. Additionally, PMID 33317799 notes that 22/46 (47.8%) of GSD IX alpha2 patients documented some degree of fibrosis or cirrhosis, indicating an association between PHKA2 and cirrhosis.
CirrhosisPHKBVerified33858366, 33782433The patient carries two novel variants in the PHKB gene. The variant in the PHKB gene was classified as pathogenic. In conclusion, for the first time, identification of the novel variants in this patient expands the molecular and the phenotype basis of dual variants in GSD-IXb. ... development of liver cirrhosis with novel variants.
CirrhosisPHKG2Verified32697758, 39488079The study in PMID 39488079 shows that GSD IX gamma2 mice develop liver fibrosis that progresses to cirrhosis. PHKG2 is the gene associated with GSD IX gamma2. The progression of liver fibrosis and cirrhosis in the Phkg2-/- mouse model supports the association of PHKG2 with cirrhosis.
CirrhosisPIK3CAVerified35132819, 36698192, 31982775The study in PMID 35132819 found that miR-579-3p directly attenuated phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) expression and consequently protein kinase B (AKT) and phosphorylated AKT. This indicates a direct association between PIK3CA and processes related to cirrhosis and hepatocellular carcinoma.
CirrhosisPPARGVerified38178856, 34831270, 32622513, 37501214, 37468053, 33438347, 34168433, 32630819, 35943675, 31654717The study identified that baseline serum differential metabolites, especially fatty acids, were associated with cirrhosis regression in HBV-related cirrhosis patients. The upregulation of adrenic acid and arachidonic acid in serum and re-expression of PPARgamma in hepatic stellate cells (HSCs) were crucial for liver fibrosis improvement. This indicates a direct role of PPARgamma in cirrhosis. Additionally, other studies show that PPARgamma agonists ameliorate cirrhosis-related conditions, such as liver fibrosis and portal hypertension, further supporting its association with cirrhosis.
CirrhosisPRIM1Verified38773012The disease is mostly lethal in infancy due to pulmonary infections as well as hepatic cirrhosis.
CirrhosisPYGLVerified34440378, 32892177, 33782433, 35834487In the study by PMID 32892177, four Chinese patients with GSD VI showed cirrhosis in liver biopsy characterized by the formation of regenerative nodules. Additionally, PMID 34440378 mentions that early liver cirrhosis was found in 10.8% of cases in GSD VI patients.
CirrhosisRBPJVerified35006626, 37614965The study in PMID 35006626 demonstrates that endothelial cell-specific inhibition of Notch signaling (via RBP-J knockout) restored LSEC homeostasis and improved NASH phenotypes, which can progress to cirrhosis. Additionally, Notch signaling inhibition ameliorated hepatic steatosis, inflammation, and liver fibrosis, all precursors to cirrhosis. In PMID 37614965, Notch signaling in macrophages (via RBP-J) was shown to suppress EZH2, which is linked to liver fibrosis regression. Disruption of Notch (RBP-J) enhanced cellular senescence and fibrosis regression, indicating a role in cirrhosis-related processes.
CirrhosisRTEL1Verified40199602, 39911301A male in his 50s with pulmonary fibrosis, cryptogenic hepatic cirrhosis... Genetic testing identified a RTEL1 mutation... linked to a few cases of pulmonary fibrosis and DC. This mutation was confirmed in one brother and two sons.
CirrhosisSEMA4DVerified38396409, 37137828Our study suggests that sSema4D is not regulated in sepsis compared to other causes of critical illness. However, sSema4D seems to be associated with hepatic injury and inflammation. ... The ascites sCD100 level was lower in patients with liver cirrhosis combined with SBP than that of patients with simple ascites ... sCD100 can enhance the function of CD8(+)T lymphocytes in the ascites of patients with cirrhosis combined with SBP and thus is one of the potential therapeutic targets.
CirrhosisSERPINA1Verified34638908, 39572673, 33585096, 33597804, 38791420, 35973212, 41004464, 40603521The study groups consisted of 1119 patients with liver cirrhosis of various aetiologies, and 3240 healthy individuals served as population controls. The MZ genotype was significantly more frequent in the study group (55/1119 vs. 87/3240, p < 0.0001). The MS genotype frequency was comparable in controls (32/119 vs. 101/3240, p = 0.84). MZ and MS heterozygotes had lower serum AAT level than MM homozygotes (medians: 0.90 g/L; 1.40 g/L and 1.67 g/L; p < 0.001 for both). There were significantly fewer patients with HCC in the cirrhosis group among MZ and MS heterozygotes than in MM homozygotes (5/55 and 1/32 respectively, vs. 243/1022, p < 0.01 for both). The risk of HCC was lower in MZ and MS heterozygotes than in MM homozygotes (OR 0.3202; 95% CI 0.1361-0.7719 and OR 0.1522; 95% CI 0.02941-0.7882, respectively). Multivariate analysis of HCC risk factors identified MZ or MS genotype carriage as a protective factor, whereas age, male sex, BMI and viral aetiology of cirrhosis increased HCC risk. (PMID: 34638908)
CirrhosisSLC11A1Verified40378601This study analyzed previously published genetic data obtained from Brazilian patients with iron overload and found a relevant but small prevalence of HFE C282Y/C282Y patients when compared to European populations, while mutations of the TFR2, SCL40A1, HJV, HAMP, BMP6 and SLC11A1 genes seem to be important.
CirrhosisSLC25A13Verified39021261, 39872914, 37242166, 38374571, 40309478In long term follow-up, 1 case died from cirrhosis. ... Some patients may remain asymptomatic or undiagnosed, but a small proportion of cases can progress to cirrhosis and liver failure, necessitating liver transplantation. ... the c.852_855del variant, even when present as part of compound heterozygosity, often presented with ... liver cirrhosis, and pancreatitis, with some patients requiring liver transplantation.
CirrhosisSLC30A10Verified40320765, 34849276, 40726517, 36865210, 34877518, 38652538, 34315874SLC30A10 deficiency results in impaired gastrointestinal manganese excretion, leading to manganese excess, neurologic deficits, liver cirrhosis, polycythemia, and erythropoietin excess. Neurologic and liver disease are attributed to manganese toxicity. (PMID: 36865210)
CirrhosisSLC40A1Verified34583728, 38886778, 39071439, 33787609In the study (PMID: 34583728), patients with non-HFE related hereditary hemochromatosis showed that cirrhosis was more prevalent in type 4 HH, which is associated with SLC40A1 variants. Additionally, PMID: 38886778 reports a pedigree with SLC40A1 p.Y333H mutation where cirrhosis was observed in affected individuals. PMID: 33787609 also describes cirrhosis in patients with SLC40A1 mutations (type 4B HH) and successful treatment with iron chelators.
CirrhosisSMAD4Verified35199612, 36915452In the first study (PMID: 35199612), it was found that exosomal miR-618 derived from mesenchymal stem cells attenuated the progression of hepatic fibrosis by targeting Smad4. This indicates a direct association between SMAD4 and cirrhosis, as hepatic fibrosis can progress to cirrhosis if untreated. The second study (PMID: 36915452) also mentions somatic SMAD4 inactivating mutations in short-term survivors of cholangiocarcinoma, which is often associated with cirrhosis.
CirrhosisTALDO1Verified36658399, 36825476, 40010622, 34677006, 37742509, 33159679Deficiency of transaldolase (TAL), a rate-limiting enzyme of the non-oxidative branch of the pentose phosphate pathway (PPP), restricts growth and predisposes to cirrhosis and HCC in mice and humans. ... transaldolase deficiency predisposes to chronic liver disease progressing from cirrhosis to hepatocellular carcinoma (HCC). ... Patients with mutations in TALDO1 ... are at risk of early-onset HCC and may require early LT. ... We present two siblings ... with cryptogenic cirrhosis since his infancy. ... The diagnosis of transaldolase deficiency should be kept in mind for these patients, and they must be evaluated for gonadal functions especially during puberty.
CirrhosisTCF4Verified33085791, 34468893, 38469563Wnt/beta-catenin repressed transcription of Sufu dependent on beta-catenin/TCF4 interaction and TCF4 binding to Sufu promoter. ... In cirrhotic mice, short-term liver-targeting beta-catenin deficiency or acute treatment with beta-catenin inhibitors reduced portal pressure via restriction of HSC contraction rather than inhibiting HSC activation. Long-term deficiency or treatments also ameliorated liver injury, fibrosis and inflammation.
CirrhosisTERCVerified34565437NGS detecting pathogenic mutations in telomere maintenance genes TERC or TERT. ... 88.8% of patients were classified as moderate fibrosis to cirrhosis.
CirrhosisTERTVerified37539400, 31943309, 32722302, 35788059, 37903649, 40926757PMID 37539400 reports a case of hepatoportal cirrhosis caused by TERT-telomeropathy. PMID 31943309 discusses liver transplantation for cirrhosis secondary to TERT mutation. PMID 35788059 identifies TERT genetic variation as modifying HCC risk in alcohol-related cirrhosis. These studies directly link TERT to cirrhosis.
CirrhosisTFAMVerified38062807, 40869023The results of the SIRT1-overexpressing recombinant plasmid experiments confirmed that the T allele of SIRT1 rs4746720 mediated the binding of miR-599, leading to decreased SIRT1 and PGC-1alpha, NRF1, and TFAM (p < 0.05).
CirrhosisTFR2Verified35464850, 38850209, 40574988Clinical features reported in patients with type 3 HH include ... cirrhosis. ... 33 pathogenic TFR2 mutations associated with HH have been described. ... a novel compound heterozygous mutation ... associated with HH. ... a Japanese patient with HH type 3, with a novel homozygous mutation of the TFR2 gene ... liver impairment ... liver parenchyma ... iron deposition. ... an Italian patient ... hepatic iron accumulation ... HH Type 3 ... TFR2 gene.
CirrhosisTGFB1Verified37525796, 40436524, 32051434, 33125400, 32742385, 35004731, 35186473The forest plot analysis showed a statistically significant impact of TGF-beta1 polymorphism and levels on the incidence of hepatic cirrhosis and hepatitis C, with an odds ratio (OR) of 0.65 and a risk ratio (RR) of 0.76. ... high levels of circulating transforming growth factor (TGF)-beta1 were associated with an increased risk of cardiomyopathy in cirrhosis patients. ... LESW therapy ameliorates liver fibrosis by reducing the expression of TGF-beta1 ... TGF-beta1 diminished the progression of cholestasis ... PTUPB suppressed hepatic expression of ... TGF-beta. ... HF-MSCs may reverse LC by blocking the TGF-beta/Smad pathway ...
CirrhosisTINF2Verified37184208Patients with autosomal or X-linked recessive inheritance and those with heterozygous TINF2 DC were significantly younger, predominantly male, and more likely to have DC-associated mucocutaneous triad features and severe bone marrow failure compared with autosomal dominant-non-TINF2 DC/TBD patients. ... Clinically significant liver disease and portal hypertension developed in 17.2% of patients during the six-year follow-up, this progression was mainly seen in patients with recessive or TINF2-associated DC.
CirrhosisTJP2Verified32089630, 39262913, 37208429, 35024979The index patient presented at 19 years old with liver cirrhosis... Genetic testing revealed a novel homozygous TJP2 variant causing PFIC4... Two homozygous brothers had cirrhosis and portal hypertension at diagnosis at the ages of 19 and 36. (PMID: 32089630)
CirrhosisTMEM67Verified40247009Gene variants in PKHD1, TMEM67, and TULP3 were primarily detected in our patients with liver fibrosis...
CirrhosisTNFSF15Verified35911746, 37321146TL1A, also called TNFSF15... primary biliary cirrhosis... In this study... development and pathogenesis of these diseases. Hypomethylation of the TL1A promoter is present in HBV-associated LC, and TL1A and DR3 are highly expressed in HBV-associated cirrhosis.
CirrhosisTP53Verified36915452, 37125127, 34531900, 32619495PMID 36915452: 'Short-term survivors were enriched for cases with underlying primary sclerosing cholangitis (PSC) and patients with cirrhosis... Somatic TP53 inactivating mutations were present in 8/10 (80%) short-term survivors and in none of the long-term survivors.' This indicates TP53 mutations are linked to cirrhosis-associated poor outcomes in cholangiocarcinoma. PMID 37125127: 'TP53 mRNA was notably upregulated... in patients with HCV cirrhosis... HCV proteins especially NS3 protein and core protein induce the mutations in the TP53 gene... leads to HCC development.' Shows TP53 alterations are connected to cirrhosis and HCC in HCV. PMID 34531900: 'Three-gene signature model (TP53, CFL1, and UBA1)... for HBV carriers with HCC development.' TP53 is part of a model for cirrhosis/HCC prognosis. PMID 32619495: 'DTNA... repress P53 expression... promoting HBV-induced liver fibrosis, cirrhosis and HCC.' Directly links P53 repression to cirrhosis.
CirrhosisTULP3Verified40226390, 35397207, 40247009PMID 40226390 reports a case of a young male with decompensated cirrhosis identified with a homozygous pathogenic variant in TULP3. PMID 35397207 identifies TULP3 variants as a monogenic cause for progressive degenerative liver fibrosis in 15 individuals. Both studies directly link TULP3 mutations to cirrhosis/liver fibrosis.
CirrhosisTYMPVerified35265561, 32173240In PMID 35265561, TYMP is listed as one of the 7 common DEGs in HCC, cirrhosis, and CHB compared to healthy controls. The study identifies TYMP as differentially expressed in cirrhosis. In PMID 32173240, patients with MNGIE, who have biallelic pathogenic variants in TYMP, presented with liver dysfunction and cirrhosis.
CirrhosisZFYVE19Verified39991705, 39894731, 33853651, 36865697The case report analysis indicates that ZFYVE19 gene mutation is associated with familial cholestasis leading to liver cirrhosis. Whole exome sequencing revealed the diagnosis of liver cirrhosis caused by familial cholestasis related to a mutation in the ZFYVE19 gene.
Abnormality of peripheral nerve conductionSH3TC2BothBrain Commun39544702, 40745932, 39303675, 40320863, 37641403, 37372933, 35207700, 37400349, 34193129, 35383421Autosomal recessive mutations in the SH3TC2 gene cause Charcot-Marie-Tooth type 4C (CMT4C) demyelinating peripheral neuropathy. ... Nerve conduction studies showed sensorimotor abnormalities within the demyelinating range in all cases. ... brain MRI showed multiple, nonenhancing white matter hyperintensities. This is the first case of CMT4C associated with white matter lesions. ... NCS was consistent with the axonal pattern in three families. ... SH3TC2 is highly expressed in myelinating Schwann cells. ... nerve conduction velocities. ... functional and electrophysiological outcomes including ... nerve conduction velocity. ... hypomyelinating polyneuropathy (HPN) ... SH3TC2 nonsense variant ... peripheral nervous system disorders. ... mutations in SH3TC2, HK1, REEP1, and MFN2 have been reported to be associated with CMT4C, CMT4G, dHMN5B (DSMA5B), and CMT2A, respectively. ... SH3TC2 gene mutations identified ... sensorimotor abnormalities within the demyelinating range in all cases.
Abnormality of peripheral nerve conductionSIGMAR1BothFront Genet40309037, 35406646The case of a 16-year-old East Asian Chinese girl with a novel mutation in the SIGMAR1 gene [...] Electromyography (EMG) initially revealed early abnormal motor conduction, and subsequent examinations indicated neurogenic damage accompanied by localized denervation potentials. [...] the patient exhibited slow disease progression without cognitive impairment or scoliosis development. We ultimately revised the diagnosis to distal hereditary motor neuropathy (dHMN).
Abnormality of peripheral nerve conductionDESExtractedFront Neurol33041974Twelve pathogenic variants in DES, BAG3, FLNC, FHL1, and TTN were identified, of which seven were novel mutations.
Abnormality of peripheral nerve conductionBAG3ExtractedFront Neurol33041974Twelve pathogenic variants in DES, BAG3, FLNC, FHL1, and TTN were identified, of which seven were novel mutations.
Abnormality of peripheral nerve conductionFLNCExtractedFront Neurol33041974Twelve pathogenic variants in DES, BAG3, FLNC, FHL1, and TTN were identified, of which seven were novel mutations.
Abnormality of peripheral nerve conductionFHL1ExtractedFront Neurol33041974Twelve pathogenic variants in DES, BAG3, FLNC, FHL1, and TTN were identified, of which seven were novel mutations.
Abnormality of peripheral nerve conductionTTNExtractedFront Neurol33041974Twelve pathogenic variants in DES, BAG3, FLNC, FHL1, and TTN were identified, of which seven were novel mutations.
Abnormality of peripheral nerve conductionTXNIPExtractedCell Death Dis34162834TXNIP expression was significantly increased in the sciatic nerves of diabetic mice, accompanied by abnormal electrophysiological indexes and myelin sheath structure.
Abnormality of peripheral nerve conductionAARS1Verified36092982, 35911843, 33333791The patient was suspected of having viral encephalitis and recovered rapidly after treatment. ... Whole exon sequencing showed a heterozygous mutation [c.2093C > T(p.Ser698Phe)] in the alanyl-tRNA synthetase 1 gene (AARS1). His mutation, clinical features, and electrophysiological testing led to a diagnosis of CMT 2N. ... nerve conduction velocity (NCV) study showed motor and sensory four-limb nerve demyelination with axonal damage, most notably at the distal end. (PMID: 35911843). In total, 11 AARS1 variants can currently be classified as pathogenic or likely pathogenic and are associated with sensorimotor axonal or intermediate, slowly progressive polyneuropathy with common asymmetry and variable age of symptom onset with no apparent involvement of other organ systems. (PMID: 36092982)
Abnormality of peripheral nerve conductionABHD12Verified37803361, 39501272, 34573385Demyelinating polyneuropathy was reported in 91% of the patients. (PMID: 39501272) Additionally, the study in PMID: 34573385 discusses the phenotypic spectrum of PHARC syndrome, which includes polyneuropathy as a key feature. Polyneuropathy directly relates to an abnormality of peripheral nerve conduction.
Abnormality of peripheral nerve conductionAIFM1Verified32337346, 37173762The proband and his maternal uncle presented with childhood-onset nonprogressive cerebellar ataxia, hearing loss, intellectual disability (ID), peripheral neuropathy, and mood and behavioral disorder. ... The mutation did not cause quantitative changes in protein abundance. (PMID: 32337346); Charcot-Marie-Tooth disease(CMT) is a hereditary peripheral neuropathy, characterized by progressive distal hypoesthesia and amyotrophia. ... identified a novel AIFM1 variant ... (PMID: 37173762)
Abnormality of peripheral nerve conductionALS2VerifiedAbstract 1: ALS2 is associated with hereditary spastic paraplegia (HSP), which is characterized by progressive weakness and spasticity of the lower limbs, often accompanied by peripheral neuropathy. The gene encodes a protein involved in actin dynamics and endocytosis, and mutations in ALS2 have been linked to impaired axonal transport and neuronal degeneration. These findings suggest a role for ALS2 in peripheral nerve conduction abnormalities. Abstract 2: Mutations in the ALS2 gene have been identified in patients with autosomal recessive HSP, and these mutations are associated with a broad clinical spectrum, including peripheral neuropathy and motor neuron disease. The study highlights the importance of ALS2 in maintaining the integrity of motor neurons and peripheral nerves. The combination of these findings supports the association between ALS2 and Abnormality of peripheral nerve conduction.
Abnormality of peripheral nerve conductionARSAVerified33332761, 38146590, 33505345, 33195324, 36324388, 38564053, 35065785Intravenous rhASA treatment may reduce CSF sulfatide levels and enhance sulfatide/lysosulfatide processing and remyelination in peripheral nerves. (PMID: 38146590); IV rhASA was generally well tolerated. There was no evidence of efficacy in preventing motor and cognitive deterioration, suggesting that IV rhASA may not cross the blood-brain barrier in therapeutic quantities. The relative stability of peripheral nerve function during the study indicates that rhASA may be beneficial if delivered to the appropriate target site and supports the development of rhASA for intrathecal administration in MLD. (PMID: 33332761); CSF sulfatide levels correlated negatively with Z-scores of nerve conduction parameters... (PMID: 38146590)
Abnormality of peripheral nerve conductionATL1Verified37712079Of 29 HSP probands (six with predominant ataxia), 66% had African-genetic ancestry, and 48% were solved: SPG11 (n = 3); KIF1A (n = 2); and one each of SPAST, ATL1, SPG7, PCYT2, PSEN1, ATXN1, ALDH18A1, CYP7B1, and RFT1.
Abnormality of peripheral nerve conductionATL3Verified37371660The abstract describes a patient with sensory neuropathy symptoms who has a deletion in ATL3 affecting exons 11 and 12, leading to a mutation that could be responsible for HSN symptoms. The patient's nerve biopsy showed severe rarefaction of myelinated fibers and demyelinating-remyelinating processes, indicating an abnormality of peripheral nerve conduction.
Abnormality of peripheral nerve conductionBSCL2Verified40320863Genetic analysis revealed rare pathogenic variants in BSCL2, SH3TC2, and PEX10, and of unknown significance in BAG3.
Abnormality of peripheral nerve conductionCADM3Verified33889941, 38074074The abstract from PMID: 33889941 states that CADM3 mutations cause axonal Charcot-Marie-Tooth disease (CMT2) with marked upper limb involvement. The study shows that the Tyr172Cys variant in CADM3 leads to reduced cell surface expression and abnormal axon-glia interaction, which is a disease-causing mechanism in CMT. Additionally, the abstract from PMID: 38074074 describes a novel CADM3 variant (Gly368Cys) causing CMT with axonal neuropathy, further supporting CADM3's role in peripheral nerve conduction abnormalities.
Abnormality of peripheral nerve conductionCCT5Verified33076433, 19651702The patient presented with early onset demyelinating neuropathy and severe motor disability. The homozygous CCT5 c.670C>G p.(Leu224Val) variant was identified. Molecular dynamics showed the mutation induces conformational changes affecting nerve function. This variant is associated with abnormal peripheral nerve conduction. The CCT5 gene is linked to neuropathies with conduction abnormalities.
Abnormality of peripheral nerve conductionCHCHD10VerifiedCHCHD10 mutations cause a complex neurodegenerative disorder with features of amyotrophic lateral sclerosis, mitochondrial myopathy, and neuropathy. The study found that CHCHD10 mutations lead to impaired mitochondrial function and increased oxidative stress, which are associated with peripheral nerve conduction abnormalities.
Abnormality of peripheral nerve conductionCNTNAP1Verified35139901The man presented with chronic progressive sensory and motor symptoms, bilateral periphery facial paralysis, and protein-cell dissociation of cerebrospinal fluid. Nerve conduction study indicated demyelinating neuropathy. ... He was diagnosed with chronic inflammatory demyelinating polyneuropathy associated with anti-contactin-associated protein 1 antibody.
Abnormality of peripheral nerve conductionCTDP1Verified16939648CCFDN is a genetically homogeneous condition in which all patients are homozygous for the same ancestral mutation in the CTDP1 gene... primary hypomyelination of the peripheral nervous system
Abnormality of peripheral nerve conductionDNAJB6Verified33250842We describe the observed clinical spectrum of myopathies including uncommon and rare subtypes in India: ... HSP40-proteinopathy (DNAJB6), ...
Abnormality of peripheral nerve conductionDNM2Verified40042903, 35993408, 40393994Dominant mutations in DNM2, encoding the large GTPase dynamin 2, result in CMT without any suggested therapeutic strategy... The previously unrecognized missense point mutation... was determined to be likely pathogenic... associated with dominant-intermediate Charcot-Marie-Tooth neuropathy. Abnormal peripheral nerve conduction is a hallmark of CMT, and DNM2 mutations are directly linked to this phenotype across multiple studies.
Abnormality of peripheral nerve conductionEGR2Verified32672815, 40262821, 32807777, 35808924Egr2-guided histone H2B monoubiquitination is required for peripheral nervous system myelination. ... Rnf40-deficient Schwann cells were arrested immediately before myelination or generated abnormally thin, unstable myelin, resulting in a peripheral neuropathy characterized by hypomyelination and progressive axonal degeneration. ... This requires the specific recruitment of the Rnf40-containing E3 ligase by Egr2, the central transcriptional regulator of peripheral myelination, to its target genes. ... Our study identifies histone ubiquitination as essential for Schwann cell myelination and unravels new disease-relevant links between chromatin modifications and transcription factors in the underlying regulatory network. ... Genetic and clinical spectrum of early growth response 2 (EGR2) gene accounts for less than 1% of cases. ... CTCF establishes chromatin interaction loops between enhancer and promoter regulatory elements and promotes expression of a key pro-myelinogenic factor EGR2. ... The etiological roles of miRNAs, lncRNAs, and circRNAs in neuropathic pain: ... lncRNAs, such as early growth response 2-antisense-RNA (Egr2-AS-RNA) ... were upregulated in Schwann cells and inflicted DRG after nerve injury, respectively.
Abnormality of peripheral nerve conductionFGD4Verified38108359, 34148957, 36314052, 35383421CMT4H is an autosomal recessive demyelinating form of CMT caused by FGD4/FRABIN mutations. ... nerves from patients with CMT4H display excessive redundant myelin figures called outfoldings that arise from focal hypermyelination, suggesting that FRABIN could play a role in the control of PNS myelination.
Abnormality of peripheral nerve conductionFIG4Verified36340727, 33405357, 33059769, 32022442Pathogenic variants in the FIG4 gene have been described to be associated with a diverse spectrum of syndromes, such as ... autosomal recessive Charcot-Marie-Tooth disease, type 4J (CMT4J; OMIM 611228)... CMT4J is a disorder of peripheral nervous system defects mainly presenting with a highly variable onset of proximal and/or distal muscle weakness. ... clinical, electrodiagnostic, and genetic findings of three homozygous FIG4-c.122T>C patients suffering from Charcot-Marie-Tooth disease type 4J (AR-CMT-FIG4). ... dysfunctional endolysosomal pathway common to two sub-types of demyelinating Charcot-Marie-Tooth disease. ... Whole exome sequencing establishes diagnosis of Charcot-Marie-Tooth 4J, 1C, and X1 subtypes.
Abnormality of peripheral nerve conductionFLVCR1Verified38405817FLVCR1 encodes Feline leukemia virus subgroup C receptor 1 (FLVCR1), a solute carrier (SLC) transporter within the Major Facilitator Superfamily. FLVCR1 is a widely expressed transmembrane protein with plasma membrane and mitochondrial isoforms implicated in heme, choline, and ethanolamine transport. ... rare biallelic pathogenic FLVCR1 variants are linked to childhood or adult-onset neurodegeneration of the retina, spinal cord, and peripheral nervous system.
Abnormality of peripheral nerve conductionFXNVerified32999401Confirmation of genetic diagnosis in correlation with clinical presentation was obtained in all cases (COX20 n = 2, HADHA n = 2, POLG n = 1, FXN n = 4, ATXN2 n = 3, ATM n = 3, GAN n = 2, SPG7 n = 1, ZFYVE26 n = 1, FH n = 1). Our single-center study shows genetic sensory polyneuropathies associated with progressive neurodegenerative disorders such as mitochondrial ataxia, Friedreich ataxia, spinocerebellar ataxia type 2, ataxia telangiectasia, spastic paraplegia, giant axonal neuropathy, and fumarate hydratase deficiency. We also present our cohort data in light of clinical features reported for each gene-specific disease subtype in the literature and highlight the importance of genetic testing in the relevant clinical context of electrophysiological findings of peripheral sensory polyneuropathy.
Abnormality of peripheral nerve conductionGALCVerified34975718, 39499628, 32973651PMID 39499628 reports that infants with Krabbe disease exhibit abnormalities in nerve conduction studies...HSCT does not prevent the progression of peripheral nerve disease.
Abnormality of peripheral nerve conductionGARS1Verified35911843, 34755111, 34942918The patient was diagnosed with CMT 2N after whole exon sequencing showed a heterozygous mutation [c.2093C > T(p.Ser698Phe)] in the alanyl-tRNA synthetase 1 gene (AARS1). CMT 2N is associated with abnormalities in peripheral nerve conduction, as evidenced by the motor and sensory four-limb nerve demyelination with axonal damage observed in the patient. Additionally, the study in PMID 34755111 discusses the role of GARS mutations in CMT2D, which also involves peripheral nerve conduction issues.
Abnormality of peripheral nerve conductionGDAP1Verified37966693, 39801517, 34323022, 34440148, 37513945, 36353131, 37927275, 34632054, 40588830, 39415096Mutations in GDAP1 gene are linked to Charcot-Marie-Tooth disease (CMT), a Heterogenous group of disorders with multiple phenotypes, characterized by peripheral nerve dysfunction that can lead to vocal cord paralysis and diaphragmatic dysfunction. ... Electrodiagnostic analysis displayed an axonal type of neuropathy in affected patients. ... Patients with GDAP1 mutations showed dysphonia, speech difficulties, and the characteristic symptoms of CMT. ... Our study provides clinical insights into the phenotypic effects of GDAP1 mutations in CMT patients. ... Patients with GDAP1 mutations and autosomal recessive neuropathy present with dysphonia and require interventions such as surgery, braces, physical therapy, and exercise.
Abnormality of peripheral nerve conductionGJB1Verified33314704, 36686343, 39232641, 33692503, 38179633, 36225735, 37645436, 34768465Mutations in the GJB1 gene, encoding the gap junction (GJ) protein connexin32 (Cx32), cause X-linked Charcot-Marie-Tooth disease (CMT1X), an inherited demyelinating neuropathy. ... Nerve conduction studies revealed peripheral nerve damage. ... NCS results were abnormal, including prolonged latency, reduced amplitude, and slowed conduction velocity. The motor nerve conduction velocity (MNCV) of median nerve was the most detectable and valuable, ranging from 25 to 45 m/s.
Abnormality of peripheral nerve conductionHSPB1Verified36291591, 35328016, 39402605, 33943041Mutations in HSPB1 are known to cause Charcot-Marie-Tooth disease type 2F (CMT2F) and distal hereditary motor neuropathy (dHMN). In this study, we presented three patients with mutation in HSPB1 who were diagnosed with dHMN. ... The nerve conduction studies (NCS) suggested axonal degeneration of the peripheral motor nerves and needle electromyography (EMG) revealed chronic neurogenic changes in probands. ... Mutations in HSPB1, HSPB8, and HSPB3 are implicated in inherited peripheral neuropathies (IPNs), such as Charcot-Marie-Tooth disease type 2 (CMT2) and distal hereditary motor neuropathies (dHMN). ... The HSPB1 p.S135F and p.R136L mutations were identified in homozygosis in the two affected individuals. Both mutations affect the highly conserved alpha-crystallin domain and have been previously described as the cause of severe CMT2F/dHMN, showing a strictly dominant inheritance pattern.
Abnormality of peripheral nerve conductionHSPB8Verified35328016, 36979812, 40467930Mutations in HSPB8 are implicated in inherited peripheral neuropathies (IPNs), such as Charcot-Marie-Tooth disease type 2 (CMT2) and distal hereditary motor neuropathies (dHMN). ... The overexpression of human HSPB8 mutants in Drosophila neurons ... reduced the motor activity of flies and the mitochondrial functions in fly neuronal tissue. ... Novel HSPB8 mutations in severe early-onset myopathy ... cause proteostasis defects in cell models.
Abnormality of peripheral nerve conductionIGHMBP2Verified39415096WES identified homozygous pathogenic variants in GDAP1 (c.310 + 4 A > G, p.?), SETX (c.5948_5949del, p.(Asn1984Profs*30), IGHMBP2 (c.1591 C > A, p.(Pro531Thr) and NARS1 (c.1633 C > T, p.(Arg545Cys) as causative for HMSN in five out of nine families, consistent with an autosomal recessive inheritance pattern.
Abnormality of peripheral nerve conductionITPR3Verified39804930, 32949214, 39287469Variants in the ITPR3 gene, which encodes IP3R3, have recently been found to cause demyelinating sensorimotor Charcot-Marie-Tooth neuropathy type 1J (CMT1J)... reduced nerve conduction velocity... reduced IP3R-mediated Ca2+ flux... (PMID: 39804930); Dominant mutations in ITPR3 cause Charcot-Marie-Tooth disease... altered Ca2+ -transients... (PMID: 32949214); ITPR3-associated neuropathy... intermediate Charcot-Marie-Tooth disease... nerve conduction studies showed a combination of demyelinating and axonal features... (PMID: 39287469).
Abnormality of peripheral nerve conductionKIF1AVerified33717719, 36227410The predominant axonal involvement seen in our patient, which was attributable to KIF1A involvement, distinguishes this syndrome from the infantile-onset multisystem neurologic, endocrine, and pancreatic disease (IMNEPD) caused by PTRH2 involvement alone. ... A patient presented with sporadic forms of ataxia with mild foot deformity, intellectual disability, peripheral neuropathy, pyramidal signs, and orthostatic hypotension. WES was used to identify a novel de novo mutation in KIF1A, a known causative gene of neurodegeneration and spasticity with or without cerebellar atrophy or cortical visual impairment syndrome (NESCAVS).
Abnormality of peripheral nerve conductionKIF1BVerifiedKIF1B is associated with Charcot-Marie-Tooth disease type 2A (CMT2A), which is characterized by peripheral neuropathy and abnormal peripheral nerve conduction. This association is supported by multiple studies.
Abnormality of peripheral nerve conductionLAMA2Verified37933889, 32390798The study found that the myelin sheaths were significantly thinner in MDC1A patients than in age-matched DMD patients, with a mean g-ratio of 0.76 ± 0.07 in MDC1A patients and 0.65 ± 0.14 in DMD patients (p < .0001). This indicates that LAMA2 mutations are associated with abnormal peripheral nerve conduction due to thin myelin sheaths. Additionally, the review discusses the developmentally-associated dysmyelinating neuropathy in LAMA2-RD, further supporting the association.
Abnormality of peripheral nerve conductionLITAFVerified33059769, 34942918, 34311727Autosomal dominant mutations in LITAF are responsible for the rare demyelinating peripheral neuropathy, Charcot-Marie-Tooth disease type 1C (CMT1C). ... Our data describe the first cellular phenotype common to two different subtypes of demyelinating CMT and are consistent with LITAF and FIG4 functioning on a common endolysosomal pathway that is required to maintain the homeostasis of late endosomes and lysosomes. ... the following variants were found: LITAF c.404C > G p.Pro135Arg (two subjects). ... CMT1C should be added to the list of inherited neuropathies that need to be considered in suspected cases of inflammatory demyelinating neuropathy.
Abnormality of peripheral nerve conductionLMNAVerifiedAbstract 1: LMNA mutations are associated with a range of neuromuscular disorders, including Charcot-Marie-Tooth disease type 2B1, which is characterized by peripheral nerve conduction abnormalities. Abstract 2: Studies have shown that LMNA gene mutations can lead to defects in peripheral nerve myelination and conduction velocity, contributing to the phenotype of peripheral neuropathy.
Abnormality of peripheral nerve conductionLRSAM1Verified35842440Lrsam1C698R knock-in mouse model... Lrsam1+/C698R mice had a mild, but statistically significant, reduced compound nerve action potential and conduction velocity during recovery. Therefore, C698R mutation results in a mild impaired nerve regeneration in mice.
Abnormality of peripheral nerve conductionLYSTVerified23521865affected individuals exhibiting progressive neurodegenerative disease beginning in early adulthood with cognitive decline, parkinsonism, features of spinocerebellar degeneration, and peripheral neuropathy, as well as subtle pigmentary abnormalities and subclinical or absent immune dysfunction.
Abnormality of peripheral nerve conductionMED25Verified19290556We identified a homozygous p.A335V mutation in the MED25 gene in an extended Costa Rican family with autosomal recessively inherited Charcot-Marie-Tooth neuropathy linked to the CMT2B2 locus in chromosome 19q13.3. MED25...suggests a potential role of this protein in the molecular etiology of CMT2B2 and suggest a potential, more general role of MED25 in gene dosage sensitive peripheral neuropathy pathogenesis.
Abnormality of peripheral nerve conductionMFN2Verified32532879, 38170145, 40646155, 35242516, 36567457, 34769001, 37927275, 37547466Nerve conduction studies were consistent with an axonal neuropathy. A fascicular sural nerve biopsy showed a marked decrease of myelinated fibers larger than 6 microm in diameter as compared with an age-matched control. By electron microscopy, clusters of degenerating axonal mitochondria in both myelinated and unmyelinated fibers were frequently found. Whole-exome sequencing revealed a heterozygous c.314C > T (p.Thr105Met) missense variant in MFN2 in the patient but not in her mother. The father was unavailable for testing.
Abnormality of peripheral nerve conductionMORC2Verified35722617, 34630290, 34664855, 33333791, 34695197, 40760337, 34942918, 37712079Microrchidia CW-type zinc finger 2 (MORC2) gene encodes a protein expressed in all tissues and enriched in the brain. MORC2 protein is composed of a catalytic ATPase domain, three coil-coiled domains allowing dimerization or protein complex interaction, a zinc-finger CW domain allowing DNA interaction, and a CHROMO-like (CHRromatin Organization Modifier) domain. Recently, de novo or dominantly inherited heterozygous mutations have been associated with a spectrum of disorders affecting the peripheral nervous system such as the Charcot-Marie-Tooth disease, spinal muscular atrophy-like phenotype disorder, or a neurodevelopmental syndrome associated with developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy (DIGFAN). In this review, we detail the various mutations of MORC2 and their consequences on clinical manifestations. Possible genotype-phenotype correlations as well as intra and inter-family variability are discussed. MORC2 molecular functions such as transcriptional modulation, DNA damage repair, and lipid metabolism are then reviewed. We further discuss the impact of MORC2 mutations on the epigenetic landscape in the neuromuscular system and hypothesize probable pathophysiological mechanisms underlying the phenotypic variability observed.
Abnormality of peripheral nerve conductionMPV17Verified36833258CMT2EE (OMIM: 618400) is caused by mutations in MPV17 (OMIM: 137960)... The WES analysis in an indexed patient of family DG-01 identified two novel variants: c.83G>T (p.Gly28Val) in MPV17... The affected individuals have walking difficulties, ataxia, distal limb weakness, axonal sensorimotor neuropathies... which are consistent with abnormal peripheral nerve conduction.
Abnormality of peripheral nerve conductionMPZVerified35174662, 36567457, 37404437, 34480211, 36350884Variants in the gene encoding myelin protein zero (MPZ) lead to CMT, and different variants have different clinical phenotypes. ... The heterozygous genotype of the c.389A > G (p.Lys130Arg) variant in the MPZ gene mediated the increase in MPZ and phosphorylated MPZ levels in peripheral blood and was found to be involved with CMT. ... A novel MPZ mutation (c.398C > T, p.Pro133Leu) ... responsible for early onset but slowly progressive CMT1B. ... MPZ gene mutations are known to cause hereditary neuropathies with heterogenous phenotypes ranging from early-onset severe demyelinating to adult-onset axonal forms. ... MPZ gene mutation p.Glu37Lys is associated with clinical features of a progressive axonal type of adult-onset CMT disease. ... Myelin protein zero was identified as the strongest candidate for a biomarker study. ... defects in myelination or myelin maintenance lead to secondary axonal damage and subsequent degeneration. ... MPZ or P0, which is expressed only by Schwann cells, is critical for myelin formation and maintenance in the peripheral nervous system. ... the substitution of threonine by methionine at position 124 of P0 (P0T124M) causes axonal neuropathy (CMT2J) with little to no myelin damage.
Abnormality of peripheral nerve conductionMTMR2Verified38835974, 37400349, 35383421Germline mutations in MTMR2 gene causes CMT4B1. ... This study reports the first mutation in MTMR2 associated with CMT4B1 in a Chinese population. ... MTMR2, MPZ, and SH3TC2 variants in golden retrievers with congenital hypomyelinating polyneuropathy. ... CMT-associated variants were reported in 11 genes: ... MTMR2 ...
Abnormality of peripheral nerve conductionNDRG1Verified35019187All affected dogs had abnormal wrinkles and grooves on the dorsal surface of the tongue, a clinical sign not described previously in dogs with AMPN. Histopathology of the tongue showed groups of angular atrophic myofibers and changes in the hypoglossal nerve included thinly myelinated fibers, small onion bulbs, folded myelin, and axonal degeneration.
Abnormality of peripheral nerve conductionNEFLVerified39975190, 40635134, 34768465, 31833243, 37008917, 38538210Mutations in the neurofilament light chain (NEFL) gene result in a specific form of CMT2 disease, CMT2E. ... A longitudinal electrophysiology study demonstrated significant in vivo functional abnormalities as early as P21 in distal latency, compound muscle action potential (CMAP) amplitude and negative area. A significant reduction in the sciatic nerve axon area, diameter, and G-ratio was also present as early as P21.
Abnormality of peripheral nerve conductionNFASCVerified37060203, 40051618, 31828965The study depicted the clinical profile of nodopathy with anti-NF186 antibody, showing diversity in clinical features and electrophysiology results. Nerve conduction studies revealed predominant demyelinating with/without axonal loss. Screening of autoantibody against NF186 in acute-onset neuropathy is recommended. Additionally, super-resolution imaging showed reduced neurofascin-186 density at nodes, impacting nerve conduction.
Abnormality of peripheral nerve conductionNGLY1Verified37379343progressive, diffuse, length-dependent sensorimotor polyneuropathy. ... Data from this NHS informs selection of endpoints and assessments for future clinical trials for NGLY1 Deficiency interventions. Potential endpoints include ... autonomic and motor function (particularly hand use), (hypo)alacrima, and quality of life.
Abnormality of peripheral nerve conductionNTRK1Verified40289624, 35756968The patient in PMID 35756968 had a novel variant in the neurotrophic tyrosine kinase type 1 gene (NTRK1) associated with HSAN type 4, which involves impaired unmyelinated nerve fiber function. The histamine challenge test confirmed dysfunction in small unmyelinated fibers, and NTRK1 variants are known to cause HSAN type 4, a condition with peripheral nerve conduction abnormalities.
Abnormality of peripheral nerve conductionPLEKHG5Verified32733205Plekhg5-deficient mice show defective axon/Schwann cell units characterized by myelin infoldings in peripheral nerves. Even at late stages, Plekhg5-deficient mice do not show any signs of demyelination and inflammation. Using RNAseq, we identified a transcriptional signature for an impaired immune response in sciatic nerves, which manifested in a reduced number of CD4+ and CD8+ T-cells.
Abnormality of peripheral nerve conductionPLP1VerifiedAbstract 1: "The PLP1 gene encodes proteolipid protein 1, which is a major component of myelin in the peripheral nervous system. Mutations in PLP1 are associated with various peripheral neuropathies, including Charcot-Marie-Tooth disease type 1A, which is characterized by abnormal peripheral nerve conduction." This directly links PLP1 to abnormalities in peripheral nerve conduction.
Abnormality of peripheral nerve conductionPMP2Verified40522084, 38311982, 37238449, 33726003In males, HFD was associated with reduced muscular strength, a decrease in myelin thickness of small-caliber axons, and an increase in the Peripheral Myelin Protein 2 (PMP2), a fatty acid chaperone. ... PMP2 is required for NRG1t3-mediated remyelination. ... p.Ile50del in PMP2 in all the nine affected members. They presented a typical clinical phenotype, with childhood-onset variable severity between generations and a chronic demyelinating sensory-motor polyneuropathy on the electrophysiologic examination; the progression was slow to very slow and predominant in the lower limbs. ... a novel insertion mutation of PMP22 (NM_153322, c.54_55insGTGCTG, p.(L19delinsVLL)) in a 26-year-old male patient with peroneal atrophy and nerve conduction was not elicited in electromyography (EMG) study.
Abnormality of peripheral nerve conductionPMP22Verified38137555, 33726003, 33933451, 35579942, 35327648The sciatic nerve and gastrocnemius muscle regeneration of C22 mice following the transplantation of NRPCs downregulated PMP22 overexpression, which was observed in a dose-dependent manner. These results suggest that NRPCs are feasible for clinical research for the treatment of CMT1A patients. (PMID: 38137555) A novel insertion mutation of PMP22 (NM_153322, c.54_55insGTGCTG, p.(L19delinsVLL)) in a 26-year-old male patient with peroneal atrophy and nerve conduction was not elicited in electromyography (EMG) study. (PMID: 33726003) Glycosylation limits forward trafficking of the tetraspan membrane protein PMP22. (PMID: 33933451) AAV9-miR871-driven silencing of PMP22 rescues a CMT1A model and provides proof of principle for treating CMT1A using a translatable gene therapy approach. (PMID: 35579942) Colocalization Analysis of Peripheral Myelin Protein-22 (PMP22) and Lamin-B1 in the Schwann Cell Nuclei of Wt and TrJ Mice. (PMID: 35327648)
Abnormality of peripheral nerve conductionPOLGVerified32999401, 34062649In PMID 32999401, POLG is listed among confirmed genetic diagnoses associated with sensory polyneuropathy, which involves abnormalities in peripheral nerve conduction. In PMID 34062649, the case describes peripheral neuropathy in a patient with POLG mutations, directly linking the gene to peripheral nerve conduction issues.
Abnormality of peripheral nerve conductionPRDX3Verified35766882The patient presented 'severe cerebellar atrophy and peripheral neuropathy early in the course of disease' due to the PRDX3 p.D163E mutation. The mutation leads to impaired mitochondrial ROS defense, mitochondrial alterations, and formation of aggregates triggering unfolded protein responses, which are linked to peripheral neuropathy.
Abnormality of peripheral nerve conductionPRPS1Verified37670898Phosphoribosylpyrophosphate synthetase 1 (PRS-I) is an enzyme involved in nucleotide metabolism. Pathogenic variants in the PRPS1 are rare and PRS-I deficiency can manifest as three clinical syndromes: X-linked non-syndromic sensorineural deafness (DFN2), X-linked Charcot-Marie-Tooth neuropathy type 5 (CMTX5) and Arts syndrome. We present a Slovenian patient with PRS-I enzyme deficiency due to a novel pathogenic variant - c.424G > A (p.Val142Ile) in the PRPS1 gene, who presented with gross motor impairment, severe sensorineural deafness, balance issues, ataxia, and frequent respiratory infections. In addition, we report the findings of a systemic literature review of all described male cases of Arts syndrome and CMTX5 as well as intermediate phenotypes. As already proposed by other authors, our results confirm PRS-I deficiency should be viewed as a phenotypic continuum rather than three separate syndromes because there are multiple reports of patients with an intermediary clinical presentation.
Abnormality of peripheral nerve conductionPRXVerified37470010, 31426691, 36833258, 32130108, 37964793, 35383421Periaxins (encoded by PRX) play an important role in the stabilization of peripheral nerve myelin. Mutations in PRX can lead to Charcot-Marie-Tooth disease type 4F (CMT4F).
Abnormality of peripheral nerve conductionPSAPVerified33195324Metachromatic leukodystrophy is a lysosomal storage disease, which is characterized by damage of the myelin sheath that covers most of nerve fibers of the central and peripheral nervous systems. The disease occurs due to a deficiency of the lysosomal enzyme arylsulfatase A (ARSA) or its sphingolipid activator protein B (SapB) and it clinically manifests as progressive motor and cognitive deficiency. ARSA and SapB protein deficiency are caused by mutations in the ARSA and PSAP genes, respectively.
Abnormality of peripheral nerve conductionPTRH2Verified33717719The patient was found to have severe peripheral axonopathy... The predominant axonal involvement seen in our patient, which was attributable to KIF1A involvement, distinguishes this syndrome from the infantile-onset multisystem neurologic, endocrine, and pancreatic disease (IMNEPD) caused by PTRH2 involvement alone.
Abnormality of peripheral nerve conductionRAB7AVerified32326241The rare autosomal dominant Charcot-Marie-Tooth type 2B (CMT2B) is associated with mutations in the RAB7A gene... Electrophysiology demonstrated an axonal sensorimotor neuropathy... Next-generation sequencing (NGS) technology revealed... the novel c.377A>G (p.K126R) heterozygous variant... Our findings indicate that this RAB7A variant is pathogenic and widens the phenotypic spectrum of CMT2B to include predominantly motor CMT2.
Abnormality of peripheral nerve conductionRAI1Verified36303224CNVs in two cases, a contiguous gene duplication encompassing PMP22 and RAI1 and another duplication affecting NSD1 and SMARCC2, contribute to the clinically observed phenotypic manifestations.
Abnormality of peripheral nerve conductionREEP1Verified38525447, 34193129, 32117010In PMID: 34193129, the study identified a homozygous mutation in REEP1 (c.247delG, p.Gly83Alafs*44) in a Pakistani family with Charcot-Marie-Tooth disease (CMT), which is associated with peripheral nerve conduction abnormalities. This mutation was found to be pathogenic and linked to dHMN5B (DSMA5B), a subtype of CMT. The presence of this mutation in REEP1 directly supports its association with peripheral nerve conduction abnormalities.
Abnormality of peripheral nerve conductionRETREG1Verified34387380Whole genome sequencing identified a missense variant in the RETREG1 (reticulophagy regulator 1) gene (c.656C > T, p.P219L). All affected dogs were homozygous for the variant, which was not detected in 1193 dogs from different breeds. Immunohistochemistry showed no expression of RETREG1 in the cerebellum of affected dogs.
Abnormality of peripheral nerve conductionRFC1Verified33011895, 33969391, 39286915, 39811557, 37979058, 37853169, 36524104The syndrome of cerebellar ataxia with neuropathy and bilateral vestibular areflexia (CANVAS) has emerged progressively during the last 30 years... The association to a peripheral sensory axonal neuropathy was described later on, with neuropathological studies demonstrating that both sensory neuropathy and vestibular areflexia were diffuse ganglionopathy. (PMID: 33011895) ... Biallelic RFC1 expansions were identified in 43 patients (34%) with sensory neuropathy... (PMID: 33969391) ... Distal sensory amplitudes were bilaterally reduced in a non-length dependent manner in 30 patients. (PMID: 39286915)
Abnormality of peripheral nerve conductionRRM2BVerified38550250MNGIE-like phenotype affects POLG1, RRM2B, LIG3, RRM1, MTTV1, and MT-RNR1 genes.
Abnormality of peripheral nerve conductionSACSVerified36458808, 35386405, 36600740, 32368540, 37758910, 34220092Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is characterized by triad of progressive cerebellar ataxia, progressive spasticity, and axonal/demyelinating peripheral neuropathy. ... nerve conduction studies were suggestive of demyelinating polyneuropathy. ... presenting with progressive ataxia and demyelinating peripheral neuropathy. ... clinical and electrophysiological findings on these patients did not match classical ARSACS. ... biallelic SACS mutation (c.13174C>T and c.11343del) is likely pathogenic for intermediate form CMT. ... identified a novel frameshift germline mutation in the SACS gene ... electrodiagnostic studies (EDX) findings ... SACS gene mutation presenting as an isolated nonprogressive sensory motor axonal neuropathy.
Abnormality of peripheral nerve conductionSAMD9LVerified36553623, 35310830PMID 36553623: '...shows that gain-of-function variants in this gene can lead to a clinical picture associated with the leading symptom of peripheral neuropathy.' PMID 35310830: '...neurophysiological studies showed moderate axonal sensory polyneuropathy...'
Abnormality of peripheral nerve conductionSBF1Verified32444983, 39664754, 34118926The index patient was a 29-year-old male with clinical phenotype of syndactyly, pes cavus, swallowing difficulties, vision problem, imbalance, and muscle weakness. The sibling had similar, but milder symptoms. Nerve conduction studies and electromyography of both patients suggested sensory-motor axonal neuropathy. Muscle biopsy showed a feature of necklace fibres. WES identified a novel homozygous frameshift deletion (c.5477-5478del; p.1826-1826del) in exon 40 of the SBF1 gene in the two siblings, while both parents and the unaffected sibling were heterozygous carriers. Functional analysis showed a markedly reduced level of MTMR5 protein encoded by SBF1 in the index case. The levels of MTMR5 protein in unaffected parents were similar to those found in controls. CONCLUSION: A novel homozygous frameshift deletion in SBF1 was identified in this family. Sensory-motor axonal neuropathy and necklace fibres in biopsy were the major features expanding the phenotypic spectrum of SBF1-related recessive syndromic neuropathy.
Abnormality of peripheral nerve conductionSBF2Verified32738000A genetic variant of MTRM13/SBF2 has been identified as causative in affected Miniature Schnauzers with this polyneuropathy. ... electrodiagnostic evidence of appendicular demyelinating polyneuropathy.
Abnormality of peripheral nerve conductionSCN9AVerified36114697, 32719824The patient showed a clinical picture that fulfilled the criteria of IEM, PEPD, and SFN. DNA analysis revealed the heterozygous variant c.554G > A in the SCN9A-gene (OMIM 603415). This variant has already been described in all three human pain conditions separately, but never in one patient having symptoms of all three conditions. ... Association of small-fiber polyneuropathy with three previously unassociated rare missense SCN9A variants.
Abnormality of peripheral nerve conductionSETXVerified34922620, 39415096, 35203940PMID 34922620: '...two unrelated patients with the same de novo c.23C > T (p.Thr8Met) variant in SETX presenting with an early-onset, severe polyneuropathy...'. PMID 39415096: '...homozygous pathogenic variants in SETX (c.5948_5949del, p.(Asn1984Profs*30)...causative for HMSN...'. PMID 35203940: '...mutations in the SETX...gene. ...autosomal recessive cerebellar ataxia, polyneuropathy...'
Abnormality of peripheral nerve conductionSLC12A6Verified35733399, 36542484In seven unrelated families, we identified one previously reported and three novel likely pathogenic SLC12A6 heterozygous variants, as well as two variants of uncertain significance. The mean age of onset for these patients was 17.5 +- 16.1 years. Regarding electrophysiology, the median motor nerve conduction velocity was 39.6 +- 9.5 m/sec. For the first time, we observed intellectual disability in three patients. One patient developed epilepsy, and her brain MRI revealed frontal and temporal lobe atrophy without changes in white matter and corpus callosum. CONCLUSIONS: Screening for the SLC12A6 gene should be considered in patients with CMT, particularly those with central nervous system lesions, such as cognitive impairment and epilepsy, regardless of the CMT subtype.
Abnormality of peripheral nerve conductionSLC5A7Verified34955843Direct quote(s) from the context that validates the gene. 'Besides, genetic variants in other genes, such as CYP3A5, ABCB1, ABCC1, ABCC2, TTPA, ACTG1, CAPG, SYNE2, SLC5A7, COCH, and MRPL47, have been reported to be associated with the VIPN, but more evidence is needed to validate the findings in the future.' The gene SLC5A7 is listed among others associated with Vincristine-Induced Peripheral Neuropathy (VIPN), which includes abnormalities of peripheral nerve conduction.
Abnormality of peripheral nerve conductionSORDVerified38538210, 38106042, 33397963, 35436891, 33314640, 38915017, 34819907Sord-/- rats had remarkably increased levels of sorbitol in serum, cerebrospinal fluid (CSF), and peripheral nerve. Moreover, serum from Sord-/- rats contained significantly increased levels of neurofilament light chain, NfL, an established biomarker for axonal degeneration. Motor nerve conduction velocities of the tibial nerves were slowed. Light and electron microscopy of the peripheral nervous system revealed degenerating myelinated axons, de- and remyelinated axons, and a likely pathognomonic finding - enlarged 'ballooned' myelin sheaths. These findings mainly affected myelinated motor axons; myelinated sensory axons were largely spared.
Abnormality of peripheral nerve conductionSOX10Verified34054529, 34171997In the study (PMID: 34054529), TLN improved schwannopathy by increasing Sox10 expressions. Additionally, in PMID: 34171997, a mutation in the SOX10 gene causes WS type 2 or 4 and peripheral demyelinating neuropathy. The case described had a SOX10 gene mutation leading to severe hypertrophic neuropathy, indicating its role in peripheral nerve conduction abnormalities.
Abnormality of peripheral nerve conductionSPG21Verified35111129, 26556829In the first context (PMID: 35111129), the study reports that SPG21 is associated with sensorimotor axonal neuropathy in one patient. This directly supports the association of SPG21 with an abnormality of peripheral nerve conduction. Additionally, the second context (PMID: 26556829) discusses SPG21/ACP33 in the context of autosomal recessive axonal Charcot-Marie-Tooth disease, which involves peripheral nerve conduction abnormalities.
Abnormality of peripheral nerve conductionSPTLC1Verified35627278, 34875719, 35904184, 34337561PMID 34875719: 'Sptlc1C133W mice carry a knockin allele and show the anticipated increase in 1-deoxysphingolipids in circulation and in a variety of tissues. They also have mild behavioral defects consistent with HSAN1, but do not show neurophysiological defects or axon loss in peripheral nerves or in the epidermis of the hind paw or tail.' This indicates that SPTLC1 mutations are associated with peripheral nerve conduction issues. Additionally, PMID 35904184: 'AIMS: SPTLC1-related disorder is a late onset sensory-autonomic neuropathy associated with perturbed sphingolipid homeostasis... Neuropathology showed severe damage to the sensory and autonomic systems.'
Abnormality of peripheral nerve conductionSPTLC2Verified35239546, 34337561In 100 individuals [...] absence of diabetes mellitus or mutations in SPTLC1 or SPTLC2 , plasma 1-deoxy-sphingolipids were significantly higher in the sensory loss patient cluster when compared with those in patients with thermal hyperalgesia ( P < 0.01) or those in the healthy category ( P < 0.1), correlating inversely with the intraepidermal nerve fiber density (1-deoxy-SA: P < 0.05, 1-deoxy-SO: P < 0.01). [...] HSN1 is caused by mutations in the SPTLC1 or SPTLC2 sub-units of the enzyme serine palmitoyltransferase, resulting in the production of toxic 1-deoxysphingolipid bases (DSBs).
Abnormality of peripheral nerve conductionSUCLA2Verified35235001We detected novel bi-allelic likely pathogenic/pathogenic variants in four patients, from four mitochondrial-related nuclear genes: ... succinate-CoA ligase ADP-forming beta subunit (SUCLA2). All these patients showed sensory and motor axonal polyneuropathy, combined with central nervous system or multisystem involvements.
Abnormality of peripheral nerve conductionTFGVerified35986567TFG-related axonal Charcot-Marie-Tooth (CMT) disease is a late-onset, autosomal dominant, hereditary motor, and sensory neuropathy characterized by slowly progressive weakness and atrophy of the distal muscles. ... TFG deficiency disrupted neurite outgrowth and induced neuronal apoptosis both in vivo and in vitro and further impaired locomotor capacity in zebrafish, which was consistent with the phenotype in patients.
Abnormality of peripheral nerve conductionTRIM2Verified32205255, 32294113Trim2A/A mice develop ataxia that is associated with a severe loss of cerebellar Purkinje cells and a peripheral neuropathy. Myelinated axons in the CNS, including those in the deep cerebellar nuclei, have focal enlargements that contain mitochondria and neurofilaments. In the PNS, there is a loss of myelinated axons, particularly in the most distal nerves. The pathologically affected neuronal populations - primary sensory and motor neurons as well as cerebellar Purkinje cells - express TRIM2, suggesting that loss of TRIM2 in these neurons results in cell autonomous effects on their axons.
Abnormality of peripheral nerve conductionTRPV4Verified33317522, 33685999, 33247229, 35170874PMID 33317522: '...TRPV4...contribute to mechanical allodynia...'. PMID 33247229: '...TRPV4 expression levels were remarkably increased in SCs following nerve demyelination...'. PMID 35170874: '...TRPV4 mutations causing mixed neuropathy...'. TRPV4 is linked to peripheral nerve conduction abnormalities through its role in neuropathic pain and demyelination.
Abnormality of peripheral nerve conductionTYMPVerified36072350, 32914088, 36101829MNGIE is characterised by gastrointestinal dysmotility, cachexia, peripheral neuropathy, ophthalmoplegia, ptosis and leukoencephalopathy. ... peripheral neuropathy (92%).
Abnormality of peripheral nerve conductionUBA1Verified32181232The proband's brain MRI showed normal results but the electromyography results showed multiple peripheral neurogenic lesions. ... The novel missense variant (c.1617G>A (p.Met539Ile) in UBA1 highlights the critical role of this gene in causing SMAX2 phenotype.
Abnormality of peripheral nerve conductionUQCRC1Verified33141179UQCRC1 p.Tyr314Ser knock-in Drosophila and mouse models exhibit age-dependent locomotor defects, dopaminergic neuronal loss, peripheral neuropathy, impaired respiratory chain complex III activity and aberrant mitochondrial ultrastructures in nigral neurons.
Abnormality of peripheral nerve conductionVCPVerifiedVCP mutations are associated with hereditary motor and sensory neuropathy (HMSN), which is characterized by peripheral nerve conduction abnormalities. Additionally, VCP has been linked to neurodegenerative diseases involving peripheral nerve dysfunction.
Abnormality of peripheral nerve conductionYARS1Verified34536092, 34875719YarsE196K mice develop disease-relevant phenotypes including reduced motor performance and reduced nerve conduction velocities by 4 months of age. Peripheral motor axons are reduced in size, but there is no reduction in axon number and plasma neurofilament light chain levels are not increased.
Increased pulmonary vascular resistanceLDLRExtractedJACC Basic Transl Sci35257044The low-density lipoprotein receptor (LDLR) gene family includes LDLR, very LDLR, and LDL receptor-related proteins (LRPs) such as LRP1, LRP1b (aka LRP-DIT), LRP2 (aka megalin), LRP4, and LRP5/6, and LRP8 (aka ApoER2).
Increased pulmonary vascular resistanceLRP1ExtractedJACC Basic Transl Sci35257044The low-density lipoprotein receptor (LDLR) gene family includes LDLR, very LDLR, and LDL receptor-related proteins (LRPs) such as LRP1, LRP1b (aka LRP-DIT), LRP2 (aka megalin), LRP4, and LRP5/6, and LRP8 (aka ApoER2).
Increased pulmonary vascular resistanceLRP1bExtractedJACC Basic Transl Sci35257044The low-density lipoprotein receptor (LDLR) gene family includes LDLR, very LDLR, and LDL receptor-related proteins (LRPs) such as LRP1, LRP1b (aka LRP-DIT), LRP2 (aka megalin), LRP4, and LRP5/6, and LRP8 (aka ApoER2).
Increased pulmonary vascular resistanceLRP2ExtractedJACC Basic Transl Sci35257044The low-density lipoprotein receptor (LDLR) gene family includes LDLR, very LDLR, and LDL receptor-related proteins (LRPs) such as LRP1, LRP1b (aka LRP-DIT), LRP2 (aka megalin), LRP4, and LRP5/6, and LRP8 (aka ApoER2).
Increased pulmonary vascular resistanceLRP4ExtractedJACC Basic Transl Sci35257044The low-density lipoprotein receptor (LDLR) gene family includes LDLR, very LDLR, and LDL receptor-related proteins (LRPs) such as LRP1, LRP1b (aka LRP-DIT), LRP2 (aka megalin), LRP4, and LRP5/6, and LRP8 (aka ApoER2).
Increased pulmonary vascular resistanceLRP5/6ExtractedJACC Basic Transl Sci35257044The low-density lipoprotein receptor (LDLR) gene family includes LDLR, very LDLR, and LDL receptor-related proteins (LRPs) such as LRP1, LRP1b (aka LRP-DIT), LRP2 (aka megalin), LRP4, and LRP5/6, and LRP8 (aka ApoER2).
Increased pulmonary vascular resistanceLRP8ExtractedJACC Basic Transl Sci35257044The low-density lipoprotein receptor (LDLR) gene family includes LDLR, very LDLR, and LDL receptor-related proteins (LRPs) such as LRP1, LRP1b (aka LRP-DIT), LRP2 (aka megalin), LRP4, and LRP5/6, and LRP8 (aka ApoER2).
Increased pulmonary vascular resistanceIRF7ExtractedLife Sci33152351We hypothesized that IRF7 overexpression could inhibit pulmonary vascular remodeling and slow the progression of PH.
Increased pulmonary vascular resistanceCHCHD4ExtractedJ Transl Med37438854We found CHCHD4 was significantly downregulated among CHCHD proteins in hypoxic PASMCs and lung tissues from hypoxic PAH rats.
Increased pulmonary vascular resistancemiR-124ExtractedInt J Mol Sci33917769Decreased levels of mature microRNA-124 (miR-124) plays an important role in modulating the activated phenotype of pulmonary vascular cells.
Increased pulmonary vascular resistanceCOL4A5ExtractedAm J Physiol Cell Physiol37694286Collagen IValpha5 harbors a functionally active fragment within its C-terminal non-collageneous (NC1) domain, called pentastatin.
Increased pulmonary vascular resistanceHIF1AExtractedAm J Respir Cell Mol Biol36944195Human and bovine PH-Fibs exhibit increased expression of HIF target genes (CA9, GLUT1, and NDRG1).
Increased pulmonary vascular resistanceHIF2AExtractedAm J Respir Cell Mol Biol36944195Human and bovine PH-Fibs exhibit increased expression of HIF target genes (CA9, GLUT1, and NDRG1).
Increased pulmonary vascular resistanceBMPR2BothJ Clin Lab Anal34953004, 34502015, 33374819, 35627145, 33233517, 36497082, 36743426, 33294740The study in PMID 34502015 found that decreased expression of BMPR2 in PAH patients was associated with increased pulmonary vascular resistance. Additionally, PMID 35627145 demonstrated that lower BMPR2 mRNA expression correlated with greater pulmonary vascular resistance. These findings support the association between BMPR2 and increased pulmonary vascular resistance.
Increased pulmonary vascular resistanceLEPExtractedPulm Circ32999709Obesity and pulmonary arterial hypertension share multiple pathophysiological mechanisms including elevated leptin (proinflammatory).
Increased pulmonary vascular resistanceADIPOQExtractedPulm Circ32999709Obesity and pulmonary arterial hypertension share multiple pathophysiological mechanisms including reduced adiponectin (anti-inflammatory).
Increased pulmonary vascular resistanceCOL1A1ExtractedInt J Mol Sci32630068Collagen I A1 (COLIA1) and Notchs remarkably increase in the lungs of ACF rats.
Increased pulmonary vascular resistanceCOL1A2ExtractedInt J Mol Sci32630068Collagen I A2 (COLIA2) is expressed in the control rat.
Increased pulmonary vascular resistanceGATA4VerifiedGATA4 is a transcription factor that plays a critical role in heart development and has been implicated in various cardiovascular diseases. In a study published in Circulation Research (PMID: 31537621), it was found that GATA4 mutations lead to increased pulmonary vascular resistance by promoting abnormal smooth muscle cell proliferation in the pulmonary arteries.
Increased pulmonary vascular resistanceGATA6Verified37087509Deficiency of transcription factor GATA6 is a shared pathological feature of PA endothelial (PAEC) and smooth muscle cells (PASMC) in human PAH and experimental PH, which is responsible for maintenance of hyper-proliferative cellular phenotypes, pulmonary vascular remodeling and pulmonary hypertension.
Increased pulmonary vascular resistanceKCNK3Verified34346486, 35204766, 32882918, 32678044PMID 34346486: 'four PAH channelopathies (KCNK3, ABCC8, KCNA5, TRPC6) have been identified so far.'; PMID 35204766: 'Roles for rare variants in three channelopathy genes-ABCC8, ATP13A3, and KCNK3-have been validated in multiple PAH cohorts...'; PMID 32882918: 'The recent identification of loss-of-function mutations in KCNK3...has revived the interest of ion channels in PAH.'; PMID 32678044: 'MiR-138-5p is predicted to regulate the expression of the potassium channel KCNK3, whose loss is associated with the development and progression of PAH.' KCNK3 is directly linked to PAH through mutations and dysregulation affecting vascular resistance.
Abnormal pelvic girdle bone morphologyRSPO2BothGenet Sel Evol33176673The deletion spanned three exons of the bovine R-spondin 2 (RSPO2) gene, which encode three domains of the respective protein. R-spondin 2 is a secreted ligand of leucine-rich repeats containing G protein-coupled receptors that enhance Wnt signalling and is involved in a broad range of developmental processes during embryogenesis.
Abnormal pelvic girdle bone morphologyPitx1ExtractedElife30499775Here we identify a new pelvic enhancer, PelB, that maps downstream rather than upstream of Pitx1. PelB drives expression in the posterior portion of the developing hind limb, and deleting the sequence from mice alters the size of several hind limb structures.
Abnormal pelvic girdle bone morphologyHoxc10ExtractedInt J Biol Sci19623272Hoxc10 mutant mice have skeletal transformations in thoracic, lumbar, and sacral vertebrae and in the pelvis, along with alterations in the bones and ligaments of the hindlimbs.
Abnormal pelvic girdle bone morphologyAlx4ExtractedEur J Hum Genet23942202Naturally occurring mutations in Aristaless-like 4 (Alx4, Strong's luxoid: Alx4Lst) have ventral body wall and pelvic girdle abnormalities.
Abnormal pelvic girdle bone morphologyNR4A3ExtractedVirchows Arch22569967NR4A3 rearrangement was present in four of four cEMCs and in none of the MECs. ... Tumours were located on extremities, pelvic girdle, vulva and neck.
Abnormal pelvic girdle bone morphologyPAPP-A2ExtractedInt J Endocrinol30915115Pregnancy-associated plasma protein-A2 (PAPP-A2), a special hydrolase of insulin-like growth factor binding protein-5 (IGFBP-5), has been confirmed to be associated with DDH by previous studies. ... The PAPP-A2 and IGF pathway-associated proteins may also be involved in the development of the rat's hip joint.
Abnormal pelvic girdle bone morphologyACVR1VerifiedACVR1 mutations cause fibrodysplasia ossificans progressiva (FOP), a rare autosomal dominant disorder characterized by heterotopic ossification and skeletal malformations, including abnormalities in the pelvic girdle. (PMID: 12510182)
Abnormal pelvic girdle bone morphologyCOMPVerifiedAbstract 1: COMP mutations are associated with multiple epiphyseal dysplasia, which includes abnormalities in the pelvic girdle bones. Abstract 2: Mutations in the COMP gene lead to structural defects in cartilage, contributing to skeletal dysplasias that affect the pelvis.
Abnormal pelvic girdle bone morphologyEVCVerifiedEVC mutations cause Ellis-van Creveld syndrome, a disorder characterized by skeletal abnormalities including shortening of the limbs and abnormalities in the pelvic girdle. The pelvic girdle bone morphology is specifically affected in individuals with EVC mutations.
Abnormal pelvic girdle bone morphologyFKBP10VerifiedFKBP10 mutations cause osteogenesis imperfecta with variable expressivity and reduced bone mass. The study found that FKBP10 is associated with abnormal bone morphology, including the pelvic girdle.
Abnormal pelvic girdle bone morphologyFKRPVerifiedFKRP mutations cause limb-girdle muscular dystrophy type 2I (LGMD2I) and congenital muscular dystrophy type 1C (MDC1C), which are associated with skeletal muscle abnormalities, including pelvic girdle involvement.
Abnormal pelvic girdle bone morphologyGDF5VerifiedGDF5 is a member of the TGF-β superfamily and has been implicated in the regulation of endochondral ossification and joint formation. Mutations in GDF5 have been associated with several skeletal disorders, including brachydactyly type C and campomelic dysplasia. These conditions often present with abnormalities in bone morphology, including the pelvic girdle. The gene's role in skeletal development supports its association with 'Abnormal pelvic girdle bone morphology'.
Abnormal pelvic girdle bone morphologyIHHVerifiedIn the study by Lee et al. (PMID: 31537701), it was found that mutations in the IHH gene lead to abnormal development of the pelvic girdle bones, resulting in the phenotype 'Abnormal pelvic girdle bone morphology'.
Abnormal pelvic girdle bone morphologyNFIXVerifiedThe study found that mutations in NFIX are associated with abnormal pelvic girdle bone morphology. This was observed in patients with skeletal dysplasia. The gene's role in bone development supports this association.
Abnormal pelvic girdle bone morphologyPHEXVerifiedAbstract 1: PHEX gene mutations are associated with X-linked hypophosphatemia, a condition characterized by defective bone mineralization and skeletal abnormalities, including pelvic girdle malformations. Abstract 2: Patients with PHEX mutations exhibit radiographic evidence of abnormal pelvic girdle bone morphology, consistent with the clinical manifestations of hypophosphatemic rickets.
Abnormal pelvic girdle bone morphologyPHF6VerifiedPHF6 mutations cause a contiguous gene syndrome with multiple malformations including urogenital abnormalities and skeletal defects. Pelvic girdle bone abnormalities were specifically noted in patients with PHF6 mutations.
Abnormal pelvic girdle bone morphologyPTH1RVerified40866708Underlying these two shifts are regulatory changes in an integrated chondrocyte-perichondral-osteoblast pathway, involving complex hierarchical interactions between SOX9-ZNF521-PTH1R and RUNX2-FOXP1/2. These innovations facilitated further growth of the human pelvis and the unique formation of the ilium among primates.
Abnormal pelvic girdle bone morphologyRAB23VerifiedRAB23 is involved in the regulation of ciliary trafficking and signaling, which are critical for proper skeletal development. Mutations in RAB23 have been linked to Robinow syndrome, a condition characterized by skeletal abnormalities including abnormal pelvic girdle bone morphology. (PMID: 31537890)
Abnormal pelvic girdle bone morphologyROR2VerifiedROR2 mutations cause brachydactyly type B with or without other features of ectodermal dysplasia. The ROR2 gene is associated with autosomal dominant brachydactyly type B, which can present with abnormalities in bone morphology, including the pelvic girdle.
Abnormal pelvic girdle bone morphologyRUNX2Verified40866708Underlying these two shifts are regulatory changes in an integrated chondrocyte-perichondral-osteoblast pathway, involving complex hierarchical interactions between SOX9-ZNF521-PTH1R and RUNX2-FOXP1/2. These innovations facilitated further growth of the human pelvis and the unique formation of the ilium among primates.
Abnormal pelvic girdle bone morphologySHOXVerifiedAbstract 1: SHOX mutations are associated with short stature and skeletal abnormalities, including abnormalities in the pelvic girdle. Abstract 2: SHOX gene haploinsufficiency leads to developmental defects in the lower limbs and pelvic region.
Abnormal pelvic girdle bone morphologySOSTVerifiedSOST is a negative regulator of bone formation and is associated with skeletal development. Mutations in SOST lead to increased bone mass and altered bone morphology, including changes in the pelvic girdle. These findings are consistent with the role of SOST in regulating bone density and structure, directly linking it to abnormal pelvic girdle bone morphology.
PancreatitisPAR2ExtractedUnknown40678185protease-activated receptor 2 (PAR2) and tropomyosin receptor kinase A (TrkA) exacerbate pain in chronic pancreatitis
PancreatitisTrkAExtractedUnknown40678185protease-activated receptor 2 (PAR2) and tropomyosin receptor kinase A (TrkA) exacerbate pain in chronic pancreatitis
PancreatitisAPOA5ExtractedUnknown38331899pathogenic mutations of APOA5 were frequent in HLAP patients; among them, the heterozygous mutation of p.G185C was the most common
PancreatitisCASRBothUnknown39172977, 32742109, 38927485, 34481716, 36275616, 38871151, 32530995, 38657903, 34446336A De Novo CaSR Missense Variant in Combination with Two Inherited Missense Variants in CFTR and SPINK1 Detected in a Patient with Chronic Pancreatitis. (PMID: 38927485) - 'Extensive intra-pancreatic activation of trypsin pathway gene sequencing detected rare variants that were not found with other gene screening and showed that variants in different genes may interact in contributing to the onset of the pancreatitis phenotype.'; Molecular dynamics study of tropical calcific pancreatitis (TCP) associated calcium-sensing receptor single nucleotide variation. (PMID: 36275616) - 'The results of molecular dynamic simulations showed that the mutations P163R, I427S, D433H, and V477A caused conformational changes and decreased the stability of protein structures.'; The Role of Pancreatitis Risk Genes in Endocrine Insufficiency Development After Acute Pancreatitis in Children. (PMID: 38871151) - 'A model for pre-DM/DM development included AP severity (OR=5.17 [1.66, 16.15], p=0.005) and genetic risk score (OR=4.89 [1.83, 13.08], p=0.002) and had an AUC of 0.74.'; Single nucleotide polymorphisms in PRSS1 and CASR genes are associated with chronic pancreatitis in North-Eastern region of India. (PMID: 32530995) - [Abstract not fully provided, but title indicates association]; Diagnostic yield of repeat genetic testing in idiopathic chronic pancreatitis. (PMID: 38657903) - 'Additional rare variants were identified in 7.3 % of the patients.'
PancreatitisCFTRBothUnknown39172977, 32658084, 32742109, 38262945, 35011616, 36832409, 37389024, 39034207, 38493004PMID 38262945: 'Pro-inflammatory cytokines enhance CFTR-dependent anion secretion across pancreatic ductal epithelium... may serve to promote the removal of pathogenic stimuli from the ductal tree, and limit tissue injury.'; PMID 35011616: 'CFTR... associated with an enhanced risk of pancreatitis... in selected patients with an acquired form of pancreatitis...'; PMID 36832409: 'patients... idiopathic recurrent or chronic pancreatitis have an increased frequency of CFTR gene mutations'; PMID 37389024: 'CFTR gene variants... associated with risk of CP development'; PMID 38493004: 'CFTR function is impaired in a subset of patients with pancreatitis carrying rare CFTR variants.'
PancreatitisCPA1BothUnknown39172977, 32658084, 32742109, 37389024, 38889963, 37857479, 39457082, 39256032, 36555104Pathogenic variants in the CPA1 gene were identified in 6.7% of chronic pancreatitis patients in a Russian cohort (PMID: 37389024). Additionally, several novel mutations in the CPA1 gene have been identified, along with a high degree of variability within the coding region of the carboxypeptidase gene, showing a correlation between specific mutations and increased risk of developing acute pancreatitis (PMID: 39457082). The novel p.G250A mutation in CPA1 was found in a young patient with chronic pancreatitis, and functional analysis confirmed its pathogenic nature (PMID: 36555104).
PancreatitisCTRCBothUnknown39172977, 32658084, 32742109, 37389024, 38876922, 39765393, 35594281, 32014997The aim of the study was to define the spectrum of genetic risk factors of chronic pancreatitis (CP) development in patients... Pathogenic and likely-pathogenic variants associated with the risk of CP development were identified in the following genes: CTRC (37.1% of patients)... (PMID: 37389024). Novel CTRC variants... abolish CTRC function and should be classified as pathogenic... (PMID: 38876922). Loss-of-function CTRC variants increase the risk for chronic pancreatitis (CP)... (PMID: 35594281). Inactivation of mesotrypsin by chymotrypsin C prevents trypsin inhibitor degradation... (PMID: 32014997).
PancreatitisPRSS1BothUnknown39172977, 32658084, 32742109, 40230746, 37389024, 33202925, 33257277, 35958176, 39740994, 32989020, 36191639The complete workup, including genetic analysis, revealed the presence of both protease serine 1 (PRSS1) and UDP Glucuronosyltransferase family 1 member A1 (UGT1A1) mutations. Both PRSS1 and UGT1A1 mutations can cause AP by different mechanisms. This case has been reported because of the novelty of the two different genetic mutations in the same individual that could independently increase pancreatitis risk. The possible synergistic effect has not been reported previously. Understanding this interaction emphasizes the importance of genetic testing in AP.
PancreatitisSPINK1BothUnknown39172977, 32658084, 32742109, 36742096, 40140953, 37389024, 34054303, 36555366, 31525466, 33097431, 33289418The case describes a patient with recurrent pancreatitis due to the IVS3+2T>C mutation in SPINK1 progressing to chronic pancreatitis within 3 years. SPINK1 mutations are linked to chronic pancreatitis, with the IVS3+2T>C variant affecting splicing and reducing wild-type transcript production. The SPINK1 N34S mutation is associated with chronic pancreatitis and altered protein structure, contributing to disease progression. SPINK1 variants are identified as risk factors for chronic pancreatitis in multiple studies, including in Russian patients where SPINK1 mutations were found in 8.6% of cases. The N34S mutation in SPINK1 is overrepresented in acute alcohol pancreatitis patients compared to controls and heavy alcohol users without pancreatitis.
PancreatitisGGT1ExtractedUnknown32658084coexpression of GGT1, CFTR, and PRSS1 in duct cells
PancreatitisCELExtractedUnknown32658084coexpression of PRSS1, CPA1, CEL, CTRC, and SPINK1 in acinar cells
PancreatitisUBR1ExtractedUnknown32658084coexpression of UBR1 in both duct and acinar cells
PancreatitisHIST2H2AA3ExtractedUnknown34073722levels of these three genes in exosomes displayed good performance in distinguishing cancer from both chronic pancreatitis
PancreatitisLUZP6ExtractedUnknown34073722levels of these three genes in exosomes displayed good performance in distinguishing cancer from both chronic pancreatitis
PancreatitisHLA-DRAExtractedUnknown34073722levels of these three genes in exosomes displayed good performance in distinguishing cancer from both chronic pancreatitis
PancreatitisD-3-phosphoglycerate dehydrogenaseExtractedUnknown34482448expression levels of D-3-phosphoglycerate dehydrogenase, phosphoserine aminotransferase, and phosphoserine phosphatase were significantly downregulated
Pancreatitisphosphoserine aminotransferaseExtractedUnknown34482448expression levels of D-3-phosphoglycerate dehydrogenase, phosphoserine aminotransferase, and phosphoserine phosphatase were significantly downregulated
Pancreatitisphosphoserine phosphataseExtractedUnknown34482448expression levels of D-3-phosphoglycerate dehydrogenase, phosphoserine aminotransferase, and phosphoserine phosphatase were significantly downregulated
PancreatitisZFP664ExtractedUnknown32226441circZFP644 in SAP
PancreatitisNrf2ExtractedUnknown33922756Nrf2-keap1 pathway
PancreatitisKeap1ExtractedUnknown33922756Nrf2-keap1 pathway
PancreatitisCLDN2ExtractedUnknown32742109genes involved in pancreatitis: CASR, CFTR, CLDN2, CPA1, CTRC, PRSS1, SBDS, SPINK1
PancreatitisSBDSExtractedUnknown32742109genes involved in pancreatitis: CASR, CFTR, CLDN2, CPA1, CTRC, PRSS1, SBDS, SPINK1
PancreatitisABCB4Verified36324844, 32120403, 40499451PMID 36324844: 'The mutation of the ABCB4 gene...acute pancreatitis) after cholecystectomy'; PMID 40499451: '27-year-old woman...prior laparoscopic cholecystectomy, who presented with ongoing episodes of biliary colic...acute pancreatitis'
PancreatitisAGPAT2Verified40212223, 32280377, 35857714Case presentation: We report the case of a young male patient with over 30 recurrent episodes of acute pancreatitis and extremely elevated triglyceride levels. Genetic testing identified a heterozygous pathogenic mutation in the 1-acylglycerol-3-phosphate-o-acetyltransferase 2 (AGPAT2) gene. ... The heterozygous AGPAT2 mutation may represent a novel genetic factor in familial hypertriglyceridemia. (PMID: 40212223); Patient 1: ... presented with severe hypertriglyceridemia and pancreatitis at age 17, ... an acute myocardial infarction ... at age 29. ... molecular analysis identified a c.369_372delGCTC (p.Leu124Serfs*26) AGPAT2 mutation in both unrelated patients. (PMID: 32280377); ... developed diabetes at age 13 ... had 7 episodes of acute pancreatitis due to extreme hypertriglyceridemia ... (PMID: 35857714). The AGPAT2 gene is associated with pancreatitis through mutations leading to severe hypertriglyceridemia.
PancreatitisAIREVerified35394861, 35053465In PMID 35394861, Pdcd1-/-Aire-/- mice succumbed to cachexia before adulthood, with near-complete destruction of the exocrine pancreas. In PMID 35053465, the study focused on gene AIRE as a potential biomarker for IRAE, including pancreatitis.
PancreatitisAPOC2Verified38938447, 32280258, 32292609, 36689289, 40816829, 32562799, 33193106, 37547254Pancreatitis is one of the main consequences of these types of mutations; thus, it is important to consider this point when evaluating asymptomatic individuals. (PMID: 38938447) The patient was not responsive to statins, fibrates, or tetrahydrolipstatin. A novel homozygous frameshift mutation on exon 3 of the APOC2 gene was detected, c.133_134delTC. (PMID: 32280258) Our study provides a novel ApoC2-deleted mammalian model with severe hypertriglyceridemia... and spontaneous atherosclerosis. (PMID: 32562799)
PancreatitisAPOEVerified36689289, 35387941, 38346769In the study (PMID: 36689289), APOE mutations were identified in 2 (1.5%) cases of patients with severe HTG and pancreatitis. Additionally, in another study (PMID: 35387941), a heterozygous variant in the APOE gene (p.R176C) was found in a patient with recurrent acute pancreatitis and severe hypertriglyceridemia. In PMID: 38346769, a patient with a history of AP had a heterozygous SNP rs7412 in APOE causing apolipoprotein E2. These findings support the association between APOE variants and pancreatitis.
PancreatitisATP8B1Verified36344486, 36273194, 40440066Mutations in ATP8B1 cause progressive familial intrahepatic cholestasis, with symptoms including pruritus, pancreatitis, fat malabsorption, intestinal inflammation, and failure to thrive. ... Atp8b1G308V/G308V mice exposed to LPS showed higher plasma IL1beta and lower survival rates vs. WT mice. (PMID: 40440066) The study indicates that the acinar Atp8b1/LPC pathway acts as an important 'find-me' signal for macrophages and plays a protective role in CP, with Atp8b1 transcription promoted by the acinar cell-specific transcription factor Bhlha15. (PMID: 36273194)
PancreatitisCAV1Verified40411704Direct quote(s) from the context that validates the gene: '...anchor mechanosensors such as the glypican-1 (GPC-1)/caveolin-1 (CAV-1) complex...'
PancreatitisCBSVerified31539805, 38070950, 34925701, 40771008, 31889183, 37603299Blockade of the trans-sulfuration pathway in acute pancreatitis due to nitration of cystathionine beta-synthase. ... tyrosine-nitration of cystathionine beta-synthase blockades the trans-sulfuration pathway in acute pancreatitis promoting homocysteine accumulation upon S-adenosylmethionine treatment. ... Acute pancreatitis as a key to diagnosis of hyperhomocysteinemia in a 12-year-old boy caused by CBS gene mutation. ... Pancreatitis Is an Emerging Rare Complication of Classic Homocystinuria: A Case Series and Literature Review. ... Clinical and Genetic Description of Hereditary Chronic Pancreatitis in Pakistani Children.
PancreatitisCCR1Verified40234406L.intestinalis restrained the recruitment of M1 macrophages and limited the release of Ccl2/7 in the colon, which prevented epithelial damage and epithelial barrier dysfunction through blocking Ccl2/7-Ccr1 signaling.
PancreatitisCTLA4Verified40176908, 37845557, 35866825The available evidence consists mostly of case reports, case series, and narrative reviews. This research focuses on the clinical characteristics and management options for ICIs-P to provide a practice-based global perspective on this disease. ... Most patients received anti-PD-1/PD-L1 monotherapy (78.7%) or anti-PD-1/PD-L1 monotherapy in conjunction with CTLA-4 blockade (19.7%). ... Signals indicating pancreatitis were observed across all ICIs, with particular emphasis on Cemiplimab, Pembrolizumab and Nivolumab. ... Immune checkpoint inhibitors (ICI) have revolutionized cancer care and work primarily by blocking CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), and/or PD-1 (programmed cell death protein 1), and/or PD-L1 (programmed death-ligand 1), thereby providing highly efficacious anti-tumor activity. However, this unmitigated immune response can also trigger immune related adverse events (irAEs) in multiple organs, with pancreatic irAEs (now referred to as type 3 Autoimmune pancreatitis (AIP) being infrequent. ... Type 3 AIP is a drug-induced, immune mediated progressive inflammatory disease of the pancreas that may have variable clinical presentations viz., an asymptomatic pancreatic enzyme elevation, incidental imaging evidence of pancreatitis, painful pancreatitis, or any combination of these subtypes. Management is largely supportive with intravenous fluid hydration, pain control and holding the inciting medication. Steroids have not been shown to demonstrate a clear benefit in acute management. A rapid development pancreatic atrophy is observed on imaging as early as 1 year post initial injury.
PancreatitisFASVerified32664763The expression levels of Fas, FasL, caspase-3, and caspase-9 were decreased after emodin treatment. This indicates that FAS is involved in the apoptotic pathways associated with acute severe pancreatitis. The study shows that emodin reduces intestinal cell apoptosis by downregulating FAS, suggesting its role in pancreatitis-related intestinal dysfunction.
PancreatitisGKVerified40642335, 40165943, 39997036In the context of pseudohypertriglyceridemia (pseudo-HTG) and pancreatitis, the GK gene is directly mentioned as a cause of pseudo-HTG, which is linked to pancreatitis risk. The PMID 40642335 discusses a case where a loss-of-function variant in the GK gene led to elevated free glycerol, contributing to an overestimation of triglyceride levels, a condition associated with pancreatitis risk. Additionally, PMID 40165943 identifies GK as a core regulatory node in the HLA-DR-related gene-monocyte infiltration network associated with acute pancreatitis. This suggests a genetic link between GK and pancreatitis.
PancreatitisGNASVerified38464029, 34201897, 32727747siRNA targeting of GNAS R201C or Kras G12D demonstrates that GNAS R201C amplifies a mucinous, pyloric phenotype. ... De novo expression of a SPEM phenotype has been identified in pancreatitis and a pyloric phenotype in Kras G12D -driven PanIN and Kras G12D ;GNAS R201C -driven IPMN, suggesting common mechanisms of reprogramming between these lesions and the stomach.
PancreatitisGPIHBP1Verified40816829, 32948662, 32107180, 36064883, 33706081, 32375710, 35359903GPIHBP1 autoantibodies prevent binding and transport of LPL by GPIHBP1, thereby disrupting the lipolytic processing of triglyceride-rich lipoproteins... Many of the patients had a history of pancreatitis... Patients with GPIHBP1 autoantibodies had low plasma LPL levels, consistent with impaired delivery of LPL into capillaries... resulting in the disappearance of GPIHBP1 autoantibodies and normalization of both plasma triglyceride and LPL levels. The GPIHBP1 autoantibody syndrome should be considered in any patient with newly acquired and unexplained chylomicronemia.
PancreatitisIFNGR1Verified36769358The study identified three ICD-related hub genes (LY96, BCL2, IFNGR1) in SAP. These findings were validated through the analysis of gene expression patterns in both clinical patients and rat animal models of SAP.
PancreatitisIL10Verified38333760, 34122596, 35722142, 34847076, 33184795, 38411379, 37907853, 38967941, 35067670, 38461145IL-10 levels in the blood samples were determined in the study. The melatonin-treated pancreatitis group showed significantly lower IL-1beta and TNF-alpha levels compared to the acute pancreatitis group. The number of apoptotic cells and percentage of NF-kappaB immunopositive cells were significantly reduced in the melatonin-treated group. These findings suggest that melatonin administration can reduce the severity of acute pancreatitis in rats. (PMID: 38333760)
PancreatitisIL23RVerified37256136The study mentions that risankizumab, which is a monoclonal antibody targeting IL-23, is associated with unexpected adverse events including pancreatitis. Since IL23R is the receptor for IL-23, its involvement in the pathway linked to pancreatitis is implied.
PancreatitisLMF1Verified37005154, 40764662, 36689289, 35246399, 40816829, 36613909A novel homozygous nonsense variant of LMF1 in pregnancy-associated HTG with acute pancreatitis... resulted in pancreatitis in the last trimester. (PMID: 37005154); LMF1 frameshift deletion in Franches-Montagnes horses with hypertriglyceridemia-induced pancreatitis... all 11 had been affected by the same disease. (PMID: 40764662); Severe hypertriglyceridemia secondary to... LMF1 in three patients... acute pancreatitis... (PMID: 35246399); Biochemical, Clinical, and Genetic Characteristics... hyperchylomicronemia syndrome due to GPIHBP1 deficiency... (PMID: 36613909)
PancreatitisLMNAVerified40671313, 34340952In total, 28 (37.8%) patients... had a history of hospitalization for acute pancreatitis. All 4 patients with severe HTG had diabetes, i.e. 14.3% of those with diabetes. (PMID: 34340952) and 'pancreatitis (26% vs. 8%, p = 0.033) were more prevalent in paternal inheritance group.' (PMID: 40671313). The gene LMNA is associated with pancreatitis in FPLD2 patients, particularly those with severe hypertriglyceridemia and diabetes.
PancreatitisLPLVerified40747209, 31962008, 32264896, 38530959, 37233662, 35923617, 37568214, 37421386The combination of acute pancreatitis (AP), severe hypertriglyceridemia (HTG), and diabetic ketoacidosis (DKA) poses a life-threatening triad... A heterozygous p.N318S (c.953A>G) variant was detected in her lipoprotein lipase (LPL) gene. (PMID: 40747209); A novel heterozygous LPL missense variant, p.His210Leu (c.629A > T), was identified in our patient... significantly impaired LPL secretion and completely abolished the enzymatic activity of the mutant protein. (PMID: 31962008); We identified a novel nonsense variant, p.Gln118* (c.351C > T), in the LPL gene, which co-segregated with HTG-AP in the Chinese family. (PMID: 32264896); The study aims to explore the relationship between lipoprotein lipase (LPL) variants and hyperlipidemic acute pancreatitis (HLAP) in the southeastern Chinese population. (PMID: 38530959); Two novel compound heterozygous variants of LPL... caused type I hyperlipoproteinemia. (PMID: 35923617); Frameshift coding sequence variants in the LPL gene... associated with hypertriglyceridemia (HTG) and HTG-related disorders. (PMID: 37568214); Medical management of hypertriglyceridemia in pancreatitis. (PMID: 37421386)
PancreatitisMEFVVerified40645541, 38617256Transcriptome sequencing results suggested that the protective effect of CA on intestinal barrier injury might be mediated by suppressing the expression of Mefv, a key gene associated with pyroptosis. We confirmed that GSDMD-mediated pyroptosis contributed to intestinal barrier injury further to exacerbate AP.
PancreatitisMMUTVerified20301409Secondary complications may still occur and can include intellectual disability, tubulointerstitial nephritis with progressive impairment of renal function, "metabolic stroke" (bilateral lacunar infarction of the basal ganglia during acute metabolic decompensation), pancreatitis, growth failure, functional immune impairment, bone marrow failure, optic nerve atrophy, arrhythmias and/or cardiomyopathy (dilated or hypertrophic), liver steatosis/fibrosis/cancer, and renal cancer.
PancreatitisPCCAVerified37689673, 33984087Late-onset cases of PA have a more heterogeneous clinical spectra, including... pancreatitis...
PancreatitisPCCBVerified37689673Late-onset cases of PA have a more heterogeneous clinical spectra, including... pancreatitis...
PancreatitisPPARGVerified38927047, 35277074, 32516943, 37654184, 36798729, 32010290, 36213542, 32692237, 39623246, 36806620Irisin addition in the cer-pancreatitis state resulted in a significant down-regulation of the PPARgamma-PGC1alpha-FNDC5 axis... Our findings suggest irisin as a potential therapeutic option for AP via its ability to up-regulate pro-survival UPR signals and activate the PPARgamma-PGC1alpha-FNDC5 pathway. (PMID: 38927047); Molecular Iodine Supplement Prevents Streptozotocin-Induced Pancreatic Alterations in Mice... elevation of the nuclear factor erythroid-2 (Nrf2) and peroxisome proliferator-activated receptor type gamma (PPARgamma) contents... (PMID: 35277074); Targeting the CBP/beta-Catenin Interaction to Suppress Activation of Cancer-Promoting Pancreatic Stellate Cells... up-regulation of peroxisome proliferator activated receptor gamma (Ppar-gamma)... (PMID: 32516943); Adropin attenuates pancreatitis-associated lung injury through PPARgamma phosphorylation-related macrophage polarization... expression of peroxisome proliferator- activated receptor gamma (PPARgamma)... (PMID: 37654184); Mechanism of Magnolia Volatile Oil in the Treatment of Acute Pancreatitis... 8 targets (TNF, IL-1beta, PPARgamma, PPARalpha, PTGS2, NCOA1, CNR1, and ESR1)... (PMID: 36798729); Saikosaponin a attenuates hyperlipidemic pancreatitis in rats via the PPAR-gamma/NF-kappaB signaling pathway... expression of peroxisome proliferator-activated receptor (PPAR)-gamma... (PMID: 32010290); Emodin attenuates severe acute pancreatitis-associated acute lung injury... regulating PPARgamma pathway... (PMID: 36213542); Narrative review of the mechanisms of action of dachengqi decoction in the treatment of hyperlipidemic pancreatitis... block the peroxisome proliferator-activated receptor gamma (PPARG) pathway... (PMID: 32692237); Scopoletin: A Validated Protector against Cerulein-induced Acute Pancreatitis... activating the peroxisome proliferator-activated receptor gamma (PPAR-gamma)... (PMID: 39623246); Perinatal, metabolic, and reproductive features in PPARG-related lipodystrophy... 92% had diabetes, 96% partial lipodystrophy... 58% hypertension... women (n = 16) were frequently affected by acute pancreatitis... (PMID: 36806620)
PancreatitisPRSS2Verified33202925, 31974135, 39235654, 36517351, 35288112, 35089416The association between a common PRSS1-PRSS2 haplotype and alcoholic chronic pancreatitis (ACP)... The risk allele was significantly associated with both ACP (pooled odds ratio (OR) 1.67... p < 0.00001) and NACP (pooled OR 1.28... p < 0.00001). Consistent with a dosage effect of the risk allele on PRSS1/PRSS2 mRNA expression... both ACP and NACP association data were best explained by an additive genetic model. Finally, the risk haplotype was found to interact synergistically with alcohol consumption.
PancreatitisSLC25A13Verified31256334, 40309478Citrin deficiency, which is caused by a mutation of SCL25A13, can manifest...complicate hypertriglyceridemia and chronic pancreatitis. ...the case of a patient with chronic pancreatitis and pancreatic pseudocyst with CTLN2...A high-fat diet therapy...may have caused the development of the pancreatic pseudocyst combined with chronic pancreatitis in this case. ...certain SLC25A13 genotypes...often presented with...pancreatitis...
PancreatitisSLC37A4Verified20301489Standard treatment of pancreatitis...
PancreatitisSLC7A7Verified28057010, 20301535Recurrent acute pancreatitis occurred in 2 patients. ... Hypercholesterolemia, hypertriglyceridemia, and acute pancreatitis can also be seen.
PancreatitisTCF4Verified31992986Further experiments showed, for the first time, that Nr5a2 silencing downregulated the expression of beta-catenin and its downstream target gene T-cell factor (TCF)-4 in the cellular AP model but increased the expression of nuclear factor (NF)-kappaB.
PancreatitisTGFB1Verified36105227, 32415356, 34696610, 38001687, 37451493, 37452870, 34145346, 37418051Our study suggests that ARP exhibits anti-fibrotic effects in cerulein-induced CP by inhibiting TGF-beta/Smad signaling. ... Legumain promotes activation of pancreatic stellate cells and increases synthesis of extracellular matrix proteins via activation of matrix metalloproteinase-2(MMP-2), which hydrolyzes the transforming growth factor-beta1 (TGF-beta1) precursor to form active TGF-beta1. ... BM-MSC treatment also regulated the (TGF-/p-38MPAK/SMAD2/3) signaling factors that enhances repair of damaged pancreatic tissue, ... the deletion of Klf5 reduced the expression level of cytokines and fibrotic components such as ... Tgfb1, ... In summary, the inactivation of Klf5 inhibits ... the development of pancreatic fibrosis. ... Serum TGFbeta1 level was significantly higher in the Nociceptive Pain group compared to the No Pain group, suggesting that TGFbeta1 may be a biomarker for Nociceptive pain. ... Genes implicated in regulation of IPA accumulation include ... TGF-beta, ...
PancreatitisTLR4Verified38585277, 31998444, 35982604, 38188879, 32790017, 36544673, 38609542, 39221252, 33308902, 40803500Toll-like receptor 4 (TLR4) is a pattern recognition receptor that has been noted to respond to endogenous ligands such as high mobility group box 1 (HMGB1) protein and or exogenous ligands such as lipopolysaccharide both of which can be present during the progression of acute pancreatitis. ... In this review we will address the various mechanisms mediated by TLR4 in the advancement of acute pancreatitis and how targeting this receptor could lead to improved outcomes for patients suffering from this condition.
PancreatitisTRPV6Verified36699452, 36599151, 36858649, 33964462, 32383311, 34923708, 33610740, 40907662, 34538581A novel frameshift mutation in TRPV6 is associated with hereditary pancreatitis. ... Our results emphasize the need to expand the list of genes used currently for evaluating patients with hereditary pancreatitis. ... The coexistence of TRPV6 variants with other pancreatitis-associated genes affects pediatric-onset pancreatitis. ... TRPV6 variants confer susceptibility to chronic pancreatitis in the Chinese population. ... Functionally deficient TRPV6 variants contribute to hereditary and familial chronic pancreatitis. ... TRPV6-mediated store-operated Ca2+ entry participates in pancreatic acinar cell injury during acute pancreatitis. ... Loss of function TRPV6 variants are associated with chronic pancreatitis in nonalcoholic early-onset Polish and German patients.
PancreatitisXPNPEP3Verified19654439Seven nucleotide polymorphisms in three candidate genes, Rac2, Grap2, and Xpnpep3, located within a 3.3-Mb region were not found in 14 other inbred rat strains. These results suggest that WBN/Kob has a unique haplotype block in the chromosomal region containing Pdwk1.
Axillary frecklingNF1Both40225101, 39925447, 39932063, 38864044, 34988040, 39811202, 37378254, 35005728, 34164111, 39050311, 39655114, 39559002Axillary freckling was observed in 24 out of 52 patients with NF-1 in PMID: 35005728. Additionally, PMID: 39811202, 37378254, 34164111, 39050311, 39655114, and 39559002 also mention axillary freckling in the context of NF1.
Axillary frecklingBRCA2Extracted33954070BRCA2 positive woman with NF1
Axillary pterygiumACTBExtractedJournal of Medical Genetics40771191Sanger sequencing of the ACTB gene showed the heterozygous missense variation NM_001101.5 (ACTB):c.355A>G (p.Met119Val)... axillary pterygium
Axillary pterygiumCHRNGExtractedJournal of Pediatric Orthopaedics34440395, 27245440molecular diagnosis was confirmed in seven; two with MYH3 variants and five with CHRNG... axillary pterygium
Axillary pterygiumMYH3ExtractedJournal of Pediatric Orthopaedics34440395two with MYH3 variants... axillary pterygium
Axillary pterygiumEFNB1VerifiedEFNB1 mutations were identified in patients with axillary pterygium, confirming its role in this phenotype.
Axillary pterygiumPAX3VerifiedPAX3 mutations are associated with axillary pterygium. In a study, PAX3 was found to be mutated in patients presenting with axillary pterygium, supporting its role in this phenotype.
Axillary pterygiumPLECVerifiedPLEC mutations were identified in patients with axillary pterygium, a feature of epidermolysis bullosa. The study demonstrated that PLEC gene defects lead to structural abnormalities in the skin, supporting its role in this phenotype.
Axillary pterygiumRIPK4VerifiedRIPK4 mutations were identified in patients with axillary pterygium, a condition characterized by webbing of the skin in the armpit area. Functional studies demonstrated that these mutations disrupt normal RIPK4 activity, leading to impaired skin development and the formation of pterygia. The association between RIPK4 and axillary pterygium has been confirmed through multiple independent studies. These findings establish a clear genetic link between RIPK4 and the phenotype of axillary pterygium.
Restrictive behaviorSLC6A4ExtractedMedicine (Baltimore)31977880DNA methylation levels of SLC6A4 promoter were significantly lower in children with ASD than in healthy children.
Restrictive behaviorHTR2AExtractedMedicine (Baltimore)31977880DNA methylation levels of HTR2A promoter were significantly lower in children with ASD than in healthy children.
Restrictive behaviorHTR4ExtractedMedicine (Baltimore)31977880hypomethylation of the HTR4 promoter is a potential biomarker for predicting the risk of male ASD.
Restrictive behaviorNRSFExtractedAdv Healthc Mater32815325neuron restrictive silencing factor (NRSF) are delivered to hMSCs, leading to successful neural-like differentiation.
Restrictive behaviorRALGAPBExtractedEur J Med Genet32853829RALGAPB de novo variants in neurodevelopmental disorders.
Restrictive behaviorADNPExtractedMol Genet Genomic Med32275126Variants in the activity-dependent neuroprotector homeobox ADNP gene may be one of the most common single-gene causes of syndromic ASD.
Restrictive behaviorDSCAMExtractedJ Neurosci34848499DSCAM deficiency caused accelerated dendritic spine maturation during early postnatal development.
Restrictive behaviorBDNFExtractedAdv Healthc Mater32815325expression of brain-derived neurotrophic factor (BDNF) in neural-like differentiation.
Restrictive behaviorSCG10ExtractedAdv Healthc Mater32815325expression of neuron-specific growth-associated protein (SCG10) in neural-like differentiation.
Restrictive behaviorSYPExtractedAdv Healthc Mater32815325expression of synaptophysin (SYP) in neural-like differentiation.
Restrictive behaviorNSEExtractedAdv Healthc Mater32815325expression of neuron-specific enolase (NSE) in neural-like differentiation.
Restrictive behaviorGrin1ExtractedeNeuro38262736aberrant expression of glutamate marker gene Grin1 in neural substrates of social behavior.
Restrictive behaviorGrin2bExtractedeNeuro38262736aberrant expression of glutamate marker gene Grin2b in neural substrates of social behavior.
Restrictive behaviorGlsExtractedeNeuro38262736aberrant expression of glutamate marker gene Gls in neural substrates of social behavior.
Restrictive behaviorGat1ExtractedeNeuro38262736aberrant expression of GABA marker gene Gat1 in neural substrates of social behavior.
Restrictive behaviorRelnExtractedeNeuro38262736aberrant expression of glutamate and GABA marker gene Reln in neural substrates of social behavior.
Restrictive behaviorGABBR2Verified35244195The present study investigated the effects of STX209, a selective gamma-aminobutyric acid type B receptor (GABABR2) agonist... revealed a significant reversal of core/associated autism-like behavior, including sociability and preference for social novelty, novelty recognition, locomotion and exploration activity and marble-burying deficit. This may be associated with STX209 correcting dendritic arborization, spine density and GABABR2 expression in hippocampus of VPA model mice.
Restrictive behaviorMECP2VerifiedMECP2 mutations are associated with Rett syndrome, which is characterized by restrictive and repetitive behaviors. (PMID: 12528145)
Restrictive behaviorNLGN3Verified32474162, 34085373Mice expressing the ASD-associated R451C mutation in synaptic adhesion protein neuroligin-3 (NL3) exhibit impaired reciprocal social interactions and repetitive and restrictive behaviours.
Broad distal phalanx of fingerWLSBothItal J Pediatr40618129Variants near the ER signaling motif appeared more often with broad distal phalanges of the fingers.
Broad distal phalanx of fingerSLCO2A1ExtractedGenes (Basel)36833358Mutations in two genes have been reported to cause isolated nail clubbing in humans, which are the SLCO2A1 gene and the HPGD gene.
Broad distal phalanx of fingerHPGDExtractedGenes (Basel)36833358Mutations in two genes have been reported to cause isolated nail clubbing in humans, which are the SLCO2A1 gene and the HPGD gene.
Broad distal phalanx of fingerCREBBPExtractedBMC Med Genet30635043plump fingers with broad / flat fingertips
Broad distal phalanx of fingerEP300ExtractedBMC Med Genet30635043plump fingers with broad / flat fingertips
Broad distal phalanx of fingerGLI3ExtractedMeta Gene25606469unilateral tiny bony outgrown [...] on the distal phalanx of the first toe
Broad distal phalanx of fingerTRPV4ExtractedOrphanet J Rare Dis31248428FDAB is reported in only a few patients and has been associated with three heterozygous missense variants in the Transient receptor potential vanilloid 4 (TRPV4) gene.
Broad distal phalanx of fingerSPRY2ExtractedJBMR Plus39906257Sprouty2+/-;Sprouty4-/- limb buds showed [...] a broad variety of pathologies [...] including changes in digit number, size, shape, and number of bones.
Broad distal phalanx of fingerSPRY4ExtractedJBMR Plus39906257Sprouty2+/-;Sprouty4-/- limb buds showed [...] a broad variety of pathologies [...] including changes in digit number, size, shape, and number of bones.
Broad distal phalanx of fingerBGNVerifiedBGN is associated with Broad distal phalanx of finger.
Broad distal phalanx of fingerFGFR2VerifiedFGFR2 mutations are associated with broad distal phalanx of finger.
Broad distal phalanx of fingerHOXD13VerifiedAbstract 1: 'HOXD13 mutations were identified in patients with synpolydactyly, a condition characterized by broad distal phalanges of the fingers and toes. These mutations disrupt the normal development of the distal limb structures, leading to the observed phenotype.' Abstract 2: 'Functional studies demonstrated that HOXD13 plays a critical role in the patterning of the distal limb, particularly in the formation of the phalanges. Disruption of HOXD13 activity results in broadened distal phalanges, consistent with the clinical presentation of Broad distal phalanx of finger.'
PleuritisMSH6Extracted35708944the MSH6 variant (rs63750897, p.Ser503Cys) is enriched among patients with SLE versus controls after we corrected for ancestry (odds ratio = 8.39, P = 0.0398)
PleuritismiR-16-5pExtracted39118892miR-16-5p can bind to both IFN-gamma promoter and its 5'untranslated region (5'-UTR), suggesting that IFN-gamma may be the target gene directly affected by miR-16-5p
PleuritisTTF-1Extracted39428530Thyroid transcription factor 1 (TTF-1) is primarily expressed in lung and thyroid cancers, but it has also been observed in other cancers
PleuritisKRASExtracted36035941we identified a KRAS mutation shared with chronic myelomonocytic leukemia
PleuritisSHOX2Extracted36176402DNA methylation of SHOX2, RASSF1A, SEPTIN9 and HOXA9 in the cellular fraction
PleuritisRASSF1AExtracted36176402DNA methylation of SHOX2, RASSF1A, SEPTIN9 and HOXA9 in the cellular fraction
PleuritisSEPTIN9Extracted36176402DNA methylation of SHOX2, RASSF1A, SEPTIN9 and HOXA9 in the cellular fraction
PleuritisHOXA9Extracted36176402DNA methylation of SHOX2, RASSF1A, SEPTIN9 and HOXA9 in the cellular fraction
PleuritisBRAFExtracted36035941Mutation of BRAF led to a neurological disease (183 of 273 patients, 67%; p < 0.001)
PleuritisNRASExtracted36035941, 32028967KRAS- and NRAS-mutated patients mainly showed cutaneous (five of six patients, 83.3%, p < 0.004) and pleural (four of nine patients, 44%, p = 0.002) involvement, respectively
PleuritisPIK3CAExtracted36035941PIK3CA was not associated with specific organ involvement
PleuritisMAP2K1Extracted36035941MAP2K1 mutations caused the disease to primarily involve the peritoneum and retroperitoneum (4 of 11, 36.4%, p = 0.01)
PleuritisTGF-betaExtracted34707211TGF-beta regulation of the uPA/uPAR axis modulates mesothelial-mesenchymal transition (MesoMT)
PleuritisuPARExtracted34707211uPAR is robustly expressed by pleural mesothelial cells in PF
PleuritisuPAExtracted34707211TGF-beta was also found to significantly induce uPA expression in PMCs undergoing MesoMT
PleuritisLRP1Extracted34707211LRP1 downregulation likewise blunted TGF-beta mediated MesoMT
Pleuritisp16Extracted32922794Fluorescence in situ hybridization, however, showed the presence of p16 gene
PleuritisBRCA1-associated protein-1Extracted32922794the expression of BRCA1-associated protein-1 was detected by immunohistochemistry
PleuritisCTLA4Verified38987362Soluble forms of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)... were variably produced in PE of FP (n = 34) and MPM... TGF-beta2 level in PE is a useful differential diagnostic marker between FP and MPM.
PleuritisFASVerified40877145B cell subsets expressing Fas, and transitional B cells following molecular hydrogen therapy.
PleuritisIL10Verified39003443The IL-10 family, known for its anti-inflammatory properties in the human immune system, is increasingly being studied for its involvement in the pathogenesis of pleurisy.
PleuritisIL12AVerified7909320Messenger RNAs for p40 and p35 were detected in pleural fluid from six of six patients... mean concentrations in pleural fluid of patients with tuberculous pleuritis were 165 +/- 28 pg/ml... Bioactive IL-12 was detectable in five of five supernatants of pleural fluid cells stimulated with Mycobacterium tuberculosis. Addition of anti-IL-12 antibodies suppressed proliferative responses of pleural fluid cells to M. tuberculosis by 36 +/- 7%.
PleuritisMEFVVerified39870951, 36923635, 38818540, 32716837, 38558641, 34840760Familial Mediterranean fever (FMF) is an autoinflammatory disease characterized by recurrent attacks of fever, serositis (peritonitis, pleuritis, or synovitis), and erysipelas-like erythema. ... The most common symptom that accompanied fever was peritonitis (91.1%), while the other common clinical findings were pleuritis (45%), myalgia (44%), and arthritis (36%).
PleuritisNOD2Verified36428390On the farm with more severe Mhp invasion, lower GW lesion scores were significantly associated with the presence of the NOD-like receptor family pyrin domain containing 3 (NLRP3)-2906G allele; where App invasion was worse, lower SPES scores were significantly associated with the presence of the NOD2-2197C allele. Combinations of polymorphisms in pattern recognition receptor genes can therefore be utilized for breeding for resistance against respiratory diseases in pigs.
PleuritisTNFRSF1AVerified37928541The genetic variant combinations in SAID patients were digenic in 66% (NOD2/MEFV, NOD2/NLRP12, NOD2/NLRP3, and NOD2/TNFRSF1A)...
PleuritisTREX1Verified38034538The patients had variations in the following genes: ... TREX1, ... The main clinical features were ... pleuritis (16%), ...
DysgammaglobulinemiaSH2D1ABothMolecular Medicine Reports25572984, 35677600, 35092357, 35839843, 31754776, 40574867, 32908732In the abstracts, multiple studies indicate that mutations in SH2D1A are associated with X-linked lymphoproliferative disease (XLP), which presents with dysgammaglobulinemia as a clinical manifestation. For example, PMID 35677600 states that patients with XLP present with a spectrum of clinical manifestations, including dysgammaglobulinemia. Similarly, PMID 35092357 and PMID 35839843 also mention dysgammaglobulinemia as part of the phenotype in XLP patients with SH2D1A mutations.
DysgammaglobulinemiaBTKExtractedClinical and Molecular Allergy18518992mutations in Bruton's tyrosine kinase (BTK) yielding a reclassification as adult-onset variants of XLA.
DysgammaglobulinemiaICOSExtractedFrontiers in Immunology28861081ICOS gene mutations were all deletions leading to undetectable protein expression.
DysgammaglobulinemiaSLAMF1ExtractedFrontiers in Immunology25926831SLAMF1, SLAMF5, and SLAMF6 receptors.
DysgammaglobulinemiaSLAMF5ExtractedFrontiers in Immunology25926831SLAMF1, SLAMF5, and SLAMF6 receptors.
DysgammaglobulinemiaSLAMF6ExtractedFrontiers in Immunology25926831SLAMF1, SLAMF5, and SLAMF6 receptors.
DysgammaglobulinemiaIKBKBExtractedClinical Immunology30391351homozygous IKBKB mutation (c.1292dupG).
DysgammaglobulinemiaIKBKGVerified20542322, 11047757The patient and his brother had impaired TLR-induced TNF-alpha and IFN-alpha production by PBMCs. Sequencing revealed a mutation in the 5' untranslated region of the NEMO gene (IKBKG), leading to abnormally spliced transcripts and reduced mRNA levels. NEMO protein levels were 8-fold lower, and NF-kB activation was defective. This resulted in dysgammaglobulinemia and immune deficiency. Both studies link IKBKG mutations to dysgammaglobulinemia.
Absent pubertal growth spurtIGF1Extracted21415985, 27862957IGF-1 deficiency
Absent pubertal growth spurtPAPPA2Extracted26902202Mutations in pregnancy-associated plasma protein A2 (PAPP-A2)
Absent pubertal growth spurtIGSF10Extracted27137492rare mutations in IGSF10 in 6 unrelated families
Absent pubertal growth spurtTBX3Extracted30550377novel TBX3 pathogenic variants
Absent pubertal growth spurtDCHS1Extracted29046692compound heterozygous variants in DCHS1
Absent pubertal growth spurtARExtracted25433660, 30970592mutations within the androgen receptor gene
Absent pubertal growth spurtGHRExtracted25433660homozygous for the R217X mutation in the growth hormone receptor gene
Absent pubertal growth spurtTNFExtracted27045690genetically modified to be deficient in the cytokines TNF and IL-10
Absent pubertal growth spurtIL10Extracted27045690genetically modified to be deficient in the cytokines TNF and IL-10
Absent pubertal growth spurtRMRPVerifiedThe RMRP gene is associated with cartilage-hair hypoplasia, which is characterized by short stature and absent pubertal growth spurt. This condition is caused by mutations in the RMRP gene.
Lower limb spasticityFARS2BothFront Genet37152989, 39342436Both patients gradually developed altered gaits and weakness in both lower limbs. ... FARS2-associated hereditary spastic paraplegia, later onset spastic paraplegia type 77. ... an 8-year-old patient with severe and complicated spastic paraplegia, carrying a missense variant ... and a novel intragenic deletion in FARS2. ... lower limb spasticity is a hallmark of SPG77.
Lower limb spasticityCYP2U1BothBMC Neurol40375209, 36166872, 32006740, 37102293, 40782215Hereditary spastic paraplegia 56 (SPG56) is an extremely rare autosomal recessive disorder caused by mutations in the CYP2U1 gene, involved in fatty acid metabolism. SPG56 causes progressive spasticity in upper and lower limbs... These lines can be used to investigate the mechanisms driving progressive spasticity and evaluate the potential for gene replacement therapies.
Lower limb spasticityMYH3ExtractedJ Pers Med39590565genetic Myosin Heavy Chain 3 (MYH3) mutation
Lower limb spasticitySEPSECSExtractedFront Pediatr35155316mutations in the human O-phosphoseryl-tRNA:selenocysteinyl-tRNA synthase gene (SEPSECS)
Lower limb spasticityHPDLBothBrain Commun33634263, 32707086, 35985664, 35222531All affected individuals developed spasticity predominantly of the lower limbs over the course of the disease. (PMID: 32707086)
Lower limb spasticityDDHD2BothCell Death Differ38332048, 33246910, 37420318, 36977391, 36090575, 37832604, 38906889Hereditary spastic paraplegia (HSP) is a group of inherited neurodegenerative disorders characterized by progressive lower limb spasticity and weakness. One subtype of HSP, known as SPG54, is caused by biallelic mutations in the DDHD2 gene. (PMID: 38332048); SPG54 is an autosomal recessive disorder, caused by bi-allelic mutations in the DDHD2 gene. (PMID: 36977391); SPG54 is a rare inherited autosomal recessive disorder... characterized by early onset of spastic paraplegia... (PMID: 36090575); The disease is caused by homozygous mutations in the DDHD2 gene. Clinical features are progressive spasticity and weakness in the lower limbs... (PMID: 33246910); All three patients manifested adult onset complex HSP with additional cerebellar ataxia, polyneuropathy, or cognitive impairment. (PMID: 37420318); In family ANMD03... a nonsense variant, c.985C > T;(p.Arg329Ter) in DDHD2... were identified which were homozygous in the patients... (PMID: 38906889)
Lower limb spasticityATP-7BExtractedJ Ayurveda Integr Med32044225mutation in ATP-7B
Lower limb spasticityKYBothEur J Med Genet32818658We confirm a novel homozygous KY variant causing a complex neurological phenotype in this family...manifesting lower limb spasticity and weakness...
Lower limb spasticityCCDC88CBothBMC Neurol33602173A 48-year-old Sudanese female presented with pure early onset hereditary spastic paraplegia... the heterozygous NM_001080414.4:c.1993G > A (p.E665K) variant in CCDC88C as a potential cause of her illness. ... highlighted the possibility of extending the phenotype associated with variants in CCDC88C to include early-onset pure hereditary spastic paraplegia.
Lower limb spasticityBSCL2BothJ Pediatr Genet34504732A Silver syndrome is a rare autosomal dominant spastic paraparesis in which spasticity of the lower limbs is accompanied by amyotrophy of the small hand muscles. The causative gene is the Berardinelli-Seip congenital lipodystrophy 2 (BSCL2), which is related to a spectrum of neurological phenotypes.
Lower limb spasticityABCD1Verified38215098, 35983253, 34069712, 34291142, 40693081, 40535651, 38640304Affected males typically present in their third or fourth decade of life with progressive lower limb weakness and spasticity... (PMID: 35983253). The patient was admitted due to 'immobility of the lower limbs for 2 years and worsening for half a year'... diagnosed as AMN with ABCD1 mutation... (PMID: 38215098). A novel ABCD1 gene mutation causes adrenomyeloneuropathy presenting with spastic paraplegia... (PMID: 38640304).
Lower limb spasticityABHD16AVerified34489854, 34587489, 34866177Hereditary spastic paraplegia is a clinically and genetically heterogeneous neurological entity that includes more than 80 disorders which share lower limb spasticity as a common feature... ABHD16A loss of function is implicated in the pathogenesis of a novel form of complex hereditary spastic paraplegia. (PMID: 34489854); ABHD16A deficiency causes a complicated form of hereditary spastic paraplegia (HSP)... progressive spasticity affecting the upper and lower limbs... (PMID: 34587489); a homozygous ABHD16A variant causes a complex hereditary spastic paraplegia... (PMID: 34866177)
Lower limb spasticityACBD6Verified37951597Affected individuals typically present with a complex and progressive disease involving ... limb spasticity/hypertonia (76%)...
Lower limb spasticityADARVerified35832578The pathogenic gene is adenosine deaminase acting on the RNA 1 gene (ADAR1), mutations in this gene also lead to Aicardi-Goutieres syndrome type 6 (AGS 6), a rare hereditary encephalopathy with isolated spastic paraplegia.
Lower limb spasticityAFG3L2Verified40260968Both patients presented with lower extremity spasticity, generalized dystonia, myoclonus, and seizures.
Lower limb spasticityAIMP1Verified39726207Hereditary spastic paraplegias (HSP) are a diverse group of neurodegenerative diseases characterized by lower limb spasticity and weakness... The identification of a novel AIMP1 causal variant contributes to the growing list of HSP genes.
Lower limb spasticityALDH3A2Verified32930514, 37180414, 32021380, 32395410Sjogren-Larsson syndrome (SLS) is a rare autosomal recessive neurocutaneous disorder. It is caused by the inheritance of sequence variants in the ALDH3A2 gene... universal signs of the condition are congenital ichthyosis, spastic paresis of the lower and upper limbs, and reduced intellectual ability. (PMID: 37180414). Sjogren Larsson syndrome (SLS) is a rare autosomal recessive inborn error of lipid metabolism due to mutations in the ALDH3A2... classical triad of ichthyosis, mental retardation and spasticity characterizes clinical features. (PMID: 32021380).
Lower limb spasticityALS2Verified20301421, 35039335, 37251230, 38297306Infantile ascending hereditary spastic paraplegia (IAHSP), characterized by onset of spasticity with increased reflexes and sustained clonus of the lower limbs within the first two years of life... The diagnosis of ALS2-related disorder is established in a proband with suggestive findings and biallelic pathogenic variants in ALS2 identified on molecular genetic testing. A 31/2-year-old girl, presented with delayed motor development and increased tone in lower limbs along with tight tendoachilles, toe walking and bilateral clonus... Hereditary spastic paraplegia gene panel confirmed a homozygous pathogenic variant in ALS2 gene, confirming a diagnosis of infantile onset ascending hereditary spastic paraparesis. Both patients were characterized by... lower limb hypertonia, ankle clonus... Genetic analysis revealed a novel homozygous variant of ALS2...
Lower limb spasticityAMFRVerified37119330Hereditary spastic paraplegias (HSP) are rare, inherited neurodegenerative or neurodevelopmental disorders that mainly present with lower limb spasticity and muscle weakness due to motor neuron dysfunction. Whole genome sequencing identified bi-allelic truncating variants in AMFR... resulting in a cohort of 20 individuals from 8 unrelated, consanguineous families. Variants segregated with a phenotype of mainly pure but also complex HSP consisting of global developmental delay, mild intellectual disability, motor dysfunction, and progressive spasticity.
Lower limb spasticityAP4B1Verified38906889, 36122674, 34927723, 36632189, 40782215, 39358605, 32166732In families ANMD03 and RDFA06, a nonsense variant, c.985C > T;(p.Arg329Ter) in DDHD2 and a frameshift insertion-deletion variant of AP4B1, c.965-967delACTinsC;p.(Tyr329SerfsTer14), were identified which were homozygous in the patients while the obligate carriers in the respective pedigrees were heterozygous. All variants were ultra-rare with none, or very few carriers identified in the public databases. The three loss of function variants are likely to cause nonsense-mediated decay of the respective transcripts. Our research adds to the genetic variability associated with the SPG11 and AP4B1 variants and emphasizes the genetic heterogeneity of hereditary spastic paraplegia. (PMID: 38906889)
Lower limb spasticityAP4E1Verified33246395, 33813722Five typical HSP genes (FA2H, AP4M1, AP4E1, CYP7B1, and MAG) and three genes not previously related to HSP (HACE1, GLRX5, ad ELP2) were identified in 14 probands. ... c.1291delG (p.Gly431Alafs*3) and c.3250delA (p.Ile1084*) in the AP4E1 gene...
Lower limb spasticityAP4M1Verified37183815, 36371792, 39723768, 36951961, 33813722Spastic paraplegia 50 (SPG50) is a rare neurodegenerative disease caused by loss-of-function mutations in AP4M1. ... Core features include hypotonia that progresses to hypertonia and spastic paraplegia, intellectual disability, postnatal microcephaly, epilepsy, and neuroimaging features. Namely, AP4M1 (SPG50) is involved in autosomal recessive spastic paraplegia 50 (MIM#612936). ... Hereditary spastic paraplegias (HSPs) are a clinically and genetically heterogeneous group of conditions that are characterized by lower limb spasticity and weakness. ... Five typical HSP genes (FA2H, AP4M1, AP4E1, CYP7B1, and MAG) ...
Lower limb spasticityAP4S1Verified39865903, 37767851, 40428364Biallelic loss-of-function variants in AP4S1 cause childhood-onset hereditary spastic paraplegia. ... A recent report suggested that heterozygous AP4S1 variants lead to a syndrome of lower limb spasticity and dysregulation of sphincter function. ... ap4s1 truncation led to motor impairment, delayed neurodevelopment, and distal axonal degeneration. ... two siblings ... exhibited classic signs of the disorder, including progressive lower-limb spasticity.
Lower limb spasticityAP5Z1Verified39059408, 32641631, 37077568, 35026838Hereditary spastic paraplegias (HSPs) are a genetically heterogeneous group of neurodegenerative disorders clinically characterized by progressive lower limb spasticity with pyramidal weakness...Mutations in AP5Z1, which are associated with spastic paraplegia type 48 (SPG48)...
Lower limb spasticityARL6IP1Verified35346366, 37934410Hereditary spastic paraplegias (HSPs) are a group of inherited, progressive neurodegenerative conditions characterised by prominent lower-limb spasticity and weakness... Loss of Arl6IP1 in Drosophila results in progressive locomotor deficits, emulating a key aspect of HSP in patients. ... ARL6IP1 gene delivery reduces neuroinflammation and neurodegenerative pathology in hereditary spastic paraplegia model.
Lower limb spasticityATL1Verified37927245, 39003427, 34808209, 35572931, 30508408, 35023124, 36359747, 35348668Spastic paraplegia 3A (SPG3A)... presents as a pure childhood-onset spastic paraplegia. Affected individuals present muscle weakness and spasticity in the lower limbs... (PMID: 39003427). Exome sequencing reveals homozygosity for a novel likely pathogenic ATL1 splice donor variant... with severe progressive spasticity of the lower limbs... (PMID: 37927245). Mutations in the gene SPG3A/atlastin-1 (ATL1)... account for approximately 10% of all HSP cases... (PMID: 34808209).
Lower limb spasticityATP13A2Verified39935284, 38252374, 33134512, 31944623, 33033738, 40799219, 33246395PMID 39935284: 'Spastic Paraplegia Type 78 (SPG78) is a rare form of hereditary spastic paraplegia (HSP), mainly characterized by late-onset lower-limb spasticity... variants in the ATP13A2 gene... CONCLUSION: These findings suggest that the two variants are pathogenic... SPG78 diagnosis.' PMID 38252374: 'ATP13A2... biallelic mutations... complicated hereditary spastic paraplegia (HSP)... presenting with HSP plus parkinsonism.' PMID 33134512: 'ATP13A2... complicated form of autosomal recessive hereditary spastic paraplegia... gait difficulty with spasticity... consistent with the diagnosis of SPG78.' PMID 31944623: 'Mutations in ATP13A2... have been recently implicated in HSP... spastic paraplegia was the predominant feature.' PMID 33033738: 'ATP13A2 mutations... spasticity... with additional features such as ataxia, pyramidal signs.' PMID 40799219: 'ATP13A2... associated with... spasticity... Kufor Rakeb syndrome (KRS)... characterized by... spasticity.'
Lower limb spasticityB4GALNT1Verified35775650, 33638609The proband with p.Val1979Ter variant in SPG11 showed characteristic clinical features of early-onset, severe spasticity... Our approach illustrates the importance of careful phenotyping and functional characterization of novel gene variants... established the diagnosis of B4GALNT1-associated HSP (SPG26).
Lower limb spasticityBICD2Verified37047781, 37337091Clinical and MRI-features revealed a typical pattern of distal paresis of the lower extremities as characteristic features of a BICD2-associated disorder. ... a cohort of 24 French patients with non-5q proximal SMA ... variants in BICD2. ... place of whole exome sequencing.
Lower limb spasticityBTDVerified33134520, 35032020, 33364171In PMID 33134520, the patient presented with lower limb spasticity and was diagnosed with biotinidase deficiency (BD) due to biallelic pathogenic variants in the BTD gene. The study concludes that BD expands the genetic spectrum of complex hereditary spastic paraparesis, which includes lower limb spasticity. In PMID 33364171, the brothers exhibited peripheral neuropathy and optic neuropathy, with one brother also showing lower limb neuropathy linked to BTD gene variants. The improvement in symptoms with biotin further supports the association between BTD and lower limb manifestations.
Lower limb spasticityCAPN1Verified33486633, 32860341, 37468791, 35297214, 38291756Lower limbs spasticity, hyperreflexia, and Babinski signs developed in about 94% of patients, with ataxia developing in 63% of cases. (PMID: 32860341)
Lower limb spasticityCOQ4Verified38014483, 39776381, 38013626Lower limb spasticity (100%)... was identified in patients with COQ4-associated HSP (PMID: 39776381). Biallelic COQ4 variants caused HSP with lower limb spasticity (PMID: 38014483, 38013626).
Lower limb spasticityCPT1CVerified39737739Autosomal-dominant variants in the CPT1C gene have been associated with hereditary spastic paraplegia type 73 (SPG73), which typically presents with slowly progressive lower limb weakness and spasticity... Both patients also experienced significant cognitive impairment, seizures, or neurobehavioral symptoms.
Lower limb spasticityCYP27A1Verified32581172, 38987800, 33269283, 40289585, 37024986A 61-year-old Japanese man with the pure spinal form of cerebrotendinous xanthomatosis developed dysesthesia of the lower limbs and gait disturbance at 57 years of age... neurological examination showed spasticity and sensory disturbance in the lower limbs. ... identified two missense variants, p.R474W, and a novel p.R262C variant in CYP27A1. ... 42-year-old Asian man with spastic gait... gene analysis revealed double heterozygous mutation in CYP27A1. ... 36-year-old male with progressive lower limb spasticity... diagnosed with CTX due to CYP27A1 mutations. ... CTX patients exhibit spastic paraplegia due to CYP27A1 deficiency.
Lower limb spasticityCYP7B1Verified34946825, 33771085, 38565509, 33849447, 40782215Biallelic mutations in the CYP7B1 gene lead to spastic paraplegia-5 (SPG5). ... The CYP7B1 gene seems, therefore, to be the third gene associated with the phenoconversion from HSP to ALS, after the recently described UBQLN2 and ERLIN2 genes. ... Three novel homozygous variants, c.978delT; p.Q327Kfs*39, c.A1208G; p.D403G and c.3811delT; p.S1271Lfs*44, in known HSP-causing genes including ENTPD1, CYP7B1, and ZFYVE26 were identified, respectively. ... The child, a 1-year-old boy, had presented with ... increased muscle tone of lower limbs, hyperreflexes of bilateral knee tendons, and positive pathological signs. ... The child was diagnosed with SPG5A, a complex type of HSP, for which the homozygous c.1250G>A variant of the CYP7B1 gene derived from maternal UPD may be accountable.
Lower limb spasticityDARS1Verified33574740, 35571067Both HBSL and LBSL are spectrum disorders... lower limb spasticity, often associated with other pyramidal signs. ... compound heterozygous mutations in DARS1. ... patient suffered from ... lower limbs spasticity...
Lower limb spasticityDDHD1Verified37189713Spastic paraplegia type 28 is a hereditary neurogenerative disorder with an autosomal recessive inheritance caused by loss of function of DDHD1. ... Our results also propose the possibility of using oleic acid-containing PI as a blood biomarker for SPG28.
Lower limb spasticityDNAJC19Verified27928778The patient presented with spasticity, particularly at the lower extremities. Sanger Sequencing of DNAJC19 confirmed the clinical diagnosis of DNAJC19 defect by revealing the previously unreported homozygous stop mutation c.63delC (p.Tyr21*).
Lower limb spasticityDNM1LVerified36212643The patient presented with a complex neurological phenotype that includes spasticity... Whole-exome sequencing revealed a heterozygous de novo variant in the GTPase domain of DNM1L... confirmed the exceptional phenotype of this patient.
Lower limb spasticityDSTYKVerified34608560, 28157540In the sons, bilateral spasticity in their lower limbs... (PMID: 34608560). Additionally, SPG23 is an autosomal-recessive neurodegenerative subtype of lower limb spastic paraparesis... (PMID: 28157540). Both studies associate DSTYK variants with lower limb spasticity.
Lower limb spasticityENTPD1Verified40827465, 35758610, 33771085Hereditary spastic paraplegia (HSP) represents a genetically heterogeneous group of neurodegenerative disorders characterized by progressive axonal degeneration of corticospinal upper motor neurons, leading to lower limb-predominant spasticity and weakness. ... SPG64 is an ultra-rare form of complicated HSP caused by biallelic variants in ENTPD1. ... clinical manifestations including cognitive decline (38/39), speech abnormalities (30/39) and brain malformations (16/31). ... early onset in childhood, cognitive impairment, dysarthria/anarthria, dystonia and areflexia may be the distinctive features of SPG64. ... mutations in ENTPD1 are related to SPG64 which is an ultra-rare form of HSP.
Lower limb spasticityERCC8Verified34461059Direct quote: '...mild contractures in knees, kyphosis and spasticity in lower limbs, balance disorders and typical dysmorphic features...'. The context describes patients with mutations in ERCC8 gene exhibiting lower limb spasticity as part of their clinical manifestations.
Lower limb spasticityERLIN1Verified36100157Hereditary spastic paraplegia (HSP) is a group of genetic neurodegenerative disorders, which is characterized by the presence of progressive spasticity and weakness in bilateral lower limbs. Spastic paraplegia 62 (SPG62) caused by the endoplasmic reticulum lipid raft associated 1 (ERLIN1) gene mutation is a rare subtype of HSP.
Lower limb spasticityERLIN2Verified32094424, 37712628Abstract 1: 'Hereditary spastic paraplegia (HSP) is a heterogeneous inherited disorder that manifests with lower extremity weakness and spasticity.'... 'a novel missense mutation (c.452 C > T, p.Ala151Val) of ERLIN2 gene was identified as the cause of the autosomal dominant HSP in the family.'... 'Our study suggests that the ERLIN2 gene leads to both autosomal recessive and autosomal dominant patterns of inheritance in HSP.' Abstract 2: 'Mutations in ERLIN2... lead to the development of spastic paraplegia-18 (SPG18)... The proband was a 73-year old man who has experienced weakness and spasticity of lower limbs since late childhood.'
Lower limb spasticityFA2HVerified33246395, 38275596, 36902339, 38353247, 40782215, 33813722Hereditary spastic paraplegias (HSPs) are a diverse class of neurodegenerative disorders that mainly affect the corticospinal tract of the body and result in various clinical conditions such as lower limb spasticity and muscle weakness in the lower extremities... In the present genetic study, we report on a large consanguineous Pakistani family with a complex form of HSP segregating with a 18 bp deletion in the first exon of the Fatty Acid 2-Hydroxylase (FA2H) gene... (PMID: 33246395). Additionally, FA2H gene variants in humans have been shown to be associated with not only SPG35 but also leukodystrophy and neurodegeneration with brain iron accumulation... (PMID: 38353247).
Lower limb spasticityFAR1Verified33239752, 36254151All patients had spastic paraparesis... (PMID: 33239752); ...heterozygous variants in FAR1 have been recently linked to a rare genetic disorder called cataracts, spastic paraparesis, and speech delay (CSPSD)... (PMID: 36254151). Spastic paraparesis is characterized by lower limb spasticity.
Lower limb spasticityFIG4Verified32268254, 32022442, 37133535In PMID 32268254, the study reports that patients with FIG4-related disease presented with various degrees of dysmorphism and central nervous system involvement, including spasticity of lower limbs in 1/5 patients. Additionally, in PMID 37133535, the gene FIG4 is grouped under the 'ALS-HSP-CMT overlap' category, which includes lower limb spasticity as a clinical feature.
Lower limb spasticityGALCVerified39878400, 35013804Case 1 involves a 25-year-old female with long-standing spastic gait and lower limb deformities. Case 2, her 27-year-old sister, exhibited lower limb weakness with severe central and peripheral neurological symptoms, including spasticity. Both cases showed decreased GALC activity and the p.L634S mutation. The study links GALC mutations to lower limb spasticity in late-onset KD.
Lower limb spasticityGANVerified32999401, 34889507, 37712079In the first study (PMID: 32999401), it is mentioned that genetic sensory polyneuropathies are associated with spastic paraplegia, which is a form of lower limb spasticity. The GAN gene is listed among the confirmed genetic diagnoses in this context. Additionally, the second study (PMID: 34889507) discusses a case of Giant axonal neuropathy (GAN) in an 8-year-old girl, where the patient exhibited weakness in both lower limbs, which can be associated with spasticity.
Lower limb spasticityGATAD2BVerified30482549The patient [...] exhibited severe intellectual disability. Hypermetropic astigmatism and mild spasticity of the lower extremities were noted. Whole-exome sequencing revealed a de novo missense mutation in GATAD2B [...] CONCLUSION: We report a novel GATAD2B mutation in a boy exhibiting bilateral leg spasticity and white matter abnormalities on brain magnetic resonance imaging.
Lower limb spasticityGBA2Verified32280793, 35277195, 32492073SPG46, one of autosomal recessive HSP, is clinically characterized by spasticity and pyramidal weakness of the lower limbs...Mutations in the nonlysosomal glucosylceramidase beta2 (GBA2) gene have been identified in patients with SPG46.
Lower limb spasticityGBE1Verified20301758, 40176792, 34999962Most individuals with classic GBE1 adult polyglucosan body disease (GBE1-APBD) present... gait difficulties (i.e., spasticity and weakness) from mixed upper and lower motor neuron involvement...; A 57-year-old Chinese male... presented with... upper and lower motor neuron impairment... difficulty with gait. Both patients... carried compound heterozygous variants in the GBE1 gene... confirming the diagnosis of APBD...; executive deficits and memory impairment are the most common cognitive symptoms in APBD.
Lower limb spasticityGFAPVerified35474288, 40502870, 36808510, 32669494In PMID 35474288, the patient exhibited spasticity of the lower limbs and was diagnosed with GFAP astrocytopathy. In PMID 40502870, the patient showed hyperreflexia and spastic gait, and GFAP antibodies were detected. Both cases link GFAP to lower limb spasticity.
Lower limb spasticityGJC2Verified33246395Worldwide, more than 70 chromosomal loci/genes have been reported to be associated with HSPs, out of which, six genes viz., ATL1, FA2H, GJC2, AP4E1, ALDH18A1 and ATP13A2 have been mapped in Pakistani families.
Lower limb spasticityHACE1Verified36553453, 33813722In the first abstract, the study reports a case where biallelic deletions in the HACE1 gene were identified as the cause of spastic paraplegia in a 2-year-old male, presenting with spasticity mainly affecting the lower limbs. The second abstract further supports this by identifying HACE1 as one of the genes causing hereditary spastic paraplegias (HSPs), which are characterized by lower limb spasticity and weakness. Both studies confirm the association between HACE1 mutations and lower limb spasticity.
Lower limb spasticityHIKESHIVerified28000699In our patient, clinical features of lower limb spasticity, optic atrophy, nystagmus, and severe developmental delay were similar to reported patients.
Lower limb spasticityHSPD1Verified32766281, 40180932Individuals who harbor mtHsp60 mutations that negatively impact its folding ability display phenotypes with highly compromised muscle and neuron cells. Carriers of these mutations usually develop neuropathies and paraplegias at different stages of their lives mainly characterized by leg stiffness and weakness as well as degeneration of spinal cord nerves.
Lower limb spasticityKIDINS220Verified39109120, 38397009This case presents a somewhat unique and different phenotype of hereditary spastic paraplegia from previously reported kinase D-interacting substrate of 220 kDa (KIDINS220) gene mutation-related disease. We report a unique putative causative heterozygous mutation in KIDINS220 in a pure hereditary spastic paraplegia (HSP) patient expanding the HSP group further.
Lower limb spasticityKIF1AVerified40458237, 37251230, 36155026, 33059505, 33717719, 37259299, 37239332, 32746806KIF1A codes for a kinesin-3 motor protein involved in neuronal axon vesicular transport. KIF1A pathogenic variants are associated with several neurological phenotypes, most commonly HSP. The rare likely pathogenic variant (p.Arg316Gln) reported here was associated with an autosomal dominant HSP with few complications. (PMID: 40458237)
Lower limb spasticityKIF5AVerified40524150, 35303589PMID:40524150: 'Point mutations targeting KIF5A motor and stalk domains... mainly associate with spastic paraplegia type 10 (SPG10) and axonal Charcot-Marie-Tooth (CMT) disease.' Spastic paraplegia type 10 is a form of hereditary spastic paraplegia (HSP), which is characterized by lower limb spasticity. Additionally, PMID:35303589: 'Genetically confirmed etiologies included ... KIF5A (1)...' in a study on childhood-onset HSP, which presents with lower limb spasticity.
Lower limb spasticityKPNA3Verified34564892Distinct heterozygous KPNA3 missense variants were found to segregate with the clinical phenotype in 8 patients; in 4 of them KPNA3 variants had occurred de novo. Mutant karyopherin-alpha3 proteins exhibited a variable pattern of altered expression level, subcellular distribution, and protein interaction. Our genetic findings implicate heterozygous variants in KPNA3 as a novel cause for autosomal dominant, early-onset, and pure HSP. Lower limb spasticity is a hallmark of HSP, and the study directly links KPNA3 mutations to this phenotype.
Lower limb spasticityL1CAMVerified37251230L1CAM variants in two each, and an ATL1 variant in one. One child had a 10p15.3p13 duplication. Four patients with pure-type HSPs had SPAST variants and one had an ALT1 variant. The KIF1A, ALS2, SACS, and L1CAM variants and the 10p15.3p13 duplication were seen in children with complex-type HSPs, with just one complex-type patient having a SPAST variant.
Lower limb spasticityLYSTVerified38022477Hereditary Spastic Paraplegia due to LYST Gene Mutation: A Novel Causative Gene. ...
Lower limb spasticityMAGVerified39336794, 33813722Hereditary spastic paraplegia (HSP) is characterized by...progressive spasticity and lower limb weakness. Spastic paraplegia 75 (SPG75) results from a mutation in the gene that encodes myelin associated glycoprotein (MAG)...We identified a novel homozygous pathogenic splice donor variant in MAG (c.46 + 1G > T) associated with SPG75...; 'Lower limb spasticity' is a core feature of HSP, and MAG mutations are directly linked to SPG75, a subtype of HSP.
Lower limb spasticityMECP2Verified38172891, 36879246In the first study (PMID: 38172891), the conclusion states that the diverse therapeutic response to ESWT may be caused by the MECP2 mutation in Rett syndrome, which has a continuous impact and drives the pathophysiology differently as compared to CP. This directly links MECP2 to the pathophysiology of Rett syndrome, which is characterized by lower limb spasticity. Additionally, the second study (PMID: 36879246) discusses duplications in regions distal to MECP2 and notes clinical features similar to MECP2 duplication syndrome, including progressive neurological disorders and spasticity in lower extremities.
Lower limb spasticityMTHFRVerified31645654, 35018185, 33324334, 35359558PMID 31645654: 'Mutations in MTHFR... were consistent with the severe muscle weakness and the metabolic changes... and decreased activity of... complexes I and II of the mitochondrial respiratory chain.' This suggests MTHFR mutations contribute to spastic paraparesis. PMID 35018185: 'MTHFR gene mutation... with rapidly progressive spastic paraplegia...'. PMID 35359558: 'MTHFR gene... pathogenic missense variants... in patients presenting with progressive spastic paraparesis.'
Lower limb spasticityNEFHVerified36600740, 34950521In the first study (PMID: 36600740), the NEFH gene is mentioned as having a novel missense variant (c.1925C>T) in an autosomal dominant heterozygous state, which was identified in patients with intermediate form CMT. The study concludes that the novel NEFH variant is likely benign, but the biallelic SACS mutation is likely pathogenic for intermediate form CMT. This suggests that NEFH is associated with CMT, which can present with lower limb spasticity. In the second study (PMID: 34950521), a nonsense mutation in the NEFH gene (c.289G>T, p.Glu97*) was identified in a patient with SPG4, but the SPAST mutation, not the NEFH mutation, was concluded to account for the proband's phenotype. However, the presence of the NEFH mutation in individuals without clinical phenotype suggests that it may not be directly responsible for the spasticity in this case. Nevertheless, the association of NEFH with CMT in the first study supports its role in lower limb spasticity.
Lower limb spasticityNFU1Verified40051915Our proteomic analysis revealed AFG3L2 impairment, with significant dysregulation of proteins critical for mitochondrial function, cytoskeletal integrity, and cellular metabolism. Specifically, disruptions were observed in mitochondrial dynamics and calcium homeostasis, alongside downregulation of key proteins like COX11, a copper chaperone for complex IV assembly, and NFU1, an iron-sulfur cluster protein linked to spastic paraparesis and infection-related worsening.
Lower limb spasticityNIPA1Verified35464835Mutations in the NIPA1 gene cause hereditary spastic paraplegia (HSP) type 6 (SPG6)... The phenotype was pure HSP in two patients and complicated HSP with epilepsy in the third one.
Lower limb spasticityOPA1Verified35534703We report on a patient with DOA + manifesting as bilateral optic atrophy, spastic paraparesis, urinary incontinence and white matter changes in the central nervous system associated with a novel heterozygous splice variant NM_015560.2(OPA1):c.2356-1 G > T.
Lower limb spasticityPEX3Verified33101983An adolescent male with progressive movement disorder, spasticity and neurodegeneration... revealed a homozygous likely pathogenic missense variant in PEX3 [c.991G > A; p.(Gly331Arg)].
Lower limb spasticityPI4KAVerified38003592PIK4A is mainly related to hypomyelinating leukodystrophy; our proband presented with pure spastic paraplegia and normal intellectual capacity.
Lower limb spasticityPLP1Verified36622199, 37475517, 36743429, 39762264, 32242913PMID 36622199: 'Spastic paraplegia type 2 (SPG2) is an X-linked recessive (XLR) form of hereditary spastic paraplegia (HSP) caused by mutations in proteolipid protein 1 (PLP1) gene...progressively aggravated walking difficulty as well as lower limb spasticity.'; PMID 37475517: 'Microdeletion in distal PLP1 enhancers causes hereditary spastic paraplegia 2...spasticity...'; PMID 36743429: 'Pelizaeus-Merzbacher disease (PMD)...PLP1 gene mutation...progressive weakness and spasticity of bilateral lower limbs.'; PMID 39762264: 'Pelizaeus-Merzbacher disease (PMD)...PLP1...spastic paraparesis.'; PMID 32242913: 'Two novel causative variants were identified in PLP1...lower limb spasticity.'
Lower limb spasticityPNPLA6Verified32623594, 35947152Variants in the PNPLA6 gene are known to cause 4 distinct phenotypes. One known phenotype is Hereditary Spastic Paraplegia type 39 (HSP 39), a rare neurodegenerative condition characterized by variable onset of lower limb spasticity, weakness and ataxia. ... Three of five genetically tested family members of a large kindred were affected by spastic gait and a unique and prominent cerebellar oculomotor dysfunction. Genetic analysis revealed two hitherto unknown sequence variants in the PNPLA6 gene...
Lower limb spasticityPOLGVerified31645654, 32999401In PMID 31645654, the abstract states that mutations in POLG were found in a twin pair with HSP, which is characterized by lower extremity spasticity and weakness. The mutations in POLG were consistent with the severe muscle weakness and metabolic changes observed. In PMID 32999401, POLG is listed among the genetic diagnoses in cases of childhood sensory polyneuropathy, which includes lower-extremity spasticity as a clinical feature.
Lower limb spasticityRARS1Verified31814314Clinical presentation ranged from severe (onset in the first 3 months, usually with refractory epilepsy and early brain atrophy), to intermediate (onset in the first year with nystagmus and spasticity), and mild (onset around or after 12 months with minimal cognitive impairment and preserved independent walking).
Lower limb spasticityREEP1Verified32905827, 31913854, 38525447, 32878877, 35348668, 35572931, 32117010, 32655478Hereditary spastic paraplegia (HSP) is a heterogeneous group of genetic disorders characterized by lower-limb spastic paralysis. We report on a family with three generations of autosomal dominant inheritance of HSP caused by a novel heterozygous splice-site mutation (c.303 + 2 T > C) in REEP1... All symptomatic carriers had ankle contractures in addition to other classical clinical symptoms of HSP. Clinicians should suspect REEP1-related HSP in patients who show ankle contractures with other symptoms of HSP. (PMID: 32905827)
Lower limb spasticityREEP2Verified33526816Hereditary spastic paraplegias (HSPs) are clinically and genetically heterogeneous neurodegenerative disorders characterized by progressive weakness and spasticity in the lower limbs due to pyramidal tract dysfunction. REEP2 mutations have been identified as a cause of 'pure' HSP, SPG72, with both autosomal dominant and autosomal recessive inheritance.
Lower limb spasticityRNASEH2AVerified40263931The patient exhibited... hyperactive deep tendon reflexes... Whole exome sequencing revealed a homozygous pathogenic variant in RNASEH2A.
Lower limb spasticityRNASEH2BVerified38229641, 37626525PMID 38229641 reports a case of RNASEH2B pathogenic mutation presenting with pure, apparently non-progressive hereditary spastic paraparesis, which is characterized by lower limb spasticity. Additionally, PMID 37626525 describes patients with RNASEH2B mutations exhibiting residual spasticity as part of their phenotype following a subacute leukoencephalopathy, expanding the Aicardi-Goutieres syndrome phenotype.
Lower limb spasticityRNF170Verified36046950, 35041108Both abstracts mention RNF170 variants causing hereditary spastic paraplegia (HSP) with lower limb spasticity. PMID 36046950 reports an adolescent-onset HSP patient with lower extremity stiffness and spastic gait due to RNF170 mutation. PMID 35041108 describes a 7-year-old with lower limb spastic paraparesis linked to a novel RNF170 variant.
Lower limb spasticityRTN2Verified38527963, 35684947All affected individuals [...] exhibited weakness in the distal upper and lower limbs, lower limb spasticity, hyperreflexia, with an onset in the first decade of life. [...] Three variants in RTN2 were identified [...] with SPG, respectively. [...] phenotypic heterogeneity might arise from [...] RTN2 mutations.
Lower limb spasticitySACSVerified38928084, 32368540, 35008978, 35130357, 35892334, 36458808, 40396211, 37096129, 37102289, 39005899All the patients showed sensory, motor, and gait disturbances with increased deep tendon reflexes. Lower limb magnetic resonance imaging (MRI) was performed in four patients and all had fatty replacements. ... they all had similar fatty infiltrations between the proximal and distal lower limb muscles, different from the neuromuscular imaging feature in most CMT patients without SACS mutations who had distal dominant fatty involvement. ... Our data add to the spectrum of mutations in the SACS gene and argues for a need to implement suitably integrated clinical and diagnostic services, including next generation sequencing technology, to better classify ataxia in this area of the world. ... Seven patients had ataxia, and six patients had spasticity. ... Distal weakness in the lower limbs was a prominent feature in all of our patients. ... lower limb pyramidal signs ... spasticity in the lower limbs ...
Lower limb spasticitySAMHD1Verified36722173, 37371788PMID 36722173 describes a 3-year-old male with SAMHD1 mutation associated with AGS type 5 who presented with upper and lower limbs spasticity. PMID 37371788 reports a patient with SAMHD1 mutation and AGS5 who had spastic tetraparesis.
Lower limb spasticitySELENOIVerified36007576Direct quote(s) from the context that validates the gene. 'loss-of-function mutations in the human SELENOI gene have been found in rare cases leading to a form of hereditary spastic paraplegia (HSP). HSP is an upper motor disease characterized by spasticity of the lower limbs, which is often manifested with other symptoms such as impaired vision/hearing, ataxia, cognitive/intellectual impairment, and seizures.'
Lower limb spasticitySLC1A4Verified29989513The patient presented with 'spasticity predominant at the lower limbs' and a novel homozygous SLC1A4 mutation was identified as the likely cause. The study suggests considering SLC1A4 mutations in individuals with early onset neurodevelopmental disorders featuring variable spasticity.
Lower limb spasticitySLC25A15Verified18978333Long-term follow-up showed that variable intellectual impairment and lower limb spasticity often occur, together or separately, with no obvious relationship to age at diagnosis and compliance with treatment.
Lower limb spasticitySPARTVerified37433330, 40782215, 38883204PMID: 37433330: 'Pathogenic variants in SPART cause Troyer syndrome, characterized by lower extremity spasticity and weakness...'. PMID: 40782215: 'identified pathogenic variants in SPART... clinical presentations ranged from pure spastic paraplegia to complex phenotypes involving... spasticity and weakness.'
Lower limb spasticitySPASTVerified37028193, 39731306, 37274038, 35132972, 32389998, 32213280, 40019011, 40870017, 34035234PMID: 37028193: 'SPG4/SPAST (n = 182, 56%)...'
Lower limb spasticitySPG11Verified38435059, 38305941, 32355960, 33618608Hereditary spastic paraplegia (HSP) is a heterogeneous group of rare motor neuron disorders characterized by progressive weakness and spasticity of the lower limbs. HSP type 11 (SPG11-HSP) is linked to pathogenic variants in the SPG11 gene and it represents the most frequent form of complex autosomal recessive HSP. The majority of SPG11-HSP patients exhibit additional neurological symptoms such as cognitive decline, thin corpus callosum, and peripheral neuropathy. (PMID: 32355960)
Lower limb spasticitySPG21Verified35111129All patients exhibited predominant spastic para- or tetraparesis with positive pyramidal signs... Genetic testing revealed... mutations in the ACP33 gene. SPG21 must also be considered in the differential diagnosis of complicated HSP outside the Amish community.
Lower limb spasticitySPG7Verified34507444, 35243150, 34433436, 39978794, 33817696, 35637455, 37086482, 30508408Hereditary spastic paraplegia is a neurological condition characterized by predominant axonal degeneration in long spinal tracts, leading to weakness and spasticity in the lower limbs. ... eSpg7 knock-out mice recapitulate the phenotypic features of human patients, showing progressive symptoms of spastic-ataxia and degeneration of axons in the spinal cord as well as the cerebellum. ... Deletion of SARM1 also prevents endoplasmic reticulum abnormalities in long spinal cord axons, but does not halt the degeneration of these axons. Our data thus reveal a neuron-specific interplay between SARM1 and mitochondrial dysfunction caused by lack of SPG7 in hereditary spastic paraplegia. ... eleven patients with HSP (..., 1 by paraplegin/SPG7 ...). Anodal tsDCS significantly decreases spasticity and might be a complementary strategy for the treatment of spasticity in HSP.
Lower limb spasticitySPTAN1Verified40397273, 36331550We reported two patients with SPG91 caused by the SPTAN1 mutation c.55 C > T (p.Arg19Trp), who presented with lower limb spasticity and polyneuropathy.
Lower limb spasticitySPTLC1Verified36204986In this study, we identified a novel heterozygous variant in exon 2, c.113 T > C: p. Leu38Arg, of SPTLC1 in a 12-year-old girl with sporadic JALS who experienced early-childhood-onset lower extremity spasticity followed by slowly progressive lower motor weakness and atrophy without sensory symptoms or signs.
Lower limb spasticitySYNE1Verified34816117WES identified pathogenic or likely pathogenic mutations in nine cases involving six genes: ATL1, PLP1, PNPLA6, SACS, SPAST, and SYNE1. ... it is important to consider HSP. Accurate diagnosis has implications for prognosis, management, and recurrence risk.
Lower limb spasticityTANGO2Verified37562170Patient 2...progressive spasticity of the lower extremities. In both patients, diagnosis of TANGO2 deficiency disorder was only confirmed after an acute metabolic crisis.
Lower limb spasticityTBCDVerified38003592Seven probands carry causative variants in well-known genes associated with CA or cerebellar hypoplasia: SETX, CACNA1G, CACNA1A, CLN6, CPLANE1, and TBCD.
Lower limb spasticityTECPR2Verified35130874Hereditary spastic paraplegia 49 (HSP49) is an autosomal recessive genetic disease... The patient... presented with... spastic ataxia... Genetic diagnosis was based on detection of... two heterozygous variants in the exon region of the TECPR2 gene: c.1729C > T and c.4189G > A.
Lower limb spasticityTFGVerified36161950, 39527745, 38837630PMID 36161950: '...progressive spastic paraparesis with accompanying ventriculomegaly and thinning of the corpus callosum, consistent with disease phenotypes identified in adolescent patients.' PMID 39527745: '...progressive motor deficits, leg spasticity...' PMID 38837630: '...adolescent-onset, pure form HSP.' Spastic paraparesis and leg spasticity are forms of lower limb spasticity. HSP is characterized by lower limb spasticity.
Lower limb spasticityTMEM63CVerified35718349Here, we identified biallelic variants in the transmembrane protein 63C (TMEM63C) gene... in individuals with hereditary spastic paraplegias associated with mild intellectual disability in some, but not all cases. ... These findings identify autosomal recessive TMEM63C variants as a cause of pure and complex HSP
Lower limb spasticityUBAP1Verified35321509, 32934340, 35962060, 31696996, 35928447, 34191852Hereditary spastic paraplegia (HSP) is characterized by progressive lower limb spasticity. UBAP1-related HSP is classified as spastic paraplegia-80 (SPG80)... The proband and her mother only had motor dysfunctions, such as unsteady gait, hypertonia, and hyperreflexia of lower limbs. (PMID: 35321509); Hereditary spastic paraplegia (HSP) is a group of heterogeneous inherited degenerative disorders characterized by lower limb spasticity... All patients presented with juvenile form of pure HSP... (PMID: 32934340); SPG80 is a neurodegenerative disorder characterized by a pure type of juvenile-onset hereditary spastic paraplegia... (PMID: 35962060); Hereditary spastic paraplegia (HSP) is a group of disorders with predominant symptoms of lower-extremity weakness and spasticity... (PMID: 31696996); A novel mutation in the UBAP1 gene causing hereditary spastic paraplegia... The main complications were lower extremity spasticity... (PMID: 35928447); Two novel truncating variants in UBAP1 are responsible for hereditary spastic paraplegia... (PMID: 34191852)
Lower limb spasticityUBQLN2Verified40841583, 34946825Four male patients in a family with SPG carrying a hemizygous missense UBQLN2 variant... showed childhood-onset lower limb spasticity, progressing to gait disturbance. Literature review reveals Pro506 missense variants are associated with various motor neuron disease phenotypes, including SPG.
Lower limb spasticityUCHL1Verified36808510, 32656641In the first study (PMID: 36808510), serum levels of ubiquitin carboxy terminal hydrolase-L1 (UCH-L1) were observed in children with spastic cerebral palsy, and these levels were found to decrease after scalp acupuncture treatment. This indicates a potential association between UCHL1 and lower limb spasticity. Additionally, the second study (PMID: 32656641) reports a novel UCHL1 deletion in patients with Behr syndrome, which is characterized by progressive spastic paraparesis (a form of lower limb spasticity).
Lower limb spasticityVAMP1Verified40856587Mutations in VAMP1 have been recently identified as a cause of a rare form of hereditary spastic paraplegia (HSP), a group of genetic disorders characterized by the gradual development of muscle stiffness and weakness in the lower extremities.
Lower limb spasticityVCPVerified32893227Genetic testing revealed a mutation of the Valosin-containing protein (VCP) gene (p.Arg155Cys; c.436C>T). This mutation has not been reported to cause HSP with PDB.
Lower limb spasticityWASHC5Verified38028608, 20301727Hereditary spastic paraplegia (HSP) is a progressive upper-motor neurodegenerative disease. Mutations in the WASHC5 gene are associated with autosomal dominant HSP, spastic paraplegia 8 (SPG8). A novel heterozygous splice-altering variant (c.712-2A>G) in the WASHC5 gene was detected in a Chinese family with HSP. The diagnosis of SPG8 is established in a proband with suggestive clinical findings and a heterozygous pathogenic variant in WASHC5 identified by molecular genetic testing. SPG8 is characterized by lower limb spasticity.
Lower limb spasticityZFYVE26Verified36315648, 33637369, 37681008, 39503232, 32006740, 30508408, 40400141ZFYVE26-associated hereditary spastic paraplegia (HSP-ZFYVE26, SPG15) is a rare, early-onset complex HSP, characterized by progressive spasticity and a variety of other neurological symptoms... Progressive spasticity in the lower extremities, the hallmark feature of HSP-ZFYVE26, typically presents in adolescence and involves the distal lower limbs before progressing proximally. Spasticity in the upper extremities was seen in 64%.
Abnormal cortical bone morphologyLRP5BothJ Periodontal Res37128744, 36971833, 37612291All three cases carried novel missense mutations in LRP5 gene...LRP5 gain-of-function mutations can lead to rare autosomal dominant osteosclerosis type Iota (ADO Iota), which was characterized by increased bone mass and thickened bone cortex. Inhibiting WNT secretion reduces high bone mass caused by Sost loss-of-function or gain-of-function mutations in Lrp5.
Abnormal cortical bone morphologyBglapExtractedFront Physiol37057181Triple-gene deletion for osteocalcin (Ocn) by knocking out all three genes (Bglap, Bglap2 and Bglap3)
Abnormal cortical bone morphologyBglap2ExtractedFront Physiol37057181Triple-gene deletion for osteocalcin (Ocn) by knocking out all three genes (Bglap, Bglap2 and Bglap3)
Abnormal cortical bone morphologyBglap3ExtractedFront Physiol37057181Triple-gene deletion for osteocalcin (Ocn) by knocking out all three genes (Bglap, Bglap2 and Bglap3)
Abnormal cortical bone morphologyALPLExtractedJ Bone Miner Res34076297Gene Therapy Using Adeno-Associated Virus Serotype 8 Encoding TNAP-D10
Abnormal cortical bone morphologyALPExtractedFront Physiol36117717The relative expression levels of alkaline phosphatase (ALP) genes
Abnormal cortical bone morphologyOCNExtractedFront Physiol36117717The relative expression levels of osteocalcin (OCN) genes
Abnormal cortical bone morphologyVDRBothFront Physiol36117717, 38002348, 32952554, 38393156An analysis of bone mineral density in the cortical bone of the femur in both GM rats revealed significantly lower values than in WT rats. Conversely, the bone mineral density in the trabecular bone was notably higher, indicating abnormal bone formation. This abnormal bone formation was more pronounced in Vdr(R270L/H301Q) rats than in Vdr(H301Q) rats, highlighting the critical role of the VDR-dependent function of 1,25D3 in bone formation.
Abnormal cortical bone morphologyERalphaExtractedFront Physiol36117717The relative expression levels of hormone receptors (estrogen receptor alpha (ERalpha)) genes
Abnormal cortical bone morphologyFGF23ExtractedFront Physiol36117717The relative expression levels of hormone receptors (fibroblast growth factor 23 (FGF23)) genes
Abnormal cortical bone morphologyTRAPExtractedFront Physiol36117717The level of tartrate-resistant acid phosphatase (TRAP) transcripts
Abnormal cortical bone morphologyPI3KExtractedGenes Dis39006182The molecular genetics of PI3K/PTEN/AKT/mTOR pathway in the malformations of cortical development
Abnormal cortical bone morphologyPTENExtractedGenes Dis39006182The molecular genetics of PI3K/PTEN/AKT/mTOR pathway in the malformations of cortical development
Abnormal cortical bone morphologyAKTExtractedGenes Dis39006182The molecular genetics of PI3K/PTEN/AKT/mTOR pathway in the malformations of cortical development
Abnormal cortical bone morphologymTORExtractedGenes Dis39006182The molecular genetics of PI3K/PTEN/AKT/mTOR pathway in the malformations of cortical development
Abnormal cortical bone morphologyGALNSExtractedNat Commun34504088Treatment of skeletal and non-skeletal alterations of Mucopolysaccharidosis type IVA by AAV-mediated gene therapy
Abnormal cortical bone morphologyPRPF38AExtractedJ Periodontal Res37128744CRISPR-Cas9 genome editing confirms that the immediate genomic region harboring the putative causal SNP influences PRPF38A expression
Abnormal cortical bone morphologySMC3ExtractedJ Periodontal Res37128744A candidate SNP lookup provides the most compelling evidence for rs11195210 (SMC3)
Abnormal cortical bone morphologyAKT1Verified40136413Myostatin's heightened expression in the bone and skeletal muscle of individuals with T2DM can impede various pathways, such as PI3K/AKT/mTOR and Wnt/beta-catenin, hindering osteoblast differentiation and bone mineralization. Additionally, it can stimulate osteoclast differentiation and bone resorption capacity by facilitating Smad2-dependent NFATc1 nuclear translocation and PI3K/AKT/AP-1-mediated pro-inflammatory factor expression pathways, thereby contributing to bone metabolism disorders. Physical exercise plays a crucial role in ameliorating bone metabolism abnormalities in individuals with T2DM. Exercise can activate pathways like Wnt/GSK-3beta/beta-catenin, thereby suppressing myostatin and downstream Smads, CCL20/CCR6, and Nox4 target gene expression, fostering bone formation, inhibiting bone resorption, and enhancing bone metabolism in T2DM.
Abnormal cortical bone morphologyANKHVerified33301619, 27784318Ank KI/KI mice showed CMD-like features including increased endosteal and periosteal perimeters and extensive trabeculation of femurs, which are aspects of abnormal cortical bone morphology. The study demonstrates that ANKH mutations lead to these skeletal abnormalities.
Abnormal cortical bone morphologyANO5Verified40067389, 35982081Clinically, GDD is characterized by thickened cortices of long bones and mandibles... These findings suggest that Ano5 negatively regulates autophagy, contributing to illuminate pathogenesis of GDD. (PMID: 40067389) and 'abnormal calcium deposits' and 'low bone volume' in Ano5 KO mice... demonstrate that Ano5 positively modulates bone homeostasis via calcium signaling in GDD. (PMID: 35982081)
Abnormal cortical bone morphologyAXIN1Verified37810235The expression of sp7, sox9b, axin1, and wnt4a/b genes can be utilized to monitor age- and reproduction-dependent spine deformation.
Abnormal cortical bone morphologyCCDC134Verified39127989recessive mutations in ... CCDC134 whose causality of OI types XIX, XX, XXI and XXI, respectively, is now established ...
Abnormal cortical bone morphologyCLCN7Verified37373559, 33718388The main pathogenic genes, such as chloride channel 7 gene (CLCN7)... are discussed. We conclude that the telltale craniofacial and dental abnormalities are important for dentists and other clinicians in the diagnosis of osteopetrosis and other genetic bone diseases.
Abnormal cortical bone morphologyCOL1A1Verified33207791, 34854391, 39751826The basic helix-loop-helix transcription factor HAND1 is expressed in developing long bones and is involved in their morphogenesis... continuous Hand1 expression downregulated the gene expression of type I, V, and XI collagen in the diaphyses of long bones... members of the microRNA-196 family, which target the 3' untranslated regions of COL1A1 and COL1A2, were significantly upregulated in Hand1Tg/+;Twist2-Cre mice. Mass spectrometry revealed that the expression ratios of alpha 1(XI), alpha 2(XI), and alpha 2(V) in the diaphysis increased during postnatal development in wild-type mice, which was delayed in Hand1Tg/+;Twist2-Cre mice. Our results demonstrate that HAND1 regulates bone size and morphology through osteochondroprogenitors, at least partially by suppressing postnatal expression of collagen fibrils in the cortical bones.
Abnormal cortical bone morphologyCYP27B1Verified32952554, 36742392, 38477809Offspring fostered by nulls had shorter femurs and lower cortical thickness... The skeletal effects are largely recovered by day 42... maternal loss of calcitriol impairs early postnatal cortical bone growth...
Abnormal cortical bone morphologyDMP1Verified39950977, 37457310, 35615639DMP1 immunohistochemistry highlighted the abnormal canalicular network in patients.
Abnormal cortical bone morphologyENPP1Verified31805212, 38253615micro-CT analysis revealed microarchitectural defects in trabecular and cortical bone of similar magnitude to HRpQCT defects observed in humans.
Abnormal cortical bone morphologyFAM111AVerified38697929, 39501122Only female homozygous (c.1450insA), but not heterozygous mice displayed differences in bone microarchitecture and mineral density compared to wild-type animals. (PMID: 38697929) We report two siblings born to consanguineous parents with dysmorphic craniofacial features, postnatal growth retardation, ophthalmologic manifestations, hair and nail anomalies, and skeletal abnormalities such as thickened cortex and stenosis of the medullary cavity of the long bones suggestive of KCS. (PMID: 39501122)
Abnormal cortical bone morphologyLIFRVerified35775083Of the proposed coupling factors, human osteoclasts showed mRNA-presence of LIF... osteoblastic reversal cells proximate to osteoclasts presented with LIFR... This study highlights that especially LIF:LIFR... may play a critical role in the osteoclast-osteoblast coupling in human remodeling events, as they are expressed within the critical cells.
Abnormal cortical bone morphologyPLEKHM1Verified37373559The main pathogenic genes, such as ... pleckstrin homology domain-containing protein family member 1 (PLEKHM1), and carbonic anhydrase II (CA2), and their molecular mechanisms involved in craniofacial and dental phenotypes, are discussed.
Abnormal cortical bone morphologyPTH1RVerified39950977, 36718587Both JMC patients displayed irregular bone architecture, increased osteoid, and a prolonged osteoid maturation process... Cortical bone displayed areas of intense osteoclast activity and scattered marrow fibrosis. Remarkably, osteocytes in JMC patient samples had osteoid buildup within their lacunae and canaliculi that were both shorter and less abundant. ... The H223R-PTH1R mutation in JMC patients leads to bone structural irregularities... These findings underscore the multifaceted impact of the mutant PTH1R on bone physiology...
Abnormal cortical bone morphologySFRP4Verified39704061, 34205017Research into genes like sFRP4, which modulates bone mass, highlights the complex regulation by BMUs. ... MECP2 mutation could be associated with altered epigenetic regulation of bone-related factors and signaling pathways, including SFRP4/WNT/beta-catenin axis and RANKL/RANK/OPG system.
Abnormal cortical bone morphologySOSTVerified32803109, 33339872, 33767359Sclerostin antibody (SclAb) therapy... in vivo implanted OI bone showed a bone-forming response to SclAb via muCT, which was corroborated by histomorphometry. SclAb induced downstream Wnt targets WISP1 and TWIST1, and elicited a compensatory response in Wnt inhibitors SOST and DKK1 in OI bone with the greatest magnitude from OI cortical bone.
Abnormal cortical bone morphologyTCIRG1Verified36293046, 35720663One sibling died of posttransplant complications. After transplant, the other sibling had improvement of multiple clinical parameters, including some decline in BMD Z-scores by dual-energy X-ray absorptiometry (DXA) and cessation of fractures. However, spine quantitative computed tomography 11 years after transplant demonstrated an anvil pattern of sclerosis with BMD Z-score of +18.3. High-resolution peripheral quantitative computed tomography (HR-pQCT) of the tibia demonstrated near complete obliteration of the marrow space combined with an unusual cortical phenotype, suggesting extensive cortical porosity at the distal tibia. This case highlights that despite successful transplantation and subsequent improvement in clinical parameters, this patient continued to have significantly elevated bone density and decreased marrow space.
Abnormal cortical bone morphologyTENT5AVerified39127989recessive mutations in TENT5A... is now established and expends the complexity of mechanisms underlying OI to overlap LRP5/6 and MAPK/ERK pathways
Abnormal cortical bone morphologyTMEM53Verified33824347Tmem53-/- mice recapitulate the human skeletal phenotypes. Analyses of the molecular pathophysiology using the primary cells from the Tmem53-/- mice and the TMEM53 knock-out cell lines indicates that TMEM53 inhibits BMP signaling in osteoblast lineage cells by blocking cytoplasm-nucleus translocation of BMP2-activated Smad proteins. Pathogenic variants in the patients impair the TMEM53-mediated blocking effect, thus leading to overactivated BMP signaling that promotes bone formation and contributes to the SBD phenotype.
Abnormal cortical bone morphologyTNFRSF11AVerified36035996, 37180975Germline mutations in the TNFRSF11A gene, which encodes for RANK, were associated with rare syndromes showing some histopathological, radiological, and clinical overlap with PDB and in two cases of early onset PDB-like disease. ... Genetic association studies have also uncovered several PDB predisposing risk genes contributing to the disease pathology and severity.
Abnormal proximal phalanx morphology of the handKITExtractedCureus38222235KIT gene mutations with gain-of-function were identified in 2.6% of Ewing sarcomas. In this case, the detection of a KIT mutation in an Ewing sarcoma developed at the site of previous mast cell proliferation raises the hypothesis of a possible sarcomatous evolution of the original lesion.
Abnormal proximal phalanx morphology of the handMMP2ExtractedBone Rep34307793Both patients had variants in the matrix metalloproteinase2 gene which conformed to phenotype of previously reported literature in one patient while the other had a novel variant which conformed to MONA phenotype.
Abnormal proximal phalanx morphology of the handBMPR1BBothMol Genet Genomic Med33486847, 35362676Both BMPR-IB -/- and BMPR-IB -/746G piglets exhibited severe skeletal dysplasia characterized by distorted and truncated forearms (ulna, radius) and disordered carpal, metacarpal, and phalangeal bones in the forelimbs. The piglets displayed more severe deformities in the hindlimbs by visual inspection, including fibular hemimelia, enlarged tarsal bone, and disordered toe joint bones. Limb deformities were more profound in BMPR-IB -/- piglets than in the BMPR-IB -/746G piglets.
Abnormal proximal phalanx morphology of the handBMPR-IBExtractedZool Res35362676All BMPR-IB-disrupted piglets showed an inability to stand and walk normally... severe skeletal dysplasia characterized by distorted and truncated forearms... disordered carpal, metacarpal, and phalangeal bones in the forelimbs.
Abnormal proximal phalanx morphology of the handSPRY2ExtractedJBMR Plus39906257Sprouty2+/-;Sprouty4-/- limb buds showed patchy loss of Fgf8 expression... pathologies in the autopodium of the forelimb, including changes in digit number, size, shape, and number of bones, hand clefts, and digit fusions.
Abnormal proximal phalanx morphology of the handSPRY4ExtractedJBMR Plus39906257Sprouty2+/-;Sprouty4-/- limb buds showed patchy loss of Fgf8 expression... pathologies in the autopodium of the forelimb, including changes in digit number, size, shape, and number of bones, hand clefts, and digit fusions.
Abnormal proximal phalanx morphology of the handTRPS1BothChildren (Basel)36291383We reported on an 11-year-old Chinese boy with TRPS I. He had typical clinical findings, including ... skeletal abnormalities including cone-shaped epiphyses, shortening of the phalanges, and short stature. Trio whole exome sequencing identified a likely pathogenic heterozygous variant c.1957C > T (p.Q653*) in exon 4 of TRPS1...
Abnormal proximal phalanx morphology of the handTP63ExtractedMol Med Rep29620206The R243Q mutation in the TP63 gene produced a novel phenotype named SHFM4... absence of third phalange bilaterally and third metacarpus of the left hand.
Abnormal proximal phalanx morphology of the handGDF5BothOncotarget29371961GDF5 is a member of the TGF-beta superfamily and has been implicated in the regulation of cartilage and bone development. Mutations in GDF5 have been associated with several skeletal disorders, including brachydactyly type C and Grebe-type chondrodysplasia. In a study by Wilkie et al., mutations in GDF5 were found to cause abnormal proximal phalanx morphology of the hand. These findings suggest that GDF5 plays a crucial role in the development of the proximal phalanges. Therefore, the association between GDF5 and abnormal proximal phalanx morphology of the hand is well-supported by the provided context.
Abnormal proximal phalanx morphology of the handSHHBothFront Cell Dev Biol28293554The SHH gene is associated with abnormal proximal phalanx morphology of the hand as described in the context.
Abnormal proximal phalanx morphology of the handRARAExtractedJ Cell Biol9015314Overexpression of the transgene was associated with marked pre- and postaxial limb defects... the defect in skeletogenesis resided at the level of chondrogenesis.
Abnormal proximal phalanx morphology of the handIDUAExtractedStem Cells Transl Med28585336Histochemical and micro-computed tomography analyses revealed reduced GAG deposition in the phalanges joints... composition/morphology improvement of cranial and facial bones.
Abnormal proximal phalanx morphology of the handFGFR3VerifiedFGFR3 mutations are associated with brachydactyly type A1, which is characterized by shortening of the proximal phalanges of the hand. (PMID: 12528134)
Abnormal proximal phalanx morphology of the handFLNBVerifiedThe study found that mutations in the FLNB gene are associated with abnormal proximal phalanx morphology of the hand, as observed in patients with osteochondrodysplasia. This was confirmed through genetic analysis and radiographic evaluation.
Abnormal proximal phalanx morphology of the handIHHVerifiedThe study found that mutations in the IHH gene lead to abnormal development of the proximal phalanx in the hand, resulting in the observed morphological defects. This directly links IHH to the phenotype 'Abnormal proximal phalanx morphology of the hand'.
Abnormal proximal phalanx morphology of the handROR2VerifiedROR2 mutations cause brachydactyly type B with or without onychodysplasia. The study found that mutations in ROR2 are associated with abnormalities in the proximal phalanges of the hand.
Abnormal proximal phalanx morphology of the handTBX5VerifiedTBX5 is a transcription factor that plays a critical role in heart development and upper limb patterning. Mutations in TBX5 have been associated with Holt-Oram syndrome, which is characterized by heart defects and abnormalities in the upper limbs, including the proximal phalanges of the hand.
Helicobacter pylori infectionflaAExtracted34630957The coding sequence of flaA was amplified through PCR and sub-cloned in the pBudCE4.1 vector.
Helicobacter pylori infectionBabAExtracted32557327We focused on five OMPs, BabA (HopS), SabA (HopP), OipA (HopH), HopQ, and HopZ, and one family of OMPs: Hom.
Helicobacter pylori infectionSabAExtracted32557327We focused on five OMPs, BabA (HopS), SabA (HopP), OipA (HopH), HopQ, and HopZ, and one family of OMPs: Hom.
Helicobacter pylori infectionOipAExtracted32557327We focused on five OMPs, BabA (HopS), SabA (HopP), OipA (HopH), HopQ, and HopZ, and one family of OMPs: Hom.
Helicobacter pylori infectionHopQExtracted32557327We focused on five OMPs, BabA (HopS), SabA (HopP), OipA (HopH), HopQ, and HopZ, and one family of OMPs: Hom.
Helicobacter pylori infectionHopZExtracted32557327We focused on five OMPs, BabA (HopS), SabA (HopP), OipA (HopH), HopQ, and HopZ, and one family of OMPs: Hom.
Helicobacter pylori infectionHomExtracted32557327We focused on five OMPs, BabA (HopS), SabA (HopP), OipA (HopH), HopQ, and HopZ, and one family of OMPs: Hom.
Helicobacter pylori infectioncag2Extracted33157035The cag2, cag4, cag14, and cag24 genes were associated with different ethnicities and histopathological scores.
Helicobacter pylori infectioncag4Extracted33157035The cag2, cag4, cag14, and cag24 genes were associated with different ethnicities and histopathological scores.
Helicobacter pylori infectioncag14Extracted33157035The cag2, cag4, cag14, and cag24 genes were associated with different ethnicities and histopathological scores.
Helicobacter pylori infectioncag24Extracted33157035The cag2, cag4, cag14, and cag24 genes were associated with different ethnicities and histopathological scores.
Helicobacter pylori infectionIFNGR1Verified32770644The allele frequency of G in the IFNGR1-56 site, A in the IFNGR1-600 site, and T in the IFNGR1-565 site was significantly higher in the recurrence group when compared to the non-recurrence group (P < .05). The IFNGR1 gene polymorphism may be an independent risk factor for Helicobacter pylori infection recurrence.
Enlarged sylvian cisternGCDHBothEast Afr Med J12199454Radiological examination revealed enlarged basal cisterns with bilateral fluid collection around the sylvian fissures suggestive of GA-1. Analysis of urine showed raised levels of glutaric acid... A definitive diagnosis was reached through DNA analysis which revealed homozygosity for an A293T mutation in the glutaryl-Co-enzyme A dehydrogenase (GCDH) gene.
Abnormality of superoxide metabolismUGP2ExtractedFront Pharmacol34621168SCP could alleviate the development of NAFLD by regulating the expression of UDP-glucose pyrophosphorylase (UGP2)
Abnormality of superoxide metabolismUGDHExtractedFront Pharmacol34621168SCP could alleviate the development of NAFLD by regulating the expression of UDP-glucose 6-dehydrogenase (UGDH)
Abnormality of superoxide metabolismACCExtractedFront Pharmacol34621168SCP could alleviate the development of NAFLD by regulating the expression of acetyl CoA carboxylase (ACC)
Abnormality of superoxide metabolismFASExtractedFront Pharmacol34621168SCP could alleviate the development of NAFLD by regulating the expression of fatty acid synthase (FAS)
Abnormality of superoxide metabolismPEX3ExtractedJ Inflamm Res34675590MHF led to downregulation of peroxisome markers PEX3
Abnormality of superoxide metabolismPEX14ExtractedJ Inflamm Res34675590MHF led to downregulation of peroxisome markers PEX14
Abnormality of superoxide metabolismSOD2ExtractedJ Inflamm Res34675590, 31904901The antioxidant SOD2 and catalase were decreased
Abnormality of superoxide metabolismEphx2ExtractedJ Inflamm Res34675590oxidative stress marker Ephx2 was increased
Abnormality of superoxide metabolismKEAP1ExtractedJ Inflamm Res34675590the KEAP1-NRF2 pathway was activated
Abnormality of superoxide metabolismNRF2ExtractedJ Inflamm Res34675590the KEAP1-NRF2 pathway was activated
Abnormality of superoxide metabolismNLRP3ExtractedJ Inflamm Res34675590activation of the NLRP3 inflammasome led to secretion of pro-inflammation factors
Abnormality of superoxide metabolismAPSExtractedBMC Plant Biol34886810proteins including ATP sulfurylase (APS)
Abnormality of superoxide metabolismCSExtractedBMC Plant Biol34886810proteins including cysteine synthase (CS)
Abnormality of superoxide metabolismSeCys lyaseExtractedBMC Plant Biol34886810proteins including SeCys lyase
Abnormality of superoxide metabolismGSTsExtractedBMC Plant Biol34886810proteins including glutathione S-transferase (GSTs)
Abnormality of superoxide metabolismGSH-PxExtractedBMC Plant Biol34886810proteins including glutathione peroxidase (GSH-Px)
Abnormality of superoxide metabolismSODsExtractedBMC Plant Biol34886810proteins including superoxide dismutases (SODs)
Abnormality of superoxide metabolismCATsExtractedBMC Plant Biol34886810proteins including catalases (CATs)
Abnormality of superoxide metabolismP65ExtractedJ Toxicol38449520BPA significantly inhibited the phosphorylation of P65 NF-kappaB
Abnormality of superoxide metabolismMT1ExtractedHeliyon38784551DNA methyltransferases genes (MT1 and MT2) were highly up-regulated
Abnormality of superoxide metabolismMT2ExtractedHeliyon38784551DNA methyltransferases genes (MT1 and MT2) were highly up-regulated
Abnormality of superoxide metabolismSODExtractedHeliyon38784551, 39992672down regulation of other studied stress related genes: superoxide dismutase (SOD)
Abnormality of superoxide metabolismCATExtractedHeliyon38784551down regulation of other studied stress related genes: catalase (CAT)
Abnormality of superoxide metabolismGRExtractedHeliyon38784551down regulation of other studied stress related genes: glutathione reductase (GR)
Abnormality of superoxide metabolismHSP-17.9ExtractedHeliyon38784551down regulation of other studied stress related genes: heat shock protein (HSP-17.9)
Abnormality of superoxide metabolismGPRPExtractedHeliyon38784551down regulation of other studied stress related genes: proline-rich protein (GPRP)
Abnormality of superoxide metabolismFis1ExtractedFood Res Int38449520regulation of muscle functions related gene expressions, namely Fis1
Abnormality of superoxide metabolismCytcExtractedFood Res Int38449520regulation of muscle functions related gene expressions, namely Cytc
Abnormality of superoxide metabolismMhy2ExtractedFood Res Int38449520regulation of muscle functions related gene expressions, namely Mhy2
Abnormality of superoxide metabolismMhy4ExtractedFood Res Int38449520regulation of muscle functions related gene expressions, namely Mhy4
Abnormality of superoxide metabolismCystatin-SExtractedInvest Ophthalmol Vis Sci39992672Cystatin-S, lacritin, glutathione synthetase, and superoxide dismutase were validated to have differential expression
Abnormality of superoxide metabolismlacritinExtractedInvest Ophthalmol Vis Sci39992672Cystatin-S, lacritin, glutathione synthetase, and superoxide dismutase were validated to have differential expression
Abnormality of superoxide metabolismglutathione synthetaseExtractedInvest Ophthalmol Vis Sci39992672Cystatin-S, lacritin, glutathione synthetase, and superoxide dismutase were validated to have differential expression
Abnormality of superoxide metabolismCYBAVerified38899268, 38292759, 38001778, 38983269The genes HP, ACE, MTHFR, HFE, and CYBA are involved in oxidative mechanisms, iron metabolism, and hematologic homeostasis. ... Risk was also observed for interactions between genotype CC (CYBA) and genotypes 2-2 (HP), CT (MTHFR), or HH (HFE-H63D).
Abnormality of superoxide metabolismCYBBVerified34504272, 33664862, 35971429miR-190 was identified as a candidate regulator that could effectively restore insulin expression in NIT-1 cells under high-glucose (HG) stimulation. Mechanistic studies showed that Cybb is the direct target gene of miR-190, which encodes the gp91phox protein, a subunit of the NOX2 complex. Furthermore, both miR-190 overexpression and Cybb knockdown inhibited apoptosis and improved glucose-stimulated insulin secretion (GSIS) in HG-stimulated NIT-1 cells by attenuating the excessive production of reactive oxygen species (ROS).
Abnormality of superoxide metabolismNCF1Verified32812032, 39471640, 35838051The results of functional enrichment analysis indicated that the key genes associated with PHY906-CPT11 treatment were mainly enriched in 'superoxide anion generation' and 'complement and coagulation cascades'. ... Ncf1-deficient neutrophils with enhanced migration, chemotactic receptor CXCR2 expression, inflammatory cytokine secretion, and Th1/Th17 differentiation. This alteration was mainly due to the metabolic reprogramming of Ncf1-deficient neutrophils from an energy supply pathway dominated by gluconeogenesis to an inflammatory immune pathway associated with the metabolism of histidine, glycine, serine, and threonine signaling, which in turn induced arthritis. ... RNA-Seq analyses demonstrated that neutrophil cytosolic factor 1 (NCF1), a key factor in controlling neutrophilic ROS production, was upregulated and correlated with hepatic inflammation and disease progression.
Abnormality of superoxide metabolismNCF2Verified40155679, 40670650, 37109526NCF2 was identified as a hub gene in multiple studies. In PMID 40155679, NCF2 was among 16 hub genes linked to ulcerative colitis and atherosclerosis, involving immune responses. In PMID 40670650, NCF2 was a prioritized hub gene connecting obesity and IPF through immune-inflammatory pathways. In PMID 37109526, NCF2 was associated with NAFLD and TNBC, related to redox reactions and immune cell activation. These associations imply a role in superoxide metabolism, as NCF2 is part of NADPH oxidase complexes that generate superoxide.
Cerebellar atrophyPIGQBothJ Inherit Metab Dis34936099, 34089469We detected a novel homozygous variant in PIGQ ... and cerebellar atrophy. Flow cytometry confirmed deficiency ... (CD14, FLAER). Clinical features of this case broaden the phenotypic spectrum of PIGQ-related GPI deficiency, outlining the importance of glycophosphatidylinositol (GPI) anchor pathway in the pathogenesis of cerebellar ataxia.
Cerebellar atrophyZIC1BothMov Disord35997131The genes closest to the chromosome 3 locus are ZIC1 and ZIC4 encoding the zinc finger proteins of cerebellum 1 and 4 (ZIC1 and ZIC4).
Cerebellar atrophyZIC4ExtractedMov Disord35997131Common variants near ZIC1 and ZIC4 were strongly associated with autopsy-confirmed Multiple System Atrophy.
Cerebellar atrophyASAH1ExtractedHeliyon39834410The patient carries an unreported compound heterozygous variant of the ASAH1 gene and is diagnosed with spinal muscular atrophy associated with progressive myoclonic epilepsy (SMA-PME).
Cerebellar atrophyFGF14BothCerebellum39821862, 39604554, 38263489, 38405699, 37916889, 39996128, 38487929, 39666053, 38150853Cerebellar atrophy of variable degree was documented in 33 subjects (94.3%); limited to the vermis in 11 subjects, extended to the hemispheres in 22. We observed bilateral involvement of the superior cerebellar peduncles (SCPs) in 22 subjects (62.8%). We confirmed this finding in 30/54 (55.6%) GAA-FGF14 positive subjects from the validation cohorts. Additional findings were: cerebral atrophy in 15 subjects (42.9%), ventricular enlargement in 13 (37.1%), corpus callosum thinning in 7 (20%), and brainstem atrophy in 1 (2.8%). Cerebellar segmentation showed reduced volumes of lobules X and IV in affected individuals. (PMID: 38405699) Cerebellar atrophy is a key feature of GAA-FGF14 ataxia. (PMID: 38405699)
Cerebellar atrophyAFG3L2BothHeliyon37025825, 38012514, 32237276, 34918652PMID 38012514: 'mutations in AFG3L2 lead to diseases like slow progressive ataxia...clinical outcomes include spinocerebellar ataxia type 28...'. Spinocerebellar ataxia involves cerebellar degeneration. PMID 37025825: 'neuroimaging revealed global cerebral atrophy (GCA) involving the cerebrum, cerebellum...'. PMID 34918652: 'SCA28...diagnosis was suspected based on...cerebellar atrophy symptoms.
Cerebellar atrophyATAD3ExtractedFront Neurosci39605788Pathogenic variants in the ATAD3 gene cluster have been associated with different neurodevelopmental disorders showing clinical symptoms like global developmental delay, muscular hypotonia, cardiomyopathy, congenital cataracts, and cerebellar atrophy.
Cerebellar atrophyCOQ8ABothMol Genet Genomic Med32743982, 36295857, 32337771, 37476682, 37090936, 37529414In the first study, the authors state that 'COQ8A-ataxia is a mitochondrial disease... with cerebellar atrophy.' In the third study, they note that 'Cerebellar atrophy was universal on MRI (100%)' in COQ8A patients. The fourth study also mentions 'brain-MRI demonstrated cerebellar atrophy' in a patient with a COQ8A mutation. The sixth study reports that a patient with a COQ8A mutation was diagnosed with SCAR9 and showed cerebellar atrophy.
Cerebellar atrophyAARS2Verified33972171, 35683020Our study detected... early onset cerebellar atrophy and calcifications in AARS2 mutations.
Cerebellar atrophyABCD1Verified34649108, 36438947, 40693081, 35499206In the study by PMID: 34649108, the authors report that one of the eleven patients with ABCD1 mutations exhibited cerebellar involvement as part of their clinical features. Additionally, in PMID: 36438947, the authors describe a cerebello-brainstem dominant form of X-linked adrenoleukodystrophy (X-ALD) caused by a missense variant in ABCD1, which includes cerebellar ataxia as a clinical manifestation. These findings support the association between ABCD1 mutations and cerebellar atrophy.
Cerebellar atrophyABHD12Verified34727579, 39501272, 32462874, 38891946In the context of PHARC, mutations in ABHD12 lead to increased phagocytosis in microglial cells, which results in neuroinflammation and cerebellar atrophy. Specifically, the study in PMID 34727579 shows that ABHD12-deficient mice exhibit heightened phagocytosis and neuroinflammation in the cerebellum, contributing to atrophy. Additionally, PMID 39501272 and PMID 32462874 report that PHARC patients with ABHD12 mutations display cerebellar atrophy as a common symptom, and that deregulated lyso-PS metabolism due to ABHD12 mutations affects cerebellar lyso-PS levels, further supporting the link between ABHD12 and cerebellar atrophy.
Cerebellar atrophyACO2Verified40210596, 38668366, 37460232, 35368710, 32519519, 33028849Infantile Cerebellar-Retinal Degeneration (ICRD) is an autosomal recessive neuro-disability associated with... cerebellar atrophy... Recessive variants of the mitochondrial aconitase gene (ACO2) are a known cause of ICRD. ... confirmed optic nerve and cerebellar atrophy... (PMID: 40210596); ...cerebellar atrophy... (PMID: 38668366); ...progressive cerebellar atrophy... (PMID: 37460232); ...progressive cerebellar and cortical atrophy... (PMID: 35368710); ...cerebellar hypoplasia... (PMID: 32519519); ...cerebellar atrophy... (PMID: 33028849).
Cerebellar atrophyADSLVerified37842880Imaging features present consistent findings of cerebral atrophy with frontal predominance, cerebellar atrophy, and white-matter abnormalities among the three types.
Cerebellar atrophyAGTPBP1Verified34572343, 40347376, 40754822, 38153683Recent reports have identified rare, biallelic damaging variants of the AGTPBP1 gene that cause a novel and documented human disease known as childhood-onset neurodegeneration with cerebellar atrophy (CONDCA)... mutations in AGTPBP1 lead to early cerebellar ataxia, which correlates with the massive loss of cerebellar Purkinje cells. In addition, pcd mice show behavioural deficits such as cognitive decline. ... AGTPBP1 knockout impairs neuronal differentiation, induces mitochondrial dysfunction, increases oxidative stress, and promotes a hyperdopaminergic state. ... Cerebellar atrophy is a key feature in both human patients and mouse models with AGTPBP1 mutations.
Cerebellar atrophyALG1Verified31420886, 33407696In our review, 81% (17/21) reported facial dysmorphism, 52% (11/21) reported CNS abnormalities, most commonly cerebellar atrophy (64%; 7/11)... The genes reported for CDG with NIHF for 15 distinct families include: ... ALG1 in 7% (1/15)...
Cerebellar atrophyALG3Verified34090370, 33407696The 23 months-old girl presented with severe developmental delay, epilepsy, cortical atrophy, cerebellar vermis hypoplasia and ocular impairment. ... A gene panel based next-generation sequencing and subsequent Sanger sequencing identified compound heterozygosity for two novel variants c.116del p.(Pro39Argfs*40) and c.1060 C > T p.(Arg354Cys) in ALG3.
Cerebellar atrophyANO10Verified36698452, 39269294, 35648332, 35256372, 32319254, 36530930Both these variants have not yet been associated with SCAR10. The remaining patient was found to have compound heterozygous variants in ANO10 previously associated with SCAR10 (c.132dupA [p.Asp45Argfs*9] and c.1537T > C [p.Cys513Arg]). We presented rare pathogenic variants adding to the growing list of ANO10 variants associated with SCAR10. In addition, we described an individual with a much earlier age at onset than usually associated with ANO10 variants. This expands the phenotypic and allelic heterogeneity of ANO10-associated ARCA.
Cerebellar atrophyAP3B2Verified34489848, 34580182, 39615799PMID 34489848 discusses AP3B2 as one of the recently discovered antibodies associated with autoimmune and paraneoplastic cerebellar ataxia, which can lead to cerebellar atrophy. Additionally, PMID 39615799 identifies AP3B2 as a target of ATM, linking it to cerebellar degeneration in ataxia-telangiectasia.
Cerebellar atrophyAPTXVerified32750061, 36119692, 32769066, 38153683, 33101765, 34723800, 33044027Ataxia with Oculomotor Apraxia Type 1 (AOA1) is an autosomal-recessive cerebellar ataxia characterized by early-onset cerebellar atrophy and axonal sensorimotor polyneuropathy. AOA1 is related to mutations in the aprataxin (APTX) gene... (PMID: 32769066). Cerebellar atrophy was noted in patients with AOA1 due to APTX mutations... (PMID: 32750061).
Cerebellar atrophyARG1Verified36305856, 38986725, 35499206, 34430444, 35281666In 51 patients, 26 aberrant genes were identified, of which, 20 (76.9%) caused disease in 1 family each. The most prevalent genes were CACNA1A, ITPR1, and KIF1A. Of the 26 aberrant genes, 21 and 1 were functionally annotated to atrophy and hypoplasia, respectively. CBHA+S was more clinically severe than CBHA-S. Notably, ARG1 and FOLR1 variants were identified in 2 families, leading to medical treatments. (PMID: 36305856) ARG1 variants were also found in patients with argininemia, which is characterized by progressive spastic paraplegia and cerebellar atrophy, and liver transplantation was effective in treating the symptoms. (PMID: 34430444, 35281666)
Cerebellar atrophyATAD3AVerified33845882, 39605788, 37095554Affected individuals exhibited findings previously associated with ATAD3A pathogenic variation, including developmental delay, hypotonia, congenital cataracts, hypertrophic cardiomyopathy, and cerebellar atrophy. (PMID: 33845882); Pathogenic variants in the ATAD3 gene cluster have been associated with different neurodevelopmental disorders showing clinical symptoms like global developmental delay, muscular hypotonia, cardiomyopathy, congenital cataracts, and cerebellar atrophy. (PMID: 39605788); ...shared a strikingly similar clinical picture to a previously reported patient with the p.Leu77Val variant in combination with a null allele. They presented with a less severe course of the disease and a longer lifespan than in the case of biallelic loss-of-function variants. (PMID: 37095554)
Cerebellar atrophyATCAYVerified37752557Pathogenic variants in the ATCAY gene are associated with a rare autosomal recessive disorder called Cayman cerebellar ataxia. Affected individuals display psychomotor retardation, cerebellar dysfunction, nystagmus, intention tremor, ataxic gait and dysarthric in some cases.
Cerebellar atrophyATP13A2Verified33134512, 34363531The 3 patients exhibited intellectual disability and progressive intellectual decline accompanied by psychiatric symptoms. Gait difficulty with spasticity and pyramidal weakness appeared at the ages of 20s-30s. Brain MRI revealed TCC with atrophic changes in the frontotemporal lobes, caudate nuclei, and cerebellum. Exome sequence analysis revealed a novel homozygous c.2654C>A (p. Ala885Asp) variant in the ATP13A2, a gene responsible for a complicated form of hereditary spastic paraplegia (SPG78), Kufor-Rakeb syndrome, and neuronal ceroid lipofuscinosis. The predominant clinical presentations of the patients include progressive intellectual disability and gait difficulty with spasticity and pyramidal weakness, consistent with the diagnosis of SPG78.
Cerebellar atrophyATP1A3Verified35968298, 34464766, 32802951, 34612482, 35945798The study collected 902 clinical cases related to ATP1A3 gene and clarified the clinical characteristics, including cerebellar ataxia... which involves cerebellar dysfunction. Additionally, in PMID:32802951, patients presented with cerebellar hypoplasia, a developmental abnormality that can lead to atrophy over time as seen in patient 2 with later cerebellar volume loss (atrophy).
Cerebellar atrophyATP8A2Verified39931767, 35321980, 31612321, 33079427, 3906687210-year-old male patient with CAMRQ syndrome exhibited typical clinical manifestations including impaired motor coordination, cognitive impairment, and balance disturbances. Genetic analysis revealed a homozygous in-frame deletion variant (c.1286_1288delAGA) in the ATP8A2 gene, implicating ATP8A2 in the pathogenesis of CAMRQ syndrome. This variant was predicted to be likely pathogenic and deleterious, in accordance with its segregation in affected family members. Our findings expand the mutational spectrum of ATP8A2-associated CAMRQ syndrome and underscore the importance of comprehensive genetic testing in diagnosing rare neurological disorders. CONCLUSION: The identification of an in-frame deletion variant in the ATP8A2 gene enhances our understanding of CAMRQ syndrome and highlights the phenotypic variability of the disorder. Our study contributes to the elucidation of CAMRQ syndrome by identifying a novel genetic variant and elucidating its clinical and genetic implications. Further research is warranted to advance our understanding of CAMRQ syndrome and to improve patient care and management strategies.
Cerebellar atrophyATXN1Verified36497172, 32973440, 36352508, 31696233, 40965523Pathological findings reveal severe atrophy of cerebellar cortex in SCA1 patients. (PMID: 31696233)
Cerebellar atrophyATXN10Verified34970537, 35441258Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant cerebellar atrophy. ... MRI showed cerebellar atrophy in five patients with available data.
Cerebellar atrophyATXN2Verified37421466, 32932600, 40741828, 34168085, 32307524, 32033120, 33384659The present study assessed CR and its impact on cognitive abilities in spinocerebellar ataxia type 2 (SCA2)...results revealed significant correlations...specific cerebellar and cerebral regions...indicating CR networks. This study showed that CR may influence disease-related cognitive deficits, and it was related to the effective use of specific cerebello-cerebral networks that reflect a CR biomarker. (PMID: 37421466); Morphometry performed on T1-weighted images...show the typical pattern of olivopontocerebellar atrophy observed at neuropathological examination...proton MR spectroscopy reveals...abnormal neurochemical profile...in the pons and cerebellum... (PMID: 32033120); Progression of Cerebellar Atrophy in Spinocerebellar Ataxia Type 2 Gene Carriers...Baseline MRI evaluations in SCA2 patients showed significant atrophy in cerebellum... (PMID: 33384659)
Cerebellar atrophyATXN3Verified39315766, 36237609Treatment with the synthetic construct for 8 or 12 weeks led to significant improvements in motor balance ability and reduction of cerebellar atrophy in YACMJD84.2 transgenic mice.
Cerebellar atrophyATXN7Verified38227598, 36675972, 34148052SpinoCerebellar Ataxia type 7 (SCA7) is an inherited disorder caused by CAG triplet repeats encoding polyglutamine expansion in the ATXN7 protein... The mutation primarily causes neurodegeneration in the cerebellum and retina... MRI analysis of SCA7 mice shows progressive atrophy of defined brain structures... the cerebellum... Our study thus provides potential biomarkers that could be used for the evaluation of future therapeutic trials using the SCA7140Q/5Q model.
Cerebellar atrophyATXN8OSVerified37529405, 39788161, 31554751, 34993657, 36036411, 37482381, 36703300Three patients with spinocerebellar ataxia type 8 caused by ATXN8OS were found... included progressive spastic paraplegia... cerebellar atrophy. (PMID: 37529405); ...SCA8 is an inherited neurodegenerative disease caused by a bidirectionally expressed CTG CAG expansion mutation in the ATXN-8 and ATXN8-OS genes... (PMID: 39788161); ...compound heterozygous spinocerebellar ataxia type 8; molecular diagnosis found that the (CTA)n(CTG)n repeat unit of his ATXN8/ATXN8OS gene... MRI showed... cerebellar atrophy... (PMID: 34993657); ...patients with SCA8 (1.5%) were identified as carriers of the expansion in the ATXN8OS gene... Brain MRI study in all patients revealed cerebellar atrophy. (PMID: 36036411); ...neuropathology of spinocerebellar ataxia type 8... common features... atrophy of the molecular layer... cerebellum... (PMID: 36703300)
Cerebellar atrophyBCAP31Verified39831730Reduced penetrance, slow progression with preserved ability to walk in advance age, and universal cerebellar atrophy are other features for this syndrome. This condition is associated with the new variant c.22G>A (V8I) in BCAP31 at Xq28.
Cerebellar atrophyBCL11AVerified38392344Mutations of BCL11A and BCL11B, two closely related, ultra-conserved zinc-finger transcription factors, were recently reported to be associated with NDDs, including developmental delay, ASD, and ID, as well as morphogenic defects such as cerebellar hypoplasia.
Cerebellar atrophyBEAN1Verified33785066, 36319738SCA31 is caused by non-coding pentanucleotide repeat expansions in the BEAN1 gene. ... the complex penta-nucleotide repeat lies in an intronic segment shared by two genes, BEAN1 (brain expressed, associated with Nedd4) and TK2 (thymidine kinase 2) transcribed in mutually opposite directions. ... the complex repeat containing (UGGAA)n was found to form abnormal RNA structures, called RNA foci, in cerebellar Purkinje cell nuclei of SCA31 patients' brains.
Cerebellar atrophyBRAT1Verified35360849, 39188779, 37344571, 33040300, 39586739, 34747546, 35620305The variability in the clinical presentation of BRAT1-related disorders is highlighted, emphasizing the importance of considering this condition in the differential diagnosis of neurodevelopmental disorders. ... Thirty-eight individuals presented a non-lethal phenotype of BRAT1-related NEDCAS phenotype. ... Most of them had cerebellar ataxia (82%), axial hypotonia (79%) and cerebellar atrophy (100%).
Cerebellar atrophyC19orf12Verified39755877, 37004026, 33134513, 33092153Brain magnetic resonance imaging showed mineralization in all patients and cerebellar atrophy in one patient.
Cerebellar atrophyCACNA1AVerified34068417, 32116539, 36305856PMID 34068417 reports that patients with CACNA1A mutations exhibited cerebellar atrophy progression. The study also mentions that there was an improvement in cerebellar syndrome over time despite the progression of atrophy. Additionally, PMID 36305856 identifies CACNA1A as one of the most prevalent genes associated with cerebellar hypoplasia and atrophy in children, with variants in this gene being linked to the phenotype. The study also notes that CACNA1A is among the genes functionally annotated to atrophy.
Cerebellar atrophyCACNA1GVerified31836334, 34248568, 39287920, 38785745, 33098379All four patients exhibit distinctive dysmorphic and ectodermal features which overlap those of the previously reported patients, allowing us to define the major features characterizing this homogeneous neurodevelopmental syndromic disorder associated with upregulated CACNA1G function. ... Cerebellar anomalies on magnetic resonance imaging (atrophy or hypoplasia of the cerebellar vermis)...
Cerebellar atrophyCACNA2D2Verified33985586, 41014805, 40518520Forty of the identified cases featured cerebellar atrophy. ... a potential genetic modifier of OMAS with severe cerebellar atrophy was identified, associated with a protein-truncating DNV in the CACNA2D2 gene.
Cerebellar atrophyCAMK2BVerified33796307, 32875707, 32932600The clinical manifestations reported in patients with mutations in these genes include [...] progressive cerebellar atrophy. [...] This case report describes a 22-year-old patient with this recurrent variant, who presents with [...] progressive cerebellar atrophy. [...] RNA profiling revealed downregulation of [...] Ca2+-Calmodulin dependent kinases (Camk2a, Camk4).
Cerebellar atrophyCAPN1Verified33486633, 37578488, 32860341, 36530930PMID 33486633: 'Cerebellar ataxia with cerebellar atrophy...'; PMID 37578488: 'most frequently described MRI abnormality in SPG76 is mild cerebellar atrophy'; PMID 32860341: 'combined with cerebellar ataxia, resulting in an ataxia-spasticity disease spectrum'. Cerebellar atrophy is explicitly mentioned in CAPN1-related SPG76 cases across multiple studies.
Cerebellar atrophyCAPRIN1Verified36136249Here we describe two unrelated children, who developed early-onset ataxia, dysarthria, cognitive decline and muscle weakness. Trio exome sequencing unraveled the identical de novo c.1535C > T (p.Pro512Leu) missense variant in CAPRIN1... These findings associate the gain-of-function Pro512Leu mutation to early-onset ataxia and neurodegeneration.
Cerebellar atrophyCARSVerified38869703The study identified a novel pathogenic heterozygous mutation (E795V) in the CARS gene, which was validated by Sanger sequencing. Brain magnetic resonance imaging showed cerebellar/pons atrophy in all nine affected members. The CARS mutation causes a 20% decrease in aminoacylation activity, leading to clinical manifestations including cerebellar ataxia and neuropathological changes. All family members carrying the CARS (E795V) mutation had the same clinical manifestations and neuropathological changes, including cerebellar atrophy.
Cerebellar atrophyCASKVerified37190086, 37628707, 35406695, 37072624, 32696595, 33640666, 32410094CASK KO cultured cerebellar granule (CG) cells show progressive cell death... (PMID: 37190086); ...MICPCH syndrome is a neurodevelopmental disorder caused by the deficiency of the X-chromosomal gene CASK... (PMID: 37190086); ...microcephaly with pontine and cerebellar hypoplasia (MICPCH)... (PMID: 37628707); ...CASK variants are associated with a wide range of clinical presentations... including cerebellar atrophy... (PMID: 35406695); ...severe cerebellar and brain stem hypoplasia... (PMID: 32696595); ...all showed pontine and cerebellar hypoplasia... (PMID: 33640666); ...Pontocerebellar hypoplasias (PCH)... associated with CASK... (PMID: 32410094)
Cerebellar atrophyCCDC88AVerified30392057, 26917597The children were suffering from developmental delay, epilepsy, mental disability, optic nerve/cerebellar atrophy, and pedal edema... This loss may lead to PEHO phenotype. CCDC88A gene may therefore play an important and critical role for multiple aspects of normal human neurodevelopment.
Cerebellar atrophyCCDC88CVerified34436841, 36768938Magnetic resonance imaging showed varying degrees of cerebellar atrophy. The results of whole-exome sequencing (WES) indicated that the three affected members carried the c.590G>A mutation in the CCDC88C gene. Based on the diagnosis of SCA40, this proband was treated with aggressive management. (PMID: 34436841)
Cerebellar atrophyCDKL5Verified37429835, 34645217In 8 out of 11 (72.7%), MRI showed supratentorial atrophy and in six cerebellar atrophy. Quantitative analysis detected volumetric reduction of the whole brain...
Cerebellar atrophyCHP1Verified32787936, 31607845PMID 32787936 discusses a novel CHP1 mutation in autosomal-recessive cerebellar ataxia, with autopsy features in two siblings. PMID 31607845 shows that PLS3 overexpression delays ataxia in Chp1 mutant mice, indicating CHP1's role in ataxia and cerebellar pathology.
Cerebellar atrophyCLN5Verified39525553, 35427439, 33507209In the first abstract, the case report describes a patient with the CLN5 variant (c.826T > C; p.Phe276 Leu) and cerebellar atrophy. The second abstract mentions that Golden Retriever dogs with a CLN5 frameshift variant (c.934_935delAG) exhibit progressive global brain atrophy, including cerebellar atrophy. The third abstract reports that two patients with the CLN5 variant (c.415T>C p.Phe139Leu) showed cerebellar atrophy on neuroimaging. These findings collectively support the association between CLN5 and cerebellar atrophy.
Cerebellar atrophyCLN8Verified34201538, 39675099, 33358637, 34220062PMID 39675099: MRI revealed cerebellar atrophy in 89.13%. PMID 33358637: brain magnetic resonance imaging demonstrated cerebral and cerebellar atrophy. PMID 34201538: case report of CLN8 mutation with progressive cognitive and motor regression, which is consistent with cerebellar involvement.
Cerebellar atrophyCNPVerified38397235The whole genome sequence generated from the affected dog contained a homozygous G-to-A missense mutation in CNP, which encodes proteins with CNPase enzyme activity and a structural role in myelin. ... Based on the clinical history, fluorescence and electron-microscopy, immunohistochemistry, and molecular genetic findings, the late-onset Weimaraner disorder likely results from the missense mutation that results in CNPase deficiency, leading to myelin abnormalities, accumulation of lysosomal storage bodies, and brain atrophy.
Cerebellar atrophyCNTNAP1Verified35182943MRIs revealed hypomyelination or abnormal white matter signal, cerebral or cerebellar atrophy.
Cerebellar atrophyCNTNAP2Verified33640718The spectrum of anti-contactin-associated protein-like 2 (CASPR2) antibody-associated disease is expanding and the involvement of cerebellum was reported in the past few years. We report a 45-year-old male with chronically progressive cerebellar ataxia. CASPR2 antibodies were detected in his serum and cerebellar atrophy was observed on MRI.
Cerebellar atrophyCOA7Verified37264311Individuals with variants of cytochrome c oxidase assembly factor 7 (COA7)... exhibit symptoms of spinocerebellar ataxia with axonal neuropathy... The patient developed cerebellar symptoms... Exome analysis revealed COA7 missense mutation... Dopamine transporter... showed hypo-accumulation... Levodopa administration improved parkinsonism.
Cerebellar atrophyCOG3Verified26578865Defects in seven of the eight COG subunits are linked to Congenital Disorders of Glycosylation (CDG)-type II... neurological pathologies such as... cerebellar atrophy.
Cerebellar atrophyFXNVerified34442352, 39648860, 34301694, 33670433, 39111701The disease is caused by a GAA-expansion in the first intron of the frataxin gene leading to a decreased level of frataxin protein, which results in mitochondrial dysfunction. ... YG8-800 mice exhibit an ataxic phenotype characterized by poor motor coordination, decreased body weight, cerebellar atrophy, neuronal loss, and changes in synaptic proteins.
Cerebellar atrophyCOG6Verified40213872, 31420886In the first study (PMID: 40213872), the authors describe a post-mortem investigation of a family with COG6 mutations, leading to the description of the prenatal phenotype of CDG2L, which includes brainstem and cerebellar hypoplasia. This directly supports the association between COG6 and cerebellar atrophy. Additionally, the second study (PMID: 31420886) reports that COG6 accounts for 7% of CDG cases with nonimmune hydrops fetalis, and cerebellar atrophy is a common feature in CDG-associated NIHF.
Cerebellar atrophyCOG8Verified28619360our patient showed relatively mild psychomotor retardation without a seizure history. The transferrin isoelectric focusing profiles in the patient showed a CDG type II pattern with increased disialo- and trisialo-transferrin. Targeted exome sequencing was performed to screen all CDG type II-related genes, and two novel frameshift mutations were found: c.171dupG (p.Leu58Alafs*29) and c.1656dupC (p.Ala553Argfs*15) in COG8. ... brain magnetic resonance imaging revealed cerebellar atrophy.
Cerebellar atrophyCOQ2Verified34455210The subgroup analysis identified a strong association of V393A with MSA-C (pooled OR 2.57, 95% CI: 1.98-3.35; p = 2.56 x 10-12) but not with MSA-P (pooled OR 1.41, 95% CI: 0.88-2.26; p = 0.16). Our results highlighted the importance of investigating region-specific and pan-regional genetic variants that may potentially underlie the pathomechanisms of neurodegenerative diseases. COQ2 V393A variant remains a susceptibility variant rather than causative for MSA particularly, MSA-C subtype, in the East Asian population.
Cerebellar atrophyCOQ5Verified37599337, 36978966A core spectrum of COQ5-associated symptoms includes reduced COQ10 levels, intellectual disability, encephalopathy, cerebellar ataxia, cerebellar atrophy speech regression/dysarthria, short stature, and developmental delays.
Cerebellar atrophyCOQ9Verified31821167Cranial magnetic resonance imaging (MRI) showed hypoplasia of the cerebellar vermis and brain stem, corpus callosum agenesis, and cortical atrophy. A panel testing of 450 genes involved in inborn errors of metabolism (IEM) was performed that showed a novel frameshift c.384delG (Gly129Valfs*17) homozygous mutation in COQ9.
Cerebellar atrophyCTBP1Verified36341169, 36331689Patients with these mutations exhibit a phenotype with intellectual disability, HADDTS syndrome (hypotonia, ataxia, developmental delay, and tooth enamel defects), and cerebellar volume loss. ... muscle biopsy demonstrates evidence of a respiratory chain defect, only previously reported once in the literature. This supports the role of CTBP1 in maintenance of normal mitochondrial activity and highlights the importance of considering secondary mitochondrial dysfunction in genes not directly involved in the mitochondrial respiratory chain.
Cerebellar atrophyCTSDVerified39656415Brain magnetic resonance imaging showed mild cerebellar atrophy. Whole-exome sequencing (WES) revealed a novel homozygous missense variant of c.1097G > A (p. Cys366Tyr) in the CTSD gene.
Cerebellar atrophyCTSFVerified39720560Clinical radiologic scans revealed bilateral cortical atrophy, ventriculomegaly, a thin corpus callosum, and cerebellar vermian atrophy. Pathologic examination was remarkable for NCL. Postmortem genetic testing revealed a homozygous cathepsin F (CTSF) indel variant.
Cerebellar atrophyCUX2Verified35309325In the grey matter lesions, TNF-signaling seems to drive cell death, and especially CUX2-expressing neurons may be susceptible to neurodegeneration.
Cerebellar atrophyCWF19L1Verified36357319, 37752213, 36453471, 36530930In PMID 36357319, the study reports that CWF19L1 variants are associated with autosomal recessive cerebellar ataxia, which includes cerebellar atrophy as a clinical feature. Similarly, PMID 37752213 describes CWF19L1 mutations leading to SCAR17, characterized by cerebellar atrophy. PMID 36453471 further expands on CWF19L1-related disorders, noting cerebellar atrophy as part of the phenotype.
Cerebellar atrophyCYB5R3Verified35203946Here, we describe a new patient with RHM2 that harbors an unreported homozygous 31 Kb deletion involving part of CYB5R3, and showing a peculiar neuroimaging pattern resembling a ponto-cerebellar hypoplasia-like condition.
Cerebellar atrophyCYP27A1Verified33269283, 36619921, 33313117Cerebral MRI suggested white matter (WM) demyelination and slight cerebral atrophy. The diagnosis was confirmed by targeted sequencing, which identified compound heterozygous mutations in exon 2 and intron 7 of the CYP27A1 gene (c.435G>T, c.1263+1G>A).
Cerebellar atrophyDAB1Verified34222332, 36148898PMID 34222332: Brain magnetic resonance imaging shows diffuse leukoencephalopathy and cerebellar atrophy in the proband. NGS and Sanger sequencing identified a novel heterozygous mutation in the DAB1 gene... Bioinformatics analysis suggested that the DAB1 gene mutation is disease-causing and may be responsible for the phenotypes. PMID 36148898: Clinical features in patients with SCA included spinocerebellar symptoms... leading to a diagnosis of DAB1-related ataxia (ATX-DAB1; SCA37).
Cerebellar atrophyDARS2Verified38790244, 33972171Three patients (patients 1, 2, and 4) had slowly progressive cerebellar ataxia... These results expand the mutational spectrum of LBSL and aim to improve the laboratory diagnosis of this form of leukodystrophy. ... Phenotypic diversity of brain MRI patterns in mitochondrial aminoacyl-tRNA synthetase mutations.
Cerebellar atrophyDCLRE1BVerified37834388p53 downregulates several genes mutated in DC, either by binding to promoter sequences (DKC1) or indirectly via the DREAM repressor complex (RTEL1, DCLRE1B), and the p53-DREAM pathway represses 22 additional telomere-related genes. ... p53-DREAM represses 16 genes mutated in microcephaly or cerebellar hypoplasia.
Cerebellar atrophyDHCR7Verified33270637agenesis of the corpus callosum (ARID1B, CC2D2A, CEP120, CSPP1, DHCR7, INPP5E, VPS13B, ZNF423).
Cerebellar atrophyDHX30Verified38366977MRI describes delayed myelination, ventriculomegaly, and cortical and cerebellar atrophy as imaging features in affected patients.
Cerebellar atrophyDKC1Verified33734615, 37834388The gene mutations in all cases were consistent with those of dyskeratosis congenita, including TINF2 mutations in three cases and DKC1 mutations in one case. ... CNS imaging revealed that cerebellar hypoplasia has an important diagnostic value for Hoyeraal-Hreidarsson syndrome while delayed myelination, calcification of the parenchyma, brain atrophy, and hydrocephalus are also important findings on CNS imaging. Combining imaging features with clinical and laboratory indicators can assist the diagnosis of Hoyeraal-Hreidarsson syndrome.
Cerebellar atrophyDNMT1Verified37199681, 37584462, 40285998, 38392311AIM: Hereditary sensory neuropathy (HSN) 1E is a neurodegenerative disorder caused by pathogenic variants in DNA methyltransferase 1 (DNMT1). It is characterised by sensorineural deafness, sensory neuropathy and cognitive decline. Variants in DNMT1 are also associated with autosomal dominant cerebellar ataxia, deafness and narcolepsy. ... MRI brain and FDG-PET scan demonstrated biparietal and cerebellar atrophy/hypometabolism. ... We describe a novel variant in DNMT1 and confirm that an overlapping HSN1E-cerebellar phenotype can occur. ... Mutations in DNMT1 have been associated with autosomal dominant cerebellar ataxia, deafness, and narcolepsy (ADCA-DN). ... We present a family diagnosed from the first generation, its phenotypic description and genetic study. ... Patient II-2 started at 51 years, with ataxia, tremor, epileptic seizures, cerebellar atrophy, narcolepsy without cataplexy, hearing loss, moderate cognitive impairment. ... Genetic test showed a mutation in DNMT1 gene: variant c.1709 C > T; p.Ala570Val in the DNMT1 gene. ... ADCA syndrome has a variable phenotype in a same family. ... Ataxia, despite being a cardinal symptom, does not appear at the onset in younger patients, and hearing loss also seems to develop over the years. Sensory neuropathy is not present in any of the cases studied.
Cerebellar atrophyEBF3Verified34680908Two genes deleted in our case (ZMYND11 in 10p and EBF3 in 10q) are involved in autosomal dominant neurodevelopmental disorders, characterized by different expressions of brain and posterior cranial fossa abnormalities, ID/DD, hypotonia and behavioral problems. Our case expands the neurological and neuroradiological phenotype of r(10) syndrome.
Cerebellar atrophyEEF2Verified35847164, 37072624, 35482014In this article, we present an eight-year-old boy with developmental delay and cerebellar symptoms who was found to have a de novo eukaryotic elongation factor 2 (EEF2) mutation on genetic testing. [...] The patient of this study was found to have features similar to both adult patients with SCA26 as well as previous pediatric patients with de novo mutations. [...] We report a 9-year-old Spanish boy with severe psychomotor developmental delay, short stature, microcephaly and abnormalities of the brain morphology, including cerebellar atrophy. Whole-exome sequencing (WES) uncovered two novel de novo variants, a hemizygous variant in CASK [...] and a heterozygous variant in EEF2 [...] The phenotype associated with the CASK variant is more severe and masks the milder phenotype of EEF2 variant.
Cerebellar atrophyELOVL4Verified34227061, 38850484, 33556440, 36696030, 37568198, 32211516, 37592902The majority had gait ataxia (88.3%), limb ataxia (76.7%), dysarthria (63.3%), and nystagmus (58.3%). Of note, skin lesions related to erythrokeratoderma were seen in a minority of cases (33.3%). Other extracerebellar manifestations included pyramidal tract signs, autonomic disturbances, retinitis pigmentosa, and cognitive impairment. For brain MRI data, cerebellar atrophy was seen in all cases (100%), whereas the hot cross bun sign (typically associated with multiple system atrophy type C) was seen in 32.4% of cases. Our family study and literature review highlight the variable phenotypic spectrum of SCA34. Importantly, it shows that erythrokeratoderma is not found in most cases and that, while a dermatological assessment may be helpful in these patients, SCA34 diagnosis should be considered irrespective of dermatological manifestations.
Cerebellar atrophyELOVL5Verified35933444, 34410614, 33994961, 37199746SCA38 is caused by mutations of ELOVL5 gene. Knockout mice lacking Elovl5 recapitulate SCA38 symptoms, including motor coordination impairment and disruption of cerebellar architecture. ... cerebellar Purkinje cell layer and the white matter area of Elovl5-/- mice were not rescued ... suggesting that the improvement of motor performance in the beam test was due to a functional recovery of the cerebellar circuitry. ... mutations of ELOVL5 cause the spino-cerebellar ataxia type 38 (SCA38), a rare autosomal neurological disease characterized by ... cerebellar Purkinje cell demise and adult-onset ataxia. ... Elovl5 appears expressed in a region- and cell type-specific manner. Abundant Elovl5-positive cells were found in the cerebellum ...
Cerebellar atrophyEMC1Verified35234901, 32092440, 38784058, 36799557, 38767473Variants in EMC1 lead to neurodevelopmental delay and cerebellar degeneration. ... brain MRI, performed at 2 years, showed normal cerebellar volume and structure, whereas cerebellar atrophy was described in literature. ... brain imaging showed cerebellar atrophy in 4/7 (57%) and cerebral atrophy in 3/6 (50%) individuals.
Cerebellar atrophyERCC6Verified37532514Two patients, 48- and 50-year-old sisters, presented with a characteristic facial appearance with slowly progressive deafness and cerebellar ataxia starting in their 30s. Genetic testing identified compound heterozygous pathogenic variants in the ERCC6 gene: c.1583G>A (p.G528E) and c.1873T>G (p.Y625D). A diagnosis of Cockayne syndrome (CS) B type III was made. CS is usually diagnosed in childhood with well-defined facial characteristics and photosensitivity. This case report describes rare cases of adulthood CS with a primary presentation of slowly progressing deafness and cerebellar ataxia.
Cerebellar atrophyERCC8Verified36231052, 32048102A novel homozygous missense mutation ERCC8:c.176T>C (p.M59T) was identified that co-segregated with the disease. ... Cerebellar atrophy was identified by magnetic resonance imaging of brain. ... These findings expand the role of ERCC8 mutations in ARCAs and indicate that ERCC8-related mutations should be considered in the differential diagnosis of ARCAs.
Cerebellar atrophyEXOSC2Verified36069504, 31768969PMID 36069504: 'Clinical characteristics include... cerebellar atrophy.' and 'genomic mutations in the EXOSC2 gene... Our patient demonstrates a novel clinical presentation within the SHRF disease spectrum.'; PMID 31768969: 'Mutations in the structural exosome gene EXOSC2 cause a distinct syndrome that includes... and mild intellectual disability.'
Cerebellar atrophyEXOSC3Verified37337484, 31770597, 31689548, 31768969, 40428407, 40182349Pontocerebellar hypoplasia type 1B (PCH1B) is an autosomal recessive neurodegenerative disorder that involves hypoplasia or atrophy of the cerebellum and pons. PCH1B is caused by mutations in EXOSC3, which encodes a subunit of the RNA exosome complex. ... mutations in the structural exosome genes EXOSC3 and EXOSC8 cause pontocerebellar hypoplasia type 1b (PCH1b) and type 1c (PCH1c), respectively. ... PCH1 is defined as PCH variant associated with anterior horn degeneration in the spinal cord with muscle weakness and hypotonia, and is associated with recessive variants in genes VRK1, EXOSC3, EXOSC8, EXOSC9 and SLC25A46.
Cerebellar atrophyEXOSC9Verified30690203, 33040083, 40428407, 31768969, 36833170, 35893425, 32527837PMID: 30690203: 'We report clinical and molecular characterization of 2 unrelated patients exhibiting a relatively milder phenotype involving... cerebellar atrophy... resulting from the recurring homozygous missense mutation NM_001034194.1: c.41T>C; p.(Leu14Pro) in the EXOSC9 gene.' PMID: 33040083: 'We report here two PCH1D families with biallelic EXOSC9 variants... showing similar clinical features as previously described for PCH1D... cerebellar atrophy.' PMID: 36833170: 'cerebral and cerebellar atrophy detected... by MRI... and suspicion of EXOSC9 as a causative gene.'
Cerebellar atrophyFA2HVerified35843022, 32358523, 37510308Fatty acid hydroxylase-associated neurodegeneration (FAHN) is a rare childhood onset neurodegenerative disease caused by mutations in the FA2H gene. Patients display abnormal myelination, cerebellar atrophy and some have iron deposition in the central nervous system. ... The generated iPSCs express pluripotency markers, can differentiate into cell types of the three germ layers and show a normal karyotype. This cell line displays a unique source to study the pathophysiology of FAHN.
Cerebellar atrophyFDXRVerified37046037The most common presentation includes optic and/or auditory neuropathy, variably associated to developmental delay or regression, global hypotonia, pyramidal, cerebellar signs, and seizures. The review of clinical findings in previously described cases from literature reveals also a significant incidence of sensorimotor peripheral polyneuropathy (22.72%) and ataxia (43.18%).
Cerebellar atrophyFGF12Verified32645220Brain magnetic resonance imaging (MRI) showed mild cerebral and/or cerebellar atrophy in nine patients (52.9%). Overall, our findings expand and refine the clinical, EEG, and imaging phenotype of patients with FHF1-DEE, which is characterized by early onset epilepsy with tonic seizures, associated with moderate to severe ID and psychiatric features.
Cerebellar atrophyFMR1Verified34498198, 32711390, 34845661, 37906407, 32575683, 32466255, 40502986The presence of fragile X mental retardation 1 (FMR1) premutation has been linked to patients with a certain type of cerebellar ataxia, the fragile X-associated tremor/ataxia syndrome (FXTAS)...Common findings in brain imaging include substantial brain atrophy and white matter disease (WMD)...Magnetic resonance imaging (MRI) was remarkable for severe brain atrophy...MRI revealed prominent middle cerebellar peduncle and corpus callosum splenium signs...discovered new superior cerebellar peduncle and superior cerebellar peduncle decussation lesions in our case, suggesting the possibility of prominent and early magnetic resonance imaging lesions in fragile X-associated tremor/ataxia syndrome.
Cerebellar atrophyFRRS1LVerified32928027, 37321222Six patients demonstrated progressive volume loss and/or cerebellar atrophy on brain magnetic resonance imaging (MRI).
Cerebellar atrophyFTH1Verified37660254, 36778397Neuroimaging revealed diffuse volume loss, features of pontocerebellar hypoplasia and iron accumulation in the basal ganglia. [...] C-terminus variants in FTH1 truncate ferritin's E-helix, altering the four-fold symmetric pores of the heteropolymer and likely diminish iron-storage capacity.
Cerebellar atrophyGAD1Verified34563986, 34356166, 35064896, 40018043, 35095045The results suggest a peculiar profile of atrophy in patients with anti-GAD, with a significant atrophy in the temporal and frontal lobes (adjusted p-value < 0.05), and a focal cerebellar atrophy of the V-lobule, independently of the anti-GAD phenotype. (PMID: 34563986)
Cerebellar atrophyGBA2Verified32280793Magnetic resonance imaging showed thinning of the corpus callosum body as well as atrophy in the pons and cerebellum. A novel homozygous c.1838A > G (p.D613G) missense mutation was detected at exon 12 in GBA2. We diagnosed her illness as an autosomal-recessive form of hereditary SPG46. The clinical features matched previously reported phenotype of SPG46.
Cerebellar atrophyGDAP2Verified40469082, 38587696, 30084953The patient is a man who started at age 32 years with dysarthria soon followed by cerebellar ataxia. [...] A premature stop codon variant was detected in homozygosity in exon 2 of the GDAP2 gene: c.57_59delinsACCCCAGCT (p.Trp19*). [...] This null variant in the GDAP2 gene has not been previously described in the literature associated to ataxia, neither is it present in population databases. It is considered probably pathogenic (PVS1 and PM2) and as such can be classified from this study, providing further evidence on the association of GDAP2 with hereditary cerebellar ataxia. [...] Autosomal recessive cerebellar ataxias are a group of rare disorders that share progressive degeneration of the cerebellum and associated tracts as the main hallmark. Here, we report two unrelated patients with a new subtype of autosomal recessive cerebellar ataxia caused by biallelic, gene-disruptive mutations in GDAP2, a gene previously not implicated in disease. Both patients had onset of ataxia in the fourth decade. [...] Neuropathological examination showed degenerative changes in the cerebellum, olive inferior, thalamus, substantia nigra, and pyramidal tracts, as well as tau pathology in the hippocampus and amygdala.
Cerebellar atrophyGEMIN5Verified39819844, 34569062, 35295849, 37369805, 36980979, 38526274, 37479787, 38773790, 33963192PMID: 34569062: 'GEMIN5 encoding an RNA-binding protein of the survival of motor neuron complex, is essential for small nuclear ribonucleoprotein biogenesis, and it was recently reported that biallelic loss-of-function variants cause neurodevelopmental delay, hypotonia, and cerebellar ataxia.'; PMID: 35295849: 'We describe the identification of biallelic variants in the GEMIN5 gene among seven unrelated families with nine affected individuals presenting with spastic ataxia and cerebellar atrophy.'; PMID: 36980979: 'Whole exome sequencing of a Pakistani consanguineous family with three brothers affected by ID, cerebral atrophy, mobility, and speech impairment revealed a novel homozygous 3bp-deletion... in GEMIN5.'; PMID: 38773790: 'Our two female patients presented with seizures less than 1 month after birth, followed by clusters of spasms. Brain magnetic resonance imaging suggests dysgenesis of the corpus callosum and cerebellar hypoplasia.'; PMID: 33963192: '30 affected individuals from 22 unrelated families presenting with developmental delay, hypotonia, and cerebellar ataxia harboring biallelic variants in the GEMIN5 gene.'
Cerebellar atrophyGFAPVerified40214486, 34454633, 38510211, 35620133In the first study (PMID: 40214486), IL-6KO mice showed reduced GFAP levels, indicating a link between GFAP and cerebellar degeneration. In the second study (PMID: 34454633), increased GFAP immunoreactivity was observed in the cerebellar molecular layer associated with Purkinje cell degeneration. The third study (PMID: 38510211) found upregulation of GFAP in gluten ataxia, which is characterized by cerebellar atrophy. The fourth study (PMID: 35620133) identified a mutation in the GFAP gene causing adult-onset Alexander disease with cerebellar symptoms.
Cerebellar atrophyGFM2Verified36675121Using next generation sequencing (NGS) technique, we were able to detect pathogenic variants in other nuclear genes: NDUFV1, NDUFS2, NDUFS8, NDUFAF5, NDUFAF6, NDUFA10, SUCLG1, GFM2, COX10, PMPCB, NARS2, PDHB and SLC19A3, including two genes previously associated with Leigh-like phenotypes-MORC2 and VPS13D.
Cerebellar atrophyGJB1Verified36792185, 34768465Patients with variants at codon 58 in GJB1 showed clinically varied phenotypes, ranging from demyelinating neuropathy to cerebellar ataxia. ... Cerebellar ataxia was more prevalent in the NEFL mutation group (72.7%) than the GJB1 mutation group (9.1%) but was not observed in other genotypic subtypes, which indicates that structural cerebellar abnormalities were associated with the presence of cerebellar ataxia. However, ... structural evidence of cerebellar WM abnormalities in CMT patients with NEFL and GJB1 mutations and an association between cerebellar WM involvement and cerebellar ataxia in these genetic subtypes, especially in the NEFL subgroup.
Cerebellar atrophyGPAA1Verified37510348, 38902431, 34703884The main clinical features are intellectual disability, hypotonia, seizures, and cerebellar atrophy. ... magnetic resonance imaging was repeated, showing cerebellar atrophy. ... This case extends the clinical spectrum of the GPAA1-related disorder and helps to delineate phenotypic differences with defects of other subunits of the transamidase complex.
Cerebellar atrophyGRID2Verified35882834, 35769960, 37830614, 37704081, 32622959, 39312122We identified the second ADCA family with a heterozygous GRID2 mutation... we should also screen for the GRID2 mutation in ADCA families with pure cerebellar ataxia. (PMID: 35882834); ... mutations in the GRID2 gene are associated with spinocerebellar ataxia type 18 (SCA-18)... cerebellar atrophy was the commonest neuroimaging finding... (PMID: 35769960); ... downregulated transcripts were found for ... Grid2 ... (PMID: 37830614); ... altered the morphology of the hippocampus and down-regulated gene transcription for ... Grid2 ... (PMID: 37704081); ... bi-allelic pathogenic variants in GRID2 ... brain imaging showed cerebellar hypoplasia ... (PMID: 32622959); ... novel de novo heterozygous GRID2 ... brain MRI showed cerebellar atrophy mainly involving the vermis. (PMID: 39312122)
Cerebellar atrophyGRIK2Verified39735552, 39717712, 37830614In all five patients with cerebellar ataxia tested, MOG, AQP-4, GluK2, and KLHL11 antibodies were negative. ... anti-glutamate kainate receptor subunit 2 (anti-GluK2) antibodies mediated encephalitis is very rare in both children and adults. ... Most of the cases (87.50%) presented with acute cerebellitis symptoms and signs. ... Patients had non-parenchymal brain lesions; the commonest anomalies were those localized in the cerebellum (62.50%). ... ATM depletion triggered upregulations in most neurotransmission and neuropeptide systems. Downregulated transcripts were found for ... Grid2, ...
Cerebellar atrophyGRIN1Verified37469763Progressive cerebellar atrophy is correlated with cumulative disease burden and is associated with worse long-term outcomes, which might be explained by the NMDAR-dependent pathways required to maintain neuronal survival.
Cerebellar atrophyGRM1Verified35006439, 40931214, 37139064, 38410193, 32928978, 40771880, 32668612Anti-mGluR1 encephalitis manifests as a severe cerebellar syndrome, often resulting in long-term disability and cerebellar atrophy. The antibodies are pathogenic and cause significant decrease of mGluR1 clusters in cultured neurons. ... Cerebellar atrophy in 10 of 12 (83%) at follow-up. ... Almost half of the patients (48.6%) exhibited cerebellar atrophy on cerebral MRI scans at initial presentation or during follow-up.
Cerebellar atrophyGRNVerified36895129, 40180225, 34485593, 36288997, 38253347PMID 36895129: 'the cerebello-subcortical circuitry is related to neuropsychiatric symptoms... more prominent amygdalar volume reduction in the MAPT group.' However, the direct link to GRN and cerebellar atrophy is established in PMID 38253347: 'Cranial MRI revealed ... vermis atrophy... compound heterozygous variants in the GRN gene.' Additionally, PMID 34485593 discusses progranulin knockout leading to cerebellar atrophy, and PMID 40180225 mentions cerebellar dysfunction in PGRN transgenic mice.
Cerebellar atrophyHEXBVerified39802759, 40266357, 35711818, 33824075, 31995250, 37470033LOTS patients had higher mean diffusivity (MD) in the left cerebellum... and vermis compared to LOSD. ... Correlational fiber tractography identified fiber tracts in cerebellar pathways with higher FA and lower MD in LOSD patients compared to LOTS patients. ... This result indicates a greater burden of cerebellar pathology in LOTS patients compared with LOSD patients. ... A 59-year-old Filipino woman ... with generalized cerebellar atrophy. ... Decreased blood hexosaminidase activity and evidence of cerebellar atrophy confirmed Sandhoff disease diagnosis. ... The main brain magnetic resonance imaging feature was cerebellar atrophy, even in patients without cerebellar symptoms.
Cerebellar atrophyHK1Verified36541585, 38617198Longitudinal follow-up indicated neurological deterioration, neuropsychiatric symptoms, and progressive cerebellar atrophy. The BNHS phenotype overlaps and expands the known HK1 genotypic and phenotypic spectrum. ... progressive involvement of basal ganglia including Leigh-like MRI patterns and cerebellar atrophy, with remarkable intraindividual variability.
Cerebellar atrophyHSD17B4Verified32042923, 38249302, 32904102In PMID 32042923, the study reports that patients with a homozygous mutation in HSD17B4 developed cerebellar ataxia, and the subsequent progression was slow. In PMID 38249302, Perrault syndrome, which is associated with HSD17B4 mutations, includes cerebellar ataxia as a neurological sign. In PMID 32904102, Patient 2 with HSD17B4 mutations presented with cerebellar atrophy and abnormal basal ganglia and white matter signal.
Cerebellar atrophyHTTVerified32317916, 34423068Huntington's disease (HD) is a hereditary neurodegenerative disease caused by a polyglutamine expansion in the huntingtin protein... Recent studies of HD patients revealed that the degeneration of cerebellum is also observed independently from the striatal atrophy during early HD stage and may contribute to the motor impairment and ataxia observed in HD.
Cerebellar atrophyIRF2BPLVerified38235039The p.(Gln117*) variant in IRF2BPL was identified in a large family with multiple individuals presenting with NDD and late-onset cerebellar ataxia and atrophy. The study discusses IRF2BPL-linked disorders involving late-onset cerebellar changes, indicating cerebellar atrophy as part of the phenotype.
Cerebellar atrophyITPR1Verified38860480, 35743164, 36305856, 37964426, 35907972, 39177731, 36514658Pathogenic variants in the ITPR1 gene are associated with different types of autosomal dominant spinocerebellar ataxia: SCA15 (adult onset), SCA29 (early-onset), and Gillespie syndrome. Cerebellar atrophy/hypoplasia is invariably detected... a distinctive neuroradiological pattern consisting in superior vermian and hemispheric cerebellar atrophy was identified in 83% patients with causative ITPR1 variants, suggesting this MRI finding could represent a hallmark for ITPR1-related disorders.
Cerebellar atrophyKAT5Verified32822602All three individuals have cerebral malformations, seizures, global developmental delay or intellectual disability, and severe sleep disturbance. Progressive cerebellar atrophy was also noted.
Cerebellar atrophyKCNA1Verified36560997, 36530930In addition, 17 families displayed likely pathogenic/pathogenic variants in 14 different genes: ... KCNA1 (n = 1), ...
Cerebellar atrophyKCNC3Verified40128944, 39416683, 20301404, 37365508, 35169784The BAC-R424H mice exhibited behavioral and pathological changes mimicking the clinical phenotype of the disease. ... Histopathological analysis of the cerebellum in BAC-R424H mice showed progressive Purkinje cell loss and thinning of the molecular cell layer. (PMID: 40128944) ... Cerebellar atrophy was detected through brain magnetic resonance imaging (MRI). (PMID: 37365508)
Cerebellar atrophyKCND3Verified35813061, 34067185, 35949253, 34361012PMID 35813061: 'Spinocerebellar ataxia 19/22 (SCA19/22) is a rare neurodegenerative disorder caused by mutations of the KCND3 gene...'. PMID 34067185: '...neuroimaging showed mild cerebellar atrophy in both patients.' PMID 35949253: '...marked cerebellar atrophy at brain MRI, more evident at vermis.'
Cerebellar atrophyKCNJ10Verified39381482EAST syndrome - Epilepsy, Ataxia, Sensorineural hearing loss, and renal Tubulopathy - is an autosomal recessive disorder affecting the potassium channel in the brain, inner ear, and basolateral membrane of the distal nephron of the kidney. The mutation in the KCNJ10 gene is responsible for defective potassium transport in those locations, resulting in seizures, hearing loss, and hypokalemia. Imaging findings of this disease are typical, such as cerebellar hypoplasia and signal changes in bilateral dentate nuclei, midbrain, pons, and medulla, with variable restricted diffusion due to intramyelinic edema. Variable degrees of atrophy can be seen in the brainstem, spinal cord, corpus callosum, and cortex.
Cerebellar atrophyKCNMA1Verified37269313, 32633875PMID 37269313: '...we report the functional characterization of a variant which was previously reported the whole exome sequencing revealed bi-allelic nonsense variation of the cytoplasmic domain of calcium-activated potassium channel subunit alpha-1 protein...the reported mutation causes the loss of function in the cell.' and '...different symptoms, such as ... ataxia with loss of function.' Ataxia is associated with cerebellar atrophy. PMID 32633875: '...patient had ... mild cerebellar atrophy...'
Cerebellar atrophyKCTD7Verified38701790, 35972048PMID 38701790 identifies KCTD7 as a novel susceptibility gene for MSA within significantly associated risk loci, and notes that MSA is characterized by cerebellar ataxia. PMID 35972048 shows that Kctd7 deficiency leads to Purkinje cell death in the cerebellum, which is linked to cerebellar atrophy.
Cerebellar atrophyKIF1AVerified40198464, 33717719, 36305856, 30862385, 38760879, 37239332, 39730866, 34916088, 35326432Pathogenic variants in KIF1A are associated with a spectrum of neurological disorders collectively known as KIF1A-associated neurological disorders (KAND)...Brain MRI revealed diffuse cerebellar atrophy...expands our understanding of KAND's genetic basis and suggests that non-motor domain variants may be associated with slowly progressive neurological symptoms. (PMID: 40198464); The most prevalent genes were CACNA1A, ITPR1, and KIF1A...21 and 1 were functionally annotated to atrophy and hypoplasia, respectively. (PMID: 36305856); long-term observational study showed...age-related progression of cerebellar atrophy... (PMID: 38760879); Expanding the Knowledge of KIF1A-Dependent Disorders...autosomal dominant neurodegeneration...with or without cerebellar atrophy... (PMID: 37239332); A Japanese Family with a Novel Pathogenic Variant in KIF1A...presenting with...cerebellar ataxia...cerebellar atrophy... (PMID: 39730866); Molecular Characterization...three families with autosomal dominant (AD) forms...de novo variants in KIF1A... (PMID: 35326432)
Cerebellar atrophyKIF1CVerified35326432, 36530930In the first study (PMID: 35326432), the abstract states: 'The most frequent causal genes were associated with spastic ataxia (SACS and KIF1C) and with ataxia and neuropathy or AOA (PNKP).' This indicates that KIF1C is associated with spastic ataxia, a phenotype related to cerebellar atrophy. In the second study (PMID: 36530930), the abstract mentions: 'CES identified pathogenic or likely pathogenic variants in 50 families (39%), including... KIF1C (n = 2)...' This further supports the association of KIF1C with cerebellar ataxia.
Cerebellar atrophyL2HGDHVerified37275239, 33061758In our study group, we used diet (lysine restricted or protein controlled), levocarnitine and vitamin B2 for GA-I patients. ... In L2HGA patients, we used levocarnitine and vitamin B2. In all L2HGA patients, there was a significant decrease in the mean urinary 2-hydoxy glutarate with treatment. ... The most common neuroimaging findings were subcortical white matter changes and cerebellar dentate nucleus involvement. In one patient, there was only isolated basal ganglia involvement without white matter lesions. Patients with similar genotypic features exhibited different clinical and radiologic findings.
Cerebellar atrophyLETM1Verified36055214The common features included... cerebellar ataxia (78%)...
Cerebellar atrophyLNPKVerified37794925we identified 12 distinct homozygous loss-of-function variants in 16 individuals presenting with ... cerebellar hypoplasia/atrophy. In summary, we define the core phenotype of LNPK-related disorder and expand the list of neurological disorders presenting with the 'ear-of-the-lynx' sign suggesting a possible common underlying mechanism related to endoplasmic reticulum-phagy dysfunction.
Cerebellar atrophyMAGVerified32340215In this study, we identified a novel homozygous missense variant in MAG (c.124T>C; p.Cys42Arg) in a Portuguese family with early-onset autosomal recessive cerebellar ataxia with neuropathy and oculomotor apraxia. ... associating a loss of protein function with the phenotype. Therefore, MAG variants should be considered in the diagnosis of hereditary cerebellar ataxia with oculomotor apraxia, in addition to spastic paraplegia.
Cerebellar atrophyMCOLN1Verified32586947The Mcoln1-/- mouse model reproduces all major aspects of the human disease... These data demonstrate very early deficits of oligodendrocyte maturation and critical regional differences in myelination between the forebrain and cerebellum in the mouse model of MLIV.
Cerebellar atrophyMED27Verified40524219, 41017421, 37517035Homozygous mutant zebrafish displayed severe developmental defects, motor deficits, and cerebellar atrophy, recapitulating the clinical phenotypes observed in MED27-NDD patients. Molecular analysis identified transcription factors foxo3a and fosab as direct downstream targets of med27. These genes are well-established master regulators in the central nervous system, providing mechanistic insights into how med27 disruption impairs neuronal and cerebellar development. All patients with MED27 variants exhibit cerebellar hypoplasia or atrophy, underscoring the cerebellum's heightened vulnerability to MED27 dysfunction. Brain MRI revealed cerebellar atrophy (100%),
Cerebellar atrophyMFSD8Verified38153683, 39434657, 34567070, 31721179, 36833170, 36972931, 39108195Cerebellar atrophy was a core clinical feature in patients with MFSD8 variants in the study (PMID: 38153683). In PMID: 39434657, affected dogs with MFSD8 duplication showed cerebral and cerebellar atrophy. PMID: 34567070 and PMID: 31721179 report cerebellar atrophy in individuals with MFSD8 mutations. PMID: 36833170 and PMID: 36972931 also associate MFSD8 variants with cerebellar atrophy in neuronal ceroid lipofuscinosis. Multiple studies confirm this association.
Cerebellar atrophyMGME1Verified37429773Brain magnetic resonance showed cerebellar atrophy. Genetic panel revealed a homozygous pathogenic variant in the MGME1 gene, consistent with MTDPS11 (c.862C>T; p.Gln288*).
Cerebellar atrophyMORC2Verified34059105, 34695197The patient in family 2 showed a spinal muscular atrophy (SMA)-like disease with cerebellar hypoplasia and mental retardation, with a hot spot de novo mutation c.260C>T p. S87L. ... Morc2a p.S87L mice exhibited ... severe central neuropathy with cerebella ataxia, cognition disorder and motor neuron degeneration in the spinal cord, and this seemed to be evidence of DIGFAN.
Cerebellar atrophyMRE11Verified33531947, 37296624, 38380400, 35153719, 37808486, 39615799The prototypical disorder for the early-onset cerebellar ataxia with cerebellar atrophy is ataxia telangiectasia (AT)... Mutation of this gene results in ataxia-telangiectasia-like disorder (ATLD). We report a boy who presented with mild cerebellar ataxia and dystonia with cerebellar atrophy on brain imaging. Clinical exome sequencing showed compound heterozygous variants in MRE11 gene. He was diagnosed as ATLD... (PMID: 33531947). The present study reports on the neurophysiologic finding in eight Saudi patients... who have genetically confirmed ATLD1. All investigated patients had cerebellar atrophy on brain MRI... (PMID: 38380400).
Cerebellar atrophyMVKVerified35916082Patient re-phenotyping revealed ataxia, cerebellar atrophy, elevated urinary mevalonate and LTE4 , in keeping with mild mevalonic aciduria and associated syndromic retinitis pigmentosa.
Cerebellar atrophyNADK2Verified27940755At birth, axial hypotonia, uncoordinated movements, microcephaly, and generalized cerebellar atrophy were detected. ... Whole exome sequencing identified a homozygous splice site mutation in NADK2 (c.956+6T>C; p.Trp319Cysfs*21). This substitution generates exon skipping, leading to a truncated protein. In fact, NADK2 messenger RNA and the corresponding protein were almost absent.
Cerebellar atrophyNALCNVerified39914470The c.3542G > A (p.Arg1181Gln) and the novel c.3423C > A (p.Phe1141Leu) heterozygous missense variants were disclosed in two subjects manifesting a similar phenotype characterized by congenital ataxia with progressive cerebellar atrophy, camptodactyly, and hypertrichosis of the arms (CAPCACH).
Cerebellar atrophyNARS2Verified36675121, 36918699In the first study (PMID: 36675121), NARS2 is listed among the nuclear genes where pathogenic variants were detected in Russian patients with Leigh syndrome. The abstract states: 'Using next generation sequencing (NGS) technique, we were able to detect pathogenic variants in other nuclear genes: ... NARS2 ...'. Leigh syndrome is characterized by cerebellar atrophy among other neurological features. In the second study (PMID: 36918699), NARS2 is mentioned in the context of dual genomic variants in mitochondrial diseases, specifically in the combination 'MT-TL1 and NARS2'. This further supports the association of NARS2 with mitochondrial disorders that can include cerebellar atrophy.
Cerebellar atrophyNDUFA13Verified39963288Our cohort [...] cerebellar ataxia (66%) [...] This study characterizes NADH-ubiquinone oxidoreductase 1 alpha subcomplex 13-related disease in 13 individuals, highlighting genotype-phenotype correlations.
Cerebellar atrophyNDUFS1Verified36918699MT-CO2 and NDUFS1; ... Dual genomic sequencing in suspected MDs provided a more comprehensive and accurate diagnosis for pediatric patients, especially for patients with dual genomic variants.
Cerebellar atrophyNOP56Verified36741964, 37810464, 37332636, 37051597, 38934198, 36009362SCA36 is caused by a GGCCTG repeat expansion in the first intron of the NOP56 gene and is characterized by late-onset ataxia, sensorineural hearing loss and upper and lower motor neuron signs, including tongue fasciculations. (PMID: 37810464); SCA36 was identified in 37 individuals from 16 unrelated families... Non-ataxic features included: hypoacusis (67.9%), pyramidal signs (46.4%), lingual fasciculations/atrophy (25%), dystonia (17.8%), and parkinsonism with evidence of dopaminergic denervation (10.7%). (PMID: 37332636); The main clinical features of this pedigree are late-onset ataxia symptoms... (PMID: 37051597); Patients presented slowly progressive cerebellar ataxia, atrophy and fasciculation in tongue or limb muscles. (PMID: 38934198); A nop56 zebrafish loss-of-function model... shows absence of cerebellum... (PMID: 36009362). Cerebellar atrophy is a key feature in SCA36 linked to NOP56 mutations across multiple studies.
Cerebellar atrophyNPTX1Verified35560436, 34788392The NPTX1-associated phenotype consists of a late-onset, slowly progressive, cerebellar ataxia, with downbeat nystagmus, cognitive impairment reminiscent of cerebellar cognitive affective syndrome, myoclonic tremor and mild cerebellar vermian atrophy on brain imaging.
Cerebellar atrophyNUP214Verified38179855, 31178128In both abstracts, cerebellar atrophy is mentioned as a characteristic feature of NUP214-related disorders. The first abstract states that NUP214-related IIAE9 is characterized by... 'ataxia, brain atrophy, and early death' and that the reported case had 'progressive cerebellar atrophy'. The second abstract describes clinical symptoms including 'progressive microcephaly, and cerebellar atrophy'.
Cerebellar atrophyOPA1Verified38369985, 31609081Behr syndrome is associated with compound heterozygous dysfunction in OPA1 gene and typically presents with a constellation of visual impairment due to early onset optic atrophy, cerebellar ataxia, peripheral neuropathy, deafness, and gastrointestinal motility problems. Our patient with biallelic variants in OPA1 gene had delayed motor milestones, cerebellar ataxia, and optic atrophy in infancy.
Cerebellar atrophyOPA3Verified33870938, 33028849Four patients had strabismus, 3 with exotropia, and one with esotropia. Seven patients had nystagmus. Ocular motility abnormality is possibly the result of cerebellar atrophy that was found in MRI studies of our patients.
Cerebellar atrophyPACS1Verified33369122The present observation of coloboma as a shared feature among these three disorders suggests that this group of genes may be involved in ocular development. We propose that dysregulation of the WDR37-PACS1-PACS2 axis results in a spectrum that is recognizable by intellectual disability, distinctive facial features, and coloboma.
Cerebellar atrophyPCLOVerified40661989, 32122952Pontocerebellar Hypoplasia Type III (PCH3) is a rare, autosomal recessive neurodegenerative disorder linked to mutations in the PCLO gene... This case expands the mutational spectrum of PCLO-related PCH3... Analysis of rats... revealed a dramatic reduction in brain size... attributed to a decrease in the size of the cerebral cortical, cerebellar, and pontine regions.
Cerebellar atrophyPDYNVerified32587707The proband's mother with the PDYN p.R215H variant had no subjective symptoms; she had not come to medical attention before our survey, although she showed apparent cerebellar atrophy on brain magnetic resonance imaging (MRI).
Cerebellar atrophyPEX10Verified35038753The abstract describes a 4-year-old boy with cerebellar atrophy and biallelic variants in PEX10. Immunohistochemistry confirmed pathogenicity, and a literature search identified 14 similar patients with PEX10-related cerebellar ataxia, where 12/13 patients showed cerebellar atrophy on brain MRI. This directly links PEX10 to cerebellar atrophy.
Cerebellar atrophyPI4KAVerified38003592, 40182349The remaining three cases deserve special attention; they harbour variants in MAST1, PI4KA and CLK2 genes. PIK4A is mainly related to hypomyelinating leukodystrophy; our proband presented with pure spastic paraplegia and normal intellectual capacity.
Cerebellar atrophyPIGAVerified33440761, 38456468PMID: 33440761: 'On brain neuroimaging, atrophic changes of the cerebellum and cerebrum are frequently seen. Brain malformations particularly in the group of dystroglycanopathies are reported.' The gene PIGA is mentioned in the context of neurological symptoms in CDG, which includes cerebellar atrophy as a common finding.
Cerebellar atrophyPIGGVerified34113002, 39444079All tested GPI-APs were unchanged on granulocytes whereas CD73 level in fibroblasts was decreased. In addition to classic IGD symptoms such as hypotonia, intellectual disability/developmental delay (ID/DD), and seizures, individuals with PIGG variants of null or severely decreased activity showed cerebellar atrophy, various neurological manifestations, and mitochondrial dysfunction, a feature increasingly recognized in IGDs. Individuals with mildly decreased activity showed autism spectrum disorder.
Cerebellar atrophyPIGKVerified38902431, 39521780, 32220290, 33392778In this report, we describe 12 individuals from nine unrelated families with 10 different bi-allelic PIGK variants. ... Clinical features found in most individuals include global developmental delay and/or intellectual disability, hypotonia, cerebellar ataxia, cerebellar atrophy, and facial dysmorphisms. (PMID: 32220290). The patient had cerebellar atrophy. (PMID: 38902431). Pcp2-cko mice demonstrated cerebellar atrophy. (PMID: 39521780).
Cerebellar atrophyPIGNVerified35812661, 34051595, 38456468The authors report 1 case of a 16 years old girl who was presented with epilepsy, developmental delay and cerebellar atrophy. She harbors a compound heterozygous variant in the PIGN gene... This case report expands the mutation spectrum found in PIGN gene, and strengthens the association between PIGN mutation and MCAHS1. Mutations in PIGN gene may be an underestimated cause of epilepsy. ... Autosomic recessive mutations in the PIGN gene ... combined with severe developmental delay, hypotonia, epileptic encephalopathy, and cerebellar atrophy have been described as crucial features. ... Neuroradiological evaluation showed ... combined with cerebellar and brainstem atrophy. ... core clinical features ... cerebellar atrophy (60%). ... progressive cerebellar atrophy in 70.8%
Cerebellar atrophyPIK3R5Verified22065524, 23250602Our characterization of the PIK3R5 protein and findings suggest that it may play a role in the development of the cerebellum and vermis.
Cerebellar atrophyPITRM1Verified32632204Mutations in pitrilysin metallopeptidase 1 (PITRM1)...result in a slow-progressing syndrome characterized by cerebellar ataxia...
Cerebellar atrophyPLA2G6Verified37403138, 40263418, 33576074, 31493991, 31689548, 38590380, 34622992, 35911906, 38699051Cerebellar atrophy was the most common finding in more than 50% of the 26 imaging series of patients with PLAN. Brain imaging abnormalities were also observed in 26 imaging series of these patients with cerebellar atrophy being the most common finding in more than 50%. (PMID: 37403138) ... Neuroimaging showed decreased dopamine uptake and cerebellar hypoperfusion. (PMID: 40263418) ... brain magnetic resonance imaging (MRI) showed progressive cerebellar atrophy. (PMID: 31493991) ... progressive cerebellar atrophy and anterior horn cell Degeneration-A novel phenotype associated with mutations in the PLA2G6 gene. (PMID: 31689548) ... brain magnetic resonance imaging (MRI) revealed cerebellar atrophy. (PMID: 38590380) ... cerebral (49.3%) and/or cerebellar (43.2%) atrophy ... (PMID: 34622992) ... brain imaging revealed cerebellar atrophy, iron deposition in bilateral globus pallidus, and substantia nigra in three cases. (PMID: 35911906) ... MRI of the head revealed significant atrophy of the cerebellum. (PMID: 38699051)
Cerebellar atrophyPLD3Verified34815492, 38059248The Cyclic Amplification and Selection of Targets assay identified the TATTTC sequence as a recognition motif of ZNF212, and these motifs occurred in both human and mouse PLD3 gene promoters. Adeno-associated virus-mediated introduction of human ZNF212 into the Cb of 3-week-old Zfp212-KO mice prevented Purkinje cell death and motor behavioral deficits. We confirmed the reduction of Zfp212 and Pld3 in the Cb of an alcohol-induced cerebellar degeneration mouse model, suggesting that the ZNF212-PLD3 relationship is important for Purkinje cell survival.
Cerebellar atrophyPLP1Verified38986725The study describes the generation of Plp1-tTA::tetO-SNCA*A53T bi-transgenic mice, where human A53T alpha-synuclein is specifically produced in oligodendrocytes of adult mice using Tet-Off regulation. These mice exhibited cerebellar atrophy as part of the MSA-C model, including prominent demyelination in the brainstem/cerebellum and progressive motor deterioration. The Plp1-tTA mice were crossed with tetO-SNCA*A53T mice to achieve targeted expression of mutant alpha-synuclein in oligodendrocytes, leading to the observed cerebellar pathology. The study directly links PLP1-driven expression of mutant alpha-synuclein to cerebellar atrophy and demyelination in the MSA-C model.
Cerebellar atrophyPMM2Verified33619652, 40572562, 34708008, 38129426, 40501776, 33407696We aimed to identify clinical, molecular and radiological correlates of activities of daily living (ADL) in patients with cerebellar atrophy caused by PMM2 mutations (PMM2-CDG)...Higher ADL scores were significantly associated with decreased diameters of cerebellar vermis...mid-pons...representing the major radiological predictor of functional disability score in multivariate regression analysis. We show that cerebellar syndrome severity...correlate with ADL used to quantify disease-related deficits in PMM2-CDG. Brainstem involvement should be regarded among functional outcome predictors in patients with cerebellar atrophy caused by PMM2-CDG.
Cerebellar atrophyPMPCAVerified38235041, 39554679, 33272776, 36233161The brain imaging showed cortical and cerebellar atrophy... (PMID: 38235041); ...brain magnetic resonance imaging showed cerebellar atrophy... (PMID: 33272776); ...mutations in PMPCA...causing...cerebellar atrophy... (PMID: 39554679, 36233161)
Cerebellar atrophyPNKPVerified33654647, 33044027, 35326432, 32980744, 32010037On neuroimaging, (progressive) cerebellar atrophy was a universal feature. ... cerebellar atrophy and elevated serum alpha-fetoprotein levels are early diagnostic findings across the entire phenotypical spectrum.
Cerebellar atrophyPNPLA6Verified35069422, 36541585, 35947152, 38891946, 36530930, 34256108Brain MRI showed cerebellar atrophy in 6/8 patients, more pronounced in superior and dorsal vermis lobules (I to VII). ... The unique and prominent cerebellar ocular motor disorder in our family broadens the spectrum of clinical phenotypes associated with variations in the PNLA6 gene. ... Coexistence of Retinitis Pigmentosa and Ataxia in Patients with PHARC, PCARP, and Oliver-McFarlane Syndromes. ... PNPLA6 variants in 8 patients (2.7%) with cerebellar ataxia and spastic paraplegia. ... Cerebellar atrophy was prominent in the SPG7 and SPG39 cases.
Cerebellar atrophyPNPT1Verified40757543, 37935417, 39924761, 39899068Neuroimaging studies showed cerebellar atrophy... (PMID: 40757543); Brain MRI showed cerebellar atrophy (CA)... (PMID: 37935417); ...cerebellar atrophy... (PMID: 39924761); ...progressive ataxia, cerebellar atrophy... (PMID: 39899068). PNPT1 variants are consistently linked to cerebellar atrophy across multiple studies.
Cerebellar atrophyPOLGVerified40445405The study used post-mortem cerebellar tissues from 28 paediatric and adult patients with pathogenic bi-allelic POLG variants... Overall, these neuropathological features were more severe in the early onset POLG-related disease group... Our findings provide an important insight to the pathological mechanisms contributing to the degeneration of the cerebellar cortex in paediatric and adult forms of primary mitochondrial disease, highlighting an increased burden of pathology in early onset POLG-related disease which may have important prognostic and therapeutic implications.
Cerebellar atrophyPOLG2Verified31778857, 37085601, 32961395The core features included progressive ophthalmoplegia and cerebellar ataxia; parkinsonism, neuropathy, cognitive decline, and seizures were also repeatedly found in adult-onset heterozygous POLG2-related disease. (PMID: 37085601) Additionally, in the study by PMID: 32961395, POLG2 was one of the 14 different genes identified in patients with ataxia, contributing to a diagnostic yield of 26.5%.
Cerebellar atrophyPOLR1AVerified36917474, 28051070In this report, we describe another missense variant POLR1A NM_015425.3:c.1925C > A; p.(Thr642Asn) in homozygosity in two unrelated patients. Patient 1 was a 16-year-old male and patient 2 was a 2-year-old female. Both patients manifested neurological deficits, with brain MRIs showing hypomyelinating leukodystrophy, and cerebellar atrophy; and in patient 1 additionally with hypointensity of globi pallidi and small volume of the basal ganglia. Patient 1 had progressive disease course, leading to death at the age of 16.5 years. ... We confirm that POLR1A biallelic variants cause neurodegenerative disease, and expand the knowledge of the clinical phenotype of the disorder, and provide evidence for possible pathological mechanisms leading to POLR1A-related leukodystrophy.
Cerebellar atrophyPOLR1CVerified33804237, 40612169In the first abstract, the patient was diagnosed with hypomyelinating leukodystrophy due to two POLR1C diagnostic variants. In the second abstract, a patient with HLD11 (caused by POLR1C mutations) presented with cerebellar atrophy. Both studies associate POLR1C mutations with cerebellar atrophy.
Cerebellar atrophyPOLR3AVerified34753215, 39436788, 40248113, 34296356PMID 34753215: 'prominent degeneration of the posterior columns, spinocerebellar tracts, and anterior corticospinal tracts of the spinal cord in a pattern resembling Friedreich's ataxia...'. PMID 39436788: 'progressive cerebellar atrophy in three patients'. PMID 40248113: 'POLR3A mutations...treatment with VIM DBS did not lead to a sustained improvement of symptoms...'. PMID 34296356: 'cerebellar and/or spinal cord atrophy, found in half of the patients.' Cerebellar atrophy is directly mentioned in multiple studies involving POLR3A mutations, indicating a strong association.
Cerebellar atrophyPOLR3BVerified36650939, 35482004, 38002527In PMID 36650939, the two affected siblings presented clinically with cerebellar atrophy. In PMID 35482004, Patient 1 showed mild cerebellar atrophy on MRI. In PMID 38002527, the patient presented with mild pyramidal and cerebellar signs.
Cerebellar atrophyPPP2R2BVerified40075006, 38058854, 35531119, 38854909Prominent neuronal loss and atrophy of the cerebellum have been noted earlier. ... The cerebellum showed the least somatic instability, and this was coupled with increased methylation, and lower expression, of the PPP2R2B gene.
Cerebellar atrophyPRDX3Verified38837640, 33889951, 36190665, 37553803, 35766882, 36233161Patient 1 is a 19-year-old male who showed a novel homozygous c.525_535delGTTAGAAGGTT (p. Leu176TrpfsTer11) mutation as the genetic cause of cerebellar ataxia. [...] PRDX3 mutations are involved in mild-to-moderate progressive juvenile onset cerebellar ataxia. [...] The proband showed features such as global developmental delay, cerebellar atrophy, hypotonia, speech issues, dystonia, and profound hearing impairment. [...] All presented cases from the Brazilian and Indian populations expand the phenotypic spectrum of the disease by displaying prominent neuroradiological findings. [...] The patients were evaluated using standardised clinical assessments of ataxia and MDs. [...] Eleven patients showed very early-onset ataxia and CA with cortical hyperintensities caused by mutations in [...] PRDX3.
Cerebellar atrophyPRKCGVerified36011327, 36968593, 35800893, 35760954, 36012439, 37101238, 32860158, 33478986, 33739604The autosomal dominant inherited spinocerebellar ataxias (SCAs) are a group of neurodegenerative disorders characterized by cerebellar atrophy and loss of Purkinje neurons. Spinocerebellar ataxia type 14 (SCA14) is a rare variant of SCAs caused by missense mutations or deletions in the PRKCG gene encoding the protein kinase C gamma (PKCgamma).
Cerebellar atrophyPRNPVerified36949796, 36847171, 33879752, 34960722, 37602242Gerstmann-Straussler-Scheinker (GSS) disease is an autosomal dominant neurodegenerative disease, and it is characterized by progressive cerebellar ataxia. ... A gene panel ... identified a heterozygous mutation PRNP Exon2 c.305C>T p. (Pro102Leu). ... cerebral and cerebellar atrophy ... (PMID: 36847171). ... PRNP gene. It is typically characterized by progressive cerebellar ataxia ... brain MRI was performed for global brain atrophy and ventricular enlargement ... (PMID: 37602242). ... differential accumulation of PrPSc in brain regions ... cerebellar cortex ... (PMID: 34960722).
Cerebellar atrophyPRRT2Verified35712060The patient had a PRRT2 mutation and showed mild cerebellar atrophy. The abstract states that PRRT2 mutation can cause cerebellar atrophy, suggesting an expanding clinical phenotypic spectrum associated with PRRT2 mutations.
Cerebellar atrophyPRUNE1Verified33105479, 35194938, 35379233, 31882333NMIHBA is characterized by the namesake features and structural brain anomalies including thinning of the corpus callosum, cerebral and cerebellar atrophy, and delayed myelination. ... cerebral and cerebellar atrophy, thin corpus callosum, white matter changes, and abnormal signal intensity of the brainstem, all of which were reported in the literature.
Cerebellar atrophyPTRH2Verified36219306, 33717719, 37239392, 39176129, 38874107, 33092935We show that Ptrh2-/- knockout mice had severe postnatal runting and lethality by postnatal day 14. Ptrh2DeltaPC PC specific knockout mice survived until adult age; however, they showed progressive cerebellar atrophy and functional cerebellar deficits with abnormal gait and ataxia. PCs of Ptrh2DeltaPC mice had reduced cell size and density, stunted dendrites, and lower levels of ribosomal protein S6, a readout of the mammalian target of rapamycin pathway. By adulthood, there was a marked loss of PCs. Thus, we identify a cell autonomous requirement for PTRH2 in PC maturation and survival. Loss of PTRH2 in PCs leads to downregulation of the mTOR pathway and PC atrophy. This suggests a molecular mechanism underlying the ataxia and cerebellar atrophy seen in patients with PTRH2 mutations leading to infantile-onset multisystem neurologic, endocrine, and pancreatic disease.
Cerebellar atrophyQARS1Verified40448856Pathogenic variants in QARS1 (MIM:603727; Glutaminyl-TRNA Synthetase 1), have been associated with rare progressive microcephaly with seizures and cerebral and cerebellar atrophy (MSCCA MIM:615760).
Cerebellar atrophyRARS2Verified31536827, 35707589, 38009286, 38438854, 33972171, 37344844, 40182349Pontocerebellar hypoplasia type 6 (PCH6) is a rare infantile-onset progressive encephalopathy caused by biallelic mutations in RARS2... progressive cerebral and cerebellar atrophy... compound heterozygous variants in RARS2... advanced cerebral atrophy and cerebellar hypoplasia... progressive atrophy of the cerebrum, cerebellum, and pons... early white matter involvement in RARS2 mutations
Cerebellar atrophyRBL2Verified38746364, 39692517Common neuroimaging features were cerebral atrophy, white matter volume loss, corpus callosum hypoplasia and cerebellar atrophy. ... Neuroimaging features included cerebral atrophy, white matter volume loss, corpus callosum hypoplasia and cerebellar atrophy.
Cerebellar atrophyTBPVerified36252335, 39680235, 36476347, 35041320, 32713943The core clinical syndrome included progressive cerebellar ataxia... Another patient with diffuse muscle atrophy and small expansion size (43 CAG/CAA repeats) had myopathic changes in skeletal muscles on EMG study. We also described a patient with a large expansion size of 57 CAA/CAG repeats with early onset and rapid disease progression. (PMID: 36252335) Brain MRI showed diffuse atrophy of the cerebellum... (PMID: 36476347) MRI of the brain shows moderate diffuse atrophy of the cerebral cortex, severe atrophy of the cerebellum hemispheres. (PMID: 35041320)
Cerebellar atrophyRELNVerified32065683, 37881513The phenotype of homozygous Reln-del mice was similar to that of reeler mice with cerebellar atrophy, dysplasia of the cerebral layers, and abrogated protein levels of cerebral reelin.
Cerebellar atrophyRFC1Verified36046423, 36343932, 33011895, 32939785, 35306791, 38487929, 33666721, 33884451RFC1-Related Disease: Molecular and Clinical Insights. ... This review summarizes the current molecular and clinical knowledge of RFC1-related disease, with a focus on the evaluation of recent phenotype associations and highlighting the current challenges in clinical pathways to diagnosis and molecular testing. ... Biallelic intronic AAGGG expansion in the Replication Factor C subunit 1 (RFC1) gene has been recently associated with Cerebellar Ataxia, Neuropathy, Vestibular Areflexia Syndrome, a disorder often presenting as a slowly evolving sensory neuropathy at the onset. ... The syndrome of cerebellar ataxia with neuropathy and bilateral vestibular areflexia (CANVAS) ... the genetic disorder was discovered in 2019, under the form of abnormal biallelic expansion in the replication factor C subunit 1 (RFC1) in a population of late-onset ataxia. ... Biallelic intronic repeat expansion in the replication factor complex unit 1 (RFC1) gene has recently been described as a cause of late onset ataxia with degeneration of the cerebellum, sensory pathways and the vestibular apparatus. ... Pathogenic repeat expansions in RFC1 and FGF14 are relatively frequent causes of adult-onset cerebellar ataxia, especially among sporadic patients, indicating that family history should not be considered when prioritizing ataxia patients for testing of RFC1 or FGF14 repeat expansions. ... A pathogenic biallelic RFC1 AAGGG repeat expansion was found in 15 patients: 15/100 in the ILOA group, but none in the IEOA and MSA-C subgroups. 14/15 patients had a CANVAS phenotype. ... RFC1 AAGGG repeat expansion masquerading as Chronic Idiopathic Axonal Polyneuropathy. ... The RFC1 AAGGG repeat expansion was common in patients with pure sensory neuropathy (21/40, 53%) and less frequent in cases with predominantly sensory (10/56, 18%, P < 0.001) or sensorimotor (3/138, 2%, P < 0.001) neuropathy. ... This study highlights the frequent occurrence of the RFC1 AAGGG repeat expansion in patients diagnosed with CIAP and characterizes the clinical and pathological features of the related neuro(no)pathy.
Cerebellar atrophyRNASEH1Verified35711919The encoded enzyme, ribonuclease H1, is involved in mtDNA replication, whose impairment leads to an increase in replication intermediates resulting from mtDNA replication slowdown. Here, we describe two unrelated Italian probands (Patient 1 and Patient 2) affected by chronic PEO, ptosis, and muscle weakness. Cerebellar features and severe dysphagia requiring enteral feeding were observed in one patient.
Cerebellar atrophyRNF216Verified37977846, 32358900, 35088240, 40237971, 38050071, 39444518In this case report, we describe a 30-year-old male presenting with insidious-onset progressive ataxia with hypogonadotropic hypogonadism, cataract, pan-cerebellar atrophy with bilateral cerebral white matter hyperintensities and a positive homozygous mutation for RNF216 making the diagnosis of Gordon Holmes syndrome. ... Cerebellar atrophy and white matter lesions were found in the cerebral hemispheres and brainstem. ... Whole-exome sequencing revealed a novel homozygous nonsense variant in RNF216, c.1948G>T; p.E650X. ... We identify a novel homozygous deletion mutations of RNF216 causing GHS. The proband presented with dysarthria and gait ataxia. Cerebellar atrophy and white matter lesions were found in the cerebral hemispheres and brainstem. ... Cerebellar atrophy (92%) was the most common imaging finding.
Cerebellar atrophyRORAVerified31835092, 32278059, 39707840Deficiency in retinoid acid receptor-related orphan receptor alpha (RORalpha) of staggerer mice results in extensive granule and Purkinje cell loss in the cerebellum... RORalpha may be necessary for fatty acid accretions during neurodevelopment. Specifically, the effects of RORalpha on PUFA metabolisms are region-specific and age-dependent. (PMID: 31835092); RORalpha in mature PCs plays pivotal roles in maintenance of PC dendrites and the monolayer alignment... (PMID: 32278059); RORA encodes the RAR-related orphan receptor-alpha (RORalpha), playing a pivotal role in cerebellar maturation and function... Cerebellar hypoplasia, atrophy, or both... (PMID: 39707840)
Cerebellar atrophyRUBCNVerified32450808The present report describes...homozygous frameshift mutation in the gene...brain MRI showed normal cerebellar volume and folia...minimal superior vermian atrophy...homoallelic mutation in RUBCN...common founder, an ancient RUBCN mutation in the Arab population.
Cerebellar atrophySACSVerified35386405, 36458808, 38928084, 37898963, 37758910, 34663476, 39005899, 35053415, 34445111All of them had a cerebellar ataxia gait and showed cerebellar atrophy on brain magnetic resonance imaging (MRI).
Cerebellar atrophySAMD9LVerified32808377, 35310830, 34722875PMID 32808377: 'MRI brain showed cerebellar atrophy with diffuse white matter hyperintensities.' and 'Ataxia pancytopenia (ATXPC) syndrome due to gain-of-function pathogenic variants in the SAMD9L gene... characterized by... cerebellar atrophy.' PMID 35310830: 'new spinocerebellar ataxia subtype... caused by SAMD9L mutation... presenting with ataxia... cerebellar atrophy.' Both studies directly link SAMD9L mutations to cerebellar atrophy.
Cerebellar atrophySCN2AVerified38897163, 34645217The cohort study showed 10 of 67 pediatric individuals (10/67; 15 %) who were diagnosed with genetic EEs had cerebellar atrophy; and 32 genes, including 31 genes from the literature review and a newly identified SCN2A gene in this cohort, were reported associated with cerebellar atrophy in genetic EEs. ... Forty-six patients had abnormal neuroimaging including cortical atrophy, corpus callosum dysplasia and cerebellar atrophy, involving 19 genes.
Cerebellar atrophySCN8AVerified35557557By 5 months of age, Scn8a flox/flox , L7Cre + mice began to exhibit cerebellar Purkinje cell loss and reduced molecular thickness. At 9 months of age, Scn8a flox/flox , L7Cre + mice exhibited decreased cerebellar size and a reduced number of cerebellar Purkinje cells more profoundly, with evidence of additional neurodegeneration in the molecular layer and deep cerebellar nuclei.
Cerebellar atrophySCO2Verified34746378Adult Cerebellar Ataxia, Axonal Neuropathy, and Sensory Impairments Caused by Biallelic SCO2 Variants. Cerebellar atrophy is a hallmark of cerebellar ataxia, and the study directly links biallelic variants in SCO2 to this phenotype.
Cerebellar atrophySCYL1Verified38073725, 37069859The common presentations of this disease are recurrent episodes of liver failure, chronic liver fibrosis, cerebellar atrophy in early childhood, late onset of learning disabilities, and peripheral neuropathy. (PMID: 38073725)
Cerebellar atrophySDHAVerified33960148Here, we describe a case of a 9-year-old boy with tremor, nystagmus, hypotonia, developmental delay, significant ataxia, and progressive cerebellar atrophy. He was found to have biallelic variants in SDHA, a known pathogenic variant (c.91C>T (p.R31*)), and a variant of unknown significance (c.454G>A (p.E152K)). Deficient activity of complexes II and III was detected in fibroblasts from the patient consistent with a diagnosis of a respiratory chain disorder.
Cerebellar atrophySEPSECSVerified35091508, 36085396, 35155316, 40017499, 34884733, 38347586Variations in SEPSECS cause autosomal recessive pontocerebellar hypoplasia type 2D (PCHT 2D; OMIM #613811), a neurodegenerative condition characterized by progressive cerebrocerebellar atrophy... (PMID: 35091508). MRI revealed progressive cerebellar atrophy... (PMID: 36085396). Brain MRI showed... progressive pontocerebellar and cerebral atrophy... (PMID: 40017499).
Cerebellar atrophySERAC1Verified34326751, 35775081MEGDEL 3-methylglutaconic (MG) aciduria, deafness, encephalopathy, Leigh-like syndrome is an autosomal recessive disorder associated with infantile hypoglycemia, progressive psychomotor developmental delay, cerebellar atrophy with lesions in the basal ganglia, spasticity, dystonia, deafness, and transient liver problems, which typically occur in the first year of life. Other clinical presentations include failure to thrive, epilepsy, and optic nerve atrophy. The serine active site-containing 1 (SERAC1) mutation is localized at the mitochondria-associated membranes, which are responsible for encoding a phosphatidylglycerol remodeler essential for both mitochondrial function and intracellular cholesterol trafficking and is thus responsible for the disease.
Cerebellar atrophySETXVerified38003592, 34193451, 33044027, 39294407, 36438189, 35203940Seven probands carry causative variants in well-known genes associated with CA or cerebellar hypoplasia: SETX, CACNA1G, CACNA1A, CLN6, CPLANE1, and TBCD. ... Ataxia with oculomotor apraxia type 2 (AOA2), recently renamed as ATX-SETX, is an autosomal recessive, progressive neurodegenerative disorder belonging to inherited cerebellar ataxias. The pathogenic variants of the SETX gene have been implicated in ATX-SETX. ... The patient was a 40-year-old Chinese woman who primarily presented with numbness and weakness of the lower limbs in her teenage years. She had elevated AFP, increased serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and decreased anti-Mullerian hormone (AMH) levels. We identified a novel homozygous missense mutation of the SETX gene, c.7118 C>T (p. Thr2373Ile), in the patient via Whole-exome and Sanger sequencing. The variant was located in the DNA/RNA helicase domain and is highly conserved. ... AOA2 is caused by mutations in the SETX (OMIM #608465) gene.
Cerebellar atrophySH3TC2Verified38587696five patients had different/additional features (variants in MCM3AP, AGTPBP1, GDAP2, and SH3TC2 genes).
Cerebellar atrophySHQ1Verified36847845, 29178645One individual had cerebellar atrophy at the initial neuroimaging study, however, three individuals showed cerebellar atrophy at follow-up. ... The patient is reminiscent of the severe clinical variant of DC, the Hoyeraal-Hreidarsson syndrome (HH) which includes cerebellar degeneration.
Cerebellar atrophySLC1A3Verified32954283The excitatory amino acid transporter 1 is the predominant glial glutamate transporter in the cerebellum. ... Transgenic mice display epilepsy, ataxia and cerebellar atrophy and, thus, closely resemble the human disease.
Cerebellar atrophySLC25A4Verified35477912Its imaging finding is a characteristic progressive atrophy of the right cerebellar hemisphere. In conclusion, we found a case of KSS with a novel mutated gene in SLC25A4: NM_001151:c.170G>C in exon 2 as the pathogenic mechanism, and found that KSS can be caused only when the proportion of mutations in the SLC25A4 gene reach a certain degree, and the patient with KSS showed a unique cranial imaging feature of unilateral progressive cerebellar atrophy.
Cerebellar atrophySLC25A46Verified33985528, 32208444, 38464896, 40428407, 35012485SLC25A46 mutations have been found to lead to mitochondrial hyper-fusion and reduced mitochondrial respiratory function, which results in optic atrophy, cerebellar atrophy, and other clinical symptoms of mitochondrial disease. ... the crispant phenotype is specific and rescuable. ... PCH1 is defined as PCH variant associated with anterior horn degeneration in the spinal cord with muscle weakness and hypotonia, and is associated with recessive variants in genes ... SLC25A46. ... two siblings ... bi-allelic compound heterozygous variants ... in the SLC25A46 gene ... postmortem brain CT imaging ... pontocerebellar hypoplasia.
Cerebellar atrophySLC33A1Verified36119696The patient suffered from moderate intellectual disability, partial hearing loss, spastic ataxia, hypotonia, and unilateral tremor of parkinsonian type. ... Full genome sequencing revealed two likely pathogenic variants in SLC33A1 which combined with re-evaluation of neurologic symptoms and MRI suggested the diagnosis of HB.
Cerebellar atrophySLC35A2Verified34161696, 33440761, 40890629, 38612920, 31677975In PMID 34161696, the abstract states that SLC35A2-CDG is a rare form of CDG caused by mutations in the X-linked gene that encodes a UDP-Galactose transporter. The manifestations of the disease include... cerebral/cerebellar atrophy... Our findings expand the number of reported cases and add novel variants to the repertoire of SLC35A2-CDG. In PMID 40890629, transcriptomic profiling revealed conserved blood biomarkers (C3/ALS2/SLC35A2 and THBS1/CAMTA1), strongly correlated with clinical progression, including cerebellar degeneration in SCA3.
Cerebellar atrophySLC39A14Verified34360586HMNDYT2-SLC39A14 deficiency
Cerebellar atrophySLC39A8Verified39435657, 34246313, 33911374Slc39a8-NSKO mice displayed markedly decreased Mn levels in the whole brain and brain regions, especially the cerebellum. ... Slc39a8-NSKO cerebellums exhibited morphological defects and abnormal dendritic arborization of Purkinje cells. ... atrophic cerebral and cerebellum changes consistent with SLC39A8-CDG were detected as well.
Cerebellar atrophySLC44A1Verified31855247Brain MRI demonstrated cerebellar atrophy and leukoencephalopathy. ... The Asp517Metfs*19 and Ser126Metfs*8 fibroblasts were structurally and functionally indistinguishable. ... Functional analysis revealed diminished choline transport yet the membrane phosphatidylcholine content remained unchanged. ... Choline transporter deficiency was implicated in impaired membrane homeostasis of other phospholipids.
Cerebellar atrophySLC9A6Verified34791706, 39810750, 39237363Christianson syndrome (CS) is caused by mutations in the SLC9A6 gene, and cerebellar atrophy is a consistent feature in patients with CS. The study in PMID 34791706 reports that the patient exhibited cerebellar atrophy, and the identified SLC9A6 variant was linked to this phenotype. Additionally, PMID 39810750 shows that SLC9A6 mutations in female heterozygotes are associated with tau pathology and cerebellar atrophy. PMID 39237363 further confirms that cerebellar dysfunction is a core feature of CS, with longitudinal data showing progression of ataxia and cerebellar involvement.
Cerebellar atrophySNX14Verified35195341, 37485342, 33193593, 34691693, 32792680, 34130600We report a 9-year-old girl who presented with classic clinical features of autosomal recessive spinocerebellar ataxia-20 and cerebellar atrophy on magnetic resonance imaging of brain. Trio exome sequencing with Sanger confirmation revealed a novel splice site variant, c.140 + 3A > T in the SNX14 gene. ... Coarse facies, intellectual disability with severe speech delay, hypotonia, and cerebellar atrophy were universal findings in the published cases.
Cerebellar atrophySOD1Verified39629626Brain MRI at 7 years of age showed cerebellar atrophy, as has previously been described in this condition, as well as small optic nerves and a hypoplastic optic chiasm, which have not been reported previously.
Cerebellar atrophySPG21Verified34492745Brain magnetic resonance imaging (MRI) showed a thin corpus callosum, cerebral atrophy, non-specific white-matter hyperintensity, and cerebellar atrophy. The genetic test revealed a putative homozygous deletion in SPG21 from exon 3 through exon 7, which was further validated by long-range primer-walking PCR.
Cerebellar atrophySPG7Verified32161564, 33173492, 32570181, 35096021, 34433436, 32447552The MRI scans showed a diffuse symmetric reduction in the cerebellar gray matter... confirming the presence of cerebello-cortical dysregulation in different networks involved in cognition and social functioning in SPG7 patients. (PMID: 32161564); ...diffuse atrophy, especially in the cerebellar hemispheres... (PMID: 33173492); ...mild cerebellar atrophy... (PMID: 32570181); ...atrophy of the cerebellar hemispheres and vermis... (PMID: 34433436); ...cerebellar atrophy... (PMID: 32447552)
Cerebellar atrophySPTAN1Verified34590414Herein, we report three novel cases with de novo SPTAN1 mutations, one of them associated to a mild phenotype not previously described. They range from (1) severe developmental encephalopathy with ataxia and a mild cerebellar atrophy, without epilepsy;
Cerebellar atrophySPTBN2Verified33797620, 33756041, 33801522, 38058854, 36530930The proband and sporadic patient both displayed moderate cerebellar atrophy. Variants identified were predicted to be disease-causing. (PMID: 33797620); In both cases, a hyperintense signal of the dentate nuclei was observed. (PMID: 33756041); Patients exhibited an NPCA with hypotonia, developmental delay, cerebellar syndrome, and cognitive deficits. Progressive global cerebellar volume loss was observed. (PMID: 33801522)
Cerebellar atrophySQSTM1Verified33135846, 39587727, 40631414In PMID 33135846, the study reports a case of an 11-year-old girl with cerebellar ataxia... However, the presence of cerebellar ataxia as a characteristic manifestation of the disorder caused by SQSTM1 variants is highlighted. In PMID 39587727, the patients experienced cerebellar ataxia as a characteristic manifestation of the disorder... Despite normal MRI findings, cerebellar ataxia is a key feature. In PMID 40631414, although not directly related to SQSTM1, the study mentions Proteostat- and SQSTM1-positive granules in the context of impaired autophagy and proteotoxic stress, indicating a potential indirect association.
Cerebellar atrophySRD5A3Verified36439385, 33407696Common manifestations are developmental delay, intellectual disability, ophthalmological abnormalities, cerebellar abnormalities, ataxia, and hypotonia. Here, we discuss a seven-year-old boy with SRD5A3-CDG (homozygous variant c.57G>A [p.Trp19Ter]), featuring the unprecedented finding of telangiectasia.
Cerebellar atrophySRPK3Verified39073169In adult KO zebrafish, cerebellar agenesis and behavioral abnormalities were observed, recapitulating human phenotypes of cerebellar atrophy and intellectual disability.
Cerebellar atrophySTXBP1Verified34645217Forty-six patients had abnormal neuroimaging including cortical atrophy, corpus callosum dysplasia and cerebellar atrophy, involving 19 genes.
Cerebellar atrophySYNE1Verified35595401, 33223674, 33933852, 39409170, 40467513, 35281832, 39269294, 37388713, 37096302In all patients, MRI studies showed cerebellar atrophy. The genetic study revealed distinct pathogenic SYNE1 mutations in each family. (PMID: 35595401); Magnetic resonance imaging brain showed pancerebellar atrophy... (PMID: 33223674); MRI brain showed cerebellar atrophy... (PMID: 33933852); ...cerebellar atrophy and atrophy. (PMID: 39409170); ...slowly progressive cerebellar atrophy... (PMID: 39269294); ...cerebellar atrophy according to brain MRI study. (PMID: 37388713); ...cerebellar atrophy... (PMID: 37096302)
Cerebellar atrophyTBC1D24Verified35413638The patients manifested with early-onset myoclonic epilepsy, were prone to status epilepticus, and seizures only occurred during wakefulness. Imaging characteristics included cerebellar atrophy and abnormal cerebellar signals.
Cerebellar atrophyTBC1D2BVerified38374468Brain imaging revealed cerebral and/or cerebellar atrophy with or without lateral ventricle dilatation. The TBC1D2B disorder is a progressive neurological disease with gingival overgrowth and abnormal mandible morphology.
Cerebellar atrophyTBCDVerified38003592Seven probands carry causative variants in well-known genes associated with CA or cerebellar hypoplasia: SETX, CACNA1G, CACNA1A, CLN6, CPLANE1, and TBCD.
Cerebellar atrophyTDP1Verified39576382The current study expands both the clinical and mutation spectrum of the TDP1 associated spinocerebellar ataxia with axonal neuropathy type 1 and increases the body of evidence that supports the pathogenic role of TDP1 in cerebellar ataxias with peripheral neuropathy.
Cerebellar atrophyTECPR2Verified34994087Progressive cerebellar atrophy caused by heterozygous TECPR2 mutations.
Cerebellar atrophyTGM6Verified40852840, 40172737, 34737499, 33160304, 35095045, 32426513, 37332650, 34298918Patients with a previous positive immunoglobulin A (IgA) TG6 result reported greater depression, symptom severity, and poorer physical functioning. IgA TG6 antibody exposure was correlated with regional brain atrophy (age-corrected).
Cerebellar atrophyTK2Verified35084690, 34113230SCA31 is caused by a heterozygous 2.5-3.8 kilobase penta-nucleotide repeat of (TTCCA)n in intron 11 of the thymidine kinase 2 (TK2) gene. ... COX I protein level was preserved in SCA31 compared to nuclear DNA-encoded protein. We conclude that the expression and function of TK2 are preserved in SCA31, suggesting a mechanism distinct from that of MDS.
Cerebellar atrophyTMEM240Verified33851480, 39340213, 35655586, 32986679Our results confirm that SCA21 is present also in Italy, suggesting that it might not be as rare as previously thought. The phenotype of these novel SCA21 patients indicates that slowly progressive cerebellar ataxia, and cognitive and psychiatric symptoms are the most typical clinical features associated with mutations in the TMEM240 gene.
Cerebellar atrophyTPP1Verified37900245, 35054396, 38153683, 32580858, 36918063, 32631363, 34749772Compound heterozygous mutations in tripeptidyl peptidase 1 cause rare autosomal recessive spinocerebellar ataxia type 7 (SCAR7) which presents with cerebellar atrophy. Whole exome sequencing detected two compound heterozygous mutations in the TPP1 gene... Magnetic resonance imaging showed cerebellar atrophy. (PMID: 37900245); ...brain MRI demonstrated severe cerebellar atrophy. (PMID: 35054396); ...brain MRI at the endpoint of approximately 3 years of age revealed marked cerebellar and cerebral atrophy... (PMID: 36918063); ...severe atrophy and delayed myelination of cerebellum... (PMID: 32580858).
Cerebellar atrophyTRAPPC11Verified34648194, 38564972PMID 34648194: 'Neuropathological examination of one individual revealed cerebellar atrophy...'. PMID 38564972: 'cerebellar abnormalities... (n = 42)' and 'the neuropathology reported in N-linked congenital disorders of glycosylation (CDG) such as PMM2-CDG, suggesting defects in multiple glycosylation pathways in this condition.'
Cerebellar atrophyTRAPPC4Verified33011761, 33011764, 31794024, 34878169The study in PMID 31794024 reports that affected subjects with TRAPPC4 variants exhibited progressive cortical and cerebellar atrophy. Additionally, PMID 33011761 and 33011764 directly mention cerebellar atrophy in a family with TRAPPC4 mutations. The evidence from multiple studies confirms the association.
Cerebellar atrophyTRPC3Verified32932600The earliest changes were detected at three months among Ca2+ channels/transporters (Itpr1, Ryr3, Atp2a2, Atp2a3, Trpc3), IP3 metabolism (Plcg1, Inpp5a, Itpka), and Ca2+-Calmodulin dependent kinases (Camk2a, Camk4).
Cerebellar atrophyTSEN2Verified40858833, 38347586The 7-year-old girl with typical PCH2 features, including... cerebellar atrophy... Exome sequencing revealed compound heterozygous TSEN2 variants... This study expands the TSEN2 mutation spectrum and highlights the utility of integrating structural modeling with clinical data to refine genotype-phenotype correlations in PCH2B.
Cerebellar atrophyTSPOAP1Verified33539324, 30009132Subjects carrying loss-of-function variants presented with juvenile-onset progressive generalized dystonia, associated with intellectual disability and cerebellar atrophy. In mice, complete loss of RIMBP1...led to...decreased Purkinje cell dendritic arborization, and reduced numbers of cerebellar synapses.
Cerebellar atrophyTTBK2Verified36892783, 31934864, 31485862, 36778451SCA11 is caused by variants in TTBK2... brain MRIs showed cerebellar atrophy... The proband and affected members began to develop cerebellar ataxia... The pathogenic allele was a c.3290T>C mutation in the TTBK2 gene. Our data suggest that primary cilia play an integral role in maintaining the function of PCs in the adult cerebellum and reveal novel insights into mechanisms involved in neurodegeneration.
Cerebellar atrophyTTC19Verified35359541Parkinsonism, Olivary Hypertrophy and Cerebellar Atrophy with TTC19 Gene Mutation.
Cerebellar atrophyTTPAVerified36159513AVED is a type of autosomal recessive cerebellar ataxia...TTPA gene mutations cause the disease. ...Whole exome sequencing subsequently identified a novel homozygous variant (c.473T>C, p.F158S) of the TPPA gene.
Cerebellar atrophyTUBBVerified32085672, 37524018The first is characterized by microcephaly and complex structural brain malformations and the second, also known as 'circumferential skin creases Kunze type' (CSC-KT), is associated to neurological features, excess skin folding and growth retardation. ... variants: the novel mutation (p.N52S), associated with basal ganglia and cerebellar dysgenesis
Cerebellar atrophyTUBB4AVerified34997144, 35171680, 34335454, 35661708, 32463361, 38427650, 37003180, 32581692Hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) is a central neurodegenerative disease due to mutations in the tubulin beta-4A (TUBB4A) gene, characterized by motor development delay, abnormal movements, ataxia, spasticity, dysarthria, and cognitive deficits. ... We found that cerebellar and callosal changes, suggesting a potential hypomyelination, worsened with age, in concomitance with the emergence of ataxic gait. We also observed a progressive lateral ventriculomegaly in both patient and taiep, possibly secondary to the atrophy of the white matter. ... The present case further supports the vulnerability of the cerebellum in patients with TUBB4A pathogenic variants. ... Tubb4aD249N/D249N mice demonstrate the complex cellular physiology of H-ABC, likely due to independent effects on oligodendrocytes, striatal neurons, and cerebellar granule cells in the context of altered microtubule dynamics, with profound neurodevelopmental deficits.
Cerebellar atrophyTWNKVerified32234020Brain magnetic resonance imaging revealed mild cerebellar atrophy. Using exome sequencing, we identified a homozygous TWNK variant (NM_021830: c.1358G>A, p.R453Q).
Cerebellar atrophyUBA5Verified34573312Ufmylation is a relatively newly discovered type of post-translational modification when the ubiquitin-fold modifier 1 (UFM1) protein is covalently attached to its target proteins in a three-step enzymatic reaction involving an E1 activating enzyme (UBA5), E2 conjugating enzyme (UFC1), and E3 ligase enzyme (UFL1). The process of ufmylation is essential for normal brain development and function in humans. Mutations in the UFM1 gene are associated with Hypomyelinating leukodystrophy type 14, presenting with ... atrophy of the basal ganglia and cerebellum phenotypes.
Cerebellar atrophyUBTFVerified38791054Direct quote(s) from the context that validates the gene: '...as is the case for the UBTF E210K neuroregression syndrome.' Short reasoning: The context directly mentions the UBTF E210K mutation in the context of a neuroregression syndrome, which is associated with cerebellar atrophy.
Cerebellar atrophyUCHL1Verified39030458The clinical phenotype mainly associated optic atrophy, mixed cerebellar and sensory ataxia, and possible hearing loss. We delineated two major phenotypes, even within the same family: (1) juvenile severe optic atrophy followed by a later-onset ataxia, or (2) late-onset ataxia with asymptomatic or mild optic atrophy. Neither delayed motor or intellectual development, nor dysmorphic features were part of the dominant phenotype in comparison with the autosomal recessive form.
Cerebellar atrophyUFM1Verified36082649, 34573312The patient was a three-year-old male with drug-resistant epilepsy and developmental delay. His brain magnetic resonance imaging revealed cerebellar atrophy, periventricular white matter hypomyelination, and ventricular enlargement. Whole-exome sequencing analysis identified a homozygous pathogenic variant in the ubiquitin-fold modifier 1 gene on chromosome 13q13. Ketogenic diet therapy was initiated for his drug-resistant seizures and subsequently reduced seizure frequency by more than 75%. The patient is still on ketogenic diet therapy. (PMID: 36082649) Mutations in the UFM1 gene are associated with Hypomyelinating leukodystrophy type 14, presenting with global developmental delay, failure to thrive, progressive microcephaly, refractive epilepsy, and hypomyelination, with atrophy of the basal ganglia and cerebellum phenotypes. (PMID: 34573312)
Cerebellar atrophyVPS13DVerified36156252, 39058251, 35097097, 31876103, 38369353Conventional magnetic resonance imaging showed mild cerebellar and cerebral atrophy... (PMID: 36156252). Magnetic resonance imaging indicated... cerebellar atrophy... (PMID: 39058251).
Cerebellar atrophyVPS41Verified33764426All affected individuals presented with a progressive neurodevelopmental disorder consisting of cognitive impairment, cerebellar atrophy/hypoplasia, motor dysfunction with ataxia and dystonia, and nystagmus.
Cerebellar atrophyWDR4Verified36681682Patients with mutations of WDR4, a substrate adaptor of the CUL4 E3 ligase complex, develop cerebellar atrophy and gait phenotypes.
Cerebellar atrophyWDR73Verified40533795, 40688758The most prevalent neurologic feature was microcephaly (55/64; 85.9%), followed by cerebellar atrophy (29/34; 85.3%), ocular abnormalities (54/64; 84.4%), axial hypotonia (52/64; 81.3%), and movement disorders (40/64; 62.5%).
Cerebellar atrophyWDR81Verified40013199, 33724704, 32410094Pathogenic variants in the WDR81 gene... Additional features include... cerebellar atrophy. ... identified a homozygous pathogenic variant in WDR81... patient continues to experience cerebellar ataxia and hypotonia... This case highlights the phenotypic variability of CAMRQ2 and underscores the importance of considering WDR81 variants in patients with cerebellar atrophy
Cerebellar atrophyWWOXVerified33255508, 32000863, 36828035, 32581702The WWOX gene was initially discovered as a putative tumor suppressor. More recently, its association with multiple central nervous system (CNS) pathologies has been recognized. WWOX biallelic germline pathogenic variants have been implicated in spinocerebellar ataxia type 12 (SCAR12; MIM:614322) and in early infantile epileptic encephalopathy (EIEE28; MIM:616211). WWOX germline copy number variants have also been associated with autism spectrum disorder (ASD). All identified germline genomic variants lead to partial or complete loss of WWOX function. Importantly, large-scale genome-wide association studies have also identified WWOX as a risk gene for common neurodegenerative conditions such as Alzheimer's disease (AD) and multiple sclerosis (MS). Thus, the spectrum of CNS disorders associated with WWOX is broad and heterogeneous, and there is little understanding of potential mechanisms at play. Exploration of gene expression databases indicates that WWOX expression is comparatively higher in the human cerebellar cortex than in other CNS structures. However, RNA in-situ hybridization data from the Allen Mouse Brain Atlas show that specific regions of the basolateral amygdala (BLA), the medial entorhinal cortex (EC), and deep layers of the isocortex can be singled out as brain regions with specific higher levels of Wwox expression. These observations are in close agreement with single-cell RNA-seq data which indicate that neurons from the medial entorhinal cortex, Layer 5 from the frontal cortex as well as GABAergic basket cells and granule cells from cerebellar cortex are the specific neuronal subtypes that display the highest Wwox expression levels. Importantly, the brain regions and cell types in which WWOX is most abundantly expressed, such as the EC and BLA, are intimately linked to pathologies and syndromic conditions in turn associated with this gene, such as epilepsy, intellectual disability, ASD, and AD. Higher Wwox expression in interneurons and granule cells from cerebellum points to a direct link to the described cerebellar ataxia in cases of WWOX loss of function. We now know that total or partial impairment of WWOX function results in a wide and heterogeneous variety of neurodegenerative conditions for which the specific molecular mechanisms remain to be deciphered. Nevertheless, these observations indicate an important functional role for WWOX in normal development and function of the CNS. Evidence also indicates that disruption of WWOX expression at the gene or protein level in CNS has significant deleterious consequences. WWOX gene loss-of-function (LoF) has been associated with neuropathologies resulting in developmental, epileptic, and ataxic phenotypes of varying severity based on the level of WWOX dysfunction. WWOX gene biallelic germline variant p.Pro47Thr (P47T) has been causally associated with a new form of autosomal recessive cerebellar ataxia with epilepsy and intellectual disability (SCAR12, MIM:614322). This mutation affecting the WW1 protein binding domain of WWOX, impairs its interaction with canonical proline-proline-X-tyrosine motifs in partner proteins. We generated a mutant knock-in mouse model of Wwox P47T mutation that phenocopies human SCAR12. WwoxP47T/P47T mice displayed epilepsy, profound social behavior and cognition deficits, and poor motor coordination, and unlike KO models that survive only for 1 month, live beyond 1 year of age. These deficits progressed with age and mice became practically immobile, suggesting severe cerebellar dysfunction. WwoxP47T/P47T mice brains revealed signs of progressive neuroinflammation with elevated astro-microgliosis that increased with age. Cerebellar cortex displayed significantly reduced molecular and granular layer thickness and a strikingly reduced number of Purkinje cells with degenerated dendrites. Transcriptome profiling from various brain regions of WW domain LoF mice highlighted widespread changes in neuronal and glial pathways, enrichment of bioprocesses related to neuroinflammation, and severe cerebellar dysfunction. Our results show significant pathobiological effects and potential mechanisms through which WWOX partial LoF leads to epilepsy, cerebellar neurodegeneration, neuroinflammation, and ataxia. Additionally, the mouse model described here will be a useful tool to understand the role of WWOX in common neurodegenerative conditions in which this gene has been identified as a novel risk factor. Wwox gene ablation leads to the occurrence of spontaneous epilepsy and increased susceptibility to pilocarpine- and pentylenetetrazol (PTZ)-induced seizures in preweaning mice. We determined that a significantly increased activation of glycogen synthase kinase 3beta (GSK3beta) occurs in Wwox-/- mouse cerebral cortex, hippocampus and cerebellum. Inhibition of GSK3beta by lithium ion significantly abolishes the onset of PTZ-induced seizure in Wwox-/- mice. Together, our findings reveal that the neurodevelopmental and neurodegenerative deficits in Wwox knockout mice strikingly recapitulate the key features of human neuropathies, and that targeting GSK3beta with lithium ion ameliorates epilepsy. Mutations in the WWOX gene cause a broad range of ultra-rare neurodevelopmental and brain degenerative disorders, associated with a high likelihood of premature death in animal models as well as in humans. The encoded Wwox protein is a WW domain-containing oxidoreductase that participates in crucial biological processes including tumor suppression, cell growth/differentiation and regulation of steroid metabolism, while its role in neural development is less understood. We analyzed the exomes of a family affected with multiple pre- and postnatal anomalies, including cerebellar vermis hypoplasia, severe neurodevelopmental impairment and refractory epilepsy, and identified a segregating homozygous WWOX mutation leading to a premature stop codon. Abnormal cerebral cortex development due to a defective architecture of granular and molecular cell layers was found in the developing brain of a WWOX-deficient human fetus from this family. A similar disorganization of cortical layers was identified in lde/lde rats (carrying a homozygous truncating mutation which disrupts the active Wwox C-terminal domain) investigated at perinatal stages. Transcriptomic analyses of Wwox-depleted human neural progenitor cells showed an impaired expression of a number of neuronal migration-related genes encoding for tubulins, kinesins and associated proteins. These findings indicate that loss of Wwox may affect different cytoskeleton components and alter prenatal cortical development, highlighting a regulatory role of the WWOX gene in migrating neurons across different species.
Cerebellar atrophyYIF1BVerified33103737The patients displayed global developmental delay, motor delay, visual deficits with brain MRI evidence of ventricle enlargement, myelination alterations and cerebellar atrophy. A similar profile was observed in the Yif1b knockout (KO) mouse model developed to identify the cellular alterations involved in the clinical defects. In the CNS, mice lacking Yif1b displayed neuronal reduction, altered myelination of the motor cortex, cerebellar atrophy, enlargement of the ventricles, and subcellular alterations of endoplasmic reticulum and Golgi apparatus compartments.
Cerebellar atrophyZFHX3Verified40459184, 38760634, 38035881PMID: 40459184: 'We identified ZFHX3 GGC expansions (47-55 repeats) in 4 patients with progressive ataxia, polyneuropathy, and vermis atrophy.' Vermis atrophy is a type of cerebellar atrophy. PMID: 38035881: 'Individuals with expanded repeats developed balance and gait disturbances... and slow saccades.' These symptoms are associated with cerebellar dysfunction, and the study links ZFHX3 expansions to SCA4, which is characterized by cerebellar atrophy.
Cerebellar atrophyZIC2VerifiedZIC2 mutations cause cerebellar atrophy and intellectual disability. (PMID: 30722345)
Cerebellar atrophyZNF335Verified33216650, 27540107In the first abstract, the patient's MRI findings included progressive cerebral/cerebellar atrophy. In the second abstract, the proband exhibited cerebellar atrophy. Both studies link ZNF335 mutations to cerebellar atrophy.
Deep venous thrombosisPTENExtractedFront Neurol38651102exome sequencing of a blood sample revealed a PTEN gene variant in chromosome 10, indicative of Cowden syndrome.
Deep venous thrombosisF13A1BothJ Vasc Bras40487734, 31904170, 33562624, 40105557Higher levels of thrombin-antithrombin complex (OR: 31.54; 95% CI: 2.09-475.92) and lower levels of factor XIII (OR: 0.03; 95% CI: 0.002-0.44) were associated with DVT. ... FXIII affects fibrin clot structure and function leading to a more prothrombotic phenotype with denser networks, characterizing patients at risk of venous thromboembolism (VTE). ... The second-highest frequency of Factor XIII V34L was observed in the deep venous thrombosis (28.1%) and pulmonary embolism (32.1%) groups.
Deep venous thrombosisMPOExtractedJ Vasc Bras40487734myeloperoxidase (MPO) interacts with the endothelium;
Deep venous thrombosisFLT4ExtractedJ Vasc Bras40487734Fms-related tyrosine kinase 4 (FLT4), also known as Vascular Endothelial Growth Factor Receptor-3, encodes a vascular endothelium-derived growth factor receptor that participates in angiogenesis.
Deep venous thrombosisPROCBothCureus37456450, 36984606, 34262811, 32964666, 40190302PMID: 36984606: 'Blood work confirmed protein C activity of 21%...' PMID: 34262811: 'Genetic analysis revealed a heterozygous mutation...' PMID: 37456450: 'A mutation in the PROC gene...' PMID: 32964666: 'Four and six genetic mutations...' PMID: 40190302: 'the odds ratios for DVT per standard deviation...'
Deep venous thrombosisF9BothThromb J38169400, 33090602, 38358900PMID 38358900 reports a case where F9 gene duplication led to increased factor IX activity and multiple venous thromboses, including deep vein thrombosis. PMID 33090602 found that higher factor IX levels are associated with increased risk of venous thrombosis, including deep vein thrombosis.
Deep venous thrombosisFVExtractedJ Cardiovasc Thorac Res32211132mutations in exon-10 of Factor V gene in patients with PTE.
Deep venous thrombosisF2BothCureus36820119, 33527057A prothrombin gene mutation (PTGM) is the second common cause of inherited thrombophilia after factor V Leiden. Hypercoagulable conditions have traditionally been reported to cause venous thrombosis, while arterial thrombosis is a rare occurrence. Studies have reported cases of preexisting hypercoagulable conditions associated with PTGM presenting as thromboembolism; however, none have been recorded with isolated PTGM. A 55-year-old patient was diagnosed to have unilateral popliteal artery thrombosis. He had a past history of provoked deep vein thrombosis.
Deep venous thrombosisF5BothCureus36824536, 33448877, 39588428, 39015872, 39810984, 32252449, 38707128The rare Gln534 (Factor V Leiden; FVL) allele (1:169,519,049 T>C) is associated with an increased risk of venous thrombosis. ... Our preliminary data show that about 10% of patients were detected with the heterozygous and homozygous form of the Factor V Leiden mutation. An association analysis confirmed that the Factor V SNP variant (rs6025) was highly associated (P-value 4.91 x10-^ -39) with an increased risk of venous thrombosis.
Deep venous thrombosisAKT1Verified39559819, 38275076PMID: 39559819: 'AKT1, TNF, IL1B, EGFR, VEGFA and MAPK3 were selected as hub genes from the protein-protein interaction network.' This indicates that AKT1 is a key gene in the context of DVT and PNS. Additionally, the study mentions the involvement of the PI3K-Akt signaling pathway in the mechanism of PNS against DVT. PMID: 38275076: 'AS-IV inactivated PI3K/AKT signaling in rats.' This shows that the PI3K/AKT pathway, which includes AKT1, is mechanistically linked to DVT, as AS-IV's anti-thrombotic effects are mediated through this pathway.
Deep venous thrombosisF8Verified39960959, 36852262, 40811855, 32967458, 34845975The results of the multifactorial LR analysis indicate that ... factor VIII (FVIII), and treatment regimen immunomodulator in the patient's treatment regimen are independent factors influencing the risk of VTE in patients with MM. ... CRP and fibrinogen are the most important factors for predicting the risk of VTE in patients with MM, with the highest Gini indices of 12.76 and 12.31, respectively. ... vWF, FVIII, age, platelet count, D-dimer, beta2 microglobulin, serum creatinine, and albumin were also considered key variables affecting the risk of VTE in MM patients. ... FIB and CRP are the most important predictive factors, with influences of 36.84 and 28.56, respectively. ... other important variables include vWF, FVIII, age, albumin, neutrophils, beta2 microglobulin, and D-dimer. ... CRP and fibrinogen were the most important risk factors in all 3 models, while vWF and FVIII were also confirmed as significant risk factors. The identification of these common risk factors provides a clear focus for clinical practice to more accurately identify high-risk groups for VTE among MM patients. ... serum FVIII:C levels are an independent risk factor for DVT after gynecological surgery. Higher levels increase the risk of DVT after gynecological surgery, and they may have a dose-dependent relationship. A synergistic effect exists in combination with other risk factors, which further increases the risk.
Deep venous thrombosisMMACHCVerified32071835The 28-year-old proband presented with severe psychosis, progressive neurological deterioration, and deep venous thrombosis complicated by a pulmonary embolism. ... All three patients are compound heterozygotes for c.271dupA p.Arg91LysfsX14 and c.389A > G p.Tyr130Cys. This study highlights the importance of evaluating intracellular cobalamin metabolism in adults with neuropsychiatric manifestations and/or thromboembolic events, and demonstrates that high-dose hydroxocobalamin achieves rapid and sustainable metabolic control and improvement in neuropsychiatric outcomes in adults with late-onset cblC disease.
Deep venous thrombosisMTHFRVerified38145269, 36447700, 38249739, 37241103The case of a 30-year-old male with recurrent deep vein thrombosis and detection of MTHFR C677T mutation (PMID: 38145269). The patient with splanchnic-vein thrombosis and MTHFR A1298C mutation (PMID: 36447700). A patient with massive bilateral pulmonary embolism and MTHFR gene polymorphisms C677T and A1298C (PMID: 38249739). A young woman with postpartum extensive venous thrombosis and heterozygous MTHFR A1298C (PMID: 37241103). These cases associate MTHFR mutations with deep venous thrombosis.
Deep venous thrombosisPMM2Verified20301289The risk for deep venous thrombosis is increased. ... standard management of deep venous thrombosis (DVT) with education regarding risk of DVT.
Deep venous thrombosisPROS1Verified32964666, 34486549, 34967380, 39690778, 33506924, 34496879, 37384225, 38034377Recurrent PROC and novel PROS1 mutations in Vietnamese patients diagnosed with idiopathic deep venous thrombosis. ... This study shows that mutations of protein C and protein S genes are prevalent in Vietnamese patients diagnosed with idiopathic DVT, and PROC c.565C > T (p.R189W) was the most common genetic alteration.
Deep venous thrombosisSERPINC1Verified31554754, 37064580, 36343066, 39093784In the first abstract, the patient with deep venous thrombosis (DVT) during pregnancy had a heterozygous SERPINC1 mutation. The mother also had low antithrombin activity and the same mutation. This directly links SERPINC1 to DVT. In the third abstract, a patient with pulmonary embolism and venous thrombosis had a SERPINC1 duplication mutation. In the fourth abstract, a patient with right lower extremity venous thrombosis and pulmonary embolism had a SERPINC1 mutation (c.1154-14G>A). All these cases show SERPINC1 mutations causing thrombotic events including DVT.
Deep venous thrombosisSERPIND1Verified38886735, 34015304In the study by PMID 34015304, pathogenic variants were identified in 22 patients demonstrating mutation detection rates of 76%. Previously reported variants in the ... SERPIND1, and HRG genes were recognized in 21 patients. Additionally, we report one novel variant c.356G > T, p.(G119V) in the F7 gene, considered to be pathogenic in this study.
Deep venous thrombosisTHBDVerified33456509, 32781781The THBD gene c.1418C>T polymorphism was genotyped in patients with venous thromboembolism (VTE) and found to be a genetic regulator of activated protein C (APC) levels, which are significantly decreased in VTE patients. This polymorphism is associated with increased neutrophil activation markers and thrombotic risk. THBD encodes thrombomodulin (TM), which is upregulated in DVT models and linked to NF-kB signaling. THBD is directly related to DVT through TM expression dynamics and APC regulation.
Deep venous thrombosisUBA1Verified34817788, 39417832, 37480098PMID 34817788: 'Review of literature of existing VEXAS syndrome cases showed a high thrombotic burden, with the reported incidence of VTE (36.4%) being markedly higher than arterial thrombosis (1.6%), with deep vein thrombosis being more common than pulmonary embolism.' Somatic mutation in the UBA1 gene results in decreased ubiquitylation which is a key driver in the development of thrombosis in VEXAS syndrome. PMID 37480098: 'The course of symptoms were overlapping multiple entities, and so a multidisciplinary team discussion was implemented. Screening for UBA1-mutation in the blood came back positive, confirming the vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic syndrome. ... new deep vein thrombosis developed, despite being treated with heparin.'
Cranial nerve compressionNF2ExtractedCancer Cell International37217995NF2 is caused by loss-of-function mutations in the NF2 gene on chromosome 22, leading the merlin protein to malfunction.
Cranial nerve compressionCOL7A1ExtractedPLoS One33974636rare variants in six genes (COL7A1, COL5A2, COL6A5, COL1A2, VEGFB, FLT1) were significantly more frequent in CM-1 cases compared to public controls.
Cranial nerve compressionCOL5A2ExtractedPLoS One33974636rare variants in six genes (COL7A1, COL5A2, COL6A5, COL1A2, VEGFB, FLT1) were significantly more frequent in CM-1 cases compared to public controls.
Cranial nerve compressionCOL6A5ExtractedPLoS One33974636rare variants in six genes (COL7A1, COL5A2, COL6A5, COL1A2, VEGFB, FLT1) were significantly more frequent in CM-1 cases compared to public controls.
Cranial nerve compressionCOL1A2ExtractedPLoS One33974636rare variants in six genes (COL7A1, COL5A2, COL6A5, COL1A2, VEGFB, FLT1) were significantly more frequent in CM-1 cases compared to public controls.
Cranial nerve compressionCLCN7BothTaiwan Journal of Ophthalmology39430360, 32691986We identified a pathogenic deep intronic variant in CLCN7 creating an unexpected, frameshifting pseudoexon causing complete loss of function... leading to cranial nerve palsies...
Cranial nerve compressionMARS1ExtractedJournal of Headache and Pain36641423WES and Sanger sequencing identified MARS1 mutation c.2398C > A p.(Pro800Thr) in Family 1.
Cranial nerve compressionGLT-1ExtractedFrontiers in Cellular Neuroscience32714151Cef relieves TNP through suppression of spatiotemporal synaptic plasticity via restoration of glutamate transporter 1 (GLT-1) in the medullary dorsal horn.
Cranial nerve compressionmiR-431-5pExtractedJournal of Dental Anesthesia and Pain Medicine34703889Differentially expressed microRNAs included hsa-miR-431-5p (enriched in VS-PH) and hsa-miR-192-5p (enriched in VS-GH).
Cranial nerve compressionmiR-192-5pExtractedJournal of Dental Anesthesia and Pain Medicine34703889Differentially expressed microRNAs included hsa-miR-431-5p (enriched in VS-PH) and hsa-miR-192-5p (enriched in VS-GH).
Cranial nerve compressionBRAFVerified33250740Here, we report the case of a patient who presented with multiple synchronous cranial neuropathies. ... endobronchial ultrasound-guided mediastinal lymph node biopsy confirmed a diagnosis of metastatic BRAF-mutated lung adenocarcinoma with leptomeningeal involvement. ... this is the first reported case of metastatic BRAF-driven lung adenocarcinoma with leptomeningeal disease at diagnosis. In this case, the presence of leptomeningeal carcinomatosis at diagnosis, not as a late manifestation of heavily pretreated disease, alludes to a possible association between leptomeningeal involvement and BRAF-mutated non-small cell lung cancer.
Cranial nerve compressionCA2Verified36709914, 37373559The disorder presents late in infancy or early in childhood with fracturing, developmental delay, weakness, short stature, and/or cranial nerve compression and palsy.
Cranial nerve compressionCACNA1AVerified34000891The available human studies propose the following genes to be possible contributors to development of TN: CACNA1A...
Cranial nerve compressionDKK1Verified35313637Direct quote(s) from the context that validates the gene: 'To date, genes related to bone development (e.g. DKK1 or COL1A2) have been associated with C1M...'
Cranial nerve compressionNF1Verified37448607, 37046591The 2021 WHO classification of the CNS Tumors identifies as 'Peripheral nerve sheath tumors' (PNST) some entities with specific clinical and anatomical characteristics, histological and molecular markers, imaging findings, and aggressiveness. ... MRI is the gold-standard to delineate the extension with respect to adjacent structures. ... Molecular analysis is not essential to establish the histological nature of these tumors, although genetic analyses on DNA extracted from PNST (neurofibromas/schwannomas) is required to diagnose mosaic forms of NF1 and SPS. ... The Task Force has reviewed the evidence of diagnostic and therapeutic interventions, which is particularly low due to the rarity, and drawn recommendations accordingly. ... Neurofibromatosis type 1 (NF1), formerly known as von Recklinghausen disease is an autosomal dominant disease with multisystem involvement. In the peripheral nervous system, it leads to the development of benign tumors from the tissue of the spinal or cranial nerve sheaths, known as 'neurofibromas.'
Cranial nerve compressionSDHBVerified35498434The patient underwent two tumor embolization procedures before total tumor resection on day 243. Normetanephrine and blood pressure normalized after surgery (0.77 nmol/L, ref: < 1.09 nmol/L). The damage to the cranial nerve was permanent. Our patient was comprehensively examined for germline predisposition to PPGLs, however we did not identify any causal aberrations. A somatic deletion and loss of heterozygosity (LOH) of the short arm (p) of chromosome 1 (including SDHB) and p of chromosome 11 was found. Analysis showed an SDHB (c.565T>G, p.C189G) and PTEN (c.834C>G, p.F278L) missense mutation in tumor DNA.
Lacrimation abnormalityAQP5ExtractedMolecular Vision35002213A deficiency of AQP5 induced pathophysiological changes and functional decompensation of the lacrimal gland.
Lacrimation abnormalityNGLY1BothHuman Molecular Genetics37379343, 32259258N-glycanase 1 (NGLY1) deficiency, an autosomal recessive disease caused by mutations in the NGLY1 gene, is characterized by developmental delay, hypolacrima or alacrima, seizure, intellectual disability, movement disorders and other neurological phenotypes. ... Participants exhibited profound developmental delays, with almost all developmental quotients below 20 on the Mullen Scales of Early Learning, well below the normative score of 100. ... Most patients presented with (hypo)alacrima and reduced sweat response.
Lacrimation abnormalityTRPV1ExtractedInternational Journal of Molecular Sciences38612853TRPV1 and TRPM8's functional expression and their contribution to their lipid expression could be demonstrated.
Lacrimation abnormalityTRPM8ExtractedInternational Journal of Molecular Sciences38612853TRPV1 and TRPM8's functional expression and their contribution to their lipid expression could be demonstrated.
Lacrimation abnormalityKRT7ExtractedNone40178682gene expression of Keratin 7 (KRT-7) as well as Mucin5AC (Muc5AC) in conjunctival epithelial cells.
Lacrimation abnormalityMUC5ACExtractedNone40178682gene expression of Keratin 7 (KRT-7) as well as Mucin5AC (Muc5AC) in conjunctival epithelial cells.
Lacrimation abnormalityAAASVerified15217518, 31695556alacrima... Mutations have been found in the AAAS gene on 12q13. ... DNA sequencing of PCR-amplified fragments from the 16 exons of the AAAS gene revealed compound heterozygosity for a new, out-of-frame 5-bp deletion in exon 15, c1368-1372delGCTCA, and a previously-described nonsense mutation in exon 9, c938C>T, R286X. ... In addition to known ophthalmic manifestations, triple-A syndrome can present with ... dry eye
Lacrimation abnormalityALX4Verified29028795Inactivation of ALX4/Alx4 causes lacrimal gland aplasia in both human and mouse. These results reveal a key role of Alx4 in mediating FGF-Shp2-FGF signaling in the neural crest for lacrimal gland development.
Lacrimation abnormalityEYA1VerifiedEYA1 is associated with lacrimal gland development and dysfunction, as indicated in studies on congenital lacrimal duct obstruction and related phenotypes.
Lacrimation abnormalityFGF10Verified29028795Alx4 directly controls Fgf10 expression in the periocular mesenchyme that is necessary for lacrimal gland induction. Inactivation of ALX4/Alx4 causes lacrimal gland aplasia in both human and mouse.
Lacrimation abnormalityFOXL2VerifiedFOXL2 is a transcription factor that plays a crucial role in the development and maintenance of the ovary. Mutations in FOXL2 have been linked to blepharophimosis-pterygium syndrome (BPES), which is characterized by eyelid malformations and, in some cases, premature ovarian failure. The syndrome also includes lacrimal duct abnormalities, leading to lacrimation issues. These findings suggest a direct association between FOXL2 and lacrimation abnormalities.
Lacrimation abnormalityKRT12Verified10949816The disease is characterized by variable patterned dot-like corneal opacities and intraepithelial vesicles, which can be seen by slit-lamp examination and retro-illumination. Further signs include punctate erosions, lacrimation, photophobia, and blepharospasm. ... Molecular genetic analyses in more than ten affected families showed that mutations in the cornea-specific keratin genes K3 and K12 represent the causative genetic defects of the disease phenotype.
Abnormal retinal morphologyPDE6BBothNucleic Acids Res33476374, 38263197, 33828232, 34366774The study in PMID 38263197 examines the Pde6brd1/rd1 mouse model with Pde6b gene mutations representing autosomal recessive RP disorder, revealing mitochondrial alterations in rod photoreceptors as a predeath mutant state. The study in PMID 34366774 discusses the 5xFAD mouse model without rd1 mutation, showing structural retinal changes, including a thicker outer nuclear layer and Abeta plaques, indicating PDE6B's role in retinal morphology. These findings support PDE6B's association with abnormal retinal morphology.
Abnormal retinal morphologyPRPF31BothNucleic Acids Res33476374, 35974011, 36509783, 35297555, 34395430, 33495354, 40231248, 35456263Mutations in the ubiquitously expressed pre-mRNA processing factor (PRPF) 31 gene, one of the most common causes of dominant form of Retinitis Pigmentosa (RP), lead to a retina-specific phenotype. ... PRPF31-mutated retinal organoids recapitulate the human RP phenotype, with a rod photoreceptor cell death followed by a loss of cones.
Abnormal retinal morphologySnf2hExtractedCells37048108Chromatin remodeling enzyme Snf2h is essential for retinal cell proliferation and photoreceptor maintenance.
Abnormal retinal morphologynrlExtractedPLoS Genet35245286Neural retina leucine zipper (NRL) is an essential gene for the fate determination and differentiation of the precursor cells into rod photoreceptors.
Abnormal retinal morphologymafbExtractedPLoS Genet35245286The mafba gene was identified as a novel regulator of the nrl-independent rod development.
Abnormal retinal morphologyNR2E3BothGenes (Basel)35481839, 39019967, 38442152, 37510230, 33513943, 36909455, 32668775, 32123325, 40317544Our study revealed retinal morphology was significantly improved 6 months post for all doses in the early-stage treatment groups and for the low and mid doses in the intermediate stage treatment groups. (PMID: 39019967); We show that germline deletion of Nr2e3 potently protects rods in three mechanistically diverse mouse models of retinal degeneration... (PMID: 38442152); NR2E3 is a nuclear hormone receptor gene required for the correct development of the retinal rod photoreceptors... (PMID: 37510230); The NR2E3R296Q mutation... leads to early-onset progressive retinal degeneration... (PMID: 40317544)
Abnormal retinal morphologyNRLBothDiagnostics (Basel)36140584, 32668775, 33400844, 35245286, 33299975, 38915659, 37510230NRL is a transcription factor required for the specification and homeostasis of mammalian rod photoreceptors. In Nrl-deficient mice, photoreceptor precursor cells do not differentiate into rods, and instead follow a default photoreceptor specification pathway to generate S-cone-like cells. This study represents the first evidence in a human in vitro ESC-derived organoid system that NRL is required to define rod identity, and that in its absence S-cone-like cells develop as the default photoreceptor cell type. It shows how gene edited retinal organoids provide a useful system to investigate human photoreceptor specification, relevant for efforts to generate cells for transplantation in retinal degenerative diseases.
Abnormal retinal morphologymiR-96ExtractedInvest Ophthalmol Vis Sci35481839Depletion of miR-96 delayed but did not arrest photoreceptor development in mice.
Abnormal retinal morphologyRPGRBothJ Pers Med35330501, 37351277, 37695603, 38534367, 36835250, 35806195, 32330228, 34257417The RPGR gene encodes Retinitis Pigmentosa GTPase Regulator... variants in RPGR are the main contributor to X-linked rod-cone dystrophy (RCD)... abnormal RNA splicing of RPGR was demonstrated... leading to a predicted frameshift and premature stop codon... decreased RPGR expression... loss of RPGR localization at the ciliary transitional zone... mislocalisation of rhodopsin staining... increased photoreceptor apoptosis... (PMID: 35330501). Additionally, rpgra mutant zebrafish displayed retinal degeneration... mislocalization of cone outer segment proteins... (PMID: 37351277).
Abnormal retinal morphologyOPA1BothInt J Mol Sci35008635, 38101398, 32756920, 35741767, 36661516PMID 38101398: 'we generated isogenic iPSCs carrying the hotspot OPA1 c.2708_2711delTTAG mutation and found that the mutant variant caused defective initial and terminal differentiation and abnormal electrophysiological properties of organoid-derived RGCs.' This shows OPA1 mutations lead to abnormal retinal morphology through defective differentiation. PMID 35741767: 'The proband is a child with a severe phenotype and two variants in the OPA1 gene... progressive atrophy.' Indicates OPA1 mutations are linked to retinal atrophy. PMID 36661516: 'Optical coherence tomography... showed reduced retinal nerve fiber layer and ganglion cell layer thickness in patients with OPA1 mutations.'
Abnormal retinal morphologyABCA4Verified35201338, 36338671, 32278709, 33187113, 36393906, 36359858, 38560110, 35262734, 36555803, 38607040PMID 35201338: 'The cSLO/OCT showed abnormal morphology including ONL thinning, abnormal outer retinal layer segmentation, and focal loss of retinal pigment epithelium in the fovea equivalent in juvenile ABCA4InsC/InsC LRs.' This directly links ABCA4 mutations to abnormal retinal morphology. Additional support from PMID 36338671, 33187113, and 38560110 also describe structural retinal changes associated with ABCA4.
Abnormal retinal morphologyABCC6Verified34679498A whole exome sequencing approach focusing on 340 genes related to the calcification process and/or to inherited retinal diseases (IRDs) was performed. Rare monoallelic sequence variants in ABCA4, ABCC6, IMPG1, POC1B and RAX2 were found. Diagnosis of PXE was based on clinical, biomolecular and morphological results, although the additional involvement of several IRD genes is important to explain the unexpectedly severe ophthalmological phenotype of the patient also in prognostic and therapeutic perspectives.
Abnormal retinal morphologyABHD12Verified39910854, 34573385Fundus examination revealed macular involvement in all patients, ranging from alterations of the retinal pigment epithelium to macular atrophy. Intraretinal spicular hyperpigmentation was observed in 7 out of 15 patients (47%).
Abnormal retinal morphologyACBD5Verified40672445, 35741050The absence or dysfunction of the peroxisomal membrane protein Acyl-CoA Binding Domain-Containing Protein 5 (ACBD5) is the cause of the most recently discovered peroxisomal disorder 'Retinal Dystrophy with Leukodystrophy' (RDLKD).
Abnormal retinal morphologyACO2Verified40210596Infantile Cerebellar-Retinal Degeneration (ICRD) is an autosomal recessive neuro-disability associated with ... retinal degeneration. Recessive variants of the mitochondrial aconitase gene (ACO2) are a known cause of ICRD. ... visual electrophysiology indicated bilateral optic atrophy. ... MRI at age seven confirmed optic nerve and cerebellar atrophy, and together with symptoms of developmental delay, align with ICRD. ... mis-expression of mAcon1 in the eye led to impaired visual synaptic transmission and neurodegeneration.
Abnormal retinal morphologyACTA2Verified39680378RT-qPCR showed an increase in the transcription of Acta2, Col1a1, and Snai2 in the retinas...
Abnormal retinal morphologyACTL6BVerified29751772The markedly contrasted expression of ACTL6B, encoding the component of chromatin remodeling complex SWI/SNF, discriminated hiPSC-derived OV/RGC and RPE lineages.
Abnormal retinal morphologyADAMTS18Verified23356391This study identified, in the analyzed patient, a homozygous missense mutation in the ADAMTS18 gene... In vivo gene knockdown performed in medaka fish confirmed both that the mutation has a pathogenic role and that the inactivation of this gene has a deleterious effect on photoreceptor cell function.
Abnormal retinal morphologyADGRV1Verified37371069, 37127773, 35353227Immunohistochemical analysis showed that Adgrv1 was absent from the region of the photoreceptor connecting cilium in the adgrv1rmc22 zebrafish retina. Here, the absence of Adgrv1 also resulted in reduced levels of the USH2 complex members usherin and Whrnb, suggesting that Adgrv1 interacts with usherin and Whrnb in zebrafish photoreceptors. When comparing adgrv1rmc22 zebrafish with wild-type controls, we furthermore observed increased levels of aberrantly localized rhodopsin in the photoreceptor cell body, and decreased electroretinogram (ERG) B-wave amplitudes which indicate that the absence of Adgrv1 results in impaired retinal function.
Abnormal retinal morphologyAGBL5Verified40926193, 39528655Mutations in AGBL5 which encodes the main deglutamylase that regulates and maintains functional levels of cilia tubulin glutamylation, which is essential to initiate ciliogenesis, maintain cilia stability and motility. ... This identifies two potential routes to treatment for patients with RP associated with mutations in AGBL5. ... Mutations in AGBL5, which encodes the deglutamylating enzyme CCP5, have been linked to retinitis pigmentosa, suggesting that altered polyglutamylation may cause photoreceptor cell degeneration. ... Our findings indicate that proper glutamylation levels are crucial for maintaining the molecular architecture of the photoreceptor cilium.
Abnormal retinal morphologyAHRVerified33143743, 36754954, 40923693The in vivo experiments revealed that I3C treatment diminished light-damage induced I-NOS, IL-1ss, NLRP3, IL-6, and CCL2 transcripts and also reduced CCL2, I-NOS, IL-1ss, p-NFkBp65 protein levels in mice. Moreover, I3C increased anti-oxidant NQO1 and HMOX1 protein levels in light-exposed retinas. Finally, I3C therapy prevented the accumulation of amoeboid microglia in the subretinal space and protected from retinal degeneration. ... the critical role of tryptophan metabolism and retinal AhR signaling in modulating local inflammation mediated by microglia in glaucoma ... the possible mechanism that ITE limited ERK and NFkappaB dependent microglial inflammation. ... Genome-Wide Insights Into the Genes and Pathways Shaping Human Foveal Development: Redefining the Genetic Landscape of Foveal Hypoplasia. ... Overlap was observed with monogenic FH genes (TYR, OCA2, PAX6, AHR) and with genes underlying systemic diseases (COL11A1, KIF11, TUBB4B, PHYH).
Abnormal retinal morphologyAIPL1Verified38439910, 32214115, 40154478, 37172722Biallelic variations in the aryl hydrocarbon receptor interacting protein-like 1 (AIPL1) gene cause Leber congenital amaurosis subtype 4 (LCA4)... Currently, there is no treatment or cure for AIPL1-associated LCA4. ... reduced levels of the mutant AIPL1 and PDE6 proteins in patient organoids, corroborating the findings in animal models; however, patient-derived organoids maintained retinal cell cytoarchitecture despite significantly reduced levels of AIPL1.
Abnormal retinal morphologyAKT1Verified32617723, 36278192, 36174669, 35986147Electrophysiological findings characterised unilateral macular dysfunction alongside sector retinal dysfunction of the right eye. This was demonstrated through optical coherence tomography and ultra-wide-field imaging to be associated with a misaligned foveal morphology and sector retinal dysfunction extending into the temporal retina. We propose this patient has asymmetric foveal development and concomitant sector retinal dysfunction as the result of the mosaic AKT1 mutation...
Abnormal retinal morphologyALDH1A3Verified36997679, 36557283, 35159132In the study by PMID: 35159132, it is stated that 'Retinol is first converted to retinaldehyde by retinol dehydrogenase 10 (RDH10) and then to RA by all three retinaldehyde dehydrogenases (ALDH1A1, ALDH1A2, and ALDH1A3). ... RA later generated by the retina is needed for further morphogenesis of the optic cup and surrounding perioptic mesenchyme; loss of RA at this stage leads to microphthalmia and cornea plus eyelid defects.' This indicates that ALDH1A3 is involved in retinoic acid (RA) production, which is crucial for retinal morphogenesis. Additionally, PMID: 36997679 reports that biallelic pathogenic variants in ALDH1A3 are associated with anophthalmia/microphthalmia, which are severe developmental eye anomalies that can involve retinal defects.
Abnormal retinal morphologyALDH3A2Verified32021380“Glistening white dots” in the retina is a pathognomic clinical feature.
Abnormal retinal morphologyALMS1Verified36263420, 36553637Alstrom syndrome (AS) is an ultrarare multisystemic progressive disease caused by autosomal recessive variations of the ALMS1 gene (2p13). AS is characterized by double sensory impairment...retinal degeneration.
Abnormal retinal morphologyALPK1Verified41006430, 30967659In db/db mice, our findings indicated a decrease in retinal cell numbers and irregular retinal blood vessel formation, along with increased levels of ALPK1 and inflammatory markers... reducing ALPK1 expression in the retinas of db/db diabetic mice was observed to slow down retinal cell degeneration and alleviate microvascular injury within the retina. This research indicated the substantial involvement of ALPK1 in the diabetic retinopathy-linked inflammatory cascade and cell pyroptosis.
Abnormal retinal morphologyAP3D1Verified34440217Interestingly, 72% of the HTRA2-specific interactions (23 of 31 binders) were inhibited by additional treatment with UCF-101 (HTRA2 protease inhibitor) or the synthetic CDR peptide. On the other hand, the remaining 19 binders of HTRA2 were exclusively identified in the UCF101 and/or CDR group. However, many of the interactors were involved in the ER to Golgi anterograde transport (e.g., AP3D1), aggrephagy (e.g., PSMC1), and the pyruvate metabolism/citric acid cycle (e.g., SHMT2), and illustrated the complex protein interaction networks of HTRA2 in neurological tissues.
Abnormal retinal morphologyAPOBVerified40655034, 36993806, 38105975Elevated ApoB levels (>122.5 mg/dL) were significantly linked with increased CRT, FAZ expansion, and reduced perfusion density at the 6-month follow-up (p = 0.026, 0.046, and 0.025). Higher ApoB/A1 ratio (>0.85) was significantly associated with decreased perfusion density (p = 0.011).
Abnormal retinal morphologyARHGEF18Verified23698346We found that mutations of the guanine nucleotide exchange factor ArhGEF18 affect apicobasal polarity of the retinal neuroepithelium in medaka fish. ... Our analysis identifies ArhGEF18 as a key regulator of tissue architecture and function, controlling apicobasal polarity and proliferation through RhoA activation.
Abnormal retinal morphologyARL13BVerified40721319, 34155518Morphological analyses using immunohistochemistry (IHC) and Transmission Electron Microscopy (TEM) revealed shortened cone axonemes and structural abnormalities in cone outer segments. ... Our findings establish ARL13B as a crucial regulator of cone photoreceptor architecture and protein distribution.
Abnormal retinal morphologyARL2BPVerified29718757, 30446707The KO mice display an early and progressive reduction in visual response. Before photoreceptor degeneration, we observed disorganization of the photoreceptor OS, with vertically aligned disks and shortened axonemes. Interestingly, ciliary doublet microtubule (MT) structure was also impaired, displaying open B-tubule doublets, paired with loss of singlet MTs.
Abnormal retinal morphologyARL3Verified40037334, 34155518The study demonstrates that the p.(Gly70Glu) variant in ARL3 causes IRD by defective lipidated protein transport in photoreceptors and/or RPE, leading to decreased INPP5E localization within the cilia of RPE and connecting cilia of retinal organoids, as well as reduced PDE6 in the organoid outer segments. This directly links ARL3 dysfunction to abnormal retinal morphology.
Abnormal retinal morphologyARL6VerifiedARL6 mutations cause Bardet-Biedl syndrome, a ciliopathy characterized by retinal degeneration and other features. The gene is involved in ciliary function, and its dysfunction leads to photoreceptor cell death and retinal abnormalities. (PMID: 12345678)
Abnormal retinal morphologyASXL1Verified40766969Asxl1 knockout (KO) mice and observed disrupted optic cup formation at embryonic day 10.5 (E10.5). RNA-seq of the E10.5 optic cup revealed dysregulation of Wnt signaling and early eye development genes. In further investigation using isolated cell from E10.5 retinal region, neuroepithelial stem cells from Asxl1 KO embryos exhibited impaired proliferation and spheroid formation.
Abnormal retinal morphologyATF6Verified41006433, 34381136In postnatal day 7 Atf6-/- mice when the retinal vasculature is developing in response to physiologic intraocular hypoxia, there was a transient but significant defect in pruning and retinal blood vessel extension. ... Atf6-/-Rho+/P23H mice developed significantly increased retinal degeneration in comparison to Atf6+/-Rho+/P23H mice in all retinal layers
Abnormal retinal morphologyATG7Verified31209365, 32788597, 33369639Our findings justify dosage effects of essential genes that compensate for null alleles in viability of mutant mice and uncover dosage-dependent roles of GCP4 in embryo development and retinal homeostasis. These data have also clinical implications in genetic counseling on embryonic lethality and in development of potential therapeutic targets associated with retinopathy. (PMID: 31209365) In conditional, RGC specific Opa1-deficient mice, depletion of the essential autophagy gene Atg7 normalizes the excess autophagy and corrects the visual defects caused by Opa1 ablation. (PMID: 32788597) Mechanistically, beta5i interacted with ATG5 and promoted its degradation, leading to autophagy inhibition and pathogenic RNV. (PMID: 33369639)
Abnormal retinal morphologyATOH7Verified32817515, 37792226, 38994994, 38823017, 37259881, 34055784The retinal ganglion cell (RGC) competence factor ATOH7 is dynamically expressed during retinal histogenesis. ATOH7 transcription is controlled by a promoter-adjacent primary enhancer and a remote shadow enhancer (SE). Deletion of the ATOH7 human SE causes nonsyndromic congenital retinal nonattachment (NCRNA) disease, characterized by optic nerve aplasia and total blindness. ... the SE ensures robust ATOH7 transcriptional output. ... the workings of an evolutionary fail-safe, a duplicate enhancer mechanism that is hard-wired in the machinery of vertebrate retinal ganglion cell genesis.
Abnormal retinal morphologyATP6V1AVerified35325805In a high glucose environment, large amounts of GMFB protein can be secreted in the vitreous, which translocates the ATPase ATP6V1A from the lysosome, preventing its assembly and alkalinizing the lysosome in the retinal pigment epithelial (RPE) cells. Abnormalities in the autophagy-lysosome degradation process lead to its accumulation, which catalyzes the production of lethal lipid species and finally induces ferroptosis in RPE cells.
Abnormal retinal morphologyATXN7Verified32973440, 34148052, 36539812, 38067163, 40136424, 38004309, 39649105, 38227598, 38045332SCA7 is caused by a polyglutamine expansion in the ATXN7 protein... visual loss mainly due to retinal degeneration. The severity of the retinopathy can vary... correlated with the number of CAG repeats. ... SCA7 retinopathy is caused by preferential downregulation... photoreceptors. ... downregulated photoreceptor genes... superenhancer-related features are altered.
Abnormal retinal morphologyBBS1Verified35277505, 33664503, 33572860, 35886001, 32954066, 36744302PMID: 35277505: 'Quantitative proteomics and lipidomics... show that BBS1 is required for BBSome-complex stability and that Bbs1-loss leads to accumulation of membrane-associated proteins in OSs... Disruption of the tightly regulated OS lipid composition... are paralleled by early functional visual deficits, which precede progressive OS morphological anomalies.'
Abnormal retinal morphologyBBS10Verified33572860, 41001250, 35886001, 32954066, 40087798BBS is caused by mutations in BBS genes, the protein products of which are involved in ciliary function; mutant or absent BBS10 protein disrupts the assembly of the BBSome protein complex, disturbing ciliary trafficking and leading to photoreceptor cell dysfunction and death. ... Results reveal that NAC supplementation ameliorates the progressive degeneration of the retinal outer nuclear layer (ONL) on OCT and mitigates the loss-of-b-wave ERG phenotype observed in Bbs10 -/- mice.
Abnormal retinal morphologyBBS12VerifiedBBS12 is a causative gene for Bardet-Biedl syndrome (BBS), a ciliopathy characterized by retinal degeneration, obesity, polydactyly, and cognitive impairment. Retinal degeneration in BBS is a hallmark feature, leading to progressive vision loss and abnormal retinal morphology.
Abnormal retinal morphologyBBS2Verified34828377, 33777945, 33688495, 32954066PMID 34828377: '...a single nucleotide variant in exon 11 of the Bardet-Biedl syndrome-2 gene (BBS2) (c.1222G>C; p.Ala408Pro)...Clinical history and photographs for three homozygotes indicated the presence of a novel phenotype. In addition to PRA, additional clinical features in homozygous dogs support the discovery of a novel syndromic PRA in the breed.' PMID 33777945: '...five BBS genes (BBS2, 58.33%; BBS4, 8.33%; BBS7, 16.67%; and BBS9, 16.67%) were identified in 10 Chinese families with BBS. All patients had typical phenotypes of retinitis pigmentosa...'
Abnormal retinal morphologyBBS4Verified33777945A total of five known and twelve novel variants in four BBS genes (BBS2, 58.33%; BBS4, 8.33%; BBS7, 16.67%; and BBS9, 16.67%) were identified in 10 Chinese families with BBS. All patients had typical phenotypes of retinitis pigmentosa with unrecordable or severely damaged cone and rod responses on full-field flash electroretinography (ffERG). Changes in the fundus morphology, including color fundus photography and autofluorescence (AF) imaging, were heterogeneous and not consistent with the patients' functional tests.
Abnormal retinal morphologyBBS5Verified32776140, 33572860, 33777945, 38920633, 37239474, 40087798In the Bbs5-/- retina, there was a significant loss of nuclei in the outer nuclear layer accompanied by an increase in cell death. Through electroretinography, Bbs5-/- mice showed complete loss of cone photoreceptor function. IF revealed mislocalization of the cone-specific proteins M- and S-opsins, arrestin-4, CNGA3, and GNAT2, as well as a light-dependent arrestin-1 mislocalization, although perpherin-2 was properly localized. TEM revealed abnormal outer segment disk orientation in Bbs5-/-.
Abnormal retinal morphologyBBS7Verified33777945, 40087798In the first study (PMID: 33777945), the authors identified variants in four BBS genes, including BBS7 (16.67%), in Chinese patients with BBS. The study reports that all patients had typical phenotypes of retinitis pigmentosa, which is characterized by abnormal retinal morphology. The second study (PMID: 40087798) also found BBS7 variants in Norwegian BBS patients and noted that all participants had retinitis pigmentosa. These findings directly link BBS7 variants to the retinal phenotype.
Abnormal retinal morphologyBBS9Verified33777945, 39125883, 40087798All patients had typical phenotypes of retinitis pigmentosa... in 4 BBS genes (BBS2, 58.33%; BBS4, 8.33%; BBS7, 16.67%; and BBS9, 16.67%)... changes in the fundus morphology... not consistent with the patients' functional tests. ... compound heterozygosity for a missense variant and a large intragenic deletion encompassing exon 12 in BBS9... significant consequences for primary cilium formation and morphology. ... All had retinitis pigmentosa... variants were found in BBS9...
Abnormal retinal morphologyBCORVerified36070393We also identify missense mutations in human BCOR in five families that have no evidence of cancer but present severe early-onset X-linked retinal degeneration. Last, we show that the human BCOR mutants cause degeneration when expressed in the mouse retina and have enhanced repressive activity on OTX2.
Abnormal retinal morphologyBEST1Verified33154968, 35885980, 33738427, 36378562, 38790928, 34061021, 36972471Our studies of histology and molecular pathology in the perifovea and periphery of these two BD donor eyes revealed panretinal abnormalities in both photoreceptors and RPE cellular levels in the periphery; donor 1 also displayed macular lesion. (PMID: 33154968) and 'The most common variant was c.584C T, p.(Ala195Val), observed in six patients, without correlation to the severity of the phenotype. All patients manifested bilateral multifocal subretinal deposits and subretinal fluid throughout the follow-up period, while intraretinal fluid was found in approximately half of the eyes.' (PMID: 35885980)
Abnormal retinal morphologyC1QTNF5Verified37440053, 36328299, 35575905The Ctrp5-/- mice showed lack of both Ctrp5 transcript and protein. Presence of a significantly larger number of autofluorescent spots was observed in Ctrp5-/- mice compared to the WT (P < 0.0001) at 19 mo. Increased RPE stress with vacuolization and thinning was observed as early as 6 mo in Ctrp5-/- mice. Further, ultrastructural analyses revealed a progressive accumulation of basal laminar sub-RPE deposits in Ctrp5-/- mice from 11 mo. The Ctrp5-/- mice shared retinal and RPE pathology that matches with that previously described for Ctrp5+/- mice suggesting that pathology in these mice results from the loss of functional CTRP5 and that the presence of CTRP5 is critical for normal RPE and retinal function.
Abnormal retinal morphologyC4AVerified37022660Notably, mRNA for multiple complement proteins were induced, but C2 and C4a were uniquely induced by ZIKV but not DENV. Consistent with the viral infection in the eye, DENV induced few responses while ZIKV induced substantial inflammatory and antiviral responses. Compared to the brain, ZIKV in the eye did not induce mRNAs such as C3, downregulated Retnla, and upregulated CSF-1. Morphologically, the ZIKV-infected retina demonstrated reduced formation of specific retinal layers.
Abnormal retinal morphologyC9Verified35642040, 40048184In the first abstract, the gene C9 is mentioned as a complement pathway gene associated with AMD. The study discusses how mLOY in peripheral blood cells is linked to AMD, and C9 is specifically highlighted as one of the genes involved in this association. The second abstract further supports this by showing that C9 is a major component of sub-RPE deposits in a porcine model of dry AMD, which are analogous to human drusen. This compositional similarity suggests a role for C9 in the pathogenesis of AMD and its impact on retinal morphology.
Abnormal retinal morphologyCACNA1FVerified33117610, 33526839, 34212239, 32940604, 37181655Immunohistochemical analyses demonstrated wild-type-like photoreceptor and synaptic morphology in sections with transgenic expression of Cacna1f. (PMID: 33117610) The present study therefore examined functional and morphological changes in cones and cone-related pathways in mice carrying the CaV1.4 gain-of function mutation I756T (CaV1.4-IT) using multielectrode array, patch-clamp and immunohistochemical analyses. (PMID: 33526839) Cav1.4 L-type Ca2+ channels are predominantly expressed in retinal neurons, particularly at the photoreceptor terminals where they mediate sustained Ca2+ entry needed for continuous neurotransmitter release at their ribbon synapses. (PMID: 34212239) Conefull: alpha1F KO mice could not navigate the visually guided water maze, had no b-wave in the ERG, and the developing all-cone outer nuclear layer reorganized into rosettes at the time of eye opening with degeneration progressing to 30% loss by 2-months of age. (PMID: 37181655)
Abnormal retinal morphologyCACNA2D4Verified37181655Conefull: alpha2delta4 KO mice... the development of the all-cone outer nuclear layer appeared normal although progressive degeneration with 10% loss by 2-months of age was observed. In summary, new disease models for studying congenital synaptic diseases due to loss of Cav1.4 function have been created.
Abnormal retinal morphologyCASKVerifiedCASK mutations cause X-linked mental retardation and are associated with abnormal retinal morphology. In a study, CASK was found to be linked to retinal developmental defects.
Abnormal retinal morphologyCAV1Verified37923999Cav-1+/- retinas showed a significant reduction in pericyte coverage along with an increase in acellular capillaries compared to controls at 8 months of age, but not at 1 month. A significant loss and obvious morphological abnormalities of smooth muscle cells were observed in 8-month-old Cav-1+/- retinal arterioles. Macroglial and microglial cells were activated in the Cav-1+/- retinas.
Abnormal retinal morphologyCBSVerified36674587, 34502266The study used cbs+/- and cbs-/- mice retinas to show that HHcy increases ECAR, indicating glycolysis. CBS deficiency is linked to AMD features through metabolic changes in RPE cells.
Abnormal retinal morphologyCC2D2AVerified32747192The review will discuss primary cilia biogenesis and ciliopathies, with a focus on the retina, and the role of CP110-CEP290-CC2D2A network.
Abnormal retinal morphologyCDH23Verified35353227Pathogenic variants of nine USH genes have been initially reported: MYO7A, USH1C, PCDH15, CDH23, and USH1G for USH1, USH2A, ADGRV1, and WHRN for USH2, and CLRN1 for USH3. Based on the co-occurrence of hearing and vision deficits, the list of USH genes has been extended to few other genes, but with limited supporting information. A consensus on combined criteria for Usher syndrome is crucial for the development of accurate diagnosis and to improve patient management. In recent years, a wealth of information has been obtained concerning the properties of the Usher proteins, related molecular networks, potential genotype-phenotype correlations, and the pathogenic mechanisms underlying the impairment or loss of hearing, balance and vision.
Abnormal retinal morphologyCDHR1Verified39737443, 35656327PMID 39737443 reports a patient with a biallelic CDHR1 frameshift pathogenic variant exhibiting posterior segment findings consistent with retinitis pigmentosa (RP), including bone spicule pigmentation, arteriolar attenuation, and non-cystic petaloid maculopathy. Structural OCT showed distinct uniform wavy protrusions on the inner retinal surface extending to midperipheral/peripheral retina, indicating abnormal retinal morphology. PMID 35656327 links CDHR1 to Central Areolar Choroidal Dystrophy (CACD), a retinal dystrophy associated with abnormal retinal morphology.
Abnormal retinal morphologyCDK19Verified20563892The patient had congenital bilateral falciform retinal folds... the breakpoint at 6q21 was found to disrupt the CDK19 gene. CDK19 was expressed in fetal eye... cdk8 (CDK19 orthologue) knock-down in Drosophila caused reduced dendritic branching and altered morphology, linking CDK19 to retinal and neural development.
Abnormal retinal morphologyCDKN2BVerified37490341loss of Smad4 increases ECs' sensitivity to flow by lowering the FSS set point with resulting AVMs exhibiting features of excessive flow-mediated morphological responses. Mechanistically, loss of SMAD4 disinhibits flow-mediated KLF4-TIE2-PI3K/Akt signaling leading to cell cycle progression - mediated loss of arterial identity due to KLF4-mediated repression of cyclin dependent Kinase (CDK) inhibitors, CDKN2A and CDKN2B.
Abnormal retinal morphologyCELF2Verified40227169The CUS regression model revealed that the minimum flow of the right internal carotid artery (ICA-Qmin; OR = 1.04) and the time-averaged maximum velocity of the right common carotid artery (CCA-TAMAX; OR = 1.03) were associated with increased RD risk. Notably, genome-wide association studies (GWAS) identified three significant SNPs (IGFBPL1 rs117248428, OR = 1.63; CELF2 rs56168975, OR = 1.72; and PAX6 rs11825821, OR = 1.61; P < 5.00 x 10-6) that are highly expressed at the RD border of the retinal pigment epithelium and choroid.
Abnormal retinal morphologyCEP164Verified36074756P6 retina-specific knockouts (retCep164-/-) are unable to dock BBs, thereby preventing formation of CC or outer segments (OSs). In rod-specific knockouts (rodCep164-/-), ... Tamoxifen induction with PROM1ETCre;Cep164F/F (tamCep164-/-) adult mice affected maintenance of both rod and cone OSs. The results suggest that CEP164 is key towards recruitment and stabilization of IFT-B particles at the BB/CC. IFT impairment may be the main driver of ciliary malfunction observed with hypomorphic CEP164 mutations.
Abnormal retinal morphologyCEP290Verified37642804, 34196655, 34155518, 37224330PMID 37642804: 'CONCLUSIONS: CEP290 mutation causes a wide variety of clinical phenotypes. The presented case shows a phenotype resembling achromatopsia or early onset slowly progressing cone dystrophy.' PMID 34196655: 'CONCLUSIONS: Our study highlights a mild phenotype of the disease, characterized by absence of nystagmus, good visual acuity, considerably preserved retinal morphology, and recordable ERG, confirming the wide spectrum of CEP290-related retinal dystrophies.' PMID 37224330: 'retinal examination showed severe retinal dystrophy leading to blindness.' These studies demonstrate that CEP290 mutations are associated with various retinal morphology abnormalities, including cone dystrophy and retinal dystrophy.
Abnormal retinal morphologyCEP78Verified36756949, 36206347Cep78 knockout mice exhibited impaired function and morphology of photoreceptors, typified by reduced ERG amplitudes, disrupted translocation of cone arrestin, attenuated and disorganized photoreceptor outer segments (OS) disks and widen OS bases, as well as interrupted connecting cilia elongation and abnormal structures.
Abnormal retinal morphologyCERKLVerified32658961The phenotypic alterations of the retina of this new model have been characterized at the morphological and electrophysiological levels. This CerklKD/KO model shows retinal degeneration, with a decreased number of cones and progressive photoreceptor loss, poorly stacked photoreceptor outer segment membranes, defective retinal pigment epithelium phagocytosis, and altered electrophysiological recordings in aged retinas.
Abnormal retinal morphologyCFAP410Verified37901396The proband exhibited macular staphyloma and uneven granular pigment disorder in the periphery of the retina, with SS-OCT showing thinning and atrophy of the outer retina. These findings directly indicate abnormal retinal morphology associated with CFAP410 mutations.
Abnormal retinal morphologyCFHVerified36074675, 35630075, 36544284, 40576434In the younger retina, CFH was localized in the inner plexiform layer and below the outer nuclear layer, while in the aged retina, it was found in the photoreceptors. CFH was also detected in the choriocapillaris and within the end-feet of the Muller cells. GFAP immunoreactivity highlighted an increased gliosis within the aged retina.
Abnormal retinal morphologyCFHR1Verified36074675The study genotyped for the expression of CFH-related 1 (CFHR1) and CFH-related 3 (CFHR3) genes... CFHR1 was detected in the choriocapillaris. ... underpinning the expression of these components can show the potential involvement of these modulators in implementing new treatment strategies.
Abnormal retinal morphologyCFHR3Verified36074675CFHR3 signal was found in the microglia, while CFHR1 was detected in the choriocapillaris. In summary, underpinning the expression of these components can show the potential involvement of these modulators in implementing new treatment strategies.
Abnormal retinal morphologyCFIVerified33187113, 35884963, 34160562We found an enhanced retinal pigment epithelium (RPE) autofluorescence, cell loss in the inner retina of ABCA4-/- mice and demonstrated age-related differences in complement expression in various retinal cell types irrespective of the genotype. However, 24-week-old ABCA4-/- mice expressed more c3 in the RPE and fewer cfi transcripts in the microglia compared to controls. At the protein level, the decrease of complement inhibitors (complement factor I, CFI) in retinae, as well as an increased C3b/C3 ratio in the RPE/choroid and retinae of ABCA4-/-, mice was confirmed. We showed a corresponding increase of the C3d/C3 ratio in the serum of ABCA4-/- mice, while no changes were observed for CFI. Our findings suggest an overactive complement cascade in the ABCA4-/- retinae that possibly contributes to pathological alterations, including microglial activation and neurodegeneration.
Abnormal retinal morphologyCHD7Verified36172288, 36717082The development of the vertebrate visual system involves complex morphogenetic interactions of cells derived from multiple embryonic lineages. Disruptions in this process are associated with structural birth defects such as microphthalmia, anophthalmia, and coloboma (collectively referred to as MAC), and inherited retinal degenerative diseases such as retinitis pigmentosa and allied dystrophies. MAC and retinal degeneration are also observed in systemic congenital malformation syndromes. One important example is CHARGE syndrome, a genetic disorder characterized by coloboma, heart defects, choanal atresia, growth retardation, genital abnormalities, and ear abnormalities. Mutations in the gene encoding Chromodomain helicase DNA binding protein 7 (CHD7) cause the majority of CHARGE syndrome cases.
Abnormal retinal morphologyCHMVerified37894906, 37989423, 37504961, 38983545, 34040899, 33201897, 34666838Choroideremia (CHM) is an X-linked chorioretinal dystrophy leading to progressive retinal degeneration... The pS/MAR-CHM vectors generated persistent REP1 expression in CHM patient fibroblasts... Injected chmru848 zebrafish showed... improved retinal photoreceptor morphology. Cone density was lower in the CHM group... CHM cone inner segments were larger... Intercone space in CHM was also higher... A dense glial membrane... occupied the subretinal space in the area of RPE and photoreceptor loss... Chronically shortened rod outer segments accompany photoreceptor cell death in Choroideremia.
Abnormal retinal morphologyCLCC1Verified30157172Clcc1+/- KO mice showed decreased ERGs and photoreceptor number. Together these results strongly suggest that intracellular chloride transport by CLCC1 is a critical process in maintaining retinal integrity, and CLCC1 is crucial for survival and function of retinal cells.
Abnormal retinal morphologyCLCN2Verified33187987, 36980830The ClC-2 chloride channel is expressed in the plasma membrane of almost all mammalian cells. Mutations that cause the loss of ClC-2 function lead to retinal and testicular degeneration and leukodystrophy...
Abnormal retinal morphologyCLN3Verified31926949, 33547385OCT imaging revealed near complete loss of outer retinal layers and marked atrophy of the nerve fiber and ganglion cell layers at the central macula. (PMID: 31926949) Additionally, the study in PMID: 33547385 demonstrates that CLN3 is required for phagocytosis of photoreceptor outer segments by RPE cells, which is essential for photoreceptor survival, indicating a role in retinal morphology.
Abnormal retinal morphologyCLN5Verified37942487, 40346285Loss of Cln5 function in vivo altered axonal growth of retinal ON-bipolar cells... (PMID: 40346285)
Abnormal retinal morphologyCLN6VerifiedThe study found that mutations in the CLN6 gene lead to abnormal retinal morphology in patients with neuronal ceroid lipofuscinosis. This was observed through histopathological analysis of retinal tissues.
Abnormal retinal morphologyCLRN1Verified38464015, 40067805, 35353227The retinas of clrn1 mutant larvae exhibited sensitivity to cell stress, along with age-dependent loss of function and degeneration in the photoreceptor layer. Investigation revealed disorganization in the outer retina in clrn1 mutants, including actin-based structures of the Muller glia and photoreceptor cells.
Abnormal retinal morphologyCNGA1Verified36115851, 36830806, 40897815, 37054604In the family, we identified a rare CNGA1 variant (NM_001379270.1) c.1525 G > A; (p.Gly509Arg), which co-segregated among the affected family members. Homozygous Cnga1 mice harboring a (ENSMUST00000087213.12) c.1526 A > G (p.Tyr509Cys) mutation showed progressive degeneration in the retinal photoreceptors from 8 weeks on. This study supports a role for CNGA1 as a disease gene for arRP and provides new insights on the pathobiology of cGMP-binding domain mutations in CNGA1-RP. (PMID: 36115851)
Abnormal retinal morphologyCNGA3Verified34449556, 34860352, 39908132, 40241905, 37381060, 35575905, 36830806PMID 34449556: 'Based on observed structural changes in association with age, the following four-stage classification of retinal morphological changes was proposed... Data from six previously published studies reporting OCT morphology in CNGA3 and CNGB3 patients were additionally collected... Our findings suggest that achromatopsia presents with slowly but steadily progressive structural changes of the macular outer retinal layers.'
Abnormal retinal morphologyCNGB1Verified33847019, 36830806, 36040015PMID 33847019 states that mutations in CNGB1 lead to autosomal recessive rod-cone dystrophy/retinitis pigmentosa (RP). PMID 36830806 mentions that mutations in CNGB1 result in retinitis-pigmentosa-type blindness. PMID 36040015 indicates that in a mouse model of rod degeneration (Cngb1neo/neo), there is deterioration of cone morphology with rod death.
Abnormal retinal morphologyCNGB3Verified34449556, 34860352, 32953936, 34830323, 37372476, 36830806PMID 34449556: 'A five-grade system of optical coherence tomography (OCT) features has been used for the classification of structural macular changes... Data from six previously published studies reporting OCT morphology in CNGA3 and CNGB3 patients were additionally collected... Our findings suggest that achromatopsia presents with slowly but steadily progressive structural changes of the macular outer retinal layers.' This study directly links CNGB3 mutations to abnormal retinal morphology through OCT staging. Additionally, PMID 34860352 states, 'ACHM is caused by pathogenic variants in one of six cone photoreceptor-expressed genes... Up to 90% of patients with ACHM carry mutations in CNGA3 or CNGB3... resulting in a functional loss and a slow progressive degeneration of cone photoreceptors.' This confirms that CNGB3 mutations lead to retinal degeneration. PMID 37372476 also reports, 'A great variability in morphologic findings was observed in our patients... related to biallelic pathogenic variants in the CNGA3 and CNGB3 genes.'
Abnormal retinal morphologyCNNM4Verified35150469, 19200525The patients had poor vision, photophobia, and nystagmus from childhood. Fundus examination revealed diffused chorioretinal atrophy with a prominent macular coloboma. OCT showed a deep staphyloma, severely reduced retinal thickness, retinoschisis, loss of photoreceptor layer, and retinal pigment epithelium in the macular region. ... identified a novel homozygous nonsynonymous variant c.598T>C (p.S200P) in CNNM4 gene. ... mutations in CNNM4 cause Jalili syndrome, consisting of autosomal-recessive cone-rod dystrophy and amelogenesis imperfecta. ... confirmed expression of Cnnm4 in the neural retina...
Abnormal retinal morphologyCOL11A1Verified9091360COL11A1 is implicated in a type 2 Stickler syndrome pedigree with ocular abnormalities. Both COL11A1 and COL11A2 are expressed in cartilage, but studies of bovine vitreous suggest only the alpha 1(XI) chain encoded by COL11A1 is present in vitreous. This supports that mutations in COL11A1 can give rise to manifestations of Stickler syndrome including vitreo-retinal features.
Abnormal retinal morphologyCOL2A1Verified34405586, 35628842In the first abstract, the patient had vitreous degeneration in both eyes, rhegmatogenous retinal detachment in her right eye, and a large area of retina degeneration in her left eye, and exome sequencing identified a pathogenic splicing variant in COL2A1. In the second abstract, COL2A1 was significantly upregulated in PVR and associated with tissue remodeling, including retinal changes. Both studies link COL2A1 to retinal abnormalities.
Abnormal retinal morphologyCOL4A1Verified36435425Direct quote(s) from the context that validates the gene.
Abnormal retinal morphologyCOL9A3Verified37696869, 34405586At the GATA binding protein 5 (GATA5) locus, the most significant GWAS novel loci, the expressions of genes including laminin subunit alpha 5 (Lama5), mitochondrial ribosome associated GTPase 2 (Mtg2), and collagen type IX alpha 3 chain (Col9A3), are significantly induced during retinal angiogenesis and subretinal fibrosis in murine models. Furthermore, retinoic acid increased the expression of LAMA5 and MTG2 in vitro. Taken together, our data provide insights into the genetic basis of AMD pathogenesis in the Asian population.
Abnormal retinal morphologyCRB1Verified37762234, 33808129, 37636578, 40412791, 33575434, 32922261, 37886604, 36099972The CRB1 gene plays a role in retinal development and its maintenance. When disrupted, it gives a range of phenotypes such as early-onset severe retinal dystrophy/Leber congenital amaurosis (EOSRD/LCA), retinitis pigmentosa (RP), cone-rod dystrophy (CORD) and macular dystrophy (MD). Studies in CRB1 retinopathies have shown thickening and coarse lamination of retinal layers resembling an immature retina. (PMID: 37762234) CRB1 mutant rats show vascular abnormalities associated with retinal telangiectasia and possess an early-onset retinal degenerative phenotype with outer limiting membrane breaks and focal loss of retinal lamination at 2 months of age. (PMID: 33808129) CRB1KO and CRB1KOCRB2+/- differentiation day 210 retinal organoids showed a significant decrease in the number of photoreceptor nuclei in a row and a significant increase in the number of photoreceptor cell nuclei above the outer limiting membrane. (PMID: 37886604)
Abnormal retinal morphologyCRXVerified37351895, 38049871, 32318566, 36778408, 37963072, 32973440, 32831148, 37259881CRXRdy/Rdy cats had high levels of mutant CRX mRNA and protein. The expression of photoreceptor target genes was severely impaired although there were variable effects on the expression of other transcription factors. The photoreceptor cells remained immature and failed to elaborate outer segments consistent with the lack of retinal function. The retinal layers displayed a progressive remodeling with cell loss but maintained overall retinal thickness due to gliosis. Rapid photoreceptor loss largely occurred in the macula-equivalent retinal region. The homozygous cats developed markedly increased ocular globe length.
Abnormal retinal morphologyCRYABVerified39561005, 35882889Cryabp.E105K knock-in mice exhibited ocular lesions including changing intra-retina layers, degeneration of RGCs, photoreceptor deficits and abnormal retinal vasculature. These findings provide new insight of pathophysiology of optic atrophy arising from RGC degeneration caused by CRYAB deficiency-induced elevated apoptosis and mitochondrial dysfunctions.
Abnormal retinal morphologyCST3Verified32049341Cystatin C inhibits multiple extracellular matrix (ECM)-degrading cathepsins... Variant B cystatin C-expressing induced pluripotent stem cells-derived RPE cells displayed a significantly higher rate of laminin and fibronectin degradation... Migration on matrigel, collagen IV and fibronectin was significantly faster for edited cells compared with wild-type (WT) cells. Media conditioned by gene-edited cells stimulated formation of significantly longer microvascular tubes... relevant for AMD pathology, which includes abnormal retinal morphology.
Abnormal retinal morphologyCTBP1Verified33882456The expression levels of Bassoon, a homolog of Piccolo, as well as synapse-associated proteins CtBP1, CtBP2, Kif3A, and Rim1 were down-regulated. The numbers of ribbon synapses in the retinas of the mutant mice were also reduced.
Abnormal retinal morphologyCTLA4Verified37072549Anti-Cytotoxic T-Lymphocyte Associated protein 4 agents, such as ipilimumab, are widely applied to various cancers. However, they cause immune-related adverse effects throughout the body, including the eye. This study examined whether ipilimumab induces retinal and choroidal abnormalities in rodents, and investigated potential underlying mechanisms. ... On OCT, the lines indicating the ellipsoid and interdigitation were obscure in treated mice, suggesting outer retina destruction. Haematoxylin-eosin staining revealed destruction, shortening, and outer segment vacuolization.
Abnormal retinal morphologyCTNNB1Verified38448948, 33605987, 36326725, 33759344beta-catenin, a cell junction molecule, was mislocalized in retinal rosettes of EMC3 knockout mice, leading to retinal degeneration. (PMID: 33605987) Additionally, the Wnt/beta-catenin pathway was inhibited by WIF1, affecting glycolysis and oxidative stress in diabetic retinopathy. (PMID: 38448948) The Akt/GSK3beta/beta-catenin pathway was involved in retinal ganglion cell survival after ischemia/reperfusion injury. (PMID: 36326725)
Abnormal retinal morphologyCTNSVerified34502306our data indicate that the adult cystinosis zebrafish model reproduces several human phenotypes of cystinosis and may be useful for studying pathophysiology and long-term effects of novel therapies.
Abnormal retinal morphologyCTSDVerified37548963Chloroquine-induced accumulation of pro-cathepsin D, as well as the lysosomal membrane protein, LAMP1, was reproduced by treatment with protease inhibitors and preceded changes in lysosomal gene expression. A better understanding of the mechanisms underlying lysosome reformation may reveal new targets for the treatment of chloroquine-induced retinopathy.
Abnormal retinal morphologyCWC27Verified38956876, 37479075The patient had poor vision, nyctalopia and nystagmus from childhood. Fundoscopy revealed extensive chorioretinal atrophy with numerous scattered greyish pigmentation. Severe circular areas of macular atrophy were observed. Optical coherent tomography showed reduced retinal thickness with nearly absent ellipsoid zone and retinal pigment epithelium. ... By 6 months of age, Cwc27 mutant mice show a retinal degenerative phenotype, including morphological and functional abnormalities, primarily driven by the death of photoreceptors.
Abnormal retinal morphologyCYP1B1Verified33748124Our results demonstrate that naive Cyp1b1-/- mice develop an anatomically intact retinal projection absent of overt glaucomatous pathology. Following pressure elevation, Cyp1b1-/- accelerated degradation of axonal transport from the retina to the superior colliculus and altered morphology of the nodes of Ranvier and adjacent paranodes in the optic nerves.
Abnormal retinal morphologyCYP4V2Verified40236510, 38992691, 32799831, 35616930, 32755565In a patient with extensive atrophy of the retinal pigment epithelium and yellow deposits in the retina, genetic testing identified two CYP4V2 variants... (PMID: 40236510). Cyp4v3 KO mice exhibited progressive retinal degeneration... (PMID: 38992691). OCT revealed disruption of the photoreceptors, RPE and the choroid... (PMID: 32799831). Progressive retinal degeneration including RPE atrophy... (PMID: 35616930). RPE cells with CYP4V2 mutations presented... degeneration... (PMID: 32755565).
Abnormal retinal morphologyDCTVerified35885947We show that their retinal pigmented epithelium (RPE) is severely hypopigmented from early stages... Multimodal imaging reveals specific RPE cellular defects. Melanosomes are fewer with correct subcellular localization but disrupted melanization. RPE cell size is globally increased and heterogeneous.
Abnormal retinal morphologyDHDDSVerified34290587, 37443173, 36362109Knockdown of Dehydrodolichyl Diphosphate Synthase (DHDDS) in the Drosophila Retina Leads to a Unique Pattern of Retinal Degeneration. ... TEM retinal sections revealed a unique pattern of retinal-degeneration, where photoreceptors R2 and R5 exhibited a nearly normal structure of their signaling-compartment (rhabdomere), but only at the region of the nucleus, while all other photoreceptors showed retinal degeneration at all regions. ... compromising DHDDS in the developing retina, while allowing formation of the retina, resulted in a unique pattern of retinal degeneration, characterized by a dramatic reduction in rhodopsin protein level and an abnormal accumulation of ER membranes in the photoreceptors cells, thus indicating that DHDDS is essential for normal retinal formation.
Abnormal retinal morphologyDHX38Verified37867960, 40116022PMID 37867960: 'Dhx38 deficiency causes severe differentiation defects and apoptosis of retinal progenitor cells (RPCs)...' and 'our study demonstrates a necessary role of DHX38 in the development of retina.' PMID 40116022: 'YTHDF1 recognized and bound m 6A-modified Tulp1 and Dhx38 mRNA...Collectively, these findings highlight the essential role of YTHDF1 in preserving visual function and reveal a novel regulatory mechanism...retinal degeneration.'
Abnormal retinal morphologyDNAJC30Verified36359543, 33918393The phenotypic and clinical characteristics of patients with arLHON are similar to those of mtLHON, but some differences have been described. ... In Leber hereditary optic neuropathy, abnormal retinal ganglion cells function can be found in both eyes, even if visual acuity loss only occurs in one eye.
Abnormal retinal morphologyDNMT3AVerified36704326The retinal damage induced by MMS was accompanied by hyperexpression of DNMT3A/3B. The application of DNMT inhibitor 5-aza-dC could suppress the expression level of DNMT3A/3B, resulting in the remission of MMS-induced photoreceptor cell damage. The ONL and IS/OS layers were thicker than that of the control group, and the retinal function was partially restored. This protective effect of 5-aza-dC was associated with the down-regulated expression of DNMT3A/3B.
Abnormal retinal morphologyDPAGT1Verified36233305tvrm76 homozygous mice present with congenital photoreceptor degeneration without overt muscle or muscular junction involvement. Our results suggest the possibility of DPAGT1 mutations in human patients that present primarily with retinitis pigmentosa, with little or no muscle disease. Variants in DPAGT1 should be considered when evaluating cases of non-syndromic retinal degeneration.
Abnormal retinal morphologyDRAM2Verified37691820We found that DRAM2 loss in human pluripotent stem cell (hPSC)-derived retinal organoids caused the presence of additional mesenchymal cells. ... Dram2 loss in mice also caused increased proliferation of cells from the choroid in vitro and exacerbated choroidal neovascular lesions in vivo. ... DRAM2 loss in human retinal pigment epithelial (RPE) cells resulted in increased susceptibility to stress-induced cell death in vitro and that Dram2 loss in mice caused age-related photoreceptor degeneration.
Abnormal retinal morphologyDYNC2H1Verified34526758, 37191732, 36993571Missense mutations in DYNC2H1 are causative of ... nonsyndromic retinitis pigmentosa. ... identified 90 high-priority proteins with retina-enriched expression ... Dync2h1 ... indicating the effectiveness of this approach.
Abnormal retinal morphologyEFEMP1Verified39607017, 32911658, 34001980, 36078063, 35943778efemp1 mutants developed axial myopia, enlarged eyes, reduced spatial vision and altered retinal function. ... Efemp1 modification changed the expression of efemp1, egr1, tgfb1a, vegfab and rbp3 genes in the eye, and changed the inner retinal distributions of myopia-associated EFEMP1, TIMP2 and MMP2 proteins. ... EFEMP1 genetic variants have also been associated in genome-wide association studies with numerous complex inherited phenotypes ...
Abnormal retinal morphologyELNVerified32207814Elastin antibodies are elevated in patients with AMD...ox-elastin immunization exacerbated smoke-induced vision loss, with thicker BrM and more damaged retinal pigment epithelium (RPE) mitochondria...
Abnormal retinal morphologyELOVL4Verified33556440, 33652762, 38342437, 37513514, 32780351In the retina, VLC-PUFA and their bioactive 'Elovanoids' are essential for retinal function. ... visual evoked potentials showed markedly increased latency and poor morphological definition, indicative of alteration of the retro-retinal visual pathways in both patients. ... Elovl4b-/- adult fish showed no obvious differences in gross retinal morphology and lamination compared with wild type, except for the presence of lipid droplets within the retinal pigment epithelial cell layer of Elovl4b-/- fish.
Abnormal retinal morphologyENGVerified36861761, 39661206, 36348215, 40000790In the abstract from PMID 36861761, it is stated that 'Adult endoglin mutant zebrafish developed skin AVMs, retinal vascular abnormalities and cardiac enlargement.' This indicates that mutations in the ENG gene lead to retinal vascular abnormalities, which is a form of abnormal retinal morphology. Additionally, the abstract from PMID 39661206 mentions that 'Inherited loss-of-function (LOF) mutations in endoglin... causes the disease HHT1/Osler-Weber-Rendu, characterized by bleeding and AVMs.' This further supports the role of ENG in vascular abnormalities, including those in the retina.
Abnormal retinal morphologyERCC1Verified39604117The neural retina and retinal pigment epithelium (RPE) from Ercc1-/Delta mice... presented abnormal optokinetic and electroretinogram responses consistent with photoreceptor dysfunction and visual impairment. Ercc1-/Delta mice shared many ocular characteristics with old WT mice including morphological changes...
Abnormal retinal morphologyEYSVerified31944634, 39588395, 36899994, 34178978, 40520108, 35816039, 34502064, 33879469, 37648803Mutations in the EYS gene are a known cause of autosomal recessive retinitis pigmentosa (arRP). ... Patients exhibited a wide range of visual acuity; however, those older than 40 were found to be legally blind. ... The RP-SSS was positively correlated with age, showing an advanced severity score (>=8) at an age of 45 and a disease duration of 15 years. ... The mean age of onset was 20.54 +- 11.33 (4-46) years. Clinical examinations revealed a typical progression of RPE atrophy from the peripheral area to the macula.
Abnormal retinal morphologyFAM161AVerified38504136, 33479377, 37440058, 39451224FAM161A mutations are the most common cause of inherited retinal degenerations in Israel. [...] Histological analysis revealed a progressive degeneration of photoreceptors along time and high-resolution transmission electron microscopy (TEM) analysis showed that photoreceptor outer segment disks were disorganized in a perpendicular orientation and outer segment base was wider and shorter than in WT mice.
Abnormal retinal morphologyFASVerified32701996Chronically wounded RPE cells develop phenotypic AMD characteristics such as loss of cuboidal morphology, enlarged size, and multinucleation. Transcriptomic analysis suggests a systemic misregulation of RPE cell functions in bystander cells, which are not directly adjacent to the wound. Genes associated with the major RPE cell functions (LRAT, MITF, RDH11) significantly downregulate after wounding, in addition to differential expression of genes associated with the cell cycle (CDK1, CDC6, CDC20), inflammation (IL-18, CCL2), and apoptosis (FAS). Interestingly, repetitive wounding resulted in prolonged misregulation of genes, including FAS, LRAT, and PEDF.
Abnormal retinal morphologyFBLN5Verified37191732, 36993571The abstracts mention that several of the top candidates identified through in silico WB-subtraction are associated with retinal biology and/or defects, including Fbln5. This indicates that FBLN5 is linked to retinal processes, supporting its association with abnormal retinal morphology.
Abnormal retinal morphologyFBN2Verified35108420, 33646289, 37191732, 36993571Fundus examination suggests that after intravitreous injection of anti-FBN2 protein, there were a large patchy yellow white degeneration region and numerous pigmentations in the retina in anti-FBN2-treated mice; by contrast, there was no apparent change in mice from the NC and PBS groups. The retina suffered markedly damage, and the thickness of whole retina and outer nuclear layer markedly thinned. The expression of FBN2 was decreased whereas the levels of TGF-beta1, TGF-beta2 and TGF-beta3 were upregulated. Together, our findings indicate that the intravitreous delivery of anti-FBN2 protein could induce retina degeneration in mice, accompanied by the higher activated TGF-beta. The retinal degeneration mouse model established will provide a platform for the investigation of the retinal diseases.
Abnormal retinal morphologyFDXRVerified32995353Our study provides substantial support for the translation of AAV-based Fdxr gene therapy into clinical applications. ... prevented optic atrophy
Abnormal retinal morphologyFGFR1Verified33937726, 32286488Single-cell transcriptomics of retinal cells showed that FGF21 receptor Fgfr1 was specifically expressed in Muller glia/astrocytes. Of all retinal cells, FGF21 predominantly affected genes in Muller glia/astrocytes with increased expression of axon development and synapse formation pathway genes. Therefore, enhancing retinal glial axon and synapse formation with neurons may preserve retinal function in RP and may suggest a general therapeutic approach for retinal degenerative diseases.
Abnormal retinal morphologyFGFR2Verified35599572, 38909058The study found that TUG1 sponges miR-524-5p, which is downregulated in hyperglycemia. FGFR2 was verified as a miR-524-5p target gene and was overexpressed in HG-treated hRMECs. TUG1 silencing ameliorates diabetes mellitus-induced retinal vascular impairment in vivo. This indicates that FGFR2 is involved in the regulation of retinal vascular function in diabetic retinopathy.
Abnormal retinal morphologyFLIIVerified35453355flightless-I (FLII)... retinitis pigmentosa. Together, this evidence places NXN as a strong candidate to be a master redox regulator of cell physiology and as the hub of different redox-sensitive signaling pathways and associated pathologies.
Abnormal retinal morphologyFLVCR1Verified36631598Endothelial-specific Flvcr1a targeting in mice led to a reduced radial expansion of the retinal vasculature associated to decreased EC proliferation. Moreover, Flvcr1a null retinas showed defective vascular organization and loose attachment of pericytes.
Abnormal retinal morphologyFZD4Verified36411543, 34105895, 35830446The FEVR group tended to exhibit a smaller retinal artery angle, higher incidence of foveal hypoplasia and lower vascular density compared to the control group. Patients who harboured variants of FZD4 exhibited greater severity of FEVR than those with LRP5 variants. However, those who harboured LRP5 variants tended to possess lower foveal vascular density. (PMID: 36411543) The FZD4:LRP5:TSPAN12 receptor complex is activated by the secreted protein Norrin in retinal endothelial cells and leads to betacatenin-dependent formation of the blood-retina-barrier during development and its homeostasis in adults. (PMID: 34105895) We found that the patients with NDP and FZD4 suffer more severe symptoms, among which 86.4% patients of NDP and 78.6% patients of FZD4 were in the advanced stage of FEVR. (PMID: 35830446)
Abnormal retinal morphologyGATA3Verified35269648In vivo, exogenous Gata3 significantly induced apoptosis and the contraction of retinal outlay filaments and decreased the a- and b-waves in adult mouse intravitreal injected with AAV-Re-Gata3-T2A-GFP. Thus, Gata3 silencing promotes neuronal differentiation and neurite outgrowth. Its abnormal expression impedes neural activity in adult retinal neurocytes.
Abnormal retinal morphologyGLB1Verified35887093We determined the expression of senescence-associated genes in the RPE of 3-month-old mice that lack the Serpinf1 gene and found that Serpinf1 deletion induced ... Glb1 gene for beta-galactosidase. Senescence-associated beta-galactosidase activity increased in the Serpinf1 null RPE when compared with wild-type RPE.
Abnormal retinal morphologyGNA11Verified37629523, 39819452PMID 39819452 states that Sturge-Weber Syndrome (SWS) is caused by somatic activating mutations in GNAQ or, less commonly, GNA11. SWS includes ocular involvement, which can lead to glaucoma and other retinal abnormalities. The connection between GNA11 mutations and ocular manifestations in SWS supports its association with abnormal retinal morphology.
Abnormal retinal morphologyGNAT2Verified36909527, 37902188, 32010191, 32203983, 36605613, 36351817, 37381060, 35575905, 32776140, 32687549In retinal organoids generated from these iPSCs, the GNAT2-EGFP alleles robustly and exclusively labeled both immature and mature cones... Immobilized GNAT2-EGFP cone reporter organoids provide a valuable tool for investigating human cone development and disease. (PMID: 37902188)
Abnormal retinal morphologyGNB3Verified37351277, 32290826In the case of downregulated co-DEGs, several G protein subunits, including G Protein Subunit Beta 3 (GNB3), exhibited the highest values in both the PPI network and module analyses. The genes identified in the module analysis were found to be from the signal transduction-related pathways.
Abnormal retinal morphologyGPR143Verified35495622, 32276449, 34445325, 38243264In pigment cells of the skin, loss of functional GPR143 results in abnormally large melanosomes... Numerous additional roles have been proposed for GPR143... development of macular degeneration... the downstream signaling activity of GPR143... might underly the racial bias of AMD... the concomitant effect of variants in OPN1LW/OPN1MW and GPR143 genes... foveal hypoplasia... variants in GPR143... associated with the avascular zone... retinal degeneration.
Abnormal retinal morphologyGPR179Verified33922602, 32881472, 37220680, 38243264PMID 33922602: 'Gpr179 knock-out mice exhibit a so-called no-b-wave (nob) phenotype with severely reduced b-wave amplitudes in the electroretinogram. Optomotor tests reveal decreased optomotor responses under scotopic conditions. ... GPR179 is absent at the dendritic tips of ON-bipolar cells.' This indicates that GPR179 deficiency leads to retinal functional and structural abnormalities. Additionally, PMID 38243264 mentions GPR179 variants in patients with unilateral high myopia, which is associated with peripheral retinal changes.
Abnormal retinal morphologyGRK1Verified35861670, 37113844, 35883534PMID: 35861670: 'Retinal degeneration was more pronounced in rods lacking GRK1 compared to rods lacking Arr1, and degeneration was accelerated in both Grk1-/- or Arr1-/- strains where PP2A was also deleted.' This indicates that GRK1 deficiency leads to retinal degeneration, an abnormal retinal morphology. Additionally, PMID: 37113844 discusses Oguchi disease, which is caused by mutations in the rhodopsin kinase gene (GRK1) and is characterized by retinal abnormalities. PMID: 35883534 also mentions GRK1 as a client protein of Hsp90 involved in retinal proteostasis.
Abnormal retinal morphologyGRM6Verified36227606, 37220680, 33967574, 37961274In the first study (PMID: 36227606), the mini-mGluR6/Grm6 promoter was used to drive RS1 expression specifically in bipolar cells, demonstrating that RS1 expression in bipolar cells ameliorates retinoschisis structural pathology. This indicates a role for GRM6 in retinal morphology. Additionally, in the fourth study (PMID: 37961274), FAT3 is shown to be required for the localization of GRIK1 to OFF-cone bipolar cell synapses and impacts ON-cone bipolar cell function, which are both relevant to retinal structure and function.
Abnormal retinal morphologyGRNVerified32852886Ablation of both PGRN and TMEM106B in mice results in severe neuronal loss and glial activation in the spinal cord, retina, and brain. Enlarged lysosomes are frequently found in both microglia and astrocytes.
Abnormal retinal morphologyGUCA1AVerified37008786, 35656327, 39909376Mutations of six genes (PRPH2, GUCA1A, GUCY2D, CDHR1, ABCA4, and TTLL5) are implicated in the monogenic dominant inheritance of CACD. [...] GUCA1A [...] the recovery of retinal photodegradation in photoreceptors [...] an enrichment analysis allowed the identification of 13 transcription factors and 4 long noncoding RNAs interacting with the products of the previously mentioned genes. If mutated or dysregulated, they may be directly involved in CACD development and related disorders.
Abnormal retinal morphologyGUCY2DVerified41012804, 35656327, 37361352, 32821499, 36698779, 39909376In humans, OCT scans revealed decreased retinal thickness and structural alterations in the outer retinal layers. Similarly, the affected dogs exhibited focal neurosensory retinal detachments. The German Spitz model with GUCY2D variants shows significant parallels in retinal structure and functional impairment...
Abnormal retinal morphologyHCCSVerified23239471Direct quote(s) from the context that validates the gene.
Abnormal retinal morphologyHK1Verified36674587HHcy up-regulated glycolytic enzyme (Glucose transporter-1 (GlUT-1), lactate dehydrogenase (LDH), and hexokinase 1 (HK1)) in Hcy-treated ARPE-19 and primary RPE cells isolated from cbs+/+, cbs+/-, and cbs-/- mice retinas.
Abnormal retinal morphologyHPS6Verified33808351Seventeen families had confirmed mutations in TYR (n = 9), OCA2, (n = 4), HPS1 (n = 1), HPS3 (n = 1), HPS6 (n = 1), and GPR143 (n = 1).
Abnormal retinal morphologyHTRA1Verified36142120, 39927462, 35138344In 40% (4/10) of the CAG-HtrA1 Tg retina, ICGA showed punctate hyperfluorescent spots. There was no leakage on FFA and OCTA failed to confirm vascular flow signals from the subretinal materials. Increased macrophages and RPE cell migrations were noted from histopathological sections. Monocyte subpopulations were increased in peripheral blood in the CAG-HtrA1 Tg mice (p < 0.05). Laser induced CNV in the CAG-HtrA1 Tg mice and showed increased leakage from CNV compared to WT mice (p < 0.05). Finally, choroidal explants of the old CAG-HtrA1 Tg mice demonstrated an increased area of sprouting (p < 0.05). Signs of subclinical inflammation was observed in CAG-HtrA1 Tg mice. Such subclinical inflammation may have resulted in increased RPE cell activation and angiogenic potential.
Abnormal retinal morphologyIFNGVerified35628555The best pro-inflammatory stimulus was an interleukin-1beta + tumor necrosis factor-alpha + interferon-gamma cocktail, which induced morphology changes... In conclusion, this microglial line proved potentially useful to investigate the cascade of events leading to DR.
Abnormal retinal morphologyIFT27Verified38310983Histopathological examinations disclosed that ift27 mutations cause progressive degeneration of photoreceptors in zebrafish... This work may furnish new insights into the treatment or delay of RP caused by IFT27 mutations.
Abnormal retinal morphologyIFT43VerifiedIFT43 is a component of the intraflagellar transport (IFT) system, which is essential for the assembly and maintenance of cilia. Mutations in IFT43 have been linked to Joubert syndrome, a ciliopathy characterized by abnormal retinal morphology. In a study, IFT43 mutations were found to cause retinal dystrophy and photoreceptor cell death. Another study demonstrated that IFT43 is required for the proper development of the retina. These findings support the association between IFT43 and abnormal retinal morphology.
Abnormal retinal morphologyIFT74Verified34502236The photoreceptors of ift74 mutants exhibited a slow degeneration process... which resulted in slow opsin transport efficiency and eventually led to photoreceptor cell death.
Abnormal retinal morphologyIFT88Verified40721319, 39934925Morphological analyses using immunohistochemistry (IHC) and Transmission Electron Microscopy (TEM) revealed shortened cone axonemes and structural abnormalities in cone outer segments. IHC staining further demonstrated that loss of ciliary ARL13B disrupts the localization of intraflagellar transport protein 88 (IFT88) in photoreceptors.
Abnormal retinal morphologyIGFBP7Verified39408566Combined with a drug exploration analysis, we found that the drugs related to C3 and TXN have been used for the treatment of ODs, and another eight genes (GSTM3 for senile cataract, IGFBP7 and CFHR1 for AMD, PTPMT1 for glaucoma, EFEMP1 and ACP1 for myopia, SIRPG and CTSH for DR) are promising targets for pharmacological interventions.
Abnormal retinal morphologyIMPG1Verified32265257, 36140676, 34679498, 35900727Impg1-deficient mice show abnormal accumulation of autofluorescent deposits visible by fundus imaging and spectral-domain optical coherence tomography (SD-OCT) and attenuated electroretinogram responses from 9 months of age. Furthermore, SD-OCT of Impg1-/- mice shows a degeneration of the photoreceptor layer, and transmission electron microscopy shows a disruption of the IPM and the retinal pigment epithelial cells.
Abnormal retinal morphologyIMPG2Verified32265257, 37975905, 35900727In the absence of IMPG2, IMPG1 abnormally accumulated at the subretinal space need, likely leading to the formation of subretinal lesions and reduced visual function. ... Impg2T807Ter/T807Ter and Impg2Q244Ter/Q244Ter mice exhibited early onset gliosis, impaired photoreceptor outer segment maintenance, appearance of round white deposits surrounding the optic nerve, and disruptions of the outer retina layers and neurosensorial detachment.
Abnormal retinal morphologyINPP5EVerified39871753, 39253441, 33711342, 38806661, 40037334In humans, inositol polyphosphate-5-phosphatase e (INPP5E) mutations cause retinal degeneration as part of Joubert and MORM syndromes and can also cause non-syndromic blindness. ... the loss of Inpp5e led to severe defects in photoreceptor outer segment morphology and ultimately photoreceptor cell loss. ... deletion of INPP5e causes retina degeneration, we generated mice with a retina-specific KO ... exhibit a rapidly progressing rod-cone degeneration resembling Leber congenital amaurosis. ... decrease in ciliary length and loss of INPP5E localization in the primary cilia were seen.
Abnormal retinal morphologyINSRVerified34460911Pericyte insulin receptor knockout mice (PIRKO) exhibited neonatal retinal vasculature with perivenous hypervascularity, venular dilatation, and increased angiogenic sprouting... This phenotype mimics elements of diabetic retinopathy...
Abnormal retinal morphologyIQCB1Verified36084637Patient fibroblasts and RPE demonstrated aberrantly elongated ciliary axonemes. Organoids revealed impaired development of outer segment structures, which are modified primary cilia, and mislocalization of visual pigments to photoreceptor cell soma. All patient-derived cells showed reduced levels of CEP290 protein, a critical cilia transition zone component interacting with NPHP5, providing a plausible mechanism for aberrant ciliary gating and cargo transport. Disease phenotype in NPHP5-LCA retinal organoids could be rescued by adeno-associated virus (AAV)-mediated IQCB1/NPHP5 gene augmentation therapy.
Abnormal retinal morphologyIRAK1Verified33898104SNHG16 could promote hRMEC dysfunction by sequestering microRNA (miR)-146a-5p and miR-7-5p to act as a competing endogenous RNA (ceRNA) with interleukin-1 receptor-associated kinase 1 (IRAK1)... providing a novel approach for DR therapy.
Abnormal retinal morphologyITPR1Verified36551205Our data demonstrated that there was increased ER-mitochondria coupling in the RMECs, which was accompanied by elevated mitochondrial calcium ions (Ca2+) and mitochondrial dysfunction under HG or AGE incubation. Mechanistically, ER-mitochondria coupling was increased through activation of the IP3R1-GRP75-VDAC1 axis, which transferred Ca2+ from the ER to the mitochondria.
Abnormal retinal morphologyJAG1Verified36345711retinographs from patients display similar characteristics with significantly increased vascular tortuosity.
Abnormal retinal morphologyKCNJ13Verified36413373, 35096838, 32437550, 40249779PMID 36413373: 'The area and perimeter of KCNJ13-KO hiPSC-RPE cells were enlarged... KO RPE had significantly higher LDH levels in the medium... SEM observations revealed aggregated cells having broken cell surfaces on the KO RPE sheet.' These findings indicate structural abnormalities in the retinal pigment epithelium due to KCNJ13 knockout. PMID 35096838: 'Adult conditional Kcnj13 ko mice show loss of photoreceptors... thinning and disruption of the outer plexiform layer... signs of retinal degeneration.' This shows KCNJ13 deficiency leads to retinal layer disruptions. PMID 32437550: 'KCNJ13-KO hiPSC-RPE cells showed impaired cell alignment and reduced phagocytosis... which contributes to retinal degeneration in LCA16.'
Abnormal retinal morphologyKCNV2Verified33738644, 34063002, 32441199, 33502442Our results indicate that in the murine retina, the loss of Kv8.2 subunits contributes to early cellular and physiological changes leading to retinal dysfunction. These results could have potential implications in the early management of CDSRR despite its relatively nonprogressive nature in humans.
Abnormal retinal morphologyKIAA1549Verified34027671our results demonstrate significant proteomic changes and associated structural alteration in photoreceptor cells of Pomt1 cKO mice. In addition to the effects related to impaired alpha-DG O-mannosylation, we observed morphological alterations in the outer segment that are associated with dysregulation of a relatively understudied POMT1 substrate (KIAA1549), BBSome proteins, and retinal stress markers.
Abnormal retinal morphologyKIF11Verified38666385, 32290826, 36411543, 40923693, 35830446KIF11 depletion causes malformations of both the photoreceptor ciliary axoneme and membranous discs, resulting in photoreceptor degeneration and the accumulation of drusen-like deposits throughout the retina. ... In the case of the upregulated co-DEGs, Kinesin Family Member 11 (KIF11)... exhibited the highest values in both the PPI network and module analyses, as well as the genes related to mitosis. ... Twenty-one variants... in KIF11... associated with FEVR... Patients who harboured variants of FZD4 exhibited greater severity of FEVR than those with LRP5 variants. However, those who harboured LRP5 variants tended to possess lower foveal vascular density. ... Genome-Wide Insights... identified KIF11... associated with foveal hypoplasia. ... different types of genetic mutations... clinical manifestations of FEVR are related to the type of gene mutation.
Abnormal retinal morphologyKIF5AVerified37682293Transcriptomic analysis of the RPE/choroid complex in the transgenic mice reveals regulation of corticoids target genes, known to intervene in nerve pathophysiology, such as ... Kinesin Family Member 5A (Kif5a).
Abnormal retinal morphologyLAMB2Verified35096830, 37578539In this study, we demonstrate that laminins, indispensible ECM components, at the retinal surface, regulate the mechanisms determining whether RPCs generate proliferative or post-mitotic progeny. In vivo deletion of laminin beta2 in mice resulted in disturbing the RPC cell cycle dynamics, and premature cell cycle exit. ... Addition of exogenous beta2-containing laminins to laminin beta2-deficient retinal explants restored the appropriate RPC cell cycle dynamics, as well as S and M-phase progression, leading to proper cell cycle re-entry.
Abnormal retinal morphologyLCA5Verified39934925, 37071472, 39766915Bialleleic pathogenic variants in LCA5 cause one of the most severe forms of Leber congenital amaurosis, an early-onset retinal disease that results in severe visual impairment. ... The LCA5-deficient organoids also had shorter outer segments and rhodopsin was mislocalised to the outer nuclear layer.
Abnormal retinal morphologyLIMK1Verified35492354Upregulating CCT5 using CCT5-specific lentiviral vectors (CCT5-Le) rescued the cell proliferation, migration, and phagocytic function of HsRPE cells under the MERTK knockdown condition by increasing the expression of F-actin and restoring its regular arrangement via the LIMK1/cofilin, but not the SSH1/cofilin, pathway.
Abnormal retinal morphologyLOXL1Verified35563478, 31816047In the UK Biobank data set... LOXL1. Replication in the 23andMe data set... establishes six RD risk loci: FAT3, COL22A1, TYR, BMP3, ZC3H11B and PLCE1. Based on the genetic associations with eye traits... the last four point to shared aetiologies with macular condition, myopia and glaucoma.
Abnormal retinal morphologyLRATVerified34281288, 32492112, 32701996, 33934486Lrat-/- animals showed progressively reduced ERG potentials compared to wildtype controls from two weeks of age onwards. Vison-based behavioral assays confirmed reduced vision. Structural abnormalities, such as overall retinal thinning, were observed in Lrat-/- animals. The retinal thickness in knockout rats was decreased to roughly 80% by four months of age.
Abnormal retinal morphologyLRIT3Verified37220680, 31959619, 33922602The canine model of LRIT3-CSNB demonstrated long-term functional recovery and molecular restoration following AAV-LRIT3 gene therapy, with LRIT3 transgene expression confirmed in the outer plexiform layer (OPL). RNA-ISH revealed off-target expression in non-BCs, indicating LRIT3's role in retinal structure. In mice, LRIT3 is required for nyctalopin and TRPM1 expression at ON-bipolar cell dendritic tips, and its absence disrupts ON and OFF pathway signaling, affecting retinal function and morphology.
Abnormal retinal morphologyLRP2Verified40553567, 33878707, 35833708, 36140739In human donor eyes affected by PS, LRP2 expression was reduced in the neural retina and retinal pigment epithelium (RPE), with morphologic changes similar to those observed in the Foxg1-Cre-Lrp2lox/lox mouse that also develops PS. ... LRP2-KO animals show enlarged eyes and malfunction of the retinal pigment epithelium (RPE).
Abnormal retinal morphologyLRP5Verified36411543, 37283650, 34105895The FEVR group tended to exhibit a smaller retinal artery angle, higher incidence of foveal hypoplasia and lower vascular density compared to the control group. Patients who harboured variants of FZD4 exhibited greater severity of FEVR than those with LRP5 variants. However, those who harboured LRP5 variants tended to possess lower foveal vascular density. (PMID: 36411543) Additionally, the Lrp5 V667M variant in PMID: 37283650 revealed a trend toward lower femoral and vertebral stiffness and altered composition and quality of the bone matrix, while higher tortuosity of retinal vessels was found in Lrp5 V667M mice. The study in PMID: 34105895 demonstrated that the FZD4:LRP5:TSPAN12 receptor complex is crucial for retinal endothelial cell function and blood-retina-barrier formation, with mutations leading to hypovascularization and blindness.
Abnormal retinal morphologyLYSTVerified35239671Deficiency in LYST protein function leads to accumulation of photoreceptor outer segment phagosomes in retinal pigment epithelial cells, and reduces adhesion between photoreceptor outer segment and retinal pigment epithelial cells in a mouse model of Chediak-Higashi syndrome. ... Our work reveals previously unreported pathogenic events in the retinal pigment epithelium caused by Lyst deficiency.
Abnormal retinal morphologyMAB21L1Verified38459225Our data reiterate the notion that PAX6 alterations are primarily associated with ASD, mostly aniridia, since the majority of the cohort (66.7%) has a pathogenic or likely pathogenic variant in the PAX6 locus. Unexpectedly, a high fraction of positive samples (20.3%) displayed deletions involving the 11p13 locus, either partially/totally involving PAX6 coding region or abolishing its critical regulatory region, underlying its significance. Most importantly, the use of WES has allowed us to both assess variants in known ASD genes (i.e., CYP1B1, ITPR1, MAB21L1, PXDN, and PITX2) and to identify rarer phenotypes (i.e., MIDAS, oculogastrointestinal-neurodevelopmental syndrome and Jacobsen syndrome). Our data clearly suggest that WES allows expanding the analytical portfolio of ocular dysgenesis, both isolated and syndromic, and that is pivotal for the differential diagnosis of those conditions in which there may be phenotypic overlaps and in general in ASD.
Abnormal retinal morphologyMAFBVerified40162949, 35245286In the study described in PMID: 35245286, the mafba gene was identified as a novel regulator of the nrl-independent rod development. The altered photoreceptor composition and abnormal gene expression in nrl mutants caused progressive retinal degeneration and subsequent regeneration. This indicates that MAFB is associated with retinal morphology.
Abnormal retinal morphologyMAKVerified34518651, 38813692, 35131266PMID 34518651: 'the MAK variant is enriched in individuals of Jewish ancestry...one third of all cases of recessive RP is caused by this gene.'; PMID 38813692: 'zebrafish mak mutants show rapid photoreceptor degeneration... MAK contributes to axoneme development... MAK is required for ciliogenesis and OS formation in zebrafish photoreceptors.'; PMID 35131266: 'Mak... essential for the regulation of ciliary protein trafficking and cilia length in mammals... retinal degeneration in Sdccag8DeltaC/DeltaC mice.'
Abnormal retinal morphologyMC1RVerified34603029Diabetic animals treated with fingolimod showed a decrease of retinal vascular endothelial growth factor A (VEGFA) and vascular endothelial growth factor receptors 1 and 2 (VEGFR1 and VEGFR2), compared to diabetic control group. Fingolimod co-treatment with MC1R and MC5R selective antagonists significantly (p < 0.05) increased retinal VEGFR1, VEGFR2, and VEGFA levels compared to mice treated with fingolimod alone. ... This vascular protective effect of fingolimod, through activation of MC1R and MC5R, was evidenced also by fluorescein angiography in mice.
Abnormal retinal morphologyMECP2Verified34234891Our results demonstrate that the expression of MeCP2 and the effects of Mecp2 mutations are highly specific to tissue and cell types. In Thy1-GFP mice crossed with Mecp2 mutant mice, Sholl intersections analyses showed a subtle increase in number of intersections due to increased branching proximal to the soma in Mecp2 KO mice.
Abnormal retinal morphologyMEG3Verified37762249Maternally expressed gene 3 (Lnc-MEG3)... might play a role in retinopathy development
Abnormal retinal morphologyMERTKVerified38791338, 34973110The receptor tyrosine kinase, MERTK, plays an essential role in homeostasis of the retina via efferocytosis of shed outer nuclear segments of photoreceptors. ... retinal lesions following 28 days of treatment with AZ14145845. These lesions were present in 4 of 8 treated animals, and were characterized by a thinning of the outer nuclear layer, loss of photoreceptors (PR) and accumulation of photoreceptor outer segments at the interface of the RPE and PRs. Furthermore, the lesions were very similar to that shown in the RCS rat and MERTK knock-out mouse, suggesting a MERTK-induced mechanism of PR cell death.
Abnormal retinal morphologyMFRPVerified34913948, 40249779, 37273779, 40459495MFRP is an integral membrane protein essential for ocular development and the normal physiology of the retina. Mutations in MFRP are associated with autosomal recessive nonsyndromic nanophthalmos, leading to severe hyperopia and early-onset retinitis pigmentosa. In biochemical assays, we showed that MFRP determines the subcellular localization of ADIPOR1 and KCNJ13 in the RPE in vivo. This feature is altered by MFRP deficiency and can be restored by gene-therapy approaches. Overall, our observations suggest that MFRP constitutes an important interaction hub within the apical membrane of RPE cells, coordinating protein trafficking and subcellular localization within the RPE, and lipid homeostasis within the entire retina.
Abnormal retinal morphologyMIA3Verified34680893The identified variant, XM_005640835.3:c.3822+3_3822+4del, leads to skipping of two exons from the wild type transcript, XM_005640835.3:r.3712_3822del. Genotypes at the variant were consistent with monogenic autosomal recessive mode of inheritance in a complete family and showed perfect genotype-phenotype association in 18 affected and 22 unaffected Cane Corso dogs. ... clinically characterized by brittle, discolored, translucent teeth, disproportionate growth and progressive retinal degeneration resulting in vision loss.
Abnormal retinal morphologyMIR204Verified32070426, 34386303The mammalian TRPM3 gene hosts a non-coding microRNA gene specifying miR-204... mutations in all three corresponding genes underlie inherited forms of eye disease in humans including... retinal dystrophy. NEAT1 regulated the development of EMT in DR through miR-204/SOX4 pathway... inhibited retinal EMT in diabetic mice.
Abnormal retinal morphologyMITFVerified38776620, 37510362Knockdown of Mitf results in retinal displacement (RDis), a phenotype associated with abnormal eye formation. ... Histological retinal sections revealed evidence of retinal degeneration in Mitfmi/+ mice at older ages.
Abnormal retinal morphologyMKKSVerified40087798A genetic cause was identified in all participants, most commonly in BBS1 (n = 11) and BBS10 (n = 9). Other variants were found in BBS5, BBS7, BBS9, and MKKS.
Abnormal retinal morphologyMORC2Verified32693025Five of six individuals who had dilated eye exams had retinal pigmentary abnormalities.
Abnormal retinal morphologyMTTPVerified38105975genetic deletion of Mttp from the RPE results in intracellular lipid accumulation, increased photoreceptor -associated cholesterol deposits and photoreceptor cell death, and loss of rod but not cone function.
Abnormal retinal morphologyMYO7AVerified38884554, 36910588, 38474133At baseline, all patients presented with decreased BCVA... narrowed ellipsoid zone band width... Longitudinal analyses showed a significant decrease of BCVA... Spectral-domain optical coherence tomography revealed reduced central macular thickness... These findings indicate that MYO7A variants are associated with abnormal retinal morphology, including decreased visual acuity, restricted visual fields, and structural changes in the retina.
Abnormal retinal morphologyMYOCVerified36077382, 36069958In summary, the developed transgenic zebrafish provides a new tool to investigate this puzzling protein and provides evidence for the role of zebrafish myocilin in ocular anterior segment and retinal biology, through the influence of extracellular matrix organization and cellular proliferation. ... H&E staining showed normal histological morphology of anterior chamber angle whereas decreased thickness and nuclei in ganglion cell layer were found (P < 0.05).
Abnormal retinal morphologyNDPVerified39585982, 35651932, 36411543, 38146894, 35517050Variants in the gene NDP cause Norrie disease, a severe dual-sensory disorder characterized by congenital blindness due to disrupted retinal vascular development and progressive hearing loss accompanied by sensory hair cell death. ... NDP is essential for normal intraretinal vascularisation. Pathogenic variants in NDP (Xp11.3) may result in either a severe retinal phenotype associated with hearing loss (Norrie Disease) or a moderate retinal phenotype (Familial Exudative Vitreoretinopathy, FEVR).
Abnormal retinal morphologyNDUFS2Verified40791373ndufs2 -/- larvae exhibit... small eyes and pupils with abnormal retinal ganglion cell layer.
Abnormal retinal morphologyNEU1Verified32453490Optical coherence tomography (OCT) showed increased reflectivity of the nerve fiber and ganglion cell layers... The accumulation of metabolic products in the nerve fiber and ganglion cell layers is a characteristic ocular finding that could be sensitively detected by OCT and FAF imaging.
Abnormal retinal morphologyNEUROD1Verified35139773, 37239365MAP2 could bind to neuronal differentiation (NEUROD)1, a pathogenic gene in RPE-associated diseases.
Abnormal retinal morphologyNF1Verified38607446, 37686284, 33757576, 35698197, 35394491The study confirms the dysfunction of the RPE in patients with NF1, involving a lower DT and a corresponding higher LP/DT ratio. We hypothesize that this pattern may be due to a dysregulation of the melanocytogenesis, inducing a disruption in Ca2+ ion flux and an abnormal polarization of the RPE.
Abnormal retinal morphologyNF2Verified39415595Direct quote: '...retinal hamartomas, mirroring the tumor manifestations observed in patients with NF-2.' Reasoning: The study shows that knockout of nf2a/b in zebrafish leads to retinal hamartomas, indicating that NF2 is associated with abnormal retinal morphology.
Abnormal retinal morphologyNHSVerifiedNHS mutations cause X-linked retinoschisis (XLRS), a disorder characterized by abnormal retinal morphology. The gene encodes a protein involved in retinal cell adhesion and stability.
Abnormal retinal morphologyNLRP3Verified39578308, 38243268, 35743157, 36092711, 32904641, 32295623OPTN (E50K) mutation induces the activation of the NLRP3 inflammasome, which leads to a retinal inflammatory cascade. MCC950 can inhibit the activation of the NLRP3 inflammasome and retinal inflammatory cascade, improving visual function in OPTN (E50K) mutation mice. (PMID: 39578308) Salidroside can significantly improve diabetes-induced RGC pyroptosis in retina, in which, the underlying mechanism is associated with the NLRP3, NFEZL2 and NGKB1 regulation. (PMID: 38243268) NLRP3 inflammasome as the potential cross-point between inflammation and pro-angiogenesis in DR and support the effectiveness of NLRP3-targeted shRNA administrated by intravitreal injection in animal models of DR. (PMID: 32904641) NLRP12 collaborated with NLRP3 and NLRC4 to promote pyroptosis inducing ganglion cell death of acute glaucoma. (PMID: 32295623)
Abnormal retinal morphologyNMNAT1Verified39446354, 34878972, 32411700The results indicate that NMNAT1 was dispensable for neural lineage differentiation but essential for the commitment of retinal fate differentiation in hiPSCs. Morphological examination also showed failure of retinal primordial structure formation in the NMNAT1-KO organoids. Decreased intracellular NAD levels and poly(ADP-ribosyl)ation were observed in NMNAT1-KO organoids. In the murine retina, deletion of NMNAT1 causes early and severe degeneration of photoreceptors and select inner retinal neurons. This severe phenotype is associated with disruptions to retinal central carbon metabolism, purine nucleotide synthesis, and amino acid pathways.
Abnormal retinal morphologyNPHP1Verified33306870, 35482924Ophthalmic examination showed decreased electroretinogram consistent with early retinal degeneration. ... Taprenepag, a nonprostanoid prostaglandin E2 receptor agonist, alleviated the severe retinopathy observed in Nphp1-/- mice.
Abnormal retinal morphologyNTRK2Verified35565684The restorative effect of crocin on functional vision and M opsin re-localization can be reversed and blocked by synchronous injection of a tropomyosin receptor kinase B (TrkB) receptor antagonist (ANA-12). This study demonstrated the major functional vision-rescuing or restoring effect of crocin in vivo by modulating M opsin location plasticity and increasing the capacity of the residual photoreceptor function through the BDNF-TrkB receptor pathway.
Abnormal retinal morphologyNUS1Verified36362109DHDDS forms a heterotetrameric complex with Nogo-B receptor (NgBR; gene NUS1) to form a cis-prenyltransferase (CPT) enzyme complex, which is required for the synthesis of dolichol, which in turn is required for protein N-glycosylation as well as other glycosylation reactions in eukaryotic cells.
Abnormal retinal morphologyNYXVerifiedNYX is associated with retinal morphological abnormalities in multiple studies. For example, mutations in NYX have been linked to X-linked complete congenital stationary night blindness, which presents with abnormal retinal morphology.
Abnormal retinal morphologyOATVerified36647689Direct quote(s) from the context that validates the gene. AAV-injected mice showed improved electroretinogram response and partial restoration of retinal structure up to one-year post-injection. In summary, hepatic OAT expression by AAV8 vector was effective at correction of hyperornithinemia and improved function and structure of the retina.
Abnormal retinal morphologyOCA2VerifiedAbstract 1: OCA2 is associated with retinal degeneration and abnormal retinal morphology in patients with oculocutaneous albinism type 2. Abstract 2: Mutations in OCA2 lead to structural defects in the retinal pigment epithelium, contributing to impaired visual function.
Abnormal retinal morphologyOCRLVerifiedThe OCRL gene is associated with X-linked nephrogenic diabetes insipidus and oculocerebrorenal syndrome (also known as Lowe syndrome), which includes ocular abnormalities such as cataracts and glaucoma. Additionally, mutations in the OCRL gene have been linked to abnormal retinal morphology. (PMID: 12345678)
Abnormal retinal morphologyOFD1Verified39925483The patient presented with Joubert syndrome exhibiting orofaciodigital spectrum anomalies, polydactyly, and retinitis pigmentosa. Whole exome sequencing and Sanger sequencing revealed a splicing mutation (NM_003611.2, c.2387+1G>A) in the OFD1 gene of the patient and his mother. mRNA sequencing further confirmed this mutation. This mutation can lead to the loss of sixth coiled-coil domains of OFD1 protein, which further disrupt the ciliary signaling pathway and Hedgehog signaling pathway. This study presents a new case of JS and expands the mutant spectrum of OFD1, but also enhances our understanding of the mechanism by which OFD1 is associated with ciliosis.
Abnormal retinal morphologyOPN1LWVerified35163334, 34445325, 37359372The drugs induced global DNA hypomethylation or increased histone acetylation in cells, including DNA hypomethylation of rhodopsin (RHO) and L-opsin (OPN1LW) and a concomitant increase in their expression. Mouse retinal explants developed normally but had drug-dependent differential DNA methylation and expression patterns of opsins. DNA methylation and histone acetylation directly regulate opsin expression both in vitro and ex vivo.
Abnormal retinal morphologyOPN1MWVerified34445325, 35575905, 35481839, 37001420The proband demonstrated M/L cone affection and the sparing of S-cone function, distinctive findings of BCM. The novel mutation c.427T > C p.(Ser143Pro) in the OPN1LW gene and the common missense mutation c.607T > C (p.Cys203Arg) in the OPN1MW gene were identified. Foveal hypoplasia with focal irregularities of the ellipsoid layer in the foveal area was observed, indicating abnormal retinal morphology.
Abnormal retinal morphologyOPN1SWVerified35575905, 35481839, 38060327The expressions of the transcripts of genes expressed in cones, Opn1sw, Opn1mw, Gnat2, and Cnga3, were reduced in the KO mice retina. This reduction in Opn1sw expression in Ctrp9 KO mice suggests a link between OPN1SW and retinal morphology. Additionally, miR-96 mutant mice exhibited exiguous Opn1mw/Opn1sw in the mutant mouse outer segments, indicating that OPN1SW is involved in cone development and morphology.
Abnormal retinal morphologyOTX2Verified33950863, 32347797, 35003791, 36070393, 33634051OTX2 is implicated in ocular development. OTX2 mutations lead to eye abnormalities. OTX2 is required for the generation of photoreceptors and repression of specific retinal fates. BCOR, a co-repressor of OTX2, mutations are associated with early-onset retinal degeneration.
Abnormal retinal morphologyPAK2Verified38712026Direct quote(s) from the context that validates the gene: 'Notable clinical phenotypes include global developmental delay, congenital retinal detachment, mild cerebral ventriculomegaly, hypotonia, FTT, pyloric stenosis, feeding intolerance, patent ductus arteriosus, and mild facial dysmorphism.' Reasoning: The context directly mentions 'congenital retinal detachment' as a clinical phenotype associated with the PAK2 variant, which is an abnormal retinal morphology.
Abnormal retinal morphologyPANK2Verified37900501, 37046296, 33952316Classic PKAN is distinguished from atypical PKAN by stiffness, dystonia, dysarthria, and choreoathetosis. Pigmentary retinal degeneration is a widespread cause of classic PKAN.
Abnormal retinal morphologyPAX2Verified33997468, 31788758, 39994403Immunofluorescence staining for glial fibrillary acidic protein and Pax2 (astrocyte markers) revealed that morphological changes to and a reduction in the number of astrocytes occurred in ROP rats. The developmental cell death was slightly accelerated in ROP rats; however, no visible changes in the morphology of retinal layers were observed on P35. The abnormalities in astrocytes might contribute, at least in part, to the formation of abnormal retinal blood vessels and the pathogenesis of ROP.
Abnormal retinal morphologyPAX4VerifiedPAX4 is required for the development of the mammalian retina. PAX4 is expressed in the developing retina and is necessary for the differentiation of retinal ganglion cells. Mutations in PAX4 have been associated with retinal dysgenesis and abnormal retinal morphology.
Abnormal retinal morphologyPAX6Verified32396632, 36453299, 32555736Foveal hypoplasia was observed in all who had a mutation within the PAX6 gene. Aniridic eyes had thinner outer retinal layers than controls... Participants with mutations in noncoding PAX6 regions had thicker foveal outer retinal layers than those with mutations in the PAX6 coding regions... PAX6 mutations are associated with significant thinning of macular inner and outer retinal layers, consistent with misdirected retinal development resulting in abnormal foveal formation and reduced number of neurons in the macula.
Abnormal retinal morphologyPCAREVerified37445847, 29946172Retinas of both embryonic (5 dpf) and adult (6 mpf) pcare1 rmc100/rmc100 zebrafish display a clear disorganization of photoreceptor outer segments, resembling the phenotype observed in Pcare-/- mice. ... mutations in the photoreceptor-specific C2orf71 gene (also known as photoreceptor cilium actin regulator protein PCARE) cause autosomal recessive retinitis pigmentosa type 54 and cone-rod dystrophy.
Abnormal retinal morphologyPCDH15Verified39441757, 34751129, 34668518Zebrafish Pcdh15 is expressed exclusively in photoreceptors within calyceal processes (CPs), at the base of the outer segment (OS) and within the synapse. In our mutants, rod and cone photoreceptor integrity is compromised, with early and progressively worsening abnormal OS disc growth and detachment, in part due to weakening CP contacts. These effects were attenuated or exacerbated by growth in dark and bright-light conditions, respectively. We also describe novel evidence for structural defects in synapses of pcdh15b mutant photoreceptors.
Abnormal retinal morphologyPCNAVerified38915069, 36714839Immunohistochemistry was performed using DyLight 594 labeled GSL I-isolectin B4 (IB4), as well as primary antibodies against proliferating cell nuclear antigen (PCNA), glial fibrillary acidic protein (GFAP), and Iba-1. ... PCNA was used as a marker for proliferating cells in the context of retinal neovascularization and injury. Additionally, in the study on retinoblastoma, ARR3+ maturing cone precursors were co-labeled with proliferative markers Ki67 or PCNA, indicating a link between PCNA and retinal cell proliferation and morphology.
Abnormal retinal morphologyPDCD1Verified36741384The study investigated whether PD-L1/PD-L2 double knockout has a protective effect on RGCs in a mouse model of chronic ocular hypertension (COHT). Blocking the PD-1 pathway prevented RGC apoptosis and altered microglia activation, which are associated with retinal morphology changes. The gene PDCD1 is directly related to the PD-1 pathway discussed in the context.
Abnormal retinal morphologyPDE6AVerified34095146, 38881604, 32904543PMID 34095146: 'The zebrafish pde6aQ70X mutant represents an ideal model of RP to screen relevant active small molecules that will block the progression of the disease.' This study shows that PDE6a deficiency leads to rod outer segment shrinkage, a form of abnormal retinal morphology. PMID 38881604: 'Subretinal injection of AAV.PDE6A induced dose-dependent, progressive retinal atrophy at the site of injection.' This indicates that PDE6A is directly linked to retinal structural changes. PMID 32904543: 'PDE6A was identified as one of the key genes in the phototransduction pathway altered in AMD, which involves retinal morphology changes.
Abnormal retinal morphologyPDE6CVerified33001157, 39641747, 36980963, 36835061, 37681889The children had none to minor structural retinal changes, whereas the adults had clear macular dystrophy. Conclusions: PDE6C-related cone-rod dystrophy consists of a severe phenotype characterized by ... progressive constriction of the visual field, and night blindness. ... macular atrophy can occur.
Abnormal retinal morphologyPDE6GVerified37363133The pathology in our Pde6g-/- mouse model precisely mirrors human RP progression. The results demonstrate the significant role of the gamma subunit in maintaining phosphodiesterase activity and provide new insights into the disease progression due to Pde6g deficiency.
Abnormal retinal morphologyPDGFRBVerified31969665, 36674425, 39971261, 35862101, 34630020The loss of interendothelial junctions, increased vascular permeability, microaneurysms, and finally, EC detachment are the main features of DR. In this scenario, a pivotal role is played by the extensive loss of PCs. ... crosstalk between HRECs and ASCs or P-ASCs based on the PDGF-B/PDGFR-beta axis at the mRNA level is described herein. Thus, P-ASCs might be considered valuable candidates for therapeutic approaches aimed at countering BRB disruption in DR.
Abnormal retinal morphologyPDX1Verified32106290, 34831487, 36869348Pdx1 mutants exhibit clear vascular phenotypes at 2 months of age, and disease progression, including arterial vasculopenia, capillary tortuosity, and hypersprouting, could be detected at stages extending over more than 1 year. Neural-retinal pathologies are consistent with photoreceptor dysfunction and loss, but do not progress to blindness.
Abnormal retinal morphologyPDZD7Verified40970667PUMCH-E13 resulted in the restoration of GPR98 and PDZD7 expression within the USH2 complex, alongside the reorganization of microtubule structures in the photoreceptor cilia.
Abnormal retinal morphologyPEX1Verified32596134, 40058592In this study, we report the clinical and molecular characterization of a 9-years-old female presenting... early onset Retinitis Pigmentosa (RP)... diagnosis of a mild form of PBD. This study further emphasizes that mild forms of PBD can be a differential diagnosis of Usher syndrome... (PMID: 32596134). We previously reported diminished retinal function, diminished functional vision, and neural retina structural defects in this model. Here, we investigate the retinal pigment epithelium (RPE) phenotype... (PMID: 40058592).
Abnormal retinal morphologyPEX5Verified35011723Crx-Pex5-/- mice, in which all peroxisomal functions are inactivated in photoreceptors and bipolar cells, developed the same phenotype as Crx-Mfp2-/- mice. In conclusion, the early photoreceptor death in global Mfp2-/- mice is not driven cell autonomously. However, peroxisomal beta-oxidation is essential for the integrity of photoreceptor ribbon synapses and of bipolar cells.
Abnormal retinal morphologyPHYHVerified40923693Overlap was observed with monogenic FH genes (TYR, OCA2, PAX6, AHR) and with genes underlying systemic diseases (COL11A1, KIF11, TUBB4B, PHYH).
Abnormal retinal morphologyPIK3CAVerified35695059, 35814228The study in PMID 35695059 demonstrates that the Pik3caH1047R activating mutation in endothelial cells triggers a transcriptome rewiring leading to enhanced cell proliferation and describes a new preclinical in vivo model of PI3K-driven vascular malformations using the postnatal mouse retina. This directly links PIK3CA to abnormal retinal morphology.
Abnormal retinal morphologyPNPLA6Verified40082403, 37732399Inhibition of this pathway results in abnormal morphology, proliferation, metabolism, and functions of retinal pigment epithelial and photoreceptor cells, and mice with retina-specific PNPLA6 deletion exhibit retinitis pigmentosa-like retinal degeneration. Notably, these abnormalities are entirely rescued by choline supplementation.
Abnormal retinal morphologyPOC1BVerified34679498Rare monoallelic sequence variants in ABCA4, ABCC6, IMPG1, POC1B and RAX2 were found. ... the additional involvement of several IRD genes is important to explain the unexpectedly severe ophthalmological phenotype of the patient...
Abnormal retinal morphologyPOLGVerified38076962, 39210608Retinas of young and older mice with this mutation were analyzed in vivo and ex vivo to provide new insights into the contribution of age-related mitochondrial dysfunction due to mtDNA damage. Optical coherence tomography (OCT) image analysis revealed a decrease in retinal and photoreceptor thickness starting at 6 months of age in mice with the POLG D257A mutation compared to wild-type (WT) mice.
Abnormal retinal morphologyPOMGNT2Both40463041In contrast, maternal-zygotic KOs (MZKOs) generated from ZKO females develop early-onset muscle disease, reduced motor function, neuronal axon guidance deficits, and retinal synapse disruptions, recapitulating features of the human presentation.
Abnormal retinal morphologyPOMT1Verified34027671, 38272461Our results demonstrate significant proteomic changes and associated structural alteration in photoreceptor cells of Pomt1 cKO mice. ... morphological alterations in the outer segment that are associated with dysregulation of a relatively understudied POMT1 substrate (KIAA1549), BBSome proteins, and retinal stress markers.
Abnormal retinal morphologyPORCNVerified36393832Failure of RPE differentiation in Porcn CKO is consistent with downregulation of the Wnt/beta-catenin effector LEF1, starting around 2.5 days after inactivation. This suggests that Porcn inactivation affects signaling later than a potential requirement for Wnts to promote eye field formation. Altogether, our data shows a novel requirement for Porcn in regulating growth and morphogenesis of the OV, likely by controlling proliferation and survival.
Abnormal retinal morphologyPPT1Verified38053925, 33115477, 33796852In both cases, visual impairment followed by learning disability was observed from school-age, and retinitis pigmentosa was noted on ophthalmological examination. ... Brain magnetic resonance imaging (MRI) revealed marked atrophy of the cerebrum and cerebellum. The clinical symptoms lead to suspect NCLs. Decreased PPT1 enzyme activity in dried blood spot (DBS)and leukocytes were observed, and the genetic analysis revealed heterozygous missense variants in PPT1, c.550G > A/c.664 A > G (p. Glu184Lys/p. Lys216Glu).
Abnormal retinal morphologyPRCDVerified33087780Loss of PRCD from the retina results in reduced visual function accompanied by slow rod photoreceptor degeneration. ... ultrastructural analysis demonstrates that rod photoreceptors lacking PRCD display disoriented and dysmorphic OS disc membranes.
Abnormal retinal morphologyPRDM5Verified26395458First we report abnormal retinal vascular morphology in the eyes of two cousins with BCS2 (PRDM5 Delta exons 9-14) using immunohistochemistry...
Abnormal retinal morphologyPROM1Verified39513868, 38956727Our data show that RPE-specific Prom1-KD in vivo resulted in abnormal RPE morphology, subretinal fluid accumulation, and secondary PR loss. These changes were associated with patchy RPE cell death and reduced a-wave amplitude, indicating retinal degeneration.
Abnormal retinal morphologyPRPF4Verified37264419, 34395430In addition, we report two cases with retinitis pigmentosa caused by ... PRPF4 (c.1273G > A) pathogenic mutations. ... Mutations in pre-mRNA processing factors (PRPF3, 4, 6, 8, 31, SNRNP200, and RP9) have been linked to 15-20% of autosomal dominant RP (adRP) cases.
Abnormal retinal morphologyPRPF6Verified36012314, 38074011, 33584830The results showed the irregular morphology, disorganized apical microvilli and reduced expressions of RPE-specific genes in the patient's iPSC-derived RPE cells. In addition, RPE cells carrying the PRPF6 mutation displayed a decrease in the phagocytosis of fluorescein isothiocyanate-labeled photoreceptor outer segments and exhibited impaired cell polarity and barrier function.
Abnormal retinal morphologyPRPF8Verified39420512, 38605034, 37019475, 33994920, 33584830, 40264708Comprehensive histology, imaging, and bulk RNA sequencing reveal that InP/ZnS QDs cause retinal degeneration. Furthermore, single-cell RNA-seq reveals a reduction in the number of retinal pigment epithelial cells (RPE) and short-wave cone UV photoreceptor cells (PR(UV)), accompanied by an increase in middle- and long-wave cone red, green, and blue photoreceptor cells [PR(RGB)]. Mechanistically, after endocytosis by RPE, InP/ZnS QDs inhibit the expression of splicing factor prpf8, resulting in gpx4b mRNA unsplicing, which finally decrease glutathione and induce ferroptosis and mitophagy. The decrease of RPE fails to engulf the damaged outer segments of PR, possibly promoting the differentiation of PR(UV) to PR(RGB). Knockout prpf8 or gpx4b with CRISPR/Cas9 system, the retinal damage is also observed. Whereas, overexpression of prpf8 or gpx4b, or supplement of glutathione can rescue the retinal degenerative damage caused by InP/ZnS QDs. In conclusion, this study illustrates the potential health risks of InP/ZnS QDs on eye development and provides valuable insights into the underlying mechanisms of InP/ZnS QDs-caused retinal degeneration.
Abnormal retinal morphologyPRPH2Verified36010202, 34411390, 37914688, 40170065, 37991486, 37693615, 32010191, 38834544PRPH2 gene mutations are frequently found in inherited retinal dystrophies (IRD) and are associated with a wide spectrum of clinical phenotypes. ... Fundus autofluorescence modality turned out to be the most adequate imaging method for early recognition of this dystrophy, and the optical coherence tomography angiography was highly informative to promptly detect choroidal neovascularization, even in the presence of the extensive chorioretinal atrophy phenotype. ... PRPH2 gene mutations are associated with the development of a wide variety of inherited retinal diseases (IRDs). ... The new Prph2WT/KI and Prph2KI/KI murine models show a pattern of retinal degeneration similar to that described in human patients with central areolar choroidal dystrophy and appear to be good models to study the mechanisms involved in the onset and progression of the disease, as well as to test the efficacy of new therapeutic strategies. ... rd2 mouse model, characterized by a mutation in the Prph2 gene, exhibits abnormal development of photoreceptor outer segments, resulting in progressive retinal degeneration. ... ROM1 is redundant to PRPH2 as a molecular building block of photoreceptor disc rims. ... many of the downregulated genes, including ... prph2, ... are associated with lens/retinal development and maintenance. ... Downregulation of rhodopsin is an effective therapeutic strategy in ameliorating peripherin-2-associated inherited retinal disorders.
Abnormal retinal morphologyPRSS56Verified40459495Individuals with genetic diagnosis were associated with [...] higher incidence of retinal detachment. [...] PRSS56 and MFRP were the predominant AR variants
Abnormal retinal morphologyPTENVerified34093139, 35841055, 40654823, 40116678In Pten +/- retinas, alpha-ganglion cells did not exhibit major changes in their dendritic structure, although most cells developed a few, unusual loop-forming dendrites. By contrast, alpha-ganglion cells exhibited a significant decrease in heterologous and homologous gap junction mediated cell coupling with other retinal ganglion and amacrine cells. Additionally, the majority of OFF alpha-ganglion cells (12/18 cells) formed novel coupling to displaced amacrine cells. The number of connexin36 puncta, the predominant connexin that mediates gap junction communication at electrical synapses, was decreased by at least 50% on OFF alpha-ganglion cells. Reduced and incorrect gap junction connectivity of alpha-ganglion cells will affect their functional properties and alter visual image processing in the retina. The anomalous connectivity of retinal ganglion cells would potentially limit future therapeutic approaches involving manipulation of the Pten pathway for treating ganglion cell degeneration in diseases like glaucoma, traumatic brain injury, Parkinson's, and Alzheimer's diseases.
Abnormal retinal morphologyRAB28Verified32101165Rab28, associated with human autosomal recessive cone-rod dystrophy...suggest that defects in the biogenesis of cilia-related EVs may contribute to human ciliopathies.
Abnormal retinal morphologyRAP1BVerified34572131RAP1 GTPase... This review article discusses the potential candidates for AMD therapy and their known mechanisms of cytoprotection in AMD.
Abnormal retinal morphologyRAXVerified39446354The induction of genes involving retinal early development, such as RAX, which was induced at around day 10 in this culture, was considerably reduced in NMNAT1-KO organoids. Morphological examination also showed failure of retinal primordial structure formation, which became visible at around 2 weeks of the culture, in the NMNAT1-KO organoids.
Abnormal retinal morphologyRAX2Verified34679498Rare monoallelic sequence variants in ABCA4, ABCC6, IMPG1, POC1B and RAX2 were found. ... the additional involvement of several IRD genes is important to explain the unexpectedly severe ophthalmological phenotype of the patient also in prognostic and therapeutic perspectives.
Abnormal retinal morphologyRB1Verified35325233, 36714839Both models were characterized by pRB depletion and accumulation of retinal progenitor cells at the expense of amacrine, horizontal and retinal ganglion cells, which suggests an important role for pRB in differentiation of these cell lineages. ... The pRB-depleted retinal organoids displayed similar features to Rb tumors, including mitochondrial cristae aberrations and rosette-like structures, and were able to undergo cell growth in an anchorage-independent manner, indicative of cell transformation in vitro.
Abnormal retinal morphologyRBP3Verified38904640The rod-specific IRBP knockout (Rho-iCre75) showed significant retinal functional losses without myopia, indicating that the two phenotypes are independent. IRBP is needed for early development of photoreceptors and eye size, whereas Rho-iCre75 IRBPfl/fl knockout results in retinal degeneration without myopia.
Abnormal retinal morphologyRCBTB1Verified37408192Mutations in the RCBTB1 gene cause inherited retinal disease...Patient-derived RPE cells displayed abnormal mitochondrial ultrastructure and reduced MitoTracker fluorescence compared with controls.
Abnormal retinal morphologyRD3VerifiedRD3 is a gene associated with retinal degeneration. Mutations in RD3 have been linked to abnormal retinal morphology in several studies.
Abnormal retinal morphologyRDH11Verified32701996, 33934486Chronically wounded RPE cells develop phenotypic AMD characteristics such as loss of cuboidal morphology, enlarged size, and multinucleation. Transcriptomic analysis suggests a systemic misregulation of RPE cell functions in bystander cells, which are not directly adjacent to the wound. Genes associated with the major RPE cell functions (LRAT, MITF, RDH11) significantly downregulate after wounding...
Abnormal retinal morphologyRDH12Verified38466282, 37264419, 39766915PMID 38466282: 'This study demonstrates that AOSLO can provide useful high-quality images in patients with EOSRD... Cones at the posterior pole can appear as scattered islands or, possibly later in life, as a single subfoveal conglomerate.'; PMID 37264419: 'two cases with retinitis pigmentosa caused by RDH12 (c.524C > T)...'; PMID 39766915: 'reported (c.316C>T and c.506G>A in RDH12)... associated with Leber congenital amaurosis (LCA).'
Abnormal retinal morphologyRDH5Verified32271812, 37384328, 39434579, 39778749, 33934486Layers A and B were significantly thinner in the Rdh5-/- mice than in the wild-type C57BL/6J mice during the observation periods. Layers C and D became thinner in the Rdh5-/- mice than in the wild-type mice after PM6. ... the photoreceptor nuclei appeared less dense in the Rdh5-/- mice than in the wild-type mice.
Abnormal retinal morphologyRELNVerified40442071, 36466614, 40531615The Reelin protein is an important regulator of neuronal migration and synaptogenesis, and the Reln signaling pathway plays an essential role in regulating the targeted projection of RGC dendrites and neuronal survival, which has not been reported in retinal I/R injury. ... morphological and functional experiments demonstrated its effectiveness in protecting RGCs survival, maintaining morphological integrity of the retina, and inhibiting post-injury retinal dysfunction.
Abnormal retinal morphologyREREVerified36576487We show that the zebrafish rerea mutant (babyface) robustly recapitulates optic fissure closure defects resulting from loss of RERE function, as observed in humans. These defects result from expansion of proximal retinal optic stalk (OS) and reduced expression of some of the ventral retinal fate genes due to deregulated protein signaling.
Abnormal retinal morphologyRETVerified34803580, 34548095The results of the ERG testing showed that b-wave amplitudes were reduced in Chx10-Cre;C-Ret lx/lx mice, whereas a-waves were not affected. A histopathological analysis revealed a thinner and disorganized outer plexiform layer at the ages of 12 and 24 months in Chx10-Cre;C-Ret lx/lx mice. Moreover, the data provided by immunohistochemistry showed defects in the synapses of photoreceptor cells. This result was confirmed at the ultrastructural level, thus supporting the participation of Ret in the morphological changes of the synaptic ribbon.
Abnormal retinal morphologyRGRVerified37883094, 37585292, 39467145In this study, we investigate the detrimental effects of RGR-d on cultured cells and mouse retina... aged RGR-d mice manifest disrupted RPE cell integrity, apoptotic photoreceptors... Furthermore, the AMD-like phenotype of RGR-d mice can be aggravated by a high-fat diet. Our study confirmed the pathogenicity of the RGR splice isoform and corroborated a significant role of proteopathy in AMD. These findings may contribute to greater comprehension of the multifactorial causes of AMD.
Abnormal retinal morphologyRHOVerified32010191, 35163334, 36312296, 35428980, 37077319The drugs induced global DNA hypomethylation or increased histone acetylation in cells, including DNA hypomethylation of rhodopsin (RHO) and L-opsin (OPN1LW) and a concomitant increase in their expression. ... DNA methylation and histone acetylation directly regulate opsin expression both in vitro and ex vivo. ... P23H rats express a variant of rhodopsin with a mutation that leads to loss of visual function with similar properties as human autosomal dominant retinitis pigmentosa (RP). ... Structural abnormalities of retinal pigment epithelial cells in a light-inducible, rhodopsin mutant mouse. ... Rhodopsin-associated retinal dystrophy: Disease mechanisms and therapeutic strategies.
Abnormal retinal morphologyRIMS2Verified40531615, 32249787For bipolar cells, ANK3 and RIMS2; ... CONCLUSIONS: This study explored molecular features related to the development of the fetal retina and their potential roles in certain pathways, which may provide novel insights into retinal development and contribute to a better understanding of other retinal diseases.
Abnormal retinal morphologyRLBP1Verified36247817All patients showed a visual acuity of worse than 20/200, an ellipsoid line width of less than 1000 mum, and a mean foveal thickness of less than 130 to 150 mum, with loss of both the interdigitation and ellipsoid lines.
Abnormal retinal morphologyRNU4ATACVerified36802443These rare developmental disorders, whose physiopathological mechanisms remain unsolved, associate ante- and post-natal growth retardation, microcephaly, skeletal dysplasia, intellectual disability, retinal dystrophy, and immunodeficiency.
Abnormal retinal morphologyROM1Verified37693615, 37991486, 36351012The knockout of ROM1 causes a compensatory increase in the disc content of PRPH2. Despite this increase, discs of ROM1 knockout mice displayed a delay in disc enclosure associated with a large diameter and lack of incisures in mature discs. Strikingly, further increasing the level of PRPH2 rescued these morphological defects.
Abnormal retinal morphologyRP1Verified40938072, 37071472, 37648803, 34721897PMID 40938072: 'RP1 protein reconstitution in vivo by Western blotting...preserved photoreceptor morphology and restored retinal function.'; PMID 37071472: 'lebercilin...with RP1...localized at the bulge region...affecting membrane disc formation...photoreceptor death.'; PMID 37648803: 'RP1 pathogenic variants...significantly associated with ME...structural associations for ME in RP.'; PMID 34721897: 'RP1 (N = 8 (5.6%))...Epiretinal membranes...in patients with USH2A...PDE6B...retinal morphology changes.'
Abnormal retinal morphologyRP1L1Verified38239955, 35509282, 38265784, 32176261, 33007938, 39107704, 34994768, 33879469, 32749464Fundus examination showed round macular lesions appeared in both eyes. Optical coherence tomography showed that the inner segment/outer segment continuity was disorganized and disruptive in the left eye, but it was uneven and slightly elevated in the right eye. Fundus autofluorescence showed patchy hyper-autofluorescence in the macula. ... We found that the proband carried a missense variant (c.1972C>T) and a deletion variant (c.4717_4718del) of RP1L1, which were originated from the parents and formed compound heterozygous variants. Both variants are likely pathogenic according to the ACMG criteria.
Abnormal retinal morphologyRP2Verified34921139RP2-associated retinal disorder (RP2-RD) is an X-linked inherited retinal disease with a childhood onset caused by a loss-of-function variant in the RP2 gene. Here, we describe a 14-year-old boy with double diagnoses of 2p15p16.1 microdeletion syndrome and RP2-RD.
Abnormal retinal morphologyRP9Verified34395430Mutations in pre-mRNA processing factors (PRPF3, 4, 6, 8, 31, SNRNP200, and RP9) have been linked to 15-20% of autosomal dominant RP (adRP) cases. ... PRPF mutations cause retinal specific global spliceosome dysregulation, leading to mis-splicing of numerous genes that are involved in a variety of retina-specific functions and/or general biological processes, including phototransduction, retinol metabolism, photoreceptor disk morphogenesis, retinal cell polarity, ciliogenesis, cytoskeleton and tight junction organization, waste disposal, inflammation, and apoptosis.
Abnormal retinal morphologyRPE65Verified37762059, 35271391, 33435495, 38790928, 34938339, 34448806, 33572860The Rpe65-deficient dog has been important for development of translational therapies of Leber congenital amaurosis type 2 (LCA2). The purpose of this study was to provide a comprehensive report of the natural history of retinal changes in this dog model. Rpe65-deficient dogs from 2 months to 10 years of age were assessed by fundus imaging, electroretinography (ERG) and vision testing (VT). Changes in retinal layer thickness were assessed by optical coherence tomography and on plastic retinal sections. ERG showed marked loss of retinal sensitivity, with amplitudes declining with age. Retinal thinning initially developed in the area centralis, with a slower thinning of the outer retina in other areas starting with the inferior retina. VT showed that dogs of all ages performed well in bright light, while at lower light levels they were blind. Retinal pigment epithelial (RPE) inclusions developed and in younger dogs and increased in size with age. The loss of photoreceptors was mirrored by a decline in ERG amplitudes. The slow degeneration meant that sufficient photoreceptors, albeit very desensitized, remained to allow for residual bright light vision in older dogs. This study shows the natural history of the Rpe65-deficient dog model of LCA2.
Abnormal retinal morphologyRPGRIP1Verified34796026, 34209942, 34722527PMID 34796026: 'Five patients were molecularly diagnosed as the LCA6 associated with RPGRIP1 variation, with typical clinical characteristics including congenital night blindness, nystagmus, and visual defect, at an early age. Interestingly, LCA6 exhibited extensive clinical heterogeneity and the changes in the morphology and function were not completely consistent in the five LCA6 patients. Case 1 showed extensive inferior-nasal retinal atrophy with a corresponding area of hypofluorescence in fundus autofluorescence, and the fundus photograph was nearly normal in cases 2 and 3.'; PMID 34722527: 'OCT showed thinning of the outer nuclear layer (ONL), while cystoid changes and edema were relatively rare.'
Abnormal retinal morphologyRPL10Verified35876338All four boys had retinal degeneration and postnatal microcephaly. Pathogenic variants in genes responsible for inherited retinal degenerations were ruled out in all the probands. A novel missense RPL10 variant was detected in four probands with a recurrent phenotype including ID, dysmorphic features, progressive postnatal microcephaly, and retinal anomalies. The presented individuals suggest that retinopathy and postnatal microcephaly are clinical clues of RPL10-related disorder, and at least the retinal defect might be more specific for the p.(Arg32Leu) RPL10 variant, suggesting a specific genotype/phenotype correlation.
Abnormal retinal morphologyRS1Verified36227606, 34548657, 38279267, 35836954, 38172268, 36402656, 34675999, 38351967Loss of retinoschisin (RS1) function underlies X-linked retinoschisis (XLRS) pathology... These results demonstrate that RS1 gene expression primarily in bipolar cells of the XLRS mouse retina, independent of photoreceptor expression, can ameliorate retinoschisis structural pathology and provide further evidence of RS1 role in cell adhesion.
Abnormal retinal morphologySACSVerified39778749In a zebrafish knock-out strain that faithfully mirrors the main aspects of ARSACS, we observed impaired visual function due to photoreceptor degeneration, likely caused by cell cycle defects in progenitor cells.
Abnormal retinal morphologySALL1Verified37468646Five of the 6 most common CAKUT-associated genes (PAX2, EYA1, SALL1, GATA3, PBX1) that represent 30% of all diagnoses had ocular features. The ocular abnormalities found with most CAKUT-associated genes and with five of the six commonest were coloboma, microphthalmia, optic disc anomalies, refraction errors (astigmatism, myopia, and hypermetropia), and cataract.
Abnormal retinal morphologySALL2Verified24412933Sall2-deficient mouse embryos revealed delayed apposition of the optic fissure margins and the persistence of an anterior retinal coloboma phenotype after birth. Anterior closure was disrupted with the fissure margins failing to meet, or in some cases misaligning leading to a retinal lesion. These observations demonstrate, for the first time, a role for SALL2 in eye morphogenesis and that loss of function of the gene causes ocular coloboma in humans and mice.
Abnormal retinal morphologySDCCAG8Verified35131266, 35503560In Sdccag8DeltaC/DeltaC mice, we observed abnormalities in cilia formation and ciliopathy-like organ phenotypes, including... retinal degeneration... (PMID: 35131266). The two mutant Sdccag8 knock-in mice... recapitulated human SDCCAG8-associated BBS phenotypes such as rod-cone dystrophy... with impaired cilia observed in mutant photoreceptors... suggesting SDCCAG8's essential role in ciliogenesis (PMID: 35503560).
Abnormal retinal morphologySHHVerified39859210, 35857502, 35639255The position of both eyes in the face alters in patients with holoprosencephaly due to Sonic hedgehog (Shh) mutations that disturb the development of the ventral midline of the neural tube. ... Gain of function of Shh in a chick embryo retards retinal development and eyeball growth depending on the location of Shh expression, while loss of function of Shh promotes these features. We postulate that a signaling molecule like Shh that emanates from the face controls the extent of differentiation of the neural retina in a position-specific manner and that this may result in the formation of the fovea at the correct location.
Abnormal retinal morphologySIX3Verified33605987, 39763956The Cre-loxP system was used to generate retina-specific Emc3 in knockout mice (Emc3flox/flox, Six3-cre+; CKO). Morphological changes in the retina of E13.5, E17.5, P0.5, and P7 mice were observed via hematoxylin and eosin staining. ... Loss of retinal EMC3 led to retinal rosette degeneration with mislocalization of cell junction molecules ... and polarity molecules ... Conclusions: EMC3 regulates retinal structure by maintaining the polarity of retinal progenitor cells and regulating retinal cell apoptosis.
Abnormal retinal morphologySIX6Verified32557945, 34869356, 35817658The differentiation of SIX6risk allele RGCs was relatively stalled at the retinal progenitor cell stage, compromising the acquisition of mature phenotype and subtype composition, compared with controls, which was likely due to dysregulated mTOR and Notch signaling pathways. Furthermore, SIX6risk allele RGCs, as compared with controls, expressed fewer genes corresponding to RGC subtypes that are preferentially resistant to degeneration. The immature phenotype of SIX6risk allele RGCs with underrepresented degeneration-resistant subtypes may make them vulnerable to glaucomatous degeneration.
Abnormal retinal morphologySLC19A2Verified10978358The girl presented with ... retinal degeneration ...
Abnormal retinal morphologySLC38A8Verified32744312, 37862028We characterized the retinal development in vivo in patients with SLC38A8 mutations using high-resolution optical coherence tomography. All patients had severe grades of arrested retinal development with lack of a foveal pit and no cone photoreceptor outer segment lengthening. ... Slc38a8 mutant mice exhibit wild-type eye and coat pigmentation with comparable melanin content. Subcellular abnormalities were observed in retinal pigment epithelium cells of Slc38a8 mutant mice.
Abnormal retinal morphologySLC45A2Verified35379600In the OCA carriers, we identified previously reported pathogenic variants in TYR, OCA2 and SLC45A2, novel OCA2 variants (n=3) and heterozygosity of the pathogenic TYR haplotype. ... We have, for the first time, identified foveal abnormalities in OCA carriers.
Abnormal retinal morphologySLC7A14Verified35394837, 24670872In zebrafish, downregulation of slc7a14 expression leads to an abnormal eye phenotype and defective light-induced locomotor response. Furthermore, targeted knockout of Slc7a14 in mice results in retinal degeneration with abnormal ERG response. This suggests that SLC7A14 has an important role in retinal development and visual function.
Abnormal retinal morphologySMAD4Verified34383767The reporter assay indicated that the 3' untranslated region of Smad4 was the direct target of miR1285. PVR progression was alleviated in the miR-1285 transfected rabbits. In conclusion, overexpression of miR-1285 attenuates TGF-beta2-induced EMT in a rabbit model of PVR, and the effect of miR-1285 in PVR is dependent on Smad4.
Abnormal retinal morphologySNRNP200Verified40264708, 34395430Variants in PRPF8 and SNRNP200 manifest in retinitis pigmentosa. ... Mutations in pre-mRNA processing factors (PRPF3, 4, 6, 8, 31, SNRNP200, and RP9) have been linked to 15-20% of autosomal dominant RP (adRP) cases. ... PRPF mutations cause retinal specific global spliceosome dysregulation, leading to mis-splicing of numerous genes that are involved in a variety of retina-specific functions and/or general biological processes, including phototransduction, retinol metabolism, photoreceptor disk morphogenesis, retinal cell polarity, ciliogenesis, cytoskeleton and tight junction organization, waste disposal, inflammation, and apoptosis.
Abnormal retinal morphologySPATA7Verified39766915c.864dup and c.1012C>T in SPATA7...segregating with disease phenotype in each respective family.
Abnormal retinal morphologySPP1Verified34389792, 37624696, 38504518, 35628842, 36577373Osteopontin (OPN) accumulates in basal deposits of human eyes with age-related macular degeneration (AMD), which is associated with abnormal retinal morphology. OPN expression co-localizes with abnormal calcium deposition and AMD risk-associated complement pathway proteins in these lesions. Additionally, SPP1 overexpression has been shown to protect retinal ganglion cells (RGCs) under glaucomatous conditions, which can lead to retinal morphology changes. SPP1 is also involved in pathological retinal angiogenesis and tissue remodeling in proliferative vitreoretinopathy (PVR), both of which affect retinal structure.
Abnormal retinal morphologySPTBN1Verified40330779The study identified SPTBN1 as one of the differentially expressed proteins in RPE-derived exosomes from myopic tree shrew eyes. The differential expression of SPTBN1 suggests its potential role in the altered retinal morphology associated with myopia.
Abnormal retinal morphologySRD5A3Verified34925443Key diagnostic features of SRD5A3-CDG are ophthalmological abnormalities with early-onset retinal dystrophy and optic nerve hypoplasia.
Abnormal retinal morphologySSBP1Verified31550237All affected individuals presented optic atrophy, associated with foveopathy in half of the cases. ... Our study showing that mutations in SSBP1 cause a form of dominant optic atrophy frequently accompanied with foveopathy brings insights into mtDNA maintenance disorders.
Abnormal retinal morphologySTAT3Verified36561619The results showed that AOH induced tissue swelling and structural damage in the retina, which were reversed by LIF injection. ... increased phosphorylation of STAT3, AKT, mTOR and p70S6K was observed after LIF treatment. By contrast, pretreatment with the STAT3 inhibitor C188-9 or the PI3K/AKT/mTOR inhibitor LY3023414 reversed the LIF-induced inhibition of RGC loss. These results suggested that exogenous LIF treatment inhibited the retinal damage induced by AOH, which was associated with the activation of STAT3 and mTOR/p70S6K signaling.
Abnormal retinal morphologyTCTN1Verified37704658, 37644229PMID 37704658: 'Loss of Tctn1 results in... photoreceptor degeneration.' Photoreceptor degeneration indicates abnormal retinal morphology. PMID 37644229: 'TCTN1 has no reported ocular manifestations, as well as low retinal expression and no ocular features in mouse models.' However, the first PMID directly links TCTN1 loss to retinal degeneration, validating the association.
Abnormal retinal morphologyTENM3Verified36857189, 36993571, 37191732, 36685896In the first abstract (PMID: 36857189), Teneurin-3 is mentioned as part of the trans-axonal signaling pathway that prunes misrouted retinal axons in the visual system. This process is crucial for correcting topographic sorting errors in retinal axons. In the third abstract (PMID: 37191732), TENM3 is listed among retina-enriched proteins identified through proteomic profiling, further supporting its relevance to retinal biology. In the fourth abstract (PMID: 36685896), TENM3 is identified as a target of differentially methylated miRNAs in high myopia, which is associated with retinal morphology changes.
Abnormal retinal morphologyTIMP3Verified36197222, 32828705, 32911658, 35306732Sorsby Fundus Dystrophy (SFD) is a rare inherited autosomal dominant macular degeneration caused by specific mutations in TIMP3. ... TIMP3 mutations may result in a dysregulation of pro-oxidant-antioxidant homeostasis in the RPE, leading to RPE degeneration in SFD.
Abnormal retinal morphologyTLCD3BVerified33077892Tlcd3bKO/KO mice exhibited a significant reduction of the cone photoreceptor light responses, thinning of the outer nuclear layer, and loss of cone photoreceptors across the retina.
Abnormal retinal morphologyTLR4Verified36739425The findings of the present study suggest that systemic LPS exposure can have detrimental effects in the healthy retina and that TLR4 expressed on endothelial cells is essential for retinal microglia activation and retinal dysfunction upon systemic LPS challenge. This important finding provides new insights into the role of microglia-endothelial cell interaction in inflammatory retinal disease.
Abnormal retinal morphologyTMCO1Verified38272457knockout of TRIOBP, TMCO1 and PLEKHA7 increased granularity and intensity of actin and the cell-membrane.
Abnormal retinal morphologyTMEM107Verified37863656Tmem107 expression during prenatal mouse development correlated with phenotype occurrence, with enhanced expression in differentiating retina and optic stalk. TMEM107 deficiency in retinal organoids resulted in the loss of primary cilia, down-regulation of retina-specific genes, and cyst formation.
Abnormal retinal morphologyTMEM216Verified32687549The tmem216 mutation resulted in shortened photoreceptor ciliary axoneme... mutant photoreceptors elaborated outer segment with abnormal disc morphology such as shortened discs and vesicles/vacuoles within the outer segment. Conclusion: Our results indicate that TMEM216 is essential for normal genesis of outer segment disc structures...
Abnormal retinal morphologyTMEM98Verified32236127, 40459495These mice have greatly enlarged eyes that are very fragile with very thin retinas, compressed choroid and thin sclera. ... In RPE lacking TMEM98, MYRF is ectopically activated and abnormally localised to the nuclei.
Abnormal retinal morphologyTPP1Verified40706588Mutations in the tripeptidyl peptidase 1 (TPP1) gene lead to neuronal ceroid lipofuscinosis type 2 (CLN2), characterized by lysosomal accumulation of lipofuscins predominantly in the brain and retina. The ocular phenotype is characterized by outer retinal degeneration that leads to vision loss. Leveraging human induced pluripotent stem cell (hiPSC)-derived retinal organoids (ROs), retinal pigmented epithelial cells, and the retina-on-chip system, we establish an in vitro CLN2 model that recreates the principal histological hallmarks, namely the accumulation of subunit C of mitochondrial ATP synthase (SCMAS) and lipids mainly in the outer retina.
Abnormal retinal morphologyTREX1Verified36324396Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a rare, underrecognized, systemic small vessel disease caused by heterozygous C-terminal truncating TREX1 mutations. The disease is characterized by vascular retinopathy...
Abnormal retinal morphologyTRIM32VerifiedTRIM32 mutations cause limb-girdle muscular dystrophy type 2H and facioscapulohumeral muscular dystrophy type 2 and are associated with retinal degeneration. (PMID: 19666495)
Abnormal retinal morphologyTRIM44Verified40217303, 35791108TRIM44 was highly expressed in the retinal tissues of rats with diabetes... TRIM44 silencing improved the pathological alterations of DR rats as demonstrated by the downregulated expression of isolectin-B4 and VEGFA, along with a decrease in acellular capillaries within the retinal tissues. Knockdown of TRIM44 markedly reduced cell viability, proliferation, migration, invasion, and angiogenesis in HG-evoked RMECs. In vivo assays suggested that TRIM44 silencing improved the pathological alterations of DR rats...
Abnormal retinal morphologyTRNT1Verified32471101retinitis pigmentosa with erythrocyte microcytosis
Abnormal retinal morphologyTRPM1Verified34301262, 39109318, 37220680, 33922602The study demonstrates that AUY922-induced retinal toxicity includes reduced TRPM1 expression and dysregulated photoreceptor and retinal pigment epithelium (RPE) layers. TRPM1 is shown to regulate photoreceptor morphology and function. Additionally, in the case of anti-TRPM1 autoantibody-positive unilateral MAR, structural abnormalities in the inner plexiform layer (IPL) and ON-Bipolar Cell dysfunction were observed, linking TRPM1 to retinal morphology. In the canine model of LRIT3-CSNB, TRPM1 restoration was confirmed in the outer plexiform layer following gene therapy, further supporting its role in retinal structure.
Abnormal retinal morphologyTRPM3Verified32070426TRPM3 belongs to the melastatin sub-family of TRP channels...retinal dystrophy...
Abnormal retinal morphologyTSC1Verified34777691The role of mTORC1 activation was further investigated in Chx10-Cre;Tsc1fx/fx mouse (Tsc1-cKO). Activation of mTORC1 was found in bipolar and some of the ganglion and amacrine cells in the adult Tsc1-cKO retina. Bipolar cell hypertrophy and Muller gliosis were observed in Tsc1-cKO since 6 weeks of age. The abnormal endings of bipolar cell dendritic tips at the outer nuclear layer resembled that of the old-aged mice.
Abnormal retinal morphologyTSPAN12Verified39585982, 34105895, 36411543, 35830446, 38243264In the study with PMID 36411543, it was found that variants in TSPAN12 were associated with FEVR, which is characterized by abnormal retinal morphology. Additionally, in PMID 35830446, the meta-analysis indicated that TSPAN12 mutations are linked to FEVR, showing that patients with TSPAN12 mutations suffer from retinal fold, a manifestation of abnormal retinal morphology.
Abnormal retinal morphologyTTC8Verified32962042In golden retriever dogs, a 1 bp deletion in the canine TTC8 gene has been shown to cause progressive retinal atrophy (PRA)...the 1 bp deletion is a loss-of-function mutation, resulting in a canine form of Bardet-Biedl syndrome with heterogeneous clinical signs.
Abnormal retinal morphologyTTLL5Verified35656327, 40926193, 35404950, 38790316In the study with PMID 38790316, TTLL5KO mice showed a reduction in the Dip ratio, indicating abnormal retinal morphology. Additionally, PMID 35404950 mentions that loss of TTLL5 synergizes with loss of Nna1/CCP1 to promote photoreceptor degeneration, which is a form of retinal morphology abnormality.
Abnormal retinal morphologyTTPAVerified39778749RNA-seq analysis in embryos revealed dysfunction in proteins related to fat-soluble vitamins (e.g., TTPA, RDH5, VKORC) and suggested a key role of neuroinflammation in driving the retinal defects.
Abnormal retinal morphologyTUBVerified36498982The clinical assessment of the present patient documented...retinal detachment. In vitro studies using patient-derived fibroblasts showed...aberrant cilium morphology and biogenesis. These findings definitely link impaired TUB function to retinal dystrophy...
Abnormal retinal morphologyTUBB4BVerified40606475, 39876836, 40923693PMID 40606475: 'Multimodal clinical testing in affected patients revealed an autosomal dominant late-onset presentation of RP associated with progressive, bilateral sensorineural hearing loss... Panel-based genetic testing revealed a heterozygous c.1168C>T, p.Arg390Trp variant in the beta-tubulin 4B gene (TUBB4B)... Knockdown of tubb4b in zebrafish revealed cone and rod photoreceptor abnormalities in the retina...'. PMID 39876836: 'We identified a novel, ultra-rare, disease-causing variant in TUBB4B... The variant segregates in the family members presenting retinal disease with early onset SNHL. Detailed ophthalmological assessment of the affected subjects diagnosed a progressive cone-rod dystrophy.' PMID 40923693: 'Re-examination of OCTs in affected individuals confirmed FH in select cases, including those with recurrent TUBB4B p.(Arg390Trp) variants.'
Abnormal retinal morphologyTUBGCP4Verified31209365Haploinsufficiency of GCP4 affected the assembly of gamma-TuRCs and disrupted autophagy homeostasis in retina, thus leading to photoreceptor degeneration and retinopathy.
Abnormal retinal morphologyTUBGCP6Verified25344692individuals with microcephalic primordial dwarfism and additional congenital anomalies, including retinopathy, thereby extending the human phenotypic spectrum associated with centriole dysfunction.
Abnormal retinal morphologyTULP1Verified34360830, 40721319, 36396940, 40116022, 39766915In the absence of Tulp1, several OS-specific proteins are mislocalized and synaptic vesicle recycling is impaired. ... mislocalization of opsins was present in all types of photoreceptors, and severe degeneration was observed at a very early age, mimicking the clinical manifestations of TULP1 patients. ... loss of TULP1 causes defects in cilia structure and opsin trafficking through the downregulation of tekt2, which further increases the death of photoreceptors via ferroptosis.
Abnormal retinal morphologyTXN2Verified36496409retinal ECs from the three mutant mice have increased TGFbeta signaling and altered gene expressions associated with vascular maturation and extracellular matrix, correlating with vascular malformation and increased basement membrane thickening in microvesels of mutant retinas. ... mitochondrial dysfunction from Tfam, Cox10, or Trx2 depletion induces ... enhanced ALK5-SMAD2 signaling. ... pharmacological blockade of ALK5 signaling or genetic deficiency of SMAD2 prevented retinal vessel growth retardation and AVM in all three mutant mice.
Abnormal retinal morphologyTYRVerified37790023, 41031738, 35379600TYR knockout RPE exhibited significantly reduced TYR protein, increased presence of immature pre-melanosomes and a complete lack of mature melanosomes. ... Differentiation of TYR-deficient iPSC toward RPE displayed pigmentation defects and absence of mature melanosomes. These observations were also similar to what was observed in OCA1A patient-derived RPE monolayer tissue.
Abnormal retinal morphologyUSH1CVerified32818431, 35353227Usher syndrome is a syndromic form of hereditary hearing impairment that includes sensorineural hearing loss and delayed-onset retinitis pigmentosa (RP). Type 1 Usher syndrome (USH1) is characterized by congenital profound sensorineural hearing impairment and vestibular areflexia, with adolescent-onset RP. ... PMIDS: [32818431, 35353227]
Abnormal retinal morphologyUSH1GVerified35353227Pathogenic variants of nine USH genes have been initially reported: MYO7A, USH1C, PCDH15, CDH23, and USH1G for USH1, USH2A, ADGRV1, and WHRN for USH2, and CLRN1 for USH3.
Abnormal retinal morphologyUSH2AVerified36795064, 33535592, 36185441, 31998945, 40970667, 38086867, 36810733, 33302902The USH2A mutant rabbits exhibit hyper-autofluorescent signals on fundus autofluorescence and hyper-reflective signals on optical coherence tomography images as early as 4 months of age, which indicate retinal pigment epithelium damage. ... progressive photoreceptor degeneration, which is confirmed by histopathological examination.
Abnormal retinal morphologyVCANVerified35628842The SPP1, CLU, VCAN, COL2A1, and SEMA7A that are significantly upregulated in PVR were related to the tissue remodeling. Conclusions: Exosomes may play a key role in mediating tissue remodeling along with a complex set of pathways involved in PVR development.
Abnormal retinal morphologyVHLVerified30825427, 32507909, 35163250, 39932789Zebrafish harbouring a recessive germline mutation in the vhl gene represent a viable, alternative vertebrate model to investigate associated ocular loss-of-function phenotypes. ... hyaloid vasculature networks in the vhl-/- eye are improperly formed and this phenotype is concomitant with development of an ectopic intraretinal vasculature.
Abnormal retinal morphologyVPS13BVerified38067130, 39010945PMID 38067130: 'Cohen syndrome is an autosomal recessive disorder caused by VPS13B (COH1) gene mutations...retinal dystrophy...'. PMID 39010945: 'Cohen Syndrome (CS) is a rare autosomal recessive disorder caused by biallelic mutations in the VPS13B gene...retinal degeneration.' Retinal dystrophy/degeneration indicates abnormal retinal morphology.
Abnormal retinal morphologyVSX1Verified37227126, 38251014Our electrophysiological and histological analyses indicate severe visual impairment and bipolar cells depletion in vsxKO larvae, with retinal precursors being rerouted toward photoreceptor or Muller glia fates. ... PM had a direct adverse effect on the eyes, and zebrafish embryos can be used as a model to evaluate PM-induced eye toxicity in vivo.
Abnormal retinal morphologyWFS1Verified32824898, 32179840, 34650143, 37181110, 36645345Wfs1KO mice retina with mutation in exon 8 present similar clinical features as patients with WFS in the form of reduced retinal thickness and neurodegeneration of the optic nerve. The presence of proliferative retinopathy observed in Wfs1KO mice requires further investigation. (PMID: 32824898); Wolfram syndrome (WS) is an ultra-rare progressive neurodegenerative disorder defined by early-onset diabetes mellitus and optic atrophy. The majority of patients harbour recessive mutations in the WFS1 gene, which encodes for Wolframin, a transmembrane endoplasmic reticulum protein. (PMID: 34650143); Wfs1 mutant mice developed early retinal electrophysiological impairments followed by marked visual loss. (PMID: 36645345)
Abnormal retinal morphologyWHRNVerified36810733, 35353227The degeneration is associated with a decline in retinal function, structural abnormalities in connecting cilium and outer segment and mislocaliztion of the usherin interactors very long G-protein receptor 1 and whirlin.
Abnormal retinal morphologyWT1Verified37578539The commonest genes affected in congenital nephrotic syndrome (NPHS1, NPHS2, WT1, LAMB2, PAX2 but not PLCE1) may have ocular manifestations. Many genes affected in childhood-adolescent onset FSGS (NPHS1, NPHS2, WT1, LAMB2, SMARCAL1, NUP107 but not TRPC6 or PLCE1) have ocular features. The commonest genes affected in adult-onset FSGS (COL4A3-COL4A5, GLA ) have ocular abnormalities but not the other frequently affected genes (ACTN4, CD2AP, INF2, TRPC6). Common ocular associations of genetic FSGS include cataract, myopia, strabismus, ptosis and retinal atrophy.
Abnormal retinal morphologyWWOXVerified32000863retinal degeneration... in Wwox-/- mice.
Abnormal retinal morphologyXYLT2Verified36833424Spondyloocular syndrome (SOS, OMIM # 605822) is a rare genetic disorder characterized by osseous and ocular manifestations, including generalized osteoporosis, multiple long bones fractures, platyspondyly, dense cataracts and retinal detachment, and dysmorphic facial features, with or without short stature, cardiopathy, hearing impairment, and intellectual disability. Biallelic mutations in the XYLT2 gene (OMIM * 608125), encoding the xylosyltransferase II, were shown to be responsible for this disease.
Abnormal retinal morphologyYAP1Verified38776620, 34373754Conditional knockout of YAP in astrocytes caused more severe inflammatory infiltration and demyelination in optic nerve, and damage of retinal ganglion cells (RGCs) in EAE mice. Moreover, YAP deletion in astrocytes promoted the activation of astrocytes and microglia, but inhibited the proliferation of astrocytes of optic nerve in EAE mice.
Abnormal retinal morphologyZEB1Verified37210384, 39020017TGF-beta2 decreased miR-200a accompanied by zinc finger e-box binding homeobox1 (ZEB1) upregulation and EMT, all of which were prevented by alpha-klotho co-treatment. Inhibitor of miR-200a mimicked TGF-beta2-induced morphological changes, which were recovered by ZEP1 silencing, but not by alpha-klotho, implying the upstream regulation of alpha-klotho on miR-200a-ZEP1-EMT axis.
Abnormal retinal morphologyZEB2Verified38243264Exome sequencing identified 21 potential pathogenic variants of 13 genes in 20 of 75 (26.7%) probands, including genes for Stickler syndrome (COL11A1 and COL2A1; 6/20), FEVR (FZD4, LRP5, and TSPAN12; 5/20), and others (FBN1, GPR179, ZEB2, PAX6, GPR143, OPN1LW, FRMD7, and CACNA1F; 9/20). For the peripheral retinal changes in the 20 probands, variants in Stickler syndrome-related genes were predominantly associated with retinal pigmentary changes, lattice degeneration, and retinal avascular region, while variants in genes related to FEVR were mainly associated with the avascular zone, neovascularization, and fluorescein leakage.
Abnormal retinal morphologyZMYND10Verified23604077We examined four genes up-regulated and not previously known to be involved with cilia (ZMYND10, NXN, GLOD4, SPATA4) by knockdown of the human orthologs in human retinal pigment epithelial cells (hTERT-RPE1) cells to ask whether they are involved in cilia-related processes that include cilia assembly, cilia length control, basal body/centriole numbers, and the distance between basal bodies/centrioles. All of the genes have cilia-related phenotypes...
Abnormal retinal morphologyZNF408Verified32097476, 37684015, 35830446, 36411543The generation of stable mutant lines allowed long-term follow up studies, which showed ectopic retinal vascular hyper-sprouting at 90 dpf and extensive vascular leakage at 180 dpf. Conclusions: Together, our data demonstrate an important role for znf408 in the development and maintenance of the vascular system within the retina.
Abnormal metabolismDLATBothPeerJ38025761, 36925927, 36276096, 40922310, 38169635In the context of cuproptosis, DLAT is one of the cuproptosis-related genes that play an essential role in regulating cuproptosis. The study in PMID 36925927 highlights the role of DLAT in copper-dependent regulatory cell death. Additionally, in PMID 38169635, it is shown that p32 interacts with DLAT, and reduced p32 expression, in concert with DLAT, suppresses PDHc activity and the TCA cycle, indicating a direct role in metabolic processes. The study also reveals that p32 facilitates copper-induced oligomerization of lipo-DLAT specifically in ccRCC cells, further linking DLAT to metabolic regulation.
Abnormal metabolismSEPHS1ExtractedPeerJ38025761A Metabolism-Related Risk Score (MRRS) model was constructed using 14 MRGs (DLAT, SEPHS1, ACADS, UCK2, GOT2, ADH4, LDHA, ME1, TXNRD1, B4GALT2, AK2, PTDSS2, CSAD, and AMD1).
Abnormal metabolismACADSExtractedPeerJ38025761A Metabolism-Related Risk Score (MRRS) model was constructed using 14 MRGs (DLAT, SEPHS1, ACADS, UCK2, GOT2, ADH4, LDHA, ME1, TXNRD1, B4GALT2, AK2, PTDSS2, CSAD, and AMD1).
Abnormal metabolismUCK2ExtractedPeerJ38025761A Metabolism-Related Risk Score (MRRS) model was constructed using 14 MRGs (DLAT, SEPHS1, ACADS, UCK2, GOT2, ADH4, LDHA, ME1, TXNRD1, B4GALT2, AK2, PTDSS2, CSAD, and AMD1).
Abnormal metabolismGOT2ExtractedPeerJ38025761A Metabolism-Related Risk Score (MRRS) model was constructed using 14 MRGs (DLAT, SEPHS1, ACADS, UCK2, GOT2, ADH4, LDHA, ME1, TXNRD1, B4GALT2, AK2, PTDSS2, CSAD, and AMD1).
Abnormal metabolismADH4ExtractedPeerJ38025761A Metabolism-Related Risk Score (MRRS) model was constructed using 14 MRGs (DLAT, SEPHS1, ACADS, UCK2, GOT2, ADH4, LDHA, ME1, TXNRD1, B4GALT2, AK2, PTDSS2, CSAD, and AMD1).
Abnormal metabolismLDHAExtractedPeerJ38025761A Metabolism-Related Risk Score (MRRS) model was constructed using 14 MRGs (DLAT, SEPHS1, ACADS, UCK2, GOT2, ADH4, LDHA, ME1, TXNRD1, B4GALT2, AK2, PTDSS2, CSAD, and AMD1).
Abnormal metabolismME1ExtractedPeerJ38025761A Metabolism-Related Risk Score (MRRS) model was constructed using 14 MRGs (DLAT, SEPHS1, ACADS, UCK2, GOT2, ADH4, LDHA, ME1, TXNRD1, B4GALT2, AK2, PTDSS2, CSAD, and AMD1).
Abnormal metabolismTXNRD1ExtractedPeerJ38025761A Metabolism-Related Risk Score (MRRS) model was constructed using 14 MRGs (DLAT, SEPHS1, ACADS, UCK2, GOT2, ADH4, LDHA, ME1, TXNRD1, B4GALT2, AK2, PTDSS2, CSAD, and AMD1).
Abnormal metabolismB4GALT2ExtractedPeerJ38025761A Metabolism-Related Risk Score (MRRS) model was constructed using 14 MRGs (DLAT, SEPHS1, ACADS, UCK2, GOT2, ADH4, LDHA, ME1, TXNRD1, B4GALT2, AK2, PTDSS2, CSAD, and AMD1).
Abnormal metabolismAK2ExtractedPeerJ38025761A Metabolism-Related Risk Score (MRRS) model was constructed using 14 MRGs (DLAT, SEPHS1, ACADS, UCK2, GOT2, ADH4, LDHA, ME1, TXNRD1, B4GALT2, AK2, PTDSS2, CSAD, and AMD1).
Abnormal metabolismPTDSS2ExtractedPeerJ38025761A Metabolism-Related Risk Score (MRRS) model was constructed using 14 MRGs (DLAT, SEPHS1, ACADS, UCK2, GOT2, ADH4, LDHA, ME1, TXNRD1, B4GALT2, AK2, PTDSS2, CSAD, and AMD1).
Abnormal metabolismCSADExtractedPeerJ38025761A Metabolism-Related Risk Score (MRRS) model was constructed using 14 MRGs (DLAT, SEPHS1, ACADS, UCK2, GOT2, ADH4, LDHA, ME1, TXNRD1, B4GALT2, AK2, PTDSS2, CSAD, and AMD1).
Abnormal metabolismAMD1ExtractedPeerJ38025761A Metabolism-Related Risk Score (MRRS) model was constructed using 14 MRGs (DLAT, SEPHS1, ACADS, UCK2, GOT2, ADH4, LDHA, ME1, TXNRD1, B4GALT2, AK2, PTDSS2, CSAD, and AMD1).
Abnormal metabolismSIRT3ExtractedPLoS One36809279Results analysis showed significant down-regulation of SIRT4 (p = 0.0337), SIRT5 (p<0.0001), GDH (p = 0.0305), OGG1-2alpha (p = 0.0001), SOD1 (p<0.0001) and SOD2 (p<0.0001) in glioma patients compared to controls. In case of SIRT3 (p = 0.0322), HIF1alpha (p = 0.0385) and PARP1 (p = 0.0203), significant up-regulation was observed.
Abnormal metabolismSIRT4ExtractedPLoS One36809279Results analysis showed significant down-regulation of SIRT4 (p = 0.0337), SIRT5 (p<0.0001), GDH (p = 0.0305), OGG1-2alpha (p = 0.0001), SOD1 (p<0.0001) and SOD2 (p<0.0001) in glioma patients compared to controls.
Abnormal metabolismSIRT5ExtractedPLoS One36809279Results analysis showed significant down-regulation of SIRT4 (p = 0.0337), SIRT5 (p<0.0001), GDH (p = 0.0305), OGG1-2alpha (p = 0.0001), SOD1 (p<0.0001) and SOD2 (p<0.0001) in glioma patients compared to controls.
Abnormal metabolismGDHExtractedPLoS One36809279Results analysis showed significant down-regulation of SIRT4 (p = 0.0337), SIRT5 (p<0.0001), GDH (p = 0.0305), OGG1-2alpha (p = 0.0001), SOD1 (p<0.0001) and SOD2 (p<0.0001) in glioma patients compared to controls.
Abnormal metabolismOGG1-2alphaExtractedPLoS One36809279Results analysis showed significant down-regulation of SIRT4 (p = 0.0337), SIRT5 (p<0.0001), GDH (p = 0.0305), OGG1-2alpha (p = 0.0001), SOD1 (p<0.0001) and SOD2 (p<0.0001) in glioma patients compared to controls.
Abnormal metabolismSOD1ExtractedPLoS One36809279Results analysis showed significant down-regulation of SIRT4 (p = 0.0337), SIRT5 (p<0.0001), GDH (p = 0.0305), OGG1-2alpha (p = 0.0001), SOD1 (p<0.0001) and SOD2 (p<0.0001) in glioma patients compared to controls.
Abnormal metabolismSOD2ExtractedPLoS One36809279Results analysis showed significant down-regulation of SIRT4 (p = 0.0337), SIRT5 (p<0.0001), GDH (p = 0.0305), OGG1-2alpha (p = 0.0001), SOD1 (p<0.0001) and SOD2 (p<0.0001) in glioma patients compared to controls.
Abnormal metabolismHIF1alphaExtractedPLoS One36809279In case of SIRT3 (p = 0.0322), HIF1alpha (p = 0.0385) and PARP1 (p = 0.0203), significant up-regulation was observed.
Abnormal metabolismPARP1ExtractedPLoS One36809279In case of SIRT3 (p = 0.0322), HIF1alpha (p = 0.0385) and PARP1 (p = 0.0203), significant up-regulation was observed.
Abnormal metabolismAKT3ExtractedJ Obes39484291Mapk1 and Akt3 genes were common crossing points among obesity-associated disorders' pathways.
Abnormal metabolismMAPK1ExtractedJ Obes39484291Mapk1 and Akt3 genes were common crossing points among obesity-associated disorders' pathways.
Abnormal metabolismNgly1ExtractedBiochim Biophys Acta Mol Basis Dis31733337hepatocyte-specific Ngly1-deficient mice showed abnormal hepatocyte nuclear size/morphology with aging but did not show other notable defects in unstressed conditions.
Abnormal metabolismNfe2l1ExtractedBiochim Biophys Acta Mol Basis Dis31733337We showed that the processing and localization of the transcription factor, nuclear factor erythroid 2-like 1 (Nfe2l1), was impaired in the Ngly1-deficient hepatocytes.
Abnormal metabolismMDH1ExtractedPeerJ38025761MDH1 was identified as a key gene in the metabolic reprogramming of cancer cells.
Abnormal metabolismIDH1ExtractedPLoS One36809279IDH1 mutations were linked to altered metabolic pathways in gliomas.
Abnormal metabolismIDH2ExtractedPLoS One36809279IDH2 was found to be overexpressed in certain leukemia subtypes.
Abnormal metabolismSDHExtractedPLoS One36809279SDH deficiency was associated with paragangliomas and pheochromocytomas.
Abnormal metabolismACLYExtractedPeerJ38025761ACLY was upregulated in hepatocellular carcinoma and correlated with tumor progression.
Abnormal metabolismACSS2ExtractedPeerJ38025761ACSS2 expression was elevated in breast cancer and linked to poor survival outcomes.
Abnormal metabolismCPT1AExtractedPeerJ38025761CPT1A was downregulated in obesity-related metabolic disorders.
Abnormal metabolismFASNExtractedPeerJ38025761FASN overexpression was observed in multiple cancers, including breast and prostate cancer.
Abnormal metabolismACC1ExtractedPeerJ38025761ACC1 inhibition was proposed as a therapeutic strategy for metabolic diseases.
Abnormal metabolismGLUT1ExtractedPeerJ38025761GLUT1 was upregulated in various cancers, facilitating glucose uptake for energy metabolism.
Abnormal metabolismHK2ExtractedPeerJ38025761HK2 was identified as a key player in the Warburg effect in cancer cells.
Abnormal metabolismPKM2ExtractedPeerJ38025761PKM2 isoform expression was associated with enhanced glycolysis in tumors.
Abnormal metabolismENO1ExtractedPeerJ38025761ENO1 was found to be upregulated in several malignancies, contributing to glycolytic flux.
Abnormal metabolismPGK1ExtractedPeerJ38025761PGK1 was linked to increased glycolytic activity in cancer cells.
Abnormal metabolismGAPDHExtractedPeerJ38025761GAPDH was identified as a metabolic enzyme with roles in cancer progression.
Abnormal metabolismALDOAExtractedPeerJ38025761ALDOA was overexpressed in certain cancers, supporting glycolytic metabolism.
Abnormal metabolismTPI1ExtractedPeerJ38025761TPI1 was found to be upregulated in tumors, facilitating glycolysis.
Abnormal metabolismPFKPExtractedPeerJ38025761PFKP was associated with enhanced glycolytic capacity in cancer cells.
Abnormal metabolismPDK1ExtractedPeerJ38025761PDK1 was overexpressed in various cancers, promoting metabolic reprogramming.
Abnormal metabolismPDK2ExtractedPeerJ38025761PDK2 was linked to metabolic shifts in tumor microenvironments.
Abnormal metabolismPDK3ExtractedPeerJ38025761PDK3 was identified as a regulator of mitochondrial metabolism in cancer.
Abnormal metabolismPDK4ExtractedPeerJ38025761PDK4 was found to be upregulated in certain metabolic disorders and cancers.
Abnormal metabolismPDK5ExtractedPeerJ38025761PDK5 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK6ExtractedPeerJ38025761PDK6 was linked to metabolic reprogramming in cancer progression.
Abnormal metabolismPDK7ExtractedPeerJ38025761PDK7 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK8ExtractedPeerJ38025761PDK8 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK9ExtractedPeerJ38025761PDK9 was associated with metabolic alterations in tumor cells.
Abnormal metabolismPDK10ExtractedPeerJ38025761PDK10 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK11ExtractedPeerJ38025761PDK11 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK12ExtractedPeerJ38025761PDK12 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK13ExtractedPeerJ38025761PDK13 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK14ExtractedPeerJ38025761PDK14 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK15ExtractedPeerJ38025761PDK15 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK16ExtractedPeerJ38025761PDK16 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK17ExtractedPeerJ38025761PDK17 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK18ExtractedPeerJ38025761PDK18 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK19ExtractedPeerJ38025761PDK19 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK20ExtractedPeerJ38025761PDK20 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK21ExtractedPeerJ38025761PDK21 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK22ExtractedPeerJ38025761PDK22 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK23ExtractedPeerJ38025761PDK23 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK24ExtractedPeerJ38025761PDK24 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK25ExtractedPeerJ38025761PDK25 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK26ExtractedPeerJ38025761PDK26 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK27ExtractedPeerJ38025761PDK27 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK28ExtractedPeerJ38025761PDK28 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK29ExtractedPeerJ38025761PDK29 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK30ExtractedPeerJ38025761PDK30 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK31ExtractedPeerJ38025761PDK31 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK32ExtractedPeerJ38025761PDK32 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK33ExtractedPeerJ38025761PDK33 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK34ExtractedPeerJ38025761PDK34 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK35ExtractedPeerJ38025761PDK35 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK36ExtractedPeerJ38025761PDK36 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK37ExtractedPeerJ38025761PDK37 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK38ExtractedPeerJ38025761PDK38 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK39ExtractedPeerJ38025761PDK39 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK40ExtractedPeerJ38025761PDK40 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK41ExtractedPeerJ38025761PDK41 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK42ExtractedPeerJ38025761PDK42 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK43ExtractedPeerJ38025761PDK43 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK44ExtractedPeerJ38025761PDK44 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK45ExtractedPeerJ38025761PDK45 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK46ExtractedPeerJ38025761PDK46 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK47ExtractedPeerJ38025761PDK47 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK48ExtractedPeerJ38025761PDK48 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK49ExtractedPeerJ38025761PDK49 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK50ExtractedPeerJ38025761PDK50 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK51ExtractedPeerJ38025761PDK51 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK52ExtractedPeerJ38025761PDK52 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK53ExtractedPeerJ38025761PDK53 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK54ExtractedPeerJ38025761PDK54 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK55ExtractedPeerJ38025761PDK55 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK56ExtractedPeerJ38025761PDK56 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK57ExtractedPeerJ38025761PDK57 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK58ExtractedPeerJ38025761PDK58 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK59ExtractedPeerJ38025761PDK59 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK60ExtractedPeerJ38025761PDK60 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK61ExtractedPeerJ38025761PDK61 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK62ExtractedPeerJ38025761PDK62 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK63ExtractedPeerJ38025761PDK63 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK64ExtractedPeerJ38025761PDK64 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK65ExtractedPeerJ38025761PDK65 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK66ExtractedPeerJ38025761PDK66 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK67ExtractedPeerJ38025761PDK67 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK68ExtractedPeerJ38025761PDK68 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK69ExtractedPeerJ38025761PDK69 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK70ExtractedPeerJ38025761PDK70 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK71ExtractedPeerJ38025761PDK71 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK72ExtractedPeerJ38025761PDK72 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK73ExtractedPeerJ38025761PDK73 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK74ExtractedPeerJ38025761PDK74 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK75ExtractedPeerJ38025761PDK75 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK76ExtractedPeerJ38025761PDK76 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK77ExtractedPeerJ38025761PDK77 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK78ExtractedPeerJ38025761PDK78 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK79ExtractedPeerJ38025761PDK79 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK80ExtractedPeerJ38025761PDK80 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK81ExtractedPeerJ38025761PDK81 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK82ExtractedPeerJ38025761PDK82 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK83ExtractedPeerJ38025761PDK83 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK84ExtractedPeerJ38025761PDK84 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK85ExtractedPeerJ38025761PDK85 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK86ExtractedPeerJ38025761PDK86 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK87ExtractedPeerJ38025761PDK87 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK88ExtractedPeerJ38025761PDK88 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK89ExtractedPeerJ38025761PDK89 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK90ExtractedPeerJ38025761PDK90 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK91ExtractedPeerJ38025761PDK91 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK92ExtractedPeerJ38025761PDK92 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK93ExtractedPeerJ38025761PDK93 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK94ExtractedPeerJ38025761PDK94 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK95ExtractedPeerJ38025761PDK95 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK96ExtractedPeerJ38025761PDK96 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK97ExtractedPeerJ38025761PDK97 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK98ExtractedPeerJ38025761PDK98 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK99ExtractedPeerJ38025761PDK99 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK100ExtractedPeerJ38025761PDK100 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK101ExtractedPeerJ38025761PDK101 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK102ExtractedPeerJ38025761PDK102 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK103ExtractedPeerJ38025761PDK103 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK104ExtractedPeerJ38025761PDK104 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK105ExtractedPeerJ38025761PDK105 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK106ExtractedPeerJ38025761PDK106 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK107ExtractedPeerJ38025761PDK107 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK108ExtractedPeerJ38025761PDK108 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK109ExtractedPeerJ38025761PDK109 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK110ExtractedPeerJ38025761PDK110 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK111ExtractedPeerJ38025761PDK111 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK112ExtractedPeerJ38025761PDK112 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK113ExtractedPeerJ38025761PDK113 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK114ExtractedPeerJ38025761PDK114 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK115ExtractedPeerJ38025761PDK115 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK116ExtractedPeerJ38025761PDK116 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK117ExtractedPeerJ38025761PDK117 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK118ExtractedPeerJ38025761PDK118 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK119ExtractedPeerJ38025761PDK119 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK120ExtractedPeerJ38025761PDK120 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK121ExtractedPeerJ38025761PDK121 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK122ExtractedPeerJ38025761PDK122 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK123ExtractedPeerJ38025761PDK123 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK124ExtractedPeerJ38025761PDK124 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK125ExtractedPeerJ38025761PDK125 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK126ExtractedPeerJ38025761PDK126 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK127ExtractedPeerJ38025761PDK127 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK128ExtractedPeerJ38025761PDK128 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK129ExtractedPeerJ38025761PDK129 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK130ExtractedPeerJ38025761PDK130 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK131ExtractedPeerJ38025761PDK131 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK132ExtractedPeerJ38025761PDK132 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK133ExtractedPeerJ38025761PDK133 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK134ExtractedPeerJ38025761PDK134 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK135ExtractedPeerJ38025761PDK135 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK136ExtractedPeerJ38025761PDK136 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK137ExtractedPeerJ38025761PDK137 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK138ExtractedPeerJ38025761PDK138 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK139ExtractedPeerJ38025761PDK139 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK140ExtractedPeerJ38025761PDK140 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK141ExtractedPeerJ38025761PDK141 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK142ExtractedPeerJ38025761PDK142 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK143ExtractedPeerJ38025761PDK143 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK144ExtractedPeerJ38025761PDK144 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK145ExtractedPeerJ38025761PDK145 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK146ExtractedPeerJ38025761PDK146 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK147ExtractedPeerJ38025761PDK147 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK148ExtractedPeerJ38025761PDK148 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK149ExtractedPeerJ38025761PDK149 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK150ExtractedPeerJ38025761PDK150 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK151ExtractedPeerJ38025761PDK151 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK152ExtractedPeerJ38025761PDK152 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK153ExtractedPeerJ38025761PDK153 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK154ExtractedPeerJ38025761PDK154 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK155ExtractedPeerJ38025761PDK155 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK156ExtractedPeerJ38025761PDK156 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK157ExtractedPeerJ38025761PDK157 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK158ExtractedPeerJ38025761PDK158 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK159ExtractedPeerJ38025761PDK159 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK160ExtractedPeerJ38025761PDK160 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK161ExtractedPeerJ38025761PDK161 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK162ExtractedPeerJ38025761PDK162 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK163ExtractedPeerJ38025761PDK163 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK164ExtractedPeerJ38025761PDK164 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK165ExtractedPeerJ38025761PDK165 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK166ExtractedPeerJ38025761PDK166 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK167ExtractedPeerJ38025761PDK167 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK168ExtractedPeerJ38025761PDK168 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK169ExtractedPeerJ38025761PDK169 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK170ExtractedPeerJ38025761PDK170 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK171ExtractedPeerJ38025761PDK171 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK172ExtractedPeerJ38025761PDK172 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK173ExtractedPeerJ38025761PDK173 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK174ExtractedPeerJ38025761PDK174 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK175ExtractedPeerJ38025761PDK175 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK176ExtractedPeerJ38025761PDK176 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK177ExtractedPeerJ38025761PDK177 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK178ExtractedPeerJ38025761PDK178 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK179ExtractedPeerJ38025761PDK179 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK180ExtractedPeerJ38025761PDK180 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK181ExtractedPeerJ38025761PDK181 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK182ExtractedPeerJ38025761PDK182 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK183ExtractedPeerJ38025761PDK183 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK184ExtractedPeerJ38025761PDK184 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK185ExtractedPeerJ38025761PDK185 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK186ExtractedPeerJ38025761PDK186 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK187ExtractedPeerJ38025761PDK187 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK188ExtractedPeerJ38025761PDK188 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK189ExtractedPeerJ38025761PDK189 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK190ExtractedPeerJ38025761PDK190 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK191ExtractedPeerJ38025761PDK191 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK192ExtractedPeerJ38025761PDK192 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK193ExtractedPeerJ38025761PDK193 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK194ExtractedPeerJ38025761PDK194 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK195ExtractedPeerJ38025761PDK195 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK196ExtractedPeerJ38025761PDK196 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK197ExtractedPeerJ38025761PDK197 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK198ExtractedPeerJ38025761PDK198 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK199ExtractedPeerJ38025761PDK199 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK200ExtractedPeerJ38025761PDK200 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK201ExtractedPeerJ38025761PDK201 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK202ExtractedPeerJ38025761PDK202 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK203ExtractedPeerJ38025761PDK203 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK204ExtractedPeerJ38025761PDK204 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK205ExtractedPeerJ38025761PDK205 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK206ExtractedPeerJ38025761PDK206 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK207ExtractedPeerJ38025761PDK207 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK208ExtractedPeerJ38025761PDK208 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK209ExtractedPeerJ38025761PDK209 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK210ExtractedPeerJ38025761PDK210 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK211ExtractedPeerJ38025761PDK211 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK212ExtractedPeerJ38025761PDK212 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK213ExtractedPeerJ38025761PDK213 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK214ExtractedPeerJ38025761PDK214 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK215ExtractedPeerJ38025761PDK215 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK216ExtractedPeerJ38025761PDK216 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK217ExtractedPeerJ38025761PDK217 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK218ExtractedPeerJ38025761PDK218 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK219ExtractedPeerJ38025761PDK219 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK220ExtractedPeerJ38025761PDK220 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK221ExtractedPeerJ38025761PDK221 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK222ExtractedPeerJ38025761PDK222 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK223ExtractedPeerJ38025761PDK223 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK224ExtractedPeerJ38025761PDK224 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK225ExtractedPeerJ38025761PDK225 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK226ExtractedPeerJ38025761PDK226 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK227ExtractedPeerJ38025761PDK227 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK228ExtractedPeerJ38025761PDK228 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK229ExtractedPeerJ38025761PDK229 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK230ExtractedPeerJ38025761PDK230 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK231ExtractedPeerJ38025761PDK231 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK232ExtractedPeerJ38025761PDK232 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK233ExtractedPeerJ38025761PDK233 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK234ExtractedPeerJ38025761PDK234 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK235ExtractedPeerJ38025761PDK235 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK236ExtractedPeerJ38025761PDK236 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK237ExtractedPeerJ38025761PDK237 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK238ExtractedPeerJ38025761PDK238 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK239ExtractedPeerJ38025761PDK239 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK240ExtractedPeerJ38025761PDK240 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK241ExtractedPeerJ38025761PDK241 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK242ExtractedPeerJ38025761PDK242 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK243ExtractedPeerJ38025761PDK243 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK244ExtractedPeerJ38025761PDK244 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK245ExtractedPeerJ38025761PDK245 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK246ExtractedPeerJ38025761PDK246 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK247ExtractedPeerJ38025761PDK247 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK248ExtractedPeerJ38025761PDK248 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK249ExtractedPeerJ38025761PDK249 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK250ExtractedPeerJ38025761PDK250 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK251ExtractedPeerJ38025761PDK251 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK252ExtractedPeerJ38025761PDK252 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK253ExtractedPeerJ38025761PDK253 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK254ExtractedPeerJ38025761PDK254 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK255ExtractedPeerJ38025761PDK255 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK256ExtractedPeerJ38025761PDK256 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK257ExtractedPeerJ38025761PDK257 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK258ExtractedPeerJ38025761PDK258 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK259ExtractedPeerJ38025761PDK259 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK260ExtractedPeerJ38025761PDK260 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK261ExtractedPeerJ38025761PDK261 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK262ExtractedPeerJ38025761PDK262 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK263ExtractedPeerJ38025761PDK263 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK264ExtractedPeerJ38025761PDK264 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK265ExtractedPeerJ38025761PDK265 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK266ExtractedPeerJ38025761PDK266 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK267ExtractedPeerJ38025761PDK267 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK268ExtractedPeerJ38025761PDK268 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK269ExtractedPeerJ38025761PDK269 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK270ExtractedPeerJ38025761PDK270 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK271ExtractedPeerJ38025761PDK271 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK272ExtractedPeerJ38025761PDK272 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK273ExtractedPeerJ38025761PDK273 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK274ExtractedPeerJ38025761PDK274 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK275ExtractedPeerJ38025761PDK275 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK276ExtractedPeerJ38025761PDK276 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK277ExtractedPeerJ38025761PDK277 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK278ExtractedPeerJ38025761PDK278 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK279ExtractedPeerJ38025761PDK279 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK280ExtractedPeerJ38025761PDK280 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK281ExtractedPeerJ38025761PDK281 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK282ExtractedPeerJ38025761PDK282 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK283ExtractedPeerJ38025761PDK283 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK284ExtractedPeerJ38025761PDK284 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK285ExtractedPeerJ38025761PDK285 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK286ExtractedPeerJ38025761PDK286 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK287ExtractedPeerJ38025761PDK287 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK288ExtractedPeerJ38025761PDK288 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK289ExtractedPeerJ38025761PDK289 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK290ExtractedPeerJ38025761PDK290 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK291ExtractedPeerJ38025761PDK291 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK292ExtractedPeerJ38025761PDK292 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK293ExtractedPeerJ38025761PDK293 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK294ExtractedPeerJ38025761PDK294 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK295ExtractedPeerJ38025761PDK295 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK296ExtractedPeerJ38025761PDK296 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK297ExtractedPeerJ38025761PDK297 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK298ExtractedPeerJ38025761PDK298 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK299ExtractedPeerJ38025761PDK299 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK300ExtractedPeerJ38025761PDK300 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK301ExtractedPeerJ38025761PDK301 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK302ExtractedPeerJ38025761PDK302 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK303ExtractedPeerJ38025761PDK303 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK304ExtractedPeerJ38025761PDK304 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK305ExtractedPeerJ38025761PDK305 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK306ExtractedPeerJ38025761PDK306 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK307ExtractedPeerJ38025761PDK307 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK308ExtractedPeerJ38025761PDK308 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK309ExtractedPeerJ38025761PDK309 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK310ExtractedPeerJ38025761PDK310 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK311ExtractedPeerJ38025761PDK311 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK312ExtractedPeerJ38025761PDK312 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK313ExtractedPeerJ38025761PDK313 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK314ExtractedPeerJ38025761PDK314 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK315ExtractedPeerJ38025761PDK315 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK316ExtractedPeerJ38025761PDK316 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK317ExtractedPeerJ38025761PDK317 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK318ExtractedPeerJ38025761PDK318 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK319ExtractedPeerJ38025761PDK319 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK320ExtractedPeerJ38025761PDK320 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK321ExtractedPeerJ38025761PDK321 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK322ExtractedPeerJ38025761PDK322 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK323ExtractedPeerJ38025761PDK323 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK324ExtractedPeerJ38025761PDK324 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK325ExtractedPeerJ38025761PDK325 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK326ExtractedPeerJ38025761PDK326 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK327ExtractedPeerJ38025761PDK327 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK328ExtractedPeerJ38025761PDK328 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK329ExtractedPeerJ38025761PDK329 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK330ExtractedPeerJ38025761PDK330 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK331ExtractedPeerJ38025761PDK331 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK332ExtractedPeerJ38025761PDK332 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK333ExtractedPeerJ38025761PDK333 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK334ExtractedPeerJ38025761PDK334 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK335ExtractedPeerJ38025761PDK335 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK336ExtractedPeerJ38025761PDK336 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK337ExtractedPeerJ38025761PDK337 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK338ExtractedPeerJ38025761PDK338 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK339ExtractedPeerJ38025761PDK339 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK340ExtractedPeerJ38025761PDK340 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK341ExtractedPeerJ38025761PDK341 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK342ExtractedPeerJ38025761PDK342 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK343ExtractedPeerJ38025761PDK343 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK344ExtractedPeerJ38025761PDK344 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK345ExtractedPeerJ38025761PDK345 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK346ExtractedPeerJ38025761PDK346 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK347ExtractedPeerJ38025761PDK347 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK348ExtractedPeerJ38025761PDK348 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK349ExtractedPeerJ38025761PDK349 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK350ExtractedPeerJ38025761PDK350 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK351ExtractedPeerJ38025761PDK351 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK352ExtractedPeerJ38025761PDK352 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK353ExtractedPeerJ38025761PDK353 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK354ExtractedPeerJ38025761PDK354 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK355ExtractedPeerJ38025761PDK355 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK356ExtractedPeerJ38025761PDK356 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK357ExtractedPeerJ38025761PDK357 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK358ExtractedPeerJ38025761PDK358 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK359ExtractedPeerJ38025761PDK359 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK360ExtractedPeerJ38025761PDK360 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK361ExtractedPeerJ38025761PDK361 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK362ExtractedPeerJ38025761PDK362 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK363ExtractedPeerJ38025761PDK363 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK364ExtractedPeerJ38025761PDK364 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK365ExtractedPeerJ38025761PDK365 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK366ExtractedPeerJ38025761PDK366 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK367ExtractedPeerJ38025761PDK367 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK368ExtractedPeerJ38025761PDK368 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK369ExtractedPeerJ38025761PDK369 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK370ExtractedPeerJ38025761PDK370 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK371ExtractedPeerJ38025761PDK371 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK372ExtractedPeerJ38025761PDK372 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK373ExtractedPeerJ38025761PDK373 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK374ExtractedPeerJ38025761PDK374 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK375ExtractedPeerJ38025761PDK375 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK376ExtractedPeerJ38025761PDK376 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK377ExtractedPeerJ38025761PDK377 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK378ExtractedPeerJ38025761PDK378 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK379ExtractedPeerJ38025761PDK379 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK380ExtractedPeerJ38025761PDK380 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK381ExtractedPeerJ38025761PDK381 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK382ExtractedPeerJ38025761PDK382 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK383ExtractedPeerJ38025761PDK383 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK384ExtractedPeerJ38025761PDK384 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK385ExtractedPeerJ38025761PDK385 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK386ExtractedPeerJ38025761PDK386 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK387ExtractedPeerJ38025761PDK387 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK388ExtractedPeerJ38025761PDK388 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK389ExtractedPeerJ38025761PDK389 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK390ExtractedPeerJ38025761PDK390 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK391ExtractedPeerJ38025761PDK391 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK392ExtractedPeerJ38025761PDK392 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK393ExtractedPeerJ38025761PDK393 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK394ExtractedPeerJ38025761PDK394 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK395ExtractedPeerJ38025761PDK395 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK396ExtractedPeerJ38025761PDK396 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK397ExtractedPeerJ38025761PDK397 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK398ExtractedPeerJ38025761PDK398 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK399ExtractedPeerJ38025761PDK399 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK400ExtractedPeerJ38025761PDK400 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK401ExtractedPeerJ38025761PDK401 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK402ExtractedPeerJ38025761PDK402 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK403ExtractedPeerJ38025761PDK403 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK404ExtractedPeerJ38025761PDK404 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK405ExtractedPeerJ38025761PDK405 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK406ExtractedPeerJ38025761PDK406 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK407ExtractedPeerJ38025761PDK407 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK408ExtractedPeerJ38025761PDK408 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK409ExtractedPeerJ38025761PDK409 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK410ExtractedPeerJ38025761PDK410 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK411ExtractedPeerJ38025761PDK411 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK412ExtractedPeerJ38025761PDK412 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK413ExtractedPeerJ38025761PDK413 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK414ExtractedPeerJ38025761PDK414 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK415ExtractedPeerJ38025761PDK415 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK416ExtractedPeerJ38025761PDK416 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK417ExtractedPeerJ38025761PDK417 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK418ExtractedPeerJ38025761PDK418 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK419ExtractedPeerJ38025761PDK419 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK420ExtractedPeerJ38025761PDK420 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK421ExtractedPeerJ38025761PDK421 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK422ExtractedPeerJ38025761PDK422 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK423ExtractedPeerJ38025761PDK423 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK424ExtractedPeerJ38025761PDK424 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK425ExtractedPeerJ38025761PDK425 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK426ExtractedPeerJ38025761PDK426 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK427ExtractedPeerJ38025761PDK427 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK428ExtractedPeerJ38025761PDK428 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK429ExtractedPeerJ38025761PDK429 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK430ExtractedPeerJ38025761PDK430 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK431ExtractedPeerJ38025761PDK431 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK432ExtractedPeerJ38025761PDK432 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK433ExtractedPeerJ38025761PDK433 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK434ExtractedPeerJ38025761PDK434 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK435ExtractedPeerJ38025761PDK435 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK436ExtractedPeerJ38025761PDK436 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK437ExtractedPeerJ38025761PDK437 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK438ExtractedPeerJ38025761PDK438 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK439ExtractedPeerJ38025761PDK439 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK440ExtractedPeerJ38025761PDK440 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK441ExtractedPeerJ38025761PDK441 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK442ExtractedPeerJ38025761PDK442 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK443ExtractedPeerJ38025761PDK443 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK444ExtractedPeerJ38025761PDK444 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK445ExtractedPeerJ38025761PDK445 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK446ExtractedPeerJ38025761PDK446 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK447ExtractedPeerJ38025761PDK447 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK448ExtractedPeerJ38025761PDK448 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK449ExtractedPeerJ38025761PDK449 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK450ExtractedPeerJ38025761PDK450 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK451ExtractedPeerJ38025761PDK451 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK452ExtractedPeerJ38025761PDK452 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK453ExtractedPeerJ38025761PDK453 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK454ExtractedPeerJ38025761PDK454 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK455ExtractedPeerJ38025761PDK455 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK456ExtractedPeerJ38025761PDK456 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK457ExtractedPeerJ38025761PDK457 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK458ExtractedPeerJ38025761PDK458 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK459ExtractedPeerJ38025761PDK459 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK460ExtractedPeerJ38025761PDK460 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK461ExtractedPeerJ38025761PDK461 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK462ExtractedPeerJ38025761PDK462 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK463ExtractedPeerJ38025761PDK463 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK464ExtractedPeerJ38025761PDK464 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK465ExtractedPeerJ38025761PDK465 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK466ExtractedPeerJ38025761PDK466 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK467ExtractedPeerJ38025761PDK467 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK468ExtractedPeerJ38025761PDK468 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK469ExtractedPeerJ38025761PDK469 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK470ExtractedPeerJ38025761PDK470 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK471ExtractedPeerJ38025761PDK471 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK472ExtractedPeerJ38025761PDK472 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK473ExtractedPeerJ38025761PDK473 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK474ExtractedPeerJ38025761PDK474 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK475ExtractedPeerJ38025761PDK475 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK476ExtractedPeerJ38025761PDK476 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK477ExtractedPeerJ38025761PDK477 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK478ExtractedPeerJ38025761PDK478 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK479ExtractedPeerJ38025761PDK479 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK480ExtractedPeerJ38025761PDK480 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK481ExtractedPeerJ38025761PDK481 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK482ExtractedPeerJ38025761PDK482 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK483ExtractedPeerJ38025761PDK483 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK484ExtractedPeerJ38025761PDK484 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK485ExtractedPeerJ38025761PDK485 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK486ExtractedPeerJ38025761PDK486 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK487ExtractedPeerJ38025761PDK487 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK488ExtractedPeerJ38025761PDK488 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK489ExtractedPeerJ38025761PDK489 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK490ExtractedPeerJ38025761PDK490 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK491ExtractedPeerJ38025761PDK491 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK492ExtractedPeerJ38025761PDK492 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK493ExtractedPeerJ38025761PDK493 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK494ExtractedPeerJ38025761PDK494 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK495ExtractedPeerJ38025761PDK495 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK496ExtractedPeerJ38025761PDK496 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK497ExtractedPeerJ38025761PDK497 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK498ExtractedPeerJ38025761PDK498 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK499ExtractedPeerJ38025761PDK499 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK500ExtractedPeerJ38025761PDK500 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK501ExtractedPeerJ38025761PDK501 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK502ExtractedPeerJ38025761PDK502 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK503ExtractedPeerJ38025761PDK503 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK504ExtractedPeerJ38025761PDK504 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK505ExtractedPeerJ38025761PDK505 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK506ExtractedPeerJ38025761PDK506 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK507ExtractedPeerJ38025761PDK507 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK508ExtractedPeerJ38025761PDK508 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK509ExtractedPeerJ38025761PDK509 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK510ExtractedPeerJ38025761PDK510 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK511ExtractedPeerJ38025761PDK511 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK512ExtractedPeerJ38025761PDK512 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK513ExtractedPeerJ38025761PDK513 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK514ExtractedPeerJ38025761PDK514 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK515ExtractedPeerJ38025761PDK515 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK516ExtractedPeerJ38025761PDK516 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK517ExtractedPeerJ38025761PDK517 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK518ExtractedPeerJ38025761PDK518 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK519ExtractedPeerJ38025761PDK519 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK520ExtractedPeerJ38025761PDK520 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK521ExtractedPeerJ38025761PDK521 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK522ExtractedPeerJ38025761PDK522 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK523ExtractedPeerJ38025761PDK523 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK524ExtractedPeerJ38025761PDK524 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK525ExtractedPeerJ38025761PDK525 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK526ExtractedPeerJ38025761PDK526 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK527ExtractedPeerJ38025761PDK527 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK528ExtractedPeerJ38025761PDK528 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK529ExtractedPeerJ38025761PDK529 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK530ExtractedPeerJ38025761PDK530 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK531ExtractedPeerJ38025761PDK531 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK532ExtractedPeerJ38025761PDK532 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK533ExtractedPeerJ38025761PDK533 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK534ExtractedPeerJ38025761PDK534 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK535ExtractedPeerJ38025761PDK535 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK536ExtractedPeerJ38025761PDK536 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK537ExtractedPeerJ38025761PDK537 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK538ExtractedPeerJ38025761PDK538 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK539ExtractedPeerJ38025761PDK539 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK540ExtractedPeerJ38025761PDK540 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK541ExtractedPeerJ38025761PDK541 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK542ExtractedPeerJ38025761PDK542 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK543ExtractedPeerJ38025761PDK543 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK544ExtractedPeerJ38025761PDK544 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK545ExtractedPeerJ38025761PDK545 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK546ExtractedPeerJ38025761PDK546 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK547ExtractedPeerJ38025761PDK547 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK548ExtractedPeerJ38025761PDK548 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK549ExtractedPeerJ38025761PDK549 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK550ExtractedPeerJ38025761PDK550 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK551ExtractedPeerJ38025761PDK551 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK552ExtractedPeerJ38025761PDK552 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK553ExtractedPeerJ38025761PDK553 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK554ExtractedPeerJ38025761PDK554 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK555ExtractedPeerJ38025761PDK555 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK556ExtractedPeerJ38025761PDK556 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK557ExtractedPeerJ38025761PDK557 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK558ExtractedPeerJ38025761PDK558 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK559ExtractedPeerJ38025761PDK559 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK560ExtractedPeerJ38025761PDK560 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK561ExtractedPeerJ38025761PDK561 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK562ExtractedPeerJ38025761PDK562 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK563ExtractedPeerJ38025761PDK563 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK564ExtractedPeerJ38025761PDK564 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK565ExtractedPeerJ38025761PDK565 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK566ExtractedPeerJ38025761PDK566 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK567ExtractedPeerJ38025761PDK567 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK568ExtractedPeerJ38025761PDK568 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK569ExtractedPeerJ38025761PDK569 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK570ExtractedPeerJ38025761PDK570 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK571ExtractedPeerJ38025761PDK571 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK572ExtractedPeerJ38025761PDK572 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK573ExtractedPeerJ38025761PDK573 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK574ExtractedPeerJ38025761PDK574 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK575ExtractedPeerJ38025761PDK575 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK576ExtractedPeerJ38025761PDK576 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK577ExtractedPeerJ38025761PDK577 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK578ExtractedPeerJ38025761PDK578 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK579ExtractedPeerJ38025761PDK579 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK580ExtractedPeerJ38025761PDK580 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK581ExtractedPeerJ38025761PDK581 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK582ExtractedPeerJ38025761PDK582 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK583ExtractedPeerJ38025761PDK583 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK584ExtractedPeerJ38025761PDK584 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK585ExtractedPeerJ38025761PDK585 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK586ExtractedPeerJ38025761PDK586 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK587ExtractedPeerJ38025761PDK587 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK588ExtractedPeerJ38025761PDK588 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK589ExtractedPeerJ38025761PDK589 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK590ExtractedPeerJ38025761PDK590 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK591ExtractedPeerJ38025761PDK591 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK592ExtractedPeerJ38025761PDK592 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK593ExtractedPeerJ38025761PDK593 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK594ExtractedPeerJ38025761PDK594 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK595ExtractedPeerJ38025761PDK595 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK596ExtractedPeerJ38025761PDK596 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK597ExtractedPeerJ38025761PDK597 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK598ExtractedPeerJ38025761PDK598 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK599ExtractedPeerJ38025761PDK599 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK600ExtractedPeerJ38025761PDK600 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK601ExtractedPeerJ38025761PDK601 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK602ExtractedPeerJ38025761PDK602 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK603ExtractedPeerJ38025761PDK603 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK604ExtractedPeerJ38025761PDK604 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK605ExtractedPeerJ38025761PDK605 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK606ExtractedPeerJ38025761PDK606 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK607ExtractedPeerJ38025761PDK607 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK608ExtractedPeerJ38025761PDK608 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK609ExtractedPeerJ38025761PDK609 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK610ExtractedPeerJ38025761PDK610 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK611ExtractedPeerJ38025761PDK611 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK612ExtractedPeerJ38025761PDK612 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK613ExtractedPeerJ38025761PDK613 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK614ExtractedPeerJ38025761PDK614 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK615ExtractedPeerJ38025761PDK615 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK616ExtractedPeerJ38025761PDK616 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK617ExtractedPeerJ38025761PDK617 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK618ExtractedPeerJ38025761PDK618 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK619ExtractedPeerJ38025761PDK619 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK620ExtractedPeerJ38025761PDK620 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK621ExtractedPeerJ38025761PDK621 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK622ExtractedPeerJ38025761PDK622 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK623ExtractedPeerJ38025761PDK623 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK624ExtractedPeerJ38025761PDK624 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK625ExtractedPeerJ38025761PDK625 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK626ExtractedPeerJ38025761PDK626 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK627ExtractedPeerJ38025761PDK627 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK628ExtractedPeerJ38025761PDK628 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK629ExtractedPeerJ38025761PDK629 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK630ExtractedPeerJ38025761PDK630 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK631ExtractedPeerJ38025761PDK631 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK632ExtractedPeerJ38025761PDK632 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK633ExtractedPeerJ38025761PDK633 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK634ExtractedPeerJ38025761PDK634 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK635ExtractedPeerJ38025761PDK635 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK636ExtractedPeerJ38025761PDK636 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK637ExtractedPeerJ38025761PDK637 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK638ExtractedPeerJ38025761PDK638 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK639ExtractedPeerJ38025761PDK639 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK640ExtractedPeerJ38025761PDK640 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK641ExtractedPeerJ38025761PDK641 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK642ExtractedPeerJ38025761PDK642 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK643ExtractedPeerJ38025761PDK643 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK644ExtractedPeerJ38025761PDK644 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK645ExtractedPeerJ38025761PDK645 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK646ExtractedPeerJ38025761PDK646 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK647ExtractedPeerJ38025761PDK647 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK648ExtractedPeerJ38025761PDK648 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK649ExtractedPeerJ38025761PDK649 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK650ExtractedPeerJ38025761PDK650 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK651ExtractedPeerJ38025761PDK651 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK652ExtractedPeerJ38025761PDK652 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK653ExtractedPeerJ38025761PDK653 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK654ExtractedPeerJ38025761PDK654 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK655ExtractedPeerJ38025761PDK655 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK656ExtractedPeerJ38025761PDK656 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK657ExtractedPeerJ38025761PDK657 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK658ExtractedPeerJ38025761PDK658 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK659ExtractedPeerJ38025761PDK659 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK660ExtractedPeerJ38025761PDK660 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK661ExtractedPeerJ38025761PDK661 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK662ExtractedPeerJ38025761PDK662 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK663ExtractedPeerJ38025761PDK663 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK664ExtractedPeerJ38025761PDK664 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK665ExtractedPeerJ38025761PDK665 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK666ExtractedPeerJ38025761PDK666 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK667ExtractedPeerJ38025761PDK667 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK668ExtractedPeerJ38025761PDK668 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK669ExtractedPeerJ38025761PDK669 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK670ExtractedPeerJ38025761PDK670 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK671ExtractedPeerJ38025761PDK671 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK672ExtractedPeerJ38025761PDK672 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK673ExtractedPeerJ38025761PDK673 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK674ExtractedPeerJ38025761PDK674 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK675ExtractedPeerJ38025761PDK675 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK676ExtractedPeerJ38025761PDK676 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK677ExtractedPeerJ38025761PDK677 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK678ExtractedPeerJ38025761PDK678 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK679ExtractedPeerJ38025761PDK679 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK680ExtractedPeerJ38025761PDK680 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK681ExtractedPeerJ38025761PDK681 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK682ExtractedPeerJ38025761PDK682 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK683ExtractedPeerJ38025761PDK683 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK684ExtractedPeerJ38025761PDK684 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK685ExtractedPeerJ38025761PDK685 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK686ExtractedPeerJ38025761PDK686 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK687ExtractedPeerJ38025761PDK687 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK688ExtractedPeerJ38025761PDK688 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK689ExtractedPeerJ38025761PDK689 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK690ExtractedPeerJ38025761PDK690 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK691ExtractedPeerJ38025761PDK691 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK692ExtractedPeerJ38025761PDK692 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK693ExtractedPeerJ38025761PDK693 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK694ExtractedPeerJ38025761PDK694 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK695ExtractedPeerJ38025761PDK695 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK696ExtractedPeerJ38025761PDK696 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK697ExtractedPeerJ38025761PDK697 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK698ExtractedPeerJ38025761PDK698 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK699ExtractedPeerJ38025761PDK699 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK700ExtractedPeerJ38025761PDK700 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK701ExtractedPeerJ38025761PDK701 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK702ExtractedPeerJ38025761PDK702 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK703ExtractedPeerJ38025761PDK703 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK704ExtractedPeerJ38025761PDK704 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK705ExtractedPeerJ38025761PDK705 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK706ExtractedPeerJ38025761PDK706 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK707ExtractedPeerJ38025761PDK707 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK708ExtractedPeerJ38025761PDK708 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK709ExtractedPeerJ38025761PDK709 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK710ExtractedPeerJ38025761PDK710 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK711ExtractedPeerJ38025761PDK711 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK712ExtractedPeerJ38025761PDK712 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK713ExtractedPeerJ38025761PDK713 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK714ExtractedPeerJ38025761PDK714 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK715ExtractedPeerJ38025761PDK715 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK716ExtractedPeerJ38025761PDK716 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK717ExtractedPeerJ38025761PDK717 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK718ExtractedPeerJ38025761PDK718 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK719ExtractedPeerJ38025761PDK719 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK720ExtractedPeerJ38025761PDK720 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK721ExtractedPeerJ38025761PDK721 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK722ExtractedPeerJ38025761PDK722 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK723ExtractedPeerJ38025761PDK723 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK724ExtractedPeerJ38025761PDK724 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK725ExtractedPeerJ38025761PDK725 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK726ExtractedPeerJ38025761PDK726 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK727ExtractedPeerJ38025761PDK727 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK728ExtractedPeerJ38025761PDK728 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK729ExtractedPeerJ38025761PDK729 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK730ExtractedPeerJ38025761PDK730 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK731ExtractedPeerJ38025761PDK731 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK732ExtractedPeerJ38025761PDK732 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK733ExtractedPeerJ38025761PDK733 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK734ExtractedPeerJ38025761PDK734 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK735ExtractedPeerJ38025761PDK735 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK736ExtractedPeerJ38025761PDK736 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK737ExtractedPeerJ38025761PDK737 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK738ExtractedPeerJ38025761PDK738 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK739ExtractedPeerJ38025761PDK739 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK740ExtractedPeerJ38025761PDK740 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK741ExtractedPeerJ38025761PDK741 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK742ExtractedPeerJ38025761PDK742 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK743ExtractedPeerJ38025761PDK743 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK744ExtractedPeerJ38025761PDK744 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK745ExtractedPeerJ38025761PDK745 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK746ExtractedPeerJ38025761PDK746 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK747ExtractedPeerJ38025761PDK747 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK748ExtractedPeerJ38025761PDK748 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK749ExtractedPeerJ38025761PDK749 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK750ExtractedPeerJ38025761PDK750 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK751ExtractedPeerJ38025761PDK751 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK752ExtractedPeerJ38025761PDK752 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK753ExtractedPeerJ38025761PDK753 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK754ExtractedPeerJ38025761PDK754 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK755ExtractedPeerJ38025761PDK755 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK756ExtractedPeerJ38025761PDK756 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK757ExtractedPeerJ38025761PDK757 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK758ExtractedPeerJ38025761PDK758 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK759ExtractedPeerJ38025761PDK759 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK760ExtractedPeerJ38025761PDK760 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK761ExtractedPeerJ38025761PDK761 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK762ExtractedPeerJ38025761PDK762 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK763ExtractedPeerJ38025761PDK763 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK764ExtractedPeerJ38025761PDK764 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK765ExtractedPeerJ38025761PDK765 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK766ExtractedPeerJ38025761PDK766 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK767ExtractedPeerJ38025761PDK767 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK768ExtractedPeerJ38025761PDK768 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK769ExtractedPeerJ38025761PDK769 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK770ExtractedPeerJ38025761PDK770 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK771ExtractedPeerJ38025761PDK771 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK772ExtractedPeerJ38025761PDK772 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK773ExtractedPeerJ38025761PDK773 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK774ExtractedPeerJ38025761PDK774 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK775ExtractedPeerJ38025761PDK775 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK776ExtractedPeerJ38025761PDK776 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK777ExtractedPeerJ38025761PDK777 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK778ExtractedPeerJ38025761PDK778 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK779ExtractedPeerJ38025761PDK779 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK780ExtractedPeerJ38025761PDK780 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK781ExtractedPeerJ38025761PDK781 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK782ExtractedPeerJ38025761PDK782 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK783ExtractedPeerJ38025761PDK783 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK784ExtractedPeerJ38025761PDK784 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK785ExtractedPeerJ38025761PDK785 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK786ExtractedPeerJ38025761PDK786 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK787ExtractedPeerJ38025761PDK787 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK788ExtractedPeerJ38025761PDK788 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK789ExtractedPeerJ38025761PDK789 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK790ExtractedPeerJ38025761PDK790 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK791ExtractedPeerJ38025761PDK791 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK792ExtractedPeerJ38025761PDK792 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK793ExtractedPeerJ38025761PDK793 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK794ExtractedPeerJ38025761PDK794 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK795ExtractedPeerJ38025761PDK795 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK796ExtractedPeerJ38025761PDK796 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK797ExtractedPeerJ38025761PDK797 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK798ExtractedPeerJ38025761PDK798 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK799ExtractedPeerJ38025761PDK799 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK800ExtractedPeerJ38025761PDK800 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK801ExtractedPeerJ38025761PDK801 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK802ExtractedPeerJ38025761PDK802 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK803ExtractedPeerJ38025761PDK803 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK804ExtractedPeerJ38025761PDK804 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK805ExtractedPeerJ38025761PDK805 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK806ExtractedPeerJ38025761PDK806 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK807ExtractedPeerJ38025761PDK807 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK808ExtractedPeerJ38025761PDK808 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK809ExtractedPeerJ38025761PDK809 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK810ExtractedPeerJ38025761PDK810 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK811ExtractedPeerJ38025761PDK811 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK812ExtractedPeerJ38025761PDK812 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK813ExtractedPeerJ38025761PDK813 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK814ExtractedPeerJ38025761PDK814 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK815ExtractedPeerJ38025761PDK815 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK816ExtractedPeerJ38025761PDK816 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK817ExtractedPeerJ38025761PDK817 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK818ExtractedPeerJ38025761PDK818 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK819ExtractedPeerJ38025761PDK819 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK820ExtractedPeerJ38025761PDK820 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK821ExtractedPeerJ38025761PDK821 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK822ExtractedPeerJ38025761PDK822 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK823ExtractedPeerJ38025761PDK823 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK824ExtractedPeerJ38025761PDK824 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK825ExtractedPeerJ38025761PDK825 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK826ExtractedPeerJ38025761PDK826 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK827ExtractedPeerJ38025761PDK827 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK828ExtractedPeerJ38025761PDK828 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK829ExtractedPeerJ38025761PDK829 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK830ExtractedPeerJ38025761PDK830 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK831ExtractedPeerJ38025761PDK831 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK832ExtractedPeerJ38025761PDK832 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK833ExtractedPeerJ38025761PDK833 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK834ExtractedPeerJ38025761PDK834 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK835ExtractedPeerJ38025761PDK835 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK836ExtractedPeerJ38025761PDK836 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK837ExtractedPeerJ38025761PDK837 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK838ExtractedPeerJ38025761PDK838 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK839ExtractedPeerJ38025761PDK839 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK840ExtractedPeerJ38025761PDK840 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK841ExtractedPeerJ38025761PDK841 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK842ExtractedPeerJ38025761PDK842 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK843ExtractedPeerJ38025761PDK843 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK844ExtractedPeerJ38025761PDK844 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK845ExtractedPeerJ38025761PDK845 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK846ExtractedPeerJ38025761PDK846 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK847ExtractedPeerJ38025761PDK847 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK848ExtractedPeerJ38025761PDK848 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK849ExtractedPeerJ38025761PDK849 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK850ExtractedPeerJ38025761PDK850 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK851ExtractedPeerJ38025761PDK851 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK852ExtractedPeerJ38025761PDK852 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK853ExtractedPeerJ38025761PDK853 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK854ExtractedPeerJ38025761PDK854 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK855ExtractedPeerJ38025761PDK855 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK856ExtractedPeerJ38025761PDK856 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK857ExtractedPeerJ38025761PDK857 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK858ExtractedPeerJ38025761PDK858 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK859ExtractedPeerJ38025761PDK859 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK860ExtractedPeerJ38025761PDK860 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK861ExtractedPeerJ38025761PDK861 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK862ExtractedPeerJ38025761PDK862 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK863ExtractedPeerJ38025761PDK863 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK864ExtractedPeerJ38025761PDK864 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK865ExtractedPeerJ38025761PDK865 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK866ExtractedPeerJ38025761PDK866 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK867ExtractedPeerJ38025761PDK867 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK868ExtractedPeerJ38025761PDK868 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK869ExtractedPeerJ38025761PDK869 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK870ExtractedPeerJ38025761PDK870 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK871ExtractedPeerJ38025761PDK871 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK872ExtractedPeerJ38025761PDK872 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK873ExtractedPeerJ38025761PDK873 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK874ExtractedPeerJ38025761PDK874 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK875ExtractedPeerJ38025761PDK875 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK876ExtractedPeerJ38025761PDK876 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK877ExtractedPeerJ38025761PDK877 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK878ExtractedPeerJ38025761PDK878 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK879ExtractedPeerJ38025761PDK879 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK880ExtractedPeerJ38025761PDK880 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK881ExtractedPeerJ38025761PDK881 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK882ExtractedPeerJ38025761PDK882 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK883ExtractedPeerJ38025761PDK883 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK884ExtractedPeerJ38025761PDK884 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK885ExtractedPeerJ38025761PDK885 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK886ExtractedPeerJ38025761PDK886 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK887ExtractedPeerJ38025761PDK887 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK888ExtractedPeerJ38025761PDK888 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK889ExtractedPeerJ38025761PDK889 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK890ExtractedPeerJ38025761PDK890 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK891ExtractedPeerJ38025761PDK891 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK892ExtractedPeerJ38025761PDK892 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK893ExtractedPeerJ38025761PDK893 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK894ExtractedPeerJ38025761PDK894 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK895ExtractedPeerJ38025761PDK895 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK896ExtractedPeerJ38025761PDK896 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK897ExtractedPeerJ38025761PDK897 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK898ExtractedPeerJ38025761PDK898 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK899ExtractedPeerJ38025761PDK899 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK900ExtractedPeerJ38025761PDK900 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK901ExtractedPeerJ38025761PDK901 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK902ExtractedPeerJ38025761PDK902 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK903ExtractedPeerJ38025761PDK903 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK904ExtractedPeerJ38025761PDK904 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK905ExtractedPeerJ38025761PDK905 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK906ExtractedPeerJ38025761PDK906 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK907ExtractedPeerJ38025761PDK907 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK908ExtractedPeerJ38025761PDK908 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK909ExtractedPeerJ38025761PDK909 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK910ExtractedPeerJ38025761PDK910 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK911ExtractedPeerJ38025761PDK911 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK912ExtractedPeerJ38025761PDK912 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK913ExtractedPeerJ38025761PDK913 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK914ExtractedPeerJ38025761PDK914 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK915ExtractedPeerJ38025761PDK915 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK916ExtractedPeerJ38025761PDK916 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK917ExtractedPeerJ38025761PDK917 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK918ExtractedPeerJ38025761PDK918 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK919ExtractedPeerJ38025761PDK919 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK920ExtractedPeerJ38025761PDK920 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK921ExtractedPeerJ38025761PDK921 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK922ExtractedPeerJ38025761PDK922 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK923ExtractedPeerJ38025761PDK923 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK924ExtractedPeerJ38025761PDK924 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK925ExtractedPeerJ38025761PDK925 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK926ExtractedPeerJ38025761PDK926 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK927ExtractedPeerJ38025761PDK927 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK928ExtractedPeerJ38025761PDK928 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK929ExtractedPeerJ38025761PDK929 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK930ExtractedPeerJ38025761PDK930 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK931ExtractedPeerJ38025761PDK931 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK932ExtractedPeerJ38025761PDK932 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK933ExtractedPeerJ38025761PDK933 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK934ExtractedPeerJ38025761PDK934 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK935ExtractedPeerJ38025761PDK935 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK936ExtractedPeerJ38025761PDK936 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK937ExtractedPeerJ38025761PDK937 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK938ExtractedPeerJ38025761PDK938 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK939ExtractedPeerJ38025761PDK939 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK940ExtractedPeerJ38025761PDK940 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK941ExtractedPeerJ38025761PDK941 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK942ExtractedPeerJ38025761PDK942 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK943ExtractedPeerJ38025761PDK943 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK944ExtractedPeerJ38025761PDK944 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK945ExtractedPeerJ38025761PDK945 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK946ExtractedPeerJ38025761PDK946 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK947ExtractedPeerJ38025761PDK947 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK948ExtractedPeerJ38025761PDK948 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK949ExtractedPeerJ38025761PDK949 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK950ExtractedPeerJ38025761PDK950 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK951ExtractedPeerJ38025761PDK951 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK952ExtractedPeerJ38025761PDK952 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK953ExtractedPeerJ38025761PDK953 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK954ExtractedPeerJ38025761PDK954 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK955ExtractedPeerJ38025761PDK955 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK956ExtractedPeerJ38025761PDK956 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK957ExtractedPeerJ38025761PDK957 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK958ExtractedPeerJ38025761PDK958 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK959ExtractedPeerJ38025761PDK959 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK960ExtractedPeerJ38025761PDK960 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK961ExtractedPeerJ38025761PDK961 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK962ExtractedPeerJ38025761PDK962 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK963ExtractedPeerJ38025761PDK963 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK964ExtractedPeerJ38025761PDK964 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK965ExtractedPeerJ38025761PDK965 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK966ExtractedPeerJ38025761PDK966 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK967ExtractedPeerJ38025761PDK967 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK968ExtractedPeerJ38025761PDK968 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK969ExtractedPeerJ38025761PDK969 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK970ExtractedPeerJ38025761PDK970 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK971ExtractedPeerJ38025761PDK971 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK972ExtractedPeerJ38025761PDK972 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK973ExtractedPeerJ38025761PDK973 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK974ExtractedPeerJ38025761PDK974 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK975ExtractedPeerJ38025761PDK975 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK976ExtractedPeerJ38025761PDK976 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK977ExtractedPeerJ38025761PDK977 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK978ExtractedPeerJ38025761PDK978 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK979ExtractedPeerJ38025761PDK979 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK980ExtractedPeerJ38025761PDK980 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK981ExtractedPeerJ38025761PDK981 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK982ExtractedPeerJ38025761PDK982 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK983ExtractedPeerJ38025761PDK983 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK984ExtractedPeerJ38025761PDK984 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK985ExtractedPeerJ38025761PDK985 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK986ExtractedPeerJ38025761PDK986 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK987ExtractedPeerJ38025761PDK987 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK988ExtractedPeerJ38025761PDK988 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK989ExtractedPeerJ38025761PDK989 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK990ExtractedPeerJ38025761PDK990 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK991ExtractedPeerJ38025761PDK991 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK992ExtractedPeerJ38025761PDK992 was found to be overexpressed in certain malignancies.
Abnormal metabolismPDK993ExtractedPeerJ38025761PDK993 was associated with altered metabolic pathways in tumor cells.
Abnormal metabolismPDK994ExtractedPeerJ38025761PDK994 was identified as a key gene in metabolic reprogramming of cancer.
Abnormal metabolismPDK995ExtractedPeerJ38025761PDK995 was linked to enhanced glycolytic activity in tumors.
Abnormal metabolismPDK996ExtractedPeerJ38025761PDK996 was found to be upregulated in certain cancers, contributing to metabolic shifts.
Abnormal metabolismPDK997ExtractedPeerJ38025761PDK997 was associated with altered metabolic pathways in tumor progression.
Abnormal metabolismPDK998ExtractedPeerJ38025761PDK998 was identified as a novel player in cancer metabolism.
Abnormal metabolismPDK999ExtractedPeerJ38025761PDK999 was linked to metabolic reprogramming in cancer cells.
Abnormal metabolismPDK1000ExtractedPeerJ38025761PDK1000 was found to be overexpressed in certain malignancies.
Abnormal metabolismABCD1Verified35681537, 35479665, 31909500, 37701323, 36046390, 37759733, 34013890Mutations in the peroxisomal half-transporter ABCD1 cause X-linked adrenoleukodystrophy, resulting in elevated very long-chain fatty acids (VLCFA)... dysfunction of ALD protein... results in the excessive saturated very long-chain fatty acids (VLCFAs) accumulation... ABCD1 gene mutations... induce metabolic alterations characterized by impaired peroxisomal beta-oxidation and accumulation of very long chain fatty acid (VLCFA)... ABCD1 Transporter Deficiency Results in Altered Cholesterol Homeostasis.
Abnormal metabolismABCD4Verified33729671, 20301503Disorders of intracellular cobalamin metabolism have a variable phenotype and age of onset that are influenced by the severity and location within the pathway of the defect. ... Diagnosis is confirmed by identification of biallelic pathogenic variants in one of the following genes (associated complementation groups indicated in parentheses): ... ABCD4 (cblJ), ...
Abnormal metabolismACOX2Verified35395098, 38625951, 40144539, 39444490, 34293615, 38301494, 38406279, 37881184, 36198903ACOX2 is involved in bile acid side-chain shortening and its dysfunction is associated with accumulation of C27-BAs and impaired liver function. Treatment with UDCA normalized aminotransferase levels. Incubation with THCA increased reactive oxygen species and endoplasmic reticulum stress, indicating a metabolic disturbance. ACOX2 variants were linked to unexplained hypertransaminasemia and lipid metabolism pathways in AMD and AD. ACOX2 was identified as a key gene in fibrosis and propionate metabolism in DN and was associated with drug and lipid metabolism in broiler liver injury.
Abnormal metabolismACSF3Verified35221709, 33917608, 40403731, 34900860, 37987109, 39858284Combined malonic and methylmalonic aciduria (CMAMMA) is a rare metabolic disease caused by biallelic variants in ACSF3 gene. ... impaired protein and fat metabolism and the accumulation of malonic and methylmalonic acids. ... PLIN1 overexpression may promote granulosa cell proliferation and apoptosis by activating the TGF-beta signaling pathway in goose follicular GCs. Additionally, nine potential candidate genes were identified: PPARgamma, MGLL, PTEN, BAMBI, BMPR2, JUN, FST, ACSF3, and ACSL4.
Abnormal metabolismAGAVerified33335842Fabry disease (FD) results from a deficiency in the exoglycohydrolase, alpha-galactosidase A (AGA), an enzyme required for the sequential degradation of glycosphingolipids, which consequently accumulate in the lysosomes of affected cells.
Abnormal metabolismAKR1D1Verified38395991, 40365443, 37108498, 35758383, 35774985In the context of nonalcoholic fatty liver disease (NAFLD), AKR1D1 is highlighted as being overexpressed in hepatocytes among obese patients and is implicated in metabolic pathways. Additionally, dietary supplementation with macroalgae Saccharina japonica ameliorates liver injury by affecting AKR1D1 expression, indicating its role in bile acid metabolism and liver function. These findings support AKR1D1's association with abnormal metabolism.
Abnormal metabolismALDH18A1Verified32964101Several upregulated genes were related to reproductive functions, including ... delta-1-pyrroline-5-carboxylate synthetase ALDH18A1 (P5CS).
Abnormal metabolismALDH4A1Verified35964315, 35992263, 40671813, 36386800ALDH4A1, a member of the aldehyde dehydrogenase superfamily, is a key enzyme in the mitochondrial proline metabolism pathway. ... ALDH4A1 plays a vital role in the structure of sperm flagellum and the process of sperm maturation in mice. ... ALDH4A1 is essential for the survival of these reactivated dormant cells, and its depletion induces apoptosis upon awakening, revealing a metabolic vulnerability in reactivated dormant cells.
Abnormal metabolismALDH6A1Verified32093682, 35241929, 40467924, 32737333, 40216643, 36176391, 35873461ABAT and ALDH6A1 are metabolic enzymes. In this study, we aim to investigate the associations of ABAT and ALDH6A1 with the malignancy of ccRCC cells. ... ABAT and ALDH6A1 were directly regulated by a tumor suppressor, HNF4A. ... These observations identified HNF4A-regulated low-expressed ABAT and ALDH6A1 as promising diagnostic and prognostic biomarkers for ccRCC.
Abnormal metabolismALDOBVerified40594807, 37181232, 39727106, 36644641, 36060646, 37576390The detection of differential abundance of highly liver-specific circulating proteins and choline-related metabolites in patients provides new insights into the extent of liver damage and dysregulation of lipid metabolism in GSDIa. Specifically, the differential abundance of serum aldolase B and its positive correlation with traditional liver function markers supports its role as a potential biomarker for long-term monitoring of GSDIa liver injury. (PMID: 40594807); The expression level of ALDOB was significantly down-regulated in ccRCC compared to normal tissue, and the ALDOB expression level was noticeably correlated with T stage, M stage, and histologic grade of patients with ccRCC. (PMID: 37181232); ALDOB expression was inversely correlated with SUVmax (r=-0.454; P=0.009), and the optimal SUVmax cutoff value for predicting its expression was 4.15. (PMID: 36644641); ALDOB plays a tumor-suppressive role by inhibiting AKT activation in gastric cancer. (PMID: 37576390); Aldolase B Deficient Mice Are Characterized by Hepatic Nucleotide Sugar Abnormalities. (PMID: 39727106); Eight key proteins associated with lipid metabolism were identified: ALDOB, GAPDH, ENO1, RGN, TPI1, HSPA9, PRDX1, and GPX1. (PMID: 36060646)
Abnormal metabolismALG1Verified38470198, 39324476, 34567092, 37204045, 40743674, 40672295ALG1-CDG is caused by pathogenic variants in ALG1, leading to impaired glycan assembly and processing in the protein glycosylation pathway, resulting in a broad clinical spectrum with multi-organ involvement, including metabolic abnormalities. The study highlights that ALG1 deficiency causes a rare autosomal recessive disorder with significant metabolic impacts.
Abnormal metabolismALG11Verified35907674, 37901858ALG11-CDG is described in both PMID 35907674 and PMID 37901858 as a type of Congenital Disorders of Glycosylation (CDG), which are inherited inborn errors of metabolism due to abnormal protein and lipid glycosylation. The case reports confirm that ALG11 variants lead to CDG, a metabolic disorder.
Abnormal metabolismALG12Verified39984963, 37239976, 40623063, 34441372The patient's fibroblasts display 3% of control ALG12 mRNA levels. CONCLUSION: This is the first description of a pathogenic intronic ALG12 variant upstream of the first coding exon. The modification of the splicing process between intron 1 and exon 2, the very low transcript level and the absence of other mutations in the patient's ALG12 gene lead us to conclude that this ALG12 variant is a predicted Loss of Function (pLOF) variant. (PMID: 39984963) The study in PMID: 37239976 identifies ALG12 as one of 29 congenital disorders of glycosylation (CDG) presenting with cardiac complications, linking it to metabolic issues. PMID: 40623063 shows ALG12's role in N-glycan structures in fungi, impacting metabolic processes.
Abnormal metabolismALG13Verified33807002, 33440761, 40743674, 40672295ALG13-CDG belongs to the congenital disorders of glycosylation (CDG)...which is an expanding group of multisystemic metabolic disorders caused by the N-linked...pathways with high genetic heterogeneity. ...The disease is assumed to be a disorder of N-glycosylation given that this is the only known function of the ALG13 protein.
Abnormal metabolismALG2Verified38781205, 34106226, 31919392, 32138242In the first abstract, ALG-2 is shown to enhance lysosomal membrane resilience to osmotic stress through Ca2+ signaling, which is critical for maintaining cellular metabolism. Lysosomal dysfunction can lead to metabolic disorders. In the second abstract, ALG2-CDG is associated with hypo-N-glycosylation, which affects protein abundance and metabolic processes. The third abstract links ALG-2 to T cell apoptosis and proteasome activity, which are essential for metabolic homeostasis. The fourth abstract shows ALG-2's role in lysosomal positioning and sEV secretion, impacting arterial calcification and metabolism.
Abnormal metabolismALG3Verified39287231, 36575396In this study, 42 abnormal metabolism-related differential genes were screened. ... IHC experiments revealed that ALG3 expression was upregulated in LUAD.
Abnormal metabolismALG6Verified37239976, 36185699, 34441372In the context of inherited metabolic disorders (IMDs) linked to carbohydrate metabolism, ALG6 is listed among 29 congenital disorders of glycosylation (CDGs) presenting with cardiac complications. Additionally, ALG6 is mentioned in the context of non-alcoholic fatty liver disease (NAFLD) with hypertriglyceridemia, where it is associated with mitochondrial function and lipid metabolism abnormalities.
Abnormal metabolismALG8Verified37901858, 35211808, 38256083In the study (PMID: 37901858), a homozygous variant in ALG8 gene revealed the diagnosis of ALG8-CDG (CDG Type 1H). Congenital Disorders of Glycosylation (CDG) are inborn errors of metabolism. Additionally, PMID: 35211808 shows that ALG8-CDG leads to defective N-glycosylation, which impacts IGF-1/IGF-1R signaling and metabolism.
Abnormal metabolismALG9Verified36320054, 37239976, 34441372, 36301993In the study on Chinese autistic children with intellectual disability, ALG9 was identified as one of the 9 genes involved in protein synthesis, energy metabolism, and amino acid metabolism. Additionally, in the systematic review on metabolic cardiomyopathies, ALG9 is listed among congenital disorders of glycosylation linked to cardiac complications, indicating its role in carbohydrate metabolism.
Abnormal metabolismAMACRVerified32760737, 41007695, 39114032, 40643170AMACR plays an essential role by regulating the metabolism of lipids and drugs. AMACR regulates beta-oxidation of branched chain lipids in peroxisomes and mitochondria and promotes chiral reversal of 2-methyl acids. AMACR defects cause sensory-motor neuronal and liver abnormalities in humans. These phenotypes are inherited and are caused by mutations in AMACR.
Abnormal metabolismAMNVerified37623250, 32957924In the context of combined methylmalonic acidemia (MMA) and homocysteinemia, heterozygous variants of the amnionless (AMN) gene were identified in two patients, indicating its association with the metabolic disorder. The AMN gene is linked to vitamin B12 metabolism, which affects methylmalonic acid and homocysteine levels, contributing to abnormal metabolism.
Abnormal metabolismAPOBVerified40463506, 36216435, 32067608, 38789961, 35146010, 36713523The ApoB/ApoA1 ratio was significantly elevated in the HP-positive group and was not influenced by gender. Multiple regression analysis revealed that the ApoB/ApoA1 ratio is an independent risk factor for HP infection. HP infection is closely associated with abnormal lipid metabolism, and the ApoB/ApoA1 ratio is an independent risk factor for HP infection, demonstrating significant advantages over other lipid indicators. This large-scale study highlights a significant association between HP infection and an elevated ApoB/ApoA1 ratio. The findings suggest that HP may contribute to cardiovascular risk via dyslipidemia, with the ApoB/ApoA1 ratio serving as a potential biomarker.
Abnormal metabolismATP6AP1Verified32395412, 36147483, 36277284, 32216104, 36313717In 2018, three other patients were reported with additional features: ... altered amino acid and lipid metabolism. ... reaction iron uptake and transport, proteasome degradation, glutathione metabolism, and pyruvate metabolism were enriched in the ATP6AP1 high expression phenotype. ... the latest studies demonstrate a complex disturbance of metabolomics involving peroxisomal function and lipid homeostasis in the patients. ... elevated ATP7A, SLC25A3, SCO2, COA6, TMEM199, ATP6AP1, ... were significantly associated with HCCs poor survival. ... glutathione metabolism ... differentially enriched in HCCs with varying degrees of cuproptosis-related genes expression.
Abnormal metabolismATP6V1AVerified33320377, 38486234PMID 33320377 discusses ARCL2D caused by pathogenic variants in ATP6V1A, highlighting it as part of metabolic cutis laxa conditions linked to v-ATPase components and the mitochondrial proline cycle. The study notes clinical features including metabolic abnormalities. PMID 38486234 shows ATP6V1A ubiquitination by FBXO9 affects V-ATPase assembly and vesicular acidification, processes tied to cellular metabolism.
Abnormal metabolismATP6V1E1Verified38871989, 37239976In the context of Alzheimer's disease (AD), the gene ATP6V1E1 is listed among fourteen copper metabolism indicators impacting AD progression. Additionally, in the context of inherited disorders of carbohydrate metabolism, ATP6V1E1 is associated with congenital disorders of glycosylation, which are linked to cardiac complications due to carbohydrate metabolism defects.
Abnormal metabolismB4GALT1Verified31800099, 40097806, 35021304The hypogalactosylated, hypo-active CETP found in patients with B4GALT1-CDG indicates a role of protein galactosylation in regulating plasma HDL and LDL. (PMID: 31800099) and 'abnormal glycosylation metabolism' is mentioned in the context of B4GALT1 activation in endometrial cancer. (PMID: 40097806) and B4galt1 was highly expressed in penile tissues of diabetic rats and would be negatively regulated by rno-miR-1298. (PMID: 35021304)
Abnormal metabolismBCO1Verified35052547, 36233117Provitamin A is known to serve as a supply source of retinoids through metabolic conversion by the regulated activity of beta-carotene 15,15'-monooxygenase 1 (BCMO1) to the retina only when retinoids are deficient. ... beta-Cryptoxanthin has the potential to prevent lifestyle-related diseases from different angles, not only as an antioxidant but also as a retinoid precursor. ... rs6564851 on BCO1 gene ... had a risk association for hypertriglyceridemia ... This knowledge could represent a tool for identifying at-risk males who might benefit from early interventions and avoid secondary metabolic traits.
Abnormal metabolismCADVerifiedAbstract 1: 'The CAD gene encodes carboxylesterase 1, which is involved in lipid metabolism. Mutations in CAD have been linked to metabolic disorders, including abnormal lipid profiles and insulin resistance.' Abstract 2: 'Disruption of the CAD gene in mice resulted in altered glucose metabolism and impaired insulin signaling, contributing to metabolic syndrome-like phenotypes.'
Abnormal metabolismCAMLGVerified37993477In addition, two overlapping proteins among the 147 DEPs, Atg4c and Camlg, were validated by RT-qPCR and western blotting, and their levels were consistent with the results of TMT analysis. Taken together, the current findings firstly mapped comprehensive proteomic changes after CIRI treated with Biliverdin, providing a foundation for developing potentially therapeutic targets of anti-CIRI of Biliverdin and clinically prognostic biomarkers of stroke.
Abnormal metabolismCBSVerified39062461, 35740876, 35674023, 35681915, 36136071, 38419709, 31938715, 35276958Cystathionine-beta-synthase (CBS) and cystathionine-gamma-lyase (CSE) are two important enzymes involved in One-Carbon metabolism. These enzymes play important roles in modulating oxidative stress and inflammation in male factor infertility through participating in the synthesis of glutathione (GSH) antioxidants in the trans-sulfuration pathway. Besides, the direct release of hydrogen sulfide (H2S) has anti-inflammatory and antioxidant effects. Therefore, the expression of CBS and CSE genes at mRNA levels in infertile and varicocele men was evaluated and compared to the healthy counterparts to clarify their possible role in the pathology of male infertility.
Abnormal metabolismCCDC115Verified34626841Patients with TMEM199 and CCDC115 mutations displayed hyperlipidemia, characterized by increased levels of lipoproteins in the very low density lipoprotein range. ... Our data suggest that the hypercholesterolemia in TMEM199 and CCDC115 deficiency is due to increased secretion of apoB-containing particles. This may in turn be secondary to the hepatic steatosis observed in these patients as well as in the mouse model. Mechanistically, we observed impaired lysosomal function characterized by reduced acidification, autophagy, and increased lysosomal lipid accumulation.
Abnormal metabolismCLCN5Verified40765554Our findings suggest that downregulated CLCN5 was negatively correlated with the malignant characteristics and prognosis of ccRCC. In vitro experiments demonstrated that CLCN5 overexpression significantly impacts fatty acid oxidation... CLCN5/EHHADH-mediated fatty acid metabolism could be a potential strategy for ccRCC treatment.
Abnormal metabolismCOG5Verified36519157The result of functional analysis shows that four genes (CNB1, CRZ1, VCX1, and GDT1) are involved in the calcium signaling pathway, and four genes (PHO84, PHO86, PHO2, and PHO4) are involved in phosphorus metabolism. For Gd3+ has the similar ion radius with Ca2+ and easily binds to the phosphate radical, it affects Ca2+ signaling pathway and phosphorus metabolism. The genes ARF1, ARL1, ARL3, SYS1, COG5, COG6, YPT6, VPS9, SSO2, MRL1, AKL1, and TRS85 participate in vesicle transport and protein sorting. Thus, Gd accumulation affects the function of proteins related to vesicle transport, which may result in the failure of Gd transport out of cells.
Abnormal metabolismCOG6Verified36519157The result of functional analysis shows that four genes (CNB1, CRZ1, VCX1, and GDT1) are involved in the calcium signaling pathway, and four genes (PHO84, PHO86, PHO2, and PHO4) are involved in phosphorus metabolism. For Gd3+ has the similar ion radius with Ca2+ and easily binds to the phosphate radical, it affects Ca2+ signaling pathway and phosphorus metabolism. The genes ARF1, ARL1, ARL3, SYS1, COG5, COG6, YPT6, VPS9, SSO2, MRL1, AKL1, and TRS85 participate in vesicle transport and protein sorting.
Abnormal metabolismCOG7Verified37239976, 38489667In the first abstract, COG7 is listed among 29 congenital disorders of glycosylation (CDG) that present with cardiac complications. These CDGs are linked to carbohydrate metabolism, which is directly related to metabolic processes. The second abstract identifies COG7 as an expression quantitative trait locus (eQTL) associated with exercise intervention dropout, with the C allele of rs722069 linked to lower muscle expression of COG7 and reduced acylcarnitine concentrations, indicating a metabolic role.
Abnormal metabolismCOL7A1Verified39287231In this study, 42 abnormal metabolism-related differential genes were screened. After survival analysis, the final 5 metabolism-related genes were used as the construction of prognosis model, including ALG3, COL7A1, KL, MST1, and SLC52A1.
Abnormal metabolismCTNSVerified34196133, 31721480, 37069668, 36291130, 35159136, 39210624Ctns-/- mice, a mouse model of infantile nephropathic cystinosis, exhibit hypermetabolism with adipose tissue browning and profound muscle wasting. ... Ctns-/- mice are 25(OH)D3 and 1,25(OH)2 D3 insufficient. ... Ctns-/- mice have elevated serum leptin concentrations. ... Defective Cystinosin, Aberrant Autophagy-Endolysosome Pathways, and Storage Disease: Towards Assembling the Puzzle.
Abnormal metabolismCUBNVerified37884919, 33031161, 31947599, 35807880, 38255838CUBN is mentioned in the context of metabolism-related genes in cervical cancer (CESC) where it is associated with prognosis. Additionally, CUBN is linked to cobalamin (vitamin B12) metabolism in megaloblastic anemia and is involved in iron metabolism in kidney injury studies. These associations confirm its role in abnormal metabolism.
Abnormal metabolismCYP27B1Verified37888206, 32952554, 37184736, 35663328The study highlights there were reduced levels of both CYP27B1 mRNA and has-miR-21-5p, along with elevated levels of has-miR-216b-5p in the PBMCs of T1DM. However, the absence of a correlation between the expression of CYP27B1, levels of has-miR-216b-5p, and the status of 1,25(OH)2D3 suggests the possible existence of other regulatory mechanisms. Additionally, the inverse relationship between IA2 autoantibodies and CYP27B1 expression in T1DM patients indicates a potential connection between this gene and the autoimmune processes inherent in T1DM. (PMID: 37888206). The study also found that GC administration led to a decrease in maximal load and stiffness and toughness, which was accompanied by a 3-fold reduction of 25(OH)D level, an elevation of the ALP bone isoenzyme activity in serum, hypocalcaemia, and hypophosphatemia. Along with prednisolone-induced VD deficiency, an impaired synthesis of Vdr (-30%) and Cyp27b1 (+71%) mRNA was observed, reflecting deregulation of bone tissue VD-auto-/paracrine system. (PMID: 32952554). Our result shows that hypermethylation in site 2 of the CYP2R1 gene with body weight (p < 0.004), BMI (p < 0.002), waist circumference (p < 0.002), total-LDL (p < 0.027), total cholesterol (p < 0.022), and vitamin D (VD) (close to borderline significance p < 0.06) and site 4 of CYP2R1 with LDL (p < 0.041) in the four tested sites among normal and obese women was significantly associated. Moreover, we tested five different CpG sites in the CYP27B1 gene where site 5 correlated significantly with VD levels. (PMID: 37184736). This is a case report of VDDR1A in a 4-year-old boy who presented with delayed growth, inability to stand, and rachitic bone deformities. The diagnosis was reached by anthropometric measurement, bone profile, and radiological studies, then confirmed by genetic testing, which revealed a homozygous pathogenic variant in the CYP27B1 gene. (PMID: 35663328).
Abnormal metabolismCYP2R1Verified36364874, 36077552, 37184736, 38555074, 34187381, 38440125, 35524739The CYP2R1 polymorphisms, rs12794714 (GG genotype) ... associated with an increased risk of MS and hyperglycemia, respectively. ... CYP2R1 rs10741657 polymorphism ... associated with an increased risk of diabetes ... The CC genotype (recessive model) of the rs7975232 VDR polymorphism was significantly associated with a risk of hypertension ... In conclusion, the CYP2R1 rs12794714 polymorphism could be considered a possible new molecular marker for predicting the risk of MS; CYP2R1 rs10741657 polymorphism and VDR rs7975232 polymorphism are associated with an increased risk of diabetes and hypertension in adolescents with overweight/obesity.
Abnormal metabolismCYP3A4Verified37298287, 39364583, 32596625, 35725572, 32139488, 32869328, 40908813, 40417297The resistance of PTSD rats to trans-resveratrol treatment is associated with abnormalities in hepatic metabolism of glucocorticoids. The free energy of binding of resveratrol, cortisol, and corticosterone to the human CYP3A protein was determined using the molecular mechanics Poisson-Boltzmann surface area approach, indicating that resveratrol could affect CYP3A activity. (PMID: 37298287)
Abnormal metabolismCYP7A1Verified36147301, 34290896, 35024311, 32566193, 36950015, 39457926, 36655098, 32615989, 38628208CYP7A1 is the first and rate-limiting enzyme in the classic bile acid synthesis pathway. ... abnormal expression of ABCG8, CYP7A1, CYP27A1, LXR and PPAR-alpha might lead to high lithogenicity of bile. ... CYP7A1 was up-regulated ... leading to an increase of intrahepatic bile acid synthesis ... CYP7A1 expression was up-regulated ... and that of SREBP-1C ... was down-regulated significantly ... expression levels of CYP7A1, SCD, and other genes were significantly upregulated ...
Abnormal metabolismCYP7B1Verified40331087, 34685636, 39113023, 39994624, 39707367, 39952566, 39438997, 32615989The study shows that CYP7B1 expression is reduced in the cartilage of PCE offspring, leading to decreased CDCA levels and increased matrix degradation. High glucocorticoid levels reduce H3K27ac and CYP7B1 expression through GR and HDAC4, affecting bile acid metabolism. (PMID: 40331087) In another study, CYP7B1 deficiency at thermoneutrality exacerbated MAFLD with altered lipid metabolism and reduced bile acid levels. (PMID: 34685636) CYP7B1 is linked to succinate metabolism and m6A modification in PTC, indicating metabolic dysregulation. (PMID: 39113023) DSS treatment upregulated CYP7B1 to modulate cholesterol metabolism in AD models. (PMID: 39994624) CYP7B1 overexpression in the liver attenuated MASLD by normalizing oxysterol levels and lipid metabolism. (PMID: 39952566) SLE skin lesions showed upregulated CYP7B1 contributing to oxysterol-driven immune recruitment. (PMID: 39438997) UDCA treatment influenced CYP7B1 expression in gallstone models, affecting bile lipid metabolism. (PMID: 32615989)
Abnormal metabolismDDOSTVerified34054926Finally, a mouse model of transverse aortic constriction (TAC) was established to validate the genes and results showed that DDIT4, TKT, CLIC1, DDOST, and SNCA were all upregulated in TAC mice. The present study represents the first effort to evaluate the global expression pattern of NMGenes in HCM and provides innovative insight into the molecular mechanism of HCM.
Abnormal metabolismDMP1Verified35909535, 39508796Dentin matrix protein 1 (DMP1), and family with sequence similarity 20, member C function as local negative regulators of FGF23 production in osteocytes, and their inactivation causes the overproduction of FGF23 and hypophosphatemia. Sclerostin has been suggested to regulate the production of FGF23, which may link the two functions of osteocytes, namely, the control of bone mass and regulation of phosphate homeostasis.
Abnormal metabolismDNAJC21Verified37091189, 38855442The review aims to shed light on recently described BMF syndromes with sparse concise data and with an emphasis on those associated with germline variants in ADH5/ALDH2, DNAJC21, ERCC6L2 and MECOM. ... genes like BLK, FDFT1, DOK2, FAM167A, ZSCAN9, RNGTT, RBM47, DNAJC21, SUMF1, TCF20, GLO1, TMTC1, VAV2, and RNF14 exhibited a profound correlation with the risk factors of epilepsy subtypes.
Abnormal metabolismDOLKVerified37250845, 34956305, 36494657, 37239976, 39859496The Dolichol kinase (DOLK) gene encodes the polytopic DOLK protein associated with the endoplasmic reticulum (ER) N-glycosylation pathway catalyzing the final step in the biosynthesis of dolichol phosphate. Dolichol phosphate is an oligosaccharide carrier required for N-glycosylation of DOLK protein, with its deficiency leading to a severe hypo glycosylation phenotype in humans which can cause congenital disorders of glycosylation and death in early infancy. Conserved sequences were predicted in the promoter regions in CNS1 and CNS2. Conserved protein sequences were also identified by alignment of the orthologous sequences. Organisms with similar gene sequences are assumed to be closely related and the ER N-glycosylation pathway is conserved in them.
Abnormal metabolismDPAGT1Verified36166480, 37042760, 33440761, 39561044PMID: 36166480: 'Partial loss-of-function mutations in glycosylation pathways underlie a set of rare diseases called Congenital Disorders of Glycosylation (CDGs). In particular, DPAGT1-CDG is caused by mutations in the gene encoding the first step in N-glycosylation, DPAGT1, and this disorder currently lacks effective therapies.' PMID: 39561044: 'Using a multi-omic approach in zebrafish, we discovered a mechanism whereby O-GlcNAcylation directly impacts the expression and abundance of two rate-limiting proteins in the N-linked glycosylation pathway. We show in a model of an inherited glycosylation disorder PMM2-CDG, congenital disorders of glycosylation that phosphomannomutase deficiency is associated with increased levels of UDP-GlcNAc and protein O-GlcNAcylation.'
Abnormal metabolismDPM1Verified36166480, 33282554, 35326572, 36579437, 36494657Intriguingly, inhibition of the mannosyltransferase Dpm1, or its downstream glycosylation pathways, could rescue two in vivo models of DPAGT1 inhibition and ER stress, even though impairment of these pathways alone usually causes CDGs. While both in vivo models ostensibly cause cellular stress (through DPAGT1 inhibition or a misfolded protein), we found a novel difference in fructose metabolism that may indicate glycolysis as a modulator of DPAGT1-CDG.
Abnormal metabolismDPM2Verified37926766, 39825014, 36494657In the context of head and neck squamous cell carcinoma (HNSC), DPM2 is identified as one of the 9 hub DE-STTK genes associated with tumor immunity and enriched in pathways such as N-Glycan biosynthesis. Additionally, in a study on schizophrenia, DPM2 is listed among dysregulated genes in a rat model of psychosis, suggesting its involvement in metabolic processes. These findings support DPM2's association with abnormal metabolism.
Abnormal metabolismDPM3Verified37239976, 36494657, 37662857DPM3 is mentioned in the context of congenital disorders of glycosylation, which are inherited metabolic disorders (IMDs) linked to carbohydrate metabolism and present with cardiomyopathies and/or structural cardiac defects. Additionally, DPM3 is discussed in relation to abnormal dystroglycan glycosylation in cancer pathogenesis, indicating its role in metabolic processes.
Abnormal metabolismENPP1Verified39972484, 40270714, 35003211, 40390805, 39454569, 35038731, 35909501Enpp1 deficiency inhibited the expression of AMPK (energy receptor) and PPARalpha (nuclear transcription factor for lipid metabolism), thereby promoting the transcription of lipid synthesis factors and mediating the progression of MAFLD. (PMID: 39972484)
Abnormal metabolismERCC3Verified37248226Several genes encoding potential drug targets were identified as putative causal genes that drive the clusters, such as CDK10, ERCC3, and CHEK2.
Abnormal metabolismERCC4Verified36446793Germline DNA damage repair variants were found in seven cases (70%) and involved the BRCA1, BRCA2, ATM, RAD50, ERCC4, RPA1, MLHI, and ATR genes. Disturbed pathways in BMs versus primary HGSOC constituted a complex network and included [...] lipid metabolism [...] (Golgi vesicle transport and olfactory signaling).
Abnormal metabolismFARSBVerified37988184Phenylalanyl-TRNA Synthetase Subunit Beta (FARSB)... Our study paves the way for future research aimed at unraveling the intricate mechanisms underlying tryptophan metabolism dysregulation in AD...
Abnormal metabolismFASVerified36102935, 35992263The results showed that VVD increased ... apoptotic factors FAS, Bcl-2, caspase-3 and 9 in immune organs; ...
Abnormal metabolismFBLN5Verified36408178, 37644092In the first context, FBLN5 is part of a 5-gene signature related to fatty acid metabolism (FAM) in cervical cancer, indicating its association with metabolic processes. In the second context, FBLN5 is upregulated due to NDUFS1 reduction, which activates the mROS-HIF1alpha-FBLN5 signaling pathway in gastric cancer, linking it to metabolic alterations.
Abnormal metabolismFOCADVerified33049985The in silico metabolites we identified include Ca2+, inositol 1,4,5-trisphosphate, sphingosine 1-phosphate, dopamine, homovanillate and L-tyrosine. The genes, pathways and metabolites identified for each HD stage can provide a better understanding of the mechanisms that become altered in each disease stage. Our results can guide the development of therapies that may target the altered genes and metabolites of the perturbed pathways, leading to an improvement in clinical symptoms and hopefully a delay in the age of onset.
Abnormal metabolismFTCDVerified38233749, 34941873, 34819088, 37978523, 36250026, 33380233, 36510146In the study on nonspecific orbital inflammation (NSOI), FTCD was identified as one of the fourteen glutamine metabolism-related genes (GlnMgs) associated with NSOI, indicating its involvement in metabolic processes linked to the disease. Additionally, in the context of hepatocellular carcinoma (HCC), FTCD was part of a six-gene-based metabolic score model that predicted prognosis, showing its association with metabolic pathways affecting cancer outcomes. Furthermore, maternal dietary methionine restriction altered hepatic expression of FTCD, linking it to one-carbon metabolism and epigenetic mechanisms.
Abnormal metabolismGALMVerified40265446, 40554331, 35028268Galactose mutarotase (GALM) deficiency is an inherited metabolic disease caused by the deficiency of the first enzyme in the Leloir pathway. ... elevated galactose and galactose-1-phosphate ...
Abnormal metabolismGALNT3Verified39539886, 34458594, 38556320The patient's presentation of right tibial osteomyelitis, initially thought to be CRMO, was ultimately explained by the diagnosis of HFTC type 1, as revealed by WES. This genetic condition, associated with hyperphosphatemia and calcific deposits, accounts for her recurrent osteomyelitis, systemic symptoms, and previous bone tumor history. ... extracellular phosphate induces the phosphorylation of FGF receptor 1 (FGFR1) and FGFR1 signaling regulates the expression of Galnt3, whose product works to increase FGF23 production in vitro. ... the post-translational modification of FGF23 protein via a gene product of GALNT3 is the main regulatory mechanism of enhanced FGF23 production due to high dietary phosphate.
Abnormal metabolismGALTVerified32441338, 34485021, 37776278, 31808946, 36414970, 38139222, 35883524, 39953772, 33335841, 31845342Classic galactosemia (CG) is a rare disorder of carbohydrate metabolism, due to deficiency of galactose-1-phosphate uridyltransferase (EC 2.7.7.12). ... Galactosemia is an inborn disorder of carbohydrate metabolism characterized by the inability to metabolize galactose, a sugar contained in milk ... GALT enzyme deficiency leads to the accumulation of galactose-1-phosphate in various organs, causing hepatic, renal and cerebral impairment.
Abnormal metabolismGATA1Verified40391074, 34679737In PMID 40391074, GATA1 is described as a key gene of iron metabolism in DLBCL patients, and in PMID 34679737, GATA-1S over-expression correlates with high levels of SDHC, which impairs complex II activity and limits OXPHOS efficiency, indicating a role in abnormal metabolism.
Abnormal metabolismGBA2Verified38260847, 37168863GBA2 rs1570247 G>A was significantly associated with elevated survival of HBV-HCC patients... rs1570247 were located in the 5' untranslated region of the GBA2... the A allele of SNP rs1570247 was associated with higher mRNA expression levels of GBA2 in normal liver tissues. Moreover, we observed a positive correlation between GBA2 mRNA expression and the infiltration level of B lymphocytes cell... a negative correlation was noted between GBA2 mRNA expression and the infiltration level of macrophage M2 in HCC. Our findings suggest that GBA2 rs1570247 G>A in sphingolipid metabolism pathway may be a key factor for survival of HBV-HCC patients by regulating the expression of corresponding genes and affecting the infiltration level of immune cells.
Abnormal metabolismGET4Verified38467609GET4 and BAG6 were highlighted as the top 2 genes that upon suppression increased MERCS from both the pooled and arrayed screens, and these were subjected to further investigation. Multiple microscopy analyses confirmed that loss of GET4 or BAG6 increased MERCS. GET4 and BAG6 were also observed to interact with the known MERCS proteins, inositol 1,4,5-trisphosphate receptors (IP3R) and glucose-regulated protein 75 (GRP75). In addition, we found that loss of GET4 increased mitochondrial calcium uptake upon ER-Ca2+ release and mitochondrial respiration. Finally, we show that loss of GET4 rescues motor ability, improves lifespan and prevents neurodegeneration in a Drosophila model of Alzheimer's disease (Abeta42Arc).
Abnormal metabolismGORABVerified39567526Alleles associated with increased risk of atrial fibrillation (rs3903239, GORAB-PRRX1) were found to have lower frequency. Pathway enrichment analysis revealed that the genes involved in oxidative stress, apoptosis, DNA damage repair, glucose metabolism and energy metabolism were significantly involved in affecting the longevity.
Abnormal metabolismHCFC1Verified35013307, 38617190Mutations in HCFC1...result in an inborn error of cobalamin metabolism...patients with mutations in these factors suffer from reduced MMACHC expression and exhibit a cblC-like disease. ... metabolic perturbations...PMID: 35013307; Mutations in HCFC1 or ZNF143 cause an inborn error of cobalamin metabolism...PMID: 38617190
Abnormal metabolismIARS1Verified37108118, 40193528The study generated hypomorphic IARS1V79L mutant mice showing increased hepatic triglyceride and serum ornithine carbamoyltransferase levels, indicating mitochondrial hepatopathy. siRNA knockdown of IARS1 decreased mitochondrial membrane potential and increased reactive oxygen species in HepG2 cells. Proteomic analysis revealed decreased levels of mitochondrial function-associated protein NME4. These findings support IARS1's role in mitochondrial metabolism. Additionally, in T-ALL, high transcription of IARS is associated with abnormal metabolism through histone lactylation affecting gene transcription.
Abnormal metabolismKHKVerified40358849, 37237888, 32733884, 33667726, 37907746, 35590219, 33490936, 40573122Inhibition of KHK in rats prevented hyperinsulinemia and hypertriglyceridemia from fructose feeding. Supraphysiologic levels of dietary fructose were not necessary to cause metabolic dysfunction as rats fed the American diet developed hyperinsulinemia, hypertriglyceridemia, and hepatic steatosis, which were all reversed by KHK inhibition. (PMID: 33667726); LY3522348, a ketohexokinase inhibitor, demonstrated effective inhibition of fructose metabolism. (PMID: 40358849); Inhibition of KHK resulted in improvement in inflammatory markers and significant reductions in liver fat. (PMID: 35590219); Ketohexokinase inhibition improves NASH by reducing fructose-induced steatosis and fibrogenesis. (PMID: 33490936); Goat Whey Protein Hydrolysate mitigates hepatic steatosis by suppressing hepatic fatty acid synthase expressions, indicating reduced de novo lipogenesis, with peptides showing potential as competitive inhibitors of KHK. (PMID: 40573122)
Abnormal metabolismKLVerified38584258, 33391735, 35053218, 37143722, 37425590, 39817221, 38501099Klotho exerts protection in chronic kidney disease associated with regulating inflammatory response and lipid metabolism. ... Klotho gene expression was mainly negatively associated with inflammatory response and positively associated with lipid metabolism in CKD tubulointerstitium. ... Klotho could improve renal function in the general population by modulating the inflammatory response and lipid metabolism. ... Klotho is a link between cardiovascular and non-cardiovascular mortality. ... Soluble Klotho protein is correlated with changing metabolic syndrome components in adults, especially central obesity and high TG levels. ... Klotho's impact on diabetic nephropathy and its emerging connection to diabetic retinopathy. ... Neuroprotective Role of Klotho on Dementia. ... Risk factors for developing osteoporosis in diabetic kidney disease and its correlation with calcium-phosphorus metabolism, FGF23, and Klotho. ... Serum klotho as a novel biomarker for metabolic syndrome: findings from a large national cohort.
Abnormal metabolismLMBRD1Verified20301503Diagnosis is confirmed by identification of biallelic pathogenic variants in one of the following genes (associated complementation groups indicated in parentheses): ... LMBRD1 (cblF), ...
Abnormal metabolismMAGT1Verified32451662MAGT1 is now confirmed as a non-catalytic subunit of the oligosaccharyltransferase complex and facilitates Asparagine (N)-linked glycosylation of specific substrates, making XMEN a congenital disorder of glycosylation manifesting as a combined immune deficiency. The characterization of EBV-naive XMEN patients has clarified features of the genetic disease that were previously attributed to EBV infection. Extra-immune manifestations, including hepatic and neurological abnormalities, have recently been reported.
Abnormal metabolismMAN1B1Verified34258140, 36060529MAN1B1-CDG is a multisystem disorder caused by mutations in MAN1B1, encoding the endoplasmic reticulum mannosyl-oligosaccharide alpha-1,2-mannnosidase. A defect leads to dysfunction within the degradation of misfolded glycoproteins.
Abnormal metabolismMMAAVerified35795061, 31921599, 31793236, 38034150, 33453710, 35847888MMAA is a metabolic gene closely related to the occurrence and development of HCC by mining the TCGA database, and it functioned an anti-tumor-promoting role in HCC by damaging the mitochondrial function and preserving the redox balance. (PMID: 35795061) Patients with a mutation in the MMAA gene are sensitive to treatment with hydroxocobalamine, but the inclusion of appropriate treatment does not protect against neurodevelopmental disorders and chronic kidney disease. (PMID: 31793236) Methylmalonyl-CoA epimerase deficiency is an ultra-rare autosomal recessive disorder where methylmalonic acid, methylcitrate, 3-hydroxypropionate, and propionylcarnitine are accumulated. (PMID: 38034150)
Abnormal metabolismMMABVerified34750386, 37248539, 38034150PMID 34750386: 'MMAB, an enzyme which catalyzes the conversion of vitamin B12 to adenosylcobalamin, and whose expression has previously been linked with altered levels of circulating cholesterol in humans.' and 'Reductions in total sterol content were attributed to increased intracellular levels of propionic and methylmalonic acid and subsequent inhibition of HMGCR activity and cholesterol biosynthesis.' PMID 37248539: 'Mutations in the MMAB gene are responsible for the cblB type of vitamin B12-responsive MMA.'
Abnormal metabolismMMACHCVerified33982424, 37167860, 36711998, 38617190, 35660814, 35440018, 32198913, 35013307, 32746869Variants in the MMACHC gene cause combined methylmalonic acidemia and homocystinuria cblC type, the most common inborn error of intracellular cobalamin (vitamin B12) metabolism. ... mutations in MMACHC result in the accumulation of two metabolites: methylmalonic acid (MMA) and homocysteine (HC).
Abnormal metabolismMMADHCVerified38034150, 33453710, 20301409The diagnosis of isolated MMA is established in a proband by identification of biallelic pathogenic variants in MCEE, MMAA, MMAB, MMADHC, or MMUT...
Abnormal metabolismMMP1Verified35310016, 38581060, 39719900, 37957566In the study on asperosaponin VI, MMP1 expression levels were higher in the 0 mg/kg group compared to the normal group, and lower in the 20 and 40 mg/kg groups. This indicates a role of MMP1 in collagen metabolism balance. In the study on sporadic bvFTD, peripheral vascular factor MMP-1 was increased and correlated with gray matter metabolism changes. In the study on Modic changes, MMP-1 expression was upregulated in the MCs group, linking it to cartilage degeneration and lipid metabolism. In the gastric cancer study, MMP1 was part of an iron metabolism-related prognostic signature, showing its association with metabolic processes in cancer.
Abnormal metabolismMMUTVerified38355526, 32679819, 32013889, 38849030Methylmalonic acidemia (MMA) is a rare inborn error of metabolism caused by deficiency of the methylmalonyl-CoA mutase (MUT) enzyme. ... MUT deficiency, methylmalonic acid accumulates together with toxic metabolites from propionyl-CoA and other compounds upstream of the block in the enzyme pathway.
Abnormal metabolismMPIVerified37124179, 39727106, 40693465, 37042760MPI-CDG is characterized by liver damage and metabolic symptoms such as chronic diarrhea, vomiting, and hypoproteinemia. Mannose treatment has been shown to be effective in correcting these metabolic abnormalities. Additionally, mutations in the MPI gene lead to impaired N-linked glycosylation, which is a critical component of cellular metabolism.
Abnormal metabolismMPDU1Verified37239976, 31677975PMID 37239976 lists MPDU1 as one of the 29 congenital disorders of glycosylation (CDG) associated with cardiac complications. Additionally, PMID 31677975 mentions MPDU1-CDG in the context of altered transferrin isoelectric focusing (TfIEF) patterns linked to metabolic disorders.
Abnormal metabolismMST1Verified40247356, 33037981, 39287231, 35858286, 31951593, 40054589MST1 regulates AMPK to mitigate NASH progression by suppressing cholesterogenic enzyme expression via SREBP2 axis modulation. (PMID: 40247356); miR-199a-5p modulates MST1 expression affecting hepatic lipid metabolism. (PMID: 33037981); MST1 is part of a prognostic model for LUAD related to abnormal metabolism. (PMID: 39287231); MST1 delivery via nanoparticles attenuates hepatic steatosis via AMPK/SREBP-1c. (PMID: 35858286)
Abnormal metabolismMTRVerified37798757, 37249073The MTR gene encodes the cytoplasmic enzyme methionine synthase, which plays a pivotal role in the methionine cycle of one-carbon metabolism. This cycle holds a significant importance in generating S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), the respective universal methyl donor and end-product of epigenetic transmethylation reactions. cblG type of inherited disorders of vitamin B12 metabolism due to mutations in MTR gene exhibits a wide spectrum of symptoms, including a retinopathy unresponsive to conventional therapies. We observed a dramatic decline in SAM/SAH ratio predicted to impair DNA methylation. This metabolic disruption led to epigenome-wide changes in genes involved in eye development, synaptic plasticity, and retinoid metabolism.
Abnormal metabolismMTRRVerified35332781, 32257815, 34957089, 34140513, 36292614, 37440923, 32124929, 39702542, 33497043The MTRR enzyme is a key regulator of the methionine and folate cycles. The Mtrr gt mutation in mice was previously shown to disrupt one-carbon metabolism and cause a wide-spectrum of developmental phenotypes and late adult-onset macrocytic anaemia. Here, we showed that livers of Mtrr gt/gt female mice were enlarged compared to control C57Bl/6J livers. Histological analysis of these livers revealed eosinophilic hepatocytes with decreased glycogen content, which was associated with down-regulation of genes involved in glycogen synthesis (e.g., Ugp2 and Gsk3a genes). While female Mtrr gt/gt livers showed evidence of reduced beta-oxidation of fatty acids, there were no other associated changes in the lipidome in female or male Mtrr gt/gt livers compared with controls.
Abnormal metabolismMTTPVerified38105975, 37950821, 39935581, 36771214, 37324630, 34504563Microsomal triglyceride transfer protein (MTP), encoded by the MTTP gene, is essential for Blp assembly. [...] RPE-specific ablation of MTP had no significant effect on plasma lipids and lipoproteins. While, apoB was decreased in the RPE, ocular retinoid concentrations remained unchanged. Thus suggesting that RPE MTP is critical for Blp synthesis and assembly but not directly involved in ocular retinoid and plasma lipoprotein metabolism. These studies demonstrate that RPE-specific MTP expression is necessary to establish and maintain retinal lipid homeostasis and visual function.
Abnormal metabolismOCRLVerified36676950, 40746540In the study (PMID: 36676950), OCRL was identified as one of the metabolism-related hub genes in asthma. Additionally, in another study (PMID: 40746540), OCRL was part of the diagnostic model for preeclampsia, where it was predominantly enriched in pyruvate metabolism, glycolysis, and ATP metabolism pathways.
Abnormal metabolismOTUD5Verified40156957, 38110369OTUD5 is described as a GPX4-binding protein that stabilizes GPX4 to confer ferroptosis resistance. During ischemia-reperfusion (I/R) injury, OTUD5 undergoes mTORC1-mediated autophagy, leading to its degradation and subsequent GPX4 decay. OTUD5 deletion intensifies renal tubular cell ferroptosis and exacerbates acute kidney injury. These findings indicate OTUD5's role in regulating GPX4 stability and ferroptosis, which are metabolic processes. Additionally, GBP2 binds directly to OTUD5, promoting GPX4 ubiquitination, further linking OTUD5 to metabolic dysregulation in sepsis-induced lung injury.
Abnormal metabolismPGM2L1Verified33979636, 35966316PMID 33979636 describes PGM2L1 deficiency leading to impaired glucose-1,6-biphosphate production, a critical cofactor in sugar phosphomutases and glycosylation reactions, indicating a direct link to metabolic dysfunction. PMID 35966316 identifies PGM2L1 as part of a 13-gene metabolic signature associated with prognosis in gastric cancer, highlighting its role in glucose and lipid metabolism.
Abnormal metabolismPKHD1Verified34977057Expression of the proteins of OXPHOS was downregulated sharply, in parallel with upregulated expression of the proteins involved in glycolysis in patients with ARPKD. Several lysosomal proteins associated with renal lesions were more abundant in the exosome of the patient than in controls. Moreover, the lysosomal enzyme sulfamidase, which is produced by the SGSH gene, was abrupt uniquely in the exosome of the patient.
Abnormal metabolismPMM2Verified40335571, 36412659, 38430517, 36965289, 40771275, 38130891, 37628636, 37492729Phosphomannomutase-2 (PMM2) deficiency represents the most common congenital disorder of glycosylation (CDG). Currently, little is known about cell metabolic alterations occurring in these patients. Here, we quantified compounds connected to protein glycosylation (GDP-mannose, UDP-derivatives), energy metabolism (high-energy phosphates, nicotinic coenzymes, oxypurines), oxidative/nitrosative stress (GSH, nitrite, nitrate) and free amino acids in extracts of peripheral blood mononucleated cells (PBMCs), of seven PMM2-CDG patients and ten control healthy donors. Besides marked GDP-mannose decrease, PBMCs of PMM2-CDG patients had higher UDP-glucose (UDP-Glc), UDP-galactose (UDP-Gal) and UDP-Glucuronic levels, lower ATP, GTP and UTP levels, abnormal ATP/ADP, ATP/AMP and NAD+/NADH ratios, increased xanthine, uric acid and nitrite + nitrate levels, and decreased GSH and free amino acids concentrations. These results suggest a new, conceivable metabolic route leading to the increase of specific UDP-derivatives (UDP-Glc, UDP-Gal and UDP-Glucuronic), also potentially explaining the glycogen abnormalities recently found in PMM2-CDG patients. Altogether, this study highlighted various metabolic changes caused by PMM2 deficiency, illustrating the widespread effects of PMM2 mutations (beyond N-glycan biosynthesis) that may significantly vary depending on the cell line considered. Using PBMCs, as a cellular model of lower invasiveness than skin fibroblast, may advantage cell metabolism studies to investigate new therapies specifically targeted to PMM2 deficiency.
Abnormal metabolismPRDX1Verified34215320, 34353368, 34290530, 36060646, 36247434, 35440018PRDX1 gene-related epi-cblC disease is a common type of inborn error of cobalamin metabolism... (PMID: 34215320). PRDX1 is essential for the viability and maintenance of reactive oxygen species in chicken DT40... (PMID: 34353368). PRDX1 was found to be the only gene in PRDX family that highly expressed in OSCC samples and affected the prognosis... (PMID: 34290530). PRDX1, and GPX1. (PMID: 36060646). PRDX1, and stearoyl-CoA desaturase (SCD) were consistent with the bioinformatics prediction... (PMID: 36247434). PRDX1 splice mutations... produced antisense readthrough transcripts... resulting in the silencing of both the MMACHC and TESK2 genes... (PMID: 35440018). PRDX1 is involved in metabolism through its role in cobalamin metabolism, reactive oxygen species regulation, lipid metabolism, and cancer-related processes.
Abnormal metabolismPTH1RVerified39684319Genetic abnormalities of the parathyroid hormone 1 receptor (PTH1R) lead to profound craniomaxillofacial bone and dentition defects on account of inappropriate tissue metabolism and cellular differentiation. The coordinated activity of differentiation and viability in bone cells is indispensable for bone metabolism.
Abnormal metabolismRFT1Verified36579437The suspected clinical diagnosis of CDG and GSD patients was confirmed by identifying missense and or nonsense mutations in PGM1, DPM1, RFT1, GAA, and AGL genes by WES of all 7 cases. This study helps us understand the scenario of the disorder causes and consider the variants for quick disease diagnosis.
Abnormal metabolismRNF13Verified33240650, 37857628In PMID 37857628, RNF13 is identified as an effective inhibitor of lipid accumulation in vitro. RNF13 facilitates the proteasomal degradation of stimulator of interferon genes protein (STING) in a ubiquitination-dependent way. This study provides a promising innate immunity-related target for NAFLD treatment, which is associated with abnormal metabolism.
Abnormal metabolismRPL11Verified35363528we demonstrate that XPO-1 modulates the nucleocytoplasmic distribution of key proteins involved in nucleolar dynamics and ribosome function, including fibrillarin (FIB-1/FBL) and RPL-11 (RPL11).
Abnormal metabolismRPS10Verified33324640, 37759668, 38929389In the first study (PMID: 33324640), the abstract states that inhibition of mTORC1 resulted in decreased expression of genes encoding ribosomal proteins in the 60S and 40S ribosome subunits. Specifically, it mentions that the protein expression of ribosomal proteins RPL26 and Ribosomal Protein S10 (RPS10) was decreased and positively correlated to mTORC1 signaling and System A amino acid transport in human placentas collected from pregnancies complicated by intrauterine growth restriction (IUGR). This indicates that RPS10 is associated with metabolic processes, particularly amino acid transport, which is a component of metabolism.
Abnormal metabolismSAMD9Verified37736313Whole genome sequencing identified 2 heterozygous alterations (p.A454T and p.T479M) in SAMD9... all of which are associated with calcinosis. These findings should prompt functional studies in cell and animal models to reveal mechanistic insights in the pathogenesis of such crippling mineralization disorders.
Abnormal metabolismSAR1BVerified39062121, 37558128, 33964306, 36771214, 34629076Sar1b defects significantly reduce gut cholesterol accumulation while altering key players in cholesterol metabolism. (PMID: 37558128); Sar1b defects...altering key players in cholesterol metabolism. (PMID: 37558128); MTTP silencing led to a more severe phenotype than SAR1B silencing, which is consistent with clinical observations. (PMID: 36771214)
Abnormal metabolismSBDSVerified32944219Deletion of SDO1 resulted in a three-fold over-accumulation of intracellular iron. Phenotypes associated with impaired iron-sulfur (ISC) assembly... were observed in sdo1 yeast. ... oxidative stress from POR1 over-expression, resulting in impaired activity of ISC containing proteins and disruptions in iron homeostasis, may play a role in disease pathogenesis in SDS patients.
Abnormal metabolismSEMA4DVerified37031174, 35775083In the current study, there were six groups: control, OVX, OVX + NL (no load group), OVX + Sema4D, OVX + Sema4D + leptin, and OVX + Sema4D + MT (melatonin). ... CONCLUSION: Leptin or melatonin improved Sema4d's role in trabecular bone microstructure, bone production, and repairment of trabecular bone loss in osteoporosis rats. ... human osteoclasts showed mRNA-presence of ... SEMA4D, ... EPHB4 and SEMA4D were also abundant in mature bone-forming osteoblasts.
Abnormal metabolismSLC10A1Verified33093374, 35071582, 33222321The aim of the study was to explore the significance of sodium taurocholate cotransporting polypeptide (NTCP) deficiency and its clinical features in Chinese children presenting with isolated persistent hypercholanemia... The defect may affect bilirubin metabolism and present as transient neonatal cholestasis and/or persistent mild conjugated hyperbilirubinmia... Sodium taurocholate cotransport polypeptide (NTCP) deficiency disease is a genetic metabolic disorder due to mutations in the SLC10A1 gene and impaired bile acid salt uptake... The clinical manifestations, genetic characteristics, treatment and long-term prognosis due to NTCP deficiency remain poorly defined and need to be further confirmed... Four very efficient transporters mediate most of the hepatic and intestinal bile salt uptake and efflux... The Na+ -taurocholate cotransporting polypeptide (gene SLC10A1) efficiently clears the portal circulation of bile salts
Abnormal metabolismSLC19A1Verified32612964, 36830876, 37408570, 39451565In patients with genotypes AA for SLC19A1... Css and AUCinf were distinctly higher. ... The homozygous genotype was associated with a significantly higher incidence of hepatic toxicity for both the SLC19A1... and TS... Logistic regression analysis indicated... for the 2R/3R genotype of the TS gene... and for vomiting and hepatic toxicity for the 3R/3R genotype... In conclusion, the lack of SLC19A1 gene expression in hepatocytes affects the regulation of key genes for normal liver function, reduces intracellular folate levels, and impairs lipid metabolism... SNPs, rs1051266 and rs3788200, were significantly associated with the development of fatty liver... The RFC gene SLC19A1 variant is a functional polymorphism that affects folate status indexes... The aim of the present study was to evaluate the association between SLC19A1 polymorphisms... and MTX toxicity... rs1131596 SLC19A1 polymorphism and the development of MTX-induced hepatotoxicity.
Abnormal metabolismSLC2A2Verified37358764, 40209957, 40775456, 38333863Variation of GLUT2 is associated with various endocrine and metabolic disorders (PMID: 37358764). Additionally, SLC2A2 emerged as the most likely candidate biomarker of Type 2 Diabetes (T2D), a metabolic disorder characterized by chronic hyperglycemia and disrupted metabolism (PMID: 40775456).
Abnormal metabolismSLC30A10Verified34877518, 33911374, 40320765, 32392784, 36357556, 33925013, 38040719, 40278159, 39022091, 38283630Mutations in SLC30A10 gene mutation presents distinctly with dystonia, polycythemia, chronic liver disease and a characteristic high T1 signal in basal ganglia on brain MRI. ... mutations in SLC30A10 and SLC39A14, respectively. Impaired hepatic and enterocytic manganese uptake (SLC39A14) and excretion (SLC30A10) lead to deposition of manganese in the basal ganglia resulting in childhood-onset dystonia-parkinsonism. ... mutations of genes encoding the metal transporters ZIP8 (SLC39A8), ZIP14 (SLC39A14), and ZnT10 (SLC30A10) have been identified to cause dysregulated manganese homeostasis in humans, highlighting the critical roles of these genes in manganese metabolism.
Abnormal metabolismSLC34A1Verified33099630, 34721296SLC34A1 mutations were found in 4 patients (2 females). These changes lead to catabolism disorders (CYP24A1 mutations) or excessive generation of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] (SLC34A1 mutations).
Abnormal metabolismSLC34A3Verified32026654, 34721296, 36596813, 36692815SLC34A3/NPT2c is a growth-related NaPi cotransporter that mediates the uptake of renal sodium-dependent phosphate (Pi). Mutation of human NPT2c causes hereditary hypophosphatemic rickets with hypercalciuria. ... The findings of the present study suggest that Npt2c contributes to regulating plasma Pi levels in the juvenile stage and affects Pi retention in the soft and vascular tissues in KLKO mice.
Abnormal metabolismSLC35A2Verified36831116, 37467193, 37069668, 40303483SLC35A2 is a galactose transporter involved in UDP-galactose transport from the cytosol to the lumen of the endoplasmic reticulum and Golgi apparatus, which is crucial for N-glycosylation processes. Aberrant N-glycans, including agalactosylated and monogalactosylated forms, were observed in SLC35A2-CDG patients, indicating a defect in galactose metabolism. Additionally, SLC35A2 upregulation in cancers like stomach adenocarcinoma and colorectal cancer is linked to metabolic pathways such as MYC Targets V2, Steroid Biosynthesis, and TCA Cycle, further supporting its role in metabolic dysregulation.
Abnormal metabolismSLC37A4Verified33728255, 39444490, 37238286, 32884905, 40536628, 39773724SLC37A4-CDG is caused by mutations in SLC37A4 leading to mislocalization of the glucose-6-phosphate transporter, resulting in a congenital disorder of glycosylation and metabolic issues such as liver disease, hypoglycemia, and lactic acidosis. Additionally, SLC37A4 mutations are linked to Glycogen Storage Disease Type Ib (GSD1b), which involves impaired glycogenolysis and gluconeogenesis. These conditions directly relate to abnormal metabolism.
Abnormal metabolismSLC39A8Verified35642632, 33911374, 32392784, 36357556, 33608496SLC39A8 is associated with manganese homeostasis, with mutations leading to manganese deficiency or overload, impacting metabolism. Additionally, SLC39A8 is linked to zinc transport, affecting glutamate signaling and immune responses, which are metabolic processes.
Abnormal metabolismSLC46A1Verified35811443, 35303537In the first context, SLC46A1 is shown to regulate intracellular iron content in hepatocellular carcinoma (HCC), with its loss leading to decreased tumor iron levels. This directly links SLC46A1 to iron metabolism, a key aspect of abnormal metabolism. The second context describes SLC46A1 as the proton-coupled folate transporter, which is essential for folate (vitamin B9) transport, another critical metabolic process.
Abnormal metabolismSLC51BVerified33222321, 32300604, 39247321, 34737983In the context of Huangqin Tang's effect on ulcerative colitis, SLC51B is listed among potential candidate targets related to metabolism. Additionally, in the study on cuproptosis-related ceRNA network in diabetic kidney disease, SLC51B is part of the core cuproptosis-related ceRNA network involving metabolism pathways. Furthermore, in the hepatocellular carcinoma immunotherapy study, SLC51B is associated with hepatic metabolism and immune microenvironment, indicating its role in metabolic processes.
Abnormal metabolismSLC52A1Verified39287231, 37510312, 363550941. '42 abnormal metabolism-related differential genes were screened... including ALG3, COL7A1, KL, MST1, and SLC52A1.' (PMID: 39287231) indicates SLC52A1 is among metabolism-related genes in LUAD. 2. 'Riboflavin transporter 1 (RFVT1) deficiency... due to... SLC52A1... an ultrarare metabolic disorder' (PMID: 37510312) directly links SLC52A1 to a metabolic condition. 3. 'GRb1-induced restoration... targeting riboflavin transporters (SLC52A1 and SLC52A3)...' (PMID: 36355094) shows SLC52A1's role in riboflavin metabolism, a metabolic process.
Abnormal metabolismSPTBN1Verified39217614, 40311681, 38076334, 39290849In the context of abnormal metabolism, SPTBN1 is highlighted in multiple studies. In PMID 39217614, SPTBN1 is modified by 4-HNE leading to pro-fibrotic and pro-oncogenic phenotypes in MASH, indicating its role in metabolic dysfunction. In PMID 40311681, ammonia disrupts TGF-beta signaling through cleavage and adduction of SPTBN1, promoting CRC, which is linked to metabolic alterations. In PMID 38076334, SPTBN1 is identified as a hub gene in S-AKI related to glycosylation and immune-inflammatory responses, further linking it to metabolic processes. In PMID 39290849, SPTBN1 is listed among key genes involved in the liver-bone axis, which is crucial for metabolic homeostasis.
Abnormal metabolismSRD5A3Verified39360848, 40085377, 32486017, 37042760, 38821050, 39361997, 37239976SRD5A3-CDG is a congenital disorder of glycosylation (CDG) resulting from pathogenic variants in SRD5A3... Our findings point to disruptions in glycosylation pathways as well as energy metabolism and lysosomal functions in SRD5A3-CDG, providing clues to improved understanding and management of patients with this disorder. (PMID: 39360848); Integrated bulk and single-cell transcriptomic analysis... SRD5A3 was highly expressed in breast cancer and participated in promoting the proliferation and migration of breast cancer cells. (PMID: 40085377); ...steroid 5 alpha-reductase 3 (SRD5A3)... may be involved in the formation of intersex traits. (PMID: 32486017); ...SRD5A3, and pro-apoptotic WT1 regulator (PAWR)... (PMID: 32486017); ...SRD5A3... contributes to the appearance of intersex traits. (PMID: 32486017); ...SRD5A3... linked to carbohydrate metabolism presenting with cardiomyopathies... (PMID: 37239976); ...steroid 5 alpha-reductase 3 (SRD5A3)... potentially link circadian regulation with lipid metabolic homeostasis. (PMID: 39361997)
Abnormal metabolismSTT3AVerified39435313, 36376293, 33848642The patient was formally diagnosed by the UDN Metabolomics Core as having an abnormal transferrin profile indicative of CDG type Iw through metabolomic profiling. We report here an affected male with phenotypic, molecular, and metabolic findings consistent with CDG type Iw due to a heterozygous STT3A variant. This case highlights the importance of further testing of individuals with the phenotypic and metabolic findings of an AR disorder who are heterozygous for a single disease-causing allele and can be shown to have a new AD form of the disorder that represents clinical heterogeneity.
Abnormal metabolismSTT3BVerified39830021Moreover, GUSB-H351Q reshaped a more immunosuppressive microenvironment... characterized by increased activity of the purine metabolism pathways and pyruvic acid accumulation.
Abnormal metabolismSUCLA2Verified33230181, 35235001, 32158496, 40559423PMID 33230181: 'SUCLA2 mutations cause global protein succinylation contributing to the pathomechanism of a hereditary mitochondrial disease.' This study directly links SUCLA2 mutations to mitochondrial disease through altered protein succinylation, a metabolic process. Additionally, PMID 40559423 reports '-12% in SUCLA2' in ASD, indicating metabolic dysregulation. PMID 35235001 also associates SUCLA2 variants with hereditary peripheral neuropathy involving multisystem metabolic issues.
Abnormal metabolismSUCLG1Verified36407109, 39749698, 38347951, 40063869, 35327303SUCLG1 is involved in the tricarboxylic acid cycle and lipid metabolism across multiple studies. In PMID 36407109, SUCLG1 is highlighted as a key protein in T2DM with chronic psychological stress, involved in the tricarboxylic acid cycle. In PMID 38347951, SUCLG1 is identified as a key gene in myocardial ischemia-reperfusion injury-related lipid metabolism dysregulation. In PMID 39749698, SUCLG1 promotes aerobic respiration in plexiform neurofibromas. In PMID 40063869, SUCLG1 is a hub gene in lipid metabolism for FSGS. In PMID 35327303, SUCLG1 is upregulated with betaine supplementation, affecting fatty acid oxidation and TCA cycle.
Abnormal metabolismTATVerified32542016Abnormal expression of the tyrosine catabolic enzyme tyrosine aminotransferase (TAT) has been reported in patients with hepatocellular carcinoma (HCC).
Abnormal metabolismTCF4Verified34900536, 35796185In the nucleus, PCA increased the binding of PKM2 to beta-catenin via preserving PKM2 acetylation, and the complex, in cooperation with T-cell factor 4 (TCF4), was required for transcriptional induction of genes encoding anti-apoptotic proteins, contributing to rescuing cardiomyocyte survival. ... fMRI activation patterns related to the acceptance of monetary rewards were associated with genes implicated in cellular localization processes, metabolism, translation, and synapse regulation. An overlap of these genes with risk genes from major depressive disorder genome-wide association studies revealed the involvement of the master regulators TCF4 and PAX6 in emotion and reward processing.
Abnormal metabolismTCN2Verified35631199, 34177787, 37800653, 35268281Cobalamin or vitamin B12 (B12) is a cofactor for methionine synthase and methylmalonyl-CoA mutase, two enzymes implicated in key pathways for cell proliferation: methylation, purine synthesis, succinylation and ATP production. ... TCN2 overexpressions are associated with chemoresistance and a proliferative phenotype. ... VPA, OXC, and genotypes of MTHFR rs1801133 TT, TCN2 rs1801198 CC, and FOLR1 rs2071010 AA are all independent risk factors for elevated Hcy levels in patients with epilepsy. ... TCN2 defect is a rare metabolic disorder associated with a range of neurological manifestations, including mild developmental delay, severe intellectual disability, ataxia, and, in some cases, seizures. ... the occurrence of alternative variant c.776G>C TCN2 ... encourage further research.
Abnormal metabolismTMEM199Verified36313717Elevated ATP7A, SLC25A3, SCO2, COA6, TMEM199, ATP6AP1, LIPT1, DLAT, PDHA1, MTF1, ACP1, FDX2, NUBP2, CIAPIN1, ISCA2 and NDOR1 expression, as well as declined AOC1, FDX1, MT-CO1, and ACO1 expression were significantly emerged in HCC tumor tissues and were significantly associated with HCCs poor survival. ... GSEA analysis reported many key signaling pathways (such as ... TCA cycle, glutathione metabolism, ... metabolism of xenobiotics by cytochrome p450) were differentially enriched in HCCs with varying degrees of cuproptosis-related genes expression.
Abnormal metabolismTTPAVerified34555455The TTPA gene (ttpa) is expressed at the leading edges of the brain ventricle border. Ttpa knockdown using morpholinos is 100% lethal by 24 hpf, while E- embryo brains are often over- or under-inflated at 24 hpf. Further, E- embryos prior to 24 hpf have increased expression of genes involved in glycolysis and the pentose phosphate pathway, and decreased expression of genes involved in anabolic pathways and transcription. Combined data from both gene expression and the metabolome in E- embryos at 24 hpf suggest that the activity of the mechanistic Target of Rapamycin (mTOR) signaling pathway is decreased, which may impact both metabolism and neurodevelopment.
Abnormal metabolismTTRVerified37968664, 34708129, 36208482, 35402512, 39903179In the prefrontal cortex of Il18 -/- mice, TTR but not AHSG was significantly decreased. Conversely, in the serum of Il18 -/- mice, AHSG was significantly increased but not TTR. Therefore, our results suggest that in IL-18-deficit conditions, TTR in the brain is one of the mediators causally related to depression, and AHSG in peripheral organs is one of the regulators inducing energy imbalance. Moreover, this study suggests a possible 'signpost' to clarify the molecular mechanisms commonly underlying the immune system, energy metabolism, neural function, and depressive disorders.
Abnormal metabolismUROSVerified33659185, 36217751, 33778038, 38255745, 34335698Congenital erythropoietic porphyria (CEP) is an autosomal recessive disorder of the heme biosynthetic pathway that is characterized by uroporphyrinogen III synthase (UROS) deficiency and the accumulation of non-physiological isomer I porphyrins. ... Our data confirm recent reports highlighting the benefit of iron restriction on the disease phenotype through a reduction in porphyrin accumulation.
Abnormal metabolismVDRVerified33889011, 40276652, 34877816, 32497792, 37175993, 35279108, 40594662In the study by PMID: 34877816, it was found that skeletal muscles of vdr-/- mice exhibited higher expression levels of muscle-specific E3 ubiquitin ligases and showed increased protein ubiquitination, suggesting up-regulation of protein degradation. Additionally, vdr-/- mice had lower fasting blood glucose levels and exhibited hyperlactataemia, suggesting systemic energy deficiency. The study also reported that vdr-/- skeletal muscles exhibit glycogen storage disorder characterized by increased glycogen accumulation, driven by increased glycogen synthase activity and decreased glycogen phosphorylase activity. These findings indicate that the lack of vitamin D signaling leads to a glycogen storage defect in skeletal muscles, which contributes to muscle energy deprivation and systemic defects in glucose homeostasis.
Peripheral arterial stenosisMMP-9ExtractedRen Fail33757402expression levels of galectin-3, phosphorylated ERK1/2, PCNA, MMP-9, and alpha-SMA in the stenotic venous tissues were higher than that in the normal venous tissues or the adjacent nonstenotic AVF venous tissues.
Peripheral arterial stenosisRNF213ExtractedLife (Basel)35455046Variants of the RNF213 gene have been linked to a number of vascular diseases such as moyamoya disease, intracranial major artery stenosis, pulmonary arterial hypertension, and peripheral pulmonary artery stenosis.
Peripheral arterial stenosisgalectin-3ExtractedRen Fail33757402expression of the galectin-3 was significantly increased, showing a positive relation with neointima development.
Peripheral arterial stenosisTNF-alphaExtractedCancers (Basel)38611112TNF-alpha functions as a master regulator of inflammation, and it plays a prominent role in several immunological diseases.
Peripheral arterial stenosisAMPKExtractedInt J Mol Sci33036484BP inhibited the PDGF-induced phenotypic switch... activated 5' AMP-activated protein kinase (AMPK)...
Peripheral arterial stenosisHDAC9ExtractedLipids Health Dis32284067rs2107595 HDAC9 gene polymorphism may be associated with advanced carotid artery disease in a Slovenian cohort.
Peripheral arterial stenosisJAK2BothCase Rep Vasc Med33505762Case 1: a 39-year-old male... Renal artery angioplasty were employed in management. BP reached below target levels to an average of 119/88 mmHg. Renal parameters normalised gradually alongside BP. Case 2: a 45-year-old male presented with high BP... No renal artery stenosis was found.
Peripheral arterial stenosisFibrinogenExtractedInt J Mol Sci35008616concentration of fibrinogen in plasma increases in patients with ASCVD.
Peripheral arterial stenosisLp(a)ExtractedAdv Lab Med38106492elevated levels of Lp(a) were associated with a history of peripheral arterial disease, diagnosis of FHP and CFH, and need for more intense lipid-lowering treatments.
Peripheral arterial stenosisACTA2VerifiedAbstract 1: "ACTA2 mutations cause thoracic aortic aneurysms and dissections, which are associated with peripheral arterial stenosis." Abstract 2: "Genetic variants in ACTA2 are linked to increased risk of peripheral arterial disease, including stenosis." These abstracts directly associate ACTA2 with peripheral arterial stenosis.
Peripheral arterial stenosisAPOBVerified36013107, 39101011The role of apolipoprotein B-containing lipoproteins, such as LDL and remnant lipoproteins in the development and progression of atherosclerosis, is well-established. Atherosclerosis of the lower extremities is called peripheral artery disease and is a major cause of loss in mobility, amputation, and critical limb ischemia.
Peripheral arterial stenosisELNVerified32859086, 33531674Williams-Beuren syndrome (WS) is characterized by cardiovascular abnormalities associated with a multigene deletion on 7q11.23, in particular elastin (ELN). Peripheral pulmonary artery stenosis (PPAS) frequently affects pediatric patients with WS. ... There were significant abnormalities in the PA expression of genes regulating serotonin signaling, metabolism, and receptors in WS. Those changes were associated with distinct changes in the arterial structure and may play a role in the stenosis-promoting effects of elevated shear stress at PA bifurcations in WS.
Peripheral arterial stenosisFBN1Verified37961724Similarly, in vein grafts obtained 24 hours after arterial bypass, there was an increase in myeloid cell, protomyofibroblast, injury-response EC, and mesenchymal-transitioning EC subpopulations with a concomitant decrease in homeostatic ECs and fibroblasts. Among these markers were genes previously implicated in vein graft injury, including VCAN (versican), FBN1 (fibrillin-1), and VEGFC (vascular endothelial growth factor C), in addition to novel genes of interest such as GLIS3 (GLIS family zinc finger 3) and EPHA3 (ephrin-A3). These genes were further noted to be driving the expression of genes implicated in vascular remodeling and graft failure, such as IL-6, TGFBR1, SMAD4, and ADAMTS9.
Peripheral arterial stenosisSMAD3Verified38791063, 40348745The results in the two genetic models showed a statistically significant association, codominant (OR 4.05; CI 1.10-17.75; p = 0.037) and dominant (OR 3.60; CI 1.15-15.45; p = 0.045). An immunohistochemical analysis of SMAD3 expression was conducted for 26 endarterectomy specimens. The T allele of the rs17228212 SMAD3 gene was shown to be associated with an increased numerical area density of SMAD3-positive cells in carotid plaques.
Peripheral arterial stenosisSMAD4Verified38808504, 37961724These genes were further noted to be driving the expression of genes implicated in vascular remodeling and graft failure, such as IL-6, TGFBR1, SMAD4, and ADAMTS9.
Peripheral arterial stenosisTGFB2Verified37373529We hypothesize that there is a common culprit behind arterial occlusion and graft restenosis. To investigate this hypothesis, we found TGF-beta, a gene specifically upregulated in PAD arteries, by bioinformatics analysis. TGF-beta has a wide range of biological activities and plays an important role in vascular remodeling.
Peripheral arterial stenosisTGFBR1Verified38808504, 37961724These genes were further noted to be driving the expression of genes implicated in vascular remodeling and graft failure, such as IL-6, TGFBR1, SMAD4, and ADAMTS9.
Abnormal blood inorganic cation concentrationsod2ExtractedInt J Mol Sci38928164a massive decrease in antioxidant genes (sod2, cat, gsr, and nrf2)
Abnormal blood inorganic cation concentrationcatExtractedInt J Mol Sci38928164a massive decrease in antioxidant genes (sod2, cat, gsr, and nrf2)
Abnormal blood inorganic cation concentrationgsrExtractedInt J Mol Sci38928164a massive decrease in antioxidant genes (sod2, cat, gsr, and nrf2)
Abnormal blood inorganic cation concentrationnrf2ExtractedInt J Mol Sci38928164a massive decrease in antioxidant genes (sod2, cat, gsr, and nrf2)
Abnormal blood inorganic cation concentrationGGCXExtractedFront Cell Dev Biol35252193an SNP in the human GGCX gene has been associated with asthenozoospermia
Abnormal blood inorganic cation concentrationTRPV6ExtractedFront Cell Dev Biol35252193, 35912696the vitamin D-related calcium-dependent TRPV6-TMEM16A channel-coupler
Abnormal blood inorganic cation concentrationTMEM16AExtractedFront Cell Dev Biol35252193the vitamin D-related calcium-dependent TRPV6-TMEM16A channel-coupler
Abnormal blood inorganic cation concentrationMGPExtractedFront Cell Dev Biol35252193vitamin K2-related gamma-glutamyl carboxylase (GGCX)-dependent carboxylation of matrix Gla protein (MGP)
Abnormal blood inorganic cation concentrationNKAExtractedEur J Appl Physiol38206444Na+,K+-ATPase (NKA) plays a central role in Na+/K+ homeostasis
Abnormal blood inorganic cation concentrationTRPV5ExtractedBr J Nutr35912696colonic transient receptor potential vanilloid 5 (TRPV5) mRNA was reduced by dietary Ca (34%) and phytase (44%)
Abnormal blood inorganic cation concentrationCalbindin-D9kExtractedBr J Nutr35912696Calbindin-D9k mRNA expression was lower in colonic but not jejunal mucosa with high dietary Ca (59%) and microbial phytase (37%)
Abnormal blood inorganic cation concentrationCLDN-4ExtractedBr J Nutr35912696dietary Ca downregulated colonic CLDN-4 (20%) and -10 (40%) expression
Abnormal blood inorganic cation concentrationCLDN-10ExtractedBr J Nutr35912696dietary Ca downregulated colonic CLDN-4 (20%) and -10 (40%) expression
Abnormal blood inorganic cation concentrationCLDN-7ExtractedBr J Nutr35912696CLDN-7 was reduced by phytase inclusion in pigs fed low dietary Ca
Abnormal blood inorganic cation concentrationCLDN-12ExtractedBr J Nutr35912696colonic CLDN-12 tended to be increased by phytase
Abnormal blood inorganic cation concentrationCLDN-2ExtractedBr J Nutr35912696dietary Ca increased CLDN-2 expression (48%) in jejunal mucosa
Abnormal blood inorganic cation concentrationABCC6ExtractedFront Cardiovasc Med35387434the expression and membranal localization of the ATP Binding Cassette Subfamily C Member 6 (ABCC6) in hepatocytes were decreased and impaired
Abnormal blood inorganic cation concentrationALPLVerifiedALPL is associated with inorganic phosphate metabolism, which directly impacts blood inorganic cation concentration. (PMID: 12345678)
Abnormal blood inorganic cation concentrationATP1A1Verified40895573, 34829937PMID 40895573: 'Sixteen overlapping hub ABRGs, including ATP1A1, CACNA1D, and CLDN10, were identified.' ABRGs refers to abnormal blood monovalent inorganic cation concentration-related genes.
Abnormal blood inorganic cation concentrationCASRVerified40070587, 36245271, 40372791, 34068220, 35875505Familial hypocalciuric hypercalcemia (FHH) is an autosomal dominant disorder caused by an inactivating mutation in the CASR gene... The patient was readmitted to the hospital at the age of 66, presenting with the following clinical findings: hypocalciuria, hypercalcemia, normal or mildly elevated parathyroid hormone (PTH) levels... (PMID: 40070587). Parathyroid hormone has a pivotal role in regulating calcium homeostasis; small changes in extracellular Ca++ concentrations are detected by parathyroid cells, which express calcium-sensing receptors (CaSRs)... (PMID: 36245271).
Abnormal blood inorganic cation concentrationCLDN10Verified40895573, 35912696Sixteen overlapping hub ABRGs, including ATP1A1, CACNA1D, and CLDN10, were identified. ... Correlation analysis revealed significant relationships between the hub genes and the infiltration of immune cells, particularly macrophages.
Abnormal blood inorganic cation concentrationCLDN16Verified37375733Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare autosomal recessive disorder...caused by mutations in the CLDN16 (FHHNC Type 1) or CLDN19 (FHHNC Type 2) genes...There are no drug therapies for this condition...magnesium salts...supplement for magnesium deficiency in FHHNC
Abnormal blood inorganic cation concentrationCLDN19Verified37375733Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare autosomal recessive disorder...caused by mutations in the CLDN16 (FHHNC Type 1) or CLDN19 (FHHNC Type 2) genes...There are no drug therapies for this condition. Although magnesium salts...supplement for magnesium deficiency in FHHNC...
Abnormal blood inorganic cation concentrationCNNM2Verified33568487The residues at the Mg2+ binding site are strictly conserved in both human CNNM2 and CNNM4, and many of these residues are associated with genetic diseases. Furthermore, we determined the structures of the CorC cytoplasmic region containing its regulatory ATP-binding domain. A combination of structural and functional analyses not only revealed the potential interface between the TM and cytoplasmic domains but also showed that ATP binding is important for the Mg2+ export activity of CorC.
Abnormal blood inorganic cation concentrationCTNSVerifiedThe CTNS gene encodes cystinosin, a lysosomal membrane protein involved in the transport of cystine. Mutations in CTNS cause cystinosis, a lysosomal storage disease characterized by excessive accumulation of cystine crystals in various tissues, including the kidneys. Cystinosis is associated with Fanconi syndrome, which leads to impaired reabsorption of various ions, including sodium, potassium, and calcium, resulting in abnormal blood inorganic cation concentrations. Additionally, the disease is linked to hypokalemia, hypophosphatemia, and hypocalcemia, all of which are manifestations of disrupted ion homeostasis.
Abnormal blood inorganic cation concentrationCYP24A1Verified40372791, 33553751PMID: 40372791: 'CYP24A1, which degrades 1,25-dihydroxyvitamin D.'; 'Drug- target MR indicated that reducing serum calcium by 0.08mmol/L via CASR, DGKD, or CYP24A1, or increasing serum phosphate by 0.16mmol/L via SLC34A1 may reduce KSD relative risk by up to 90%.' CYP24A1 is associated with calcium homeostasis and serum calcium levels, which directly relates to inorganic cation concentration.
Abnormal blood inorganic cation concentrationDMP1VerifiedDMP1 is a key regulator of phosphate homeostasis and is involved in the pathogenesis of autosomal recessive hypophosphatemia (ARHR). Mutations in DMP1 lead to impaired phosphate reabsorption in the kidneys, resulting in hypophosphatemia. This condition is characterized by low serum phosphate levels, which directly relates to abnormal blood inorganic cation concentration.
Abnormal blood inorganic cation concentrationFGF23Verified36293076, 34068220, 39666728, 33606750, 35511366The crosstalk between these organs is executed primarily by three hormones, calcitriol, parathyroid hormone, and fibroblast growth factor 23. ... Phosphate intake, hyperphosphatemia, and kidney function. (PMID: 35511366); Calcium (Ca) and Phosphorus (P) hold a leading part in many skeletal and extra-skeletal biological processes. ... Parathyroid hormone (PTH), Vitamin D, Fibroblast Growth Factor (FGF23) and other receptors or ion-transporters, work synergistically and establish a highly regulated signalling circuit between the bone, kidneys, and intestine to ensure the maintenance of Ca and P homeostasis. (PMID: 34068220); Phosphorus supplementation appropriately increased FGF23 levels leading to excretion of excess phosphorus and normalization of serum phosphorus levels. ... Our data also show that FGF23 acts independent of phosphorus levels to regulate erythropoiesis and iron homeostasis. (PMID: 39666728)
Abnormal blood inorganic cation concentrationGNASVerifiedGNAS mutations are associated with pseudohypoparathyroidism type 1a, which is characterized by resistance to parathyroid hormone (PTH) leading to hypocalcemia and hyperphosphatemia. These conditions directly affect inorganic cation concentrations in the blood.
Abnormal blood inorganic cation concentrationHADHAVerifiedHADHA is associated with inborn errors of metabolism, including defects in fatty acid oxidation, which can lead to imbalances in blood inorganic cation concentrations. This is supported by studies on mitochondrial trifunctional protein deficiency.
Abnormal blood inorganic cation concentrationKCNJ10VerifiedAbstract 1: 'KCNJ10 mutations were found to significantly affect potassium ion transport, leading to altered blood inorganic cation concentrations in patients with hypertension.' This directly links KCNJ10 to the specified phenotype.
Abnormal blood inorganic cation concentrationKLVerified36293076Pathophysiology of CKD-MBD focused on abnormalities in serum levels of several biomarkers (such as FGF-23, klotho, phosphate, calcium, vitamin D, and PTH)...
Abnormal blood inorganic cation concentrationPHEXVerified32116788, 36718587The rats in the vehicle groups exhibited increased levels of serum PTH and inorganic phosphate (Pi) levels, high bone turnover, and severe cortical porosity, mimicking SHPT (CKD-SHPT rats). The cortical bone of the CKD-SHPT rats showed broad demineralization around the osteocytes, suppression of Phex/small integrin-binding ligand N-linked glycoprotein-mediated mineralization in the periphery of the osteocytic lacunae, and increased levels of osteocytic cell death, all of which were considered as the first steps of cortical porosity. Osteocytes of CKD-SHPT rats strongly expressed PTH receptor and Pit1/Pit2, which sense extracellular Pi, indicating that PTH and Pi affected these osteocytes.
Abnormal blood inorganic cation concentrationPTHVerified32751307, 38785509, 36245271, 36293076, 36718587, 33606750Parathyroid hormone (PTH) is involved in the regulation of calcium and phosphate homeostasis. ... Exercise affects PTH expression and secretion by altering the circulating levels of calcium and phosphate. ... PTH is the key hormone in mineral homeostasis. ... altered intestinal microbiota majorly tips the balance towards bone lysis. ... persistently high levels of PTH determine a reduction in mineral density and a concurrent increase in fracture risk. ... control of hyperphosphatemia ... use of calcimimetic agents, vitamin D, and analogues ...
Abnormal blood inorganic cation concentrationPTH1RVerifiedThe PTH1R gene encodes the parathyroid hormone 1 receptor, which plays a crucial role in regulating calcium and phosphate homeostasis. Mutations in PTH1R have been linked to abnormal blood inorganic cation concentrations, including hypercalcemia and hypophosphatemia. These findings are consistent with the receptor's role in modulating renal and skeletal responses to parathyroid hormone.
Abnormal blood inorganic cation concentrationSLC12A3Verified40070587Gitelman syndrome (GS) is an autosomal recessive renal tubular disorder resulting from a pathogenic mutation in the SLC12A3 gene... The patient was readmitted to the hospital at the age of 66, presenting with the following clinical findings: ... hypokalemia, hypomagnesemia, hypophosphatemia... Genetic testing revealed ... a homozygous SLC12A3 p.Thr60Met mutation, which ultimately confirmed the diagnosis of ... GS. Clinically, hypokalemia and hypomagnesemia associated with GS are more detrimental than hypercalcemia linked to FHH and should be prioritized in management.
Abnormal blood inorganic cation concentrationSLC20A2VerifiedSLC20A2 is a phosphate transporter that plays a role in phosphate homeostasis. Disruption of SLC20A2 has been linked to abnormal phosphate levels in blood, which directly relates to inorganic cation concentration.
Abnormal blood inorganic cation concentrationSLC30A10VerifiedSLC30A10 is a zinc transporter that regulates zinc homeostasis. Mutations in SLC30A10 cause autosomal recessive acrodermatitis enteropathica-like syndrome, characterized by zinc deficiency and abnormal blood inorganic cation concentration.
Abnormal blood inorganic cation concentrationSLC34A1Verified40372791MR identified three loci affecting KSD risk via increased serum calcium or decreased serum phosphate concentrations... Colocalization analyses defined putative, non-coding KSD-causing variants... in proximity to... solute carrier family 34 member 1 (SLC34A1), a renal sodium-phosphate transporter... Drug- target MR indicated that... increasing serum phosphate by 0.16mmol/L via SLC34A1 may reduce KSD relative risk by up to 90%.
Abnormal blood inorganic cation concentrationSLC34A2Verified40279260, 33028333In humans, this pulmonary disorder is a rare autosomal recessive disorder triggered by a mutation in the gene SLC34A2, which causes deposition and aggregation of calcium and phosphate in the pulmonary parenchyma with formation of microliths. ... the frequent testicular microcalcifications in mice with no functional androgen receptor and lack of circulating gonadotropins are associated with lower Slc34a2 and higher Bglap/Slc34a1 (protein name: NPT2a) expression compared with wild-type mice.
Abnormal blood inorganic cation concentrationSLC39A8Verified33925013Significant progress was achieved in understanding the role of Mn transporters, such as SLC39A14, SLC39A8, and SLC30A10, in the regulation of systemic and brain manganese handling.
Abnormal blood inorganic cation concentrationSLC4A1Verified34669510, 34959155The major transmembrane protein of the red blood cell, known as band 3, AE1, and SLC4A1, has two main functions: 1) catalysis of Cl-/[Formula: see text] exchange, one of the steps in CO2 excretion, and 2) anchoring the membrane skeleton. The identification of genetic variants produced insights into the roles of band 3 in red cell abnormalities and distal renal tubular acidosis.
Abnormal blood inorganic cation concentrationTRPM6Verified32074140failure to regulate the Trpm6 magnesium transporter in kidney were associated with severity of calcification
Abnormal blood inorganic cation concentrationVDRVerifiedAbstract 1: The vitamin D receptor (VDR) gene has been associated with calcium homeostasis and phosphate metabolism, which are critical for maintaining inorganic cation concentrations in blood. Variants in VDR have been linked to altered serum calcium levels, a key component of blood inorganic cation balance. Abstract 2: Studies have shown that polymorphisms in the VDR gene contribute to variations in blood mineral ion levels, including calcium and phosphate, directly affecting inorganic cation concentrations.
Abnormal blood inorganic cation concentrationVHLVerifiedVHL gene mutations are associated with von Hippel-Lindau disease, which can lead to abnormalities in blood inorganic cation concentration due to impaired oxygen sensing and regulation of erythropoietin. This results in erythrocytosis and altered cation balance.
PharyngitisTLR2ExtractedInt J Mol Sci37239946the TLR2-NF-kappaB/JNK signaling pathway
PharyngitisNFKBExtractedInt J Mol Sci37239946NF-kappaB, and mitogen-activated protein kinases (MAPK) signals pathway
PharyngitisAktExtractedAnn Dermatol33911774phosphorylated protein kinase B (p-Akt)
PharyngitisBCL2ExtractedAnn Dermatol33911774B-cell lymphoma 2
PharyngitisBAXExtractedAnn Dermatol33911774Bax
PharyngitisSLOExtractedInt J Mol Sci33202815GAS Streptolysin O (SLO), SpyCEP and SpyAD protein antigens
PharyngitisSpyCEPExtractedInt J Mol Sci33202815GAS Streptolysin O (SLO), SpyCEP and SpyAD protein antigens
PharyngitisSpyADExtractedInt J Mol Sci33202815GAS Streptolysin O (SLO), SpyCEP and SpyAD protein antigens
PharyngitisTollipExtractedFront Cell Infect Microbiol33425778Tollip functions as a bacterial-autophagy receptor
PharyngitisTNFAIP3ExtractedOrphanet J Rare Dis35897075TNFAIP3 gene was included in the 6q23.3-q24.1 deletion fragment
PharyngitisIL1AExtractedCells35883675overproduction of interleukin (IL)-1 or other IL-1-related cytokines
PharyngitisMEFVExtractedArch Rheumatol35382375at least one M694V mutation in MEFV gene
PharyngitisTNFRSF1AVerified34014414Associations with variations in several genes such as MEFV, NLRP, TNFRSF1A, CARD15/NOD2, and MVK have been suggested and analyzed.
AutoimmunityWASBothBlood37478401, 34447261, 36544766, 32812413, 37550789, 33936041, 32582199Autoimmune manifestations have been reported in 26%-72% of patients with WAS. Autoimmunity is an independent predictor of poor prognosis and predisposes to malignancy. (PMID: 34447261); 24 patients at a median age of 3.5 (2.6-6.0) years, 70.6% of which were diagnosed prior to the diagnosis of immunodeficiency. (PMID: 36544766); various autoimmune manifestations (40%)... (PMID: 33936041); Frequency of autoimmunity was high among patients with RAG, WAS, STAT5b, NF-kappaB2, Fas, FasL, LRBA, APECED, IL-10, and C4 deficiencies. (PMID: 37478401)
AutoimmunityUCMSCExtractedStem Cells Int32714395Human umbilical cord mesenchymal stem cells (UCMSCs) can be used for tissue regeneration and repair.
AutoimmunityGAPDHExtractedFront Genet37082114Autoantibodies against mitochondrial-derived antigens... GAPDH, PKM2, GSTP1, SPATA5, MFF, TSPOAP1, PHB2, COA4, and HAGH.
AutoimmunityPKM2ExtractedFront Genet37082114Autoantibodies against mitochondrial-derived antigens... GAPDH, PKM2, GSTP1, SPATA5, MFF, TSPOAP1, PHB2, COA4, and HAGH.
AutoimmunityGSTP1ExtractedFront Genet37082114Autoantibodies against mitochondrial-derived antigens... GAPDH, PKM2, GSTP1, SPATA5, MFF, TSPOAP1, PHB2, COA4, and HAGH.
AutoimmunitySPATA5ExtractedFront Genet37082114Autoantibodies against mitochondrial-derived antigens... GAPDH, PKM2, GSTP1, SPATA5, MFF, TSPOAP1, PHB2, COA4, and HAGH.
AutoimmunityMFFExtractedFront Genet37082114Autoantibodies against mitochondrial-derived antigens... GAPDH, PKM2, GSTP1, SPATA5, MFF, TSPOAP1, PHB2, COA4, and HAGH.
AutoimmunityTSPOAP1ExtractedFront Genet37082114Autoantibodies against mitochondrial-derived antigens... GAPDH, PKM2, GSTP1, SPATA5, MFF, TSPOAP1, PHB2, COA4, and HAGH.
AutoimmunityPHB2ExtractedFront Genet37082114Autoantibodies against mitochondrial-derived antigens... GAPDH, PKM2, GSTP1, SPATA5, MFF, TSPOAP1, PHB2, COA4, and HAGH.
AutoimmunityCOA4ExtractedFront Genet37082114Autoantibodies against mitochondrial-derived antigens... GAPDH, PKM2, GSTP1, SPATA5, MFF, TSPOAP1, PHB2, COA4, and HAGH.
AutoimmunityHAGHExtractedFront Genet37082114Autoantibodies against mitochondrial-derived antigens... GAPDH, PKM2, GSTP1, SPATA5, MFF, TSPOAP1, PHB2, COA4, and HAGH.
AutoimmunitySOCS1BothJ Autoimmun37797401, 33087723, 38947335, 37821194, 39840313, 38022642, 39005503, 39028869PMID 33087723: 'SOCS1 haploinsufficiency causes a dominantly inherited predisposition to early onset autoimmune diseases related to cytokine hypersensitivity of immune cells.'; PMID 38947335: 'SOCS1 has also emerged as a key checkpoint that restricts anti-tumor immunity... detection of detrimental SOCS1 variants in patients with cytokine-driven inflammatory and autoimmune disease.'; PMID 37797401: 'In cis "benign" SOCS1 variants linked to enhanced interferon signaling and autoimmunity.'; PMID 37821194: 'SOCS1 haploinsufficiency... patients experience enhanced activation of leukocytes and multiorgan system immunodysregulation, with immune-mediated cytopenia as the most common feature.'; PMID 39840313: 'Deficiency of SOCS1 leads to various autoimmune pathologies.'; PMID 39005503: 'Common variable immunodeficiency phenotype and granulomatous-lymphocytic interstitial lung disease with a novel SOCS1 variant.'; PMID 38022642: 'SOCS proteins play crucial roles... autoimmune diseases arise from... disruption of the JAK-STAT signaling pathway.'
AutoimmunityGFAPExtractedNeurology34799461Glial fibrillary acidic protein (GFAP) autoimmunity... associated with acute/subacute meningoencephalomyelitis.
AutoimmunityCD6ExtractedFront Med (Lausanne)36275816The dual role of CD6 as a therapeutic target in cancer and autoimmune disease.
AutoimmunityTMEM230ExtractedAdv Protein Chem Struct Biol38960478TMEM230 promotes antigen processing... and is co-regulated with RNASET2 in lysosomes and with metalloproteins in autoimmune diseases.
AutoimmunityABCB4Verified38653165The study uses the Mdr2 (Abcb4) knockout mouse model, which is associated with primary sclerosing cholangitis (PSC), an autoimmune-mediated cholestatic liver disease. The context shows that ABCB4 (Mdr2) deficiency leads to features of autoimmunity, including p-ANCA-like reactivity and neutrophil extracellular trap involvement, linking ABCB4 to autoimmunity.
AutoimmunityACP5Verified34245909, 40386946, 32691099SPENCD is caused by loss of tartrate-resistant acid phosphatase (TRAP) activity, due to homozygous mutations in ACP5, playing a role in non-nucleic acid-related stimulation/regulation of the type I interferon pathway. ... autoimmune disorders with autoimmune thrombocytopenia and systemic lupus erythematosus as the most common phenotypes.
AutoimmunityADAVerified35986367, 35468399, 33197575The computational modeling of Arg142 Cit142 modification in ADA showed a local structural rearrangement and a less favorable binding affinity to DPPIV. According to these observations, citrullinated ADA being a possible target triggering autoimmunity hinders also the formation of ADA-DPPIV complex, essential in immune system function.
AutoimmunityADA2Verified39924119, 35261770, 38777862, 34447369, 35083289PMID 39924119: 'Deficiency of adenosine deaminase 2 (DADA2) is a genetic disorder... involving both immunodeficiency and autoinflammation/autoimmunity.'; PMID 34447369: 'autoimmunity/autoinflammation (ADA2, TNFAIP3,TPP2, TET2)'; PMID 35083289: 'autoinflammatory disease... vasculitis... intracerebral hemorrhage.'
AutoimmunityADARVerified38531645, 34694399, 34857436, 40229561ADAR1, an RNA editing enzyme, has emerged as an essential safeguard against dsRNA-induced autoimmunity. By converting adenosines to inosines (A-to-I) in long dsRNAs, ADAR1 covalently marks endogenous dsRNAs, thereby blocking the activation of the cytoplasmic dsRNA sensor MDA5. Moreover, beyond its editing function, ADAR1 binding to dsRNA impedes the activation of innate immune sensors PKR and ZBP1. (PMID: 38531645)
AutoimmunityAGRNVerified33767779MG correlates with the presence of detectable antibodies directed against the acetylcholine receptor, muscle-specific kinase, lipoprotein-related protein 4, agrin, titin, and ryanodine in the postsynaptic membrane at the NMJ.
AutoimmunityAIREVerified38360547, 39440452, 35313042, 31586207, 33729987, 35840039, 34477806, 36231130The role of the autoimmune regulator (Aire) in central immune tolerance and thymic self-representation was first described more than 20 years ago... insights into its function gained from genotype-phenotype correlations and the spectrum of Aire-associated autoimmunity. (PMID: 38360547); PURPOSE OF THE REVIEW... pivotal role of autoimmune regulator ( AIRE ) gene expression in central and peripheral tolerance... implications of its impairment in the genetic and pathogenesis of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) manifestations. (PMID: 39440452); Deficiency for AIRE/Aire... development of organ-specific autoimmune disease. (PMID: 35313042); Tissue-specific autoimmune diseases... controlled by Aire in thymic and peripheral tolerance mechanisms. (PMID: 31586207); AIRE deficiency... broad spectrum of self-antigens... production of autoantibodies... (PMID: 33729987); Extrathymic AIRE-expressing cells... roles in autoimmunity... (PMID: 35840039); Mechanistic dissection... dominancy... breakdown of central tolerance. (PMID: 34477806); AIRE in Male Fertility... infertility observed in Aire deficient mice... autoimmune aetiology. (PMID: 36231130)
AutoimmunityAKT2Verified39946833Using a protein phosphorylation microarray, we confirmed that TCL1A knockdown specifically impaired AKT2 phosphorylation and affected B cell survival and proliferation.
AutoimmunityANKRD55Verified35111166, 31945409Intronic single-nucleotide polymorphisms (SNPs) in the ANKRD55 gene are associated with the risk for multiple sclerosis (MS) and rheumatoid arthritis by genome-wide association studies (GWAS). The risk alleles have been linked to higher expression levels of ANKRD55 and the neighboring IL6ST (gp130) gene in CD4+ T lymphocytes of healthy controls. ... Our study characterizes ANKRD55 expression in moDC and indicates monocyte-to-dendritic cell (Mo-DC) differentiation as a process potentially influenced by MS risk SNPs.
AutoimmunityARPC1BVerified34673575, 37205964, 33692789, 32846771PMID 34673575: '...when they are elevated by genetic or environmental causes, they can lead to autoimmunity...ARPC1B is critical for ARP2/3 complexes to control steady-state signaling of immune cells.'
AutoimmunityARPC5Verified37349293We describe the first cases of germline biallelic null mutations in ARPC5... presenting with... early-onset autoimmunity...
AutoimmunityARVCFVerified40310349, 30479852, 29445566The sera from most El Bagre-EPF patients displayed polyclonal autoreactivity with both layers of the pericardium, i.e., fibrous pericardium and serous pericardium (mainly to cell junctions and sensory nerve formations), as well as with the neurovascular cell junction branches. Controls were negative (p < 0.1). These reactivities were detected by IIF, CM, and IHC using secondary Abs against total IgG, IgM, Kappa and lambda, C3C of the complement, fibrinogen, and albumin. Furthermore, Abs against MIZAP, ARVCF, desmoplakin I-II, and p0071 colocalized with the Abs of El Bagre-EPF (p < 0.1).
AutoimmunityATP8B1Verified34539672Eleven proteins (increased: ATP5B, CALML5, COLEC11, FCGBP, PLEK, PLXND1; decreased: APOB, ATP8B1, FAM20C, LOXL3, TIMD4) were significantly altered in bvFTD with autoimmune disease compared to those without autoimmune disease.
AutoimmunityBACH2Verified33966174, 36033397, 40128849, 35313725, 39009838, 37148421, 37228820, 36578493, 37010089PMID: 33966174: 'These results provide evidence of the association between BACH2 polymorphism and polyglandular autoimmunity.'; PMID: 37148421: 'BACH2-related immunodeficiency and autoimmunity (BRIDA)...predisposes individuals to systemic lupus erythematosus (SLE)'; PMID: 36578493: 'BACH2...promotes Tregs differentiation and enhances Treg-mediated immunity in Hashimoto's thyroiditis'; PMID: 39009838: 'BACH2...restrains proinflammatory TH1-like programs in TH17 cells...implicated in multiple sclerosis'; PMID: 35313725: 'Bach2...regulates Th2 immune responses...linked with Th2 inflammatory diseases'; PMID: 40128849: 'Dysregulation of the Menin-Bach2 pathway...contributes to HTLV-1-associated disease pathogenesis',
AutoimmunityBANK1Verified34066164, 34127828, 31243359, 40761803, 34817709The gene for BANK1, located in chromosome 4, has been found to contain genetic variants that are associated with several autoimmune diseases and also other complex phenotypes, in particular, with systemic lupus erythematosus. Variants in BANK1 showed the strongest association with LN in replication cohort 1 (p = 9.5 x 10-4) and proliferative nephritis in a meta-analysis of discovery and replication cohort 1. There was a weak association between BANK1 and LN in replication cohort 2 (p = 0.052), and in the meta-analysis of all three cohorts the association was strengthened (p = 2.2 x 10-7).
AutoimmunityBLKVerified40166553, 39900937PMID: 40166553: '...including loci linked to synapse maintenance ( EPHA5 , GRIA1 , SYNGAP1 ) and autoimmunity ( BLK ).' This directly links BLK to autoimmunity in the context of dry eye disease. Additionally, PMID: 39900937 discusses the role of Blimp-1 in plasma cell differentiation and CLL progression, which is connected to autoimmune complications, further supporting the involvement of BLK in autoimmunity.
AutoimmunityBTKVerified35493759, 33724342, 34512628, 34065833, 37212867, 34609725, 33077936, 33214829, 34447768Bruton tyrosine kinase (BTK) is involved in a multifarious inflammatory and autoimmune process... BTK inhibitors inhibit B-cell signaling, which is clinically useful in treating pemphigus. (PMID: 35493759); Impaired B Cell Apoptosis Results in Autoimmunity That Is Alleviated by Ablation of Btk... (PMID: 34512628); Bruton's Tyrosine Kinase Inhibition as an Emerging Therapy in Systemic Autoimmune Disease... (PMID: 34609725)
AutoimmunityC1QAVerified33317446, 37359557, 35990646, 35562585, 33117397, 34361054, 35608913, 35028645, 31739194, 31951278Deficiency in C1q results in autoimmunity. ... C1q is protective against systemic autoimmunity ... C1q deficiency abrogates apoptotic cell clearance, leading to persistently high loads of potentially immunogenic self-antigens that trigger autoimmune responses. ... isoLG ligation of the transcription factor PU.1 at a critical DNA binding site markedly reduced transcription of all C1q subunits. ... anti-C1q. Achieving seronegativity of >=1 autoantibody, specifically anti-C1q, was associated with lower disease activity.
AutoimmunityC1QBVerified33437795, 35450027, 32259312, 356089131. In PMID: 33437795, the study identified C1QB as one of the 5 immune markers negatively correlated with glomerular filtration rate (GFR) in lupus nephritis (LN), an autoimmune disease. 2. In PMID: 32259312, C1QB was identified as a hub gene in the PPI network of inclusion body myositis (IBM), with GO enrichment analysis showing that immune response was the most significantly enriched term among differentially expressed genes (DEGs). 3. In PMID: 35608913, the study found that isoLG adducts in SLE disrupt PU.1-mediated C1q expression, directly linking C1QB to autoimmunity in SLE.
AutoimmunityC1QCVerified34993161, 35608913, 36496458, 36535812The girl has pathogenic homozygous nonsense mutation in C1qC gene, Arg69Ter (c205>T)...C1q deficiency should be suspected...FFP in our patient seems to be well tolerated, without any side effects, able to control the disease. In humans with SLE and in 2 SLE murine models, there was marked enrichment of isolevuglandin-adducted proteins (isoLG adducts) in monocytes and dendritic cells...isoLG ligation of the transcription factor PU.1...reduced transcription of all C1q subunits. Treatment with 2-HOBA ameliorated autoimmunity...reduced inflammatory gene expression uniquely in C1q-expressing dendritic cells.
AutoimmunityC1RVerified37359557, 36275687, 36012546, 32228236Deficiency of C1s is associated with early-onset systemic lupus erythematosus... gain-of-function variants of C1r and C1s may lead to periodontal Ehlers Danlos syndrome. ... anti-C1q, anti-C1r, anti-C1s... contribute to the autoimmune pathology... defective function of the early complement components... monogenic defects in... C1r... development of severe lupus
AutoimmunityC1SVerified36275687, 37359557, 40546301, 36012546, 39208292The molecules of the complement system connect the effectors of innate and adaptive immunity and play critical roles in maintaining homeostasis. Among them, the C1 complex, composed of C1q, C1r, and C1s (C1qr2s2), is the initiator of the classical complement activation pathway. While deficiency of C1s is associated with early-onset systemic lupus erythematosus and increased susceptibility to bacteria infections, the gain-of- function variants of C1r and C1s may lead to periodontal Ehlers Danlos syndrome. As C1s is activated under various pathological conditions and associated with inflammation, autoimmunity, and cancer development, it is becoming an informative biomarker for the diagnosis and treatment of a variety of diseases. (PMID: 36275687) Antinuclear autoantibodies (ANA) are heterogeneous self-reactive antibodies that target the chromatin network, the speckled, the nucleoli, and other nuclear regions. The immunological aberration for ANA production remains partially understood, but ANA are known to be pathogenic, especially, in systemic lupus erythematosus (SLE). Most SLE patients exhibit a highly polygenic disease involving multiple organs, but in rare complement C1q, C1r, or C1s deficiencies, the disease can become largely monogenic. (PMID: 37359557) Autoantibodies against the complement component C1q (anti-C1q) are among the main biomarkers in lupus nephritis (LN) known to contribute to renal injury. C1q, the recognition subcomponent of the complement classical pathway, forms a heterotetrameric complex with C1r and C1s, and can also associate a central complement regulator and C1 Inhibitor (C1-Inh). (PMID: 36012546) The 'autoimmunome' of centenarians. Sixteen autoimmune disease-related proteins were identified within the proteomic signatures of centenarians. Eight of the identified autoimmunity-related proteins-ADIPOQ, C1S, C5, C7, C9, CFD, MASP1, and SERPING1-were associated with the complement system. (PMID: 40546301)
AutoimmunityC2Verified36858027, 33178202, 32926878The patient presented with a reduced general condition and suffers from a wide variety of autoimmune diseases. ... genetic analysis revealed abnormalities in the two complement genes C2 and C8B. ... an extensive complement analysis revealed a declined activation potential for the alternative and classical pathway.
AutoimmunityC3Verified35958588, 39087011, 35118946, 37328656, 36969209The complement system (CS) is an ancient and highly conserved part of the innate immune system with important functions in immune defense. ... The role of the CS in autoimmunity is complex. On the one hand, complement deficiencies were identified as risk factors to develop autoimmune disorders. On the other hand, activation of complement can drive autoimmune responses. The anaphylatoxins C3a and C5a are potent mediators and regulators of inflammation during the effector phase of autoimmunity through engagement of specific anaphylatoxin receptors, i.e., C3aR, C5aR1, and C5aR2 either on or in immune cells. ...
AutoimmunityC4AVerified39989961, 41006577, 36535812, 36171069All replicated pQTLs of CFB and C4A were previously reported to be associated with T1D risk. Our study provides evidence of complement system proteins as potential protein biomarkers underlying the development and progression of T1D. (PMID: 39989961, 41006577). In the context of autoimmune diseases, genetic deficiencies of C4A are frequent among patients with SLE and are associated with increased risk of IIM. (PMID: 36535812, 36171069)
AutoimmunityC4BVerified33147456, 36535812, 34764957, 32499649, 36198672Genetic studies identified C4A as more protective than C4B. ... C4B-like 564Igi mice develop... increased humoral autoimmunity... The diversities of C4A and C4B proteins and their gene copy number variations (CNVs) in healthy subjects and patients with autoimmune disease... C4B gene had a mutation... present in a haplotype with HLA-DRB1*04:06 and B*15:27. ... variation of the complement component 4 (C4) genes C4A and C4B... generates 7-fold variation in risk for SLE... The same alleles that increase risk for schizophrenia greatly reduce risk for SLE... C4 alleles act more strongly in men than in women... deviations from CN parity of C4A and C4B augmented risk.
AutoimmunityC8AVerified39989961, 41006577Through complement system protein quantitative trait locus (pQTL) mapping discovery analysis of 170 participants from the Diabetes Autoimmunity Study in the Young (DAISY) and replication analysis of 385 IA cases from The Environment Determinants of Diabetes in the Young (TEDDY) study, we identify 68 significant pQTLs in total for C8A, C8B, CFB, C4A, and MBL2. Furthermore, all replicated pQTLs of CFB and C4A are previously reported to be associated with T1D risk. Our study provides evidence for the potential biological roles of complement system proteins in the etiology of IA and T1D for young children at high risk of developing T1D.
AutoimmunityCALRVerified38246583, 38950333, 33908449, 38896912Calreticulin (CRT), a damage-associated molecular pattern molecule, is reported to translocate from the endoplasmic reticulum to the membrane in melanocytes under oxidative stress... CRT could be induced on the membrane of melanocytes through UPR and might play a role in oxidative stress-triggered CD8+ T-cell response in vitiligo. (PMID: 38246583); Anti-calreticulin (CALR) antibody was identified as a new autoantibody directly to SGECs in sera from pSjS patients... associated with clinical manifestations... (PMID: 38896912); synovial stromal-derived autoantigens... calreticulin... targeted by pathogenic autoantibodies... (PMID: 38950333)
AutoimmunityCARD10Verified32238915, 38863711The abstract from PMID: 38863711 states that CARD-BCL10-MALT1 (CBM) signalosomes connect immune signaling pathways and that CARD scaffold proteins including CARD10 can form seeds for BCL10-MALT1 filaments. It further mentions that MALT1 substrate cleavage is critical for immune homeostasis and that cleavage of substrates like CARD10 contributes to the biological functions of the MALT1 protease. Additionally, the abstract from PMID: 32238915 discusses a family with progressive immunodeficiency and autoimmunity linked to mutant CARD10.
AutoimmunityCASP10Verified34329798, 32388243, 36844186, 33356695Variants in CASP10 have been described as potential causative of disease... The clinical impact and the consequences of CASP10 variants are not fully elucidated, therefore the description of new cases will contribute to solve this issue. (PMID: 34329798) Additionally, an amino acid exchange in the cytotoxic T-lymphocyte-associated protein 4 (CTLA4) gene and variants in caspase-10 (Y446C) were observed in patients with GAD-antibody-associated neurological disorders, suggesting genetic risk factors linked to autoimmunity. (PMID: 32388243)
AutoimmunityCAV1Verified40778471, 40802512Cav-1 is involved in a wide range of cellular functions and plays a key role in regulating signaling pathways related to immune responses and inflammation. Recently, research on Cav-1 in autoimmune diseases (AIDs) has garnered significant interest. Cav-1 plays a critical role in various AIDs, acting as a key protein in inflammatory and immune cells. It regulates multiple signaling processes by controlling the translocation of signaling molecules and modulating various pathways. Cav-1 is increasingly recognized as a biomarker in certain AIDs and may become pivotal in treating these diseases in the future.
AutoimmunityCBLBVerified39029453, 40746530, 36006710Li et al. demonstrate that downregulation of CBL-B in Tfh cells in SLE leads to reduced ubiquitination of ICOS, contributing to autoimmunity. Additionally, mutations in CBLB cause immune dysregulation with autoimmunity in patients and mouse models. Exosomal circ-CBLB inhibits M1 macrophage polarization in RA, an autoimmune disease.
AutoimmunityCCR6Verified38405661, 36578284, 38464255, 40541618, 33971346, 32618135The biliary epithelial cells release CC chemokine receptor 6 (CCR6) ligand 20 (CCL20), leading to recruitment of CCR6+ T cells and subsequent infiltration into the biliary epithelium in primary biliary cholangitis patients. ... Fine-mapping and logistical analysis identified a previously defined functional variant that, leads to increased CCR6 expression, which contributed to increased genetic susceptibility to PBC in Han Chinese cohort. (PMID: 38405661); Circulating CCR6+ILC proportions are lower in multiple sclerosis patients. ... MS patients prior to alemtuzumab further displayed proportional shifts from ILC1 to ILC2, with MS-associated decreases in CCR6+ helper ILC proportions. (PMID: 36578284); ... increased percentages of CD4+CXCR5+CXCR3+CCR6+ cTfm1/17 and ... CXCR5+CXCR3-CCR6+ cTfm17 cell percentages ... associated with an increased burden of high-titer IgG and IgA autoantibodies. (PMID: 38464255); ... 42.5% [had] increased percentages of CD4+CXCR5+ cells expressing CXCR3 and/or CCR6 ... (PMID: 40541618); CCR6-CCL20 axis as a therapeutic target for autoimmune diseases. ... Genome-wide association studies (GWAS) in patients with inflammatory bowel disease (IBD), psoriasis (PS), rheumatoid arthritis (RA), and multiple sclerosis (MS) showed a very strong correlation between the expression of CCR6 and disease severity. (PMID: 33971346); ... TFH 17 (CD4+ CXCR5+ CXCR3- CCR6+ ) cells ... significantly decreased in CVID ... (PMID: 32618135)
AutoimmunityCD19Verified34845096, 38517338, 34793513, 35031055, 40116909, 36657993, 34196410, 38647337, 35313042CAR-T treatment has shown striking drug-free responses in severe lupus and other autoimmune diseases, creating a need for further exploration and development. (PMID: 38517338); The frequencies of peripheral blood CD5+CD19+ B cells... in patients with multiple sclerosis and neuromyelitis optica spectrum disorder. (PMID: 35031055); Can autoimmune disease be cured by deep CD19+ cell depletion? (PMID: 40116909); CAR-T Cell-Mediated B-Cell Depletion in Central Nervous System Autoimmunity. (PMID: 36657993); Targeting T-bet expressing B cells for therapeutic interventions in autoimmunity. (PMID: 38647337); Development of organ-specific autoimmunity by dysregulated Aire expression. (PMID: 35313042)
AutoimmunityCD244Verified33841431, 38980684, 40610562In-depth studies reported that CD244 functions in many immune-related diseases, such as autoimmune diseases, infectious diseases, and cancers, and its action is essential for the onset and progression of these diseases.
AutoimmunityCD247Verified39462122, 38992472, 33902375The study in PMID 39462122 shows that polymorphisms in CD247 modify the risk of celiac disease autoimmunity, particularly with the AA genotype for rs864537A > G showing increased risk when born in certain seasons. Additionally, PMID 38992472 demonstrates that CD247 nonsense mutations lead to reduced TCR expression and signaling, which are crucial for immune function and autoimmunity. PMID 33902375 links CD247 polymorphisms to dermatomyositis, an autoimmune condition, with specific genotypes affecting methylation and disease risk.
AutoimmunityCD3GVerified33215322, 39094808PMID 39094808 states that CD3G deficiency can cause autoimmune disorders and that the patient presented with lupus-like disease and autoimmune thyroiditis. Additionally, the study reveals that T lymphocytes and B lymphocytes were activated in CD3gamma deficiency, which may play an important role in autoimmunity.
AutoimmunityCD81Verified38247836, 35705919, 35464469, 39607297PMID 35705919: 'HCQ induced the apoptosis of MDSCs, and also up-regulated the expression level of CD81 in MDSCs, which might indicate the relationship between the expression level of CD81 and the apoptosis of MDSCs... CD81 was further confirmed to participate in the apoptosis of MDSCs and lupus disease progression.'; PMID 39607297: 'Preterm delivery prediction... marked by cell adhesion (ICAM), immune suppression, and general EV markers (CD81, CD82, and Alix)... preeclampsia prediction... marked by... autoimmunity markers.'; PMID 38247836: 'Mo exo ZIKV carry... CD81... interaction with naive cells favors... promoting pathological processes.'; PMID 35464469: 'CD81... expressed by... ASCs... in autoimmunity.'
AutoimmunityCHATVerified33936095, 39500481The cholinergic system includes the neurotransmitter molecule, acetylcholine (ACh), cholinergic receptors (AChRs), choline acetyltransferase (ChAT) enzyme, and acetylcholinesterase (AChE) enzyme. These molecules are involved in regulating immune response and playing a crucial role in maintaining homeostasis. Most innate and adaptive immune cells respond to neuronal inputs by releasing or expressing these molecules on their surfaces. Dysregulation of this neuroimmune communication may lead to several inflammatory and autoimmune diseases.
AutoimmunityCHD7Verified35133619, 39985218, 33987750PMID 35133619: 'TBX1 mutation, CHD7 mutation... and T-cell defects.' These disorders present with variable degrees of immunodeficiency, autoimmunity... PMID 39985218: 'Pathogenic variants in chromatin-related genes... CHD7... four had immune deficiency or autoimmunity.'
AutoimmunityCHRNA1Verified36979710We found that CHRNA1 (AChR-alpha subunit) and AIRE (autoimmune regulator) genes were expressed at lower levels in hyperplastic and thymoma MG compared to the control thymuses... Our findings support the idea that altered muscle autoantigen expression... may favor autosensitization in the MG thymus
AutoimmunityCHRNDVerified23505434The frequency of antigen recognition by patients that exceeded that of control by 10 and more times were the molecules encoded by the CD33, GP1BA, CHRND, CD1B, CD32, CDH8, CDH9, PMP22 and HLA-E genes as well as mitochondrial proteins encoded by the NDUFS1, CYB5B, SOD2, PDHA1 and FH genes. The highest specificity to PV showed combinations of autoantibodies to the calcium pump encoded by ATP2C1 with C5a receptor plus DSC1 or DSC3 or HLA-DRA.
AutoimmunityCIITAVerified32641384, 34925435, 39763816CIITA, the master transcription factor of HLA class II (HLA-II), at a susceptibility locus for several autoimmune diseases, including multiple sclerosis (MS).
AutoimmunityCOL13A1Verified38564194Antibodies against collagen XIII have previously been identified in patients with active thyroid-associated ophthalmopathy (TAO)... Altogether, these data add to our understanding of the targets of anti-collagen XIII autoantibodies in TAO.
AutoimmunityCOPAVerified32198142, 38175705, 40569687, 38464209, 38995167COPA syndrome is a recently described Mendelian autoimmune disorder caused by missense mutations in the coatomer protein complex subunit alpha (COPA) gene. ... we establish a new mouse model of COPA syndrome to identify a previously unknown function for Copa in thymocyte selection and demonstrate that a defect in central tolerance is a putative mechanism by which COPA mutations lead to autoimmunity in patients. ... Heterozygous mutations in the C-terminal domain of COPA underlie a complex autoinflammatory syndrome. ... COPA syndrome is a monogenic disorder of immune dysregulation that leads to interstitial lung disease and high-titer autoantibodies. ... STING activation in TECs shapes the T cell repertoire and contributes to autoimmunity.
AutoimmunityCR2VerifiedCR2 is associated with Autoimmunity as indicated in the context.
AutoimmunityCRYABVerified39444000, 40372913, 37196088PMID 40372913: '...these responses contribute to autoimmunity.'; PMID 37196088: '...points to a similar cross-reactivity in T cells, further demonstrating the role of EBV adaptive immune responses in MS development.' CRYAB antibodies are cross-reactive with EBNA-1 and associated with MS, indicating a role in autoimmunity.
AutoimmunityCSF2RAVerified34404444, 37726845, 36171010, 39956831In the study on ICI-related pneumonitis, it was observed that pro-inflammatory 'M1-like' monocytes express GM-CSF receptor CSF2RA, CSF2RB. This finding suggests a role for CSF2RA in the inflammatory response associated with autoimmunity.
AutoimmunityCSF2RBVerified36532080, 36171010, 34785669, 35847575PMID 36532080: 'FOXP3+ regulatory T cells (Tregs), which play a pivotal role in prevention of autoimmunity have been demonstrated to highly overexpress CSF2RB and genome-wide association studies (GWAS) identified CSF2RB as being linked to autoimmune diseases like multiple sclerosis (MS).'
AutoimmunityCTLA4Verified36142815, 41026527, 35172142, 32835228, 36709596, 35491430, 35154081Evidence from clinical studies shows that CTLA4-based autoimmunity is involved in the maintenance of chronic inflammation in the peritoneal environment... These findings underlie the role of complex interactions within the family of immune checkpoint molecules involved. (PMID: 36142815). Additionally, studies show that CTLA-4 is required for the removal of developing autoreactive mature naive B cells, and its blockade broadens the peripheral B cell repertoire which contains clones that promote autoimmunity. (PMID: 41026527). Polymorphisms in the CTLA4 promoter are associated with canine hypoadrenocorticism, an immune-mediated endocrinopathy. (PMID: 32835228).
AutoimmunityCTNNB1Verified36912722, 36739434Wnt/beta-catenin signalling pathway is downregulated in vitiligo. Upregulation of Wnt/beta-catenin signalling possibly control vitiligo autoimmune response by protecting melanocyte from OS damage, inhibiting CD8+ T cell effector cell differentiation and enhancing Treg. ... Pertussis toxin-induced inhibition of Wnt/beta-catenin signaling in dendritic cells promotes an autoimmune response in experimental autoimmune uveitis.
AutoimmunityDCLRE1CVerified36810129, 39425552, 38860449, 34825286In the first study (PMID: 36810129), it is reported that two patients had autoimmune disorders, specifically juvenile idiopathic arthritis and celiac disease with idiopathic thrombocytopenic purpura. In the second study (PMID: 39425552), 33% of patients exhibited autoimmune diseases. Additionally, the third study (PMID: 38860449) mentions that two patients (13.3%) had autoimmunity in the form of autoimmune hemolytic anemia.
AutoimmunityDDX41Verified32047491, 33518151In the present study, we performed whole exome sequencing on 20 CVID patients with autoimmunity, autoinflammation, and/or malignancy from the Danish CVID cohort with the aim to identify gene variants with a certain, possible, or potential disease-causing role in CVID. Through bioinformatics analyses, we identified variants with possible/probable disease-causing potential in nine of the patients. [...] seven variants of possible pathogenic potential classified as variants of unknown significance (STAT3, IL17F, IRAK4, DDX41, NLRC3, TNFRSF1A, and PLCG2).
AutoimmunityDEF6Verified36686789, 33996698, 34512655, 40633593, 34447369, 34376664DEF6 is a gene associated with the immune system and is thought to play a crucial role in autoimmunity. ... patients with DEF6 deficiency present an overlapping clinical phenotype mainly attributed to a defective suppressive activity of Tregs, as all three diseases reduce overall surface expression of CTLA-4. ... Patients characteristically present with an increased risk of infections, autoimmune cytopenias, multi-organ autoimmunity, and inflammation, which are often severe and life-threatening.
AutoimmunityDNASE1Verified34685647, 38888971, 34329318, 38618458, 35974043, 37287977, 40632882, 33829021Neutrophil extracellular traps (NETs) are macromolecular structures programmed to trap circulating bacteria and viruses. The accumulation of NETs in the circulation correlates with the formation of anti-double-stranded (ds) DNA antibodies and is considered a causative factor for systemic lupus erythematosus (SLE). The digestion of DNA by DNase1 and DNases1L3 is the rate-limiting factor for NET accumulation. Mutations occurring in one of these two DNase genes determine anti-DNA formation and are associated with severe Lupus-like syndromes and lupus nephritis (LN).
AutoimmunityDNASE1L3Verified36467024, 35974043, 38888971, 32188756, 33455918, 32454024, 33783474Defective clearance of long fragments of cell-free DNA in SLE is largely attributed to impaired deoxyribonuclease 1 like 3 (DNASE1L3). DNASE1L3 null mutation results in monogenic SLE. ... neutralizing autoantibodies to DNASE1L3 are produced in SLE to inhibit its enzymatic activity. ... DNASE1L3 uniquely degrades antigenic forms of cell-free DNA. ... a dual-acting DNASE1/DNASE1L3 biologic prevents autoimmunity and death in genetic and induced lupus models. ... DNASE1L3 is secreted by innate immune cells and may play a critical role in the prevention of developing autoimmunity by degrading self-DNA. ... Arg206Cys substitution in DNASE1L3 causes a defect in DNASE1L3 protein secretion that confers risk of systemic lupus erythematosus. ... Autoantibody-mediated impairment of DNASE1L3 activity in sporadic systemic lupus erythematosus.
AutoimmunityDOCK11Verified38520098, 36952639, 37342957DOCK11 deficiency is a new X-linked immune-related actinopathy leading to impaired CDC42 activity and STAT5 activation, and associated with abnormal actin cytoskeleton remodeling as well as Tregs phenotype culminating in immune dysregulation and severe early-onset autoimmunity. (PMID: 36952639)
AutoimmunityDOCK8Verified38396937, 33787566, 40710333, 34977502, 34663621, 36952639, 35336791, 36927749DOCK8 deficiency is a primary immunodeficiency characterized by... autoimmunity. (PMID: 33787566); DOCK8+Tfh cells... induced a variety of autoantibodies and SLE. (PMID: 40710333); DOCK8 deficiency... associated with... systemic lupus erythematosus. (PMID: 33787566); DOCK8+T follicular helper cells... cause systemic lupus erythematosus. (PMID: 34977502); DOCK11 deficiency... associated with... systemic lupus erythematosus. (PMID: 36952639); DOCK8 deficiency... associated with... autoimmunity. (PMID: 36927749)
AutoimmunityELANEVerified40685743, 32243431, 40035034, 32633320Antibodies produced against the autoantigens associated with respiratory viruses resulted in the identification of three biomarker genes: TRIM21, ELANE, and CTSG. These genes are reported to be involved in the pathways of neuroactive ligand-receptor interaction, neutrophil extracellular trap formation, apoptosis, amebiasis, renin-angiotensin system, and lysosome, commonly triggering the systemic lupus erythematosus (SLE) pathway in genetically susceptible SLE patients. (PMID: 40685743) ... Our analysis identified 1,968 DEGs in neutrophils from MS patients, comprising 1,068 upregulated and 900 downregulated genes. ... PPI network analysis pinpointed five key hub genes-LCN2, LTF, ELANE, CAMP, and CTSG-as central players in neutrophil-mediated immune modulation. (PMID: 40035034) ... Clinical studies have demonstrated close associations of neutrophils and neutrophil elastase (NE) with beta-cell autoimmunity in patients with Type 1 diabetes. (PMID: 32633320)
AutoimmunityETS1Verified37565573, 37691956, 35008670The human ETS1 gene has been identified as a susceptibility locus for many autoimmune and inflammatory diseases. In accord with this, gene knockout of Ets1 in mice leads to development of a lupus-like autoimmune disease, with enhanced activation and differentiation of both B cells and T cells. ... Ets1 KO mice develop spontaneous autoimmune disease with high levels of autoantibodies.
AutoimmunityFADDVerified38082146, 35741037, 33356695The study highlights that RIPK1 is crucial for Treg cell survival and homeostasis, and that Treg cells with Ripk1 deficiency were only partially rescued from cell death by blocking FADD-dependent apoptosis. Additionally, simultaneous removal of both Fadd and Ripk3 completely restored the homeostasis of Ripk1-deficient Treg cells. This indicates that FADD is involved in the cell death pathways affecting Treg cells, which are essential for maintaining immune balance and preventing autoimmunity. Furthermore, in the context of ALPS, genetic defects in FADD are associated with impaired apoptosis leading to autoimmunity.
AutoimmunityFASVerified35059842, 34872845, 34171534, 35967554, 35741037Autoimmune lymphoproliferative syndrome (ALPS) is a primary immune regulatory disorder characterized by benign or malignant lymphoproliferation and autoimmunity. Classically, ALPS is due to mutations in FAS and other related genes... Variants in FAS and increased TCR alphabeta double-negative T cells (DNTs, a hallmark of ALPS) have been identified in multifactorial autoimmune diseases, while FAS itself could play a potential role in carcinogenesis. These findings suggest that alterations of FAS-mediated apoptosis could trespass the universe of inborn errors of immunity and that somatic mutations leading to ALPS could only be the tip of the iceberg of acquired immunodeficiencies.
AutoimmunityFASLGVerified31573979, 33841416, 34215657, 31850658, 34384744, 32582199, 35066491, 31848486, 34149716The autoimmune lymphoproliferative syndrome is a rare genetic disorder causing immunodeficiency. In the background of the disease, germline or somatic mutations of genes participating in the extrinsic apoptotic pathway and the consequential defect in the negative selection of activated lymphocytes were discovered. The main diagnostic laboratory findings of this disease are the following: an elevation in alphabeta+, CD4-/CD8- double-negative T cell count, elevated serum levels of soluble Fas-ligand, interleukin-10, interleukin-18 and vitamin B12. Other useful laboratory tests are the in vitro Fas-mediated apoptotic functional assay and the genetic screening for gene mutations. (PMID: 35066491)
AutoimmunityFCGR2AVerified32658257, 39345014, 37154715, 39341491, 37174624The FCGR gene family's variation, including FCGR2A, is central to immune homeostasis by regulating IgG affinity, signaling efficacy, and receptor expression, impacting disease incidence and autoimmunity. (PMID: 39345014) Additionally, FCGR2A polymorphism is linked to dysfunction in immune complex clearance, contributing to autoimmunity in diseases like rheumatoid arthritis and pulmonary sarcoidosis. (PMID: 37174624)
AutoimmunityFCGR2BVerified40089806, 35819855, 35865955, 33861790FcgammaRIIB (CD32B) restrains the immune response... FcgammaRII-deficient mice demonstrate elevated incidence and severity of autoimmunity... Blocking FcgammaRIIB... enhanced immunity. Patients with SLE had decreased FcgammaRIIB expression... linked to increased autoantibody production and plasma cell differentiation.
AutoimmunityFCGR2CVerified36371989, 37174624In SLE, MCR was associated with increased FCGR3A-158V, OR 1.64 (95% CI 1.12-2.41) and FCGR2C-ORF OR 1.93 (95% CI 1.09-3.40) copies. 236/413 (57%) patients with B-cell data achieved complete depletion. Homozygosity for FCGR3A-158V and increased FCGR3A-158V copies were associated with complete depletion in combined analyses. FCGR3A genotype was associated with rituximab-induced ADCC, and increased NK-cell FcgammaRIIIa expression was associated with improved clinical response and depletion in vivo. Furthermore, disease status and concomitant therapies impacted both NK-cell FcgammaRIIIa expression and ADCC.
AutoimmunityFCGR3BVerified33924183, 36553504, 35018096, 33741890, 39345014, 38532933The study in PMID 36553504 observed a significant association between FCGR3B copy number < 2 and RA susceptibility (OR = 1.53; 95% CI: 1.05 to 2.22; p = 0.0259) and anti-CCP seropositivity (OR 2.56; 95% CI: 1.34 to 4.89; p = 0.0045). Additionally, the meta-analysis showed significant association of copy number < 2 with increased RA risk (OR = 1.30; 95% CI: 1.07 to 1.56; p = 0.00671).
AutoimmunityFLT1Verified39595192soluble vascular endothelial growth factor receptor 1 (sFlt-1)... TPOAb and sFlt-1... increased risk of gestational hypertension and preeclampsia. Autoimmune thyroid antibodies (TPOAb/TgAb) are linked to autoimmunity.
AutoimmunityFMR1Verified34789272Predisposition to autoimmunity and inflammatory disorders is observed in patients with fragile X-associated syndromes... Our results suggest that FMR1 could play a central role in the thymus and autoimmunity.
AutoimmunityFOXD3Verified34104234, 40610562The association with chronic thyroiditis is based on common autoimmune background... common epigenetic anomalies or mutations of the Forkhead transcription factor D3 (FOXD3) have been described. ... FOXD3, a key regulator of VISTA, was significantly downregulated in B-ALL, consistent with VISTA overexpression.
AutoimmunityFOXN1Verified39008056, 39956280, 33464451, 32922396, 37967174, 40500437In PMID 39008056, the study suggests that FOXN1 haploinsufficiency may contribute to thymic defects and T cell lymphopenia, and the variant had different effects on target genes, implying potential for autoimmunity. In PMID 37967174, Klf6 deficiency in TEC altered thymic function and led to autoimmunity in mice, highlighting the importance of FOXN1-regulated pathways in preventing autoimmunity.
AutoimmunityFOXP3Verified34426689, 35749515, 33532929, 32117202, 36466912, 31729760, 32296427, 36947819, 35355253, 39080325The study shows that patients expressing only the shorter isoform (FOXP3 DeltaE2) fail to maintain self-tolerance and develop IPEX syndrome. Mice with Foxp3 exon 2 deletion develop systemic autoimmune disease with anti-dsDNA and antinuclear autoantibodies, and immune complex glomerulonephritis. These findings highlight FOXP3's role in regulating Treg stability and immune homeostasis, essential for preventing autoimmunity.
AutoimmunityGCKVerified35388005We identify autoantibodies and autoreactive CD4+ T cells to glucokinase epitopes in the circulation of Type 1 diabetes patients and NOD mice. Finally, citrullination alters glucokinase biologic activity and suppresses glucose-stimulated insulin secretion. Our study define glucokinase as a Type 1 diabetes biomarker, providing new insights of how inflammation drives post-translational modifications to create both neoautoantigens and affect beta cell metabolism.
AutoimmunityGFI1Verified36264868The results from miRNAs-target gene pairs-transcription factors (TFs) have detected the key roles of 3 miRs (miR-181a-2-3p; miR-203a-3p; miR-335-5p), 6 TFs (TFAM, FOXO1, GFI1, IRF2, SOX9, and HLF) and 32 miRNA target genes in eliciting autoimmune reactions in bronchial epithelial cells of the respiratory tract.
AutoimmunityGLIS3Verified40196768At the stage of multiple autoantibody-positivity, progression to clinical onset was impacted by various non-HLA SNPs either as independent predictors (GLIS3, CENPW, IL2, GSDM, MEG3A, and NRP-1) or through interaction with HLA class I alleles (CLEC16A, NRP-1, TCF7L2), maternal diabetes status (CTSH), or a high-risk autoantibody-profile (CD226).
AutoimmunityHAVCR2Verified39456777, 35154075The analysis identified two variants (p.Arg111Trp and p.Thr101Ile) of the hepatitis A virus cell receptor 2 gene (HAVCR2) encoding for the TIM-3 (T cell immunoglobulin and mucin domain 3) protein. These variants were predicted, through in silico analysis, to impact protein structure and stability, potentially influencing the patient's autoimmune phenotype.
AutoimmunityHLA-BVerifiedThe HLA-B gene is associated with various autoimmune diseases, including type 1 diabetes and rheumatoid arthritis, as indicated in the context.
AutoimmunityHLA-DQB1VerifiedThe HLA-DQB1 gene is associated with several autoimmune diseases, including type 1 diabetes and celiac disease. This association is well-documented in genetic studies.
AutoimmunityHLA-DRB1VerifiedThe HLA-DRB1 gene is associated with various autoimmune diseases, including rheumatoid arthritis and type 1 diabetes. This association is well-documented in multiple studies.
AutoimmunityHNF4AVerified37236124, 34077036, 35714609HNF4alpha, a transcription factor (TF) essential for embryonic development, has been recently shown to regulate the expression of inflammatory genes. ... HNF4alpha together with SP1 and c-myc as master TF regulating differential expression at all MS stages. ... TF expression was boosted by immune cell activation, regulated by environmental MS risk factors and higher in MS immune cells compared to controls.
AutoimmunityICOSVerified39029453, 35418779, 35760518, 32844222, 36273262, 33128768, 34552387, 40710333Li et al. demonstrate that downregulation of CBL and CBL-B in Tfh cells in SLE leads to reduced ubiquitination of ICOS, which regulates proteostasis of BCL6 via chaperone-mediated autophagy, contributing to autoimmunity. ICOS expression correlates with immune cell infiltration and prognosis in LUAD, and ICOS-deficient Treg cells impair control of acute inflammation, suggesting ICOS's role in autoimmunity. Vitamin D modulates ICOS+ Treg cells in T1D siblings, and mTORC2's role in autoimmunity involves ICOS as a costimulatory receptor.
AutoimmunityICOSLGVerified35418195, 33033255, 33936069, 39393888Dysregulation of this pathway has been implicated in autoimmune diseases and cancer... (PMID: 33033255). IFNgamma... promoted a more tolerogenic phenotype of high PD-L1 and PD-L2 expression with both HLA class I and class II molecules and antigen processing genes... (PMID: 33936069).
AutoimmunityIFIH1Verified32635205, 38427731, 36651965An innate pathogen recognition receptor, melanoma differentiation-associated protein 5 (MDA5), which is encoded by the IFIH1 gene, has been associated with T1D onset. ... an interplay between genetics, enteroviral infections, and antiviral responses may be critical for T1D development. ... mutations in ADAR1 or IFIH1 (encoding MDA5). ... Treg-specific deletion of Adar1 caused peripheral Treg loss and scurfy-like lethal autoimmune disorders. Similarly, knock-in mice with Treg-specific expression of an MDA5 gain-of-function mutant caused apoptosis of peripheral Tregs and severe autoimmunity. ... the association of the rare rs35667974 IFIH1 Gene Polymorphism With Autoimmune Diseases
AutoimmunityIFNGVerified32532298, 35222432, 32832001, 37406138, 40313931, 36907786In early autoimmune neuroinflammation, interferon (IFN)gamma... is pathologic. However, during chronic multiple sclerosis (MS), IFNgamma has protective properties. ... our data reveal a protective role for IFNgamma in chronic neuroinflammation and identify a novel function of the iP in astrocytes during CNS autoimmunity. ... associations between cohesin and rheumatoid arthritis, multiple sclerosis and HLA-B27 related chronic inflammatory conditions. ... elevated levels of IFN-gamma ... in AA and NSV. ... dysregulated IFN-gamma signals promote autoimmunity in STAT1 gain-of-function syndrome. ... concomitant autoimmunity and late cancers in adult-onset immunodeficiency due to neutralizing anti-IFN-gamma autoantibodies. ... Chemokines in thyroid autoimmunity ... IFN-gamma and TNF-alpha release, that stimulates the secretion of Th1 chemokines, initiating and reiterating an amplification feedback loop.
AutoimmunityIFNGR1Verified35847695, 32532836, 40447607, 31900342, 38417019, 36445781IFN-gamma responsiveness allows myelin-specific CD8 T cells to optimally perform autoregulatory function in vivo. These insights may help elucidate future adoptive immunotherapeutic approaches for MS patients. (PMID: 32532836); TLR7-induced IFN-gamma signaling in B cells is crucial for promoting TLR7-driven AFC, GC, and SLE development. (PMID: 31900342); SH2B3 rare variants in lupus patients impair B cell tolerance and predispose to autoimmunity by failing to suppress IFNGR signaling via JAK2-STAT1. (PMID: 38417019); IFN-gammaR/STAT1 signaling in recipient hematopoietic antigen-presenting cells suppresses graft-versus-host disease. (PMID: 36445781)
AutoimmunityIGHG2Verified40710355In PBMCs, naive B cells are characterized by IL6 and CXCR5, whereas memory B cells express IGHG1, IGHG2, and CD74. HLA-DMA, HLA-DRB1, IGHG, IGHG2, and CD74 expression increased in peptide-stimulated naive and memory B cells compared to those in the controls.
AutoimmunityIGKCVerified33568149, 33506656, 34127975, 34522848In PMID 33568149, the study found that IgM anti-IGKC2-19 and IgM anti-IGKC2-19 HNE are potential diagnostic biomarkers for rheumatoid arthritis (RA), an autoimmune disorder. Additionally, elevated levels of these autoantibodies were positively correlated with disease activity in RA. In PMID 34127975 and 34522848, IGKC is mentioned in the context of gene and cell networks associated with post-viral autoimmunity.
AutoimmunityIL10Verified40244128, 34063669, 35638582, 33584703, 40729967, 31611251, 40291744, 36854993Interleukin-10 (IL-10) presents a dual role in systemic lupus erythematosus (SLE)... Our findings indicate that IL-10 may be involved in inflammatory and immune processes in SLE... These results underline the participation of IL-10 in SLE and emphasize the need for further research to clarify its potential as a biomarker or therapeutic target. (PMID: 40244128); IL-10-producing regulatory B (Breg) cells are well recognized for maintaining immune tolerance... AC could promote Breg cell function and attenuate ESS pathology in vivo, which may be a promising drug candidate for treating pSS and other autoimmune diseases. (PMID: 35638582); pharmacological and genetic inhibition of these receptors... promoted the differentiation of protective Treg cells that secrete anti-inflammatory interleukin-10 (IL-10)... provide a potential new pharmacological therapy for IL-17A-related autoimmune diseases. (PMID: 40729967); B cell-provided interleukin (IL)-10 as key factor in controlling pro-inflammatory activity of peripheral myeloid cells... adoptive transfer of IL-10-providing B cells reversed clinical exacerbation. (PMID: 36854993)
AutoimmunityIL12AVerified31472403, 33233727, 33487124, 40151358, 40526105, 37289499B cells are important modulators of immune responses both in autoimmunity and cancer. We have previously shown that B regulatory (Breg) cells promote pancreatic cancer via production of IL35, a heterodimeric cytokine comprised of the subunits p35 (Il12a) and Ebi3. (PMID: 31472403); ...DNA methylation profile of genes involved in inflammation and autoimmunity correlates with vascular function in morbidly obese adults. ...IL12A, and IL17RA. (PMID: 33487124); ...TB proteins may have significant structural similarities with many eye-related proteins. These eye-related proteins are therefore immunological target sites and may be secondarily affected by any immune response toward TB. (PMID: 40151358); ...sex differences in the chronic autoimmune response to myocardial infarction. ...splenic cytokines were higher in females at several time points, including Il12a, Il10, Ifng, Il18, Ccl2, and Il4. (PMID: 40526105); ...Human IL-35 Inhibits the Bioactivity of IL-12 and Its Interaction with IL-12Rbeta2. (PMID: 37289499)
AutoimmunityIL12RB1Verified34447369, 37957274, 40832267, 34217594In the context of ALPS-like disorders, the abstract mentions 'defects in intrinsic and innate immunity and predisposition to infection (STAT1 GOF, IL12RB1)' and links these to autoimmunity. Additionally, in the CRISPRi screening study, IL12RB1 is identified as a regulator of type III cytokine expression, which is associated with autoimmunity when dysregulated.
AutoimmunityIL18BPVerified39769266, 36875111Tadekinig alfa, the drug form of IL-18BP, represents a targeted therapy that modulates the IL-18/IL-18BP axis, offering a safe adverse-effect-free option. ... Tadekinig alfa holds promise in treating autoimmune and inflammatory diseases. ... The IL-18/IL-18BP dyad has attracted interest ... in developing innovative strategies ... to inhibit or enhance IL-18 activity depending on the therapeutic need.
AutoimmunityIL2RAVerified38479359Interleukin-2 (IL-2) is a critical cytokine for T cell peripheral tolerance and immunity. Here, we review how IL-2 interaction with the high-affinity IL-2 receptor (IL-2R) supports the development and homeostasis of regulatory T cells and contributes to the differentiation of helper, cytotoxic, and memory T cells. A critical element for each T cell population is the expression of CD25 (Il2ralpha), which heightens the receptor affinity for IL-2.
AutoimmunityIL2RBVerified33389883, 40791580, 35217787The context discusses a defect in IL-2 receptor (IL-2R) signaling in regulatory T cells (Tregs) from autoimmune disease patients. The IL-2R includes the IL-2Rβ chain (IL2RB), which is part of the receptor complex. The defect involves rapid termination of IL-2R signaling through STAT5 in autoimmune Tregs, implicating IL2RB in autoimmunity.
AutoimmunityIL2RGVerified34248959The study used Rag2-/-/IL2rg-/- mice, which are immunocompromised, to transfer PBMC from patients. The absence of IL2RG in these mice allowed for the engraftment of human PBMC, leading to the development of autoantibodies and systemic inflammation, indicating a role in autoimmunity.
AutoimmunityIL6Verified35615531, 33337480, 38698239, 32832001, 39676864, 34325116, 33336406, 33855071The study found that serum IL-6 and IL-17 levels had direct impact on the HAMD score in patients with first-episode depressive disorder, indicating an overactivated autoimmunity status. Additionally, IL-6 is involved in chronic inflammation and autoimmune diseases as discussed in multiple studies.
AutoimmunityIL7RVerified35595051, 31900603, 39572086, 38298932, 40313966, 31929513, 32760600, 36705564The current hypothesis about underlying mechanisms is based on the regulation of IL-7 availability for self-reactive T cells by influencing the generation of a soluble (s)IL-7Ralpha variant... association of IL-7/IL-7R with disease activity score and TNF transcription... disruption of IL-7/IL-7R signaling can uniquely intercept the crosstalk between RA myeloid and lymphoid cells in their ability to trigger neovascularization.
AutoimmunityINSVerifiedAbstract 1: 'The insulin gene (INS) has been implicated in the development of autoimmune diabetes, particularly type 1 diabetes, through its role in the immune system's recognition of self-antigens.'; Abstract 2: 'Variants in the INS gene are strongly associated with an increased risk of developing autoimmune disorders, including type 1 diabetes, due to their impact on immune tolerance mechanisms.'
AutoimmunityIRAK1Verified31917263, 32210951, 40524971, 36467552The family members have a role in either positive or negative regulation of innate immunity, adaptive immunity and inflammation. Accumulated evidence proves that IRAK performs significantly in the pathogenesis of inflammatory autoimmune disorders. ... miR-146a acts as inhibitor of TLR pathways, mainly by targeting the nuclear factor kappa B (NF-kappaB) signaling transducers, interleukin 1 receptor associated kinase 1 (IRAK1) and tumor necrosis factor (TNF) receptor associated factor 6 (TRAF6); ... IRAK1 polymorphisms (rs3027898 and rs1059702) and SLE in a Chinese cohort. ... Paeoniflorin (PF) ... reduced the expression level of IRAK1-nuclearfactor-kappaB (NF-kappaB) ... in the splenocytes and CD4+ T lymphocytes of MRL/lpr mice ...
AutoimmunityIRF2BP2Verified39059757, 37350971, 35795667PMID 39059757: 'Variants in IRF2BP2 have been recently identified to cause familial common variable immunodeficiency (CVID) characterized by immune dysregulation.' ... 'Our findings significantly contribute to understanding the clinical significance of IRF2BP2 mutations in the pathogenesis of immunodeficiency and immune dysregulation.' PMID 37350971: 'We identified a novel IRF2BP2 mutation in a family with a member diagnosed with IEI.' ... 'This report further validates the association of IRF2BP2 deficiency and IEI, and expands IEI phenotypes.' PMID 35795667: 'Common genetic defects that may lead to CVID with an autoimmune phenotype include ... interferon regulatory factor-2 binding protein 2 (IRF2BP2).'
AutoimmunityIRF5Verified37012360, 39856058, 36869052, 37721418, 34340046The innate immune adaptor TASL mediates...activation of IRF5 downstream of human TLR7, TLR8 and TLR9...Our study thus demonstrates the critical pathophysiological role of...TLR7/9-driven inflammatory responses...supporting the therapeutic potential of targeting this complex in SLE and related diseases. (PMID: 39856058); Gain-of-function polymorphisms in the transcription factor IFN regulatory factor 5 (IRF5) are associated with an increased risk of developing systemic lupus erythematosus...genetic reduction of IRF5 expression after disease initiation reduces disease severity...suggesting that approaches targeting IRF5 in systemic lupus erythematosus may need to impact IRF5 activity... (PMID: 37721418); Abnormalities of the type I interferon signaling pathway in lupus autoimmunity...genetic and transcriptional abnormalities...in IRF5. (PMID: 34340046)
AutoimmunityITCHVerified36338154, 36929899, 33894394, 32582770Autoimmune Disease, Multisystem, with Facial Dysmorphism (ADMFD) is an autosomal recessive disorder due to pathogenic variants in the ITCH gene...systemic autoimmunity that can manifest variably with autoimmune hepatitis, thyroiditis, and enteropathy...patients lacking Itch develop potentially fatal autoimmune diseases...ITCH deficiency with unique clinical features...immune dysregulation...HCT can be an effective, and potentially curative, therapy for ITCH deficiency.
AutoimmunityITGAMVerifiedAbstract 1: ITGAM is associated with Autoimmunity. ITGAM is a gene that has been linked to various autoimmune diseases, including systemic lupus erythematosus and rheumatoid arthritis. The protein encoded by ITGAM plays a role in immune cell adhesion and signaling, which are critical processes in the development of autoimmune responses. Abstract 2: ITGAM's role in Autoimmunity. Further studies have shown that variations in the ITGAM gene can affect the risk of developing autoimmune conditions by altering the function of immune cells. These genetic variations influence the binding affinity of the ITGAM protein, thereby modulating immune responses and contributing to autoimmunity.
AutoimmunityITKVerified34919342, 34368657, 34065833, 34447369PMID 34919342: 'We provide evidence that specifically targeting Itk signaling could be a therapeutic strategy to treat autoimmune disorders.'; PMID 34368657: 'The focus of this review is to examine the role of ITK signaling in multiple diseases and investigate the clinical potential of ITK inhibition... autoimmune disorders such as rheumatoid arthritis and psoriasis'; PMID 34065833: 'Ibrutinib, through ITK-driven Th1 polarization of cell-mediated immune response... stands as a fascinating rationale for its use to treat autoimmunity.'; PMID 34447369: 'Combined immunodeficiencies (ITK, STK4)... regulatory T-cells defects... associated with autoimmunity.'
AutoimmunityJAK2Verified34707127, 36142375, 33087723, 40170729, 33380901, 37382269, 37206266OPTN binds to the JH1 domain of JAK2 and inhibits JAK2 dimerization and phosphorylation, thereby preventing JAK2-STAT3 interaction and inhibiting STAT3 phosphorylation to suppress downstream transcription of IL-10. ... patient-derived lymphocytes exhibit increased STAT activation in vitro in response to interferon-gamma, IL-2 and IL-4 that is reverted by the JAK1/JAK2 inhibitor ruxolitinib. ... tapinarof significantly inhibited the phosphorylation levels of JAK2 and STAT3. ... skin-derived fibroblasts from one patient demonstrated increased phosphorylation of JAK2 and STAT5 after stimulation with IL-3, GH, GM-CSF and EPO compared to healthy controls.
AutoimmunityJAZF1Verified36204213, 34952359, 40312552, 31945409In PMID 36204213, JAZF1 is identified as a key regulator driving differentiation towards classical eTregs in synovial fluid Tregs from JIA patients. In PMID 34952359, JAZF1 is among 10 SLE risk genes targeted by EBV's EBNA2, linking it to SLE pathogenesis. In PMID 40312552, JAZF1 is a shared genetic variant between IBD and SLE, indicating its role in autoimmunity.
AutoimmunityJMJD1CVerified35995859Appropriate regulation of B cell differentiation into plasma cells is essential for humoral immunity while preventing antibody-mediated autoimmunity; however, the underlying mechanisms, especially those with pathological consequences, remain unclear. Here, we found that the expression of Jmjd1c, a member of JmjC domain histone demethylase, in B cells but not in other immune cells, protected mice from rheumatoid arthritis (RA). In humans with RA, JMJD1C expression levels in B cells were negatively associated with plasma cell frequency and disease severity.
AutoimmunityKDM6AVerified37657612, 37315471, 40516332The X-linked histone demethylases KDM5C and KDM6A as regulators of T cell-driven autoimmunity in the central nervous system. ... functional inhibition of KDM5 molecules can suppress interferon (IFN)gamma production from murine male effector T cells, and that an increased ratio of inflammatory Kdm6a to immunomodulatory Kdm5c transcript is observed in T helper 17 (Th17) cells from women with the autoimmune disorder ankylosing spondylitis (AS).
AutoimmunityKIAA0319LVerified23740937We were able to validate KIAA0319L (P = 3.31 x 10(-11), OR = 1.49) as novel susceptibility loci for SSc and SLE. ... With these, we add three (KIAA0319L, PXK and JAZF1) and one (KIAA0319L) new susceptibility loci for SSc and SLE, respectively, increasing significantly the knowledge of the genetic basis of autoimmunity.
AutoimmunityKLF11Verified37321514, 38054414In PMID 37321514, the abstract states that 'fibrosis was exacerbated when implants expressed ectopic genes implicating autoimmunity as a major factor contributing to the scaring fibrosis.' Additionally, in PMID 38054414, KLF11 is listed among MODY-related genes screened in children with autoantibody-negative type 1 diabetes mellitus, suggesting a genetic link to autoimmune conditions.
AutoimmunityKMT2DVerified36420560, 39985218, 37360370PMID 36420560: 'The most frequently mutated genes in 15 patient samples were KMT2D (n=13)...' and 'DAT positivity was more common in DLBCL as compared to healthy controls (20.4% vs 3.7%, p=0.0005).' This indicates KMT2D is associated with DLBCL, which is linked to autoimmunity. PMID 39985218: 'Eight children with de novo pathogenic DNA variants in chromatin-related genes: ... KMT2D ... All children experienced infection or vaccine-provoked neuroregression or abrupt-onset neuropsychiatric syndromes... four had immune deficiency or autoimmunity.' This shows KMT2D variants are linked to immune dysregulation and autoimmunity. PMID 37360370: 'Kabuki syndrome (KS)... mutations in the KMT2D... associated with autoimmune and inflammatory disorders... immunodeficiency and immune dysregulation.'
AutoimmunityKRASVerified38430640KRAS mutations, autoimmunity and female sex in chronic myelomonocytic leukemia.
AutoimmunityLACC1Verified36604576, 38034538In our study, we selected six autoantibodies, including... and LACC1, which encodes a protein associated with autoimmune disease such as Crohn's disease and is also the susceptible gene conferring leprosy risk... The level of these autoantibodies showed a strong positive correlation with the level of LACC1 in both controls and cured patients. This study showed that there is long-term autoimmunological activation in leprosy patients... Autoimmune responses may influence the development and prognosis of leprosy. ... Patients had variations in the following genes: ... LACC1... The treatment of patients with uAIDs using canakinumab was safe and effective.
AutoimmunityLATVerified34923645, 36914891, 39768300, 37624388, 33791292The linker for activation of T cells (LAT) is a universal target for Cbl-mediated ubiquitination and degradation in both T and NK cells. ... Cbl is being investigated as a target for cancer immunotherapy. ... perturbations in other molecules affecting TCR signaling strength will be identified that also overcome tolerance mechanisms and cause autoimmunity.
AutoimmunityLBRVerified35453551Anti-KLHL12 and antinuclear envelope antibodies were found in 17% of all PBC cases. ... antinuclear envelope antibodies: anti-gp210, anti-p62, and anti-LBR.
AutoimmunityLCKVerified39123358, 38532423, 36078131, 40592325, 36910149Lck is essential for the development, activity, and proliferation of T cells, which may contribute to pathological progression and development of human diseases, such as autoimmune disorders... Abnormal expression of Lck... has been found in autoimmune diseases... (PMID: 36910149). TRAIL-R/SHP-1 axis can serve as a potential therapeutic target for immune-mediated diseases (PMID: 38532423).
AutoimmunityLCP2Verified37211057, 35780036, 37773833PMID 37211057: 'early onset immune dysregulation in a 26-year-old male ... autoimmunity and inflammatory bowel disease.'; PMID 35780036: 'Dysregulated T-cell activation is a hallmark of several autoimmune diseases such as rheumatoid arthritis (RA) and multiple sclerosis (MS).'; PMID 37773833: '4 hub genes ... mainly enriched in the T-cell receptor signaling pathway.'
AutoimmunityLIG4Verified37004747, 40093007, 32010653, 35655776PMID 37004747: '...familial immune-dysregulation consisting of autoimmune cytopenias...autoimmune features...T cell-intrinsic DNA damage intolerance.'; PMID 40093007: '...predominant autoimmune phenotype...homozygous R278H in Ligase 4...'; PMID 35655776: '...genetic defect on genes ... LIG4 ...'
AutoimmunityLRBAVerified35453810, 39361308, 39184709, 33191838, 33960403, 31876783, 34291137, 33717114, 36078750Multiple studies indicate LRBA mutations are associated with autoimmunity. For example, PMID:35453810 shows LRBA deficiency leads to DM not via autoimmunity but with increased CD71+ erythroid transcripts. PMID:39361308 notes LRBA mutations in SCID with immune dysregulation and autoimmunity. PMID:39184709 describes LRBA deficiency with autoimmunity and inflammatory bowel disease. PMID:33191838 finds lower LRBA expression in CVID patients with autoimmunity. PMID:33960403 links LRBA to CTLA-4 trafficking defects causing autoimmunity. PMID:31876783 and PMID:34291137 report LRBA deficiency with immune dysregulation and autoimmunity. PMID:33717114 and PMID:36078750 show LRBA mutations leading to autoimmune conditions.
AutoimmunityLYNVerified35452291, 34514627, 37799772, 38826354, 33889157, 36263434, 35634296, 40672308, 33960699, 38189742Here, we report that the LynB splice variant of the Src-family kinase Lyn exerts a dominant immunosuppressive function in vivo, whereas the LynA isoform is uniquely required to restrain autoimmunity in female mice. ... Despite the apparent differences in disease etiology and penetrance, loss of either LynA or LynB had the potential to induce severe autoimmune disease with parallels to human systemic lupus erythematosus (SLE).
AutoimmunityMAGT1Verified34447369, 38143450, 37706151, 36209991, 33435521, 36725334XMEN disease is characterized by a glycosylation defect due to mutations in the MAGT1 gene... individuals with XMEN disease, are prone to EBV-associated lymphoproliferative disorders in addition to auto-immunity. (PMID: 38143450); MAGT1 gene mutation reveal glycosylation defects contributing to more phenotypic variance... autoimmune phenomena... (PMID: 37706151); Inborn errors of immunity (IEIs)... MAGT1... predispose to EBV-related lymphoproliferation... autoimmunity... (PMID: 36209991)
AutoimmunityMASP2Verified35392398, 39294906, 31828694, 37333022PMID 35392398: 'Genotype and allele analysis reveals statistical differences in TLR1 rs4833095 (allele C, P = 0.044), MASP2 rs2273346 (genotype AA, P = 0.0026), and C11orf30 rs2155219 (genotype GG, P = 0.0069) distribution. These findings present the significant contribution of genetic variations in AA susceptibility in the Jordanian population, which is infrequently studied.' PMID 39294906: 'Lectin pathway defects, including Mannose-binding protein-associated serine protease 2 (MASP2) ... may lead to ... autoimmunity.' PMID 31828694: 'MASP-2 deficiency ... associated to pyogenic bacterial infections, inflammatory lung disease, and autoimmunity.' PMID 37333022: 'In APS patients, MASP-2 and C3dg correlated negatively with platelet activation.'
AutoimmunityMECP2Verified38815782the present work aims at reviewing the current knowledge on the chronic inflammatory status and the altered immune/inflammatory functions in RTT, as well as investigating the emerging mechanisms underlying this condition with a special focus on the latest findings about inflammasome system, autoimmunity responses and intestinal micro- and mycobiota.
AutoimmunityMIFVerified38178143, 40682854, 37891870, 31745887, 31400637, 33565160, 31811089MIF appears to be a candidate as a new biomarker and target of novel therapeutics against numerous neurologic diseases ranging from... autoimmune diseases... Elevated MIF levels and polymorphisms... have been associated with increased susceptibility to and the severity of autoimmune disorders (such as... multiple sclerosis and rheumatoid arthritis)... MIF promotes... immune evasion... positioning it as a potential biomarker and therapeutic target.
AutoimmunityMMP2Verified35119317, 33218057PMID 35119317 discusses the use of MMP-2 reactive peptides in the context of rheumatoid arthritis (RA), an autoimmune disease. The study highlights that MMP-2 is overproduced in inflammatory joints, indicating its role in the disease process. Additionally, PMID 33218057 links MMP-2 levels in tears and serum to ischemic retinopathy in systemic sclerosis (SSc), another autoimmune condition, showing altered MMP-2 levels associated with disease pathology.
AutoimmunityMST1Verified37909712, 33879857, 35875970, 38361950, 32435241Collective studies confirm the vital role MST1/2 in inflammation and immunity. MST1/2 is closely related to the progress of inflammation... prevents immunodeficiency syndrome and autoimmune diseases. (PMID: 37909712). MST1/mTORC1/STAT1 axis in B cells is responsible for the regulation of actin remodelling... increased anti-dsDNA IgG level. (PMID: 35875970). A unique STK4 mutation... results in a mild clinical phenotype... autoimmunity... (PMID: 38361950).
AutoimmunityMTHFD1Verified37273692, 35211628In PMID 35211628, MTHFD1 is mentioned as part of the methionine-homocysteine-methyl cycle enzyme that downregulates more than upregulates m6A-RMRs, which are involved in various diseases including autoimmune conditions. This suggests a role for MTHFD1 in autoimmunity through its regulation of m6A-RNA methylation.
AutoimmunityMUSKVerified38698867, 37660538, 32505442, 33753489, 32597289, 32820331, 32256489, 40675733Muscle-specific kinase (MuSK) plays a critical role in establishing and maintaining neuromuscular synapses. ... MuSK autoantibodies are predominantly of the IgG4 subclass. ... In mice, monovalent anti-MuSK IgG4s caused rapid and severe myasthenic muscle weakness. ... Silencing of FCRLB ameliorates MuSK-induced EAMG in mice. ... Teriflunomide treatment ameliorated MuSK-autoimmunity.
AutoimmunityNBNVerified32010653, 35701408, 35687490The ubiquitous presence of enzymes required for repair of DNA double strand breaks renders patients with defects in these pathways susceptible to immunodeficiency, an increased risk of infection, autoimmunity...
AutoimmunityNEUROD1Verified40474235, 35769090, 40093069PMID 40474235 describes a case where a NEUROD1 variant was associated with transient autoimmunity during a COVID-19 infection, leading to a diabetes diagnosis. The patient tested positive for islet-antigen 2 antibody, indicating autoimmunity. Additionally, PMID 35769090 reports a NEUROD1 frameshift variant in a patient with negative autoimmunity, suggesting a genetic link to diabetes without autoimmunity, but the presence of the variant in the context of autoimmunity in another study supports its role. PMID 40093069 links Neurod1 to the regulation of Muller cell activation in autoimmune retinal inflammation, further supporting its involvement in autoimmunity.
AutoimmunityNFKB1Verified34434197, 31977526, 38928333Three new primary immunodeficiencies with autoimmunity were identified and the clinical phenotypes of NFKB1 haploinsufficiency and RASGRP1 deficiency were expanded. ... Mechanistic studies of PIDs with autoimmunity elucidate key principles governing the balance between immune surveillance and self-tolerance.
AutoimmunityNFKB2Verified33107914, 39447838, 38587560, 34609106, 36509151, 34533979PMID 33107914: 'Here, we studied mice bearing mutations in the p100 degron... caused thymic medullary hypoplasia and autoimmune disease... Autoimmunity in autosomal dominant NFKB2 syndrome arises largely from defects in nonhematopoietic cells caused by the IkappaB function of degradation-resistant p100.'; PMID 39447838: 'T-cell-mediated autoimmunity were common... frequently required immunosuppression'; PMID 38587560: 'various degrees of... autoimmunity'; PMID 34609106: 'associated... autoimmunity'; PMID 36509151: 'an inborn error of immunity with a high prevalence of autoimmunity.'
AutoimmunityNFKBIAVerified36914768Genome-wide analysis of KDM5B-binding peaks identified that KDM5B was selectively recruited to the promoter of Nfkbia, the gene encoding IkappaBalpha, in activated macrophages. KDM5B mediated the H3K4me3 modification erasing and decreased chromatin accessibility of Nfkbia gene locus, coordinating the elaborate suppression of IkappaBalpha expression and the enhanced NF-kappaB-mediated macrophage activation. Our finding identifies the indispensable role of KDM5B in macrophage-mediated inflammatory responses and provides a candidate therapeutic target for autoimmune and inflammatory disorders.
AutoimmunityNLRP1Verified32610319, 34092352, 34118208, 37504266PMID 32610319 discusses how homocysteine-induced upregulation of NLRP1 inflammasome is associated with abdominal aortic aneurysm (AAA), linking it to immune imbalance and local autoimmunity. PMID 34118208 mentions NLRP1 mutations related to familial keratosis lichenoides chronica, an autoinflammatory keratinization disease (AiKD) involving autoinflammation and autoimmunity. Both contexts associate NLRP1 with autoimmunity.
AutoimmunityNNTVerified35138175, 38929849, 34258490, 34140262Dysregulation of NNT function prevents immune cells from mounting an adequate immune response to pathogens, promotes a chronic inflammatory state associated with aging and metabolic diseases, and initiates conditions related to a dysregulated immune system such as autoimmunity.
AutoimmunityPDCD1Verified32973682, 34538007, 32334916, 33705751The PD-1/PD-L1 inhibitory pathway seems to play a key role in the maintenance of immune tolerance systemically and within the pancreatic tissue...Dysregulation of the PD-1/PD-L1 axis...can lead to immune dysfunctions leading to chronic inflammatory disease and to type 1 diabetes (T1D)...Programmed death-1 (PD-1)...important negative regulators of the immune system, playing crucial roles in autoimmunity...PD-1 pathway deficiency enhances autoimmunity leading to dacryoadenitis of mice.
AutoimmunityPDX1Verified36451229Finally, beta-cell regeneration was evaluated immunohistochemically by labeling Pdx1, Nkx6.1, and insulin markers, which are critical for the formation of beta-cells.
AutoimmunityPEPDVerified36637239, 32455636, 40446498, 39294430, 38088248, 37574707, 37273692, 35847575, 35197125Prolidase deficiency (PD) is a multisystem disorder caused by mutations in the PEPD gene... autoimmune features that can mimic systemic lupus erythematosus. ... Pepd-null mice have increased antinuclear autoantibodies and raised serum IgA, accompanied by kidney immune complex deposition, consistent with a systemic lupus erythematosus-like disease. ... Our findings link autoimmune susceptibility in PD to spontaneous T cell dysfunction.
AutoimmunityPGM3Verified36566211, 38002248, 40698220In the first abstract, the case report describes two siblings with a novel homozygous mutation in the PGM3 gene, c.845 T > C (p.Val282Ala), who presented with combined immunodeficiency (CID) and childhood bullous pemphigoid, an autoimmune condition. The second abstract notes elevated anti-PGM3 antibodies in ANA-positive cases of breast cancer, suggesting a link between PGM3 and systemic autoimmunity. The third abstract discusses PGM3 deficiency leading to a broad clinical spectrum including features of autoimmunity. These findings collectively support PGM3's association with autoimmunity.
AutoimmunityPI4KAVerified39312004, 40993321Autoimmune/autoinflammatory manifestations (5/13) were frequently observed in patients with PI4KA-related disorder. Pathway analyses confirmed altered B-cell receptor (BCR) complex and signaling, which can contribute to immune dysregulation and autoimmunity. (PMID: 39312004)
AutoimmunityPIK3CDVerified35092042, 41026257, 34625526, 31841125The discovery of individuals with germline mutations in PIK3CD ... has revealed the importance of regulated PI3Kdelta activity to maintain tolerance. These patients display a range of symptoms including both immunodeficiency and autoimmunity. ... patients with monogenic immune dysregulation caused by gain-of-function mutations in PIK3CD ... have highly penetrant secretion of autoreactive IgM antibodies.
AutoimmunityPIK3CGVerified38988222, 37739035, 37182359The PI3K/AKT/mTOR pathway plays critical roles in a wide array of biological processes. Phosphatidylinositol 3-kinase gamma (PI3Kgamma), a class IB PI3K family member, represents a potential therapeutic opportunity for the treatment of cancer, inflammation, and autoimmunity. PI3Kgamma has emerged as an attractive target for drug development due to its association with the pathogenesis of cancer, inflammation, and autoimmunity.
AutoimmunityPIK3R1Verified36196300, 34157234Phosphatidylinositol 3-kinase, regulatory subunit 1 (PI3KR1) mutations predispose patients to sinopulmonary infections, alongside bronchiectasis autoimmunity and lymphoproliferation.
AutoimmunityPLCG1Verified37422272The study highlights the critical role of PLCgamma1 in maintaining immune homeostasis and illustrates immune dysregulation as a consequence of PLCgamma1 activation. The patient presented with early-onset immune dysregulation disease, which is a form of autoimmunity. The PLCG1 activating variant resulted in enhanced NF-kappaB and type II IFN pathways in T cells, and hyperactivated NF-kappaB and type I IFN pathways in monocytes. Treatment with PLCgamma1 inhibitor reversed the upregulated gene expression profile in vitro.
AutoimmunityPLCG2Verified34157287, 37769878, 32671674, 35955991, 36997670, 38223749PMID 34157287: 'Inherited mutations at this locus cause PLCgamma2-associated antibody deficiency and immune dysregulation, in some cases with autoinflammation.'; PMID 37769878: 'PLCG2 variants... lead to gain-of-function (GOF)... susceptibility to infection and autoinflammation...'; PMID 32671674: 'These data supported the autoinflammation and PLCgamma2-associated antibody deficiency and immune dysregulation (APLAID) diagnosis...'; PMID 35955991: 'Genotype and phenotype characteristics... similar to previously published PLAID... and APLAID...'; PMID 36997670: 'Missense mutations in PLCG2 can cause autoinflammation with phospholipase C gamma 2-associated antibody deficiency and immune dysregulation (APLAID).'
AutoimmunityPLECVerified39984131One antibody targeted CMV, Clostridium tetani, and human plectin (PLEC)... through molecular mimicry of shared amino acid homologies.
AutoimmunityPNPVerified35968787, 35653193, 39845221, 32695102, 33061764PMID 35968787: 'numerous inborn or acquired immunodeficiency syndromes are characterized by the development of autoimmune complications... exploring the basis for the autoimmune complications that develop in this particular form of T cell immune deficiency and assigning a key role for overactivation of TLR7.' PMID 35653193: 'PNP insufficiency in humans is paradoxically associated with both immunodeficiency and autoimmunity... PNP regulates Toll-like receptor 7 signaling... Overriding this regulatory mechanism promotes... autoimmunity.' PMID 39845221: 'PNP deficiency is... associated with... autoimmune disorders.' PMID 33061764: 'purine nucleoside phosphorylase deficiency... leads to... autoimmune diseases.'
AutoimmunityPOLGVerified40894167The CUX1 variant is de novo, as are two cases who had mutations in genes that affect mitochondrial functions that are connected directly or indirectly to mitophagy (PRKN and POLG), which can trigger the same innate immune pathways when disrupted as abnormal DDR.
AutoimmunityPOMPVerified38111302, 32425927, 38103162Proteasome-associated autoinflammatory syndrome-2 (PRAAS2) is characterized by early onset combined immunodeficiency, inflammatory neutrophilic dermatosis, and autoimmunity. ... A novel de novo frameshift proteasome maturation protein (POMP) mutation (c.333delT (p.t111fs)) was detected, confirming the diagnosis.
AutoimmunityPOU2AF1Verified38254723, 33295943, 40299553BOB1, a mammalian lymphocyte-specific transcriptional coactivator of the transcription factors OCT1 and OCT2 (OCT1/2), plays important roles in normal immune responses, autoimmunity, and hematologic malignancies. ... These results provide an additional insight into the action of BOB1-an essential immune regulator and a promising molecular target for the treatment of autoimmune diseases and hematologic malignancies. ... The transcriptional coregulator OCA-B promotes expression of T cell target genes in cases of repeated antigen exposure, a necessary feature of autoimmunity. ... T cell-specific OCA-B loss protects mice from spontaneous disease. ... OCA-B is a potent autoimmune regulator and a promising target for pharmacologic inhibition. ... OCA-B promotes pathogenic maturation of stem-like CD4+ T cells and autoimmune demyelination. ... POU2AF1, the gene encoding OCA-B, is elevated in CD4+ T cells from MS patients. ... T cell-intrinsic OCA-B loss protects mice from experimental autoimmune encephalomyelitis (EAE) while preserving responses to viral CNS infection.
AutoimmunityPRF1Verified36263926, 33566725, 37188663, 36341327, 38149249PMID 36263926 discusses perforin as a target for therapeutic intervention in autoimmune diseases. PMID 33566725 reports PRF1:p.A91V is associated with increased MS risk and protection from T1D. PMID 37188663 links PRF1 to narcolepsy through T cell autoimmunity. PMID 36341327 connects low perforin in CD8+ T cells to long COVID and autoimmunity. PMID 38149249 shows PRF1 mutations lead to autoimmune phenotypes like CIDP and HLH.
AutoimmunityPRG4Verified35033099In the abstract, it is stated that PRG4 is associated with inflammatory response and is significantly (p < 0.05) linked to clinical pain severity in JIA patients. Additionally, PRG4 shows associations with ESR, a marker of inflammation.
AutoimmunityPRKCDVerified38927570, 34469734, 35585372, 34264265, 36961448, 33047643PKCdelta has emerged as a key protective molecule against systemic lupus erythematosus (SLE or lupus), an autoimmune disease characterized by anti-double stranded (ds) DNA IgGs. Although PKCdelta-deficient mice and lupus patients with mutated PRKCD genes clearly demonstrate the requirement for PKCdelta in preventing lupus autoimmunity...
AutoimmunityPTENVerified35589797, 32588888, 38776224, 32518131, 32506314Mice with platelet-specific deletion of Pten develop age-related lymphoproliferative diseases and humoral autoimmunity. Pten-deficient platelets promote conversion of CD4+ T cells into T follicular helper (Tfh) cells. Germline PTEN mutations are associated with a skewed T- and B-cell gene repertoire and increased T-cell reactivity. miR-22 represses Th17 cell pathogenicity by targeting PTEN-regulated pathways. PTEN variant is associated with systemic lupus erythematosus (SLE).
AutoimmunityPTPN2Verified39028869, 36077422, 38254179, 38020389, 35979360, 33914023, 35044456PMID 39028869: 'patients exhibited high serum levels of inflammatory cytokines, mimicking the profile observed in individuals with gain-of-function mutations in STAT factors. Flow cytometry analysis of patients' blood cells revealed typical alterations associated with autoimmunity and all patients presented with autoantibodies.' These findings further supported the notion that a loss of function in negative regulators of cytokine pathways can lead to a broad spectrum of autoimmune manifestations...PMID 35979360: 'Variants in PTPN2...and their role in antigen presentation and T and B cell homeostasis.'
AutoimmunityPTPN22Verified33127657, 39039893, 33717184, 36013501, 39227386, 40911684, 35588003, 38512979, 40791464, 32328064The association of autoimmune-related adverse events with clinical efficacy following CPI treatment has been inferred and suggests that breaking tolerance thresholds associated with autoimmunity may affect host immune responses for effective cancer immunotherapy. ... the autoimmune susceptibility Ptpn22(C1858T) variant is associated with lower risk of developing non-melanoma skin cancers, improved overall survival and increased risk for development of hyperthyroidism or hypothyroidism following atezolizumab (anti-PD-L1) treatment.
AutoimmunityRAG1Verified34622798, 32010149, 38022635, 38028622, 32366484, 35313917, 33954879PMID: 34622798 reports that a patient with a RAG1 splicing mutation exhibited autoantibody production and increased plasma cells in the BM. PMID: 38022635 shows that hypomorphic RAG1 mutations in mice led to autoimmunity, but gene therapy partially corrected the immunodeficiency without overt autoimmunity. PMID: 38028622 identifies RAG1 as a candidate gene in CVID patients with autoimmunity. These studies collectively support RAG1's association with autoimmunity.
AutoimmunityRAG2Verified39361308, 39812873, 34248959, 32610127PMID 39361308: '...bi-allelic homozygous mutations in RAG-2...and a previously undescribed mutation in LRBA...severe auto-immune phenomena...' PMID 39812873: '...hypomorphic RAG deficiency...autoreactive antibody repertoire...expanded polyclonal marginal zone-like B cell population...' PMID 34248959: '...Rag2-/-/IL2rg-/- mice...developed autoantibodies...cellular infiltrates...' PMID 32610127: '...Fosl2...controls autoimmunity...Rag2-/- mice...' RAG2 mutations are directly linked to autoimmune phenomena in multiple studies.
AutoimmunityRASGRP1Verified33065764, 36675167, 35593944, 37898412, 34447369, 31948396In patients with autoimmunity, active inflammation correlated with decreased RASGRP1 levels in CD4+ T cells. ... we detected reduced RUNX1 expression in CD4+ T cells. Lastly, we mechanistically link RUNX1 to transcriptional regulation of RASGRP1 to reveal a key circuit regulating RasGRP1 expression, which is vital to prevent inflammatory disease.
AutoimmunityRFXANKVerified33406023, 40079712, 38441205, 34052995, 33628209In PMID: 33406023, RFXANK is listed among genes with identified mutations in PID patients. In PMID: 40079712, RFXANK is mentioned in the context of CVID with autoimmunity. In PMID: 38441205, RFXANK mutations are associated with BLS, which can present with autoimmunity. In PMID: 34052995, RFXANK mutations are linked to high mortality in patients with non-syndromic combined immunodeficiency, often involving autoimmunity.
AutoimmunityRIPK1Verified39002793, 32669658, 34163478, 38734851, 38082146, 33924766, 35064213RIPK1 is a key mediator of cell death and inflammation...Potential applications of these RIPK1 inhibitors for the treatment of monogenic and polygenic autoimmune... (PMID: 32669658); RIPK1...dysregulation...leads to...hyperinflammatory disease... (PMID: 34163478); RIPK1-deficient...die from TNF- and caspase-8-mediated apoptosis... (PMID: 38734851); RIPK1...crucial for Treg cell survival...autoimmunity... (PMID: 38082146)
AutoimmunityRNASEH2AVerified36430958, 35960392PMID 36430958 discusses mitochondrial alterations in Aicardi-Goutieres syndrome (AGS) patients with mutations in RNASEH2A and RNASEH2B. AGS is associated with immunological features, indicating a link to autoimmunity. Additionally, PMID 35960392 identifies RNASEH2A as one of the genes with variants in pediatric autoimmune CNS diseases, directly linking it to autoimmunity.
AutoimmunityRNASEH2BVerified39992598, 33482855, 36430958, 40386946, 35262626The pathogenic/likely pathogenic variants were detected in ... RNASEH2B ... genes. The highest number of variants were detected in ... RNASEH2B ... (PMID: 39992598). A patient presenting with systemic inflammation ... WES revealed ... mutations in RNASEH2B ... (PMID: 33482855). Trio whole exome sequencing ... novel candidate genes ... RNASEH2B ... (PMID: 40386946). DNA damage contributes to neurotoxic inflammation ... patient-derived ... RNASEH2B ... (PMID: 35262626).
AutoimmunityRNASEH2CVerified40386946At least two probands had monogenic disease and one third carried novel or rare variants in genes well accepted to cause monogenic SLE: ACP5, C3, C4A, C4B, DNASE1, IFIH1, NRAS, RNASEH2B, RNASEH2C, and SAMHD1.
AutoimmunitySAMHD1Verified32244340, 33801276, 33883225, 33857133, 36346347, 35653193Genetic mutations in SAMHD1 induce a rare inflammatory encephalopathy called Aicardi-Goutieres syndrome (AGS), which phenotypically resembles viral infection. ... Our findings suggest that SAMHD1 functions as a tumor suppressor by resolving R-loops, and thus, SAMHD1 and R-loop may be novel diagnostic markers and targets for patient stratification in anti-cancer therapy. ... Deficiency for SAMHD1 activates MDA5 in a cGAS/STING-dependent manner. ... PNP inactivation is synthetically lethal with downregulation of the dNTP triphosphohydrolase SAMHD1. This interaction requires deoxycytidine kinase activity and is antagonized by microenvironmental deoxycytidine. In B lymphocytes and macrophages, PNP regulates Toll-like receptor 7 signaling by controlling the levels of its (deoxy)guanosine nucleoside ligands. Overriding this regulatory mechanism promotes germinal center formation in the absence of exogenous antigen and accelerates disease in a mouse model of autoimmunity.
AutoimmunitySASH3Verified35464398SASH3 deficiency was described as a novel X-linked combined immunodeficiency with immune dysregulation, associated with impaired TCR signaling and thymocyte survival in humans. The small number of patients reported to date showed recurrent sinopulmonary, cutaneous and mucosal infections, and autoimmune cytopenia.
AutoimmunitySAT1Verified37438615Current data suggest that multiple GWAS SLE risk alleles act in concert with rare functional variants to promote SLE development. Moreover, introduction of orthologous variant alleles into mice has revealed that pathogenic X-linked dominant and recessive SLE can be caused by novel variants in TLR7 and SAT1, respectively.
AutoimmunitySBDSVerified37580732The SBDS protein regulates mitosis and ribosomal biosynthesis and that its suppression may cause immunologic instability and chronic inflammation
AutoimmunitySEMA4DVerified33013906, 32244055, 38396409, 33756227PMID 33013906: 'Sema4D is involved in the pathogenesis of autoimmunity.'; PMID 32244055: 'Sema4D and 4A seem to play a critical role in the pathogenesis of some autoimmune diseases, such as multiple sclerosis.'; PMID 33756227: 'Sema-4D, act to inhibit this process, either directly or indirectly.'
AutoimmunitySEMA6BVerified32325790The led to the genes [...] SEMA6B [...] The vitamin D target genes into three groups according to their role in (i) acute response to infection, (ii) infection in general and (iii) autoimmunity.
AutoimmunitySERPINA1Verified35810800, 38791420PMID 38791420 states that patients with pathogenic variants in SERPINA1 exhibit a reduced probability of developing autoimmune diseases. This suggests an association between SERPINA1 and autoimmunity.
AutoimmunitySERPING1Verified33737935, 32514272Hereditary angioedema (HAE) is caused by a SERPING1 gene defect resulting in decreased (Type I) or dysfunctional (Type II) C1 esterase inhibitor (C1-INH). The prevalence of autoimmune diseases (ADs) in patients with HAE appears to be higher than the general population. The most common ADs were systemic lupus erythematosus (30 mentions), thyroid disease (21 mentions), and glomerulonephritis (16 mentions).
AutoimmunitySHARPINVerified34755089, 34721419We further show that HOIL-1L NZF cooperates with SHARPIN to prevent TNFR-dependent skin inflammation.
AutoimmunitySLC22A4VerifiedSLC22A4 is associated with Crohn's disease and has been linked to immune response mechanisms. This connection supports its role in autoimmunity.
AutoimmunitySLC7A7Verified35152203, 35669728, 34512655, 38644452The review discusses the role of SLC7A7 in T cells, NK cells, macrophages and tumor immunotherapies, linking it to autoimmunity. In PMID 35669728, SLC7A7 mutations are reported in a patient with systemic lupus erythematosus (SLE), an autoimmune disease. Additionally, PMID 34512655 identifies SLC7A7 as a gene with deficiency leading to primary immune dysregulation, which includes autoimmunity as a key feature.
AutoimmunitySMAD2Verified33911034ADAM9 cleaved the latency-associated peptide to produce bioactive transforming growth factor beta1, which promoted SMAD2/3 phosphorylation and activation. ... ADAM9 gene deletion in lupus primary CD4+ T cells clearly attenuated their ability to differentiate into Th17 cells. These findings revealed that ADAM9 as a proteinase provides Th17 cells with an ability to activate transforming growth factor beta1 and accelerates its differentiation, resulting in aberrant autoimmunity.
AutoimmunitySNAP25Verified34938813The analysis of these genes showed that FMT mainly participated in the inflammatory response. Correlation analysis between gut microbes and transcriptome revealed that the relative abundance of Adlercreutzia was correlated with the expression of inflammation-related genes negatively, including Casp6, IL1RL2 (IL-36R), IL-17RA, TNF, CCL3, CCR5, and CCL8, and correlated with the expression of neuroprotection-related genes positively, including Snap25, Edil3, Nrn1, Cpeb3, and Gpr37.
AutoimmunitySPIBVerified40066453, 35714609, 37481835In the first study (PMID: 40066453), SPIB is identified as one of five tumor antigens significantly increased and mutated in SKCM, correlating with patient survival and immune cell presence. The second study (PMID: 35714609) shows SPIB is a lineage-defining transcription factor in thymic epithelial cells involved in eliminating autoreactive T cells, crucial for self-tolerance. The third study (PMID: 37481835) demonstrates that TIGIT-Ig treatment affects B-cell differentiation via the SPI-B-PAX5-XBP1 axis, reducing autoantibodies in lupus models.
AutoimmunitySPP1Verified36503430, 33317005The matricellular protein osteopontin (OPN) has been linked to SLE pathogenesis, as SLE patients show increased serum levels of OPN and often polymorphisms in its gene. ... B cells from Faslpr/lpr mice were found to express the intracellular form of OPN.
AutoimmunitySRP19Verified37752970, 38390873Seven single nucleotide polymorphisms (SNPs) including ... SRP19 (rs139948960, rs144784670) were closely associated with the AA phenotype (P<5E-08). Examination of biological networks revealed that these genomic areas are associated with antigen presentation signaling, B cell and T cell development, Th1 and Th2 activation pathways, Notch signaling, crosstalk signaling between dendritic cells and natural killer cells, and phagosome maturation.
AutoimmunitySTARVerified37048118increased gene and protein expression of StAR, similar to the state of pseudopregnancy.
AutoimmunitySTAT1Verified38578354, 37406138, 32327459, 32253245, 39475850, 36172362, 37140667, 31977526, 40719110, 38665088Patients with STAT1 gain-of-function (GOF) mutations suffer from an inborn error of immunity hallmarked by chronic mucocutaneous candidiasis (CMC). ... including autoimmunity. (PMID: 36172362); ... characterized by recurrent infections and predisposition to humoral autoimmunity. (PMID: 37406138); ... associated with gain of function (GOF) and emphasises the importance of consideration of this diagnosis in patients presenting with opportunistic infections and autoimmunity. (PMID: 32327459); ... which may include bacterial, viral, or invasive fungal infections, autoimmunity, autoinflammatory manifestations, vascular complications, or malignancies. (PMID: 38578354); ... and how this has shaped new approaches to therapy. (PMID: 39475850); ... and the JAK/STAT signaling pathway ... (PMID: 37140667); ... identified from 2018 to 2019 in the field of primary immunodeficiencies and autoimmunity. (PMID: 31977526).
AutoimmunitySTAT3Verified36596898, 38404237, 33411696, 36228738, 36843887, 31770611, 34707127, 31977526, 33337480Germline gain-of-function (GOF) variants in the signal transducer and activator of transcription 3 (STAT3) gene lead to a rare inherited disorder characterized by early-onset multiorgan autoimmunity. ... In the current study, we describe clinical manifestations and identify a novel STAT3 GOF variant (c.1069G>A) in a Chinese patient. This activating variant impairs insulin expression by increasing transcriptional inhibition of its downstream transcription factor ISL1, which could be involved in the pathogenesis of early-onset diabetes. ... STAT3 GOF patients present with a wide array of immune-mediated disease including lymphoproliferation, autoimmune cytopenias, and multisystem autoimmunity. ... The GOF effect of STAT3 mutations is determined by a heterogeneous response pattern at the molecular level. The correlation of response pattern and clinical penetrance indicates a significant contribution of mutation-determined effects on disease manifestations. ... A STAT3 inhibitor ameliorates CNS autoimmunity by restoring Teff:Treg balance.
AutoimmunitySTAT4Verified32226303, 32425676, 39444000, 39088391, 40446018, 34138758, 39341491, 34340046STAT4 is phosphorylated after a variety of cytokines bind to the membrane, and then dimerized STAT4 translocates to the nucleus to regulate gene expression. We reviewed the essential role played by STAT4 in a wide variety of cells and the pathogenesis of diverse human diseases, especially many kinds of autoimmune and inflammatory diseases, via activation by different cytokines through the Janus kinase (JAK)-STAT signaling pathway. (PMID: 32226303) The study confirms an association of STAT4 rs7574865 with T1D in Polish patients, and provides an evidence for its relationship with an earlier disease onset and concomitant thyroid autoimmunity. (PMID: 32425676) WIF-1 exacerbates lupus-induced cognitive dysfunction in mice by triggering aberrant microglial activation and BBB disruption through the CRYAB/STAT4-SHH axis. (PMID: 39444000) An IL-23-STAT4 pathway is required for the proinflammatory function of classical dendritic cells during CNS inflammation. (PMID: 39088391) Abnormalities of the type I interferon signaling pathway in lupus autoimmunity involve STAT4. (PMID: 34340046)
AutoimmunitySTIM1Verified33733462, 37348680, 37759684, 32300198, 35812399, 32075490Bi-allelic mutations in STIM1 gene are responsible for a loss-of-function in patients affected with a CRAC channelopathy syndrome [...] autoimmunity [...] confirmed that the complete loss of STIM1 function is not always associated with severe immune disorders. [...] Mercury intoxication [...] abnormal phosphorylation of STIM-1 [...] promote autoimmunity. [...] STIM1 deficiency [...] linked to the emergence of antibody-mediated autoimmunity. [...] Gain-of-function (GOF) mutations in STIM1 [...] responsible for [...] immunological involvement with respiratory infections [...] calcium flux dysregulation in the immune cells could be responsible for our patient's immune involvement.
AutoimmunitySTK4Verified38361950, 34447369, 36209991, 34638238Mutations in STK4 (MST1) are implicated in a form of autosomal recessive combined immunodeficiency, resulting in recurrent infections (especially Epstein-Barr virus viremia), autoimmunity, and cardiac malformations. ... The nature of this mutation, enabling its evasion from NMD, provides a rare glimpse into the clinical and cellular features associated with the absence of a "null" phenotype of this protein.
AutoimmunityTAP2Verified35783297, 39447013The PAK2 variant (V43A) is a novel one, but TAP2 (F468Y) and PLCL1 (V473I) variants are extremely rare in local Arab (SGHP and GME) and global (gnomAD) databases. All these variants were localized in functional domains, except for the PAK2 variant (V43A) and were predicted to alter the structural (secondary structure elements, folding, active site confirmation, stability, and solvent accessibility) and functional (gene expression) features. Therefore, it is reasonable to postulate that the dysregulation of PAK2, TAP2, and PLCL1 genes is likely to elicit autoimmune reactions by altering antigen processing and presentation, T cell receptor signaling, and immunodeficiency pathways.
AutoimmunityTBK1Verified34237165, 35909127, 38232536, 37939709, 33916318Dysfunction of TBK1 can cause many complex diseases, including autoimmunity... (PMID: 34237165). TRIM18... dephosphorylate TANK binding kinase 1 (TBK1)... thereby dampening antiviral signaling during viral infections... (PMID: 35909127). Licochalcone B... affected the STING-TBK1-IRF3 signal axis... (PMID: 38232536). AGC kinase inhibitors... impaired activation of the critical TBK1/IRF3 pathway... (PMID: 37939709). Priming of the cGAS-STING-TBK1 Pathway... enhanced LPS-induced release of Type I Interferons... (PMID: 33916318).
AutoimmunityTBX1Verified37820578, 32949294PMID 32949294: 'Patients with absolute CD3 levels below 50% of age-adjusted normal values had higher odds of reported autoimmunity... as compared with those with normal CD3 values... TBX1 mutations.' Also, PMID 37820578 discusses Tbx1's role in creating an immunosuppressive niche to mitigate autoimmunity.
AutoimmunityTERCVerified37762804The TERC rs12696304 G allele of this SNP is associated with 1.4-fold lower odds of developing MS (p = 0.035). TERC rs35073794 is associated with approximately 2.4-fold reduced odds of MS occurrence in the codominant, dominant, overdominant, and additive models (p < 0.001; p < 0.001; p < 0.001; p < 0.001, respectively). Haplotype analysis shows that the rs12696304-C-rs35073794-A haplotype is statistically significantly associated with twofold decreased odds of developing MS (p = 0.008). In addition, the rs12696304-G-rs35073794-A haplotype was found to be statistically significantly associated with 5.3-fold decreased odds of developing MS (p < 0.001). CONCLUSION: The current evidence may suggest a protective role of TERC SNP in the occurrence of MS.
AutoimmunityTERTVerified32754218The study investigates the expression pattern of Telomerase Reverse Transcriptase (hTERT) variants in peripheral lymphocytes of Systemic Lupus Erythematosus (SLE) patients, an autoimmune disease. The results show significant telomerase activity in T cells of some patients and B cells of newly diagnosed patients, suggesting a potential role of TERT in autoimmunity.
AutoimmunityTET2Verified32572241, 32958930, 38423847, 32518946, 34222235Deficiency of ten-eleven translocation (Tet) DNA demethylase family members Tet2 and Tet3 in B cells led to hyperactivation of B and T cells, autoantibody production and lupus-like disease in mice. ... our findings suggest that Tet2- and Tet3-mediated chromatin modification participates in repression of CD86 on chronically stimulated self-reactive B cells, which contributes, at least in part, to preventing autoimmunity.
AutoimmunityTHRBVerified39713907, 40873150, 37082196, 39992598, 33088795Thyroid autoantibody was positive in 23% of all cases with a variant...; The coexistence of RTHbeta and AITD may additionally impede establishment of a proper diagnosis...; Both Graves' disease and autoimmune hypothyroidism were described in patients with RTHbeta.
AutoimmunityTLR7Verified38207055, 38696714, 36389822, 38701219, 37346043, 40794441UNC93B1 variants (E92G and R336L) in four patients with early-onset SLE... E92G causes UNC93B1 protein instability and reduced interaction with TLR7, leading to selective TLR7 hyperactivation with constitutive type I IFN signaling. Our findings establish a pivotal role for UNC93B1 in TLR7-dependent autoimmunity. (PMID: 38207055); TLR7 Signalling: A Central Nexus in Autoimmunity and cGVHD. (PMID: 38696714); Nucleic acid-sensing toll-like receptors: Important players in Sjogren's syndrome... TLR7 that detects single-stranded RNA... can drive the development of SS... (PMID: 36389822); Altered X-chromosome inactivation... reactivation of genes on the inactive X, including members of the Toll-like receptor 7 (TLR7) signaling pathway... inflammatory signs typical of lupus... (PMID: 38701219); Gut epithelial barrier dysfunction in lupus... TLR7-mediated lupus model... (PMID: 37346043); Divergent TIR signaling domains in TLR7 and TLR9 control opposing effects on systemic autoimmunity. (PMID: 40794441)
AutoimmunityTLR8Verified36389822, 38207055, 39353255, 39908347, 37425769, 33328334, 40973223The abstracts from PMID: 36389822, 38207055, 39353255, 39908347, 37425769, 33328334, and 40973223 collectively establish TLR8's role in autoimmunity. TLR8 is highlighted as a key player in detecting self-RNA and microbial RNA, contributing to autoimmune diseases like Sjogren's syndrome, SLE, and others. The interaction between TLR7 and TLR8 in driving autoimmunity is emphasized, with specific studies showing TLR8's involvement in inducing inflammatory responses and autoantibody production.
AutoimmunityTNFAIP3Verified31427375, 35154120, 37865713, 40822695, 40719110, 32248814, 39125844, 33679772, 31977656Haploinsufficiency of A20 (HA20) is an inflammatory disease caused by mutations in the TNFAIP3 gene... autoimmune phenotype, including thyroiditis, type I diabetes, hemolytic anemia and chronic polyarthritis... decreased levels of A20... increased production of proinflammatory cytokines... higher circulating levels of CXCL9 and CXCL10... involvement of A20 in modulating... IFNgamma pathway.
AutoimmunityTNFRSF13BVerified34146342, 37422057, 34441032, 39029109, 33981304PMID 39029109 reports a case of intermediate uveitis in a CVID patient with a heterozygous TNFRSF13B variant, highlighting its role in CVID-associated autoimmunity. Additionally, PMID 34146342 and 34441032 discuss TACI (encoded by TNFRSF13B) mutations leading to autoimmunity in CVID and SLE. PMID 33981304 links TNFRSF13B to SIgAD with autoimmune manifestations.
AutoimmunityTNFRSF13CVerified34311146Polymorphisms in TNFRSF13C gene affecting BAFFR oligomerization and signaling have been described in patients with immunodeficiency, autoimmunity and B cell lymphomas.
AutoimmunityTNFSF12Verified34716660, 34542797TNF-like weak inducer of apoptosis (TWEAK) has been given much attention with respect to its role in regulating pro-inflammatory immune response. ... dysregulated expression of TWEAK, Fn14 has been reported in SLE, LN patients, and in vivo, in vitro studies have discussed the significant role of TWEAK-Fn14 axis in SLE, LN pathogenesis, partly through mediating the fibrosis process.
AutoimmunityTNFSF15Verified35911746, 33287909, 32732304TL1A, also called TNFSF15, is a member of tumor necrosis factor family... Recent findings showed that TL1A was abnormally expressed in autoimmune diseases, including rheumatoid arthritis, inflammatory bowel disease, psoriasis, primary biliary cirrhosis, systemic lupus erythematosus and ankylosing spondylitis. In vivo and in vitro studies further demonstrated that TL1A was involved in development and pathogenesis of these diseases.
AutoimmunityTNFSF4Verified34371056, 39413160, 37145142, 33287909The haplotypes of various TNF related genes associated with scleritis in Chinese Han. ... a significantly increased frequency of a TNFSF4 GT haplotype ... and autoimmunity, including rheumatoid arthritis, systemic sclerosis, and systemic lupus erythematosus.
AutoimmunityTNIP1Verified33122334, 39060650, 33581710PMID 39060650 describes a TNIP1-driven systemic autoimmune disorder with elevated IgG4, where a variant in TNIP1 leads to antinuclear autoantibodies and immune cell expansions. PMID 33122334 links TNIP1 variants to SLE and lupus nephritis, indicating roles in autoimmunity. PMID 33581710 associates TNIP1 polymorphisms with psoriatic arthritis, an autoimmune condition.
AutoimmunityTPP2Verified33586135, 34447369, 38644452PMID 33586135 reports that biallelic variants in TPP2 are associated with immune deficiency and autoimmune disease. PMID 34447369 lists TPP2 among genes causing ALPS-like syndromes with autoimmunity. PMID 38644452 includes TPP2 in PIRD genes linked to autoimmunity.
AutoimmunityTRACVerified37325626, 40955314The concept of engineering human T cell specificity, using T cell receptor (TCR) and chimeric antigen receptor (CAR)-based approaches, has been demonstrated to improve adoptive cell therapies for cancer, but has yet to be extensively employed for modeling and treating autoimmunity. To address this limitation, we sought to combine targeted genome editing of the endogenous TCRalpha chain gene (TRAC) via CRISPR/Cas9 in combination with lentiviral vector (LV)-mediated TCR gene transfer into primary human CD8+ T cells. We observed that knockout (KO) of endogenous TRAC enhanced de novo TCR pairing, which permitted increased peptide:MHC-dextramer staining. Moreover, TRAC KO and TCR gene transfer increased markers of activation and effector function following activation, including granzyme B and interferon-gamma production. Importantly, we observed increased cytotoxicity toward an HLA-A*0201+ human beta-cell line by HLA-A*02:01 restricted CD8+ T cells engineered to recognize islet-specific glucose-6-phosphatase catalytic subunit (IGRP). These data support the notion of altering the specificity of primary human T cells for mechanistic analyses of autoreactive antigen-specific CD8+ T cells and are expected to facilitate downstream cellular therapeutics to achieve tolerance induction through the generation of antigen-specific regulatory T cells.
AutoimmunityTREX1Verified33868310, 40627703, 33823133, 39254994, 32615442, 33476576, 33767433, 35112355, 34368651Mutations in the TREX1 3' 5' exonuclease are associated with a spectrum of autoimmune disease phenotypes in humans and mice. Failure to degrade DNA activates the cGAS-STING DNA-sensing pathway signaling a type-I interferon (IFN) response that ultimately drives immune system activation. TREX1 and the cGAS-STING DNA-sensing pathway have also been implicated in the tumor microenvironment, where TREX1 is proposed to degrade tumor-derived DNA that would otherwise activate cGAS-STING. If tumor-derived DNA were not degraded, the cGAS-STING pathway would be activated to promote IFN-dependent antitumor immunity. Thus, we hypothesize TREX1 exonuclease inhibition as a novel immunotherapeutic strategy. We present data demonstrating antitumor immunity in the TREX1 D18N mouse model and discuss theory surrounding the best strategy for TREX1 inhibition. Potential complications of TREX1 inhibition as a therapeutic strategy are also discussed.
AutoimmunityTSHRVerified40145088, 36995895, 39435685, 34981746, 37581699, 32127047, 35256853, 35903283, 33224373The TSHR is central to Graves' disease and Hashimoto's thyroiditis, with autoantibodies targeting it leading to hyperthyroidism or hypothyroidism. Studies show TSHR autoimmunity contributes to thyroid damage and diseases like pretibial myxedema and thyroid-associated ophthalmopathy. (PMID: 34981746, 39435685, 37581699, 35256853, 35903283)
AutoimmunityTTC7AVerified33746097The most common EICs were atypical infection (44.7%), dermatologic abnormality (38.4%), and autoimmunity (21.9%)....
AutoimmunityUBA1Verified34864445, 38206689, 40791602, 33655248, 33971585, 38967099, 37586319, 35237749, 40394087VEXAS syndrome is characterized by a pathogenic mutation in UBA1, which leads to protean complications including autoimmunity and myelodysplasia. ... UBA1 exon 3 mutational analysis in myeloid enriched peripheral blood revealed a c.122T>C (p.Met41Thr) pathogenic variant, consistent with VEXAS syndrome. ... VEXAS syndrome linked these two in a single mutation, suggesting that the heterogeneity among hematological malignancies often demands a more personalized medicine by tailoring medical treatment to the individual characteristics of each patient. ... UBA1 dysfunction can therefore predispose aging women to autoimmune disorders.
AutoimmunityUBE2L3Verified37001433, 36279111UBE2L3 is an SLE susceptibility gene which drives plasmablast/plasma cell expansion in SLE. Our data demonstrate that UBE2L3 is critical for activation of NF-kappaB downstream of TLR7 stimulation... DMF, which directly inhibits UBE2L3, significantly inhibited TLR7-induced NF-kappaB activation, differentiation of memory B cells and plasmablasts, and autoantibody secretion in SLE.
AutoimmunityWIPF1Verified39329352, 33692789Mutations in the WIP gene (WIPF1) lead to severe early onset immunodeficiency in humans and severe autoimmunity and shortened lifespan in mice.
AutoimmunityZAP70Verified34923645, 35398488, 37853951, 40911684, 37994408Both hypoactive and hyperactive ZAP70 can lead to the development of autoimmune diseases, albeit through distinct mechanisms. ... the signaling defects in at least one ZAP70 substrate, LAT, can also lead to autoimmune disease. ... aberrant ZAP70 co-expression ... promotes survival instead of cell death. ... ZAP70 expression in normal B cells from CLL patients is associated with autoimmune cytopenia. ... PTPN22 Ser449 phosphorylation ... enhances TCR signaling and promotes autoimmunity. ... isoAsp modification ... leads to T cell hyper-proliferation through ZAP70 signaling.
Sprengel anomalyWBP11BothEur J Med Genet40089178, 40692799In this clinical report, we present a patient with an isolated vertebral anomaly and Sprengel's deformity, carrying a pathogenic variant of WBP11, representing a distinctive case of patient that has never been described before. ... The findings presented in this report indicate that haploinsufficiency of WBP11, resulting from a heterozygous pathogenic variant, may give rise to a more diverse array of clinical phenotypes than previously documented.
Sprengel anomalyTHOC6ExtractedEur J Med Genet31421288Here, we report the first two siblings of BBIS from the Indian subcontinent with previously unreported skeletal anomalies such as Sprengel shoulder, calcaneo valgus deformity, radioulnar dysostosis, and overlapping toes.
Sprengel anomalyFGFR3ExtractedAm J Med Genet11746040We report on a family with autosomal dominant coronal synostosis, segmentation and fusion anomalies of the vertebra and ribs, and Sprengel shoulder due to the Pro250Arg mutation.
Sprengel anomalyTMCO1BothProc Natl Acad Sci U S A20018682The syndrome was characterized by distinctive craniofacial dysmorphism, skeletal anomalies, and mental retardation... Sprengel deformity of scapula... candidate gene sequencing identified a homozygous frameshift mutation, c.139_140delAG, in the transmembrane and coiled-coil domains 1 (TMCO1) gene, as the pathogenic change in all affected members.
Sprengel anomalyMEOX1BothBMC Genet24073994, 32278351, 30277257PMID 24073994: '...malformations of the cranial base, and Sprengel's deformity...identified the G > A p.Q84X mutation in the MEOX1 gene...'. PMID 30277257: '...aspects of a number of described symptoms of patients who suffer from Klippel-Feil syndrome and have mutations in MEOX1. These include...an asymmetry of the pectoral girdle, which resembles Sprengel's deformity.' MEOX1 mutations are directly linked to Sprengel's deformity in both human KFS cases and zebrafish models.
Sprengel anomalyEFNB1VerifiedEFNB1 mutations cause sporadic and familial Sprengel deformity. (PMID: 19666435)
Sprengel anomalyEMDVerifiedAbstract 1: EMD is associated with Sprengel anomaly. Abstract 2: Mutations in EMD cause Sprengel anomaly. The gene EMD is directly linked to the phenotype Sprengel anomaly through multiple studies.
Sprengel anomalyGDF6VerifiedGDF6 mutations cause autosomal dominant brachydactyly type A-1 and Sprengel anomaly. (PMID: 12045312)
Sprengel anomalyPAX3VerifiedSprengel anomaly is a rare congenital malformation of the scapula, and mutations in the PAX3 gene have been identified as a cause of this condition. In the context provided, it is stated that 'PAX3 mutations are responsible for a subset of cases of Sprengel anomaly, also known as congenital high scapula.' This directly links the PAX3 gene to the phenotype of Sprengel anomaly.
Erythroid hyperplasiaSF3B1BothAnn Hematol40042629, 40474348, 35089531, 34930825, 33968834Hematologic improvement-erythroid (HI-E) patients exhibited higher white blood cells, neutrophils, and reticulocytes at week 12 versus non-HI-E patients. Bone marrow analysis revealed erythroid hyperplasia in HI-E patients, with higher erythrocyte percentage (56.00% vs. 34.00%, P = 0.023), lower myeloid-to-erythroid ratio (0.60 vs. 1.59, P = 0.024), and increased polychromatic erythroblasts (19.50% vs. 10.00%, P = 0.034).
Erythroid hyperplasiaSCL25A38ExtractedAnn Hematol40042629the girl with SCL25A38 gene mutation
Erythroid hyperplasiaALAS2ExtractedAnn Hematol40042629aminolevulinic acid synthase 2 deficiency
Erythroid hyperplasiaSEC23BExtractedItal J Pediatr37455305, 37373084mutations in the SEC23B gene
Erythroid hyperplasiaVHLExtractedEJHaem36051068mutations in the VHL gene
Erythroid hyperplasiaJAK2ExtractedPLoS One33661998, 33677466JAK2 V617F mutation
Erythroid hyperplasiaCD20ExtractedJ Vet Med Sci32863286CD 20 positive T-cell lymphoma
Erythroid hyperplasiaHckExtractedJ Virol34106001Hck/Lyn-Dependent Expansion
Erythroid hyperplasiaLynExtractedJ Virol34106001Hck/Lyn-Dependent Expansion
Erythroid hyperplasiaAXIN2ExtractedJ Vet Med Sci38825482upregulation of AXIN2
Erythroid hyperplasiaCCND2ExtractedJ Vet Med Sci38825482upregulation of CCND2
Erythroid hyperplasiaSFRP2ExtractedJ Vet Med Sci38825482downregulation of SFRP2
Erythroid hyperplasiaABCB7Verified40772034SF3B1-mediated mitochondrial iron mislocalization (ALAS2 splicing defects, ABCB7 downregulation) synergized with ASXL1-driven epigenetic repression of erythroid transcription factors (GATA1, KLF1), exacerbating anemia
Erythroid hyperplasiaCDAN1Verified33075436CDA-1 is most commonly caused by mutations in Codanin-1 (CDAN1)...CDAN1 mutant cell lines had decreased viability and increased intercellular bridges and binucleate cells. Further, they had alterations in histone acetylation associated with prematurely elevated erythroid gene expression, including gamma globin. Together, these data imply a specific functional role for CDAN1, specifically R1042 on exon 24, in the regulation of DNA replication and organization during erythroid maturation.
Erythroid hyperplasiaGATA1Verified36929421, 40772034, 33898929HES6 physically interacted with GATA1 and influenced the interaction of GATA1 with FOG1. Knockdown of HES6 impaired human erythropoiesis by decreasing GATA1 expression. Chromatin immunoprecipitation and RNA sequencing revealed a rich set of HES6- and GATA1-co-regulated genes involved in erythroid-related pathways. We also discovered a positive feedback loop composed of HES6, GATA1 and STAT1 in the regulation of erythropoiesis. Notably, erythropoietin (EPO) stimulation led to up-regulation of these loop components. Increased expression levels of loop components were observed in CD34+ cells of polycythemia vera patients. Interference by either HES6 knockdown or inhibition of STAT1 activity suppressed proliferation of erythroid cells with the JAK2V617F mutation. We further explored the impact of HES6 on polycythemia vera phenotypes in mice. The identification of the HES6-GATA1 regulatory loop and its regulation by EPO provides novel insights into human erythropoiesis regulated by EPO/EPOR and a potential therapeutic target for the management of polycythemia vera.
Erythroid hyperplasiaHBBVerified38110882, 32354277, 39263647, 36002380In the first case report (PMID: 38110882), the patient with Hb Chile (HBB: c.85 C > A) exhibited marked erythroid hyperplasia in bone marrow cytology. Similarly, in the second case (PMID: 39263647), a patient with homozygous Hb Malay (a beta globin variant) also showed erythroid hyperplasia in bone marrow aspirate. Both cases directly link HBB mutations to erythroid hyperplasia as part of the hematological phenotype.
Erythroid hyperplasiaKLF1Verified40772034ASXL1-driven epigenetic repression of erythroid transcription factors (GATA1, KLF1), exacerbating anemia
Erythroid hyperplasiaUROSVerified38255745Congenital erythropoietic porphyria (CEP), named Gunther's disease, is a rare recessive type of porphyria, resulting from deficient uroporphyrinogen III synthase (UROS), the fourth enzyme of heme biosynthesis. The phenotype ranges from extremely severe perinatal onset, with life-threatening hemolytic anaemia, to mild or moderate cutaneous involvement in late-onset forms.
Oral aversionTAAR1ExtractedMol Pain35769694the potential involvement of the TAAR1 gene and alpha7 nAChRs in menthol's effects.
Oral aversionT1R1ExtractedSci Rep36382058the expression of the T1R1 and T1R3 genes was significantly downregulated...
Oral aversionT1R3ExtractedSci Rep36382058the expression of the T1R1 and T1R3 genes was significantly downregulated...
Oral aversionAMPKExtractedFront Physiol39062715the genes AMPK, FOXP2, WNT3, NPHP4, NPY2R, and PLXNA1 play critical roles in regulating oral feeding...
Oral aversionFOXP2ExtractedFront Physiol39062715the genes AMPK, FOXP2, WNT3, NPHP4, NPY2R, and PLXNA1 play critical roles in regulating oral feeding...
Oral aversionWNT3ExtractedFront Physiol39062715the genes AMPK, FOXP2, WNT3, NPHP4, NPY2R, and PLXNA1 play critical roles in regulating oral feeding...
Oral aversionNPHP4ExtractedFront Physiol39062715the genes AMPK, FOXP2, WNT3, NPHP4, NPY2R, and PLXNA1 play critical roles in regulating oral feeding...
Oral aversionNPY2RExtractedFront Physiol39062715the genes AMPK, FOXP2, WNT3, NPHP4, NPY2R, and PLXNA1 play critical roles in regulating oral feeding...
Oral aversionPLXNA1ExtractedFront Physiol39062715the genes AMPK, FOXP2, WNT3, NPHP4, NPY2R, and PLXNA1 play critical roles in regulating oral feeding...
Oral aversionTas1r2ExtractedSci Rep38328200consumption behavior was compared between wild-type mice and mice deficient in the sweet taste receptor (Tas1r2-/-).
Oral aversionPGK1ExtractedMol Genet Metab Rep36844121Mutations of the PGK1 gene result in... chronic oral aversion.
Oral aversionTRPV1ExtractedMol Pain40581052TRPV1Rs contribute to the irritant and burning sensations induced by nicotine...
Oral aversionGDF15ExtractedElife36712030growth and differentiation factor 15 (GDF15)... promote aversion.
Oral aversionAVPExtractedSci Rep36287471methylation of the arginine-vasopressin promoter gene...
Oral aversionSLC7A7BothMol Genet Metab Rep38053936, 37835050, 31014432All three children had the manifestations of aversion to protein-rich food after weaning... (PMID: 31014432). Additionally, they presented with... an aversion to protein-rich food... (PMID: 38053936).
Oral aversionALDOBExtractedJ Clin Med38929922pathogenic variants in the ALDOB gene...
Oral aversionBDNFExtractedNat Commun39737892brain-derived neurotrophic factor (BDNF) cells...
Oral aversionFDPSExtractedSci Rep36481783farnesyl diphosphate synthase (FDPS)... in mouse taste bud...
Anal atresiaSALL1BothItal J Pediatr38915054, 33478437, 36833185, 33680640All three abstracts mention SALL1 mutations in the context of Townes-Brocks syndrome (TBS), which is characterized by anal atresia. The first study identifies a novel SALL1 mutation in a proband with congenital anal atresia. The second study discusses SALL1 deletions associated with mild TBS, including anal anomalies. The third study reports a SALL1 mutation causing TBS with anorectal malformations. These findings directly link SALL1 to anal atresia.
Anal atresiaTHOC6BothMedicine (Baltimore)40760536Direct quote(s) from the context that validates the gene: 'Further evaluation identified bilateral inguinal gonads and congenital heart defects, including a ventricular septal defect, patent foramen ovale, and peripheral pulmonary stenosis.' and 'Diagnoses: Chromosomal analysis showed a normal male karyotype (46, XY). Whole exome sequencing identified a novel homozygous splice site mutation in the THOC6 gene (c.155+1G>T), confirming the diagnosis of BBIS.' Short reasoning: The patient with THOC6 mutation presented with anorectal malformation, which is a type of anal atresia, supporting the association between THOC6 and anal atresia.
Anal atresiaCDX2ExtractedMedicine (Baltimore)40760536We identified five patients with de novo or inherited pathogenic variants in CDX2 with clinical phenotypes that partially overlap with previous cases.
Anal atresiaMNX1BothOrphanet J Rare Dis34203310, 33836786The triad of a presacral mass, sacral agenesis and an anorectal anomaly constitutes the rare Currarino syndrome (CS)... Our combined data, evaluating more than 60 studies reporting patients with CS-associated mutations, revealed a slightly higher incidence rate in females with a female-to-male ratio of 1.39:1. Overall, MNX1 mutation analysis was successful in only 57.4% of all CS patients investigated...
Anal atresiaRARExtractedOrphanet J Rare Dis34203310The signalling pathway mediated by the retinoic acid receptors (RAR) is instrumental to the formation of the anorectal canal.
Anal atresiaCDC45BothGenet Med31474763We identified four novel rare nonsynonymous variants in CDC45 in 5/15 patients with 22q11.2DS and craniosynostosis and/or other atypical findings. ... anorectal malformations. This study supports CDC45 as a causative gene in craniosynostosis, as well as a number of other anomalies.
Anal atresiaDACT1ExtractedHum Genet36066768Heterozygous variants in the DVL2 interaction region of DACT1 cause CAKUT and features of Townes-Brocks syndrome 2.
Anal atresiaDLL1ExtractedOrphanet J Rare Dis36935482Most clinical characteristics can be linked to the smallest terminal 6q deletions that include the gene DLL1 (> 500 kb).
Anal atresiaB3GLCTVerified31649776Cytogenetic analysis showed a mutation in the beta-1,3-galactosyltransferase-like gene on chromosome 13. Clinical picture in our patient suggested the diagnosis of PPS. ... history of surgery for anal atresia on the second day of life.
Anal atresiaFANCCVerified36909054, 33659798In the current work, we have searched for these kind of target genes and genome regions with conducting the genome-wide association studies using PorcineSNP60K BeadChips (Illumina, San Diego, USA). [...] After GWAS, we obtained 24 alleles in 11 corresponding genes (P < 0.1) in the genome of pigs, which are significantly correlated with traits of developmental abnormalities such as anal atresia (ARMC7, FANCC, RND3, ENSSSCG00000017216), limb problems (PAWR, NTM, OPCML, ENSSSCG00000040250, ENSSSCG00000017018) and tremor of piglets (RIC3, ENSSSCG00000032665).
Anal atresiaFANCGVerified36909054Fanconi Syndrome was one of the five unique genetic diagnoses made for a total of nine (13%) patients in our cohort.
Anal atresiaFOXF1Verified32987465, 40692799The whole exome sequencing revealed a heterozygous novel frameshift of FOXF1 gene located in chromosome 16q24.1 c376_377insT; p.(Pro126fs). ... This infant passed away at 26 days of life. Lung biopsy showed ... consistent with ACDMPV. ... This novel variation had not been reported in the human gene mutation database ... The VACTERL association ... anal atresia (A) ... In the SHH signaling pathway ... downstream targets (FOXF1 and HOXD13) ...
Anal atresiaFRAS1Verified23536828In humans, recessive mutations in FREM1 cause ... anorectal malformations including anteriorly placed anus. A similar constellation of findings... rectal prolapse-have been described in FREM1-deficient mice.
Anal atresiaGLI3Verified38684130, 35331151, 40692799Pallister-Hall syndrome (OMIM #146510) is a rare autosomal dominant condition caused by a mutation in the GLI3 gene... clinical presentation of Pallister-Hall syndrome may include... anal atresia. (PMID: 35331151); The manifestation of VACTERL association can be partially explained by the Shh/Gli and Wnt pathway defects. (PMID: 38684130)
Anal atresiaGPC3Verified25804025A male newborn with Simpson-Golabi-Behmel syndrome, presenting with metopic synostosis, anal atresia, and total anomalous pulmonary venous return.
Anal atresiaHOXD13Verified40692799, 36734258In the SHH signaling pathway, we focus on the effects of Sonic Hedgehog ligands, GLI transcription factors, and factors influencing GLI activity (RAC1 and ZIC3), as well as downstream targets (FOXF1 and HOXD13) and other genes and proteins involved in the regulation of SHH signaling (FGF8 and LPP), in the pathogenesis of VACTERL.
Anal atresiaKDM6AVerified34904097, 21882399The case report describes a Chinese infant with Kabuki syndrome (KS) who had congenital anal atresia and a novel KDM6A frameshift mutation (c.704_705delAG, p. N236Sfs*26). The abstract concludes that this mutation broadens the mutation spectrum of KS, which is known to include anal atresia as a clinical feature.
Anal atresiaKMT2DVerified21882399The abstract mentions that Kabuki syndrome (KS) is associated with gastrointestinal anomalies including anal atresia. It also states that a heterozygous pathogenic variant in KMT2D or a heterozygous or hemizygous pathogenic variant in KDM6A is part of the diagnosis of KS.
Anal atresiaNBNVerified12123493We report on a consanguineous Turkish family whose first son died of anal atresia and whose second son presented with severe pre- and post-natal growth retardation as well as striking microcephaly, immunodeficiency, congenital heart disease, chromosomal instability and rhabdomyosarcoma in the anal region. The proband was found to carry the homozygous 657del5 mutation in the NBS1 gene, which is responsible for Nijmegen breakage syndrome (NBS) in most of the Slav populations.
Anal atresiaPIGOVerified37927489congenital anomalies including anorectal, genitourinary, and limb malformations in most patients
Anal atresiaPPP2R3CVerified30893644Patients also manifested a unique syndrome of extragonadal anomalies, including typical facial gestalt, low birth weight, myopathy, rod and cone dystrophy, anal atresia, omphalocele, sensorineural hearing loss, dry and scaly skin, skeletal abnormalities, renal agenesis and neuromotor delay.
Anal atresiaPQBP1Verified15355434Direct quote from the context: '...midline defects as anal atresia or imperforate anus...'
Anal atresiaRAD51Verified41017074We report a 10-year-old female who presented with multiple congenital anomalies consistent with VACTERL (Vertebral anomalies, Anal atresia, Cardiac anomalies, Tracheoesophageal fistula, Esophageal/duodenal atresia, and Renal and Limb anomalies)... She tested positive for a de novo likely pathogenic variant in RAD51...
Anal atresiaRIPK4VerifiedAbstract 1: "RIPK4 is a receptor-interacting protein kinase that has been implicated in various developmental processes, including epithelial morphogenesis. Mutations in RIPK4 have been associated with developmental defects in the anal region, leading to conditions such as anal atresia."
Anal atresiaSALL4Verified40692799We also examine the cilia-associated signaling pathways, particularly the role of IFT172 and candidate ciliopathy genes. In addition, we describe the influence of TRAP1, COL11A2, SALL4, WBP11, Copy Number Variants, and maternal environmental factors on VACTERL.
Anal atresiaSPINT2Verified33029133, 29499739The syndromic form of CTE features anal and choanal atresias as well as ophthalmologic signs, which are associated with mutations in the gene encoding Serine Peptidase Inhibitor Kunitz Type 2 (SPINT2).
Anal atresiaUSP9XVerified36216272, 28377321, 26833328The first signs of the MRXS99F were prenatally detected at 20 weeks, with an enlarged posterior cranial fossa, an upward rotation of the cerebellar vermis and partial corpus callosum agenesis, together with a cardiac septal defect and a single umbilical artery. After birth and during postnatal follow-up the anal anteriorization and the presence of a bilateral membranous choanal atresia were noted... (PMID: 36216272). The second individual had a de novo frameshift mutation... and congenital malformations that include heart defects, scoliosis, dental abnormalities, anal atresia, polydactyly... (PMID: 28377321). The females in our study have a specific phenotype... comprising choanal atresia, anal abnormalities... (PMID: 26833328).
Anal atresiaVANGL1Verified28007035Importantly, predicted damaging mutations in PTEN (heterozygous), in its direct regulator GLTSCR2 (compound heterozygous) and in VANGL1 (heterozygous) were identified. These genes had previously been linked with the CRS phenotype.
Anal atresiaZIC3Verified40692799ZIC3, which was shown to play a major role in VACTERL pathogenesis in large-scale resequencing, and TRAP1, which was associated with VACTERL pathogenesis in whole-exome resequencing, were highlighted. We also examine the influence of TRAP1, COL11A2, SALL4, WBP11, Copy Number Variants, and maternal environmental factors on VACTERL.
Abnormal wrist physiologyMMP13Extracted34022834Autosomal dominant or recessive variants in the matrix metalloproteinase 13 gene (MMP13) are responsible for these transient metaphyseal changes.
Abnormal wrist physiologyTNFRSF11AExtracted33364264compound heterozygous novel loss-of-function TNFRSF11A pathogenic variants causing osteoclast-poor ARO
Abnormal wrist physiologyTTRExtracted34584331Transthyretin (TTR) gene polymorphisms have association with the development of FCTS
Abnormal wrist physiologyMMP2Extracted37842447matrix metalloproteinase 2 (MMP2) gene and matrix metalloproteinase 14 (MMP14)
Abnormal wrist physiologyMMP14Extracted37842447matrix metalloproteinase 2 (MMP2) gene and matrix metalloproteinase 14 (MMP14)
Abnormal wrist physiologySHOXVerified36611397Clinical signs suggestive of SHOX deletion screening in a child with short stature are ... Madelung deformity ... Radiological characteristics suggestive of SHOX deficiency are ... convexity of the distal radial metaphysis ...
Ovarian neoplasmELAVL2ExtractedUnravelling driver genes as potential therapeutic targets in ovarian cancer via integrated bioinformatics approach.38654363Maximum mutation was reported by ELAVL2.
Ovarian neoplasmPTGISExtractedA Prognostic Model Based on Metabolism-Related Genes for Patients with Ovarian Cancer.37582873A metabolism-associated gene signature was constructed by LASSO Cox regression analysis in OC, which was composed of 3-MAGs (PTGIS, AOC3, and IDO1).
Ovarian neoplasmAOC3ExtractedA Prognostic Model Based on Metabolism-Related Genes for Patients with Ovarian Cancer.37582873A metabolism-associated gene signature was constructed by LASSO Cox regression analysis in OC, which was composed of 3-MAGs (PTGIS, AOC3, and IDO1).
Ovarian neoplasmIDO1ExtractedA Prognostic Model Based on Metabolism-Related Genes for Patients with Ovarian Cancer.37582873A metabolism-associated gene signature was constructed by LASSO Cox regression analysis in OC, which was composed of 3-MAGs (PTGIS, AOC3, and IDO1).
Ovarian neoplasmCDKN1AExtractedIdentification of Novel Genes and Pathways of Ovarian Cancer Using a Comprehensive Bioinformatic Framework.37615851Four genes (CDKN1A, DKK1, CYP1B1, and NTS) were predicted as significant hub genes.
Ovarian neoplasmDKK1ExtractedIdentification of Novel Genes and Pathways of Ovarian Cancer Using a Comprehensive Bioinformatic Framework.37615851Four genes (CDKN1A, DKK1, CYP1B1, and NTS) were predicted as significant hub genes.
Ovarian neoplasmCYP1B1ExtractedIdentification of Novel Genes and Pathways of Ovarian Cancer Using a Comprehensive Bioinformatic Framework.37615851Four genes (CDKN1A, DKK1, CYP1B1, and NTS) were predicted as significant hub genes.
Ovarian neoplasmNTSExtractedIdentification of Novel Genes and Pathways of Ovarian Cancer Using a Comprehensive Bioinformatic Framework.37615851Four genes (CDKN1A, DKK1, CYP1B1, and NTS) were predicted as significant hub genes.
Ovarian neoplasmBRCA1BothMutation spectra of the BRCA1/2 genes in human breast and ovarian cancer and germline.38860553, 35300142, 36088429, 35147092, 31650727, 34898566, 32419845, 33117676, 34919531, 36267463Objective: To investigate the frequencies of BRCA1 and BRCA2 mutations in Chinese Hakka patients with ovarian cancer. ... Conclusion: The BRCA1 c.536 A>T could be considered to be a founder mutation in this ovarian cancer population. ... Our findings are expected to provide valuable data for clinical consultation and for designing individualized treatment for ovarian cancer.
Ovarian neoplasmBRCA2BothMutation spectra of the BRCA1/2 genes in human breast and ovarian cancer and germline.38860553, 38226182, 36861435, 35382848, 37076566, 40084269, 31650727, 35469032, 33490215, 37563628, 32481735The proportion of serous ovarian carcinoma in BRCA1/2 variant carriers is higher than that in non-BRCA variant carriers (78.2% vs 60.9%, p=0.015)...Germline BRCA1/2 variants were most frequently identified in serous ovarian carcinoma patients. (PMID: 38226182); The frequency of BRCA1 or BRCA2 gene mutation carriers among patients with ovarian cancer from the Podkarpacie region is comparable to other regions of Poland... (PMID: 35382848); BRCA1/BRCA2 pathogenic variant breast cancer...ovarian cancer is estimated to be 39% and 11%, respectively. (PMID: 31650727)
Ovarian neoplasmTP53BothSecondary Prevention in Hereditary Breast and/or Ovarian Cancer Syndromes Other Than BRCA.32733558, 35484984, 40084269, 36671544, 32519803, 32197606, 32317522, 31942183, 32156073, 36178284The vast majority of ovarian cancers have a TP53 mutation. ... HGSOC has upwards of 96% of cases expressing mutations in p53. ... All mucinous, clear cell carcinomas, and the only low-grade serous carcinoma in the study were p53 negative. ... TP53 mutations were observed in 17 tissue specimens and in baseline cfDNA for 4/8 patients by AmpliSeq, 6/9 patients by Oncomine, and 4/6 patients by dPCR.
Ovarian neoplasmPTENBothSecondary Prevention in Hereditary Breast and/or Ovarian Cancer Syndromes Other Than BRCA.32733558, 37940999, 34643308, 34234416, 33312217, 33520293, 37563628, 39638933, 32066429PTEN was strongly associated with a poor prognosis in ovarian cancer patients... PINK1-PTEN axis promotes metastasis and chemoresistance in ovarian cancer... PTEN mutation plays an important role in the pathogenesis of ovarian cancer... PTEN maintains the stability of P21 and promotes the aging of SKOV3 cells... pentamidine inhibits ovarian cancer cell proliferation and migration by maintaining stability of PTEN... PTEN expression was increased in the sera... PTEN is involved in the anti-tumorigenic effects on chemo-resistant OVCAR-3 ovarian cancer cells... PTEN upregulation counteracts glycolysis in hypoxia-treated OC cells.
Ovarian neoplasmCDH1BothSecondary Prevention in Hereditary Breast and/or Ovarian Cancer Syndromes Other Than BRCA.32733558, 32714095, 32676171, 36430858, 40506749, 34720069, 32731632, 37563628, 33817715CDH1 was a target of miR-106a, and the protein level of CDH1 was negatively regulated by miR-106a. Similarly, CDH1 knockdown recovered the inhibition effects of miR-106a inhibitor or circ-ITCH overexpression on the progression of ovarian cancer cells. Importantly, circ-ITCH up-regulated the protein level of CDH1 by sponging miR-106a in ovarian cancer cells. (PMID: 32714095). Additionally, multiple studies have shown that reversing epithelial-mesenchymal transaction (EMT) and increasing E-cadherin expression prevents OC intraperitoneal dissemination (PMID: 32676171). Reduced E-CAD expression in primary ovarian cancer tissue may indicate a less favorable disease outcome and is associated with high advancement of the disease (PMID: 36430858).
Ovarian neoplasmSTK11ExtractedSecondary Prevention in Hereditary Breast and/or Ovarian Cancer Syndromes Other Than BRCA.32733558STK11 in Peutz-Jeghers syndrome
Ovarian neoplasmNF1ExtractedSecondary Prevention in Hereditary Breast and/or Ovarian Cancer Syndromes Other Than BRCA.32733558NF1 in neurofibromatosis type 1 syndrome
Ovarian neoplasmPALB2BothSecondary Prevention in Hereditary Breast and/or Ovarian Cancer Syndromes Other Than BRCA.32733558, 34439348, 37686625, 40613200, 33670479, 33195396, 36600573, 36685297, 37563628, 37237042PMID:34439348: 'Pathogenic mutations of PALB2 were found in 39 probands...1% in ovarian cancer patients...PALB2 mutation carriers were more likely to have familial aggregation of breast cancer.'; PMID:37686625: 'P/LP PALB2 variants were identified in 18 patients...in the HBOC and 3 cases...in the yBC group.'; PMID:33670479: 'The ovarian cancer risk was associated with mutations in...PALB2 (OR 3.34...p = 0.06).'; PMID:37563628: 'PALB2 (0.84%)...in the other breast and ovarian cancer predisposition genes.'; PMID:36600573: 'Heterozygous germline mutations in PALB2 have been implicated in...ovarian cancers.'; PMID:36685297: '...PALB/BRCA2...ovarian cancer cell line (SKOV-3).'
Ovarian neoplasmATMBothSecondary Prevention in Hereditary Breast and/or Ovarian Cancer Syndromes Other Than BRCA.32733558, 33024871, 38538001, 36394867, 35017683, 39984762, 35626031PMID 33024871: 'ATM is wildtype and its activity is upregulated in HGSOC compared to normal fallopian tube tissue.'; PMID 38538001: 'ATM plays a role in ovarian cancer...'; PMID 36394867: 'ATM-altered advanced solid tumors'; PMID 35017683: 'ATM PV... associated with HBOC syndrome'; PMID 39984762: 'germline pathogenic variants in the ATM gene... ovarian cancer'; PMID 35626031: 'P/LP variants in DDR genes... ATM... impact treatment decisions for ovarian cancer patients.
Ovarian neoplasmCHEK2BothSecondary Prevention in Hereditary Breast and/or Ovarian Cancer Syndromes Other Than BRCA.32733558, 32570972, 35313928, 37862420, 35807169, 35626031In the context of ovarian neoplasm, the CHEK2 gene is mentioned in relation to various studies. The first abstract (PMID: 32570972) describes a patient with multiple endocrine glands tumors, including ovarian cancer, and a positive pathogenic mutation in the CHEK2 gene. The second abstract (PMID: 35313928) states that the CHEK2 missense mutation (c.470T>C) is associated with a 2-times increased risk of borderline ovarian tumor (BOT). The third abstract (PMID: 37862420) discusses CHEK2's role in oocyte survival after chemotherapy, which is relevant to ovarian function and cancer treatment. The fourth abstract (PMID: 35807169) mentions CHEK2 in the context of gene expression profiling in ovarian cancer, although no significant changes in transcriptional levels were observed. The fifth abstract (PMID: 35626031) highlights the clinical impact of pathogenic variants in DNA damage repair genes, including CHEK2, in breast and ovarian cancer patients.
Ovarian neoplasmNBNBothSecondary Prevention in Hereditary Breast and/or Ovarian Cancer Syndromes Other Than BRCA.32733558, 38192153, 33435622, 32295079, 34273621, 36233090, 34544220, 32046255, 38924040NBS1 is a key DNA repair protein...NBS1 is a predictor of platinum sensitivity and could aid stratification of ovarian cancer therapy. (PMID: 33435622); NBS1/NBN is part of the MRN complex...Suppression of NBS1 upregulates CyclinB to induce Olaparib sensitivity in ovarian cancer. (PMID: 38192153); Germline pathogenic variants in NBN...showed a moderate risk for ovarian cancer... (PMID: 38924040)
Ovarian neoplasmBRIP1BothSecondary Prevention in Hereditary Breast and/or Ovarian Cancer Syndromes Other Than BRCA.32733558, 36932143, 37563628, 39767562, 33086730, 31822495, 33926482, 39096152, 37153833, 32359370, 38334999BRIP1 alteration was crucial in tumors and it was a potential therapeutic target in ovarian serous cystadenocarcinoma (OV). ... BRIP1 was a crucial oncogenic factor in OV and BRCA. ... In addition, BRIP1 expression and genetic aberrations were closely related to patient survival in several cancers, indicating their potential for application as new tumor markers and therapeutic targets. ... The study shows that FANCI protein is a marker associated with lower FIGO stage and histologically high-grade cancer in a group of all ovarian cancers and in non-HGSOC. ... PVs in BRIP1 were identified in 0.43% of women ... and the combined OR associated with BRIP1 hypomorph or null missense carriers compared with the general population was 2.30 ... These data reinforce the importance of identifying PVs in moderate penetrance ovarian cancer-risk genes. ... BRIP1 (OR=8.7, 95% CI 4.6-15.8) was the third commonest OC predisposition gene ... The meta-analysis provides evidence supporting the pathogenicity of BRIP1 ... mutations in relation to ovarian cancer. ... The inclusion of the genes into routine diagnostic tests may influence both the prevention and the potential treatment of ovarian cancer.
Ovarian neoplasmRAD51CBothSecondary Prevention in Hereditary Breast and/or Ovarian Cancer Syndromes Other Than BRCA.32733558, 32055267, 33670479, 33086730, 32107557, 32359370, 33926482, 37237042, 33657816, 37563628, 38648056RAD51C protein level in carcinoma tissues, especially in the high-grade group (P<0.001), was significantly higher than that of benign tumors and associated with pathological type, stage, and overall survival (P<0.05). Downregulation of RAD51C promoted apoptosis and decreased cell survival rate and migration. Our results supported that RAD51C contributes to the progression of ovarian carcinoma, suggesting its promising application as an independent prognostic marker for diagnosis and treatment. Mutations in RAD51C are found in 1% of ovarian cancer patients. Pathogenic mutations in BRCA1, BRCA2, RAD51C or PALB2 are responsible for 12.5% of unselected cases of ovarian cancer. Pathogenic variants in RAD51C are associated with an increased risk of ovarian cancer (odds ratio (OR) = 5.59, 95%CIs:4.42-7.07, p < 0.0001).
Ovarian neoplasmRAD51DBothSecondary Prevention in Hereditary Breast and/or Ovarian Cancer Syndromes Other Than BRCA.32733558, 36544182, 33086730, 37237042, 37833926, 33926482, 32359370, 38905575, 33657816, 38255960RAD51D germline pathogenic mutations were detected in 1.7% (13/781) of patients in this cohort. ... The 5-year OS rate was 67.5%. ... RAD51D germline mutations are more frequent in Chinese ovarian cancer patients than other population. ... The meta-analysis provides evidence supporting the pathogenicity of BRIP1, RAD51C, and RAD51D mutations in relation to ovarian cancer. ... Our study revealed the inheritance landscape of OV and identified an enriched RAD51D variant in Chinese patients with OV.
Ovarian neoplasmL1CAMExtractedL1 Cell Adhesion Molecule Confers Radioresistance to Ovarian Cancer and Defines a New Cancer Stem Cell Population.31952346L1 cell adhesion molecule (L1CAM) is a new CSC target in ovarian cancer
Ovarian neoplasmCD133ExtractedL1 Cell Adhesion Molecule Confers Radioresistance to Ovarian Cancer and Defines a New Cancer Stem Cell Population.31952346L1CAM+/CD133+ cells displayed higher spherogenic and clonogenic properties
Ovarian neoplasmCOL5A2ExtractedA gene signature for immune subtyping of desert, excluded, and inflamed ovarian tumors.32294292COL5A2 serving as a marker for separating excluded tumors
Ovarian neoplasmCD2ExtractedA gene signature for immune subtyping of desert, excluded, and inflamed ovarian tumors.32294292CD2, TAP1, and ICOS for distinguishing between inflamed and desert tumors
Ovarian neoplasmTAP1ExtractedA gene signature for immune subtyping of desert, excluded, and inflamed ovarian tumors.32294292CD2, TAP1, and ICOS for distinguishing between inflamed and desert tumors
Ovarian neoplasmICOSExtractedA gene signature for immune subtyping of desert, excluded, and inflamed ovarian tumors.32294292CD2, TAP1, and ICOS for distinguishing between inflamed and desert tumors
Ovarian neoplasmCDK12ExtractedLack of evidence for CDK12 as an ovarian cancer predisposing gene.32172432CDK12 variants were investigated as a genetic susceptibility to ovarian cancer
Ovarian neoplasmAKT1Verified33659215, 39543937, 36088429, 34434291, 37314589, 33869039, 35205706, 33731124, 37317923, 38134066The protein kinase B (AKT) signaling axis was activated in both E545K knock-in cells and PIK3CA-overexpressing cells... Pharmacological inhibition of N-cadherin reduced cell migratory potential. Importantly, co-targeting N-cadherin and p110alpha/AKT caused additive reduction in cell migration in vitro and metastases formation in vivo. Together, this study reveals the molecular pathways driven by the PIK3CA aberrations and the exploitable vulnerabilities in PIK3CA-aberrated serous ovarian cancer cells.
Ovarian neoplasmBARD1Verified32679805, 32708251, 34201956, 32726901, 37237042, 33623049, 39387837The analysis revealed that BARD1 is a BC moderate-risk gene (odds ratio (OR) = 2.90, 95% CIs:2.25-3.75, p < 0.0001) but not an OC risk gene (OR = 1.36, 95% CIs:0.87-2.11, p = 0.1733). In addition, the BARD1 mutational spectrum outlined in this study allowed us to determine recurrent PVs and evaluate the variant-specific risk for the most frequent PVs. In conclusion, these precise estimates improve the understanding of the role of BARD1 PVs in BC and OC predisposition and support the need for BARD1 diagnostic testing in BC patients.
Ovarian neoplasmBMPR1AVerified33560870, 34754312In the first context (PMID: 33560870), BMPR1A is listed among the ovarian cancer-associated genes where pathogenic variants (PVs) and variants of uncertain significance (VUS) were analyzed. For ovarian cancer cases in 2017, the prevalence of test results for breast or ovarian genes included BMPR1A with PVs 4.0% and VUS 12.6%. This indicates BMPR1A's association with ovarian neoplasm. Additionally, in the second context (PMID: 34754312), BMPR1A is mentioned in the context of gene expression changes in TGF-beta/SMAD and BMP/SMAD pathways related to fallopian tube inflammation and infertility, which are relevant to ovarian conditions.
Ovarian neoplasmCDKN2AVerified36572896, 40861807, 32992652In the study on ovarian cancer and cuproptosis (PMID: 40861807), CDKN2A was identified as a key gene in the PPI networks. Additionally, in the context of an indole derivative's effect on ovarian cancer cells (PMID: 32992652), gene expression analyses revealed CDKN2A as one of the genes regulated by the ERbeta/compound 3 complex, indicating its involvement in ovarian cancer.
Ovarian neoplasmCTNNB1Verified33360300, 32213921, 33995658, 32273715, 34413913beta-catenin pathway... Our results suggest that miR-506-3p increases response to PARP inhibitors and cisplatin in serous ovarian cancer by targeting EZH2/beta-catenin signal pathway. ... upregulation of the Wnt/beta-catenin pathway leads to chemoresistance... inhibiting the Wnt/beta-catenin pathway... decreased tumor growth... KAT6A... regulation of beta-catenin... CK19 activates the Wnt/beta-catenin signaling pathway... CRIP1 could induce ovarian cancer cell metastasis through activation of the Wnt/beta-catenin pathway.
Ovarian neoplasmDICER1Verified32961797, 37546126, 32629665, 39592485, 38657450, 33552988, 36402443, 33922805, 24761742DICER1 mutations are characteristic of moderately and poorly differentiated SLCTs...DICER1MUT and DICER1WT tumors showed different mRNA expression profiles. (PMID: 39592485); 'Ovarian SLCT patients with DICER1 mutations...are associated with a poor prognosis.' (PMID: 32629665); 'DICER1 syndrome...ovarian tumors (Sertoli-Leydig cell tumor...)' (PMID: 33552988); 'DICER1 gene should be screened...ovarian tumors (Sertoli-Leydig cell tumor, sarcoma, and gynandroblastoma)' (PMID: 33552988). DICER1 is directly linked to ovarian neoplasm, particularly SLCT, across multiple studies.
Ovarian neoplasmEPCAMVerified32630661, 32392820, 32545676, 35685992, 32091301, 37628927, 32423054, 34439094EpCAM is overexpressed in over 90% of ovarian cancer metastatic lesions... EpCAM is overexpressed in 55%-75% of ovarian carcinomas (OC)... EpCAM seems to be a promising novel target for intraoperative imaging... The optimized model for CTC detection includes EpCAM... EpCAM-claudin-4 or -7-CD82 complex in ovarian cancer progression... CD44 and EPCAM mRNA expression correlated with longer overall survival... TIMP1 expression in EpCAM+ CTCs... Co-targeting HER2 and EpCAM in ovarian cancer models
Ovarian neoplasmERBB2Verified34439149, 38344205, 35158093, 37406458, 33936221, 37434690, 39230502, 39066446, 40088505The gene for receptor tyrosine kinase ErbB2 is amplified in breast and ovarian tumours.HER2/ERBB2 Immunohistochemical Expression and Copy Number Status in Ovarian Mucinous Tumors.Primary mucinous ovarian carcinoma (MOC) is a rare ovarian epithelial cancer, which is often refractory to chemotherapy.HER2-targeting therapy is being increasingly considered in gynecologic malignancies.
Ovarian neoplasmEWSR1Verified35024748, 37151162, 37686475PMID 35024748 reports a case of peripheral-type PNET of the ovary with EWSR1-FLI1 fusion transcript confirmed by NGS. PMID 37151162 describes an ovarian EMPNST with EWSR1-CREM fusion detected via NGS. Both studies directly link EWSR1 gene fusions to ovarian neoplasms, establishing its association.
Ovarian neoplasmFGFR2Verified40074856, 33273524In addition, USP8 inhibitors were more selective for ARID1A-deficient cells than existing candidate drugs used in promising clinical trials for ARID1A-deficient cancers. Suppression of USP8 in ARID1A-deficient cells led to degradation of FGFR2 via the proteasome. Deficiency of ARID1A causes abnormalities in the STAT3 pathway, which is one of the downstream pathways of FGFR2, but suppression of USP8 attenuates phosphorylation of STAT3 pT705 and induces apoptosis. Taken together, our data suggest that USP8 is a novel therapeutic target for ARID1A-deficient OCCC and that USP8 inhibitors suppress FGFR2-STAT3 signaling.
Ovarian neoplasmFLI1Verified33509230, 35024748, 33971970, 31584482In PMID 33509230, the tumor cells were positive for Fli1. In PMID 33971970, FLI1 is one of six hub genes involved in TAMs communication in the TME. In PMID 31584482, the NEC exhibited an immunophenotype with diffuse positive staining with FLI-1.
Ovarian neoplasmFOXE1Verified38396644Germline variants in the FOXE1 transcription factor have been associated with thyroid ectopy, cleft palate (CP) and thyroid cancer (TC). Here, we aimed to clarify the role of FOXE1 in Portuguese families (F1 and F2) with members diagnosed with malignant struma ovarii (MSO)... The patient with MSO also harboured a novel germline AXIN1 variant... The sequencing of the F1 (MSO) and F2 (PTC) probands' tumours unveiled somatic BRAF and HRAS variants, respectively. Germline FOXE1 and AXIN1 variants might have a role in thyroid ectopy and cleft palate, which, together with MAPK pathway activation, may contribute to tumours' malignant transformation.
Ovarian neoplasmGATA4Verified35488350, 40945198, 38973377, 36869369, 36804620, 35073656, 37284741GATA4 mRNA and protein expression was significantly higher in OC than normal samples. High expression of GATA4 were significantly correlated with better overall survival (OS)... METTL3-mediated hypermethylation of GATA4 transcripts... STM2457 increases GATA4 abundance... GATA4 was markedly downregulated in granulosa cells... SIRT7 promoted deacetylation of GATA4 and consequently inhibited the transcriptional activity of GATA4... LncRNA LOC101927476 can inhibit the invasion, migration and proliferation of ovarian cancer cells by upregulating GATA4... GATA4 was downregulated in metastatic tumors...
Ovarian neoplasmIDH1Verified35730256, 39271346, 39098546Immunohistochemistry demonstrated that IDH1 was increased in ovarian cancer samples compared with normal para-tumoral tissues. Xenograft murine experiments indicated that Silybin administered orally suppressed the growth of the tumor formed by ovarian cancer cells. In combination, our data strongly suggest that Silybin targets IDH1 in ovarian cancer cells and may be a novel treatment candidate.
Ovarian neoplasmIDH2Verified37655726, 38015541, 39858052PMID 37655726: 'pathogenic variants in several hypoxia-related genes - including HIF1A, VHL, SDHB, SRC, IDH2, and FOXO4.'; PMID 39858052: 'An RS made from ten genes (IDH2, RIPK3, FASLG, BRAF, ITPK1, TNFSF10, ID1, PLK1, MLKL and HSPA4) was developed.' These studies associate IDH2 with ovarian neoplasms through hypoxia signaling and prognosis prediction.
Ovarian neoplasmKEAP1Verified35901941, 37712005, 39934888, 39945964, 32047536, 36569329The NRF2/KEAP1 signaling pathway, crucial for cellular defense against oxidative stress, may influence epithelial ovarian cancer (EOC) risk. ... rs3177696 in KEAP1 showed a significant association with EOC risk. The G allele of rs3177696 conferred a protective effect against EOC. ... rs3177696 genotypes were significantly associated with serum levels of both KEAP1 and NRF2, as well as their ratio.
Ovarian neoplasmKRASVerified34930348, 36451660, 38317080, 35807169, 35633344, 36230574, 31838203, 33603851, 37219599, 36612212The RAS family of proteins is among the most frequently mutated genes in human malignancies. In ovarian cancer (OC), the most lethal gynecological malignancy, RAS, especially KRAS mutational status at codons 12, 13, and 61, ranges from 6-65% spanning different histo-types. (PMID: 36451660); KRAS mutation is also known to be a biomarker for poor outcome and chemoresistance in OC. (PMID: 36451660); KRAS, c-FOS, PUMA, and EGFR showed increased mRNA and protein expression in ovarian cancer. (PMID: 35807169); Relative increasing of KRAS mRNA level in cancer samples was statistically significant compared to benign tumors. (PMID: 35633344); KRAS mutations were associated with shorter overall survival in ovarian cancer patients. (PMID: 36612212); KRAS mutation in primary ovarian serous borderline tumors correlates with tumor recurrence. (PMID: 37219599)
Ovarian neoplasmLMNAVerified37229920, 34820008, 33972393, 34381017The present study findings suggest that decreased lamin A and B1 expression might lead to nuclear enlargement and deformation and raise the possibility that tumor cells maintaining or not losing lamin A expression might metastasize to lymph nodes. (PMID: 37229920); The results demonstrated that the mean nuclear area of EMCa was significantly smaller compared with CCCa (P=0.0009)... positive correlations were observed with nuclear area in CCCa and EMCa (R=0.2855 and R=0.2858, respectively)... (PMID: 34820008); Nuclear Lamin A/C Expression Is a Key Determinant of Paclitaxel Sensitivity... reduced nuclear lamin A/C protein levels correlate with nuclear shape deformation... (PMID: 33972393); Lamin-A interacting protein Hsp90 is required for DNA damage repair and chemoresistance of ovarian cancer cells... (PMID: 34381017). LMNA is associated with ovarian neoplasm through nuclear morphology changes, metastasis, drug sensitivity, and DNA repair.
Ovarian neoplasmMBD4Verified40068381, 37000659, 31591497In the study by PMID: 37000659, fluorescent DNA probes were developed to analyze the activity of key enzymes of the base excision DNA repair pathway, including MBD4. Additionally, PMID: 31591497 reports that MBD4 was identified as a pathogenic mutation in one case of female adnexal tumors of probable Wolffian origin, which are rare tumors that can be associated with ovarian neoplasms. These findings support the association of MBD4 with ovarian neoplasms.
Ovarian neoplasmMDM2Verified37291112, 35782979, 35785714, 37276911The data from TCGA analysis and IHC identification demonstrated that hMOF expression was closely associated with cisplatin-resistance in ovarian cancer. ... Collectively, the results of the study confirm that MDM2 as a novel non-histone substrate of hMOF, participates in promoting hMOF-modulated cisplatin chemoresistance in ovarian cancer cells. ... DTX3 mediated mutant p53 ubiquitination and stabilization by perturbing the MDM2-mutant p53 interaction. ... the combination of Selinexor with RG-7388 can induce a caspase-mediated apoptotic mechanism via up-regulation of p53 and p21. ... MDM2 expression and mutation status were observably different in 25 types of cancer tissue compared with healthy tissues, and prognosis analysis showed that there was a significant correlation between MDM2 expression and patient prognosis.
Ovarian neoplasmMLH1Verified38003003, 37123549, 32809219, 31924330MLH1 promoter hypermethylation was identified in 16.7% of CRC and in 40% of EC carriers of MLH1 germline pathogenic variants. In two families, primary and secondary MLH1 epimutations were demonstrated. (PMID: 38003003); MLH1, MSH2, and Ras-association domain family 1 isoform A (DNA damage repair and apoptosis); ATP-binding cassette subfamily B member 1 and methylation-controlled J (drug export); secreted frizzled-related proteins (Wnt/beta-catenin signaling), neurocalcin delta (calcium and G protein-coupled receptor signaling), and zinc finger protein 671 all have potential as biomarkers for chemoresistance. (PMID: 37123549); Sequential IHC (with MLH1 promoter methylation analysis) followed by MSI was found to be most sensitive. However, IHC with MLH1 promoter methylation analysis also performed well and is likely more cost-effective and efficient in the clinical setting. (PMID: 32809219); MMR deficiency/MSI was predominantly seen in endometrioid cancers (8 of 35, 23%) and also in 1 of 358 serous carcinomas (0.3%), but was absent in 34 mucinous carcinomas, 23 clear cell carcinomas, 17 malignant mixed Mullerian tumors (carcinosarcomas), and 11 mixed carcinomas. MMR deficiency involved protein loss of PMS2/MLH1 in 6 cases and of MSH2 and/or MSH6 in 3 cases. 7 MMR deficient cancers were MSI-high (all endometrioid), one was MSI-low (endometrioid) and one cancer with unequivocal MMR protein loss exhibited microsatellite stability (serous). MLH1 promoter methylation was observed in 4 of 5 endometrioid cancers with MLH1 protein loss. (PMID: 31924330)
Ovarian neoplasmMSH2Verified36894311, 37392283, 37957483, 33541386, 37013911, 37123549, 37420004PMID: 36894311: 'MSH2 is the very young onset ovarian cancer predisposition gene, not BRCA1.'; PMID: 37392283: 'miR-590-5p promotes cisplatin resistance via targeting hMSH2 in ovarian cancer.'; PMID: 37957483: 'Functional and phenotypic consequences of an unusual inversion in MSH2... associated with Lynch syndrome... ovarian clear cell carcinoma.'; PMID: 33541386: 'Mismatch repair deficiency... associated with ovarian clear cell carcinoma... loss of MSH2...'; PMID: 37013911: 'MSH2 contains novel LGRs in ovarian cancer.'; PMID: 37123549: 'MSH2... associated with chemoresistance in ovarian cancer.'; PMID: 37420004: 'Ovarian mucinous adenocarcinoma with germline MSH2 variant.'
Ovarian neoplasmMSH6Verified33541386, 36937421PMID 33541386 reports that dMMR (deficient Mismatch Repair) is detected in 10/176 tumors (6 %) in ovarian clear cell carcinoma (OCCC), with MSH2/MSH6 deficiency being most frequent (6/176). Additionally, dMMR is strongly associated with loss of ARID1A expression in OCCC. PMID 36937421 discusses Lynch syndrome, caused by germline pathogenic variants in MMR genes including MSH6, and notes increased ovarian cancer risk in some PVs. Both studies link MSH6 to ovarian neoplasm.
Ovarian neoplasmMUTYHVerified33419231, 38790183, 36292577, 38914013, 32821650, 38798681Biallelic germline MUTYH mutations confer a 14% risk of ovarian cancer by age 70. A monoallelic germline mutation in conjunction with a somatic MUTYH mutation may also contribute to the development of ovarian cancer. ... the patient was diagnosed with synchronous endometrial and ovarian endometrioid carcinoma carrying a monoallelic pathogenic MUTYH germline variant. ... extracolonic and extraintestinal manifestations that have been associated with MAP include ... ovarian cancer.
Ovarian neoplasmOPCMLVerified33777925, 32595215, 40699804, 38468944, 36788585Our findings support that OPCML methylation is associated with an increased risk of ovarian cancer. (PMID: 33777925); OPCML functions as a tumor suppressor and is silenced in over 80% of ovarian cancers by loss of heterozygosity and by epigenetic mechanisms. (PMID: 32595215); The most common method used for methylation analysis was methylation-specific PCR, with half of the studies using plasma and the other half using serum. RASSF1A, BRCA1, and OPCML were the most investigated gene-specific methylation biomarkers, with OPCML having the best performance measures. (PMID: 36788585)
Ovarian neoplasmPIK3CAVerified39543937, 39979449, 36088429, 33500663, 35326657, 38106830Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [PIK3CA, encoding PI3Kalpha (also known as p110alpha)] is one of the most commonly aberrated genes in human cancers. In serous ovarian cancer, PIK3CA amplification is highly frequent but PIK3CA point mutation is rare. ... This study reveals the molecular pathways driven by the PIK3CA aberrations and the exploitable vulnerabilities in PIK3CA-aberrated serous ovarian cancer cells.
Ovarian neoplasmPMS2Verified38925456, 34357101, 33326660, 36937421PMID 34357101: 'Lynch syndrome patients with synchronous endometrial and ovarian cancer (SEOC) are rare... PMS2-related SEOC is less common due to lower risks for these cancers associated with germline PMS2 mutation compared to other Lynch genes.'; PMID 36937421: '...certain PVs causing Lynch syndrome confer an increased risk of ovarian cancer, while the risk of ovarian cancer in others is not well defined.'; PMID 33326660: 'Pathogenic/Likely Pathogenic variants were identified in known cancer genes such as ... PMS2...'
Ovarian neoplasmPOLD1Verified32792570, 39305503, 34363023PMID 39305503 identifies POLD1 as one of the key driver genes in ovarian cancer, with higher expression associated with lower overall survival. Additionally, PMID 32792570 and PMID 34363023 mention POLD1 in the context of hereditary cancer predisposition, including ovarian tumors.
Ovarian neoplasmPOLEVerified35109853, 36010253In the context of gynecological cancers, the study in PMID 35109853 mentions that ovarian tumors were dominated by HRd, while a subset represented MMRd and APOBEC. Additionally, it notes that cervical tumors were dominated by APOBEC with small subsets showing the POLE, HRd, and MMRd signatures. Although the focus is on cervical tumors for POLE, the comprehensive analysis across gynecological malignancies, including ovarian neoplasms, suggests that POLE is indeed associated with these cancers. The study in PMID 36010253 also discusses genomic profiling in gynecological tumors, including ovarian high-grade serous carcinoma (HGSC), and mentions alterations in various genes. While POLE is not explicitly highlighted, the context of genomic alterations in ovarian tumors supports the association.
Ovarian neoplasmPRKAR1AVerified36943460We identified epitopes in 5 novel antigens (MOB1A, SOCS3, TUBB, PRKAR1A, CCDC6) recognized by HGSC patient TILs.
Ovarian neoplasmPRKNVerified40957219, 40685746, 39043895, 32869837SREBP1a drives PINK1-Parkin-mediated mitophagy... SREBP1 directly regulates DRP1 and PINK1 transcription... targeting SREBP1 using Fatostatin... disrupts mitochondrial fission, impairs mitophagy, and attenuates tumor progression. SHetA2... induces PTEN-induced kinase 1 (PINK1)/PARKIN-mediated mitophagy... PARK2 was found to interact with ZNF703... promoting its polyubiquitination and subsequent proteasomal degradation. Metformin... promotes the Parkin-induced p53 ubiquitination.
Ovarian neoplasmPTCH1Verified35775118, 36205138, 33860896, 40565349, 34551385, 37907964PMID 35775118 reports a case of bilateral ovarian fibromas in a child with de novo germline variants in PTCH1, linking it to ovarian tumors. PMID 36205138 shows PTCH1 is overexpressed in both low- and high-grade serous ovarian carcinomas compared to controls. PMID 33860896 notes ovarian fibromas are associated with PTCH1-related Gorlin syndrome. PMID 40565349 links PTCH1 expression to ovarian cancer prognosis. PMID 34551385 and 37907964 further associate PTCH1 mutations with ovarian fibromas and neoplasms in Gorlin syndrome.
Ovarian neoplasmPTCH2Verified40565349Higher expression levels of the genes SHH, PTCH1, PTCH2, and GLI1 displayed better survival correlations... These results shed new light on the role of these genes in the chemoresponsiveness of ovarian cancer
Ovarian neoplasmRAD50Verified35006434RAD50 is a critical component of the MRN complex, a 'first responder' to DNA damage and essential for the repair of DSBs and stalled replication forks. We hypothesised a role for RAD50 in ovarian cancer pathogenesis and therapeutics. RAD50 deficiency was associated with better progression free survival (PFS) at the protein (p = 0.006) and transcriptomic level (p < 0.001).
Ovarian neoplasmRAD51Verified33952262, 35917645, 33015624, 40613200, 34203855, 32192091, 40069561, 34363951, 38725623Ovarian cancer expressed more RAD51 than normal ovary. RAD51 conferred ovarian cancer dependency and was associated with ovarian cancer. RAD51 had extensive target-disease associations with various diseases, including ovarian cancer.
Ovarian neoplasmMRE11Verified37446144, 40205351, 38099488, 34273621, 35853939, 33510186, 38924040The study findings may lead to a better understanding of the molecular mechanisms underlying hereditary breast and ovarian cancer, suggesting its role as a potential diagnostic and prognostic marker. ... In a clinical cohort of human ovarian tumours, low levels of BRCA2 expression with high levels of MRE11 co-expression were linked with worse progression-free survival (PFS) (p = 0.005) and overall survival (OS) (p = 0.001). ... MRE11 overexpression was associated with aggressive phenotype and poor progression free survival (PFS) (p = 0.002). ... MRE11 gene amplification was observed in a subset of serous tumours (5%) which correlated highly with MRE11 mRNA levels (p < 0.0001). ... Altered MRE11 levels was linked with genome wide alterations that can influence platinum sensitivity.
Ovarian neoplasmRNF43Verified39125653, 31695154, 35487932RNF43 mutations with impaired E3 ligase activity were found in several types of cancers (e.g., gastrointestinal system tumors and endometrial and ovarian cancer)... Teratoma-associated mucinous tumors were characterized by mucinous stromal dissection, SATB2 expression and RNF43 mutations.
Ovarian neoplasmSEMA4AVerified40196117The results of differential expression analysis, correlation analysis, and drug sensitivity analysis suggest that CTLA4, PD-1, TIGIT, LAG3, TIM3, NRP1, VISTA, CD80, CD86, PD-L1, PD-L2, PVR, PVRL2, FGL1, LGALS9, HMGB1, SEMA4A, and VEGFA are associated with tumor prognosis and immune cell infiltration.
Ovarian neoplasmSMAD4Verified33372356, 34747309, 32366274, 33605573, 31569186, 34820170The study in PMID 33372356 found that circATRNL1 binds to miR-378 which directly targets SMAD4, indicating SMAD4's role in ovarian cancer. Additionally, PMID 34747309 shows miR-30a inhibits cisplatin resistance through the TGF-beta/SMAD4 pathway. PMID 32366274 demonstrates miR-145-5p targets SMAD4 to regulate EOC cell proliferation. PMID 33605573 reveals GPBAR1 promotes SOC proliferation by inducing SMAD4 ubiquitination. These studies collectively validate SMAD4's association with ovarian neoplasm.
Ovarian neoplasmSOX9Verified37468993, 34881182, 35159173, 37020558, 32343928Our results showed significant upregulation of circ-PHC3 in both OC cell lines and tissues. In the luciferase reporter assay, downregulation of circ-PHC3 led to suppression of metastasis and proliferation, potentially through targeted effects on the miR-497-5p/SOX9 axis in OC. SOX9 overexpression or miR-497-5p suppression rescued OC cell proliferation and invasion following silencing of circ-PHC3. Moreover, SOX9 inhibition induced restoration of OC cell invasion and proliferation under conditions of overexpression of miR-497-5p. Thus, circ-PHC3 appears to exert effects on cancer stem cell differentiation through regulation of the miR-497-5p/SOX9 axis. (PMID: 37468993); Transcription factors of the SOX family... It plays an important role in inducing tissue and cell morphogenesis, survival, and many developmental processes. Furthermore, it has been shown to be an oncogene in many tumors. ... we discuss the role of SOX9 in gynecological malignancy pathogenesis through its mediation of important mechanisms, including tumor initiation and proliferation, apoptosis, migration, invasion, chemoresistance, and stem cell maintenance. (PMID: 34881182); ...transcription factor SOX9 showed a strong correlation with stemness-regulating ALDH1A1 and was localized predominantly in the cytoplasm of HGOC with lymph node metastasis. ... SOX9 knockdown in vitro resulted in changes in cell morphology, cell cycle, stem cell marker expression, cell invasion, and sphere formation. Furthermore, in vivo knockdown completely inhibited tumor growth in mouse xenograft model. (PMID: 35159173); ...SOX9 expression was significantly increased in fifteen cancers, including ... OV ... suggesting that SOX9 expression is upregulated in the most cancer types ... as a proto-oncogene. ... SOX9 could be a biomarker for diagnostics and prognostics for pan-cancers and an emerging target for the development of anticancer drugs. (PMID: 37020558); ...high expression of SOX9 and low expression of miR-30-5p were witnessed in OC. Furthermore, miR-30-5p ... increased the rate of cell apoptosis and enhanced the sensitivity of SKOV3/DDP cells to DDP by targeting SOX9. (PMID: 32343928)
Ovarian neoplasmSPRED1Verified37434064LOC646029 served as a miR-627-3p sponge to promote the expression of Sprouty-related EVH1 domain-containing protein 1, which is necessary for suppressing tumor metastasis and inhibiting KRAS signaling.
Ovarian neoplasmSUFUVerified40565349, 33860896, 34888241, 32957513Higher expression levels of SUFU were associated with a negative impact on ovarian cancer patients under many clinical-histopathological aspects. These results shed new light on the role of these genes in the chemoresponsiveness of ovarian cancer, especially SUFU, which could be considered a novel indicator for poor prognosis in epithelial ovarian cancer.
Ovarian neoplasmTGFBR2Verified35115831, 38214360, 38027211, 35370397In the first study (PMID: 35115831), exosomal lncRNA ATB from ovarian cancer cells promotes angiogenesis via the miR-204-3p/TGFbetaR2 axis. The second study (PMID: 38214360) shows that circ_0070203 promotes epithelial-mesenchyma...
Ovarian neoplasmWNT10AVerified39456618, 32434423The ten most significant DMRs, discriminating BOT from lgOvCa, encompassed the MHC region on chromosome 6. ... DMRs with the best discriminative capabilities overlapped the following genes: ... WNT10A, ... in BOTS and hgOvCa, respectively.
Ovarian neoplasmWRNVerified40767886, 37452354, 38756073PMID 38756073: '...seven independent OSRGs were used to construct a prognostic risk score model...WRN significantly promoted the malignancy and platinum resistance of OC cells.' This indicates WRN's role in ovarian cancer (OC) progression and drug resistance. Additionally, PMID 37452354 reports a germline WRN mutation in a patient with synchronous endometrial and ovarian cancer, linking WRN to ovarian neoplasm.
Ovarian neoplasmWT1Verified36900251, 34314463, 32960974, 32892698, 36819499WT1 is a key antigen in ovarian cancer, with studies showing its expression in various subtypes, including serous tumors, and its role in promoting cancer progression through mechanisms like E-cadherin regulation and ERK1/2 signaling. Additionally, WT1-specific immune responses were observed in patients treated with a WT1 peptide vaccine.
Ovarian neoplasmWWOXVerified31966058, 33300063The expression levels of WWOX... in epithelial ovarian cancer tissues were significantly different from those in adjacent normal tissues... The survival rate of patients with positive expression was significantly higher than that of negative expression. WWOX... was an independent factor affecting postoperative prognosis in ovarian cancer patients. WWOX activation may inhibit chemoresistance and trigger cancer cell death in EOC cells.
Ovarian neoplasmZFPM2Verified39476484, 32636682, 33161412In the study (PMID: 39476484), ZFPM2 is listed as one of the top 10 hub genes commonly identified in both ovarian and endometrial cancers, associated with DNA damage, DNA integrity, and cell-cycle checkpoint signaling pathways. Additionally, in PMID: 32636682, ZFPM2 is identified as a hub gene in the PPI network related to chemoresistance in high-grade serous ovarian cancer. In PMID: 33161412, the ZFPM2 rs4734879 G allele is associated with improved survival outcomes in ovarian cancer patients.
Abnormal posturingHPRT1ExtractedLife (Basel)40724495carried a homozygous variant of HPRT1 gene, c.135G>T (p.Arg45Ser), inherited from an asymptomatic carrier mother, which confirmed the diagnosis of LNS.
Abnormal posturingTOR1ABothLife (Basel)40724495, 40667216, 37134150, 37464831, 40557328The pathophysiological substrate of this mouse model of dystonia lies in spinal neural circuits. Together, these data provide new insights into our current understanding of dystonia pathophysiology. (PMID: 37134150); DYT1 dystonia is an inherited early-onset generalized dystonia characterized by sustained muscle contractions causing abnormal, repetitive movements or postures. (PMID: 40557328)
Abnormal posturingSGCEExtractedHuman Genome Variation35995778identified a rare variant in the SGCE gene, NM_003919.3: c.304C > T [Arg102*], in this patient.
Abnormal posturingMOCS2ExtractedZhonghua Er Ke Za Zhi35995778carried a homozygous variant of MOCS2 gene, c.19G>T(p.Val7Phe), which was a previously reported pathogenic site in the literature and could cause MoCD-B.
Abnormal posturingDAGLAExtractedBrain35737950heterozygous, de novo truncating variants in the last exon of DAGLA with a neuro-ocular phenotype characterized by developmental delay, ataxia and complex oculomotor abnormality.
Abnormal posturingGBAExtractedJ Neural Transm (Vienna)34779914identified 14 heterozygous GBA alleles consisting of altogether 17 missense variants (8 classified as pathogenic or likely pathogenic for PD) in 25 (5.0%) patients.
Abnormal posturingCelsr1ExtractedFront Neurosci34790090Celsr1 is a PCP protein and a Celsr1 KO mouse model showed hair cell disorganization in all vestibular organs, especially in the canalar ampullae.
Abnormal posturingKMT2BExtractedLife (Basel)40724495TOR1A, SGCE, and KMT2B are the most frequently reported in pediatric forms.
Abnormal posturingAOPEPVerified40841848The abstract states: 'Advances in genetics have identified key causative mutations-most notably in KMT2B, VPS16, EIF2AK2, PRKRA, and AOPEP- that contribute to disease onset and progression, with varying degrees of clinical penetrance.' Generalized dystonia is characterized by 'abnormal postures and movements' as per the abstract's background section. Since AOPEP is listed among the causative genes for generalized dystonia, which includes the phenotype of abnormal posturing, this supports the association.
Abnormal posturingPANK2Verified35655240Type 1 neurodegeneration with brain iron accumulation is a rare neurological disorder... produced by brain iron accumulation due to a defect in the gene producing pantothenate kinase 2. Clinical presentations include dystonia...
Absent inner dynein armsDNAH1ExtractedAsian J Androl36510862Three patients with dynein axonemal heavy chain 1 (DNAH1) gene compound heterozygous variations were identified.
Absent inner dynein armsDNAH10ExtractedAsian J Androl39996363two novel compound heterozygous variants in the gene, dynein axonemal heavy chain 10 (DNAH10)
Absent inner dynein armsDNAH2ExtractedFront Cell Dev Biol33968937identified a novel recessive variant (NM_020877:c.12720G > T;p.W4240C) in DNAH2
Absent inner dynein armsDNAH5ExtractedBMC Pulm Med34391405The patient carried two novel compound heterozygous mutations in DNAH5, NM_001369:c.12813G > A (p. Trp4271Term) and NM_001369:c.9365delT (p. Leu3122Term).
Absent inner dynein armsDNAH8ExtractedAsian J Androl36308074a novel homozygous frameshift variant (c.6158_6159insT) in dynein axonemal heavy chain 8 (DNAH8)
Absent inner dynein armsCFAP161ExtractedSci Rep34172766the evolutionary conserved FOXJ1 target CFAP161
Absent inner dynein armsDNAH11ExtractedBMC Pediatr35804324High frequencies of DNAH11 mutations were detected by integrating data from PCD patient cohorts in China.
Absent inner dynein armsCCNOExtractedFront Mol Biosci40182617further genetic analysis revealed biallelic pathogenic variants in CCNO in the affected individual.
Absent inner dynein armsDNAH17ExtractedAsian J Androl36308074an immunofluorescence assay showed the absence of DNAH8 and a reduction in its associated protein DNAH17 in the patients' spermatozoa.
Absent inner dynein armsRSPH3ExtractedFront Cell Dev Biol33968937Absence of DNAH2 compromises the expression of other axonemal components such as DNAH1 and RSPH3.
Absent inner dynein armsCCDC39Verified36552811, 39056782, 35795318, 33760720, 39867101, 39896853PMID 39056782: '...IDA heavy chains DNAH1, DNAH6, and DNAH7 are conspicuously absent within the respiratory ciliary axonemes...'. PMID 35795318: '...CCDC39 is essential for assembling the inner dynein arms...'. PMID 33760720: '...steepest rise in lung volumes was in CCDC39 and CCDC40...'. PMID 39867101: '...novel homozygous c.2347_2351del (p.Phe783ThrfsTer3) PVS1 null variant in exon 17 of the CCDC39 gene...associated with autosomal recessive primary ciliary dyskinesia-14...'. PMID 39896853: '...CCDC39 gene (IDA/MTD) was associated with worse olfactory dysfunction.'
Absent inner dynein armsCFAP300Verified39254424, 33635866, 36246608The proband had a PCD phenotype with laterality defects and immotile sperm flagella displaying a combined loss of the inner dynein arm (IDA) and outer dynein arm (ODA).
Absent inner dynein armsDNAAF3Verified39764684, 34553759The absence of outer dynein arms and inner dynein arms was also observed. ... The mutant Ch neuron cilia of the antenna specifically lack dynein arms, ... mutant males are infertile with immotile sperm whose flagella lack dynein arms and show axoneme disruption.
Absent inner dynein armsDNAH7Verified39056782, 36792588, 37594300, 37998386, 38312775PMID 39056782: '...the IDA heavy chains DNAH1, DNAH6, and DNAH7 are conspicuously absent within the respiratory ciliary axonemes...'. PMID 36792588: '...loss of sperm DNAH1 and DNAH7...'. PMID 37594300: '...absence of inner dynein arms... in the sperm of patients with DNAH6 variants, which are associated with DNAH7...'
Absent inner dynein armsTTC12Verified37325566, 36273201Three mutants were indicated to be damaging using in silico prediction tools, and were further confirmed by in vitro functional analysis. Hematoxylin and eosin staining and ultrastructural observation of the spermatozoa revealed multiple morphological abnormalities of flagella, with the absence of outer and inner dynein arms. ... Transmission electron microscopy analysis further identified ultrastructural defects of the inner dynein arms in this patient.
Increased circulating gonadotropin levelARVerified38973535Our results showed that the apelin, APJ and androgen receptor (AR) expression were upregulated in the anterior pituitary. Furthermore, the immunostaining of LH exhibited increased abundance than FSH. The circulating LH was also found to be elevated compared to FSH levels. The increased LH synthesis and secretion coincides with elevated apelin system in the pituitary of hyperandrogenised mice.
Increased circulating gonadotropin levelFSHBVerified34884539, 34938157, 38559622, 35645980, 37375761, 35575351, 38571513The study in PMID 34938157 shows that exposure to CB NPs increases both circulating FSH levels and pituitary FSH beta-subunit gene (Fshb) expression in female mice. This directly links FSHB to increased circulating gonadotropin levels.
Increased circulating gonadotropin levelFSHRVerified33605422, 40171200, 33321143, 36499026The olfactory preference tests revealed that injecting eCG, but not hCG, significantly increased the probe males` preference compared to HPx male odor, suggesting that the attractiveness is augmented via follicle stimulating hormone (FSH) receptor rather than luteinizing hormone receptor.
Increased circulating gonadotropin levelGATA4Verified38674332GATA4 is essential for basal Gnrh expression by binding to its enhancer region, with Oct-1 (Oct1) and CEBP-beta (Cebpb) playing regulatory roles. ... miR-466c significantly downregulates Gnrh, Gata4, and Chop mRNA and increases Per2, whereas miR-340 upregulates Gnrh, Gata4, Oct1, Cebpb, and Per2 mRNA.
Increased circulating gonadotropin levelLHBVerified34884539, 36941851, 34905605, 36952069, 38433961In the study on Hippo pathway effectors YAP and TAZ, gonadotrope-specific inactivation of Yap and Taz resulted in increased circulating levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in adult male mice... Female cKO mice had increased circulating LH (but not FSH) levels... Additionally, in the study on TGFBR3L, the presence of TGFBR3L was negatively associated with plasma gonadotropin concentrations in males (P-LH median 1.8 [IQR 1.1-3.0] in TGFBR3L positive tumours) and P-LH (median 2.8 IU/L [IQR 1.9-3.7] and median 1.8 [IQR 1.1-3.0] in TGFBR3L negative and positive tumours respectively, p = 0.03).
Increased circulating gonadotropin levelLHCGRVerified33605422, 33809538, 38187770, 31782269In infertile men, seminal fluid sLHCGR was inversely associated with serum FSH (beta 0.006, p = 0.009), sperm concentration (beta -3.5, p = 0.003) and total sperm count (beta -3.2, p = 0.007). The injection of hCG lowered sLHCGR in serum and urine of healthy men (p < 0.01).
Increased circulating gonadotropin levelMAP3K1Verified31998776, 37759668PMID 31998776 reports that MAP3K1 mutations were detected in 18.2% of GTN patients and that mRNA and protein levels of MAP3K1 were upregulated in JAR and JEG-3 choriocarcinoma cells. Given that GTN is associated with elevated hCG (a gonadotropin), and the study links MAP3K1 to GTN progression, this supports an association between MAP3K1 and increased circulating gonadotropin levels.
Increased circulating gonadotropin levelNR5A1Verified34944287, 39911518Three DEPs (FST, NR5A1, and PRL) were involved in neurochemical signal transduction, as well as endocrine and reproductive hormone regulatory processes. The Kyoto Encyclopedia of Genes and Genomes analysis indicated the involvement of several pathways, including the calcium, cAMP, gonadotropin-releasing hormone, MAPK, and neuroactive ligand-receptor signaling pathways, suggesting that induced ovulation depends on the hypothalamic-pituitary-ovarian axis.
MaculeCBLBoth38613168, 39076033PMID 38613168 reports a patient with a CBL variant presenting with cafe-au-lait macules. PMID 39076033 notes cafe-au-lait macules occur in 22% of Noonan syndrome-like disorder (NSLD) cases linked to CBL variants.
MaculeTSC1Both40655935, 36833359The clinical examination revealed: ... depigmented macules, ... Molecular diagnosis showed a pathogenic variant in the TSC1 gene, exon 13, c.1270A>T (p. Arg424*).
MaculeTSC2Both40655935, 38596252, 36895714, 38500310, 377408601. 'hypopigmented macules' were observed in a patient with TSC-LAM caused by a TSC2 gene mutation (PMID: 38596252). 2. 'hypopigmented macules' were also noted in an infant diagnosed with tuberous sclerosis complex type 2 due to a TSC2 gene deletion (PMID: 38500310). 3. A patient with TSC2/PKD1 contiguous gene deletion syndrome presented with 'hypomelanotic macules' (PMID: 36895714). These findings directly associate the TSC2 gene with the macule phenotype.
MaculePSENENBoth38420230, 33768038, 32478413, 32831371PMID: 33768038: 'Dowling-Degos is a rare autosomal dominant genodermatosis characterized by multiple hyperpigmented macules or papules in reticulate pattern... PSENEN mutation analysis revealed a splice site mutation c.62-1G>T.'; PMID: 32478413: 'Scrotal Dowling-Degos disease... A heterozygous PSENEN frameshift variant c.292delC(p.L98Wfs*47) was identified...'. PSENEN mutations are directly linked to Dowling-Degos disease, which is characterized by hyperpigmented macules.
MaculeNF1Both40741214, 35098592, 40361417, 36699773, 35756263, 40463710, 34139091, 32393377Cafe-au-lait macules (CALMs) are a hallmark of the disease... (PMID: 40361417); ...patients with cafe-au-lait macules and cutaneous neurofibromas may present with acute cervical hematoma... (PMID: 36699773); ...presence of cafe-au-lait macules... (PMID: 35756263); ...multiple cafe-au-lait macules... (PMID: 40463710); ...cafe-au-lait macules... (PMID: 32393377). The NF1 gene is directly linked to the presence of cafe-au-lait macules across multiple studies.
MaculeGNASBoth34632888, 37239810, 38387948, 38255009, 34839987, 40078582, 37560302McCune-Albright syndrome (MAS) is a rare sporadic condition defined by the classic triad of fibrous dysplasia of bone, cafe au lait skin macules, and hyperfunctioning endocrinopathies. The molecular basis of MAS has been ascribed to the post-zygotic somatic gain-of-function mutations in the GNAS gene... (PMID: 37239810); McCune-Albright syndrome is a rare genetic, non-inheritable disease and is characterized by fibrous dysplasia, hyperendocrinism, and cafe-au-lait macules... (PMID: 34632888); McCune - Albright syndrome is a genetic disease with cutaneous mosaicism caused by post-zygotic activating mutations in GNAS locus... (PMID: 34839987)
MaculeNOTCH1Extracted40469827sequencing identified mutations in the NOTCH1 and NOTCH2 genes.
MaculeNOTCH2Extracted40469827sequencing identified mutations in the NOTCH1 and NOTCH2 genes.
MaculeKRT14Both40469827, 37043976The keratin 14 (KRT14) gene mutations that cause this autosomal dominant condition result in abnormal keratinocyte activity. A variety of cutaneous symptoms are its defining characteristics. Clinically, NFJS manifests as palmoplantar keratoderma, hypo- and hyperpigmented macules, lack of dermatoglyphics, and lack of sweating.
MaculeABCB6Verified37634201, 32849825, 39557842, 40584949ABCB6 has been implicated in dyschromatosis universalis hereditaria, a condition characterized by hyperpigmented and hypopigmented skin macules. The most common gene involved in DUH is ABCB6, while the other genes include SASH 1, PER 3, and KITLG (DUH type 2).
MaculeADAM10Verified40950988pathogenic variants in ADAM10 (a disintegrin and metalloprotease 10) were identified as causative in multiple Japanese RAK pedigrees. RAK is an extremely rare autosomal dominant disorder. Cafe-au-lait macules (CALMs) represent common hyperpigmented lesions, yet no documented cases of RAK-CALMs coexistence exist in the literature to date.
MaculeADARVerified35832578, 37740860, 37770123Dyschromatosis symmetrica hereditaria (DSH), characterized by a mixture of hyper- and hypopigmented macules on the skin... The pathogenic gene is adenosine deaminase acting on the RNA 1 gene (ADAR1)... We report the first case of DSH combined with AGS caused by the homozygous mutation of the ADAR1 gene... a 6-year-old female... with hypopigmented and hyperpigmented macules and patches consistent with dyschromatosis symmetrica hereditaria (DSH)... de novo, heterozygous mutation in the adenosine deaminase acting on RNA 1 (ADAR) gene.
MaculeAKT1Verified34105192The study reports that individuals with the mosaic c.49G>A, p.Glu17Lys AKT1 variant exhibited hyperpigmented macules in 27 (53%) and hypopigmented macules in 16 (31%). These findings directly associate the AKT1 gene with the presence of macules in Proteus syndrome.
MaculeANKLE2Verified35871307Six probands had skin findings characteristic of ANKLE2 including hyper- and hypopigmented macules.
MaculeATP2A2Verified32155025The abstract states: 'It has been theorized that the mutation in ATP2A2 causes defective E-cadherin, which in turn disrupts the adhesion of melanocytes to keratinocytes, thus leading to impaired dendrite formation, hindered melanin transfer, and ultimately to melanocyte apoptosis.' This supports the association of ATP2A2 with the phenotype of macules in Darier disease, as the described pathophysiological process would result in hypopigmented macules.
MaculeBRCA1Verified40519302This eleventh FA-S proband with severe microcephaly, growth failure, duodenal stenosis, hyperpigmented macules, dysmorphic features, and abnormal chromosomal breakage, consistent with other FA-S patients.
MaculeCTLA4Verified35388753, 36891313vitiligo... (such as DDR1, XBP1, NLRP1, PTPN22, COMT, FOXP3, ACE, APE, GSTP1, TLR, SOD, and CTLA-4).
MaculeIL6Verified32411563, 39483658Vitiligo is an acquired depigmenting disorder due to the destructive loss of melanocytes, clinically presenting as hypopigmented or depigmented macules and/or patches. ... Interleukin-6 (IL-6) ... are found to be relevant in determining vitiligo disease activity.
MaculeDDB2Verified32228487We report a case of a 28-year-old Chinese woman with freckle-like hyperpigmented macules in a sun-exposed area who is prone to develop basal cell carcinomas. A genetic study revealed a novel homozygous c.111_112del deletion in exon 1 of the DDB2 gene.
MaculeENPP1Verified28964717The patients presented with hypo- and hyperpigmented macules over the body, resembling dyschromatosis universalis hereditaria in addition to punctuate palmoplantar keratosis. By homozygosity mapping and whole-exome sequencing, a biallelic p.Cys120Arg mutation in ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) was identified in all patients.
MaculeEPHB4Verified34170521, 32840927In 33 patients, a brain and spine MRI was performed, which detected a spine AVM in one symptomatic patient with sensorimotor deficits. No cerebral AVM or AVF was picked up in the cohort. A RASA 1 result was available for evaluation in 24, of which 16 (67%) were positive. An EPHB4 result was available in eight, two (25%) of which were positive. (PMID: 34170521) Additionally, all 4 patients tested for EPHB4 mutations had a positive result. (PMID: 32840927) The presence of EPHB4 mutations is associated with CM-AVM syndrome, which includes the phenotype of macules.
MaculeERCC2Verified32974964, 33996357The patient harbored a homozygous mutation of c.1802G>T, p.Arg601Leu in ERCC2... freckle-like pigmented macules in sun-exposed areas... Arg601Leu mutation in ERCC2 may be related to mild UV radiation sensitivity and moderate skin lesions.
MaculeGNAQVerified34231495A 63-year-old woman presented with a congenital, large, blue-colored macule limited to the hypochondriac area of the right breast. ... Sanger sequencing confirmed the GNAQ Q209P mutation...
MaculeIFNGVerified35884944, 40344159, 40466982PMID: 35884944: 'IFN-gamma is the primary cytokine mediator that activates the JAK/STAT pathway, causing keratinocytes to produce the key chemokines CXCL9 and CXCL10.'; PMID: 40466982: 'cytotoxic T-cell activity and interferon-gamma (IFN- ) mediated immune response have been studied extensively in disease pathogenesis.' Macule is a clinical feature of vitiligo, and IFNG is involved in the immune response leading to melanocyte apoptosis, which causes depigmented macules.
MaculeKITVerified37394438, 37089832, 37357653, 38524391, 38522933, 39269165, 32077120Multiple studies report KIT mutations in patients presenting with macules. For example, a case of maculopapular cutaneous mastocytosis (MPCM) was diagnosed with an Asp419del mutation in the KIT gene, resulting in brown macules. Additionally, piebaldism cases with KIT mutations show depigmented macules, and FPHH cases with KITLG variants present cafe-au-lait spots and hypopigmented macules, all indicating KIT's role in macule formation.
MaculeKITLGVerified34716665, 39269165, 37634201Familial Progressive Hyper- and Hypopigmentation is a pigmentary disorder characterized by a mix of hypo- and hyperpigmented lesions, cafe-au-lait spots and hypopigmented ash-leaf macules. ... We identified a de novo mutation in exon 4 of KITLG gene... (PMID: 34716665). Additionally, a case of FPHH presented with hypopigmented macules and striae along the lines of Blaschko due to a novel KITLG mutation (Ser78Leu) (PMID: 39269165).
MaculeKLLNVerified31062505By array-CGH analysis, we identified an interstitial 10q23.1q23.3 deletion in a buccal mucosa sample of Patient 1 that encompassed PTEN, BMPR1A, and KLLN, among others.
MaculeKRT5Verified40667493, 38390850, 36919394The main pathogenesis behind DDD is a mutation in the keratin 5 gene. ... The disease is caused by a loss-of-function mutation of keratin 5 (KRT5) present on the chromosome 12q gene. ... Galli-Galli disease (GGD) ... shares mutations in the KRT5 and POGLUT1 genes. ... Both DDD and GGD are associated with macular lesions, with DDD characterized by brown to black macules and GGD featuring erythematous macules and reticulate hyperpigmentation.
MaculeLZTR1Verified39258154Our study expands the LZTR1 phenotype to the presence of isolated cafe au lait macules with or without freckling. Thus, variants in the LZTR1 gene should be considered in patients with multiple cafe au lait macules.
MaculeMAP2K1Verified20301557The molecular diagnosis can be established in a proband with suggestive findings and a heterozygous pathogenic variant in one of four genes (BRAF, MAP2K1, PTPN11, and RAF1).
MaculeMLH1Verified39910726, 36897649, 39524392Patients with CMMRD present with cafe-au-lait macules that are fewer in number and larger than in patients with neurofibromatosis type 1. ... All the four CMMRD syndrome patients had CALMs since birth. ... MLH1 mutation
MaculeMSH2Verified39910726, 36897649Patients with CMMRD present with cafe-au-lait macules that are fewer in number and larger than in patients with neurofibromatosis type 1. Additional dermatological findings include hypopigmented patches and intertriginous freckling. PMS2 and MSH6 pathogenic variants are linked to the broadest spectrum of cutaneous manifestations, including vascular tumors, various nevi, and pilomatricomas.
MaculeMSH6Verified33568103, 39910726, 36897649Patients with CMMRD present with cafe-au-lait macules that are fewer in number and larger than in patients with neurofibromatosis type 1. ... PMID: 39910726; An 11-year-old girl, who presented with multiple spots resembling cafe-au-lait macules since birth, ... genetic testing revealed compound heterozygous variants, c.[2969T > A (p.Leu990*)] and [3064G > T (p.Glu1022*)] in the MSH6 gene; ... PMID: 33568103; All children with CMMRD have cafe-au-lait macules (CALMs)... PMID: 36897649
MaculeNF2Verified40843672, 35729665The objective of this study was to characterize cutaneous manifestations of NF2 in a paediatric population... Patients' dermatological examination also revealed < 6 non specific cafe au lait macules (n = 15), hypopigmented macules (n = 12) with more than 3 lesions in 4 cases, and purple reticulated macules of the trunk (n = 4).
MaculeNRASVerified32246533, 35997352The PNF had biallelic NF1 deletions, a whole deletion of NF1 and a novel intragenic deletion involving exons 25-30. The deletions were not detected in the blood, which resulted in the diagnosis of mNF1. Furthermore, the nevus cells had not only biallelic NF1 deletions but also NRAS Q61R, a common mutation found in congenital melanocytic nevi.
MaculePIK3CAVerified37965451The well-known side effects of alpelisib are hyperglycemia, rash, and diarrhea. Herein, we report a case of a woman who developed diffuse depigmented macules on the face, arms and legs, three months after initiating alpelisib. Both clinical and histopathological findings were consistent with new-onset vitiligo.
MaculePMS2Verified34247610, 39910726, 36897649Patients with CMMRD present with cafe-au-lait macules that are fewer in number and larger than in patients with neurofibromatosis type 1. ... PMS2 pathogenic variants are linked to the broadest spectrum of cutaneous manifestations, including vascular tumors, various nevi, and pilomatricomas.
MaculePOFUT1Verified32258313Novel POFUT1 mutation in patient with flexural and acral hyperpigmented reticulated macules presenting in adolescence.
MaculePOGLUT1Verified38390850The review explores the genetic, histopathological, and clinical parallels between GGD and DDD, noting their shared mutations in the KRT5 and POGLUT1 genes. This supports the hypothesis that GGD and DDD may be different phenotypic expressions of the same pathological condition, with GGD featuring brown macules predominantly on the trunk, lower limbs, and extremities.
MaculePORCNVerified36313953, 37892378Focal dermal hypoplasia is induced by a mutation in the PORCN gene. ... multi-hypopigmented reticulated atrophic macules and patches grouped in linear mode at the lines of blaschko...
MaculePTENVerified20301661, 34179044BRRS is a congenital disorder characterized by macrocephaly, intestinal hamartomatous polyposis, lipomas, and pigmented macules of the glans penis. ... Characteristic skin lesions include trichilemmomas, acral keratosis, mucocutaneous neuromas, oral papillomas, and penile macules, and are often the first clues to the underlying diagnosis.
MaculePTPN11Verified37056170Two novel variants c.1548 T > A (p.Ser516Arg) and c.1811C > A (p.Thr604Lys) in SASH1, and two recurrent variants c.1403C > T (p.Thr468Met) and c.1493G > T (p.Arg498Leu) in PTPN11, were identified in these four families. We also summarized the genes associated with ML and differential diagnosis of pigment abnormality.
MaculeRAF1Verified20301557The molecular diagnosis can be established in a proband with suggestive findings and a heterozygous pathogenic variant in one of four genes (BRAF, MAP2K1, PTPN11, and RAF1).
MaculeSASH1Verified40511878, 34174894, 32849825, 40584949, 32174800, 37634201Dyschromatosis universalis hereditaria (DUH) is a rare genodermatosis characterized by asymptomatic hyper- and hypopigmented macules appearing in infancy and persisting for life... SASH1 mutations have been associated with the pure-lentiginous phenotype of familial pigmentation. In this review of literature, we found 22 different SASH1 mutations... These variants cause distinct phenotypes, including DUH, lentiginosis... Functional studies have revealed that SASH1 acts as both a tumor suppressor and a pro-melanogenic factor. It modulates key pathways such as p53-POMC-a-MSH-MC1R-MITF and Gas-SASH1-IQGAP1-E-cadherin pathways, affecting melanosome production, transport, and melanocyte migration. This unique dual role of SASH1 highlights its importance in melanocyte homeostasis and UV-induced pigmentation. Understanding the role of SASH1 in regulating pigmentation can help foster novel therapeutic approaches for these genodermatoses and related pigmentary anomalies, ultimately improving patient care and outcomes.
MaculeSMARCAL1Verified25748404This disease involves multiple systems and is characterized by short and dissymmetric stature with spondyloepiphyseal dysplasia, progressive renal failure, lymphopenia with recurrent infections, and hyperpigmented macules.
MaculeSOX10Verified40743490, 35339139, 31361351, 35574207, 35170472In the context of vitiligo-like macules in scleroderma (PMID: 40743490), SOX10 staining was used to demonstrate absent junctional melanocytes, which is a key histopathologic feature distinguishing scleroderma from vitiligo. Additionally, in a case of eruptive facial lentiginosis-like repigmentation in vitiligo (PMID: 35339139), SOX10 immunohistochemistry showed nuclei of single melanocytes in hyperpigmented macules. These findings directly associate SOX10 with the presence or absence of melanocytes in macular lesions.
MaculeSPRED1Verified39031930, 37927732, 31573083, 32147744Legius syndrome, commonly referred to as SPRED1-related neurofibromatosis type 1-like syndrome, is a rare autosomal dominant disorder characterized by cafe-au-lait macules... The SPRED1 gene encodes the Sprouty-related protein with an EVH1 domain 1 (SPRED1)... We identified 12 novel SPRED1 damaging variants segregating with the phenotype in all families. ... Children with neurofibromatosis type 1 (NF1) may exhibit an incomplete clinical presentation... phenotypic overlap may exist in children with other RASopathies... multiple cafe-au-lait macules (CALMs)... pathogenic mutations mainly in the NF1 gene, but also in SPRED1...
MaculeSTK11Verified38626741, 40860288, 38800180, 38061703, 39080663, 20301443Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant disorder hallmarked by mucocutaneous melanocytic macules and gastrointestinal hamartomatous polyposis associated with germline/somatic pathogenic variants in the tumor suppressor STK11. ... brown macules distributed in the perioral skin, oral mucosa, hands and feet ... mucocutaneous hyperpigmentation presents in childhood as dark blue to dark brown macules around the mouth, eyes, and nostrils, in the perianal area, and on the buccal mucosa. Hyperpigmented macules on the fingers are common.
MaculeTMC6Verified33262542Next-Generation Sequencing Identifies a Homozygous Nonsense p.Tyr370* Mutation of the TMC6 Gene in a Mexican Pedigree with Epidermodysplasia Verruciformis. ... Clinical manifestations include flat, scaly, reddish hypo- and hyperpigmented macules...
MaculeTYMSVerified40207375The patient had physical and developmental features of 18p monosomy, including poor growth, feeding issues, distinctive facial features, and strabismus. In early infancy, he developed diffuse hyperpigmentation as well as numerous punctate hypopigmented macules, sparse hair, and nail dystrophy, and diagnosis of DC was confirmed with a telomere length assay.
MaculeUSB1Verified40289594Patients typically present with poikiloderma, which includes hypopigmented and hyperpigmented macules, telangiectasia, atrophy, as well as nail thickening and palmoplantar hyperkeratosis. The condition is caused by pathogenic variants in the USB1 gene...
MaculeXPAVerified36866916We herein report a case of a 4-year-old Filipino girl... confirmed by whole-exome sequencing and skin biopsy, respectively.
MaculeXPCVerified40252274, 33996357, 35170472In PMID 40252274, the patient presented with multiple discrete hyperpigmented and depigmented macules on her face, neck, upper chest, and arms. The genetic analysis identified a novel homozygous pathogenic variant in the XPC gene at c.2420 + 1 G>C. In PMID 33996357, the cases presented had freckle-like pigmentation on the face, trunk, and extremities, which progressed since childhood, with mutation analysis finding a novel pathogenic variant of XPC. These findings directly associate XPC mutations with the development of macular skin lesions.
ExstrophyWNT3ExtractedHum Mol Genet24852367a highly conserved 32 kb intergenic region between WNT3 and WNT9b as possible susceptibility locus for isolated classic exstrophy of the bladder.
ExstrophyWNT9BExtractedHum Mol Genet24852367a highly conserved 32 kb intergenic region between WNT3 and WNT9b as possible susceptibility locus for isolated classic exstrophy of the bladder.
ExstrophyPORCNExtractedPMID 2313116923131169a heterozygous mutation in the PORCN gene
ExstrophyMTHFRExtractedPMID 1660200616602006the homozygous 677T allele of the methylenetetrahydrofolate (MTHFR) gene 677C-->T polymorphism
ExstrophyTP63BothPMID 2358485023584850, 33347773Expression of p63 was lower in patients with exstrophy-epispadias complex compared to controls (p <0.0001).
ExstrophyBmpExtractedPMID 2764947527649475genetic interactions between growth factors such as bone morphogenetic proteins (Bmp) and transcription factors such as Msx1/2 and Isl1
ExstrophyMsx1ExtractedPMID 2764947527649475genetic interactions between growth factors such as bone morphogenetic proteins (Bmp) and transcription factors such as Msx1/2 and Isl1
ExstrophyMsx2ExtractedPMID 2764947527649475genetic interactions between growth factors such as bone morphogenetic proteins (Bmp) and transcription factors such as Msx1/2 and Isl1
ExstrophyIsl1ExtractedPMID 2764947527649475genetic interactions between growth factors such as bone morphogenetic proteins (Bmp) and transcription factors such as Msx1/2 and Isl1
Exstrophyp63ExtractedPMID 1707927517079275DeltaNp63 plays an anti-apoptotic role in ventral bladder development
ExstrophyIL13ExtractedPMID 2041829520418295promoter polymorphisms in interleukins 13 and 18 (IL13 and IL18)
ExstrophyIL18ExtractedPMID 2041829520418295promoter polymorphisms in interleukins 13 and 18 (IL13 and IL18)
ExstrophyOTX1ExtractedPMID 2520306225203062deletions in the 2p15 region encompassing OTX1
ExstrophyParm1ExtractedPMID 2276639922766399Parm1 gene analysis revealed no alterations...
ExstrophyISL1Verified37649128, 39687282, 39358471, 36349425, 29619236, 28176844ISL1 has been described as an embryonic master control gene expressed in the pericloacal mesenchyme. Deletion of Isl1 from the genital mesenchyme in mice leads to an ectopic urethral opening and epispadias-like phenotype. Using genome wide association methods, we identified ISL1 as the key susceptibility gene for classic bladder exstrophy (CBE), comprising epispadias and exstrophy of the urinary bladder. The most significant marker (rs6874700) identified in our recent GWAS meta-analysis achieved a p value of 1.48 x 10- 24 within the ISL1 region.
ExstrophyKRASVerified31957550, 26955660PMID 31957550 discusses malignancies after augmentation enterocystoplasty, including cases following bladder exstrophy. It reports that one of the tumors analyzed had a KRAS-p.Gly12Asp missense mutation. This directly links KRAS to malignancies in the context of exstrophy-related bladder conditions. Additionally, PMID 26955660 mentions a case of primary bladder adenocarcinoma (PBA) with wild-type KRAS, which is relevant to bladder exstrophy as PBA is commonly associated with it. Together, these studies associate KRAS with exstrophy-related bladder malignancies.
ExstrophyMED12VerifiedMED12 mutations are associated with a range of developmental disorders, including uterine didelphys and bladder exstrophy. The gene is involved in transcriptional regulation and has been linked to specific phenotypes in multiple studies.
LymphangiectasisFOXF1BothUnknown32386508, 29198536In both of these children, glomeruloid endothelial proliferation of vessels was noted in the interlobular septa. The vessels were immunohistochemically positive for D2-40, CD31, Factor VIII, and ERG, suggestive of differentiation for both lymphatic and blood vessels.
LymphangiectasisPTPN11ExtractedUnknown40041314Most are dominant gain-of-function variants [...] PTPN11 class 5 variant. [...] NS can be associated with [...] lymphatic anomalies.
LymphangiectasisADAMTS3BothUnknown37583869The abstract states that whole exome sequencing revealed heterozygous mutations of the lymphangiogenesis-controlling genes, ADAMTS3 and FLT4, and Sanger verification revealed similar lesions in the mother with no symptoms. The case presented shows that mutations in ADAMTS3 are associated with lymphangiectasia in the neonate.
LymphangiectasisFLT4ExtractedUnknown37583869heterozygous mutation of ADAMTS3 and FLT4 genes [...] congenital lymphangiectasia.
LymphangiectasisPALB2ExtractedUnknown38476606novel homozygous missense variant in PALB2 gene [...] lymphangiectasia.
LymphangiectasisBCL6ExtractedUnknown39934754heterozygous variants of BCL6 [...] may facilitate the pathogenesis of DPL.
LymphangiectasisATMExtractedUnknown39934754heterozygous variants of ATM [...] may facilitate the pathogenesis of DPL.
LymphangiectasisPIK3CAExtractedUnknown36639640search for activating mutations of the PIK3CA gene [...] in cystic lymphatic malformations.
LymphangiectasisSOS1ExtractedUnknown20673819SOS1 mutation (c.1867T > A/p.F623I) [...] pulmonary lymphangiectasis.
LymphangiectasisCCBE1BothUnknown30564329Novel mutation in CCBE 1 as a cause of recurrent hydrops fetalis from Hennekam lymphangiectasia-lymphedema syndrome-1.
LymphangiectasisELK3ExtractedUnknown11566878Net-targeted mutant mice [...] dilated lymphatic vessels (lymphangiectasis).
Motor seizureRNU4-2ExtractedNature Medicine38821540RNU4-2, which encodes U4 snRNA, a critical component of the spliceosome, was the most strongly associated gene.
Motor seizureTANC2ExtractedZhonghua Yi Xue Yi Chuan Xue Za Zhi39344613Variants of the TANC2 gene probably underlay the epilepsy and development delay in these children with NDDs.
Motor seizurePACS2BothZhonghua Er Ke Za Zhi34405643, 38545008, 37189870, 34625934, 38540691The seizures were characterized by brief, recurring tonic seizures in the upper limbs, sometimes accompanied by autonomic features. (PMID: 37189870) ... focal seizures and generalized tonic-clonic seizures. (PMID: 34405643) ... tonic seizures, and showed good response to levetiracetam and valproic acid. (PMID: 34405643)
Motor seizureSLC6A1BothFront Pediatr39906729, 39380901, 36741059, 39923323The transporter usually removes GABA from the synapse space between two neurons, limiting over-excitability in the brain, which can lead to seizures and motor deficits... (PMID: 39380901). Additionally, the study in PMID: 39923323 shows that haploinsufficiency of SLC6A1 contributes to epileptic phenotypes, including seizures, and treatment with PBA mitigated seizures in patients.
Motor seizureSCN1ABothbioRxiv38168178, 37551713, 38021637, 34980259, 20301494, 32321192, 35414300, 38785537, 35571373A 14-year-old male patient was admitted to the hospital due to epileptic seizures, which occurred at the beginning of running exercise after being stopped and fast walking. Seizures were consistently characterized by a dystonic posture of the distal portion of the left arm-flexed and adducted by the chest without loss of consciousness. We suspected that this was movement-induced reflex epilepsy and performed whole exome sequencing. Whole exome sequencing revealed a novel SCN1A missense mutation, c.5549T>G (p.Ile1850Ser). SCN1A mutations have not been reported in patients with reflex epilepsy induced by movement. This report enriches the genotypes and phenotypes of SCN1A-related epilepsy and provides further insight into the etiology of reflex epilepsy induced by movement. (PMID: 38021637)
Motor seizureGAT1ExtractedEpilepsia Open37052238E2730 is a novel, selective, uncompetitive GAT1 inhibitor, which acts selectively under the condition of increasing synaptic activity.
Motor seizureGPAA1BothZhongguo Dang Dai Er Ke Za Zhi38112147The boy was found to have delayed mental and motor development at the age of 3 months and experienced recurrent fever and convulsions since the age of 1 year... genetic testing showed compound heterozygous mutations in the GPAA1 gene. The boy was finally diagnosed with glycosylphosphatidylinositol biosynthesis deficiency 15 (GPIBD15) and periodic fever. Electroencephalography showed epilepsy
Motor seizureADAM22Verified37953841Our study indicates that a significant proportion of epilepsy in patients of Roma ancestry may be caused by homozygous c.2714C > T variants in ADAM22.
Motor seizureADNPVerified27054228, 39992398, 32661233PMID 27054228 mentions seizures as a common finding in ADNP-related disorder. PMID 39992398 also describes a case with seizures associated with an ADNP variant. Seizures are a recognized manifestation of ADNP-related disorder.
Motor seizureALDH5A1Verified40763422, 39011401Patients (age at last follow-up: 33.8 +- 8.8 years) had moderate motor deficits and variable degrees of intellectual disability, often with psychiatric symptoms. Epilepsy had heterogeneous presentations, with a mean onset age of 13.1 +- 7.7 years. Drug-resistant seizures and convulsive status epilepticus (SE) occurred in five and three patients respectively; two had possible sudden unexpected death in epilepsy. Prolonged episodes of impaired awareness that preceded or followed convulsive SE were associated with epileptic discharges on EEG and were classified as non-convulsive seizures. In two patients, add-on cenobamate led to a reduction in tonic-clonic seizures and SE.
Motor seizureALDH7A1Verified33868381, 35495162, 38419708, 32395249, 40800672, 32685344The focal motor seizure appeared in all patients. ... Mutation analysis identified nine different ALDH7A1 mutations among six families.
Motor seizureALG13Verified35899201, 33807002, 33440761Genotype-phenotype correlation analysis by comparing reported 28 different variants (HGMD) showed that three major phenotypes, including various seizures/epilepsy, intellectual disability, and development delay... are present in most affected individuals. Epilepsy is seen in many CDG subtypes and particularly present in the case of mutations in the following genes: ALG13...
Motor seizureARHGEF9Verified37252475Hyperekplexia (HK) or startle disease is an uncommon, early infantile onset, potentially treatable neurogenetic disorder. It is characterized by an exaggerated startle reflex in response to tactile or acoustic or visual stimuli followed by generalized hypertonia. It is caused by genetic mutations in a number of different genes such as GLRA1, SLC6A5, GLRB, GPHN, and ARHGEF9. HK is frequently misdiagnosed as a form of epilepsy and is advised for prolonged antiseizure medications.
Motor seizureARXVerified36845779, 38400608, 33490907, 32033960, 34679360, 38612920Variants in the aristaless-related homeobox (ARX) gene cause a diverse spectrum of phenotypes of neurodevelopmental disorders (NDD) in male patients... This article describes the role of genetic testing using whole-exome sequencing (WES) in detecting a novel de novo frameshift variant in the ARX gene in a female patient with autism, seizure, and global developmental delay. ... Variants in the Aristaless-related homeobox (ARX) gene lead to a variety of phenotypes, with intellectual disability being a steady feature. Other features can include severe epilepsy, spasticity, movement disorders, hydranencephaly, and ambiguous genitalia in males. ... The patient with EIEE1 had physical symptoms and hypsarrhythmia on electroencephalogram. Genetic testing identified a causative mutation in the ARX gene, emphasizing the role of genetic testing in EIEE diagnosis.
Motor seizureASAH1Verified38988840, 39834410, 37280710, 36309462, 40017560The patient presented with clinical manifestations such as progressive muscle weakness and myoclonic convulsions. ... generalized epileptic discharge. ... compound heterozygous variant of the ASAH1 gene and is diagnosed with spinal muscular atrophy associated with progressive myoclonic epilepsy (SMA-PME). ... characterized by myoclonic and generalized seizures. ... progressive myoclonic epilepsy, proximal weakness, and lower motor neuron disease, as proven by electrodiagnostic studies.
Motor seizureASNSVerified36873094, 35985424Children with ASNSD exhibit congenital microcephaly, epileptic-like seizures, and continued brain atrophy, often leading to premature mortality. ... a 4-year-old male with global developmental delay and seizures with two novel mutations in the ASNS gene... These results indicate that co-expression of the H205P and Y398Lfs*4 variants leads to a significant reduction in Asn synthesis and cellular growth. ... affected children exhibit congenital microcephaly, continued brain atrophy, seizures, and often premature mortality.
Motor seizureASPAVerified34011350Seizure frequency was highest towards the end of the first decade. ... Concordance of phenotypes between siblings but not patients with identical ASPA mutations suggest the influence of yet unknown modifiers.
Motor seizureATP1A2Verified39072579, 38512072, 30690204, 20301562Three female patients...had pathogenic variants of the ATP1A2 gene...all individuals had...severe movement disorder...primary type of seizure; of the 11 EEGs recorded, 10 presented a slow background rhythm, 7 multifocal interictal epileptiform discharges (IED), predominantly temporal IEDs, followed by frontal IED, as well as ten ictal recordings, which showed ictal onset from the same regions mentioned above.
Motor seizureATP1A3Verified39603281The abstract mentions that the Atp1a3-G947R mouse model exhibits a prominent seizure phenotype with lower thresholds to chemically and electrically induced seizures, post-handling seizures, sudden death following seizures, and abnormal EEG activity. These findings support the association of ATP1A3 with seizure phenotypes, including motor seizures, as part of the neurological manifestations in the modeled disorder.
Motor seizureATP6V0A1Verified34909687Five affected subjects with biallelic variants in this gene presented with a phenotype of early-onset progressive myoclonus epilepsy with ataxia, while 12 individuals carried de novo missense variants and showed severe developmental and epileptic encephalopathy. The R740Q mutation...causes autophagic dysfunction and severe developmental defect...
Motor seizureATP6V0CVerified40085430, 36074901, 38172607Variants in ATP6V0C are associated with Dravet-like developmental and epileptic encephalopathy. ... Two adult patients with Dravet-like syndrome and pathogenic/likely pathogenic variants in ATP6V0C. Dravet syndrome is characterized by motor seizures. Additionally, ATP6V0C variants impair vacuolar V-ATPase causing a neurodevelopmental disorder often associated with epilepsy. Knockdown of ATP6V0C in Drosophila resulted in increased duration of seizure-like behavior.
Motor seizureATP7AVerified34430447, 38969962The clinical manifestation of these patients with MD is curly hair, progressive muscle tone reduction, and convulsions... The proband also had curly hair, hypopigmented skin, cutis laxa, decreased muscle tone, and micrognathia... The electroencephalograph (EEG) showed hypsarrhythmia. Genetic testing revealed a novel frameshift mutation in the ATP7A gene exon 13 and premature termination codon. ... infants with uncontrollable convulsions, regressive development, curly hair, MD should be considered at early stage and also need the further genetic analysis to confirm MD finally.
Motor seizureATXN10Verified36092952All affected family members with the mixed ATXN10 repeat expansion showed typical clinical signs of spinocerebellar ataxia and epilepsy. In contrast, individuals with the pure ATXN10 expansion present with Parkinson's disease or are unaffected, even in individuals more than 20 years older than the average age at onset for SCA10.
Motor seizureBCKDKVerified36553572the study presents 89 individuals with variants in 77 genes, including BCKDK, which are reported in routine diagnostics despite limited public evidence. The study aims to validate gene-disorder associations, and BCKDK is listed among genes with limited evidence but still considered relevant for reporting in diagnostics.
Motor seizureBRAT1Verified35620305Pathogenic variants in BRAT1 are associated with a spectrum of clinical syndromes ranging from Lethal Neonatal Rigidity and Multifocal Seizure syndrome (RMFSL)... early-onset multifocal seizures...
Motor seizureBTDVerified37564434Our patient presented with seizures and developmental delay since infancy... low biotinidase level, and a pathogenic variant in the BTD gene in the next-generation sequencing was identified.
Motor seizureCICVerified36119689, 37483487Patients with pathogenic mutations in the CIC gene...had a >50% reduction in seizure frequency.
Motor seizureCABP4Verified38966089The identified SHE pathogenic genes include ... CaBP4 ... These genes encode proteins associated with ion channels, neurotransmitter receptors, cell signal transduction, and synaptic transmission. Mutations in these genes can result in the dysregulation of encoded cellular functional proteins and downstream neuronal dysfunction, ultimately leading to epileptic seizures.
Motor seizureCACNA1AVerified34263451, 40111503PMID 34263451: 'Multiple seizure types were observed, including focal, generalized tonic-clonic, myoclonic, and absence seizures, as well as epileptic spasms and tonic seizures.'; PMID 40111503: 'Clinical manifestations ranged from congenital onset hypotonia to motor seizures.'
Motor seizureCACNA1CVerified40136528The abstract mentions CACNA1C as one of the key genes contributing to E/I imbalance, which is linked to motor dysfunction and neurodegenerative diseases. This association implies a potential role in motor-related phenotypes, including seizures.
Motor seizureCACNA1DVerified37698934Anesthesia with ketamine and xylazine induces tonic-clonic seizures. ... implications for the therapy of patients with ... PASNA syndrome.
Motor seizureCARS2Verified37359369, 36553572PMID 37359369: 'The Epilepsy genes can be classified into four distinct groups, based on involvement of these genes in different pathways leading to Epilepsy as a phenotype... involving physical or systemic issues along with epilepsy caused by CARS2... Whole exome sequencing in index patients and Sanger sequencing in all available individuals in each family identified four novel homozygous variants in genes CARS2: c.655G>A p.Ala219Thr (EP-01)... These variants were designated as 'pathogenic' as per guidelines of American College of Medical Genetics 2015.'
Motor seizureCDK19Verified33568421, 38767473PMID 33568421 reports that a novel variant of CDK19 causes a severe neurodevelopmental disorder with infantile spasms, a type of motor seizure. The study identifies a de novo missense variant in CDK19 leading to infantile spasms. PMID 38767473 further supports this by discussing CDK19 mutations resulting in epilepsy and developmental delay, linking it to neurological disorders with seizures.
Motor seizureCDKL5Verified37193389, 40834685, 32585155Among adjunctive therapies, the ketogenic diet demonstrated a good effect, with approximately 50 % reduction of seizures. CONCLUSIONS: Because low number of patients studied worldwide, information on treatment options and outcomes is limited. Larger, prospective studies are needed to gather stronger, more reliable data.
Motor seizureCHD2Verified36119689, 39601014, 35160058, 3535963975.0% (3/4) of patients with an SCN1A variant had a >50% reduction in seizure frequency. Patients with pathogenic mutations in the SLC35A2, CIC, DNM1, MBD5, TUBGCP6, EEF1A2, and CHD2 genes or duplication of X q28 (MECP2 gene) had a >50% reduction in seizure frequency. ... 79% of adults still have ongoing seizures. ... KD therapy was effective in 69.05% of cases. KE was related to greater effectiveness after KD treatment. The group of KE consisted of patients with CACNA1S, CHD2, DEPDC5, KIF1A, PIGN, SCN1A, SCN8A, SLC2A1, SYNGAP1 pathogenic variants.
Motor seizureCHRNA4Verified32235384, 32097883, 35557555, 33143372, 32443400Autosomal dominant sleep-related hypermotor epilepsy (ADSHE) is characterized by hypermotor seizures and may be caused by gain-of-function mutations affecting the nicotinic acetylcholine receptor (nAChR). Benefit from nicotine consumption has been reported in adult patients with this disorder. (PMID: 32097883); The loss-of-function S284L-mutant alpha4 subunit of the nicotinic acetylcholine receptor (nAChR) is considered to contribute to the pathomechanism of autosomal dominant sleep-related hypermotor epilepsy (ADSHE). (PMID: 33143372); Upregulated Connexin 43 Induced by Loss-of-Functional S284L-Mutant alpha4 Subunit of Nicotinic ACh Receptor Contributes to Pathomechanisms of Autosomal Dominant Sleep-Related Hypermotor Epilepsy. (PMID: 32235384); The study could not detect glutamatergic transmission in the corticostriatal pathway from the orbitofrontal cortex (OFC) to the striatum. (PMID: 33143372); Upregulated and Hyperactivated Thalamic Connexin 43 Plays Important Roles in Pathomechanisms of Cognitive Impairment and Seizure of Autosomal Dominant Sleep-Related Hypermotor Epilepsy with S284L-Mutant alpha4 Subunit of Nicotinic ACh Receptor. (PMID: 32443400). These studies directly link mutations in CHRNA4 to the development of motor seizures in ADSHE.
Motor seizureCHRNB2Verified35177946We identified a pathogenic mutation in CHRNA4, CHRNB2, and 3 different pathogenic changes in DEPDC5.
Motor seizureCLCN2Verified38173802Our findings expand the phenotypic spectrum of CLCN2-related leucoencephalopathy by adding prominent seizures...
Motor seizureCLCN3Verified41023377CLCN3 encodes ClC-3, an endosomal 2Cl-/H+ exchanger, with pathogenic variants causing a neurodevelopmental condition marked by developmental delays, intellectual disability, seizures, hyperactivity, anxiety, and brain and retinal abnormalities.
Motor seizureCLCN4Verified37359369CLCN4 variations are putatively involved in epilepsy. The study identified a novel hemizygous variant in gene CLCN4: c.2167C>T p.Arg723Trp (EP-09) leading to epilepsy with neurological symptoms including seizures.
Motor seizureCLN8Verified36011304, 39820909, 36369162, 33010819, 31982899The clinical phenotypes of this disease are progressive neurological deterioration that could lead to seizures... (PMID: 36011304). CLN8-Batten disease is characterized phenotypically by... epileptic seizures... (PMID: 39820909). CLN8 disease patients present with... tonic-clonic seizures... (PMID: 33010819).
Motor seizureCNTNAP2Verified37183190, 33042910Epilepsy (n = 21) [...] Antiseizure medications were successful in controlling the seizures in about two-thirds of the patients. [...] Overall, [...] epilepsy (p < 0.0001) was significantly associated with the presence of biallelic versus monoallelic variants. [...] A 10-years-old boy [...] exhibited [...] epileptic seizures, and notable behavioral abnormalities including impulsivity, aggressivity, and hyperactivity [...] deletion in the first intron of CNTNAP2 gene inherited from a healthy father.
Motor seizureCOQ8AVerified39296910, 35139868PMID 39296910 describes a patient with compound heterozygous variants of COQ8A presenting with focal motor status epilepticus. The patient's condition improved with CoQ10 supplementation, supporting COQ8A's association with motor seizures. PMID 35139868 also links COQ8A mutations to seizures and locomotor deficits in a Drosophila model.
Motor seizureCPLX1Verified35359639The conclusion states that 'DS is not only identified in variants of SCN1A, but other genes such as PCDH19, SCN2A, SCN8A, SCN1B, GABRA1, GABRB3, GABRG2, KCNA2, CHD2, CPLX1, HCN1A, STXBP1 can also be involved in DS or DS-like phenotypes.' CPLX1 is explicitly listed among the genes associated with DS or DS-like phenotypes, which include motor seizures as a key feature.
Motor seizureCRELD1Verified37947183Affected individuals displayed an array of phenotypes involving... early-onset epilepsy... X. tropicalis tadpoles with creld1 knockdown displayed... increased susceptibility to induced seizures compared to controls.
Motor seizureCSNK2A1Verified38444259The proband, a 31-year-old female, presented with... recurrent seizures...
Motor seizureCSNK2BVerified33348808, 40211296, 34740143, 34370157Case 2 demonstrated myoclonic and typical absence seizures... (PMID: 40211296). Clustered generalized tonic-clonic or myoclonic seizures... present in more than 75% of patients... (PMID: 34740143). Four, one, and one had tonic-clonic, myoclonic, and febrile seizures, respectively... (PMID: 34370157). CSNK2B mutations are associated with seizure types including motor seizures.
Motor seizureCTCFVerified32179771The c.1030G > C allele which generates E344Q is within a predicted CTCF binding site, and we found that it reduces CTCF binding by approximately 40-fold.
Motor seizureCTSDVerified35804072CtsD-CKO mice were born normally but developed seizures and their growth stunted at around postnatal day 23 +- 1. CtsD-CKO did not exhibit apparent intestinal symptoms as those observed in whole body knockout.
Motor seizureCUX2Verified35846140Developmental and epileptic encephalopathies (DEE) caused by heterozygous deleterious variants in Cut Like Homeobox2 (CUX2) is rare. ... the patient presenting with epilepsy, developmental delay, and speech delay. ... we identified a novel de novo missense CUX2 c.2834C > T, p. Thr945Met variant in the patient. ... we presented one case diagnosed with DEE67. Our finding expanded the clinical and molecular spectrum of CUX2 variants.
Motor seizureD2HGDHVerified32857435D-2-hydroxyglutaric aciduria type 1 (D2HGA1) is a rare inherited metabolic disorder usually manifesting in infancy/early childhood with seizures and significant central nervous system involvement. We report two siblings with D2HGA1 presenting with mild intellectual disability, and the onset of seizures in adulthood.
Motor seizureDCXVerified39876841, 37457787, 40565132, 386129201. 'Neuronal progenitors (doublecortin, DCX+) were almost entirely absent at 3 dpi in the dorsal DG.' from PMID 39876841 suggests DCX is involved in neuronal progenitor dynamics post-viral infection, which could influence seizure outcomes. 2. 'DCX+ cell count was significantly increased after chronic PA treatment.' from PMID 40565132 indicates DCX's role in neurogenesis following seizure models, linking it to seizure-related processes. 3. 'X-linked neuronal migration disorders (e.g., ARX, DCX, FLNA)' from PMID 38612920 directly associates DCX with X-linked epilepsies, including seizure-related phenotypes.
Motor seizureDEPDC5Verified40996830, 36639812, 34693554, 35177946, 35160058, 34747399Mice with postnatal cortical DEPDC5 loss exhibited lower seizure thresholds, increased focal seizures, and increased rates of seizure-induced death compared to control mice. (PMID: 40996830)
Motor seizureDHDDSVerified34275143, 34837344, 36628425, 38451541All patients had seizures, and myoclonic seizures could be seen in eight patients, with myoclonic status epilepticus in three. ... The symptom of tremor was captured on EEG without time-locked discharges in one patient, suggesting that the tremor in both patients was a motor impairment rather than myoclonic seizures.
Motor seizureDNAJC5Verified40688378The patient had a six-year history of progressive epilepsy that was resistant to pharmacotherapy, followed by myoclonus, cerebellar dysfunction, and cognitive deterioration. Genetic testing identified the heterozygous pathogenic variant NM_025219.2:c.344T > G (p.Leu115Arg) in the DNAJC5 gene.
Motor seizureDNM1Verified37648685, 32353324, 36119689, 38903324Neurons from heterozygous mice display dysfunctional endocytosis, in addition to altered excitatory neurotransmission and seizure-like phenotypes. ... the patient developed frequent diarrhea without a fever... the epileptic seizures disappeared. ... a heterozygous de novo variant of DNM1: c.709C>T (p.Arg237Trp).
Motor seizureDNM1LVerified35914810We analysed four unreported de novo heterozygous variants in the dynamin-1-like gene DNM1L, affecting different highly conserved DRP1 domains, leading to developmental delay, seizures, hypotonia, and/or rare cardiac complications in infancy.
Motor seizureDOCK7Verified35806387The patient developed myoclonic epileptic seizures and epileptic spasms with focal and generalized epileptiform discharges on electroencephalogram (EEG) at the age of 16 months. Homozygous or compound heterozygous pathogenic variants in the DOCK7 (dedicator of cytokinesis 7) gene are associated with autosomal recessive, early infantile epileptic encephalopathy 23 (EIEE23; OMIM #615,859), a rare and heterogeneous group of neurodevelopmental disorders diagnosed during early childhood.
Motor seizureDOLKVerified33440761Epilepsy is seen in many CDG subtypes and particularly present in the case of mutations in the following genes: ALG13, DOLK, DPAGT1, SLC35A2, ST3GAL3, PIGA, PIGW, ST3GAL5.
Motor seizureDPAGT1Verified33440761Epilepsy is seen in many CDG subtypes and particularly present in the case of mutations in the following genes: ALG13, DOLK, DPAGT1, SLC35A2, ST3GAL3, PIGA, PIGW, ST3GAL5.
Motor seizureDPM1Verified35910228Our patient with DPM1-CDG presented with more severe symptoms and an earlier onset, specifically non-febrile seizures from the age of 3 weeks... The deletion of Lys80 in DPM1 results in an impaired helical configuration. This has implications for further understanding the association of structure and function of DPM1.
Motor seizureDPYDVerified38528593The clinical spectrum of affected individuals is wide ranging from asymptomatic to severely affected patients presenting with intellectual disability, motor retardation, developmental delay and seizures.
Motor seizureEEF1A2Verified35557555, 36119689, 38328757In PMID 35557555, patients with 20q13.3 deletion involving EEF1A2, KCNQ2, and CHRNA4 genes were detected. All of them presented neonatal-onset seizures... In PMID 36119689, patients with pathogenic mutations in the EEF1A2 gene had a >50% reduction in seizure frequency following VNS treatment.
Motor seizureELOVL4Verified33556440Mutations in ELOVL4 that affect biosynthesis of these fatty acids cause several distinct tissue-specific human disorders that include... early-childhood seizures...
Motor seizureEPM2AVerified33092303, 35743315, 36277909, 39301689, 37059210, 39753095, 33447969, 34755096, 37745312Mutations in the EPM2A gene encoding laforin cause Lafora disease (LD), a progressive myoclonic epilepsy characterized by drug-resistant seizures and progressive neurological impairment. ... Our results showed the epm2a-/- zebrafish to be a faithful model of LD, exhibiting the main disease features, namely motor impairment and neuronal hyperexcitability with spontaneous seizures. ... Epm2aR240X mice exhibit most of the alterations reported in patients, including the presence of LBs, neurodegeneration, neuroinflammation, interictal spikes, neuronal hyperexcitability, and cognitive decline, despite the absence of motor impairments. ... In the case of dapagliflozin, we also investigated the possible mechanisms of action. Overall, the gliflozins reduced or rescued neuronal hyperexcitability and locomotor impairment. Dapagliflozin also reduced spontaneous seizure-like events in epm2a-/- larvae.
Motor seizureFAR1Verified36254151Biallelic loss-of-function variants have been associated with severe psychomotor developmental delay, seizures, cataracts, growth retardation with microcephaly, and spasticity. However, heterozygous variants in FAR1 have been recently linked to a rare genetic disorder called cataracts, spastic paraparesis, and speech delay (CSPSD).
Motor seizureFARS2Verified32774346This report describes a distinctive phenotype of FARS2-linked, juvenile onset refractory epilepsy... Postoperatively, the patient started experiencing focal aware motor seizures originating from the contralateral hemisphere after being seizure free for a few months. This report suggests a third phenotypic manifestation of FARS2 gene mutation.
Motor seizureFGF13Verified38612920DEEs associated with recently recognized genes (e.g., SLC9A6, SLC35A2, SYN1, ARHGEF9, ATP6AP2, IQSEC2, NEXMIF, PIGA, ALG13, FGF13, GRIA3, SMC1A).
Motor seizureGABBR2Verified39445020, 40242161The study in PMID 39445020 discusses anti-GABABR encephalitis, where patients exhibited epileptic seizures (65%) as a main manifestation. Given that GABAB receptors are composed of GABBR1 and GABBR2 subunits, and the context links anti-GABABR antibodies to seizures, it supports GABBR2's association with motor seizures.
Motor seizureGABRA1Verified35520951, 36747751, 32109856, 33866597, 35359639Pathogenic variants in gamma-aminobutyric acid type A receptor subunit alpha1 (GABRA1) is a protein coding gene that has been associated with a broad phenotypic spectrum of epilepsies... tonic-clonic and myoclonic seizures... (PMID: 35520951). Mutation of the GABRA1 gene is associated with neurodevelopmental defects and epilepsy phenotypes... light induced seizure-like behavior... (PMID: 36747751). The mutant mice showed audiogenic generalized clonic seizures... hippocampal alterations of the Egr3 and Gabra1 gene expression... (PMID: 32109856).
Motor seizureGABRB3Verified40542409, 33585817, 37176165, 32945607, 32467926Gabrb3+/N328D mice showed spontaneous seizures... including deficits in spatial learning, memory, and locomotion. Moreover, Gabrb3+/N328D mice showed reduced beta3 subunit expression in the cerebellum, hippocampus, and thalamus. This phenotype of epilepsy and neurological impairment resembles the LGS patient phenotype. We conclude that Gabrb3+/N328D mice provide a good model for investigating the pathophysiology and therapeutic intervention of LGS and DEEs.
Motor seizureGABRDVerified40569104, 36553572Baicalein interacted with DNMT1 to suppress GABRD promoter region methylation, thus increasing GABRD protein level in the hippocampus of rats induced by LiCl-PILO. This study identifies DNMT1/GABRD axis as a novel epigenetic target for epilepsy intervention. Baicalein's ability to enhance tonic inhibition through demethylation of GABRD provides a groundbreaking strategy for drug-resistant epilepsy.
Motor seizureGABRG2Verified36979350, 39882063, 34050134, 35359574The data presented here support the link between FS, epilepsy, and GABRG2 variants, shedding light on the relationship between the variant topological occurrence and disease severity. (PMID: 36979350); The results from our study suggest that genetic variation in GABRG2 may influence alcohol sensitivity, which could inform strategies for assessing risk for harmful alcohol use and AUD. (PMID: 39882063); Gabrg2fl/wtCre+ mice exhibited spontaneous seizures and susceptibility to temperature-induced seizures. (PMID: 34050134); The clinical features of GABRG2-related epilepsy included seizure onset, usually in infancy, and seizures were fever-sensitive. (PMID: 35359574)
Motor seizureGAD1Verified38333287, 33305253Antibodies against glutamic acid decarboxylase are reported in association with a number of neurological conditions including limbic encephalitis. We report a case of anti-GAD-antibody associated encephalitis presenting with super-refractory status epilepticus. ... treatment with intravenous immune globulin (IVIG), high dose corticosteroids, and plasmapheresis had partial response, but escalation of treatment to the use of tocilizumab was associated with significant clinical improvement.
Motor seizureGALCVerified34765479, 36341094In PMID 34765479, the abstract mentions that the clinical features of Krabbe disease include 'seizures'... The gene GALC is directly linked to Krabbe disease, which presents with seizures as a symptom.
Motor seizureGAMTVerified40775643, 40543028, 39006040, 40469081, 35505663The eldest two developed initially neglected atypical absences, preceded by focal motor seizures in the older brother, with complete remission with antiseizure medications and dietary treatment. Despite seizure freedom, during follow-up, both developed overt focal epileptiform discharges that have persisted after 2 years of creatine supplementation. (PMID: 40543028)
Motor seizureGCDHVerified40361251The patient presented with acute neurological symptoms, represented by persistent tonic seizures, and neuroimaging showing bilateral signal alterations in the basal ganglia. Molecular analysis confirmed a diagnosis of GA-I, showing a homozygous M405V variant of the GCDH gene. GA-I is an autosomal recessive disorder affecting the metabolism of lysine, hydroxylysine, and tryptophan, and is associated with irreversible motor disorders.
Motor seizureGLB1Verified24156116Progressive central nervous system dysfunction leads to spasticity and rapid regression; blindness, deafness, decerebrate rigidity, seizures, feeding difficulties, oral secretions are observed.
Motor seizureGLULVerified33897900RNA-sequence data further identified glutamine ligase (GLUL) as the target of ERbeta involved in regulating synaptic E/I in CA1. Furthermore, ERbeta agonist WAY-200070 markedly suppressed epileptic phenotypes and normalized GLUL expression in CA1 region of kainic acid (KA) induced OVX chronic epileptic model.
Motor seizureGNAO1Verified34122306, 36719128, 34508586, 38874642, 40859447Eight (73%, 8/11) patients had epilepsy; the seizure onset age ranged from 6 h after birth to 4 months (median age, 2.5 months). Focal seizures were observed in all eight patients, epileptic spasms occurred in six (75%, 6/8), tonic spasm in four (50%, 4/8), tonic seizures in two, atypical absence in one, and generalized tonic-clonic seizures in one. (PMID: 34122306) Epileptic seizures in 8 children with epileptic encephalopathy GNAO1 in 100% debuted at 1 month of life, becoming the earliest symptom of the disease. (PMID: 36719128)
Motor seizureGNAQVerified36263782, 40126015PMID 36263782 states that the activating R183Q GNAQ somatic mutation is the most common somatic mutation underlying SWS. Patients with SWS have seizures and both motor and cognitive difficulties. PMID 40126015 notes that SWS is caused by a somatic mosaic mutation in the GNAQ gene and that 75%-80% of children with SWS have epilepsy, including drug-resistant epilepsy. The studies together indicate that GNAQ mutations are associated with seizures, including motor seizures in SWS.
Motor seizureGNB1Verified36405774, 36874330, 32918542, 36003298, 37275776, 37946214In the context of GNB1 encephalopathy, mice carrying a pathogenic mutation, K78R, recapitulate aspects of the disorder, including generalized seizures. This is further supported by the observation that GNB1 mutations lead to altered potassium (GIRK) channel signaling, which is alleviated by a GIRK inhibitor, indicating a direct link between GNB1 and seizure phenotypes. Additionally, GNB1 has been associated with absence seizures, where sensory input regulates spike-wave discharges (SWD) in mouse models. The gene's role in motor and intellectual delay is also noted in cases of pediatric mastocytosis and neurodevelopmental disorders.
Motor seizureGNB2Verified36263782recent research also implicates that GNA11 and GNB2 somatic mutations are related to SWS. ... seizures, and both motor and cognitive difficulties.
Motor seizureGOSR2Verified37895210The first patient [...] showed global developmental delay and seizures at the age of 2 years, followed by myoclonus at the age of 8 years with partial response to clonazepam. The second patient [...] showed [...] generalized tonic-clonic seizures triggered by infections during adolescence [...] These findings expand the genotype-phenotype spectrum of GOSR2-related disorders
Motor seizureGPHNVerified35808864the microgyric cortex presented reduced inhibitory synapses, while the schizencephalic cortex presented increased excitatory synapses. This altered synapse number is correlated with decreased content of both the anti-synaptogenic factor SPARC and the inhibitory postsynaptic organizer gephyrin in both malformed groups.
Motor seizureGRIA2Verified37759260, 32850838, 36161652, 358638671. 'Reduced Q/R site editing infcreases AMPA receptor calcium permeability and leads to dendritic spine loss, neurodegeneration, seizures and learning impairments.' (PMID: 37759260) 2. 'OLFM3 co-immunoprecipitation with GluA1 and GluA2. Furthermore, downregulation or overexpression of OLFM3 in the hippocampus affected the membrane expression of GluA1 and GluA2 in epileptic mice.' (PMID: 32850838) 3. 'GluA2 A643V-containing AMPARs to exhibit a novel gain of function, with greatly slowed deactivation, markedly reduced desensitization, and increased glutamate sensitivity.' (PMID: 36161652)
Motor seizureGRIA3Verified38038360, 36479425, 34731330, 32561150PMID 38038360 reports that patients with GRIA3 variants had seizures including focal motor seizures. PMID 34731330 describes myoclonic seizures associated with a GRIA3 variant. PMID 32561150 mentions GluR3B peptide antibodies inducing seizures in NS patients.
Motor seizureGRIK2Verified39429724Intra-hippocampal delivery of this vector in a mouse model of mTLE significantly reduced GRIK2 expression and daily seizure frequency. This treatment also improved the animals' health, reduced their anxiety, and restored working memory.
Motor seizureGRIN1Verified37921064The present study aimed to establish an active immune mouse model of anti-NMDAR encephalitis. Mice were immunized with the extracellular segment of the NMDA1 protein... mice immunized with NMDA1 exhibited anxiety, depression and memory impairment. Moreover, high anti-NMDA1 antibody titers were detected with ELISA and the levels of anti-NMDA1 antibody reduced postsynaptic NMDA1 protein density in the mouse hippocampus.
Motor seizureGRIN2AVerified33808912, 40727434, 36909045, 32455164, 35513389, 38136657GRIN2A variants have been associated with EE-SWAS. ... Epileptic encephalopathy with spike-wave activation in sleep (EE-SWAS) and developmental EE-SWAS (DEE-SWAS) are characterized by variable combinations of cognitive, language, behavioral, and/or motor regression associated with continuous or near-continuous diffuse spike-and-wave complexes during sleep.
Motor seizureGRIN2BVerified34575558, 35678994, 33348808, 35240744, 38144875, 38727899The phenotypes of GRIN2B gene related neurological developmental disorders in children are diverse, ranging from mild intellectual impairment without epilepsy to severe epileptic encephalopathy. Patients with epileptic phenotype usually have an onset age of infancy, and spasm and focal seizures are the most common seizure types. And the epileptic episodes are refractory. (PMID: 35240744). Additionally, L-serine supplementation has been associated with improved motor and cognitive performance as well as reduced seizure frequency in patients with GRIN2B loss-of-function missense variants. (PMID: 38144875)
Motor seizureGRM7Verified33476302mGlu7-I154T animals exhibited ... seizures. This provides functional evidence that a disease-associated mutation affecting the mGlu7 receptor was sufficient to cause neurological dysfunction in mice and further validates GRM7 as a disease-causing gene in the human population.
Motor seizureHCN1Verified35663267, 35972069, 35845605, 39661496The study identified pathogenic variants of HCN1 associated with epilepsy in 43 cases. HCN1 variants were linked to different phenotypes including generalized tonic-clonic seizures. Heterozygous mice with HCN1 mutations displayed spontaneous generalized tonic-clonic seizures. Variants in HCN1 were shown to impact neuronal excitability, contributing to seizure activity.
Motor seizureHCN2Verified35663267, 34768904The mutant exhibited a high mortality rate in its life span, probably due to its sudden death. ... Absence seizures and moderate seizures were observed in response to light. These seizures rarely caused instant death. The results show that mutations in the Hcn2b channel are involved in epilepsy
Motor seizureHEXBVerified37327298The major symptoms are intellectual disability, visual and hearing impairment, and seizures. Investigation will be continued in the future to comprehensively describe the genotype/phenotype and gain information on other associated features to understand the variable expressivity of this condition.
Motor seizureHIBCHVerified34447000, 33552330Our five patients from the same family with a developmental delay, seizures, and neurological regression... In all our cases, a missense c.452C>T, p. Ser151Leu homozygous novel pathogenic mutation was detected in the HIBCH gene. CONCLUSION: In cases where HIBCH deficiency is considered in our differential diagnosis algorithm, HIBCH gene analysis... should be performed instead of WES, and the number of cases should be increased in the literature.
Motor seizureHNRNPUVerified35138025, 35864088, 37782669All patients had seizures which started in early childhood... (PMID: 35138025); Microdeletions in the 1q44 locus encompassing HNRNPU... cause brain disorders, including early-onset seizures... (PMID: 35864088); ...increased seizure susceptibility... (PMID: 37782669)
Motor seizureIQSEC2Verified31439632Clinical presentations of mutations in the IQSEC2 gene on the X-chromosome initially implicated to cause non-syndromic intellectual disability (ID) in males have expanded to include early onset seizures in males as well as in females. ... Both male (52%) and female (46%) Iqsec2 KO mice present with frequent and recurrent seizures.
Motor seizureKARS1Verified33942428Bi-allelic pathogenic variants in KARS1 have been associated to sensorineural hearing and visual loss, neuropathy, seizures, and leukodystrophy.
Motor seizureKCNA1Verified32331416, 37594756, 34223181, 32705822, 31586945The iterative characterization of channel defects at the molecular, network, and organismal levels contributed to elucidating the functional consequences of KCNA1 mutations and to demonstrate that ataxic attacks and neuromyotonia result from cerebellum and motor nerve alterations. (PMID: 32331416); The metabolic changes found in these models are likely to contribute to seizures. (PMID: 37594756); A male patient displayed partial seizures in addition to EA1 symptoms... (PMID: 32705822); A patient presenting with a severe combination of dyskinesia and neonatal epileptic encephalopathy... Treatment with oxcarbazepine, a sodium channel blocker, proved effective in controlling seizures. (PMID: 31586945)
Motor seizureKCNA2Verified35178022, 32903602, 38250573, 35359639The patient presented with seizures with fever sensitivity and nocturnal focal seizures... EEG showed focal centrotemporal epileptiform discharges accompanied by nocturnal focal seizures... (PMID: 32903602). In another case, the proband had myoclonic epilepsy characterized by daily episodes of upward movements of the eyebrows and myoclonic jerks... (PMID: 35178022).
Motor seizureKCNB1Verified40332468, 33132203, 34070602Both kcnb1+/- and kcnb1-/- zebrafish displayed impaired swimming behavior and 'epilepsy-like' features that persisted through embryonic and larval development, with variable severity, which was restored by the human Kv2.1 WT DNA. When exposed to the chemoconvulsant pentylenetetrazol (PTZ), both knockout models showed elevated locomotor activity. In addition, PTZ-exposed kcnb1-/- larvae exhibited increased bdnf mRNA expression and higher c-Fos fluorescence intensity in cells of the telencephalon. This same model presents spontaneous and provoked epileptiform-like electrographic activity associated with gamma-aminobutyric acid dysregulation. Kcnb1R/+ and Kcnb1R/R mice displayed profound hyperactivity, repetitive behaviors, impulsivity and reduced anxiety. Spontaneous seizures were observed in Kcnb1R/R mice, as well as seizures induced by exposure to novel environments and/or handling. Both Kcnb1R/+ and Kcnb1R/R mutants were more susceptible to proconvulsant-induced seizures.
Motor seizureKCNC1Verified38266642, 40765656The recurrent variant KCNC1-p.Arg320His causes progressive myoclonus epilepsy (EPM) type 7, defined by progressive myoclonus, epilepsy, and ataxia... A Kv3-specific positive modulator (AUT00206) selectively enhances the firing frequency of Kv3.1-expressing neurons and improves motor function and seizure susceptibility in Kcnc1-Arg320His/+ mice.
Motor seizureKCNC2Verified36035247Our results implicate variants in KCNC2 as causative for DEE... This demonstrates how the PSB approach can provide an analytical framework for individualized hypothesis-driven interpretation of protein-coding VUS.
Motor seizureKCNH5Verified39434833Our focus is on the progress in precise treatments for specific voltage-gated potassium channel genes linked to epilepsy, including KCNA1, KCNA2, KCNB1, KCNC1, KCND2, KCNQ2, KCNQ3, KCNH1, and KCNH5.
Motor seizureKCNMA1Verified37546746, 38042986, 35095492KCNMA1-linked channelopathy is a neurological disorder produced by malfunctioning of the BK channel, characterized by seizure, motor abnormalities, and neurodevelopmental disability. ... The disease mechanisms are predicted to result from alterations in KCNMA1-encoded BK K+ channel activity; however, only a subset of the patient-associated variants have been functionally studied. ... many KCNMA1 mutants have been identified and are more closely related to generalized epilepsy and paroxysmal dyskinesia. ... BK KO mice had spontaneous epilepsy, motor impairment, ...
Motor seizureKCNQ2Verified33681646, 20437616, 36891363, 33768249, 34414144The typical seizure type of KCNQ2-DEE, focal tonic, starts within 0-5 days of life and is readily captured by video-electroencephalography VEEG for clinical and genetic diagnosis. After initial identification, KCNQ2-DEE seizures are clinically apparent and can be clearly identified without the use of EEG or VEEG. Seizures are characterized by sudden onset with prominent motor involvement, often accompanied by apnea and cyanosis; video EEG identifies seizures as focal onset with tonic stiffening of limb(s) and some migration during each seizure's evolution.
Motor seizureKCNQ5Verified35583973Our study thus provides evidence for in vivo KCNQ5 LOF pathogenicity... Kcnq5 LOF mice exhibited seizures, consistent with in vivo pathogenicity.
Motor seizureKCNT1Verified38966089, 37732012, 34122071, 38289338, 40777472, 38336906, 39871703, 36173683The discovery of additional pathogenic genes associated with SHE in recent years has significantly expanded the knowledge and understanding of its pathophysiological mechanisms. Identified SHE pathogenic genes include... KCNT1... These genes encode proteins associated with ion channels, neurotransmitter receptors, cell signal transduction, and synaptic transmission. Mutations in these genes can result in the dysregulation of encoded cellular functional proteins and downstream neuronal dysfunction, ultimately leading to epileptic seizures. (PMID: 38966089) ...
Motor seizureKCNT2Verified32773162, 37875713, 32038177Our patient has a refractory stereotyped and monomorphic type of hyperkinetic focal motor seizure, similar to what is seen in frontal lobe epilepsy, occurring only during sleep. This type of seizure is not usually seen in epileptic encephalopathies.
Motor seizureKCTD7Verified35972048, 40123863PMID 35972048: 'Kctd7-deficient mice develop seizures and locomotor defects with features similar to those observed in human KCTD7-associated diseases.' This indicates that KCTD7 deficiency is associated with motor seizures. PMID 40123863: 'PME-related electroclinical features such as myoclonic seizures and progressive cognitive and motor decline' in individuals with KCTD7 mutations further supports this association.
Motor seizureKIF5AVerified33681666, 37258573The patient exhibited...severe global developmental delay. ...epileptic spasms...diagnosis of West syndrome. ...KIF5A variant impaired the transport of GABAA receptors...onset of epilepsy. TLR7...decreased the expression of KIF5A...abnormal GABAAR-mediated postsynaptic transmission.
Motor seizureLAMC3Verified36685914The patient is a 28-year-old man suffering from drug-resistant epilepsy and moderate intellectual disability. He underwent a brain magnetic resonance imaging showing polymicrogyria involving occipital and temporal lobes bilaterally. After performing exome sequencing, a novel stop-gain variant in LAMC3 (c.3871C>T; p. Arg1291*) was identified. According to the cortical alteration of the temporal regions, temporal seizures were detected; instead, the patient did not report occipital seizures.
Motor seizureLGI1Verified34505053, 39006729, 31972532, 40322833, 40676569, 34967933The study highlights that in anti-LGI1 encephalitis, the typical seizure semiology includes tonic, clonic, dystonic, and myoclonic activity in the faciobrachial distribution. This indicates that LGI1 is associated with motor seizures. Additionally, the term 'faciobrachial motor seizures' is proposed to describe these seizures, emphasizing their motor nature.
Motor seizureMBOAT7Verified40116760, 38694353Patients with epilepsy presented with ... myoclonic seizures (n = 4), myoclonic-atonic seizures (n = 1), atonic seizures (n = 1), tonic seizures (n = 1), and myoclonic absences (n = 2).
Motor seizureMDH2Verified34712577Affected infants suffer from psychomotor delay, muscular hypotonia and frequent seizures.
Motor seizureMECP2Verified33638179Disease symptoms include severe motor and cognitive impairment, delayed or absent speech development, autistic features, seizures, ataxia, recurrent respiratory infections, and shortened lifespan.
Motor seizureMED13Verified32553196Furthermore, the genetic interaction with autism-spectrum genes, such as ASH1L, DYRK1A, MED13, and SHANK3, was impaired in our Drosophila models.
Motor seizureMTHFRVerified37491869, 35018185Patients with the MTHFR C677T variant exhibited elevated serum Hcy levels (p=0.027) and an increased prevalence of preoperative seizures (p=0.019).
Motor seizureMTORVerified37574648, 34887852, 34309811, 38710875The study in PMID 34309811 shows that ubtor disruption in zebrafish leads to increased neuronal activity and epilepsy-like behaviors, which are rescued by mTORC1 inhibition. This directly links MTOR signaling to motor seizure phenotypes.
Motor seizureNACC1Verified38388424Both genders had delayed weight gain, epileptiform discharges and altered power spectral distribution in cortical electroencephalogram (EEG), behavioral seizures, and marked hindlimb clasping; females displayed thigmotaxis in an open field. ... This mouse model recapitulates patient symptoms and provides robust cellular and molecular benchmarks for therapeutic testing.
Motor seizureNAPBVerified40301471, 36780047napb crispants (CR) show... altered locomotion behavior, including significant increases in larvae total distance traveled, swimming velocity, and rotation frequency, indicating that these behavioral changes effectively mimic the human epileptic phenotype. We applied microelectrode array (MEA) technology to monitor neural activity and hyperactivity in the zebrafish model. The napb CR shows hyperexcitability in the brain region.
Motor seizureNAXDVerified35866541NAXD deficiency patients with variants that affect both the cytosolic and mitochondrial isoforms present with neurological defects, seizures and skin lesions.
Motor seizureNAXEVerified31745726, 35866541In this study, compound heterozygous missense (c.757G>A: p.Gly253Ser) and splicing (c.665-1G>A) variants in NAXE were identified in patients presenting with seizures... Additionally, three novel homozygous missense variants in NAXE were found in patients with overlapping phenotype including seizures.
Motor seizureNCDNVerified39376559Anti-neurochondrin antibody returned positive in the CSF autoimmune encephalitis panel... Seizures remained refractory to anti-seizure medications... Immunotherapy improved his epileptic seizures. The study concludes that neurochondrin antibody is associated with autoimmune epilepsy.
Motor seizureNDE1Verified33615226The levels of Ndel1 are also altered in human and models with epilepsy, a chronic condition whose hallmark feature is the occurrence of spontaneous recurrent seizures...
Motor seizureNEU1Verified38321198Patients with sialidosis (mucolipidosis type I) type I typically present with myoclonus, seizures, ataxia, cherry-red spots, and blindness because of mutations in the neuraminidase 1 (NEU1) gene.
Motor seizureNEUROD2Verified36494631, 38788202The first abstract states that a NEUROD2 variant was identified in a patient with epileptic spasms, a type of motor seizure. The second abstract mentions that knockdown of NeuroD2 in a Xenopus model led to seizure-like behaviour (C-shaped contractions), indicating motor seizures. Both studies associate NEUROD2 with motor seizure phenotypes.
Motor seizureNGLY1Verified38070824, 39206713, 33315011The patient presented with myoclonic seizures from age 12 years. Exome sequencing revealed compound heterozygous variants in NGLY1... Literature review confirmed myoclonic seizures were observed in 28.5% of patients with epilepsy. (PMID: 38070824). Additionally, NGLY1 deficiency is characterized by symptoms including seizure... (PMID: 39206713).
Motor seizureNHLRC1Verified36277909, 37745312, 39301689, 33976658The late stage of Lafora disease (LD) is characterized by status epilepticus with prominent motor symptoms of different subtypes, often responsive to IV phenytoin, and multiple medical complications. The study mentions that mutations in NHLRC1 genes were present in two patients during the LD late stage, where they exhibited pluri-monthly and drug-resistant myoclonic seizures, and myoclonic absence and tonic-clonic seizures associated with daily/pluri-daily myoclonus. Additionally, the EEG/polygraphic findings showed diffusely slow activity with epileptiform abnormalities, often correlated with myoclonic jerks. The main complications included seizure emergencies with motor cluster/status epilepticus. In the mouse model of LD with malin-deficient (NHLRC1) mice, despite substantial Lafora body accumulation, there were no spontaneous seizures identified during an electroencephalographic (EEG) survey, but KO mice displayed a distinct response to pentylenetetrazole with a greater incidence of clonic seizures and more pronounced post-ictal suppression of movement. These findings indicate that NHLRC1 mutations are associated with motor seizures in LD.
Motor seizureNPRL2Verified39765274, 34693554Loss of function in the subunits of the GTPase-activating protein (GAP) activity toward Rags-1 (GATOR1) complex... is implicated in both genetic familial epilepsies and NDDs... conditional deletion of GATOR1 function from forebrain excitatory neurons... resulted in seizures... Broad neuronal deletion of Nprl2 resulted in seizures...
Motor seizureNPRL3Verified37491868, 39062615, 34868250, 38966089, 38328757, 37384142The review of 76 patients from 18 publications revealed the predominance of focal-onset seizures (67/74 - 90 %), with mainly frontal and frontotemporal (32/67 - 47.7 %), unspecified (19/67 - 28 %), or temporal (9/67 - 13%) onset. Epileptic syndromes included familial focal epilepsy with variable foci (FFEVF) (29/74 - 39 %) and SHE (11/74 - 14.9 %).
Motor seizureNUS1Verified34532305The mental retardation-55 with seizures (MRD55) is a rare genetic disease characterized by... multiple types of epileptic seizures. ... a novel, de novo pathogenic variant of NUS1 ... was identified in a Chinese patient with intellectual disability and epileptic seizures.
Motor seizureOPHN1Verified38956616The male patient, aged 4, began experiencing epileptic seizures at 3 months post-birth... It was confirmed that OPHN1: c.1025 + 1G > A is the pathogenic cause of X-linked intellectual disabilities in the child, with clinical phenotypes including developmental delay and seizures.
Motor seizurePAFAH1B1Verified33150866We find that now dominant IS/NFS cells are prone to entering depolarization block, causing them to temporarily lose the ability to initiate action potentials and control network excitation, potentially promoting seizures.
Motor seizurePCDH19Verified32425876, 32189863, 34575929, 36247776, 34201522, 35978409, 33399642, 38083988The clinical features of the PCDH19 gene mutation include febrile epilepsy ranging from mild to severe, with or without intellectual disability, cognitive impairment, and psych-behavioral disorders... The electroencephalography (EEG) exhibited sharp waves and sharp slow complex waves in the bilateral parietal, occipital, and posterior temporal regions during the interictal period. (PMID: 36247776)
Motor seizurePDHA1Verified32466498The result describes available models of metabolic dysfunction associated with epileptic disorder, such as ... pyruvate dehydrogenase (PDH) alpha-subunit gene (PDHA1)...
Motor seizurePGAP2Verified36636587, 38790248The patient continues to make developmental progress with significant improvement in speech and fine motor skills. Our reported case expands the clinical spectrum of HPMRS3 in which multisystem involvement is being increasingly recognized. Furthermore, it shows that miss-targeting GPI-APs and the effect on normal cellular function could provide a physiopathologic explanation for the CSF biochemical abnormalities with management implications for a group of disorders that currently has no treatment that can lead possibly to improved clinical outcomes.
Motor seizurePGAP3Verified32726939, 36304370Assessment of zebrafish neuromuscular responses revealed epileptic-like movements at early development, followed by seizure-like behavior... mimicking the clinical phenotype human patients.
Motor seizurePHACTR1Verified39919830De novo variants of human PHACTR1, associated with early-onset epilepsies (DEE70), when expressed in C. elegans resulted in constitutive PP1-PHAC-1 holoenzyme activity. Unregulated PP1-PHAC-1 signaling alters the Synapsin and Actin cytoskeleton and increases neuropeptide release by cholinergic motor neurons, which secondarily affects the presynaptic vesicle cycle. Together, these results clarify the dominant mechanisms of action of the DEE70 alleles and suggest that altered neuropeptide release may alter E/I balance in DEE70.
Motor seizurePIGAVerified33440761Epilepsy is seen in many CDG subtypes and particularly present in the case of mutations in the following genes: ALG13, DOLK, DPAGT1, SLC35A2, ST3GAL3, PIGA, PIGW, ST3GAL5.
Motor seizurePIGHVerified33156547The common clinical features in all affected individuals are developmental delay/intellectual disability and hypotonia. Variable clinical features include seizures...
Motor seizurePIGPVerified32042915The 4 affected children exhibited a severe neurodevelopmental disorder featuring... infantile spasms, focal, tonic, and tonic-clonic seizures... The homozygous c.384del variant of PIGP... is predicted to result in... impaired functionality. We demonstrated a reduced expression of the GPI-AP CD16...
Motor seizurePIGTVerified36970549Pathogenic germline variants in the PIGT gene are associated with the "multiple congenital anomalies-hypotonia-seizures syndrome 3" (MCAHS3) phenotype. So far, fifty patients have been reported, most of whom suffer from intractable epilepsy. ... Our result confirm the pathogenicity of this variant and strengthen recently reported evidence on the genotype-phenotype correlation of the PIGT variant.
Motor seizurePIGWVerified39687712, 33440761The most frequently observed neurological symptoms in congenital disorders of glycosylation (CDG) are: epilepsy, intellectual disability, myopathies, neuropathies and stroke-like episodes. Epilepsy is seen in many CDG subtypes and particularly present in the case of mutations in the following genes: ... PIGW, ...
Motor seizurePIK3CAVerified38149038, 37645923We detect a pathogenic somatic PIK3CA variant, c.1624G>A (p.E542K), in the brain tissue samples, with VAF inversely correlated with distance from the SOZ. In addition, we identify this variant in amplified electrode-derived samples, albeit with lower VAFs. ... suggesting a correlation between variant burden and SOZ.
Motor seizurePLPBPVerified33425341The vitamin B6-dependent epilepsies are caused by mutations in at least five different genes involved in B6 metabolism. A literature review revealed that only 30 patients with vitamin B6-dependent epilepsy caused by PLPBP mutation have been reported worldwide. We report a case of baby boy born to first-cousin Pakistani parents who presented with generalized as well as focal seizures starting a few hours after birth and responsive to PLP. Whole exome sequencing revealed a homozygous pathogenic variant NM_007198.4:c.46_47insCA, NP_009129.1:p.Leu17Hisfs, causing a CA duplication resulting in a frameshift in the PLPBP gene.
Motor seizurePNKPVerified35354845, 40129048In this study, we applied high-dose oral phenobarbital (PB) to children with recurrent and treatment-refractory seizures... underlying disorders or comorbidity were genetic disorders (1q14 del, compound heterozygous for the PNKP gene, Wolf-Hirschhorn syndrome, ring chromosome 14 syndrome) in 4 patients...
Motor seizurePOGZVerified40051906White-Sutton syndrome (WSS), associated with POGZ gene mutations, is a rare genetic disorder characterized by a spectrum of phenotypic features, including intellectual disabilities, developmental delays, and epilepsy. A case report described a female patient diagnosed with WSS who experienced seizures resistant to conventional antiseizure medications... After initiating an off-label treatment with cannabidiol (CBD), the patient achieved complete remission from seizures.
Motor seizurePOLGVerified39958089, 40062103A six-year-old child presented with an acute onset of refractory epileptic seizures during a coronavirus disease 2019 (COVID-19) infection... Genetic analysis revealed a homozygous mutation in the DNA Polymerase Gamma, Catalytic Subunit (POLG) gene... confirming a diagnosis of Alpers-Huttenlocher syndrome. The clinical course was characterized by refractory seizures and developmental regression... This case underscores the critical importance of early genetic evaluation in children with unexplained refractory seizures, particularly for detecting underlying mitochondrial disorders such as POLG-related syndromes.
Motor seizurePPP3CAVerified36158964The patient experienced recurrent afebrile convulsions and spasms at the age of 2 months... diagnosed with developmental regression with recurrent spasms and myoclonic seizures... showed profound global developmental delay (GDD) with intermittent absence seizures. Whole-exome sequencing (WES) identified a novel loss-of-function variant c.1258_1259insAGTG (p. Val420Glufs*32) in PPP3CA.
Motor seizurePRICKLE1Verified36641750, 36582832Human PRICKLE1 gene has been associated with epilepsy. ... Here we report a Drosophila prickle mutant pk IG1-1 exhibiting strong epileptic seizures... Therefore, our findings indicate that Prickle ensures neuron-glial interaction within neuropils... Dysregulation of this process may represent a conserved pathogenic mechanism underlying PRICKLE1-associated epilepsy.
Motor seizurePRRT2Verified32237035, 40401013, 31901402, 38785332, 38406554, 32246320, 35715422, 36913149, 36187725The clinical features of 39 patients in 19 families included ... six paroxysmal kinesigenic dyskinesias (PKD)... PRRT2 mutations can be inherited or de novo, mainly inherited. The clinical spectrum of PRRT2 mutation includes BIE, BFIE, ICCA, PKD, FS, and ECME. ... Atypical phenotypes were observed in 3 children with heterozygous PRRT2 variants; 1 child evolved from SeLIE to infantile epileptic spasms, another developed spike-wave activation in sleep, and 1 developed focal epilepsy in adolescence. ... In this report, we present a rare case of a girl with a confirmed clinical and genetic diagnosis of BFIS due to a frameshift heterozygous mutation in PRRT2 (c.649dupC). She exhibited typical neurodevelopment until 15 months of age, followed by an unexpected severe autistic regression. In addition to BFIS, PRRT2 mutations are also associated with paroxysmal kinesigenic dyskinesia (PKD) and infantile convulsions and paroxysmal choreoathetosis (ICCA), indicating a complex genotype-phenotype heterogeneity in PRRT2 mutations. ... The two probands presented with focal motor seizures at 3 months of age, with a limited course. ...
Motor seizurePTENVerified33348808, 37645923, 38446016Both perampanel and GYKI 52466 increased PTEN expression and its activity (reduced phosphorylation)... These effects of perampanel and GYKI 52466 are observed in responders... but not non-responders (whose seizure activities were uncontrolled by AMPAR antagonists).
Motor seizurePTPN23Verified31395947Direct quote from the context: 'Shared characteristics of affected individuals include... seizures.' Reasoning: The context explicitly lists seizures as a shared characteristic among patients with PTPN23 defects, indicating an association.
Motor seizurePTRH2Verified34112751, 31057140In PMID 34112751, the proband has a history of seizures. In PMID 31057140, patients have epileptic seizures. Both studies link PTRH2 mutations to seizures.
Motor seizureSMSVerified32838743one patient presented with early-onset seizures. Clinical features, genetic and in-silico analysis linked the affected patients of the family with Snyder-Robinson and suggest that this novel mutation affects the spermine synthase activity.
Motor seizurePURAVerified33777106, 38606370patients develop a variety of symptoms, including hypotonia, metabolic abnormalities as well as epileptic seizures.
Motor seizureRBL2Verified39692517Frequent features included ... seizures, and non-specific dysmorphic features.
Motor seizureROGDIVerified38172607Mutants displayed pentylenetetrazol-induced seizures, confirming epilepsy susceptibility.
Motor seizureSAMD12Verified38059543The study evaluated 125 FCMTE type 1 patients carrying the pentanucleotide (TTTCA) repeat expansion in the SAMD12 gene. 97 (77.6%) of these patients had experienced seizures, indicating an association between SAMD12 mutations and motor seizures.
Motor seizureSCN1BVerified36291443, 36684540, 35886038Individuals with DEE present with seizures of various semiologies (commonly myoclonic seizures) and status epilepticus at early infancy... (PMID: 36291443). The cohort study from India reported that SCN1B variants were associated with developmental and epileptic encephalopathies, which include motor seizures (PMID: 36684540).
Motor seizureSCN2AVerified34093402, 32400968, 33236786, 34986624, 35715422, 36320799The phenotypes of c.4712T>C(p. I1571T), c.2995G>A(p.E999K), and c.4015A>G(p. N1339D) variants showed similar characteristics, including early seizure onset with severe to profound intellectual disability. Electrophysiological recordings revealed a hyperpolarizing shift in the voltage dependence of the activation curve and smaller recovery time constants of fast-inactivation than in wild type, indicating a prominent gain of function (GOF). Moreover, pharmacological electrophysiology showed that phenytoin inhibited over a 70% peak current and was more effective than oxcarbazepine and carbamazepine. In contrast, c.4972C>T (p.P1658S) and c.5317G>A (p.A1773T) led to loss of function (LOF) changes, showing reduced current density and enhanced fast inactivation. Both showed seizure onset after 3 months of age with moderate development delay. Interestingly, we discovered that choreoathetosis was a specific phenotype feature. (PMID: 32400968) - This study directly links SCN2A variants to seizure phenotypes, including early seizure onset and specific seizure characteristics, which are indicative of motor seizures. Additionally, the study in PMID 34093402 discusses SCN2A-related epilepsy and status epilepticus during slow sleep, which is a severe form of seizure activity. The study in PMID 35715422 also mentions SCN2A as one of the genes associated with poor prognosis in Epilepsy of Infancy with Migrating Focal Seizures (EIMFS), a condition characterized by migrating focal seizures, which are a type of motor seizure.
Motor seizureSCN3AVerified36319147, 37463203, 38174099The epilepsy associated with 2q24.3 microdeletion is mainly induced by the deletion of SCN3A, SCN2A and SCN1A genes. The seizure onset age of 2q24.3 microdeletion related epilepsy was in infancy. Multiple seizure types are observed and the common seizure types include focal seizures and GTCS. Most patients have fever sensitivity and status epilepticus. Most patients have developmental delay. The phenotype of patients with deletion of SCN3A and SCN2A gene is more severe than that of patients with deletion of SCN1A gene only. (PMID: 36319147)
Motor seizureSCN8AVerified36160949, 34867351, 32853054, 38969233, 39812613, 38895634Mice harboring the patient-derived N1768D point mutation of an Scn8a allele were crossed with transgenic mice such that inhibitory Designer Receptors Exclusively Activated by Designer Drugs (DREADD) receptors were selectively expressed in excitatory forebrain neurons. We then triggered audiogenic and hippocampal (HC) stimulated seizures... the seizure behaviors, notably the tonic phase and concomitant apnea, were unchanged. ... Both mouse lines show increased seizure susceptibility and infrequent spontaneous seizures. ... Case 1 is a 6-year-old right-handed girl who presented with SCN8A-developmental and epileptic encephalopathy (SCN8A-DEE) and a missense pathogenic variant... focal motor seizures starting at 4-months. ... elevated firing rate... median survival time... These data indicate that granule cells of the dentate gyrus are a specific locus of pathology in SCN8A-DEE. ... Countable motor seizures were meaningfully reduced in 10 of 12 patients... Six patients experienced a seizure reduction above 70%, of which two achieved seizure freedom. ... only carvedilol was able to significantly increase resistance to 6 Hz- and PTZ-induced seizures in RL/+ mutants.
Motor seizureSCN9AVerified40828807, 36684540, 36319147In PMID 36684540, SCN9A variants were found in 8 children with SCN developmental and epileptic encephalopathies, which is characterized by pleomorphic seizures including motor seizures. In PMID 36319147, SCN9A was identified as one of the main pathogenic genes in 2q24.3 microdeletion associated with epilepsy, including generalized tonic-clonic seizures (GTCS) and other seizure types. These studies associate SCN9A with seizure phenotypes, including motor-related seizures.
Motor seizureSEPSECSVerified35091508The proband... showed diffuse cerebral and cerebellar white matter volume loss. Both siblings later developed ventilator-dependent respiratory insufficiency and scoliosis and are currently nonverbal and nonambulatory. Variations in SEPSECS cause autosomal recessive pontocerebellar hypoplasia type 2D (PCHT 2D; OMIM #613811), a neurodegenerative condition characterized by progressive cerebrocerebellar atrophy, microcephaly, and epileptic encephalopathy.
Motor seizureSETD1BVerified38313655, 34345025Two of the three patients in PMID 38313655 had epilepsy. Antiepileptic treatment with sodium tripolyvalproate halted the seizures in the affected child. In PMID 34345025, the study mentions variable epilepsy phenotypes among patients with SETD1B variants.
Motor seizureSLC19A3Verified34631424, 38053933The clinical picture includes symptoms of subacute encephalopathy (e.g. confusion, dysphagia, dysarthria, and seizures), which respond very well to early treatment with thiamine and biotin. ... Genetic testing demonstrated pathogenic variants in SLC19A3 gene. ... A 16-year-old girl presented ... with seizures ... Whole-exome sequencing (WES) revealed homozygosity for a likely pathogenic variant in the SLC19A3 gene. Her residual neurological symptoms resolved with biotin and thiamine treatment, with the exception of ongoing memory concerns.
Motor seizureSLC1A2Verified33113868The treatment increased the expression level of the solute carrier family 1 member 2 gene (Slc1a2, encoding excitatory amino acid transporter 2 (EAAT2)) in the hippocampus, potentially leading to a neuroprotective effect. However, the increased gene expression of proinflammatory cytokine genes (Interleukin-1beta (Il1b) and tumor necrosis factor alpha (Tnfa)) and astroglial marker genes (glial fibrillary acidic protein (Gfap) and inositol 1,4,5-trisphosphate receptor type 2 (Itpr2)) in experimental rats was not affected by anakinra treatment.
Motor seizureSLC25A12Verified38553684, 36079864PMID 38553684: 'In the brain, mutations in SLC25A12 gene, encoding for AGC1, cause an ultra-rare genetic disease, reported as a neurodevelopmental encephalopathy, whose symptoms include global hypomyelination, arrested psychomotor development, hypotonia and seizures.'
Motor seizureSLC25A22Verified34679360, 40539845In the first context, SLC25A22 is listed among genes associated with neonatal seizures. The second context shows that slc25a22a mutant zebrafish display spontaneous seizures, which are a type of motor seizure.
Motor seizureSLC2A1Verified39745620, 34573360The abstracts mention that mutations in the SLC2A1 gene lead to Glut1DS, which is associated with seizures, including motor seizures. The first abstract states, 'This disease arises from mutations in the SLC2A1 and presents with a broad clinical spectrum.' It also notes 'seizures, episodic or persistent movement disorders...paroxysmal exercise-induced dyskinesia (PED)' as clinical manifestations. The second abstract describes 'early infantile seizures' as a characteristic of GLUT1DS caused by SLC2A1 gene defects.
Motor seizureSLC35A2Verified36119689, 39460689, 34122512, 38612920, 33440761, 31677975In the study (PMID: 36119689), patients with pathogenic mutations in the SLC35A2 gene had a >50% reduction in seizure frequency. This indicates that SLC35A2 is associated with seizure phenotypes, including motor seizures. Additionally, PMID: 39460689 shows that SLC35A2 deficiency in neurons leads to early onset seizures and developmental delays, further supporting its role in seizure disorders.
Motor seizureSLC9A6Verified40722028, 35095740, 33897753, 39237363The three patients with null variants presented with refractory epilepsies and severe developmental delay; one patient with missense variant in the transmembrane region showed refractory epilepsies and speech delay; and one patient harboring missense variant located in the loop region achieved seizure-free with favorable outcome. Further analysis revealed that the proportions of brain atrophy, microcephaly, and movement disorders in patients with missense variants were significantly lower than that of patients with null variants, suggesting a genotype-phenotype correlation. Additionally, previously reported missense variants in the pore/transmembrane region led to Christianson Syndrome, whereas variants outside these regions were associated with milder phenotype, suggesting a sub-regional effect.
Motor seizureSMARCA2Verified36261270Proteins mediating excitatory and inhibitory synaptic plasticity, including SynGAP1, Pak3, GEPH1, Copine-6, and collybistin, and DNA and chromatin remodeling proteins, including Rad21, Smarca2, and Ddb1, are differentially synthesized in response to activity.
Motor seizureSMC1AVerified35712061, 38076278, 38440111, 40587154, 38421079The two girls with SMC1A mosaicism presented clusters of focal impaired awareness, myoclonic, and tonic-clonic seizures at 19 and 20 months of age. (PMID: 40587154) SMC1A variants are known to cause Cornelia de Lange Syndrome (CdLS) which encompasses a clinical spectrum... and, in some cases, epilepsy. (PMID: 35712061) The girl presented... with febrile and afebrile clusters of focal seizures. (PMID: 38076278) The analyzed cohort... shows drug-resistant epilepsy... (PMID: 38421079)
Motor seizureSNORD118Verified34220662The patient was a 4-year-and-1-month-old boy with focal seizures. The age at onset of his seizure was 10 days after birth. The seizures were well-controlled by antiepileptic treatment but reoccurred twice due to a head impact accident and a fever, respectively. He suffered from a self-limited esotropia and unsteady running gait during the seizure onset. He had the typical neuroimaging triad of multifocal intracranial calcifications, cysts, and leukoencephalopathy. Genetic analysis indicated that he carried compound heterozygous variants of n.*9C>T and n.3C>T in SNORD118, which were inherited from his parents.
Motor seizureSPTBN1Verified34211179Here we identify heterozygous SPTBN1 variants in 29 individuals with developmental, language and motor delays; mild to severe intellectual disability; autistic features; seizures; behavioral and movement abnormalities; hypotonia; and variable dysmorphic facial features.
Motor seizureSRPX2Verified33240831The hub protein in PPI network is GluN2A, which might affect language function via foxp2-srpx2/uPAR signal network.
Motor seizureST3GAL3Verified37067065, 33440761Two brothers presented with global developmental delay, motor and language impairment, hypotonia, and childhood-onset seizures. Seizures started between 2.5 and 5 years and had tonic components. Both siblings had prolonged periods of seizure freedom on carbamazepine. Tremor was present in the younger sibling. Whole exome sequencing revealed two novel pathogenic variants in ST3GAL3, (a) c.302del, p.Phe102Serfs*34 and (b) c.781C>T, p.Arg261*, which were inherited in trans. A review of the literature revealed 24 cases of ST3GAL3-related CDG. Twelve cases had information about seizures, and epilepsy was diagnosed in 8 (67%). The median age of seizure onset was 5.5 months. Epileptic spasms were most common (67%). Four children were diagnosed with Infantile Epileptic Spasms syndrome and Lennox Gastaut syndrome (57%). Most children (n = 6, 75%) had seizures despite anti-seizure medication treatment.
Motor seizureSTX1BVerified37349285, 35095745In the epileptic brain tissue, syntabulin mainly translocated syntaxin 1B (STX1B) rather than syntaxin 1A (STX1A) to the presynaptic membrane, which resulted in increased presynaptic transmitter release. Further studies showed that syntabulin had a more significant effect on presynaptic functionality of GABAergic activity over that of excitatory synapses and resulted in an excitation/inhibition (E/I) imbalance, thereby regulating the epileptic phenotype.
Motor seizureSTXBP1Verified37215006, 38015929, 32073399, 35190816The abstracts mention that STXBP1-related disorders are characterized by seizures, including infantile spasms and focal-onset seizures. Specifically, individuals with STXBP1 mutations exhibit a dynamic pattern of seizures in the first year of life, with 90% cumulative onset for infantile spasms by 6 months and focal-onset seizures by 27 months. The study also notes that individuals with protein-truncating variants and deletions in STXBP1 are more likely to have infantile spasms between 5 and 6 months followed by seizure remission, while those with missense variants have an increased risk for focal seizures and ongoing seizures after the first year. These findings directly associate STXBP1 with motor seizures, including infantile spasms and focal seizures.
Motor seizureSV2AVerified38811492, 34805114, 38776036BRV binds to SV2A with 15- to 30-fold higher affinity and greater selectivity than levetiracetam. BRV has broad-spectrum antiseizure activity in animal models of epilepsy... (PMID: 38811492). Kaempferol, quercetin, and catechin were found to have the highest binding affinity with the synaptic vesicle 2A (SV2A) protein, comparable to standard levetiracetam (LEV)... (PMID: 34805114).
Motor seizureSYNGAP1Verified32913957, 36583017, 38045990, 34954508Mutations in SYNGAP1 are associated with developmental delay, epilepsy, and autism spectrum disorder (ASD). Epilepsy is often drug-resistant in this syndrome with frequent drop attacks. ... After CBD introduction, two patients were responders since M2 and achieve a seizure reduction of 90% and 80%, respectively, at M9 with disappearance of drop attacks. ... SYNGAP1 mutations have been rarely reported in the Chinese population. ... All patients with epilepsy were sensitive to anti-seizure drugs, especially sodium valproate. ... 71% of patients had drug-resistant seizures, treated with a median of 2 antiseizure medications. ... Ten of 14 (71%) patients had drug-resistant seizures, treated with a median of 2 antiseizure medications. ... SYNGAP1-developmental and epileptic encephalopathy (SYNGAP1-DEE) ... generalized epilepsy with spontaneous and reflex seizures. ... drug-resistant epilepsy with possibility to experience pluridaily absence seizures that may lead to periods of psychomotor regressions.
Motor seizureSYNJ1Verified39624497Five patients from three unrelated families with DEEs had symptoms that started during the neonatal period with seizures and myoclonus that became refractory to antiepileptic medications. WES identified previously unreported variants in all three families: homozygous variants in GRIN1 and SYNJ1, and compound heterozygous variants in RARS2.
Motor seizureSZT2Verified37760843, 36531768, 33681650, 33333793Seizures were noted as the predominant hallmark (n = 26). ... Despite significant multifocal epileptiform abnormalities on her electroencephalogram, she had a paucity of generalized discharges indicating a functional deficiency of corpus callosum inspite of its increased thickness seen on magnetic resonance imaging. ... Mutations in seizure threshold 2 (SZT2) gene on chromosome 1p34.2 are an of late identified cause of epilepsy and epileptic encephalopathy.
Motor seizureTBC1D24Verified34020146, 32004315In PMID 34020146, TBC1D24 is listed among the genes associated with EIMFS, which is characterized by migrating focal motor seizures. In PMID 32004315, TBC1D24 mutations are linked to epilepsy and ID, with knock-in mice showing spontaneous seizures.
Motor seizureTBCDVerified34943336Clinical features included ... seizures. We established the genotype-phenotype relationship of these TBCD pathogenic variants...
Motor seizureTPK1Verified37622082Patients with TPK deficiency present with ... seizures, and other nervous system dysfunction. ... gene analysis is important for the diagnosis of TPK deficiency caused by TPK1 variants, and thiamine supplementation has been the mainstay of treatment for TPK deficiency to date.
Motor seizureTRIT1Verified40908562The proband...refractory seizures (focal motor clonic, generalized myoclonic, and tonic) since 6 months of age.
Motor seizureTSC1Verified39814050, 39722056PMID 39814050 describes a newborn with HME and a confirmed mutation in the TSC-1 gene who experienced therapy-resistant seizures. The case highlights the association between TSC1 mutations and seizure phenotypes. Additionally, PMID 39722056 notes that TSC2 mutations are more commonly linked to severe phenotypes, including drug-resistant focal seizures, indicating that both TSC1 and TSC2 are involved in seizure-related manifestations in TSC.
Motor seizureTSC2Verified32216820, 39722056, 40367637In PMID 32216820, the abstract states that four out of six patients developed seizures, with EEG abnormalities preceding clinical seizures. The two patients with the worst outcomes had pathogenic variants in the GAP domain of TSC2. In PMID 39722056, it is noted that 16 out of 22 cases had TSC2 mutations, and 6 (27%) with TSC2 mutations exhibited drug resistance for focal seizures. These findings indicate a strong association between TSC2 mutations and seizure-related phenotypes, including motor seizures.
Motor seizureTSEN54Verified20301773PCH4. Neonates often have seizures, multiple joint contractures ("arthrogryposis"), generalized clonus, and central respiratory impairment.
Motor seizureTUBA1AVerified37744437, 35017693, 35892608PMID 35017693 reports that 75% of TUBA1A tubulinopathy cases observed epilepsy, which showed infantile onset in 83% and a refractory course in 50%. One individual presented a novel TUBA1A-associated electroclinical phenotype with evolvement from early myoclonic encephalopathy to continuous spike-and-wave during sleep. PMID 35892608 describes a case with a de novo mutation in TUBA1A where seizures were refractory initially and the individual showed the picture of developmental and epileptic encephalopathy (DEE) at 1 year and 2 months of age.
Motor seizureTUBB2BVerified35892608Case 1, a 23-year-old boy, ... A de novo mutation in TUBB2B was proven through next-generation sequencing (NGS).
Motor seizureTUBB3Verified36309617Tubb3 mutations are associated with neuronal disease, including abnormal inhibitory transmission and seizure activity in patients
Motor seizureUBA5Verified37502976, 38079206Variants in the UBA5 gene are associated with developmental and epileptic encephalopathy 44 (DEE44)... characterized by... seizures. The study establishes a classification of LoF variants into mild, intermediate, and severe allelic strengths, correlating with phenotypes including seizures.
Motor seizureUBE3AVerified40935670, 39197537, 38370819, 40382580, 34676830In a Drosophila model of Dup 15q syndrome, it was recently shown glial-driven expression of the UBE3A ortholog dube3a led to a 'bang-sensitive' phenotype, where mechanical shock triggers convulsions, suggesting glial dube3a expression contributes to hyperexcitability in flies. ... glial-driven dube3a flies display spontaneous spike discharges which were bilaterally synchronized indicative of seizure activity. (PMID: 39197537)
Motor seizureUGDHVerified38292436, 32001716In this case study, we report a large consanguineous family with multiple children suffering from cerebral palsy, seizure, developmental and epileptic encephalopathy, and global developmental delay... Whole-exome sequencing (WES) analysis revealed a homozygous variant in the UDP-glucose dehydrogenase (UGDH) gene... indicating a potential disease-causing association. ... Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy. ... presenting with epileptic encephalopathy with developmental delay and hypotonia.
Motor seizureWDR45Verified32387008Most individuals experienced a decline in motor and cognitive skills. Although most individuals were affected by seizures, the spectrum ranged from provoked seizures to intractable epilepsy.
Motor seizureWWOXVerified39416860, 39101447, 39507621, 32000863, 35715422The patient had refractory epilepsy with various types of seizures during his life: mainly epileptic spasms, autonomic, myoclonic, tonic seizures, and absences. (PMID: 39507621) In the present study, a novel variant in WWOX was detected in a patient with epilepsy and his healthy parents. Case presentation: A 5-month-old boy presented with epilepsy. The main manifestations were intractable seizures, mental and motor retardation and hearing impairment. (PMID: 39416860) Our patient was a 13-month-old girl [...] She also had [...] before the age of 8 months, she was suffering from mild seizures. (PMID: 39101447)
Motor seizureYWHAGVerified40152536, 33767733, 34168609, 35481155The patient is a 6-year-2-month-old boy who developed refractory complex seizures starting at 8 months of age... WES identified the de novo occurrence of a novel heterozygous YWHAG missense variant, c.518T>C (p.L173S), in the patient. ... The identified mutations included a heterozygous truncating mutation (c.124C>T/p.Arg42Ter) and a de novo missense mutation (c.373A>G/p.Lys125Glu). The two probands experienced daily myoclonic seizures that were recorded with ictal generalized polyspike-slow waves...
Aplasia of the ulnaLRP4ExtractedMol Genet Genomic Med38013226Exome sequencing revealed a novel biallelic c.282C>A variant in low-density lipoprotein receptor-related protein 4 (LRP4; OMIM604270; NM_002334.4) causing p. (Asn94Lys) change in the encoded protein.
Aplasia of the ulnaBMPR-IBExtractedZool Res35362676All BMPR-IB-disrupted piglets showed an inability to stand and walk normally. Both BMPR-IB -/- and BMPR-IB -/746G piglets exhibited severe skeletal dysplasia characterized by distorted and truncated forearms (ulna, radius) and disordered carpal, metacarpal, and phalangeal bones in the forelimbs.
Aplasia of the ulnaLAF4ExtractedClin Genet18616733array comparative genomic hybridization (CGH) analysis revealed a de novo interstitial microdeletion of 500 kb on chromosome 2q11.1 containing the LAF4/AFF3 (lymphoid-nuclear-protein-related AF4) gene.
Aplasia of the ulnaSHOXExtractedNat Genet9590293A point mutation leading to a premature stop in exon 4 of SHOX was identified in one LWD family. ... hypoplasia/aplasia of the ulna and fibula, has been postulated to be the homozygous form of LWD.
Aplasia of the ulnaHOXDExtractedJ Med Genet15980115Patient 2, with translocation t(2;10)(q31.1;q23.33), has aplasia of the ulna, shortening of the radius, finger anomalies, and scoliosis. ... breakpoints involving chromosome 2q31 ... close to the HOXD cluster.
Aplasia of the ulnaTBX3BothEndocr Connect30550377Ulnar-mammary syndrome (UMS) is characterized by ulnar defects, and nipple or apocrine gland hypoplasia, caused by TBX3 haploinsufficiency.
Decreased circulating copper concentrationMT1AExtractedJournal of Animal Science33409464Liver Cu was decreased in Zn supplemented steers vs. CON (P = 0.02)... d 97 MT1A expression (P = 0.03) where INZN was greater than ZNBLD or CON (P <= 0.02)
Decreased circulating copper concentrationSOD1ExtractedJournal of Clinical Medicine33019780The plasma of AP patients showed an increased SOD1 concentration... The impact of SNP rs2070424 in the SOD1 gene...
Decreased circulating copper concentrationMTExtractedPoultry Science35698226Cu levels linearly increased... metallothionein (MT) and malate dehydrogenase (MDH) expression...
Decreased circulating copper concentrationMDHExtractedPoultry Science35698226Cu levels linearly increased... metallothionein (MT) and malate dehydrogenase (MDH) expression...
Decreased circulating copper concentrationATOX1ExtractedPoultry Science35698226Cu levels linearly increased... ATP7A was expressed at significantly higher levels in RA samples...
Decreased circulating copper concentrationATP7BExtractedMolecular Therapy - Methods and Clinical Development35795774mutations in ATP7B gene... AAV encoding a mini version of human ATP7B (VTX-801)...
Decreased circulating copper concentrationCPExtractedInternational Journal of Molecular Sciences34360993mutations in the CP gene give rise to aceruloplasminemia... recombinant human CP in glycoengineered Pichia pastoris...
Decreased circulating copper concentrationFDX1ExtractedFrontiers in Immunology36891318DLST was significantly lower... FDX1 was expressed at significantly higher levels in RA samples... SLC27A5 could upregulate FDX1...
Decreased circulating copper concentrationSLC27A5ExtractedAging38157255SLC27A5 might be a potential regulator of cuproptosis... SLC27A5 inhibited cell proliferation and migration of HCC cells...
Decreased circulating copper concentrationSLC31A1ExtractedBiomedicines38001885SLC31A1 encodes a protein that functions as a homotrimer for the uptake of dietary copper... SLC31A1 may be of particular relevance in immunotherapy.
Decreased circulating copper concentrationATP7AVerified32169084, 40880469, 34069220, 32010131, 36829476In the study (PMID: 36829476), chronic corticosterone exposure was found to decrease plasma copper levels and down-regulate the expression of ATP7A in the duodenum of mice. The down-regulation of ATP7A was linked to decreased copper transport, leading to reduced circulating copper concentrations.
EnuresisSHANK3Extracted35996993SHANK3 pathogenic variants (84.8%) and those with deletions (71.9%)
EnuresisTPOExtracted37780999homozygous variants in TPO: novel missense variant c.719A>G (p.Asp240Gly) in family 1 and rare c.2315A>G (p.Tyr772Cys) in family 2
EnuresisHPDLExtracted35222531a homozygous variant in the HPDL gene
EnuresisAUHExtracted35457240pathogenic variants in the AUH gene
EnuresisNIPBLExtracted36093091NIPBL gene pathogenic variant
EnuresisMUC1Extracted38027261pathogenic variants in the MUC1, UMOD, HNF1B, REN, SEC61A1, and DNAJB11 genes
EnuresisUMODExtracted38027261pathogenic variants in the MUC1, UMOD, HNF1B, REN, SEC61A1, and DNAJB11 genes
EnuresisHNF1BExtracted38027261pathogenic variants in the MUC1, UMOD, HNF1B, REN, SEC61A1, and DNAJB11 genes
EnuresisRENExtracted38027261pathogenic variants in the MUC1, UMOD, HNF1B, REN, SEC61A1, and DNAJB11 genes
EnuresisSEC61A1Extracted38027261pathogenic variants in the MUC1, UMOD, HNF1B, REN, SEC61A1, and DNAJB11 genes
EnuresisDNAJB11Extracted38027261pathogenic variants in the MUC1, UMOD, HNF1B, REN, SEC61A1, and DNAJB11 genes
EnuresisAGXTVerified39616448Patients were analyzed for genetic variations in genes associated with nocturnal enuresis, including AGXT...
EnuresisAQP2Verified38812639, 37140712, 36852848, 39616448, 36034562Primary monosymptomatic nocturnal enuresis in children could be associated with reduction of urine excretion of AQP-2 at night. Urine AQP-2 is significantly correlated with urine osmolality. Therefore, it may be a noninvasive biomarker of hydration status in children with PMNE, with good sensitivity and specificity. (PMID: 38812639); ...reduced levels of aquaporin-2 on wet nights. (PMID: 37140712); ...serum levels of copeptin (blood) and AQP2 (urine) were significantly lower in enuretic patients compared to healthy controls. (PMID: 36852848); ...variant in the AQP2 gene... (PMID: 39616448)
EnuresisAVPR2Verified39616448, 35621979The AQP2 gene is associated with autosomal dominant and autosomal recessive inherited nephrogenic diabetes insipidus (type 2) in the OMIM (Online Mendelian Inheritance in Man) database. ... gene AVPR2. ... CPT, but not OTP, acts as a selective agonist of human AVP type 1b and 2 receptors.
EnuresisBNC2Verified39616448Patients were analyzed for genetic variations in genes associated with nocturnal enuresis, including BNC2...
EnuresisCLCNKBVerified39616448Patients were analyzed for genetic variations in genes associated with nocturnal enuresis, including CLCNKB...
EnuresisDLG3Verified39616448Patients were analyzed for genetic variations in genes associated with nocturnal enuresis, including DLG3...
EnuresisFA2HVerified39616448Patients were analyzed for genetic variations in genes associated with nocturnal enuresis, including AGXT, AQP2, AVPR2, BNC2, CLCNKB, DLG3, ELN, FA2H, FAM20A, FOXP1, HPSE2, KCNJ10, MLXIPL, NPHP3, RNF168, SLC12A3, SLC25A13, SLC5A2, and SMARCA2.
EnuresisFAM20AVerified39616448Patients were analyzed for genetic variations in genes associated with nocturnal enuresis, including AGXT, AQP2, AVPR2, BNC2, CLCNKB, DLG3, ELN, FA2H, FAM20A, FOXP1, HPSE2, KCNJ10, MLXIPL, NPHP3, RNF168, SLC12A3, SLC25A13, SLC5A2, and SMARCA2.
EnuresisFOXP1Verified39616448Patients were analyzed for genetic variations in genes associated with nocturnal enuresis, including FOXP1...
EnuresisHPSE2Verified39616448, 24966895The Urofacial (Ochoa) Syndrome (UFS) is characterized by ... dysfunctional voiding ... enuresis ... HPSE2, the gene encodes Heparanse 2 ... was thought to be the only culprit gene for this syndrome.
EnuresisKCNJ10Verified32419412, 39616448SNP3 in promoter of KCNJ10 gene showed strong association with MNE children for distribution of genotype and allele frequency... TT genotype was higher and there was an increased potassium excretion in children with TT genotype (P < 0.05).
EnuresisLRIG2Verified24966895The patients show a peculiar distortion of the facial expression (grimacing as if in pain or sadness when they tried to smile or laugh) along with urinary tract infection, enuresis, vesicoureteral reflux and hydronephrosis without any underlying neurological lesion and previous urinary obstruction. ... another criminal gene, LRIG2, which encodes leucine-rich repeats and immunoglobulin-like domains 2, was also come into the light in 2012.
EnuresisMLXIPLVerified39616448Patients were analyzed for genetic variations in genes associated with nocturnal enuresis, including ... MLXIPL ...
EnuresisNPHP3Verified39616448, 11274269The responsible gene (NPHP3) maps to 3q21-q22. NPH3 shares with juvenile nephronophthisis (NPH1) the same disease manifestations such as polyuria, polydipsia, and secondary enuresis.
EnuresisSLC12A3Verified39616448Patients were analyzed for genetic variations in genes associated with nocturnal enuresis, including ... SLC12A3 ...
EnuresisSLC25A13Verified39616448Patients were analyzed for genetic variations in genes associated with nocturnal enuresis, including ... SLC25A13 ...
EnuresisSLC5A2Verified39616448Patients were analyzed for genetic variations in genes associated with nocturnal enuresis, including ... SLC5A2, ...
Aplasia cutis congenita over the scalp vertexDLL4ExtractedFront Surg36713669The infant had a large deletion encompassing the 15.1 region of chromosome 15, including the DLL4 gene.
Aplasia cutis congenita over the scalp vertexKCTD1ExtractedJ Clin Invest38113115KCTD1 mutations cause ACC, ectodermal abnormalities, and kidney fibrosis, whereas KCTD15 mutations cause ACC and cardiac outflow tract abnormalities.
Aplasia cutis congenita over the scalp vertexKCTD15ExtractedJ Clin Invest38113115KCTD1 mutations cause ACC, ectodermal abnormalities, and kidney fibrosis, whereas KCTD15 mutations cause ACC and cardiac outflow tract abnormalities.
Aplasia cutis congenita over the scalp vertexDOCK6ExtractedMedicine (Baltimore)33655927The whole exon sequencing confirmed the diagnosis of AOS with 2 AOS-gene mutations at DOCK6 and ARHGAP31.
Aplasia cutis congenita over the scalp vertexARHGAP31ExtractedMedicine (Baltimore)33655927The whole exon sequencing confirmed the diagnosis of AOS with 2 AOS-gene mutations at DOCK6 and ARHGAP31.
Aplasia cutis congenita over the scalp vertexBMS1BothPLoS Genet23785305BMS1 is mutated in aplasia cutis congenita. A heterozygous Arg-to-His missense mutation (p.R930H) in the ribosomal GTPase BMS1 is identified in ACC that is associated with a delay in 18S rRNA maturation, consistent with a role of BMS1 in processing of pre-rRNAs of the small ribosomal subunit.
Aplasia cutis congenita over the scalp vertexPLECVerifiedPLEC mutations cause autosomal recessive aplasia cutis congenita type 6 (OMIM 617199).
PolyembolokoilamaniaRAI1BothOrphanet J Rare Dis26336863, 25934608, 20301487Self-injurious behaviors including self-hitting, self-biting, skin picking, inserting foreign objects into body orifices (polyembolokoilamania), and yanking fingernails and/or toenails (onychotillomania).
SplenomegalySTAT3Both36117975, 38024861, 32200265, 37727880, 39019339, 39049194Splenomegaly was observed in 19 (76%) patients. Mutations in the STAT3 were detected in 56% of patients using next-generation sequencing. (PMID: 36117975) The genetic blockade of pS727-STAT3 in gp130F/F:Stat3SA/SA mice ameliorated the neutrophilia, thrombocytosis, splenomegaly and lymphadenopathy that are features of gp130F/F mice. (PMID: 32200265) The innate immune response in mice was drastically triggered by MRP, manifesting as splenic and systemic inflammation with splenomegaly... DhA mitigates the inflammation process induced by MRP via blocking the TLR4 cascade, highlighting the therapeutic potential of DhA in targeting S. suis infection diseases. (PMID: 38024861) Prolonged the survival of MRL/lpr mice, significantly reduced anti-dsDNA antibody production, and alleviated symptoms of lupus nephritis, splenomegaly, and lymphadenopathy... (PMID: 37727880) Stat3p.L387R/+ mice exhibited... splenomegaly... (PMID: 39019339)
SplenomegalyHLAExtracted39733427HLA - rs6457327
SplenomegalyTNFExtracted39733427TNF - rs1800630 and rs2229094
SplenomegalyGATA3Extracted39733427GATA3 - rs3824662
SplenomegalyTP53Both39733427, 34816104, 40651100, 32871937, 37588745Rbm8aKOMK mice exhibited marked thrombocytopenia, internal hemorrhage, and splenomegaly...Trp53 knockout partially restored megakaryocyte differentiation...indicating that excess p53 in part accounts for thrombocytopenia in TAR syndrome. MH TP53-mutated CLLs showed significantly greater...splenomegaly...MH vs. SH: 69 % vs.75 % and 52 % vs.75 %, respectively...AV-SMZL...TP53 mutations...B-PLL...P53 abnormalities...BR regimen...Splenomegaly was present in all three B-PLL cases.
SplenomegalyCASP9Extracted39733427CASP9 - rs4661636
SplenomegalyCASP8Both39733427, 36287014, 34956189, 37038193PMID 36287014: 'S. suis induced apoptosis in B cells, which is related to the cleavage of caspase-3 and caspase-8... S. suis induced apoptosis in the spleen through caspase-dependent and AIF-independent pathways.' This indicates CASP8's role in splenic apoptosis. PMID 34956189: 'RIP kinases work together with caspase-8 to regulate cell death... RIP1 regulated MZ B cell development... delayed T-dependent and T-independent IgG responses.' CASP8's involvement in B cell regulation and splenomegaly is shown. PMID 37038193: 'Caspase-8 deficiency... splenomegaly... diagnosed with the caspase-8 deficiency.' Directly links CASP8 deficiency to splenomegaly.
SplenomegalyCEBPEExtracted39733427CEBPE - rs2239633
SplenomegalyPIP4K2AExtracted39733427PIP4K2A - rs7088318
SplenomegalyCASC8Extracted39733427CASC8 - rs10505477
SplenomegalyIRF4Extracted39733427IRF4 - rs87207
SplenomegalyCYP1A1Extracted39733427CYP1A1 - rs4646903 and rs7089424
SplenomegalyARID5BExtracted39733427ARID5B gene
SplenomegalyCDKN1aExtracted37672319The Foxo3 target cell cycle inhibitor Cdkn1a (p21) is markedly upregulated in both mouse and patients-derived beta-thalassemic erythroid precursors.
SplenomegalySPTBBoth40090920, 39627779, 33014018, 39959857, 39760301, 36926142, 38947766Hereditary spherocytosis (HS) is an inherited disorder characterized by anemia, splenomegaly, and spherical-shaped erythrocytes, caused by mutations in erythrocyte membrane Protein Genes (ANK1, SPTB, SLC4A1, SPTA1, and EPB42). ... ten patients harbored SPTB variants ... Most ANK1 and SPTB variants were indel (5/12) or non-sense (7/10), respectively. ... variants in the ANK1 death domain were associated with lower levels of MCV and MCH compared to other ANK1 domains.
SplenomegalyPEPDBoth39086453, 32455636, 38304571, 26110198, 36637239Organomegaly (typically splenomegaly but occasionally associated with hepatomegaly) with elevated liver enzymes. ... molecular diagnosis can be established in a proband with suggestive findings and biallelic pathogenic variants in PEPD identified by molecular genetic testing.
SplenomegalyPIEZO1Both33837027, 32109669, 38033286The father of the baby suffers from haemolytic anaemia, splenomegaly and has had jaundice throughout his life. His brother and family have similar conditions. We suspect that at least one of the gene variants identified in our exome sequencing may be responsible for the illness that runs in this family, including the fetus with isolated ascites. (PMID: 33837027). In the context of Hereditary Xerocytosis (HX), affected members show compensated anemia with splenomegaly... associated with PIEZO1 variants. (PMID: 32109669). Enhanced PIEZO1-TMEM16F coupling leads to increased PS exposure, contributing to HX clinical manifestations including splenomegaly. (PMID: 38033286).
SplenomegalyABCA1Verified38538338, 39863479, 36496495Case 1 is a new ABCA1 mutation with complex pathogenicity, namely, a W484*/S1343I compound heterozygote with marked hypo-HDL cholesterolemia. ... Case 1 also had Krabbe disease. ... splenomegaly. ... Case 2, ... confirmed Tangier disease. ... splenomegaly. ... We report a case of a 47-year-old man ... splenomegaly. ... A 34-year-old man ... splenomegaly. ... ABCA1 mutations are associated with splenomegaly in Tangier disease as observed in all three cases.
SplenomegalyABCB11Verified40537152, 36550572, 39618628In the first study (PMID: 40537152), the abstract mentions that 13 out of 28 families had ABCB11 variants (PFIC2), and among the clinical features reported in these patients were splenomegaly (19.4%). This directly supports the association between ABCB11 and splenomegaly in the context of PFIC.
SplenomegalyABCB4Verified36550572, 33757843, 40729246Splenomegaly in 52.6% (50/95) of PFIC3 patients... [PMID: 36550572]; splenomegaly (4 out of 4 patients) [PMID: 33757843]; splenomegaly... [PMID: 40729246]. ABCB4 mutations are linked to splenomegaly in PFIC3.
SplenomegalyABCG5Verified40695672, 34304999, 40686589, 34969652In PMID: 40695672, the patient with sitosterolemia caused by ABCG5 variants experienced resolution of splenomegaly. In PMID: 34304999, patients with ABCG5 variants showed splenomegaly which resolved with ezetimibe. In PMID: 34969652, splenomegaly was observed in pediatric and adult patients with sitosterolemia linked to ABCG5/ABCG8 variants.
SplenomegalyABCG8Verified40686589, 34304999, 40773003Splenomegaly and xanthomas were other common associations. ... all these patients had hematologic abnormalities. ... Four homozygotes received ezetimibe, and their splenomegaly, anemia, and thrombocytopenia completely resolved except one.
SplenomegalyABL1Verified36694063, 36010887In the first abstract, the case report describes a patient with chronic myelomonocytic leukemia and the ZMIZ1-ABL1 fusion gene, where splenomegaly was a main manifestation. In the second abstract, SOS1's role in BCR-ABL-driven CML is discussed, noting that SOS1 ablation in p210BCR/ABL mice led to a reduction in splenomegaly, a hallmark of CML. Both studies link ABL1 (or its fusion/activation) to splenomegaly in myeloid disorders.
SplenomegalyADAVerified36473034Repetitive administration of DMSO for 10 days produced anemia, hemoglobinuria, hemoglobinemia, splenomegaly, and development of PH. ... DMSO-induced increase in right ventricular peak systolic pressure (RVPSP) was associated with increased release of ADA.
SplenomegalyADA2Verified37179309, 35592317Splenomegaly (30.6%)... Patients with DADA2 can have... splenomegaly...
SplenomegalyADARVerified35865544We further explored HS-specifically enriched genes (such as FKBP5, ADAR, and RPS4Y1) and found that FKBP5 was highly expressed in HCC-HS, leading to immunosuppression.
SplenomegalyAKT1Verified40275745, 32143311, 35582997Transcriptome analysis from spleen revealed significant differences in gene expression between VACV-L and VACV-H groups, but the differentially expressed genes induced by splenomegaly between VACV-L and MPXV groups were highly similar. Furthermore, pathway enrichment analysis demonstrated that the VACV-L, VACV-H, and MPXV groups were all associated with the calcium, MAPK, and PI3K-Akt signaling pathway. ... the PI3K-Akt signaling pathway may promote splenomegaly by modulating granulocyte infiltration and inflammatory responses. ... curcumin treatment reduced activation of the NFkB, MAPK, AKT and pBAD pathways either systemically, or within the inflamed kidneys. ... LY294002 treatment reversed the increased expression of ... AKT, p-AKT, ... and the decreased expression of PTEN.
SplenomegalyALAS2Verified39656107, 39995829, 33659185, 37491335Alas2-KOBM animals displayed a severe anemic phenotype characterized by ineffective erythropoiesis (IE), leading to... splenomegaly... The IE was associated with marked splenomegaly... Infusion of BM cells with 0.6-1.4 copies of the X-ALAS2-LV in Alas2-KOBM mice improved... splenomegaly... The proband was a 29-year-old man with... splenomegaly... His iron overload also responded to sustained oral iron chelation therapy with deferasirox. The screening of the entire family's kindred revealed that two other male siblings were also hemizygous for the same mutation with... splenomegaly... We observed a progressive decrease in plasma ferritin and urinary porphyrins upon treatment without inducing anemia. The patient reported improved quality of life and photosensitivity. Pretreatment with arketamine blocked increased expression of genes involved in the heme biosynthesis II pathway in LPS-treated mice, namely, 5-aminolaevulinase synthase 2 (Alas2)... There were positive correlations between the expression of these genes and spleen weight...
SplenomegalyALPK1Verified31939038, 39626775, 40925900, 40270650, 38060563, 36332842, 35868845, 36543582The clinical manifestations were relatively homogeneous, prominently presenting with juvenile onset oculopathy and splenomegaly. ... ROSAH syndrome is an autosomal dominant disorder and to date is known to be caused by either the Thr237Met or Tyr254Cys variant in the protein kinase ALPK1. ... All six patients examined display ocular inflammation and optic nerve elevation, four have retinal degeneration and four are registered blind. ... The atypical protein kinase ALPK1 is activated by the bacterial nucleotide sugar ADP-heptose and phosphorylates TIFA to switch on a signaling pathway that combats microbial infection. In contrast, ALPK1 mutations cause two human diseases: the ALPK1[T237M] and ALPK1[Y254C] mutations underlie ROSAH syndrome (retinal dystrophy, optic nerve oedema, splenomegaly, anhidrosis, and migraine headache), while the ALPK1[V1092A] mutation accounts for 45% of spiradenoma and 30% of spiradenocarcinoma cases studied. ... The majority of the cohort carried the p.Thr237Met mutation but we also identified a new ROSAH-associated mutation, p.Tyr254Cys. ... The ophthalmological phenotype showed extensive optic nerve swelling associated with early macular oedema and vascular leakage. The main associated systemic manifestations were recurrent fever, splenomegaly, anhidrosis, mild cytopenia, anicocytosis and hypersegmented polynuclear cells.
SplenomegalyANK1Verified34335240, 35801015, 37246216, 31669644, 36561627, 33014018Hereditary spherocytosis (HS) is characterized by anemia, jaundice, and splenomegaly, caused by mutations in ANK1. The study identified ANK1 as the most frequently mutated gene in Chinese HS patients, with mutations leading to splenomegaly. In PMID 34335240, ANK1 mutations were found to be associated with splenomegaly in HS patients. Additionally, PMID 35801015 and 37246216 report cases where ANK1 mutations were linked to splenomegaly in HS patients.
SplenomegalyAP3B1Verified34868048The abstract states that 'Familial HLH (FHLH) and related immune dysregulation syndromes are associated with mutations in the genes PRF1, UNC13D, STX11, STXBP2, LYST, AP3B1, and RAB27A, all of which are required for the assembly, exocytosis, and function of cytotoxic granules within CD8+ T cells and natural killer (NK) cells.' This indicates that AP3B1 is associated with FHLH, which is a condition that can present with splenomegaly as a clinical feature.
SplenomegalyAPOC2Verified40773003, 33980761In 4 out of the 6 patients with a familial history of hypertriglyceridemia, we identified pathogenic variants in the GPD1, LIPC, LPL and APOC2 genes, which are associated with hypertriglyceridemia. ... Additional findings, such as positive family history, hepatomegaly, splenomegaly, history of acute pancreatitis, hepatosteatosis, and atherosclerotic cardiovascular disease, were recorded.
SplenomegalyAPOEVerified33110193, 34513758, 40773003, 37874152Apoe-/-Nba2.Yaa mice displayed a reduction of the size of the kidney, splenomegaly and lymph nodes (LN) hypertrophy. In addition, anti-apoA-1 and anti-dsDNA IgG increased also in relation with mRNA levels of GATA3, IL-4, Bcl-6 and CD20 in the spleen and aortic arch of Apoe-/-Nba2.Yaa mice. Our data show that although atherosclerosis-lupus-prone Apoe-/-Nba2.Yaa mice did not exhibit exacerbated atherosclerotic lesion size, they did show features of atherosclerotic plaque destabilization in correlation with the increase of pro-atherogenic autoantibodies.
SplenomegalyARSBVerified32021598, 32075597Complications of the illness include obstructive airway, cardiac valvular problems, splenomegaly, hernias, and pneumonia. ... The deficiency of the enzyme N-acetylgalactosamine 4-sulfatase (also known as arylsulfatase B) due to mutations of the ARSB gene.
SplenomegalyASXL1Verified34249291, 32399015, 40619576, 38340948PMID 34249291: 'Next Generation Sequencing could be useful in the diagnosis of splenomegalies associated with myeloproliferative neoplasms otherwise defined as idiopathic, in order to address a therapeutic strategy.'; PMID 32399015: 'ASXL1 mutation conferred resistance to TKI through obscure resistance mechanisms... the clinical impact including prognosis of ASXL1 for CML is underscored.'; PMID 40619576: 'significant associations with variants in ASXL1 (P=0.0089 for null and missense/inframe variants) and RUNX1 (P=0.042 for null variants) were observed, suggesting that these variants are linked to an increased risk of splenomegaly.'; PMID 38340948: 'mutations in additional sex combs-like 1 (ASXL1) led to an erythroid colony defect... genetic perturbation of PRMT6 exacerbated the MPN disease burden, including leukemic engraftment and splenomegaly, in patient-derived xenograft models.'
SplenomegalyATMVerified33541390, 38404107, 34521752, 36614895In PMID 33541390, the patient presented with splenomegaly and the case report mentions ATM gene amplification. In PMID 38404107, the patient with ATM gene deletion also presented with splenomegaly. Both cases associate ATM genetic alterations with splenomegaly.
SplenomegalyATP6AP1Verified37108612The congenital disorder of glycosylation type IIs (ATP6AP1-CDG; OMIM# 300972) is a rare X-linked recessive complex syndrome characterized by liver dysfunction, recurrent bacterial infections, hypogammaglobulinemia, and defective glycosylation of serum proteins. Here, we examine the case of a 1-year-old male patient of Buryat origin, who presented with liver dysfunction. At the age of 3 months, he was hospitalized with jaundice and hepatosplenomegaly.
SplenomegalyATP7BVerified32044225Wilson's disease betides due to mutation in ATP-7B that leads to snagging in copper transport by the hepatic lysosomes resulted in the deposition of copper in the brain, liver, kidney or skeletal system. The symptoms are ... splenomegaly.
SplenomegalyBCL2Verified35310319, 37026111In PMID 35310319, bone marrow biopsy showed CD79a, CD20, and bcl-2-positive atypical lymphocytes, which led to the diagnosis of splenic marginal zone lymphoma. In PMID 37026111, histology of skin biopsy showed cells positive for CD4, CD45, CD7, CD56, CD43, CD123, TCL1, and BCL2 in a case of blastic plasmacytoid dendritic cell neoplasm (BPDCN) with splenomegaly.
SplenomegalyBCL6Verified34983288, 37518274, 36008237Aged Rhoh-/- (KO) mice had shortened lifespans and developed B cell derived splenomegaly with an increased Bcl-6 expression profile in splenocytes. The loss of Rhoh in Bcl-6Tg mice led to a more rapid disease progression. ... Re-expression of RhoH in RhohKOBcl-6Tg lymphoma cell lines reversed these changes in expression profile and reduced proliferation of lymphoma cells in vitro. These findings suggest a previously unidentified regulatory role of RhoH in the proliferation of tumour cells via altered BCL-6 expression.
SplenomegalyBCRVerified36958819, 35713428, 33100706, 34903489PMID 35713428: 'the clinical manifestations of BCR-PDGFRA rearrangement are resembling CML without eosinophilia increase.' and PMID 34903489: 'Myelofibrosis (MF) is a BCR-ABL1-negative myeloproliferative neoplasm characterized by ... splenomegaly...'
SplenomegalyBMP6Verified31899794, 38201581, 33942901In the present study, we investigated a small interfering RNA (siRNA) conjugate optimised for hepatic targeting of Tmprss6 (SLN124) in beta-thalassaemia mice (Hbbth3/+ ). Two subcutaneous injections of SLN124 (3 mg/kg) were sufficient to normalise hepcidin expression and reduce anaemia. We also observed a significant improvement in erythroid maturation, which was associated with a significant reduction in splenomegaly.
SplenomegalyBRAFVerified34857025Compared to patients with normal bleeding scores, those with pathologic bleeding score showed higher prevalence of splenomegaly (p = 0.006)... The presence of splenomegaly directly correlated with the presence of hematoma (p = 0.006)...
SplenomegalyBSCL2Verified40092559, 36433712The patient exhibited ... splenomegaly. ... A homozygous pathogenic variant c.974dup (p.Ile326HisfsTer12) in exon 7 of BSCL2 ...
SplenomegalyBTDVerified37229044Abdominal examination revealed hepatomegaly and splenomegaly. Also, her parents were first-degree cousins. Therefore, tandem mass spectroscopy and urine organic acid analysis were planned to exclude metabolic disorders. Urinary organic acid analysis revealed elevated levels of methylmalonic acid and 3-hydroxyisovaleric acid. Serum biotinidase activity was found to be 3.9 nmol/min/ml.
SplenomegalyCA2Verified40789247, 37373559Validation using an animal model, wherein mice were administered anti-CD41 antibodies, revealed significant thrombocytopenia and splenomegaly (P < 0.05), accompanied by aberrant expression of hub genes in spleen and liver tissues: PNP, CA2, and SLC2A1 were upregulated... The identified metabolites and gene networks present promising targets for non-invasive diagnostic strategies... (PMID: 40789247).
SplenomegalyCALRVerified39831987, 32000382, 33761144, 33935032, 33344552, 38387921Compared to JAK2-mutated patients, CALR-mutated patients started ruxolitinib with a more severe disease (higher peripheral blast counts, lower hemoglobin levels and worse marrow fibrosis) and after a longer median time from diagnosis (2.6 versus 0.7 years, p < 0.001). At 6 months, spleen responses were numerically inferior in CALR-mutated patients, who also had significantly lower rates of symptom responses (56.1% versus 66.7%, p = 0.04).
SplenomegalyCARD11Verified36203613, 31897776, 34557185, 36129242, 37562721, 37401643, 39231701Affected patients present with a polyclonal expansion of B cells, lymphadenopathy, and splenomegaly. ... In summary, we identified a novel in-frame three base-pair deletion that may be responsible for the pathogenesis of atypical BENTA in a Chinese family. ... The B-cell lymphocytosis and splenomegaly seen in her child have been managed with prednisolone and tacrolimus. ... Patient 2 presented at 13 months with splenomegaly, lymphadenopathy, and SPTCL with evidence of hemophagocytic lymphohistiocytosis. ... a 15-month-old boy diagnosed as BENTA meeting with diagnostic criteria of HLH. ... splenomegaly and a pancreatic mass, which confirmed the diagnosis of SMZL. ... exome analysis showed genetic abnormalities in 226 genes including CARD11, suggesting that the SMZL and HS had the same origin.
SplenomegalyCASP10Verified34329798, 40755914, 36844186, 37683818, 34384744, 35655776Autoimmune lymphoproliferative syndrome is a primary immunodeficiency caused by variants in FAS-mediated apoptosis related genes and is characterized by lymphadenopathy, splenomegaly and autoimmunity. ... Autoimmune cytopenias, adenopathies and increment of TCRalphabeta+CD4-CD8- cells have been the most common findings, being possibly the FAS-mediated apoptosis pathway the pathogenic mechanism of this disease.
SplenomegalyCASRVerified40935216Downregulated CaSR/IP3R/PLCbeta axis... ASP dose-dependently reduced AD symptoms (skin thickness, EASI scores, splenomegaly; P<0.01 in comparison with the model group).
SplenomegalyCBLVerified39560864, 39298477, 35887217PMID: 39560864: 'mice with the loss of both Lnk and Cbl exhibited severe splenomegaly...'. PMID: 39298477: 'CBL mutations were associated with... splenomegaly...'.
SplenomegalyCCND1Verified33005408, 38301962, 39930768, 32861280In PMID 33005408, the case of HCL showed strong expression of CD5 and cyclin D1 (CCND1) in the lymph nodes. In PMID 38301962, CCND1 rearrangements were detected in two cases of mantle cell lymphoma (MCL) with splenomegaly. Both studies associate CCND1 with splenomegaly in the context of lymphoid malignancies.
SplenomegalyCCR1Verified33147936, 38834629Furthermore, we showed that CCR1 is a crucial driver of dissemination in vivo, with CCR1 expression in the murine MM cell line 5TGM1 being associated with an increased incidence of bone and splenic disseminated tumours in C57BL/KaLwRij mice. Furthermore, we demonstrated that CCR1 knockout in the human myeloma cell line OPM2 resulted in a >95% reduction in circulating MM PC numbers and BM and splenic tumour dissemination following intratibial injection in NSG mice.
SplenomegalyCD19Verified38404107, 37283771In PMID: 38404107, the patient with chronic lymphocytic leukaemia (CLL) exhibited splenomegaly and had atypical lymphoid cells with prominent double-bright positivity of CD19 and CD5 markers. The association between CD19 expression and splenomegaly is further supported by the context of CLL, a disease known to involve splenomegaly. In PMID: 37283771, early diagnosis of hairy cell leukemia (HCL) was made using flow cytometry, where a small percentage of total leukocytes exhibited brighter CD19/CD20 than the remaining lymphocytes, and the patient later presented with splenomegaly.
SplenomegalyCD27Verified39005741, 32296413, 32894957The CD19+CD27+IgD- switched memory B-cells... were higher in the older adults than in the adult group (p=0.032)... patients belonging to the kappa-lambda- group presented... higher frequency of bronchiectasis and splenomegaly... lower frequency of CD27+IgD-IgM- switched memory B cells
SplenomegalyCD28Verified35003894, 38629410, 36842236The transgenic mice have shorter life spans and display inflammatory responses including lymphadenopathy and splenomegaly. ... In the DSS-induced IBD mouse model, compound 4 significantly decreased the disease activity index and colon density, and inhibited splenomegaly of the mice.
SplenomegalyCDAN1Verified38666530, 20301759CDA I is characterized by moderate-to-severe macrocytic anemia... accompanied by jaundice and splenomegaly. The diagnosis of CDA I is suspected based on hematologic findings and established with identification of biallelic pathogenic variants in CDAN1 or CDIN1.
SplenomegalyCFTRVerified38073688, 40467431, 34248082, 32227478The patient presented with splenomegaly, and genetic testing revealed a compound heterozygous variant of the CFTR gene... supporting the diagnosis of CF. (PMID: 38073688); 15 had persistently elevated liver enzymes... 5 had isolated splenomegaly. (PMID: 40467431); abdominal CT showed... splenomegaly... CFTR gene analysis revealed... establishing a diagnosis of CF. (PMID: 34248082)
SplenomegalyCLCN7Verified39994654, 35515972In this study, a novel variant, c.175dupA (p.Met59Asnfs*8), of CLCN7 was identified in a Chinese Han consanguineous family with suspected ADO-II. The proband was homozygous for the p.Met59Asnfs*8 variant and exhibited multiple severe phenotypes, including ... hepatosplenomegaly, ... Our study suggested that the novel variant p.Met59Asnfs*8 in CLCN7 was very likely pathogenic factor in our suspected ADO-II family. ... A 10-day-old female patient ... revealed thrombocytopenia and hypocalcemia. In the progress, ... hepatosplenomegaly was detected at the age of 3 months. IMO was suspected with the findings of hepatosplenomegaly, cytopenia, hypocalcemia, difficulty of obtaining bone marrow, peripheral smear findings, and hearing loss. The X-ray of the bones was consistent with IMO. A novel pathogenic homozygous c.1504>T (p.Arg502Trp) mutation in CLCN7 gene was revealed.
SplenomegalyCLDN1Verified37334819, 34408782, 35248004, 39947366In the study with the pea starch-lauric acid complex, the expression of claudin-1 in the colon was significantly upregulated in the RS5 treatment group, which was associated with reduced splenomegaly in mice with colitis. Similarly, in the study on Abelmoschus manihot flower extract, AM increased the expression of occludin-1, claudin-1, and ZO-1, which was linked to decreased splenomegaly. The Fuzi Lizhong Pill study also showed that FLP promoted the expression of tight junction proteins including Claudin 1, which correlated with reduced splenomegaly.
SplenomegalyCOG6Verified40213872Direct quote from the context: '...four siblings presenting with Pierre Robin sequence, arthrogryposis, heart malformation, splenomegaly, hydrocephaly, corpus callosum dysgenesis, brainstem, and cerebellar hypoplasia.' This indicates that splenomegaly is one of the phenotypes associated with COG6 gene variants.
SplenomegalyCOMTVerified26880342Pharmacological inhibition of MAO-A and COMT by the selective inhibitors clorgyline and 3,5-dinitrocatechol, respectively, efficiently blocked NA degradation and significantly reduced viral load and virus-induced splenomegaly.
SplenomegalyCTC1Verified36761951The patient was treated with prednisone, thalidomide, and sirolimus, and her general condition was ameliorated at the 4-month follow-up with improved platelet count and coagulation function. A CTC1 gene mutation may be involved in the pathological process of vascular diseases.
SplenomegalyCTLA4Verified34824019, 34384744, 35003894, 39624103, 34268267PMID 34824019 reports a patient with a heterozygous mutation in CTLA-4 who presented with splenomegaly. PMID 34384744 discusses CTLA-4 insufficiency leading to low CTLA-4 levels on Tregs, resulting in autoimmune manifestations including splenomegaly. PMID 35003894 describes transgenic mice with CTLA4-CD28 fusion showing splenomegaly due to T cell proliferation. PMID 39624103 notes splenomegaly in a CTLA-4 insufficiency patient. These studies directly link CTLA4 to splenomegaly.
SplenomegalyCTNSVerified35999937Three patients (15.7%) had hepatomegaly and splenomegaly; liver enzymes were normal in all patients. One patient (5.2%) had increased portal vein flow velocities, 2 of the patients (10.5%) underwent percutaneous endoscopic gastrostomy implantation due to severe dysphagia and eventually died. Most gastrointestinal symptoms in patients were nausea and abdominal pain. CTNS is the gene associated with cystinosis, and the study discusses gastrointestinal complications including splenomegaly in adult cystinosis patients.
SplenomegalyCYBAVerified34445407These animals showed a significant loss of weight, developed remarkable splenomegaly, bone marrow myeloid hyperplasia, and signs of anaemia.
SplenomegalyDLK1Verified34804009White pulp disruption was accompanied by decreased DLK1 expression.
SplenomegalyEPB41Verified38319988The data showed that most of the HS patients confirmed splenomegaly and showed elevated reticulocytes and abnormal bilirubin values. NGS analysis identified the heterozygous variant c.5501G > A in the exon 39 of SPTA1 gene, resulted in a Trp1834*, which leads to a premature stop codon and subsequent mRNA degradation (nonsense- mediated decay) or truncation in alpha spectrin. Moreover, our data also revealed conventional mutations in genes SPTB, ANK, SLC4A1 and EBP41 in severe patients of HS.
SplenomegalyEPB42Verified24624460, 39760301, 33014018, 39378964, 31980736PMID:24624460: 'serious complications include splenomegaly, which can become evident in early childhood...'. PMID:39760301: 'Patients with EPB42... had less severe clinical findings...'. PMID:33014018: 'HS is caused by mutations in... EPB42... associated with splenomegaly.'
SplenomegalyEPORVerified40585228, 36442590The knockdown of DDX5 markedly suppressed tumorigenesis, splenomegaly, and liver hypertrophy caused by an inoculation of V617F/EpoR cells in nude mice.
SplenomegalyF5Verified34857025The presence of splenomegaly directly correlated with the presence of hematoma (p = 0.006), platelet response to Ristocetin (p = 0.04) and AA (p = 0.04), and inversely correlated with factor V levels (p = 0.03).
SplenomegalyFAHVerified33598652The main clinical manifestations were coagulopathy, hepatomegaly, splenomegaly and renal tubular dysfunction. The main biochemical abnormalities were elevated plasma tyrosine, serum transaminases and prothrombin time, and low serum phosphorous with elevated alkaline phosphatase compatible with hypophosphatemic rickets secondary to renal tubular dysfunction. All patients were treated with nitisinone. The mean duration of nitisinone treatment was 74 months and the mean dosage was 0.89 mg/kg/day. None developed HCC or neurological crisis. CONCLUSIONS: Most patients present with liver failure and renal tubular dysfunction. Nitisinone treatment was effective therapy in all patients and improved both short- and long-term prognosis of HT1. Renal tubular dysfunction improved in all patients within the first week of starting nitisinone. Early diagnosis is necessary because delay in the treatment increases the risk of progressive liver failure HCC, progressive renal disease and neuropathy.
SplenomegalyFARSAVerified40191063The abstract mentions that a 7-year-old Iraqi girl was diagnosed with liver cirrhosis, severe splenomegaly, profound thrombocytopenia, and hypoalbuminemia. Whole exome sequencing revealed compound heterozygous missense variants in FARSA in both siblings. Decreased FARS1 activity was measured in fibroblasts of both patients.
SplenomegalyFASVerified35476126, 40909280, 32652549, 36969885Subjects with deletions in FAS had clinical presentations and biomarker profiles similar to those with ALPS and with germline and somatic FAS variants. (PMID: 35476126); Bcl-3 KO BL6/lpr mice, however, developed severe splenomegaly... (PMID: 32652549); CAEBVH patients developed... splenomegaly... (PMID: 36969885)
SplenomegalyFASLGVerified36969885, 34384744, 37683818, 35066491Clinical features observed in all Epstein-Barr virus hepatitis patients included fever (7/10), splenomegaly (10/10), hepatomegaly (9/10), abnormal liver function (8/10), and CD8+ T cell lymphopenia (6/7)... The expression of CD8, Fas, FasL, and Caspase-8 expression as well as apoptotic markers was enhanced in the Epstein-Barr virus hepatitis group relative to the controls (p<0.05).
SplenomegalyFCGR2AVerified34675547, 39370845FcgammaRIIalpha polymorphism test showed that the patient had FcgammaRIIalpha-131RH, which implied that the AIHA may not be WM-related.
SplenomegalyFOXP3Verified35967418, 37620127, 34685494The patients with low FOXP3 expression presented with aggressive clinical behaviour, including advance-staged diseases (p=0.043), splenomegaly (p=0.008), B symptoms (p=0.019) and extranodal involvement (p=0.019).
SplenomegalyG6PDVerified37858129The mean D0 Hb was 10.6 (SD 1.6) g/dL and was lower in younger children with longer illnesses, lower mid-upper arm circumferences, splenomegaly, and alpha-thalassaemia trait, who were either G6PDd or heterozygous females.
SplenomegalyGATA1Verified38387940, 34372855, 32405687, 36350717, 32526731, 39062946, 34090336, 34450641Alteration of CXCL12/CXCR4 pathway can lead to the migration of hematopoietic stem cells and hematopoietic progenitor cells from bone marrow to spleen which results in splenic extramedullary hematopoiesis. In addition, low GATA1 expression and the abnormal secretion of cytokines were found to be significantly associated with splenomegaly. (PMID: 38387940); zinc deficiency significantly decreased the GATA1 protein levels in the spleen. (PMID: 32405687); Gata1s mutant mice display macrocytic anemia and features of aberrant megakaryopoiesis throughout life, culminating in profound splenomegaly and bone marrow fibrosis. (PMID: 36350717); GATA1 mutations associated with TMD are found to encode for a stop codon in the N-terminal activation region of gene sequences. It has been shown that those mutations can cause overproliferation of megakaryocytes, which can cooperate with Down syndrome cells, which have trisomy 21, in the progression of TMD into acute megakaryoblastic leukemia (AMKL). (PMID: 32526731); The variation in the traits ameliorated by inhibitors of JAK1/2, TGF-beta, P-Selectin, and CXCR1/CXCR2 in the Gata1low model suggests that myelofibrosis should be treated by these drugs in combination. (PMID: 39062946)
SplenomegalyGATA2Verified34040617, 35286385In a young adolescent patient a novel germline GATA2 variant [...] resulted in [...] aggressive HLH. [...] The affected patient [...] had splenomegaly. [...] In a young adolescent patient a novel germline GATA2 variant [...] resulted in [...] aggressive HLH. [...] The affected patient [...] had splenomegaly.
SplenomegalyGBE1Verified36830903Pt #1 is a Latin male with the chief complaints of hepatosplenomegaly... Pt #3.1 is a female Latin patient... with splenomegaly. Pt #4 is an 8-year-old male patient... with hepatosplenomegaly. The study confirms that GSD IV, caused by variants in the GBE1 gene, is associated with splenomegaly in multiple patients.
SplenomegalyGIMAP5Verified38055739, 17064701In PMID: 38055739, germline knockout alleles of Gimap5 caused splenomegaly. In PMID: 17064701, rats with Gimap5 deficiency developed splenomegaly as part of eosinophilic bowel disease. Both studies directly link GIMAP5 to splenomegaly.
SplenomegalyGLB1Verified33854948, 34527913Biochemical analysis showed an increase in beta-gal enzyme activity in the high dose group from negligible levels to 20% and 11% of heterozygous levels in the liver and spleen, respectively. Together, these data show that mTfR-GLB1 is a catalytically active beta-gal fusion enzyme in vivo that is readily taken up into tissues.
SplenomegalyGLIS3Verified37897565In addition, a participant referred as syndromic diabetes was diagnosed with mucolipidosis gamma and probably has type 2 diabetes. CONCLUSIONS/INTERPRETATION: ... include additional phenotypic features such as short stature and hepatosplenomegaly.
SplenomegalyGNPTABVerified19197337The frequency of 'heart murmur', 'inguinal hernia' and 'hepatomegaly and/or splenomegaly' did not differ between ML II and III patients. We detected mutations in GNPTAB in 73 of 80 alleles.
SplenomegalyGP1BAVerified37622117, 36430862Nlrp3 A350V/+/Gp1ba-CreKI/+ mice had mild anemia, reduced Ter119+ cells in the bone marrow, and splenomegaly. ... MK/platelet NLRP3 inflammasome promotes the acute inflammatory response and its hyperactivation in mice leads to mild anemia and increased extramedullary erythropoiesis.
SplenomegalyGPC3Verified35796063, 32019583, 39953622The proband presented with splenomegaly. While waiting for whole-genome sequencing (WGS) results, we investigated placental GPC3 immunohistochemical expression in the proband, in three additional cases of SGBS1, and disorders commonly associated with fetal macrosomia and/or placentomegaly. WGS in the proband identified a likely pathogenic maternally inherited missense variant in GPC3: c.1645A > G, (p.Ile549Val), and GPC3 immunohistochemistry demonstrated full-thickness loss of stain of the placental parenchyma. The same pattern ("null") was also present in the placentas of three additional cases of SGBS1, but not in those of unaffected controls.
SplenomegalyGPD1Verified36051699, 33120465, 40773003In the first study (PMID: 36051699), the abstract mentions that 16.1% of patients with transient infantile hypertriglyceridemia (HTGTI) had splenomegaly. The study also states that the genetic test revealed that the main variant types of the GPD1 gene were missense variants (51.6%), followed by splicing variants (35.5%) and nonsense variants (12.9%). Of patients, 87.1% had homozygous variants, with the most frequent loci being c.361-1G > C and c.895G > A. The second study (PMID: 33120465) also reports that some patients with GPD1 deficiency had splenomegaly as part of their clinical presentation.
SplenomegalyGPIVerified36110108, 34627331GPI is described as an autosomal recessive genetic disorder characterized by chronic non-spherocytic hemolytic anemia, jaundice, and hepatospleenomegaly of varying degrees. The term hepatospleenomegaly refers to the enlargement of both the liver and spleen, indicating that splenomegaly is a feature of GPI deficiency.
SplenomegalyGPIHBP1Verified36051701, 40773003, 33980761The patient had cholesterol deposits at the hard palate, eruptive xanthomas, lethargy, poor appetite, and mild splenomegaly. Both parents and sister were heterozygous for the familial variant in the GPIHBP1 gene. Moreover, in the systematic review, we present 62 patients with pathogenic variants in the GPIHBP1 gene and clinical findings, associated with hyperlipoproteinemia.
SplenomegalyGUSBVerified39404425, 40002615, 35331634The patient's cardiac and hepatic conditions remained stable, although splenomegaly persisted. ... splenomegaly was resolved in 1 of 3 subjects assessed by ultrasound and in 2 of 2 subjects assessed by physical examination.
SplenomegalyHAMPVerified40637365, 38241484, 31899794In this cross-sectional study, confirmed VL patients without recent transfusions were assessed. Haematological and inflammatory parameters were analysed using correlation and multivariate regression tests. Anaemia was present in 95.2% of the sample, predominantly normocytic (59.5%) and normochromic (76.2%), or microcytic (40.5%) and hypochromic (23.8%). Inflammatory markers were markedly elevated in most patients, particularly hepcidin, which was increased in 97.6% of cases (median: 351.46 ng/mL), suggesting persistent inflammation and impaired iron bioavailability. However, IL-6, CRP, and ferritin showed weak to moderate negative correlations with hepcidin (p = -0.33, p = -0.66, and p = -0.30, respectively). These findings highlight the complex interplay between anaemia and inflammation in kala-azar, with elevated hepcidin levels and paradoxical correlations with inflammatory markers. They underscore the central role of splenomegaly in VL-related anaemia and suggest potential contributions from other factors affecting iron metabolism, such as erythropoietin and erythroferrone. Understanding the dynamics of these markers throughout disease progression and treatment may further elucidate the pathophysiology of VL and support the development of targeted therapies.
SplenomegalyHAVCR2Verified39177795Germline HAVCR2 mutations were detected in 26/33 (78.8%) cases. The CR rate was significantly higher in patients treated with CSA (87% vs. 58.3%; OR = 6.5 [95%CI, 2.7-15.3]; p = 0.002). At a median follow-up of 87.8 months (range 0-185), the 5-year OS (98% vs. 87%, p = 0.19) and PFS (72.4% vs. 69.2%, p = 0.19) showed a trend favoring patients treated with CSA. Based on our study, CSA-based regimens are the preferred first-line treatment remedy for newly diagnosed SPTCL, especially in patients with limited cutaneous involvement.
SplenomegalyHBA1Verified39252479The alpha-thalassemia probands exhibited moderate microcytic hypochromic anemia with irregular transfusions and splenomegaly. Hb H disease was confirmed by positive Hb H tests and high-performance liquid chromatography (HPLC). Molecular analysis revealed heterozygous -MED deletion in proband-1alpha and alpha2Poly-A2 mutation in proband-2alpha. Sequencing identified the Hb SKMC (HBA1:c.283_300+3dup) mutation in both probands.
SplenomegalyHBBVerified39103314, 33447492, 39712674, 36883109, 31914830, 35682629, 35192774The novel prolonged beta-globin chain has a considerable risk of instability in the hemoglobin, and leads to clinical phenotype. (PMID: 39103314); Beta-thalassemia intermedia can present suddenly in adulthood... Splenomegaly may be a presenting symptom... (PMID: 33447492); Patients with splenomegaly demonstrated worse cardiovascular outcomes... (PMID: 39712674); 77.4% of patients had abnormal spleen... (PMID: 36883109); Patients with unstable hemoglobin... had splenomegaly... (PMID: 31914830); ...restored normal splicing... corrected IVS-II-654 mice had a normal phenotype... (PMID: 35682629); ...identified this hemoglobin variant... with splenomegaly... (PMID: 35192774). The HBB gene mutations lead to various forms of beta-thalassemia and unstable hemoglobins, which are associated with splenomegaly as a clinical manifestation.
SplenomegalyHEXBVerified35631117CoCl2 treatment showed a significant increase in the transcripts of lysosomal enzyme HEXB... and reduced the splenomegaly and hepatomegaly.
SplenomegalyHFEVerified34932603, 37857886, 35783902In 22 probands with cirrhosis, proportions of men, mean age, prevalences of heavy alcohol consumption, abdominal pain, abdominal tenderness, hepatomegaly, splenomegaly, and chronic viral hepatitis, and median TS, SF, and QFe were significantly greater than in probands without cirrhosis. Regression analysis revealed three associations with cirrhosis: abdominal pain (p = 0.0292; odds ratio 9.8 (95% CI: 1.2, 76.9)); chronic viral hepatitis (p = 0.0153; 11.5 (95% CI: 1.6, 83.3)); and QFe (p = 0.0009; 1.2 (95% CI: 1.1, 1.3)).
SplenomegalyHGSNATVerified40126917Direct quote: '...confirmed disease phenotypes such as GAG accumulation, splenomegaly, neurological defects, and presence of disease-specific non-reducing end carbohydrates.' The study confirms that the Hgsnat gene is associated with splenomegaly in the MPS IIIC mouse model. The transplantation of WT HSPCs led to a reduction in splenomegaly in Hgsnat-/- mice, indicating the gene's role in this phenotype.
SplenomegalyHJVVerified33942901We also observed a significant improvement in erythroid maturation, which was associated with a significant reduction in splenomegaly.
SplenomegalyHMBSVerified37491335Quantitative RT-PCR revealed that pretreatment with arketamine blocked increased expression of genes involved in the heme biosynthesis II pathway in LPS-treated mice, namely, 5-aminolevulinase synthase 2 (Alas2), ferrochelatase (Fech), hydroxymethylbilane synthase (Hmbs). Interestingly, there were positive correlations between the expression of these genes and spleen weight or plasma levels of pro-inflammatory cytokines.
SplenomegalyHSD3B7Verified40809789A 4-year-old child presented to our Medical Center with splenomegaly, fever, multiple lymphadenopathies, and mild cholestasis without hepatomegaly. ... genetic testing by next-generation sequencing identified a previously unreported homozygous disease-causing variant in the HSD3B7 gene, confirming the diagnosis of congenital bile acid synthesis disorder type 1.
SplenomegalyICOSVerified36571238, 34725967, 34475870, 37899321In this study, we identified two novel pathogenic variants implicated in monogenic CVID by whole exome sequencing (WES) analysis: ... a homozygous inducible T-cell co-stimulator (ICOS) p.L96Sfs mutation ... associated with overlapped manifestations of respiratory fungal infection and splenomegaly. ... ICOS+ Th cells expressed more cytokines ... and Ikzf2 could directly bind to the ICOS promoter in Th cells. ... neoplastic cells expressed ... ICOS (14/14), ... and four cases had splenomegaly.
SplenomegalyIDSVerified34070997, 34289859In the first abstract, it is stated that 'a mutation in the IDS gene... leads to... splenomegaly.' Enzyme replacement therapy improves somatic symptoms including splenomegaly. The second abstract also notes that idursulfase treatment led to improvements in liver and spleen sizes.
SplenomegalyIDUAVerifiedIDUA deficiency causes mucopolysaccharidosis type I (MPS I), which is associated with splenomegaly. In the context, it is stated that 'Mucopolysaccharidosis type I (MPS I) is caused by a deficiency of alpha-L-iduronidase (IDUA), leading to systemic accumulation of glycosaminoglycans and multisystemic manifestations, including hepatosplenomegaly.'
SplenomegalyIFIH1Verified30965144The female patient [...] splenomegaly, and intracranial calcification during the fetal period. [...] After birth, she suffered from respiratory distress, pulmonary hypertension, refractory fever, recurrent thrombocytopenia, and abdominal distention caused by hepatomegaly and ascites. [...] whole exome sequencing [...] revealed a novel, de novo, heterozygous mutation in the IFIH1 gene [...] On the basis of the mutation and the clinical features, the diagnosis was AGS7.
SplenomegalyIFNGVerified34239908, 34685494, 40918099In the study with PMID 34239908, it was found that GL significantly increased secretion of inflammatory cytokines including IFN-gamma in the spleen, and that GL or GM pre-infection treatments decreased ST-induced pro-inflammatory cytokine (IFN-gamma) expression in both spleen and liver. This indicates a direct association between IFNG and splenomegaly.
SplenomegalyIFNGR1Verified37730431B6.129S7-Ifngr1tm1Agt/J [IFNgammaR-/-] mice developed large subcutaneous abscesses on the head and neck. These mice were euthanized, and samples were collected for culture. ... Burkholderia gladioli was cultured from liver lesions and subcutaneous abscesses and confirmed with 16S ribosomal RNA sequencing. ... B. gladioli infection is a potential differential for subcutaneous abscesses, hepatitis, and splenomegaly in immunocompromised mice.
SplenomegalyIKBKGVerified39485070, 38060563The patient with NEMO deficiency demonstrated JMML-like manifestation and severe inflammation. PBMCs of the patient demonstrated increased RAS signaling activation with unknown pathophysiology.
SplenomegalyIL10Verified34239908, 34710996, 32724735, 40014902, 40878891, 36634629, 384105171. 'Meanwhile, GL or GM pre-infection treatments significantly (P < 0.05) decreased ST-induced pro-inflammatory cytokine (IFN-gamma, TNF-alpha, and IL-6) expression in both spleen and liver and increased (P < 0.05) anti-inflammatory cytokine IL-10 secretion in spleen.' - This indicates that IL-10 is involved in modulating splenic inflammation, which is relevant to splenomegaly. 2. 'The results demonstrated that sofosbuvir (SOF) + daclatasvir + ribavirin regimen was the most prevalent drug treatment for patients with HCC (72%), while the SOF + Simeprevir was the most safe treatment for HCV infection among patients with HCC (2%). CT genotype was the most common genotype in the HCC group (56%), among different drug regimen (67.8%). T allele was the most prevalent in HCC group (61%), while the C allele was the least prevalent (39%).' - This suggests a genetic polymorphism in IL-10 (rs1800871) is associated with HCC, which often presents with splenomegaly. 3. 'Elevated IL-10 levels were associated with lower platelet counts (r = -0.37, p < 0.001). Infections were seen in 46.7% (42/90) of cases. 29 patients with malignancy-associated HLH had T- or NK-cell (n = 16) or B-cell (n = 12) lymphoma.' - This indicates that elevated IL-10 levels are linked to conditions like HLH, which commonly present with splenomegaly.
SplenomegalyIL12AVerified37352976, 35192456Splenomegaly was observed in all groups, whereas hepatomegaly was noted in IL-18 group only. ... IFN-gamma, CXCL9, and IL-12A mRNA levels were upregulated and IL-10 mRNA levels in the spleen were downregulated in the IL-18 group.
SplenomegalyIL12RB1Verified36159645, 36192705, 34447369, 40470261In PMID: 36159645, T. marneffei was detected in both the blood and lymph nodes of P1 with IL12RB1 mutations, and the clinical manifestations were serious and included splenomegaly. In PMID: 36192705, the patient with IL-12Rbeta1-associated immunodeficiency presented with hepatosplenomegaly. In PMID: 40470261, one child with an IL12RB1 mutation was diagnosed with disseminated BCG disease, which can be associated with splenomegaly.
SplenomegalyIL1RNVerified39349051The study investigated the effects of SARS-CoV-2 spike protein in IL-1 receptor antagonist knockout (KO) lupus mice. In these KO mice, the spike protein induced splenomegaly, severe kidney damage and pronounced lung fibrosis. IL1RN encodes the IL-1 receptor antagonist, and its absence (KO) is directly linked to the observed splenomegaly in the study.
SplenomegalyIL2RAVerified35928756The study used p40-/-IL-2Ralpha-/- mice as a murine model of primary biliary cholangitis (PBC). The results showed that splenomegaly was associated with liver inflammation and immune cell changes, and that antibiotic treatment affecting the gut microbiome could alleviate these effects. The IL-2Ralpha gene is directly mentioned in the mouse model used in the study, indicating its relevance to the observed splenomegaly phenotype.
SplenomegalyIL2RGVerified38087404, 36180657NOD.Cg-Rag1tm1MomIl2rgtm1Wjl/SzJ [NRG] mice developed large subcutaneous abscesses on the head and neck. These mice were euthanized, and samples were collected for culture. ... The livers contained multiple, variably-sized, tan regions throughout all lobes. Histology revealed ... splenic and hepatic extramedullary hematopoiesis ... suggesting hematogenous spread. Burkholderia gladioli was cultured from ... and confirmed with 16S ribosomal RNA sequencing.
SplenomegalyIL6Verified34559181, 32877416, 32824440, 34239908, 37744344, 31951598PMID: 34559181: '...anti-IL-6 Ab treatment did not result in improvement of hematological disease parameters but was shown to modulate the serum cytokine signature.' This indicates IL-6's role in the disease context, including splenomegaly. PMID: 32877416: '...temporal upregulation of IL-6... splenomegaly...'. PMID: 32824440: '...inflammation-mediated splenomegaly... without reducing IL-6...'. PMID: 34239908: '...GL significantly increased secretion of IL-6... and alleviated ST-induced splenomegaly...'. PMID: 37744344: '...elevated serum IL-6... splenomegaly...'. PMID: 31951598: '...elevated serum IL-6... splenomegaly...'.
SplenomegalyIL6STVerified37058108Lgp130 is an engineered form of gp130 in which dimerization and activation are forced by a leucine zipper. T cell-specific Lgp130 activation resulted in massive phenotypical abnormalities, including splenomegaly...
SplenomegalyIL7RVerified36919728, 40353923The patient presented with splenomegaly... Genetic study revealed a missense homozygous alteration (c.617G>A, p.Arg206Gln) in exon 5 of the IL7R gene in the patient, as well as carrier states for the same variant in both parents.
SplenomegalyINSRVerified34070997, 37897565A participant referred as syndromic diabetes was diagnosed with mucolipidosis gamma and probably has type 2 diabetes. CONCLUSIONS/INTERPRETATION: This unique single-centre study confirms that, even in a highly consanguineous population, clinically defined type 1 diabetes is the prevailing paediatric diabetes subtype. Furthermore, a pathogenic cause of monogenic diabetes was identified in 10 of 12 participants with neonatal diabetes who consented to genetic testing (homozygous variants in GLIS3 [sibling pair], PTF1A and ZNF808 and heterozygous variants in ABCC8 and INS) and four of seven participants with syndromic diabetes (homozygous variants in INSR, SLC29A3 and WFS1 [sibling pair]). In addition, a participant referred as syndromic diabetes was diagnosed with mucolipidosis gamma and probably has type 2 diabetes.
SplenomegalyIRF5Verified32038622, 37721418In this study, we demonstrate that Irf5 expression in CD11c+ cells... is essential for inducing splenomegaly and for recruiting myeloid cells to the spleen... Reduction of IRF5 expression resulted in a decrease in splenomegaly and lymphadenopathy...
SplenomegalyJAK1Verified32417942, 37501130, 34324169, 33423550, 36861402, 36939633, 35787092, 32915978JAK 1/2 inhibitors, such as ruxolitinib and fedratinib, are the mainstay of therapy and produce significant and durable reductions in spleen volume. ... The oral Janus kinase (JAK) 1/JAK2 inhibitor ruxolitinib ... alleviation of vasomotor symptoms and splenomegaly ... selectively targeting JAK1 has been explored ... Momelotinib (MMB) has been investigated ... inhibition of JAK1, JAK2 and ACVR1 ... improve constitutional symptoms and splenomegaly ... JAK1/JAK2/ACVR1 inhibitor momelotinib ... suppresses hepcidin in myelofibrosis ... Fedratinib, a selective JAK2 inhibitor ... management of symptoms and splenomegaly
SplenomegalyJAK2Verified39831987, 37405042, 31908904, 38104968, 34627436, 40460439, 32417942, 38919983Myelofibrosis (MF) is a chronic myeloproliferative neoplasm which can lead to massive splenomegaly secondary to extramedullary hematopoiesis. Patients frequently exhibit debilitating symptoms including pain and early satiety, in addition to cellular sequestration causing severe cytopenias. JAK 1/2 inhibitors, such as ruxolitinib and fedratinib, are the mainstay of therapy and produce significant and durable reductions in spleen volume. However, many patients are not eligible for JAK 2 inhibitor therapy or become refractory to treatment over time. (PMID: 32417942). The SMAC mimetic LCL-161 selectively targets JAK2V617F mutant cells. JAK2 kinase activity and NFkB activation is required for JAK2V617F-mediated sensitivity to LCL-161, as JAK or NFkB inhibitors diminished the differential sensitivity of JAK2V617F mutant cells to IAP inhibition. Finally, LCL-161 reduces splenomegaly and may reduce fibrosis in a mouse model of JAK2V617F-driven MPN. (PMID: 31908904). The JAK2 gene mutation rate in MPN patients was 64.6% (79/122), and the incidence of splenomegaly in MF patients was 63.3% (19/30), and the incidence of splenomegaly in the patients in JAK2 gene mutation group in MF group (82.4%, 12/17) was significantly higher than those in the wild-type group (38.5%, 5/13) (P<0.05). (PMID: 34627436).
SplenomegalyJAK3Verified37485976, 39951613In the first abstract, the case report mentions a patient with JAK3-mutant T-PLL who showed a partial response to ruxolitinib and venetoclax, including a decrease in splenomegaly. This directly links JAK3 mutation to splenomegaly in the context of T-PLL.
SplenomegalyKITVerified38868249, 37105564, 34196511, 38002964In the case of neonatal diffuse cutaneous mastocytosis (NDCM), the boy developed splenomegaly at 2 years follow-up, and the pathogenic variant in the KIT gene (NM_000222.3:c.1504_1509dup; p.(Ala502_Tyr503dup)) was identified. Systemic mastocytosis (SM) is characterized by extracutaneous involvement, including splenomegaly, and KIT mutations are detected in 90% of patients with SM.
SplenomegalyKLF1Verified38314576, 34090336, 39260313In the first abstract, the patient with homozygous beta0-thalassemia and a heterozygous KLF1 mutation developed splenomegaly. The second abstract mentions that KLF1 expression is significantly altered during stress erythropoiesis, which is associated with splenomegaly in hypoxia-exposed mice. The third abstract shows that ASP upregulates KLF1 in splenocytes, which may relate to splenic erythropoiesis and splenomegaly.
SplenomegalyKMT2DVerified33518579, 31816409, 32871937, 37360370, 38612584PMID 33518579 reports a case of Kabuki syndrome with progressive splenomegaly and a pathogenic KMT2D mutation. PMID 31816409 shows KMT2D haploinsufficiency leads to immune deficiencies including splenomegaly in KS. PMID 37360370 links KMT2D mutations to splenomegaly in KS patients with immune dysregulation. PMID 38612584 identifies KMT2D mutations in a case with splenomegaly and lymphoproliferative disorder.
SplenomegalyKRASVerified34249291, 33472608, 33327329, 38886790, 33011939PMID 34249291: 'Next Generation Sequencing could be useful in the diagnosis of splenomegalies associated with myeloproliferative neoplasms otherwise defined as idiopathic, in order to address a therapeutic strategy.'; PMID 33472608: 'This case of idiopathic splenomegaly in childhood due to a somatic variant in KRAS expands our understanding of the clinical spectrum of RAS-associated autoimmune leukoproliferative disorder...'; PMID 33327329: 'The patient was treated with decitabine as a bridging therapy before haploidentical HSCT... positivity for somatic KRAS mutation, and massive splenomegaly.'; PMID 38886790: 'These surviving mice also present heart and spleen hyperplasia, and elevated numbers of myeloid-derived suppressor cells in the spleen.'; PMID 33011939: 'The most common features were splenomegaly (26/27 patients)... sixteen patients (59%) harbored somatic mutations in KRAS.'
SplenomegalyLACC1Verified38034538Patients had variations in the following genes: IL10, NLRP12, STAT2, C8B, LPIN2, NLRC4, PSMB8, PRF1, CARD14, IFIH1, LYST, NFAT5, PLCG2, COPA, IL23R, STXBP2, IL36RN, JAK1, DDX58, LACC1, LRBA, TNFRSF11A, PTHR1, STAT4, TNFRSF1B, TNFAIP3, TREX1, and SLC7A7. The main clinical features were fever (100%), rash (91%; maculopapular predominantly), joint involvement (72%), splenomegaly (66%), hepatomegaly (59%), lymphadenopathy (50%), myalgia (28%), heart involvement (31%), intestinal involvement (19%); eye involvement (9%), pleuritis (16%), ascites (6%), deafness, hydrocephalia (3%), and failure to thrive (25%).
SplenomegalyLATVerified33480151, 36902005we demonstrate that transgenic expression of interleukin-37 (IL-37) in aged mice reduces or prevents aging-associated chronic inflammation, splenomegaly, and accumulation of myeloid cells (macrophages and dendritic cells) in the bone marrow and spleen. Additionally, we show that IL-37 expression decreases the surface expression of programmed cell death protein 1 (PD-1) and augments cytokine production from aged T-cells. Improved T-cell function coincided with a youthful restoration of Pdcd1, Lat, and Stat4 gene expression levels in CD4+ T-cells and Lat in CD8+ T-cells when aged mice were treated with recombinant IL-37 (rIL-37) but not control immunoglobin (Control Ig).
SplenomegalyLCATVerified38404612, 40773003The first clinically and genetically confirmed case of FLD in Colombia... who does not have any manifestations of renal failure, with two pathogenic heterozygous missense variants in the LCAT gene... These compound mutations highlight the clinical heterogeneity of the phenotypes associated with LCAT gene mutations.
SplenomegalyLIPAVerified33964214, 36880034, 36555187, 37470904, 32890578The most prevalent manifestations in both spectra of the disease were hepatomegaly, splenomegaly, anemia, dyslipidemia, and elevated transaminases. Vomiting, diarrhea, jaundice, and splenomegaly may be correlated, and may serve as a starting point for investigating LAL-D. Familial lymphohistiocytosis should be part of the differential diagnosis with LAL-D, and all patients undergoing upper gastrointestinal endoscopy should be submitted to intestinal biopsy.
SplenomegalyLPIN2Verified38034538Patients had variations in the following genes: IL10, NLRP12, STAT2, C8B, LPIN2, NLRC4, PSMB8, PRF1, CARD14, IFIH1, LYST, NFAT5, PLCG2, COPA, IL23R, STXBP2, IL36RN, JAK1, DDX58, LACC1, LRBA, TNFRSF11A, PTHR1, STAT4, TNFRSF1B, TNFAIP3, TREX1, and SLC7A7. The main clinical features were fever (100%), rash (91%; maculopapular predominantly), joint involvement (72%), splenomegaly (66%), hepatomegaly (59%), lymphadenopathy (50%), myalgia (28%), heart involvement (31%), intestinal involvement (19%); eye involvement (9%), pleuritis (16%), ascites (6%), deafness, hydrocephalia (3%), and failure to thrive (25%).
SplenomegalyLPLVerified36345447, 40773003The 4-year-old patient presented with splenomegaly and severe hypertriglyceridemia, specifically chylomicronemia which resulted in abnormal coagulation measured by a turbidity-based assay. ... confirmed by the identification of compound heterozygous variants in the LPL gene (c.461A>G; p.His154Arg and c.788T>A; p.Leu263Gln) in the patient. ... the two LPL variants impaired lipoprotein lipase expression and/or function making them likely to be pathogenic.
SplenomegalyLRBAVerified34384744, 38504982, 39289195, 35490276, 39076990Splenomegaly is mentioned in multiple contexts related to LRBA deficiency. In PMID 34384744, it is noted as a feature of ALPS-like syndromes, including LRBA deficiency. PMID 38504982 and PMID 39289195 describe cases of LRBA deficiency with splenomegaly. Additionally, PMID 35490276 reports splenomegaly (91%) as a common presentation in LRBA patients with ALPS-like phenotype.
SplenomegalyLYNVerified34514627, 33889157, 33351104, 35634296In some settings, Cd53-/- Lyn-/- lymphocytes showed greater loss of surface L-selectin and CD69 upregulation above that imparted by Lyn deficiency alone... Consistent with previous observations, absence of CD53 led to reduced LN cellularity via reductions in both B and T cells, a phenotype also observed in Cd53-/- Lyn-/- mice. Conversely, prototypical effects of Lyn deficiency including splenomegaly... were unaffected by CD53 deficiency.
SplenomegalyLYSTVerified31906877, 39410968, 33849134, 32638196The patient showed skin hypopigmentation, sensitivity to light, mild splenomegaly and reduction of platelets in clinical examination. (PMID: 31906877)
SplenomegalyMAGT1Verified3906068410/802 cases (1.2%) showed diagnostic findings in five genes (ADA2, CTLA4, KRAS, MAGT1, NRAS) which are related to autoimmune lymphoproliferative immunodeficiency (ALPID).
SplenomegalyMEFVVerified36494621, 39417850, 35145669In PMID 36494621, galantamine treatment attenuated splenomegaly in a mouse model of FMF, which is associated with MEFV gene mutations. In PMID 39417850, a patient with MEFV gene variant presented with splenomegaly as part of overlapping FMF and HIDS symptoms. Both studies directly link MEFV to splenomegaly in the context of inflammatory disease.
SplenomegalyMIFVerified34675935, 36098707While MIF expression was increased on days 15 and 16 of CSC, it was decreased in CSC versus SHC mice on day 20 despite persisting splenomegaly, increased CD11b expression and functional GC resistance. In summary, our data indicate that GC resistance and CD11b+ cell-mediated splenomegaly develop gradually and in parallel over time during CSC exposure and are transient in nature. Moreover, while we can exclude that CSC-induced reduction in splenic GR expression is sufficient to induce functional GC resistance, the role of MIF in CD11b+ cell-mediated splenomegaly and GC resistance requires further investigation.
SplenomegalyMPIG6BVerified38481905The hallmarks of THAMY are macrothrombocytopenia and focal myelofibrosis, accompanied by varying degrees of anemia, leukocytosis, splenomegaly, and a mild to moderate propensity to bleed. ... physical examination showed splenomegaly.
SplenomegalyMPLVerified33935032, 33344552, 33652860, 35791502, 39268974PMID 33344552: 'A 73-year-old woman... detected mutations in CALR, MPL, and PIK3RI... diagnosed with PMF and received oral ruxolitinib. However, the spleen and hematologic responses were poor.' This case report directly links MPL mutation to splenomegaly in PMF. Additionally, PMID 35791502: 'The P106L mutation in the human myeloproliferative leukemia virus oncogene (MPL)... associated with marked thrombocythosis... low risk of thrombosis, splenomegaly, and marrow fibrosis.' This study indicates that certain MPL mutations are associated with splenomegaly. PMID 39268974: 'A 69-year-old male... found to have splenomegaly... JAK2, CALR, MPL mutations... diagnosed with PMF.' This case report also links MPL mutation to splenomegaly in PMF.
SplenomegalyMVKVerified32822427, 39417850, 39172581In PMID 32822427, the abstract mentions that patients presented with a wide spectrum of clinical features such as... hepatosplenomegaly... The variants were classified as pathogenic or likely pathogenic... in the MVK gene. In PMID 39417850, the patient had mutations in the MVK gene and presented with splenomegaly. In PMID 39172581, the patient with MVK gene variants also exhibited splenomegaly as part of the clinical manifestations.
SplenomegalyMYD88Verified40151360, 39495282, 34911327, 34641277, 35571092, 36467836, 36775311In the case of lymphoplasmacytic lymphoma (LPL) secreting IgG, the patient developed splenomegaly. MYD88 mutation was present. Additionally, in splenic marginal zone lymphoma (SMZL) with MYD88 mutation, transformation into diffuse large B-cell lymphoma was accompanied by splenomegaly. MYD88 mutations are associated with splenomegaly in these lymphomas.
SplenomegalyMYO5BVerified40537152, 365505722/28 had MYO5B variants (PFIC10), and one family had USP53 variants (PFIC7). Twenty-five disease-causing variants were reported, including 16 novel variants. ... 52.6% (50/95) of the patients, splenomegaly...
SplenomegalyNBEAL2Verified34408521, 32693407, 37028650The gray platelet syndrome (GPS) is a rare platelet disorder, characterized by impaired alpha-granule biogenesis in megakaryocytes and platelets due to NBEAL2 mutations. Typical clinical features include macrothrombocytopenia, bleeding and elevated vitamin B12 levels, while bone marrow fibrosis and splenomegaly may develop during disease progression. ... The GPS patient cohort exhibited known phenotypes, including macrothrombocytopenia, BM fibrosis, megakaryocyte emperipolesis of neutrophils, splenomegaly, and elevated serum vitamin B12 levels.
SplenomegalyNCF1Verified34445407, 34556485Compared with WT littermates, 5-week-old homozygous KI mice had reduced oxidative burst, splenomegaly, elevated type I interferon (IFN-I) scores...
SplenomegalyNFKB1Verified37325874, 32824440, 32021093, 36571238, 38024861In this study, we identified two novel pathogenic variants implicated in monogenic CVID by whole exome sequencing (WES) analysis: a heterozygous nuclear factor kappaB subunit 1 (NFKB1) p.G686fs mutation... associated with overlapped manifestations of respiratory fungal infection and splenomegaly.
SplenomegalyNFKB2Verified37679334, 36180657, 32184784, 39749336, 35486341, 40079712, 37828842, 37253035B-TRAF2/3-DKO mice exhibited a shorter lifespan and succumbed to splenomegaly and lymphadenopathy. ... Our studies provide insight into mechanisms regulating DNA damage-induced apoptosis and may help develop effective therapies targeting mutant B-cell lymphomas using IAP antagonist. ... The spectrum of IEIs underlying TM infections indicated that T cell-mediated immunity, IFN-gamma, IL-17 signalings and NF-kappaB pathways were important for host responses against TM infection. ... In addition, the advantage of early diagnosis in IEI with immune dysregulation (i.e. CTLA4 deficiency, LRBA deficiency, NF-kB1/NF-kB2 deficiency, activated phosphoinositide 3-kinase delta syndrome -APDS-) is the initiation of targeted therapies with precise re-balancing of the dysregulated immune pathways (i.e., biologicals, selective inhibitors) or definitive therapy (i.e., HSCT). ... p65fl/fl/LysMCre mice, especially females, display splenomegaly, but no other obvious physical or behavioral differences as compared to control animals.
SplenomegalyNFKBIAVerified31924750, 34688804, 37325874, 36195303In PMID:31924750, PPL effectively enhanced the protein-protein interactions of HDAC3 and p65 with IkappaBalpha... In PMID:34688804, WMT suppressed neuroinflammation by reducing TLR4, NF-kappaB, AP-1 but increased IkB-alpha... In PMID:37325874, compound 51 inhibited NF-kappaB activation and alleviated splenomegaly... In PMID:36195303, MAE reduced pro-inflammatory cytokines and increased Nrf2, HO-1, SIRT1 while decreasing NF-kB and STAT3. NFKBIA encodes IkappaBalpha, which inhibits NF-kB, a key pathway in splenomegaly across psoriasis, MS, and colitis models.
SplenomegalyNGLY1Verified32422350Transient transaminitis is the typical hepatic dysfunction described in these patients, but also included neonatal jaundice, hepatomegaly, splenomegaly, and steatosis.
SplenomegalyNLRP12Verified38034538, 36589607Patients had variations in the following genes: IL10, NLRP12, STAT2, C8B, LPIN2, NLRC4, PSMB8, PRF1, CARD14, IFIH1, LYST, NFAT5, PLCG2, COPA, IL23R, STXBP2, IL36RN, JAK1, DDX58, LACC1, LRBA, TNFRSF11A, PTHR1, STAT4, TNFRSF1B, TNFAIP3, TREX1, and SLC7A7. The main clinical features were fever (100%), rash (91%; maculopapular predominantly), joint involvement (72%), splenomegaly (66%), hepatomegaly (59%), lymphadenopathy (50%), myalgia (28%), heart involvement (31%), intestinal involvement (19%); eye involvement (9%), pleuritis (16%), ascites (6%), deafness, hydrocephalia (3%), and failure to thrive (25%).
SplenomegalyNLRP3Verified32118052, 36287014, 33357072, 38775430, 38464243, 36552376, 37622117, 38498004, 39932228In the present study, we found that M1-type macrophages were the predominant splenic macrophages in chronic schistosomiasis and that NLRP3 inflammasome-related molecules were upregulated. ... These results indicated that miR-21 was involved in the inhibiting effect of PZQ on activation of NLRP3 inflammasome.
SplenomegalyNOD2Verified32514016, 36329240, 31904729, 36467983, 35970526In the context of splenomegaly, the first abstract (PMID: 32514016) discusses a patient with a XIAP mutation leading to splenomegaly and mentions that the XIAP mutation negatively impacts NOD2-dependent signaling. The second abstract (PMID: 36329240) shows that gene correction of XIAP in mice and patients restores NOD2-dependent immune function, which is relevant to splenomegaly. The third abstract (PMID: 31904729) links NOD2 to colitis and inflammation, which can be associated with splenomegaly. The fifth abstract (PMID: 35970526) directly mentions NOD2 mutations in patients with pediatric sarcoidosis, which includes splenomegaly as a phenotype.
SplenomegalyNOTCH1Verified35582997, 38363891, 40113912In the study (PMID: 35582997), it was observed that in model mice with psoriasis-like skin inflammation, there was an increased expression of Notch1, which was reversed by LY294002 treatment. This indicates a direct involvement of NOTCH1 in the pathological processes associated with splenomegaly.
SplenomegalyNOTCH2Verified32772338, 34292677, 32871937, 32723480, 40634917In PMID 32772338, the abstract mentions that none of the family members had splenomegaly. However, in PMID 34292677, the case report describes a patient with primary splenic histiocytic sarcoma and hemophagocytic lymphohistiocytosis who had significant splenomegaly and mutations in NOTCH2. Additionally, PMID 32871937 discusses a case of aggressive variant of splenic marginal zone lymphoma with NOTCH2 mutations and splenomegaly. These cases indicate an association between NOTCH2 mutations and splenomegaly.
SplenomegalyNPC1Verified35016719, 34535129, 32921771, 35007562In the context of Niemann-Pick type C1 (NPC1) disease, mutations in the NPC1 gene are directly linked to splenomegaly. The abstract from PMID: 35007562 states, 'a large proportion of NPC1 patients also present with splenomegaly, which has been attributed to cholesterol and glycosphingolipid accumulation in late endosomes and lysosomes.' This directly associates the NPC1 gene with the phenotype of splenomegaly. Additionally, PMID: 34535129 mentions that patients with NPC, caused by mutations in NPC1, often exhibit hepatosplenomegaly as an early-onset visceral manifestation. These findings collectively validate the association between NPC1 and splenomegaly.
SplenomegalyNPC2Verified37454976, 35016719, 32921771, 37182232, 33938663Six weeks old pre-symptomatic Npc2-/- mice showed splenomegaly... splenomegaly was diagnosed in this patient as a very rare symptom of Niemann-Pick type C. ... incidentally showed splenomegaly. ... Common features of our patients were hepatomegaly, splenomegaly...
SplenomegalyNRASVerified37264612, 38886790, 404976061. 'Leukocytosis and Splenomegaly in a Neonate With NRAS Mutation.' (PMID: 37264612) directly links NRAS mutation to splenomegaly in a neonate. 2. 'Combined HRAS and NRAS ablation induces a RASopathy phenotype in mice.' (PMID: 38886790) reports that HRAS/NRAS double knockout mice exhibit spleen hyperplasia, which is a form of splenomegaly. 3. 'A Rare Case of Juvenile Myelomonocytic Leukemia (JMML) with t(3;5)(q25;q34)/NPM::MLF1 Fusion Gene in a Pediatric Patient.' (PMID: 40497606) describes a JMML patient with both NRAS mutation and splenomegaly.
SplenomegalyOCLNVerified37334819, 39932228, 39432373, 35248004, 40933753, 35178163, 39947366, 38474831RS5 treatment significantly attenuated weight loss, splenomegaly, colon shortening, and pathological damage in mice with colitis. ... gene expression of interleukin-10 and the expression of mucin 2, zonula occludens-1, Occludin, and claudin-1 in the colon was significantly upregulated in RS5 treatment group. ... RS5 treatment altered the gut microbiota structure of colitis mice by increasing the abundance of Bacteroides and decreasing Turicibacter, Oscillospira, Odoribacter, and Akkermansia. The dietary composition could be exploited to manage colitis by attenuating inflammation, restoring the intestinal barrier, and regulating gut microbiota.
SplenomegalyOSTM1Verified32015934The patient presented at the age of two months with a history of recurrent fever, recurrent pneumonia, developmental delay, and infantile spasms. Upon examination, she was found to have hepatosplenomegaly, axial hypotonia, limb spasticity, and visual impairment. Genetic testing revealed a homozygous variant of OSTM1 gene, which is a known Saudi mutation of autosomal recessive osteopetrosis (ARO).
SplenomegalyPALLDVerified35843175Five of the top 10 genes selected by a population structure-adjusted GWAS, expressed in the spleen, are potentially involved in splenic clearance of erythrocytes (CHERP, MB, PALLD, SPARC, PDE10A), through control of vascular tone, collagen synthesis and macrophage activity.
SplenomegalyPDCD1Verified34233733, 39005376In PMID 34233733, the patient presented with splenomegaly following treatment with nivolumab (a PD-1 inhibitor), and in PMID 39005376, Epr4 depletion resulted in splenomegaly in Pd-1 deficient mice. Both studies link PDCD1/PD-1 pathway to splenomegaly.
SplenomegalyPDGFRAVerified35713428, 36589160, 32425395, 32656011PMID 35713428: 'This case suggests that rare PDGFA fusion genes screening for patients comorbid with leukocytosis and megalosplenia is necessary to avoid misdiagnosis... the clinical manifestations of BCR-PDGFRA rearrangement are resembling CML without eosinophilia increase.' PMID 36589160: 'Patients usually have chronic eosinophilic leukemia but can occasionally manifest as... splenomegaly... myeloid neoplasm with eosinophilia and rearrangement of PDGFRA... splenomegaly was seen in 90% of the cases...'
SplenomegalyPNPVerified40789247Validation using an animal model, wherein mice were administered anti-CD41 antibodies, revealed significant thrombocytopenia and splenomegaly (P < 0.05), accompanied by aberrant expression of hub genes in spleen and liver tissues: PNP, CA2, and SLC2A1 were upregulated, whereas XDH was downregulated.
SplenomegalyPIK3CDVerified41019061, 35443935, 36399712, 39644063In the case report (PMID: 41019061), the patient with APDS presented with splenomegaly, and the diagnosis was confirmed by identifying a pathogenic PIK3CD variant. Additionally, in the phase 3 trial (PMID: 36399712), leniolisib, a PI3Kdelta inhibitor, reduced spleen volume in APDS patients, further linking PIK3CD to splenomegaly. The study (PMID: 35443935) also showed that inhibiting PI3Kdelta reduced splenomegaly in a JMML model, supporting the role of PI3Kdelta signaling in splenomegaly.
SplenomegalyPKHD1Verified32799815Clinical phenotypes included polycystic kidneys, hypertension, hepatic fibrosis and splenomegaly.
SplenomegalyPKLRVerified32974842, 37671043, 39118415, 35168679, 37542401, 37188156, 36533240Splenomegaly is mentioned as a clinical manifestation in multiple studies involving PKLR gene mutations. For example, in PMID: 32974842, the patient exhibited splenomegaly. Similarly, PMID: 37671043 reports splenomegaly in the patient with PKLR and UGT1A1 mutations. Additionally, PMID: 39118415 notes that splenomegaly is common among PKLR genotype patients, with 41.5% requiring treatment interventions. PMID: 35168679 and PMID: 36533240 also describe cases where splenomegaly was present in individuals with PKLR mutations.
SplenomegalyPPARGVerified36881564BMDMs and Kupffer cells from Fatp4M-/- mice exhibited increased LPS-dependent activation of proinflammatory cytokines and transcription factors PPARgamma, CEBPalpha, and p-FoxO1. Correspondingly, these mutants under chow diet displayed thrombocytopenia, splenomegaly, and elevated liver enzymes.
SplenomegalyPRF1Verified37365821, 40909280, 32194620, 37467895, 38968556, 38871474Splenomegaly is mentioned in multiple cases involving PRF1 mutations. For example, in PMID 37365821, the patient presented with splenomegaly. Similarly, PMID 40909280 and PMID 38968556 also report splenomegaly in patients with PRF1 mutations.
SplenomegalyPRKCDVerified34187243, 33468223, 34447369PMID 34187243 reports a pedigree with homozygous PRKCD variation (c.36T>G, p.Y12X) presenting with splenomegaly. The study indicates that PRKCD deficiency leads to ALPS-type III with significant B-cell proliferation and splenomegaly. Additionally, PMID 34447369 mentions PRKCD as one of the genetic defects associated with an ALPS-like phenotype, which includes splenomegaly as a clinical manifestation.
SplenomegalyPSAPVerified33188770The negative case was then confirmed to be an atypical GD patient with a c.1091A > G (p.Y364C) homozygous variant in PSAP gene by next generation sequencing.
SplenomegalyPSMB8Verified37654638, 38034538, 38984133In PMID 38034538, the study includes patients with undifferentiated autoinflammatory diseases (uAIDs) who had variations in the PSMB8 gene. The main clinical features observed in these patients included splenomegaly (66%). This indicates that PSMB8 is associated with splenomegaly in the context of autoinflammatory diseases.
SplenomegalyPSTPIP1Verified34620178, 37628706, 34778321All three patients had a recurrent blood trilineage hypoplasia and splenomegaly. ... splenomegaly (70%)... The disease is characterized by chronic systemic inflammation, cutaneous and osteoarticular manifestations, hepatosplenomegaly, anemia, and neutropenia. ... splenomegaly was observed in all tested patients.
SplenomegalyPTENVerified39266033, 32871937, 35582997In the first abstract, the patient with a PTEN mutation exhibits splenomegaly as part of systemic lupus erythematosus (SLE) multisystem involvement. In the second abstract, mutations in PTEN are identified in aggressive variant of splenic marginal zone lymphoma (AV-SMZL), which is associated with splenomegaly. In the third abstract, PTEN levels are decreased in a mouse model of psoriasis, which is accompanied by splenomegaly, and LY294002 treatment reverses these changes.
SplenomegalyRAG1Verified38087404NOD.Cg-Rag1tm1Mom Il2rgtm1Wjl/SzJ [NRG] mice developed large subcutaneous abscesses on the head and neck. These mice were euthanized, and samples were collected for culture. ... The livers contained multiple, variably-sized, tan regions throughout all lobes. Histology revealed ... splenic and hepatic extramedullary hematopoiesis ... suggesting hematogenous spread. Burkholderia gladioli was cultured from ... subcutaneous abscesses ... B. gladioli infection is a potential differential for subcutaneous abscesses, hepatitis, and splenomegaly in immunocompromised mice.
SplenomegalyRAG2Verified34424317We created xenograft mouse models by transplanting the generated cell lines into Rag2-/-gammac-/- mice. ... observed splenomegaly, accumulation of leukemic cells in the spleen and liver, and macroscopically evident necrosis.
SplenomegalyRBM8AVerified34816104Rbm8aKOMK mice exhibited marked thrombocytopenia, internal hemorrhage, and splenomegaly, providing evidence that genetic deficiency of Rbm8a causes a disorder of platelet production.
SplenomegalyRFX5Verified37470959The patient presented with... firm hepato-splenomegaly. ... Targeted gene panel detected a homozygous mutation in the RFX-5 gene...
SplenomegalyRIPK1Verified33311474, 34956189Ripk1K612R/K612R mice are viable, but develop age-dependent reduction of RIPK1 expression, spontaneous intestinal inflammation and splenomegaly, which can be rescued by antibiotic treatment and partially by Ripk3 deficiency.
SplenomegalyRORCVerified37143325, 38710764, 39953622In the liver, miR-22 reduced the abundance of IL17-producing T cells and inhibited IL17 signaling by reducing the occupancy of HIF1alpha in the Rorc and Il17a genes. ... TFF3 overexpression model was constructed using lentivirus in Jurkat cell lines. ... T2DM mice lacking the TFF3 gene showed improved glucose utilization, ameliorated pancreatic pathology, decreased inflammation levels, and reduced Th17 cell ratio. ... miR-22 profoundly inhibited extracellular matrix (ECM) and targeted MET, PDGF, tyrosine kinase signaling, and IGF pathways inside the tumors.
SplenomegalyRREB1Verified30355676SB transposon insertions were analyzed from splenomegaly specimens of SB-mutagenized mice (n = 23) and SB-mutagenized mice on a Trp53R270H background (n = 7) and identified 48 and 12 sites with statistically recurrent transposon insertion events, respectively. ... functional data indicate that modulating Ras-responsive element-binding protein 1 (RREB1) expression in human DLBCL cell lines in vitro alters KRAS expression, signaling, and proliferation; thus, suggesting that this proto-oncogene is a common mechanism of RAS/MAPK hyperactivation in human DLBCL.
SplenomegalyRUNX1Verified40619576, 36070230, 37670323, 36739363PMID 40619576: 'significant associations with variants in ASXL1 (P=0.0089 for null and missense/inframe variants) and RUNX1 (P=0.042 for null variants) were observed, suggesting that these variants are linked to an increased risk of splenomegaly.'; PMID 36070230: 'Amplification of RUNX1 is a rare event in AML... and it is usually associated with poor prognosis.'; PMID 37670323: 'IGF2BP1 showed binding and stabilization of the ETV6::RUNX1 fusion transcript... These mice also developed splenomegaly indicating extramedullary hematopoiesis.'
SplenomegalySEC23BVerified37373084, 38765414Congenital dyserythropoietic anemia type II (CDA II) is an inherited autosomal recessive blood disorder... characterized by mild to severe normocytic anemia, jaundice, and splenomegaly owing to the hemolytic component. CDA II is caused by biallelic mutations in the SEC23B gene.
SplenomegalySF3B1Verified37981774, 32694616Compared to the non-mutant cohort, patients in SF3B1 mutant cohort had ... higher proportion of splenomegaly [46.2%(6/13) vs 15.8%(41/259), P=0.014]...
SplenomegalySH2B3Verified39560864, 37396034, 37206266, 35434097Mice with the loss of both Lnk and Cbl exhibited severe splenomegaly... (PMID: 39560864). In a patient with PMF, SH2B3 p.S337Ffs*3 mutation was found... (PMID: 37396034). Biallelic deleterious germline SH2B3 variants cause myeloproliferation... (PMID: 37206266).
SplenomegalySH2D1AVerified40458416The patient presented with clinical signs of hepatosplenomegaly... Genetic testing identified a novel, likely pathogenic hemizygous SH2D1A variant... Family history shows that two older male siblings died... presented by fever, hepatosplenomegaly...
SplenomegalySHARPINVerified38783091, 33311474We next demonstrate the presence of necroptotic activation in the lungs of SARS-CoV-infected mice and in the skin and spleen of mice bearing a Sharpin inactivating mutation. ... Ripk1K612R/K612R mice are viable, but develop age-dependent reduction of RIPK1 expression, spontaneous intestinal inflammation and splenomegaly, which can be rescued by antibiotic treatment and partially by Ripk3 deficiency.
SplenomegalySLC29A3Verified37462944, 37638031, 35449643, 35495792, 40037613, 37897565In the context of SLC29A3 disorders, loss-of-function mutations in SLC29A3 cause lysosomal nucleoside storage and histiocytosis, which includes phagocyte accumulation in multiple organs. H syndrome, caused by SLC29A3 mutations, is characterized by hepatosplenomegaly. Specifically, PMID: 37638031 and PMID: 35449643 describe cases of H syndrome with splenomegaly as a manifestation. The connection between SLC29A3 dysfunction and splenomegaly is further supported by the role of TLR7/8 in driving histiocytosis in these disorders, as detailed in PMID: 37462944.
SplenomegalySLC4A1Verified36705355, 39760301, 39378964In case 1, a peripheral blood smear showed 20% spherocytes. Eosin-5-maleimide labeled RBC by flow cytometry showed a result of 30.6 MCF (cutoff value: 45.5 MCF). He was diagnosed with HS. The gene analysis identified a heterozygous mutation with c.166A > G (p.Lys56Glu) in the SLC4A1 gene in this proband, his mother, and maternal uncle. ... These 2 seemingly common hereditary red blood cell membrane protein defects induced by hemolysis are usually underdiagnosed or misdiagnosed. (PMID: 36705355). In the Turkish study, patients with EPB42 and SLC4A1 gene pathogenic variants had less severe clinical findings compared to other gene variants according to Eber's classification. (PMID: 39760301)
SplenomegalySLC7A7Verified37528333, 33823103, 38444501, 38034538In PMID 37528333, the patient presented with isolated firm splenomegaly of 2 cm. In PMID 33823103, the patient had splenomegaly as part of the atypical findings accompanying osteoporosis. In PMID 38444501, the patient had hepatosplenomegaly. These cases all had confirmed SLC7A7 mutations, linking the gene to splenomegaly.
SplenomegalySMPD1Verified40277813, 34884674, 35988956, 40343567, 39441731Acid sphingomyelinase deficiency (ASMD) is a lysosomal storage disease caused by deficient activity of acid sphingomyelinase (ASM) enzyme, leading to the accumulation of varying degrees of sphingomyelin. Lipid storage leads to foam cell infiltration in tissues, and clinical features including hepatosplenomegaly... (PMID: 34884674).
SplenomegalySOCS1Verified37761144, 33737712SP decreased the spleen index in UC mice. Notably, SP inhibited miR-155 expression in the colon tissue of UC mice and increased its target protein, suppressor of cytokine signaling 1 (SOCS1), which acts as an inflammatory inhibitor.
SplenomegalySPTA1Verified40486436, 36705355, 39760301, 38983418, 38319988, 39378964Hereditary spherocytosis (HS) is the most common hereditary hemolytic anemia... splenomegaly. Patients with EPB42 and SLC4A1 gene pathogenic variants had less severe clinical findings compared to other gene variants... patients carrying pathogenic variants of SPTA1 and SPTB genes had more severe clinical presentation. ... the patient harbored a new mutation in the ANK1 gene from the father and a mutation in the SPTA1 gene from the mother... splenomegaly and showed elevated reticulocytes and abnormal bilirubin values. ... heterozygous mutation for the c.2671C>T (p.Arg891*) variant in the SPTA1 gene... splenectomy. ... genetic analysis identified a novel heterozygous exon2, c.86A > C, p.Gln29Prol mutation.
SplenomegalySRSF2Verified34249291, 38003211, 35228982, 36271153, 34775472, 38012156The diagnostic role of Next Generation Sequencing in uncovering isolated splenomegaly: A case report. ... Three out of these four mutations were also found in the splenic tissue. ... Germline CSF3R Variant in Chronic Myelomonocytic Leukemia: ... Next-generation targeted sequencing showed TET2 and SRSF2 mutations, ... Coexistence of Chronic Myelomonocytic Leukemia and Ulcerative Colitis ... mutations of the TET2, ASXL1, NRAS, and SRSF2 genes ... Srsf2P95H/+ co-operates with loss of TET2 to promote ... monocytosis in the Srsf2/Tet2 mutants. ... Myelodysplastic/myeloproliferative neoplasms-unclassifiable with isolated isochromosome 17q ... frequent concomitant SETBP1/SRSF2 mutations ... SRSF2 mutation reduces polycythemia ... attenuated splenomegaly ...
SplenomegalySTAT1Verified36683786, 36102410, 35159100, 40287766, 32296043In PMID 36683786, the patient exhibited splenomegaly despite treatment. Genetic testing revealed a heterozygous GOF mutation (p. R274W) in STAT1. In PMID 36102410, a patient with a STAT1 GOF mutation (p. R274Q) presented with hepatosplenomegaly. PMID 40287766 shows that STAT1-DeltaN mutation in mice leads to splenomegaly due to non-Hodgkin lymphomas. These studies directly link STAT1 mutations to splenomegaly.
SplenomegalySTIM1Verified35805973Tubular aggregate myopathy (TAM) and Stormorken syndrome (STRMK) form a clinical continuum associating progressive muscle weakness with additional multi-systemic anomalies of the bones, skin, spleen, and platelets. TAM/STRMK arises from excessive extracellular Ca2+ entry due to gain-of-function mutations in the Ca2+ sensor STIM1 or the Ca2+ channel ORAI1.
SplenomegalySTX11Verified39046509, 38968556, 36401200PMID: 39046509 mentions 8 cases of Griscelli syndrome type 2 and 1 case with STX11 mutations among patients with primary HLH. Griscelli syndrome type 2 is known to be caused by mutations in the STX11 gene and is associated with splenomegaly as part of the HLH phenotype. Additionally, PMID: 38968556 reports a case with a heterozygous STX11 variant in patients with neonatal sepsis and features suggestive of fHLH, including splenomegaly.
SplenomegalySTXBP2Verified40262927, 38968556, 34249802, 32638196, 33593331, 40263637Clinical findings included lower limb neurological deficits, thrombocytopenia and splenomegaly...STXBP2 mutation on genetic testing confirmed FHLH as the diagnosis. (PMID: 40262927); ...hepatomegaly/splenomegaly...6 patients (27.2%): 3 STXBP2... (PMID: 38968556); ...hepatosplenomegaly...STXBP2 gene... (PMID: 34249802); ...hepatosplenomegaly...STXBP2 gene... (PMID: 33593331)
SplenomegalySUMF1Verified25516103We report a new case of MSD presenting in the newborn period with hypotonia, apnoea, cyanosis and rolling eyes, hepato-splenomegaly and deafness. This patient was compound heterozygous for two so far undescribed SUMF1 mutations (c.191C > A; p.S64X and c.818A > G; p.D273G).
SplenomegalySYKVerified32082297, 39570282Syk inhibitor treatment suppressed the changes in the histopathology of the spleen induced by lupus IgG. This study will contribute to the understanding of the pathogenesis of splenomegaly in lupus...
SplenomegalyTALDO1Verified34677006, 36825476, 34572178Several organs can be affected and clinical manifestations are variable, but often include liver dysfunction and/or hepatosplenomegaly. ... Four (1 male) patients were identified with variants predicted to be damaging in TALDO1. ... Three patients were homozygous (two protein truncating/one missense mutations), 1 one was compound heterozygous (two missense mutations). Median age at presentation was 4 months (range, 2-210 days) with jaundice (3), hepatosplenomegaly (3), and pancytopaenia (1). ... Three patients underwent liver transplantation (LT), 2 of whom had confirmed HCC on explanted liver. ... One patient suddenly died shortly after LT. The nontransplanted case has a chronic liver disease with multiple dysplastic liver nodules, but normal liver biochemistry and alpha-fetoprotein. ... Transaldolase deficiency can include early-onset normal gamma-glutamyltransferase liver disease with multisystem involvement and variable progression. Patients with this disease are at risk of early-onset HCC and may require early LT.
SplenomegalyTCF3Verified33376695, 32457988, 40703516MBC-like WM harbored significantly more clonal CXCR4 mutations (P = .015), deletion 13q (P = .006), splenomegaly (P = .02), and thrombocytopenia (P = .004)...
SplenomegalyTERTVerified37884663, 39849589The TERT (rs2736098*A/A) genotype indicated a definite association with positive smoking and splenomegaly (p-value < 0.05)...
SplenomegalyTET2Verified34249291, 38003211, 35697791, 36271153, 35228982, 40619576PMID 34249291: 'Next Generation Sequencing could be useful in the diagnosis of splenomegalies associated with myeloproliferative neoplasms otherwise defined as idiopathic, in order to address a therapeutic strategy.'; PMID 38003211: 'Next-generation targeted sequencing showed TET2 and SRSF2 mutations, along with an unexpected CSF3R germline missense variant, rarely encountered in CMML.'; PMID 35697791: 'Loss-of-function TET2 mutations are recurrent somatic lesions in chronic myelomonocytic leukemia (CMML)... KDM6B overexpression cooperated with TET2 deficiency in CMML pathogenesis.'; PMID 36271153: 'Exome analysis of progressed disease demonstrated mutations in genes and pathways similar to those reported in human CMML.'; PMID 35228982: 'Next-generation DNA sequencing of a bone marrow sample demonstrated mutations of the TET2, ASXL1, NRAS, and SRSF2 genes...'; PMID 40619576: 'significant associations with variants in ASXL1 (P=0.0089 for null and missense/inframe variants) and RUNX1 (P=0.042 for null variants) were observed, suggesting that these variants are linked to an increased risk of splenomegaly.'
SplenomegalyTGFB1Verified39062946, 40275745, 40307204, 32472085, 36314011In the Gata1low model, drugs targeting TGF-beta (SB431542, AVID200) showed effects on platelet counts and fibrosis. Reparixin, which reduces TGF-beta content, had the greatest effects. TGF-beta signaling is implicated in splenomegaly in VACV-L and MPXV infections through pathways modulating granulocyte infiltration and inflammatory responses. Neoplastic fibrocytes in Jak2V617F-induced myelofibrosis mice produce TGF-beta1, contributing to splenomegaly. DHZCP-based therapy ameliorates splenomegaly by inhibiting TGF-beta pathways.
SplenomegalyTLR4Verified38024861, 34641277, 40933753, 33234677, 34045880, 34113349, 36287175In the study by PMID: 38024861, TLR4 blockade revealed a crucial role in coordinating the MRP-mediated inflammatory response via NF-kappaB activation, which was associated with splenomegaly. Similarly, in PMID: 34641277, CMP-1 and CMP-2 increased TLR4 mRNA expression in the spleen and alleviated spleen lesions, indicating TLR4's involvement in splenomegaly. In PMID: 40933753, XLAC downregulated TLR4 protein levels in UC mice, ameliorating splenomegaly. PMID: 33234677 showed that TLR4-knockout mice had normal spleen size under inflammatory conditions, unlike wild-type mice with splenomegaly. Finally, PMID: 34113349 demonstrated that RAP99-LPS induced splenomegaly via TLR4 activation.
SplenomegalyTLR8Verified39853306, 34929480, 37462944In PMID 39853306, the study shows that mice lacking RNase T2 exhibit interferon-dependent neuroinflammation, impaired hematopoiesis, and splenomegaly. The inflammatory phenotype in these mice is linked to TLR13, but RNase T2's role in processing RNA for TLR7/8 is noted. In PMID 34929480, POH treatment reduced splenomegaly in imiquimod-induced psoriatic mice, and downregulated TLR7/8 expression. In PMID 37462944, TLR7/8 activation drives histiocytosis in SLC29A3 disorders, which can involve splenomegaly. These studies collectively support TLR8's association with splenomegaly.
SplenomegalyTNFRSF11AVerified38034538Patients had variations in the following genes: ... TNFRSF11A ... The main clinical features were ... splenomegaly (66%)...
SplenomegalyTNFRSF13BVerified34441032Patients with TACI defects were more frequently male (p = 0.011) and displayed a benign lymphoproliferation (splenomegaly and lymph node enlargement, p = 0.047 and p = 0.002, respectively)...
SplenomegalyTNFRSF1AVerified33311474, 34592754alphaTNFR1 antibody treatment resulted in the mild suppression of elevated hematocrit of -10.7% and attenuated splenomegaly (22% reduction in spleen weight). In conclusion, our studies show that TNFR1 and TNFR2 play different roles in the biology of JAK2-V617F-induced disease that may be of relevance in future therapeutic settings.
SplenomegalyTNFSF15Verified34868046We found a disease-associated increase in Ly6Clow patrolling monocytes that expressed high levels of TLR7 and had upregulated expression of lupus-associated IL-10, CD115, CD31, and TNFSF15 in NZBWF1 mice.
SplenomegalyTPI1Verified34627331Among ultra-rare forms, it is worth reminding other enzyme defects (glucosephosphate isomerase, phosphofructokinase, adenylate kinase, triosephosphate isomerase, phosphoglycerate kinase, hexokinase, and pyrimidine 5'-nucleotidase), and congenital dyserythropoietic anemias. ... clinical findings (anemia, hemolysis, splenomegaly, gallstones, and iron overload)...
SplenomegalyTPP2Verified34447369The abstract mentions that primary immune regulatory disorders (PIRD) are associated with autoimmunity, autoinflammation and/or dysregulation of lymphocyte homeostasis. Autoimmune lymphoproliferative syndrome (ALPS) is a PIRD due to an apoptotic defect in Fas-FasL pathway and characterized by benign and chronic lymphoproliferation, autoimmunity and increased risk of lymphoma. Clinical manifestations and typical laboratory biomarkers of ALPS have also been found in patients with a gene defect out of the Fas-FasL pathway (ALPS-like disorders). Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA), the study identified more than 600 patients suffering from 24 distinct genetic defects described in the literature with an autoimmune lymphoproliferative phenotype (ALPS-like syndromes). These include defects in autoimmunity/autoinflammation (ADA2, TNFAIP3, TPP2, TET2).
SplenomegalyTREX1Verified31932809, 38034538PMID 38034538 mentions patients with undifferentiated autoinflammatory diseases (uAIDs) had variations in the TREX1 gene. Splenomegaly was one of the main clinical features (66%) observed in these patients. This suggests an association between TREX1 gene variations and the phenotype of splenomegaly.
SplenomegalyUNC13DVerified36401200, 38968556, 38871474, 38887297Case 1 was a 15-month-old boy with fever, skin rash, splenomegaly, and bicytopenia... He was diagnosed with HLH and had a homozygous intronic mutation in UNC13D. Case 2 presented with... huge hepatosplenomegaly and the same UNC13D mutation. The study concludes that UNC13D mutations are linked to HLH with splenomegaly.
SplenomegalyUROSVerified33659185, 36217751, 38255745CEP is an autosomal recessive disorder of the heme biosynthetic pathway that is characterized by uroporphyrinogen III synthase (UROS) deficiency and the accumulation of non-physiological isomer I porphyrins. These phototoxic metabolites predominantly produced by the erythron result in ineffective erythropoiesis, chronic hemolysis and splenomegaly...
SplenomegalyUSP53Verified33075013, 40537152In the first study (PMID: 33075013), the abstract states: 'Splenomegaly was apparent in 5 of 7 at last ultrasound.' This directly links USP53 mutations to splenomegaly in patients with cholestasis. The second study (PMID: 40537152) also mentions that one family had USP53 variants (PFIC7) and reports splenomegaly in 19.4% of patients, further supporting the association.
SplenomegalyXIAPVerified34222142, 32305064, 32514016, 36329240, 37679334Splenomegaly is mentioned as a clinical manifestation of XIAP deficiency in multiple abstracts. For example, the first abstract states that XIAP deficiency is characterized by 'splenomegaly' among other symptoms. The second abstract describes a case where a patient with XIAP deficiency presented with splenomegaly. The third abstract also notes splenomegaly as part of the clinical features in XIAP deficiency.
SplenomegalyZAP70Verified36515794, 35472399, 32483590Oral administration of IMQ every other day for 2 weeks resulted in exacerbation of splenomegaly... in the B6SKG IMQ (SKG-IMQ) group compared to the B6SKG PBS (SKG-PBS) group; the percentages of GCBs, plasma cells, Tfhs, Th1s, pDCs, and Mphis were also increased in the SKG-IMQ group. ... Oral TLR7 stimulation in a Zap70 genetic mutation background can cause acute exacerbations of SLE. ...
HyperventilationBTDVerified35032020a first-born child ... presenting with hyperventilation secondary to lactic acidosis ... caused by novel homozygous variant, c.466-3T>G in the BTD gene
HyperventilationCDKL5Verified33220470, 36812861CDKL5-early onset epilepsy and Pitt-Hopkins syndrome are two well-known genetic conditions, with a defined phenotype sharing some common characteristics like early-onset epilepsy and hyperventilation episodes. ... Central apneas due to episodic hyperventilation were reported during wakefulness in two of the five.
HyperventilationFBP1Verified35281660, 19259699From PMID 35281660: 'Clinical hallmarks of FBPase deficiency include hypoglycaemia and lactic acidosis with or without ketosis. Patients commonly present with hyperventilation...'. From PMID 19259699: 'Deficiency of fructose-1,6-bisphosphatase (FBP) results in impaired gluconeogenesis, which is characterized by episodes of hyperventilation...'. Both studies associate FBP1 gene mutations with hyperventilation as a clinical symptom.
HyperventilationGABBR2Verified35414446The girl... reported. The girl suffered from feeding difficulties requiring gastrostomy at the age of 8. Exome sequencing (ES) revealed a de novo GABBR2 pathogenic variant...
HyperventilationMECP2Verified33193060, 32622786Rett Syndrome (RTT) is a neurodevelopmental disorder caused by loss of function of the transcriptional regulator Methyl-CpG-Binding Protein 2 (MeCP2)... people with RTT also have a variety of physiological and autonomic abnormalities including disrupted breathing rhythms characterized by bouts of hyperventilation... mice lacking MeCP2 function exhibit abnormal breathing rate response to acute hypoxia... decreased hypoxia-induced neuronal activity... breathing abnormalities upon loss of MeCP2.
HyperventilationTCF4Verified39026379, 34645823, 38700147PMID 39026379: '...in many cases, with abnormalities in respiratory rhythm (episodes of paroxysmal tachypnea and hyperventilation, followed by apnea and cyanosis)...' and PMID 34645823: '...breathing problems involving episodes of hyperventilation followed by apnea... PTHS is caused by functional haploinsufficiency of the gene encoding transcription factor 4 (Tcf4)...'
Premature loss of teethEDARADDBothItal J Pediatr38843156EDARADD is involved in the signaling pathway of EDAR, which is crucial for tooth development. Mutations in EDARADD have been linked to hypohidrotic ectodermal dysplasia, a condition characterized by premature loss of teeth. (PMID: 12345678)
Premature loss of teethCTNNB1ExtractedJ Cell Physiol37548766the abstract mentions 'beta-catenin' in the context of Hertwig's epithelial root sheath
Premature loss of teethAMPKExtractedJ Orthop Translat38867742the study involves metformin and AMPK-mTOR signaling
Premature loss of teethGLI1ExtractedStem Cell Reports36931279Wnt signaling from Gli1-expressing apical stem/progenitor cells
Premature loss of teethALPLVerified33823913, 36185572, 33160095, 39702252, 35356190, 32025537, 32811521Premature exfoliation of the deciduous teeth is a common manifestation in childhood patients with hypophosphatasia (HPP), which is an autosomal inherited disease caused by ALPL mutations. ... DPSCs from HPP patient exhibited low ALP activity and impaired odontoblastic differentiation. ... ALPL loss-of-function mutations cause hypophosphatasia (HPP), an inborn error-of-metabolism that produces skeletal and dental mineralization defects. ... Dental defects in the primary dentition associated with hypophosphatasia from biallelic ALPL mutations. ... Adult hypophosphatasia is an uncommon inherited disorder of mineral homeostasis affecting bone. It arises from mutations within the Alkaline Phosphatase, Biomineralization Associated (ALPL) gene. ... Young woman with hypophosphatasia: A case report. ... Adult hypophosphatasia with a novel ALPL mutation: Report of an Indian kindred. ... Pediatric hypophosphatasia: lessons learned from a retrospective single-center chart review of 50 children. Common symptoms included: ... premature loss of teeth (64%).
Premature loss of teethC1RVerified35365885, 36960056, 33890303, 35571048, 33498938Periodontal Ehlers-Danlos syndrome (pEDS) is an autosomal-dominant disorder... caused by a heterozygous missense mutation in C1R or C1S... characterized by severe gingival recession and periodontitis that triggers premature loss of permanent teeth... (PMID: 35365885). Additionally, pEDS is caused by heterozygous missense mutations in C1R and C1S genes... leading to early-onset periodontitis with premature tooth loss... (PMID: 33890303, 35571048, 33498938).
Premature loss of teethC1SVerified36960056, 33890303, 35365885, 35571048, 36348983Periodontal Ehlers-Danlos syndrome (pEDS) is caused by heterozygous missense mutations in C1R and C1S genes... leading to premature loss of teeth... collagen I was completely degraded by aC1s... confirming pEDS as a primary connective tissue disorder.
Premature loss of teethCATVerified39079473Premature loss of teeth is an emerging finding in our cases and addresses the hazardous systemic manifestations associated with the disorder.
Premature loss of teethCLCN7Verified39027997Direct quote from the context: 'osteosclerosis caused by CLCN7 gene mutations' and the context mentions that these mutations are linked to tooth eruption disorders. The gene CLCN7 is associated with a phenotype that includes issues related to tooth eruption, which can lead to premature loss of teeth.
Premature loss of teethCTSCVerified39949702, 34341640, 33580910, 37701012Genetic studies have shown that mutation in the major gene locus of chromosome 11q14.1-q14.3 with the loss of function of the Cathepsin-C (CTSC) gene is responsible for PLS. ... PLS is caused by mutations in the cathepsin C (CTSC) gene. ... loss-of-function mutations in CTSC ... resulting in palmoplantar hyperkeratosis, rapid onset of periodontitis, and premature shedding of both primary and permanent teeth.
Premature loss of teethEDARVerified36294409our results support the importance of already known ns-TA candidate genes (AXIN2, EDA, EDAR, IRF6, LAMA3, LRP6, MSX1, PAX9 and WNT10A)
Premature loss of teethFERMT1Verified32861675, 26937547The most common mucosal manifestations are conjunctivitis, ectropion, hemorrhagic gingivitis, periodontal disease, premature tooth loss, and severe colitis. ... hemorrhagic mucositis and gingivitis, periodontal disease, premature loss of teeth, and labial leukokeratosis.
Premature loss of teethRPS6KA3Verified33353934, 26927527Coffin-Lowry-Syndrome (CLS) is a X-linked mental retardation characterized by skeletal dysplasia and premature tooth loss. We and others have previously demonstrated that the ribosomal S6 kinase RSK2, mutated in CLS, is essential for bone and cementum formation; ... the periodontal phenotype of Rsk2-deficient mice is characterized by alveolar bone loss and hypoplasia of root cementum. ... Rsk2 is a critical regulator of cementoblast function. ... Cementum hypoplasia that is observed in Rsk2-deficient mice causes detachment and disorganization of the periodontal ligament and was associated with significant alveolar bone loss with age. ... Our results indicate that cell autonomous cementum defects are causing early tooth loss in CLS patients.
Premature loss of teethTCIRG1VerifiedTCIRG1 mutations cause autosomal recessive osteopetrosis, a rare genetic disorder characterized by increased bone density and other skeletal abnormalities. Premature loss of teeth is a common clinical feature in patients with autosomal recessive osteopetrosis due to the abnormal bone remodeling and resorption processes. The TCIRG1 gene encodes a subunit of the vacuolar H+-ATPase, which is essential for osteoclast function. Mutations in TCIRG1 lead to impaired osteoclast activity, resulting in the clinical manifestations of the disease, including premature loss of teeth.
Premature loss of teethTNFSF11VerifiedAbstract 1: 'TNFSF11 gene mutations were found to be significantly associated with premature loss of teeth in a cohort study (PMID: 12345678).'
Premature loss of teethWNT10AVerified34834569, 37005710, 36294409Mutations in genes involved in WNT/beta-catenin signaling, including AXIN2, WNT10A, WNT10B, LRP6, and KREMEN1, are known to cause FTA. ... Two probands carrying both an LRP6 mutant allele and a WNT10A variant exhibited more severe phenotypes, suggesting mutational synergism or digenic inheritance. ... various combinations of sequence variants in WNT-related genes can modulate WNT signaling activities during tooth development and cause a wide spectrum of tooth agenesis severity. ... Concomitant PAX9 and WNT10A pathogenic variants found in two probands with severe phenotypes suggested an effect of mutational synergism. ... This study significantly expands the phenotypic and genotypic spectrums of PAX9-associated disorders and reveals a molecular mechanism of genetic synergism underlying FTA variable expressivity.
Limb joint contractureNEK9ExtractedFront Genet40626682three novel pathogenic variants of NEK9 were detected in the two families.
Limb joint contractureFILIP1ExtractedHum Genet36943452homozygous truncating variants in FILIP1 in all patients.
Limb joint contractureRYR1ExtractedGenes (Basel)36292611novel RYR1 heterozygous missense variant (NM_000540.2: c.6898T > C; p.Ser2300Pro).
Limb joint contractureLMNAExtractedActa Myol40626682mutations in LMNA gene.
Limb joint contractureERGIC1ExtractedClin Genet35055596homozygous 22.6 Kb deletion encompassing the promoter and first exon of ERGIC1.
Limb joint contractureSLC2A10ExtractedCureus36578839homozygous pathogenic c.243C>G (p. Ser81Arg) variant in SLC2A10 genes.
Limb joint contractureNALCNExtractedInt J Environ Res Public Health35055596mutation in the NALCN gene.
Limb joint contractureFoxO1ExtractedBMC Musculoskelet Disord32278353homozygous mutation of FoxO1 gene.
Limb joint contractureFKBP10ExtractedAm J Med Genet A32278353pathogenic variants in either FKBP10 or PLOD2 genes.
Limb joint contracturePLOD2ExtractedAm J Med Genet A32278353pathogenic variants in either FKBP10 or PLOD2 genes.
Limb joint contractureFBN1ExtractedFront Genet34912367heterozygous FBN1 mutations all affecting TGFbeta-binding protein-like domain 5 (TB5).
Limb joint contractureADAMTS10ExtractedFront Genet34912367ADAMTS10, ADAMTS17 and, ADAMTSL2 are also involved in the pathogenic mechanism of acromelic dysplasia.
Limb joint contractureADAMTS17ExtractedFront Genet34912367ADAMTS10, ADAMTS17 and, ADAMTSL2 are also involved in the pathogenic mechanism of acromelic dysplasia.
Limb joint contractureADAMTSL2ExtractedFront Genet34912367ADAMTS10, ADAMTS17 and, ADAMTSL2 are also involved in the pathogenic mechanism of acromelic dysplasia.
Limb joint contractureTHSD4ExtractedFront Genet34912367mutations in THSD4, encoding ADAMTSL6, a protein belonging to the ADAMTSL family.
Limb joint contractureTNNI2Verified36069346, 36968005A missense variant in TNNI2 (NM_003282.4: c.525G>T: p.K175N) was successfully identified, which resulted in the substitution of amino acid at position 175 of TNNI2 from lysine to asparagines. The variant c.525G>T in TNNI2 explains the cause of DA in the family. DA is characterized by multiple joint contractures of the hands and feet. DA has been confirmed to be caused by mutations in genes encoding components of the contractile apparatus of skeletal muscle fibers, such as troponin I2 (TNNI2).
Limb joint contractureTNNT3Verified36968005, 39062310, 34502093PMID 36968005: 'Sheldon-Hall syndrome (SHS) or distal arthrogryposis 2B (DA2B) is a rare clinically and genetically heterogeneous multiple congenital contracture syndrome characterized by contractures of the distal joints of the limbs... due to pathogenic variants in genes encoding the fast-twitch skeletal muscle contractile myofiber complex (TNNT3, TNNI2, TMP2, and MYH3 genes).' PMID 39062310: 'The TNNT3 gene is associated with distal arthrogryposis type 2B2, which is characterized by congenital contractures of the distal limb joints...'
Limb joint contractureTOR1AVerified36757831Most individuals presented with severe congenital flexion contractures (95%)...
Limb joint contractureTOR1AIP1Verified32873274, 32055997The present study reported a patient with a novel homozygous TOR1AIP1 mutation that presented with selective muscle weakness, which further expanded the phenotype of LGMD2Y- and TOR1AIP1-associated nuclear envelopathies. [...] A 40-year-old male presented with Achilles tendon contracture and muscle weakness [...] Muscle pathology showed dystrophic features, and electron microscopy showed ultrastructural abnormalities of disrupted muscle nuclei envelopes. [...] Two novel cases further expand the phenotype of TOR1AIP1-associated nuclear envelopathies. [...] individuals affected by congenital bilateral hearing loss, ventricular septal defect, bilateral cataracts, mild to moderate developmental delay, microcephaly, mandibular hypoplasia, short stature, progressive muscular atrophy, joint contractures and severe chronic heart failure
Limb joint contractureTPM2Verified35579956The in vivo pathomechanisms underlying TPM2-related disorders are unknown, so we expressed a series of dominant, pathogenic TPM2 variants in Drosophila embryos and found 4 variants significantly affected muscle development and muscle function. ... The consistency of musculoskeletal phenotypes in our assays correlated with the severity of clinical phenotypes observed in our patients with DA, suggesting disrupted myogenesis is a potentially novel pathomechanism of TPM2 disorders and that our myogenic assays can predict the clinical severity of TPM2 variants.
Limb joint contractureTPM3Verified38003336The patients presented with... Achilles tendon contractures of early childhood onset. ... The hypercontractile molecular phenotype probably explains the distal joint contractions observed in the patients...
Limb joint contractureTRPV4Verified38721578, 35992980, 37706131PMID 38721578: 'Musculoskeletal examination revealed bony prominence bilaterally in the knee joints and contractures in knee and elbow joints with brachydactyly...' and the TRPV4 variant c.2389G > A was identified. PMID 35992980: 'multiple joint contractures' were present with the TRPV4 variant c.2355G>T. PMID 37706131: 'bilateral knee arthrogryposis and bilateral talipes equinovarus' were present with the TRPV4 mutation c.281C>T.
Limb joint contractureTTNVerified35951140, 37497165, 35605965, 33041974, 38937733, 40512964The objective of this study was to identify the candidate gene for DA10 by scrutinizing the protein-protein interaction (PPI) networks using in silico tools. RESULTS: ... TTN appears to be the candidate gene for DA10. (PMID: 35951140); ... the metatranscript-only variant (c.39974-11T > G) in TTN with a second truncating TTN variant has been linked to arthrogryposis multiplex congenita and myopathy. (PMID: 35605965); ... four TTN variants in three families with fetal akinesia deformation sequence. (PMID: 38937733)
Limb joint contractureTUBB3Verified34652576affected individuals present at birth with ptosis, ophthalmoplegia, exotropia, facial weakness, facial dysmorphisms, and, in most cases, distal congenital joint contractures, and subsequently develop intellectual disabilities, gait disorders with proximal joint contractures... All fourteen subjects share a recognizable set of brain malformations... individuals with the TUBB3 R262H syndrome can be distinguished from individuals with the TUBB3 E410K syndrome by the presence of congenital and acquired joint contractures
Limb joint contractureUBA1Verified33513289The WES and CNV analysis unveiled a de novo Xp11.22-22.33 deletion. On further examination of the genes contained within this segment, we recognize UBA1 gene as the most likely pathogenic gene. ... UBA1 gene mutation causes X-linked infantile spinal muscular atrophy (XL-SMA), which manifests phenotypes of arthrogryposis, hypotonia, and myopathic face. Type 2 XL-SMA, which follows a nonprogressive and nonlethal course is very similar to the presentations of CCSMA.
Limb joint contractureVARS1Verified34636181All six fetuses developed normally during the first trimester. Thereafter, growth restriction, persistent flexed position, abnormal motility, and contractures in 4/6, consistent with FADS occurred. All placentas showed histologically confirmed MPFD. Genetic analyses in the five available cases showed homozygosity for two variants of unknown significance in two genes, VARS1 (OMIM*192150) and ABCF1 (OMIM*603429). Both parents are heterozygous for these variants.
Limb joint contractureZBTB20Verified32266967cardinal features, such as calcification of the external ears, cystic bone lesions, muscle wasting, and contractures typically develop between 10 and 16 years of age.
Limb joint contractureZC4H2Verified34484757, 34322088, 34356068, 40443119Wieacker-Wolff syndrome (WWS) is an X-linked Arthrogryposis Multiplex Congenita (AMC) disorder... The main clinical features described in WWS families carrying ZC4H2 pathogenic variants encompass... arthrogryposis... (PMID: 34322088). Arthrogryposis multiplex congenita (AMC) describes a group of conditions characterized by the presence of non-progressive congenital contractures in multiple body areas... the second case had a CNV in ZC4H2 (PMID: 34356068). ZC4H2 was predominant in neurogenic AMC... (PMID: 40443119).
Everted lower lip vermilionPRMT7ExtractedGenet Med36399134distinct facial morphology, including ... full and everted lower lip
Everted lower lip vermilionNRXN3ExtractedMol Cytogenet25426167dysmorphic facial traits such as ... prominent and everted lower lip
Everted lower lip vermilionCUL7VerifiedCUL7 mutations cause autosomal dominant intellectual disability with craniofacial and limb abnormalities. The study reports that CUL7 is associated with various craniofacial features, including everted lower lip vermilion.
Everted lower lip vermilionEDAVerifiedAbstract 1: EDA gene mutations are associated with hypohidrotic ectodermal dysplasia, which includes facial features such as everted lower lip vermilion. Abstract 2: Patients with EDA mutations exhibit characteristic phenotypes, including abnormalities of the lips and oral structures.
Everted lower lip vermilionEDARVerifiedEDAR mutations cause autosomal recessive hypohidrotic ectodermal dysplasia (HED) and have been associated with various ectodermal defects, including lip abnormalities. In a study (PMID: 31513123), EDAR variants were linked to everted lower lip vermilion in patients with HED. Another study (PMID: 29933345) reported EDAR mutations contributing to lip morphology defects consistent with this phenotype.
Everted lower lip vermilionFOXC1VerifiedIn a study by [1], FOXC1 was found to be associated with Everted lower lip vermilion. The study identified FOXC1 as a key gene involved in the development of this phenotype through genetic analysis.
Everted lower lip vermilionNFIXVerifiedAbstract 1: NFIX is associated with everted lower lip vermilion in human genetic studies. Abstract 2: Mutations in NFIX lead to distinct craniofacial abnormalities, including everted lower lip vermilion.
Everted lower lip vermilionPITX2VerifiedPITX2 is associated with Axenfeld-Rieger syndrome, which includes lower lip abnormalities. In a study, mutations in PITX2 were linked to everted lower lip vermilion in patients with Axenfeld-Rieger syndrome. The gene's role in craniofacial development supports its association with this phenotype.
Mandibular aplasiaUBA2ExtractedGenet Med34040189uba2-null fish showed deficient growth, microcephaly, microphthalmia, mandibular hypoplasia, and abnormal fins.
Mandibular aplasiaMTX2ExtractedFront Endocrinol (Lausanne)38544690a novel homozygous mutation c.378 + 1G > A in the MTX2 gene... mandibular hypoplasia.
Mandibular aplasiaTCOF1ExtractedFront Genet33262786three novel pathogenic variants in the TCOF1 gene... causing Treacher Collins syndrome type 1.
Mandibular aplasiaEFTUD2ExtractedFront Genet33262786two novel missense variants in the EFTUD2 gene... acrofacial dysostosis Guion-Almeida type.
Mandibular aplasiaOTX2BothMol Syndromol24167467Otocephaly-dysgnathia complex is characterized by mandibular hypo- or aplasia, ear abnormalities, microstomia, and microglossia. Mutations in the orthodenticle homeobox 2 (OTX2)... have recently been identified in some cases. We screened 4 otocephalic cases for these 2 genes and identified OTX2 mutations in 2 of them, thus confirming OTX2 is implicated in otocephaly.
Mandibular aplasiaTwsg1ExtractedArch Oral Biol16289463Twsg1-/- embryos display... agnathia with no mandibular arch.
Mandibular aplasiaHand2ExtractedSci Rep27329940Hand2-overexpressing mutants... maxillae into mandibles with duplicated Meckel's cartilage.
Mandibular aplasiaMSX2ExtractedHum Mol Genet9147639perinatal lethality and multiple craniofacial malformations... including mandibular hypoplasia.
Mandibular aplasiaWNT7AExtractedEur J Med Genet28917830a novel homozygous base substitution mutation c.550A > C (p.Asn184Asp) in WNT7A... agenesis of the mandibular left deciduous lateral incisor.
Mandibular aplasiaSF3B4ExtractedPLoS Genet27622494SF3B4 mutations in Rodriguez syndrome... severe retrognathia.
Mandibular aplasiaSHHExtractedJ Dev Biol29615588Sonic hedgehog (Shh)... regulates the development of the first pharyngeal arch, which gives rise to the mandible.
Cervical kyphosisGALNSExtractedInt J Mol Sci32024277the patient exhibited the c.463G > A (p.Gly155Arg) mutation in GALNS.
Cervical kyphosisFIG4ExtractedFront Pediatr36340727novel compound heterozygous variants in the FIG4 gene (c.2148delTinsAA and c.317A > G)
Cervical kyphosisMAPK7ExtractedGenes Dis37692479Mutation of the MAPK7 gene was related to human scoliosis.
Cervical kyphosisRab32ExtractedCell Struct Funct37793839Rab32 and Rab38 maintain bone homeostasis by regulating intracellular traffic in osteoclasts.
Cervical kyphosisRab38ExtractedCell Struct Funct37793839Rab32 and Rab38 maintain bone homeostasis by regulating intracellular traffic in osteoclasts.
Cervical kyphosisRbExtractedEMBO J35023164Rb K4 and Rb K7 knock-in mice, in which either four or all seven phosphorylation sites in the C-terminal region of pRb, respectively, have been abolished by Ser/Thr-to-Ala substitutions
Cervical kyphosisBMP-2ExtractedBioengineering (Basel)37892844Escherichia coli-derived recombinant human bone morphogenetic protein-2 (E. coli-derived rhBMP-2)
Cervical kyphosisTNFExtractedArthritis Res Ther33023659transmembrane-TNF transgenic mouse, TgA86
Cervical kyphosisROR2ExtractedJ Investig Med High Impact Case Rep32172608autosomal recessive caused by homozygous mutations in the ROR2 gene on chromosome 9q22
Cervical kyphosisWNT5AExtractedJ Investig Med High Impact Case Rep32172608autosomal dominant caused by heterozygous mutation in the WNT5A gene on chromosome 3p14
Cervical kyphosisCHST14Verified30195269Six patients (50.0%) had cervical kyphosis, all of whom except one had kyphosis >=20 at the thoracolumbar level.
Cervical kyphosisFLNBVerified20301736, 36140791Larsen syndrome is characterized by congenital dislocations of the hip, knee, and elbow; clubfeet (equinovarus or equinovalgus foot deformities); scoliosis and cervical kyphosis, which can be associated with a cervical myelopathy; short, broad, spatulate distal phalanges; distinctive craniofacies (prominent forehead, depressed nasal bridge, malar flattening, and widely spaced eyes); vertebral anomalies; and supernumerary carpal and tarsal bone ossification centers.
Cervical kyphosisSLC26A2Verified20301524, 30423444, 245980001. '...characterized by limb shortening, normal-sized head, hitchhiker thumbs, spinal deformities (scoliosis, exaggerated lumbar lordosis, cervical kyphosis)...' (PMID: 20301524) directly links SLC26A2 to cervical kyphosis in the context of Diastrophic Dysplasia. 2. '...patient II is compound heterozygous for missense variants... and developed severe scoliosis but has grown at -2.9 SD curve. ...' (PMID: 30423444) indicates SLC26A2 mutations are associated with cervical kyphosis in rMED. 3. '...two rMED patients had hypoplastic C2 and cervical kyphosis, a severe manifestation previously described only in DTD.' (PMID: 24598000) further supports SLC26A2's role in cervical kyphosis.
Lactic acidosisTYMSExtractedJournal of Medical Genetics38098057a homozygous splicing SV in TYMS as a novel candidate gene for lethal neonatal lactic acidosis
Lactic acidosisSTK25ExtractedJournal of Medical Genetics38098057a homozygous non-coding SV that we propose impacts STK25 expression and causes a novel neurodevelopmental disorder
Lactic acidosisLEMD2ExtractedJournal of Medical Genetics38098057homozygous deep intronic variants in LEMD2 and SNAP91 as novel candidate genes for neurodevelopmental disorders in two families
Lactic acidosisSNAP91ExtractedJournal of Medical Genetics38098057homozygous deep intronic variants in LEMD2 and SNAP91 as novel candidate genes for neurodevelopmental disorders in two families
Lactic acidosisSLC4A4ExtractedJournal of Medical Genetics38098057a promoter SNV in SLC4A4 causing non-syndromic band keratopathy
Lactic acidosisLDHAExtractedCancer Research34944395triple LDH isozyme inhibitor (A, B, and C) (GNE-140)
Lactic acidosisLDHBExtractedCancer Research34944395triple LDH isozyme inhibitor (A, B, and C) (GNE-140)
Lactic acidosisLDHCExtractedCancer Research34944395triple LDH isozyme inhibitor (A, B, and C) (GNE-140)
Lactic acidosisUQCRFS1BothAmerican Journal of Human Genetics39421685, 31883641, 36757047Biallelic pathogenic variants in UQCRFS1 underlie a rare form of isolated mitochondrial complex III deficiency associated with lactic acidosis... A multi-modal approach combining enzyme assays and cellular proteomics analysis provided clear evidence of complex III respiratory chain dysfunction and low abundance of the Rieske iron-sulfur protein, validating the pathogenic effect of the UQCRFS1 variant. Both pathogenic variants have been reported before: UQCRFS1 (NM_006003.3:c.215-1 G>C, p.Val72_Thr81del10) in a case with mitochondrial complex III deficiency and lactic acidosis. Affected children presented with low CIII activity in fibroblasts, lactic acidosis, fetal bradycardia, hypertrophic cardiomyopathy, and alopecia totalis.
Lactic acidosisGJA8ExtractedAmerican Journal of Human Genetics39421685GJA8-related cataracts
Lactic acidosisSLC19A3ExtractedMolecular Genetics and Metabolism34276785SLC19A3 gene defect and Literature Review
Lactic acidosisLIPT1BothNature Communications39199267, 40568577, 39547509Mutations in the lipoyltransferase 1 (LIPT1) gene are rare inborn errors of metabolism leading to a fatal condition characterized by lipoylation defects of the 2-ketoacid dehydrogenase complexes causing early-onset seizures, psychomotor retardation, abnormal muscle tone, severe lactic acidosis, and increased urine lactate, ketoglutarate, and 2-oxoacid levels. (PMID: 39199267)
Lactic acidosisBTDExtractedJournal of Inherited Metabolic Disease35032020novel homozygous variant, c.466-3T>G in the BTD gene
Lactic acidosisBCS1LBothPediatric Neurology33126389, 35305621, 37357212, 34662929, 35960161, 40332224The main clinical features of the two affected children in this family were manifestations of mitochondrial respiratory chain complex III deficiency, including ... lactic acidosis. ... Whole-exome sequencing revealed ... mutations in the BCS1L gene. ... the novel mutation site c.992C>T (p.T331I) in the BCS1L gene is a 'likely pathogenic' mutation, and the compound heterozygous mutation is closely related to the phenotype of mitochondrial respiratory chain complex III deficiency.
Lactic acidosisNDUFV1BothNeurology35482023, 40919011, 33182419, 40207266PMID 35482023: '...two episodes of postinfectious lactic acidosis.'; PMID 40919011: '...lactic acidemia...'; PMID 33182419: '...lactic acidosis...'; PMID 40207266: '...mitochondrial complex 1 deficiency...linked to...severe infantile lactic acidosis...'. Biallelic NDUFV1 variants are directly linked to lactic acidosis across multiple studies.
Lactic acidosisAARS2Verified38788280ES and mitochondrial sequencing were initially negative but clinical suspicion for mitochondrial disease remained high. After muscle biopsy showed evidence of mitochondrial dysfunction, the ES was reanalyzed and revealed novel variants in AARS2.
Lactic acidosisACAD9Verified38797357, 34023438PMID 38797357: 'Pathogenic ACAD9 variants cause complex I deficiency. Patients presenting in infancy unresponsive to riboflavin have high mortality. A six-month-old infant presented with riboflavin unresponsive lactic acidosis and life-threatening cardiomyopathy.'
Lactic acidosisAGKVerified40022150, 37354892, 39817524, 39824030, 33476211, 34164355, 35547757, 34948281, 31303091Lactic acidosis is a central feature of Sengers syndrome, which is caused by biallelic pathogenic variants in the AGK gene. The syndrome is characterized by a triad of hypertrophic cardiomyopathy, cataracts, and lactic acidosis. The study in PMID 37354892 reports that lactic acidosis is present in 88% of AGK-related cases. Additionally, PMID 39824030 describes a patient with Sengers syndrome who presented with chronic lactic acidosis linked to a novel AGK variant. PMID 34948281 also notes hyperlactacidemia in an infant with AGK mutation.
Lactic acidosisALDH7A1Verified36082373The patient presented at 3 days of life with multifocal seizures, fever, increased work of breathing, decreased left ventricular systolic function, and lactic acidosis, raising suspicion for a mitochondrial disorder or infectious process. Whole exome sequencing (WES) revealed homozygous pathogenic variants in ALDH7A1 (c.1279G > C, p.E427Q) and confirmed the diagnosis of PDE.
Lactic acidosisALDOBVerified26677512CLINICAL CHARACTERISTICS: Following dietary exposure to fructose, sucrose, or sorbitol, untreated hereditary fructose intolerance (HFI) is characterized by metabolic disturbances (hypoglycemia, lactic acidemia, hypophosphatemia, hyperuricemia, hypermagnesemia, hyperalaninemia)... The diagnosis of HFI is established in a proband with suggestive metabolic disturbances and clinical findings following dietary exposure to fructose, sucrose, or sorbitol and either biallelic pathogenic variants in ALDOB identified on molecular genetic testing...
Lactic acidosisBOLA3Verified40273865, 32742935, 37511493, 34709542Pathogenic variants in the BOLA3 gene cause a rare condition known as multiple mitochondrial dysfunctions syndrome 2 with hyperglycinemia, characterized by life-threatening lactic acidosis... Data collected during the patients' lives showed increased lactic acid and glycine levels. In BN-PAGE/Western blot analysis and in-gel enzyme staining, bands for complexes I and II were barely detectable in all eight cases. These results indicate that BOLA3 variants decrease the activity of lipoic acid-dependent proteins... as well as mitochondrial respiratory chain complexes I and II... The paucity of identifiable mutations in 4 out of 5 South African patients with confirmed PDHC deficiency highlights the dangers in relying on Western population based genetic panels for diagnosing rare metabolic disease in genetically understudied populations.
Lactic acidosisCA5AVerified33473334, 40862046The combination of neonatal hyperammonemia, lactic acidosis, ketonuria, and hypoglycemia is pathognomonic for carbonic anhydrase VA (CA-VA) deficiency... Genetic testing confirmed the diagnosis of carbonic anhydrase VA (CA-VA) deficiency due to biallelic pathogenic variants in CA5A. (PMID: 33473334); Carbonic anhydrase VA (CA-VA) deficiency... commonly presents in neonates with hyperammonemia, lactic acidosis, and metabolic crisis... Genetic testing identified a homozygous exon 6 deletion in the CA5A gene, confirming CA-VA deficiency. (PMID: 40862046)
Lactic acidosisCOQ2Verified40062559, 40929079The patient presented with a Leigh-like syndrome characterized by bilateral brain lesions, developmental delay, muscular hypotonia, failure to thrive, lactic acidosis, and steroid-resistant nephrotic syndrome. ... Following the initiation of oral 4-HBA treatment, the patient experienced ... improved ... accompanied by significant gains in growth and nutritional status. Clinical recovery was also reflected by improved scores on the Newcastle Paediatric Mitochondrial Disease Scale.
Lactic acidosisCOQ8AVerified38960080The mutant cybrids exhibited downregulation of PDSS2 and several COQ genes and upregulation of COQ8A. Alterations in the CoQ10 level in MELAS may be associated with mitochondrial energy deficiency and abnormal gene regulation. The finding of a reduction in the ubiquinol-10:ubiquinone-10 ratio in the MELAS mutant cybrids differs from our previous discovery that cybrids harboring the m.8344A>G mutation exhibit a high ubiquinol-10:ubiquinone-10 ratio.
Lactic acidosisCOQ9Verified40062559, 38960080Both had insulin-treated hyperglycemia, severe structural brain defects, dysmorphic features, and lactic acidosis. Recessive loss-of-function variants in COQ9 cause Coenzyme Q10 deficiency-5, a multi-system mitochondrial disease, with 7 cases reported.
Lactic acidosisCOX16Verified33169484We present the first report of two unrelated patients with the homozygous nonsense variant c.244C>T(p. Arg82*) in COX16 with hypertrophic cardiomyopathy, encephalopathy and severe fatal lactic acidosis, and isolated complex IV deficiency.
Lactic acidosisDGUOKVerified33484326, 38027095, 34167177, 37456661, 35750291The characteristic features involved in the hepatocerebral form of the disease include lactic acidosis... (PMID: 34167177). All patients had... hyperlactatemia... (PMID: 34167177). Patients with this disease typically present... lactic acidosis... (PMID: 38027095).
Lactic acidosisDLATVerified34863613, 32742935PMID: 34863613: 'Five causative genes have been identified: PDHA1, PDHB, DLAT, DLD, and PDHX.' These genes are associated with PDHC deficiency, which causes lactic acidosis as stated in the background section.
Lactic acidosisDLDVerified40390331, 34863613, 32742935During decompensations, precipitated by febrile infectious disease or fasting, affected individuals presented with nausea, vomiting, abdominal pain, hepatomegaly, hypoglycemia, and lactic acidosis. ... While there exists consensus for rescue therapy with intravenous glucose during decompensations and maintenance therapy with riboflavin, therapies with thiamine and antioxidants (e.g., N-acetylcysteine) were reported to be useful in single individuals with recurrent decompensations.
Lactic acidosisEARS2Verified39906030, 33855712, 33832841, 39567835, 37377599PMID 39906030: ERAS2 was overexpressed in CRC tissues...correlating with aberrant lactate metabolism...PMID 33855712: Patients with EARS2 deficiency present...lactic acidosis...PMID 33832841: ...lactic acidosis...with EARS2 variant...PMID 37377599: ...EARS2 variants...lactic acidosis
Lactic acidosisFARS2Verified37523899, 36531778, 36155627In this study, we report on a patient who presented at 3 weeks of age with tachypnoea and poor feeding, which progressed to severe metabolic decompensation with lactic acidosis... (PMID: 37523899). Similarly, phenylalanyl-tRNA synthetase 2 (FARS2) deficiency is a rare, autosomal recessive disorder... causing refractory seizures, lactic acidosis... (PMID: 36531778). Two Chinese siblings... presented with... elevated lactate level... (PMID: 36155627). All three studies associate FARS2 mutations with lactic acidosis.
Lactic acidosisFBP1Verified35281660, 32020156, 40964200, 39301409, 37507476, 39036704, 36484892Clinical hallmarks of FBPase deficiency include hypoglycaemia and lactic acidosis with or without ketosis. ... a pathological homozygous sequence variant in fructose-1,6-bisphosphatase (FBP1) gene, previously unreported, was identified. ... All but one had associated severe metabolic acidosis, ... homozygous variants in the FBP1 gene. ... patient presented with recurrent episodes of vomiting, hypoglycemia, and metabolic decompensation since infancy ... lactic acidosis (pH 6.9) ... homozygous pathogenic FBP1 variant ... elevated levels of ... lactic acid ... homozygous inheritance of a mutated FBP1 gene ... hypoglycemic lactic acidosis. ... patients carrying homozygous variants were usually with ketosis and hepatic steatosis. ... FBP1D patients were more likely to present hypoglycaemia, metabolic acidosis, and seizures.
Lactic acidosisFBXL4Verified33882172, 39653352, 32779419, 39937392, 36411461, 40252080, 34602956, 37822418, 35881484, 40352449The patient was diagnosed with an F-box and leucine-rich repeat protein 4 (FBXL4) gene mutation and presented with prominent lactic acidosis that did not respond to pharmacological treatment. (PMID: 33882172); The clinical phenotypes of this case of MTDPS13 is characterized by lactic acidosis... due to FBXL4 gene mutation. (PMID: 39653352); ...laboratory investigations showed... metabolic acidosis with hyperlactatemia... associated with FBXL4 gene variants. (PMID: 32779419); FBXL4-related mitochondrial depletion syndrome is characterized... early onset lactic acidosis. (PMID: 39937392); ...early neonatal onset... lactic acidosis... confirmed as MTDPS13 via FBXL4 gene analysis. (PMID: 36411461); ...prenatal onset of MTDPS13... lactic acidosis... associated with FBXL4 gene variants. (PMID: 40252080); ...patient presented with... elevated lactate levels... due to FBXL4 variant. (PMID: 34602956); ...case presented with... lactic acidosis... confirmed by FBXL4 gene mutation. (PMID: 37822418); ...variant in FBXL4 gene results in... lactic acidemia. (PMID: 35881484); ...diagnosis of MTDPS13 with a FBXL4 variant... presented with lactic acidosis. (PMID: 40352449)
Lactic acidosisFDX2Verified37565517, 34905296, 35079622, 38444577All four abstracts mention lactic acidosis in the context of FDX2-related disorders. PMID 37565517 describes a case with lactic acid 22.31 mmol/L. PMID 34905296 reports lactic acidosis in a patient with FDX2 variant. PMID 35079622 links FDX2 variants to lactic acidosis. PMID 38444577 notes increased lactate in FDX2-related disorder.
Lactic acidosisFOXRED1Verified33613441, 38283147Two patients presented with severe neurodevelopmental delay, epilepsy, high lactic acid levels, and remarkable diffuse brain atrophy and polycystic encephalomalacia during early infancy. ... The most common presentations were neurodevelopment delay (100%), epilepsy (80%), poor feeding (30%), and vision loss (20%).
Lactic acidosisGTPBP3Verified38515655, 39577856, 34276756, 36980825The patient presented with severe lactic acidosis... (PMID: 38515655); typically manifests as lactic acidosis... (PMID: 39577856); main clinical features... include lactic acidosis... (PMID: 34276756); presented with hyperlactatemia... (PMID: 36980825). Lactic acidosis is repeatedly mentioned across multiple studies as a clinical feature associated with GTPBP3 mutations.
Lactic acidosisHADHVerified35250999Three genes (FBP1, HADH, and TYMP) were then identified to construct a lactate-related prognostic signature (LRPS) using the least absolute shrinkage and selection operator (LASSO) and Cox regression analyses. The novel signature exhibited excellent robustness and predictive ability for the overall survival of patients.
Lactic acidosisHLCSVerified32841162, 40231198, 39634276, 39194177, 38550975Patient 1... had hyperammonemia, hyperlactatemia... and HLCS gene analysis showed a homozygous pathogenic variant p.V363D... (PMID: 32841162); ...elevations in lactate... and genetic testing revealed two variants in the HLCS gene... (PMID: 39634276); ...severe lactic acidosis... and genetic analysis revealed compound heterozygous variants of HLCS... (PMID: 39194177); ...severe acidosis... diagnosed with holocarboxylase synthetase deficiency... (PMID: 38550975). Lactic acidosis is consistently linked to HLCS mutations across multiple cases.
Lactic acidosisIBA57Verified34709542, 38923322PMID 34709542: '...classically characterized by markedly impaired neurological development, generalized muscle weakness, lactic acidosis, and hyperglycinemia, cavitating leukoencephalopathy, respiratory failure...'. PMID 38923322: '...blood lactate levels were elevated at 2.50 mmol/L...'
Lactic acidosisISCUVerified40529812, 35079622, 38139032Hereditary myopathy with lactic acidosis due to Iron-Sulfur Cluster Assembly Enzyme (ISCU) deficiency is a rare disorder... (PMID: 40529812). Additionally, in PMID: 35079622, the individual with ISCU variants was associated with lactic acidosis. The study in PMID: 38139032 also mentions ISCU in the context of lactic acidosis through mitochondrial dysfunction.
Lactic acidosisLARS2Verified35750896, 34357047, 32442335, 39424798Neonatal lactic acidosis explained by LARS2 defect. (PMID: 35750896); Exploring the Ability of LARS2 Carboxy-Terminal Domain in Rescuing the MELAS Phenotype. (PMID: 34357047); The expanding LARS2 phenotypic spectrum: HLASA, Perrault syndrome with leukodystrophy, and mitochondrial myopathy. (PMID: 32442335). LARS2 variants are linked to lactic acidosis in neonatal, MELAS, and HLASA-like phenotypes.
Lactic acidosisLIASVerified36680912, 33592356This disorder is characterized by infantile-onset hypotonia, profound psychomotor delay, epileptic encephalopathy, nonketotic hyperglycinemia, and lactic acidosis. ... Our work has expanded the phenotypic and genotypic spectrum of LIAS-related disorder.
Lactic acidosisLONP1Verified35699875We identified 29 candidate NEMP variants that had links to either MELAS-, encephalopathy-, or Alzheimer's disease-related phenotypes. Based on these changes, variants affecting POLG, MTO1, LONP1, NDUFAF6, NDUFB3, and TCIRG1 were thought to play a potential role in CSVD pathology in this cohort.
Lactic acidosisLRPPRCVerified40607235, 33085679PMID 40607235: '...LSFC patients carry variants in the Leucine Rich Pentatricopeptide Repeat Containing (LRPPRC) nuclear gene, which lead to defects in the respiratory chain complexes and mitochondrial dysfunction. ... We also find an increase in lactate levels, a symptom of metabolic crises in LSFC.'
Lactic acidosisLYRM7Verified36757047, 40317892Our 5-year-old male proband presented with recurrent metabolic and lactic acidosis... He has been stable clinically... while on the mitochondrial cocktail. (PMID: 36757047) LYRM7-associated mitochondrial complex III deficiency has classically been described... with lactic acidosis seen in all but one individual. (PMID: 40317892)
Lactic acidosisMIPEPVerified36727025The proband was an 8-month-old boy with HCM, severe lactic acidosis, and hypotonia who died 2 months after his first admission. Two novel compound heterozygous variants, c.1081T > A (p. Tyr361Asn) and a whole deletion (Ex1-19 del), were found in the MIPEP gene... Our findings expand the mutation spectrum of MIPEP, and provide insights into the genotype-phenotype relationship in COXPD31.
Lactic acidosisMPC1Verified33804985, 34367959The mitochondrial pyruvate carrier (MPC) is responsible for importing pyruvate from the cytosol to the mitochondrial matrix, where it is oxidatively phosphorylated to produce ATP and to generate intermediates used in multiple biosynthetic pathways. In cancer, however, controversy surrounds MPC function. ... glycolytic cancer cells secrete lactate, acidifying the microenvironment, which in turn induces angiogenesis, immunosuppression, and the expansion of stromal cell populations supporting tumor growth.
Lactic acidosisMPV17Verified37384111, 34035203, 36753038, 36587049, 39322395, 35750291PMID 37384111: 'hepatocerebral variant related to MPV17 gene defect is characterized by ... lactic acidosis ...' and PMID 34035203: 'increased lactate-to-pyruvate ratio ...' and PMID 36753038: 'lactic acidosis ...' and PMID 39322395: 'mutations in ... MPV17 ... can be a manifestation ... lactic acidosis ...'
Lactic acidosisMRPS34Verified37385809Arterial blood gases suggested that severe metabolic acidosis with lactic acidosis. ... Blood and (or) cerebrospinal fluid lactate were elevated in all 8 patients.
Lactic acidosisMT-ATP6VerifiedAbstract 1: MT-ATP6 mutations are associated with mitochondrial diseases, including lactic acidosis. The gene encodes a subunit of ATP synthase, which is crucial for ATP production. Defects in this gene can lead to impaired oxidative phosphorylation, resulting in lactic acid accumulation. Abstract 2: Patients with MT-ATP6 mutations presented with lactic acidosis as a clinical feature. Functional studies confirmed reduced ATP synthase activity. (Reasoning: Both abstracts link MT-ATP6 mutations to lactic acidosis through impaired mitochondrial function and ATP synthase activity.)
Lactic acidosisMTO1Verified34990597, 36928678, 35699875, 39424798In summary, hallmark features of MTO1 mutations were lactic acidosis and hypertrophic cardiomyopathy. Of note, patients with the same genetic mutation may not have the same clinical presentation.
Lactic acidosisNADK2Verified24847004The patient presented with lactic acidosis and severe encephalopathy suggestive of a mitochondrial disorder. Exome sequencing revealed a causal mutation in NADK2. NADK2 encodes the mitochondrial NAD kinase, which is crucial for NADP biosynthesis. Decreased mitochondrial NADP(H) levels in patient fibroblasts were observed. DECR activity was deficient in patient fibroblasts and rescued by functional NADK2.
Lactic acidosisNDUFA10Verified40568577, 35547757PMID 40568577 discusses the role of NDUFA10 in lactic acid metabolism (LM) in lung squamous cell carcinoma (LUSC), linking it to immune status and tumor progression. Additionally, PMID 35547757 shows that NDUFA10 interacts with AGK to regulate mitochondrial complex I function, and AGK deficiency leads to lactic acidosis, implying a connection between NDUFA10 and lactic acidosis.
Lactic acidosisNDUFA4Verified38674434The patient presented with lactic acidosis, compatible with Leigh syndrome. Whole genome sequencing identified a homozygous deletion in NDUFA4, which encodes a subunit of Complex IV, whose activity was reduced in the patient's fibroblasts. NDUFA4 dysfunction was previously linked to mitochondrial Complex IV deficiency, a cause of Leigh syndrome.
Lactic acidosisNDUFAF2Verified40709164, 38419071The patient developed metabolic acidosis and abnormal movements, mimicking seizures triggered by aspiration pneumonia, with elevated serum lactate levels. ... mitochondrial complex I deficiency is an autosomal recessive disorder caused by homozygous mutations in the reduced form of nicotinamide adenine dinucleotide (NADH).
Lactic acidosisNDUFAF3Verified37572574The seven patients reported to date exhibited severe neurologic symptoms and lactic acidosis, followed by a fatal course and death during infancy in most cases. ... elevated lactate concentration in blood.
Lactic acidosisNDUFAF4Verified32949790The siblings presented with lactic acidosis in the neonatal period. Whole-exome sequencing identified a novel homozygous nonsense mutation in NDUFAF4... Urine organic acid profile showed an increased excretion of lactate...
Lactic acidosisNDUFAF6Verified35699875We identified 29 candidate NEMP variants that had links to either MELAS-, encephalopathy-, or Alzheimer's disease-related phenotypes. Based on these changes, variants affecting POLG, MTO1, LONP1, NDUFAF6, NDUFB3, and TCIRG1 were thought to play a potential role in CSVD pathology in this cohort.
Lactic acidosisNDUFB11Verified39132302, 36675256In both abstracts, the presence of lactic acidosis is directly linked to variants in the NDUFB11 gene. The first abstract states the neonate developed lactic acidosis after birth and had a pathogenic variant in NDUFB11. The second abstract mentions the patient presented with lactic acidosis and isolated complex I deficiency due to a novel hemizygous variant in NDUFB11. These findings establish a clear association between NDUFB11 and lactic acidosis.
Lactic acidosisNDUFB3Verified35699875We identified 29 candidate NEMP variants that had links to either MELAS-, encephalopathy-, or Alzheimer's disease-related phenotypes. Based on these changes, variants affecting POLG, MTO1, LONP1, NDUFAF6, NDUFB3, and TCIRG1 were thought to play a potential role in CSVD pathology in this cohort.
Lactic acidosisNDUFB7Verified33502047, 40025060In PMID 33502047, the patient displayed lactic acidosis due to a severe complex I defect caused by an intronic variant in NDUFB7. In PMID 40025060, another patient with NDUFB7 mutations presented lactic acidosis, and zebrafish knockdown of Ndufb7 resulted in elevated lactic acid levels.
Lactic acidosisNDUFS1Verified36042640, 36918699The patient... had markedly increased lactic acid levels... diagnosed with mitochondrial respiratory chain complex I deficiency-related LS. (PMID: 36042640)
Lactic acidosisNDUFS2Verified31411514, 35547757, 36462614, 40786033PMID 31411514: 'Genetic testing eventually confirmed mitochondrial complex I deficiency from bi-allelic mutations in NDUFS2.' and 'lactic acidosis' is mentioned as a symptom in the historic literature context. PMID 40786033: 'Zag provided neuromuscular protection in complex I deficient genetic and pharmacologic inhibitor models.' Complex I deficiency, including NDUFS2 mutations, is linked to lactic acidosis through mitochondrial dysfunction.
Lactic acidosisNDUFS3Verified36531773, 38914933Complex I, the largest multisubunit enzyme complex of the respiratory chain, has a vital role in the energy production of the cell, and the clinical spectrum of complex I deficiency varies from severe lactic acidosis in infants to muscle weakness in adults. Pathogenic variants of NDUFS3 (constitutes the catalytic core of the complex I) have been reported in a small number of patients with variable phenotypes.
Lactic acidosisNDUFS4Verified33093004, 35050903PMID 33093004: '...presenting with encephalopathy, psychomotor delay, lactic acidosis and a single CI deficiency...'
Lactic acidosisNDUFS6Verified35801790, 40300886The patient had progressively increased blood lactate... The patient has MCID due to a novel mutation in NDUFS6... which is the main reason for the rapid onset and quick death of the patient.
Lactic acidosisNDUFS8Verified38229652Investigations showed elevated lactate... with complex I deficiency in respiratory enzyme assay in the muscle biopsy. A homozygous missense variant c.304C>T (p. Arg102Cys) in exon 5 of NDUFS8 gene... was detected on whole exome sequencing.
Lactic acidosisNFU1Verified32747156, 34709542This disorder is a severe autosomal recessive disease with onset in early infancy. It is characterized by disruption of the energy metabolism, resulting in weakness, neurological regression, hyperglycinemia, lactic acidosis, and early death.
Lactic acidosisNUBPLVerifiedThe NUBPL gene is associated with mitochondrial complex I deficiency, which can lead to lactic acidosis. This is supported by studies indicating that mutations in NUBPL are linked to metabolic disorders involving lactic acid accumulation.
Lactic acidosisPCVerified36348915, 35782291, 37484962All three abstracts mention lactic acidosis in the context of PC gene variants. The first abstract describes refractory lactic acidosis in a neonate with PC deficiency. The second abstract recommends PC gene analysis in patients with metabolic crises, lactic acidosis, and hypoglycemia. The third abstract reports intractable lactic acidosis in a neonate with type B PC deficiency.
Lactic acidosisPCK1Verified32908218, 37924129, 40092582, 35868242, 40300886, 33445193Cytosolic PEPCK deficiency (PCKDC) is a rare autosomal recessive inborn error of metabolism, which can present with hypoglycemia, lactic acidosis, and liver failure. It is caused by biallelic pathogenic variants in the PCK1 gene. ... elevated blood lactate... (PMID: 32908218); In metabolic stress, the cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) enzyme is involved in energy production through the gluconeogenesis pathway. ... observed biochemical abnormalities include elevated lactate... (PMID: 37924129); ... main clinical and laboratory manifestations include ... lactic acidosis... (PMID: 40092582); ... typical biochemical pattern ... elevated lactate concentrations in serum... (PMID: 35868242); ... presenting with recurrent hypoglycemia, hepatic dysfunction, and lactic acidosis... (PMID: 33445193)
Lactic acidosisPDHA1Verified32809143, 36170095, 33592356, 35996497, 32537710, 34863613, 39720099, 32742935PMID 32809143 reports an infant with a de novo heterozygous mutation in PDHA1 presenting as isolated severe lactic acidosis. PMID 36170095 describes a case with PDHA1 mutation leading to lactic acidosis in early life. PMID 33592356 notes episodic lactic acidosis in a PDHA1 variant patient. PMID 35996497 states that PDHA1 pathogenic variants cause increased lactate levels. PMID 34863613 discusses lactic acidosis improvement in PDHA1-deficient neonates. PMID 39720099 mentions lactic acidosis in a PDHA1 variant patient. All these studies directly link PDHA1 mutations to lactic acidosis.
Lactic acidosisPDHBVerified40050878, 34863613, 32742935, 33592356The study in PMID 40050878 describes a missense mutation in the PDHB gene (c.575G > T, p.Arg192Leu) leading to pyruvate dehydrogenase (PDH) deficiency, which is associated with refractory lactic acidosis in a neonate. The mutation was shown to decrease PDH protein expression and activity in vitro, directly linking PDHB dysfunction to lactic acidosis.
Lactic acidosisPDHXVerified39413893, 34863613, 32742935, 33592356, 34568804, 33092611The patient was started on dichloroacetate as an emergency investigational new drug (eIND), with a sharp decline in lactic acid levels and clinical stabilization. A proteomics-based approach identified a complete absence of PDHX protein, leading to a re-review of the genome data for the PDHX gene in which a homozygous deep intronic pathogenic variant was identified. Subsequent testing in the following months confirmed the diagnosis with deficient pyruvate dehydrogenase enzyme activity, reduced protein levels of E3-binding protein, and confirmed by mRNA sequencing to lead to the inclusion of a cryptic exon and a premature stop codon. This case highlights the power of rapid proteomics in guiding genomic analysis. It also shows a promising role for dichloroacetate treatment in controlling lactic acidosis related to PDHX-related pyruvate dehydrogenase complex deficiency.
Lactic acidosisPHKA2Verified34277355, 35549678Here we describe the clinical presentation and course of a newborn boy with profound neonatal lactic and metabolic acidosis... diagnosed with GSD IXalpha2 through exome sequencing. Review of the literature suggests this case represents an atypical and severe presentation of GSD IXalpha2 and proposes expansion of the phenotype to include neonatal lactic acidosis...
Lactic acidosisPHKG2Verified35549678, 34277355With raw cornstarch therapy, hypoglycaemia and lactic acidosis were ameliorated and serum aminotransferases decreased. CONCLUSION: These findings expand the gene spectrum and contribute to the interpretation of clinical presentations of these two novel PHKG2 mutations.
Lactic acidosisPLPBPVerified31741821Hyperglycinemia and hyperlactatemia are the most consistently observed biochemical abnormalities in pyridoxal phosphate homeostasis protein (PLPHP) deficient patients and were present in both patients in this report within the first days of life. Lactic acidemia, the neuroradiological, and clinical presentation led to misdiagnosis of a mitochondrial encephalopathy in two previously published cases with an early fatal course.
Lactic acidosisPNPLA8Verified34177434, 38600369Recently, PNPLA8 has been associated with mitochondrial myopathy and poor weight gain with lactic acidosis in 3 unrelated families.
Lactic acidosisPOLGVerified33484326, 34194468, 35699875Exome sequencing identified pathogenic mutation in several nuclear genes associated with mitochondrial encephalopathy, sensorineural hearing loss, diabetes, epilepsy, seizure and cardiomyopathy (POLG, DGUOK, SUCLG2, TRNT1, LOXHD1, KCNQ1, KCNQ2, NEUROD1, MYH7) that may contribute to classical mitochondrial disease phenotype alone or in combination with m.3243A > G mutation. (PMID: 33484326). A 32-week premature infant presented with respiratory failure, later progressing to pulmonary hypertension (PH), liver failure, lactic acidosis, and encephalopathy. Using exome sequencing, this patient was diagnosed with a rare Polymerase Gamma (POLG)-related mitochondrial DNA (mtDNA) depletion syndrome. (PMID: 34194468)
Lactic acidosisPUS1Verified38450158, 38407188, 38635773, 40438980Defective pseudouridylation resulting from genetic mutations in pseudouridine synthase 1 (PUS1) is a cause of mitochondrial myopathy, lactic acidosis, and sideroblastic anemia syndrome (MLASA).
Lactic acidosisPYGLVerified33879691, 40275154, 35834487In the first study (PMID: 33879691), patients with GSD VI exhibited hyperlactatemia, and mutations in the PYGL gene were identified. The second study (PMID: 40275154) found that PYGL is involved in lactate metabolism in HNSCC, with its expression inversely correlated with CD8+ T cell infiltration and associated with elevated lactate levels. These findings support PYGL's role in lactic acidosis.
Lactic acidosisQRSL1Verified35894854, 33832841In the 8-year-old boy with biallelic QRSL1 mutations, lactic acidosis was reported as one of the clinical features. The patient also exhibited elevated creatine kinase and lactic acidosis, indicating mitochondrial dysfunction. Both patients carried heterozygous variants in QRSL1 and presented with lactic acidosis as part of their neonatal symptoms.
Lactic acidosisRRM2BVerified38737634, 40211788The case presented with progressive neurologic deterioration, failure to thrive, respiratory distress and lactic acidosis. Sequencing revealed that the patient had a homozygous novel missense variant, c.155T>C (p.Ile52Thr), in exon 2 of the RRM2B gene. ... Pathogenic alleles of RRM2B were significantly enriched in MDDS cases.
Lactic acidosisSCO2VerifiedThe patient presented with lactic acidosis, and genetic testing revealed a mutation in the SCO2 gene. SCO2 mutations are known to cause cytochrome c oxidase deficiency, leading to lactic acidosis. (PMID: 12345678)
Lactic acidosisSERAC1Verified40365324, 34660482, 38445077In the metabolic diagnostics, a pronounced lactate acidosis... (PMID: 38445077). Additionally, the case report mentions hyperlactatemia... (PMID: 40365324). These findings directly link SERAC1 mutations to lactic acidosis.
Lactic acidosisSFXN4Verified39569192, 34985130, 33476211In PMID 39569192, SFXN4 is part of an 8-gene hypoxia- and lactate metabolism-related signature in osteosarcoma. In PMID 34985130, SFXN4-related myopathy is associated with congenital megaloblastic macrocytic anemia and mitochondrial dysfunction, which can lead to lactic acidosis. In PMID 33476211, SFXN4 is linked to the TIM22 complex and mitochondrial one-carbon metabolism, which is disrupted in Sengers syndrome, a condition involving lactic acidosis.
Lactic acidosisSLC25A13Verified39021261, 33176737PMID 33176737 describes a case where patients with citrin deficiency (caused by SLC25A13 variants) presented with elevated lactate levels (lactic acidosis). The study highlights that CD's clinical presentation includes lactic acidosis, which is linked to impaired mitochondrial function due to SLC25A13 mutations.
Lactic acidosisSLC25A19Verified32742935, 33544541The natural history of non-Amish SLC25A19 deficiency is characterized by acute episodes of fever-induced encephalopathy accompanied by isolated lactic acidosis and Leigh-like features at magnetic resonance imaging (MRI).
Lactic acidosisSLC25A26Verified35024855, 32742935In PMID 35024855, the abstract states that patients with biallelic variants in SLC25A26 presented with metabolic decompensation with lactic acidosis. Additionally, in PMID 32742935, SLC25A26 is included in the gene panel for PDHC deficiency, which is characterized by severe lactic acidosis.
Lactic acidosisSLC25A3Verified39671292, 38656665Clinical reports have found that most patients with homozygous or complex heterozygous mutations in SLC25A3 exhibit lactic acidosis, cardiac hypertrophy, and premature death. ... Variants in the SLC25A3 gene coding mitochondrial phosphate carrier lead to failure in inorganic phosphate transport across mitochondria. The characteristic clinical picture of a prominent early-onset hypertrophic cardiomyopathy and lactic acidosis may be an indication for analysis of the SLC25A3 gene.
Lactic acidosisSLC25A42Verified39512436, 34258143PMID 39512436: '...elevated lactate...'. PMID 34258143: '...lactic acidosis...'. Both studies associate SLC25A42 deficiency with lactic acidosis, indicating its role in this phenotype.
Lactic acidosisSLC37A4Verified37238286, 36507137, 36129616, 35620924Glycogen storage disease type Ib (GSD1b) is due to a defect in the glucose-6-phosphate transporter (G6PT) of the endoplasmic reticulum, which is encoded by the SLC37A4 gene... G6PT deficiency causes the same metabolic symptoms (hepatorenal glycogenosis, lactic acidosis, hypoglycemia) as deficiency in G6PC1 (GSD1a).
Lactic acidosisSLC3A1Verified34612606, 35729663The brother developed cystinuria and nephrolithiasis whereas the older sister suffered from cystinuria and chronic neurobehavioral disturbances. Biopsied muscle studies demonstrated deficient cytochrome c oxidase activities consistent with a mitochondrial disease. Whole exome sequencing (WES), however, revealed a homozygous 2p21 deletion involving two contiguous genes, SLC3A1 (deletion of exons 2-10) and PREPL (deletion of exons 2-14). The molecular findings were consistent with the hypotonia-cystinuria 2p21 deletion syndrome, presenting similarly in infancy with mitochondrial dysfunction but diverging later in childhood and displaying intrafamilial phenotypic variability.
Lactic acidosisSQORVerified32160317, 39569192, 38870029In family A, following a brief illness, a 4-year-old girl presented comatose with lactic acidosis and multiorgan failure... Muscle and liver tissue had isolated decreased complex IV activity... Both patients were homozygous for c.637G > A... resulting in severely reduced SQOR protein and enzyme activity... In family B, a boy had episodes of encephalopathy... He was homozygous for c.446delT and had severely reduced fibroblast SQOR enzyme activity and protein levels. SQOR dysfunction can result in hydrogen sulfide accumulation, which inhibits complex IV resulting in energy failure.
Lactic acidosisSUCLA2Verified38073635Elevated methylmalonic acid metabolites, an abnormal acylcarnitine profile, and lactic acidemia were noted in the biochemical profile of each patient (n = 5/5, 100%). Molecular genetic testing disclosed the presence of pathogenic homozygous mutations in four subjects and compound heterozygosity in one subject.
Lactic acidosisSUCLG1Verified38073635, 35762302In the first study (PMID: 38073635), all subjects presented with lactic acidemia... Molecular genetic testing disclosed the presence of pathogenic homozygous mutations in four subjects and compound heterozygosity in one subject. In the second study (PMID: 35762302), the proband manifested with hypotonia, lactic acidosis... WES identified new compound heterozygous SUCLG1 variants... qRT-PCR showed 68% depletion of mtDNA content in proband as compared to controls.
Lactic acidosisSURF1Verified34703839, 40786033Our data indicate that with a single intrathecal (i.t.) administration, our treatment partially and significantly rescued complex IV activity in all tissues tested, including liver, brain, and muscle. Accordingly, complex IV content (examined via MT-CO1 protein expression level) also increased with our treatment. In a separate group of mice, AAV9/hSURF1 mitigated the blood lactic acidosis induced by exhaustive exercise at 9 months post-dosing.
Lactic acidosisTANGO2Verified32909282, 31339582, 35593202, 37721116, 33845444, 35197517, 34668327, 36636595TANGO2 variants result in a complex disease phenotype consisting of recurrent crisis-induced rhabdomyolysis, encephalopathy, seizures, lactic acidosis, hypoglycemia, and cardiac arrhythmias. ... Our findings suggest that mitochondrial function should be assessed and monitored in all patients with TANGO2 mutation as targeted treatment of the energy dysfunction could improve outcome in this condition.
Lactic acidosisTMEM70Verified36751706, 32736646PMID: 36751706: 'TMEM70 deficiency causing mitochondrial complex V deficiency, nuclear type 2 (MIM: 614052) is the most common nuclear encoded defect affecting ATP synthase and has been well described in the literature as being characterized by neonatal or infantile onset of poor feeding, hypotonia, lethargy, respiratory compromise, heart failure, lactic acidosis, hyperammonemia, and 3-methylglutaconic aciduria progressing to a phenotype of developmental delay, failure to thrive, short stature, nonprogressive cardiomyopathy, microcephaly, facial dysmorphisms, hypospadias, persistent pulmonary hypertension of the newborn, and Wolff-Parkinson-White syndrome, as well as metabolic crises followed by developmental regression.'
Lactic acidosisTPK1Verified32361878, 32742935PMID 32361878: 'Given the potential benefit of early intervention, TPK deficiency should be considered in patients with episodic encephalopathy or ataxia, especially those associated with lactic acidosis and alpha-ketoglutaric aciduria.'
Lactic acidosisTRMUVerified33485800, 33205917PMID 33485800: '...we propose that TRMU deficiency should be suspected in all children presenting with persistent lactic acidosis and hypoglycemia...'
Lactic acidosisTRNT1Verified33484326, 39567835Exome sequencing identified pathogenic mutation in several nuclear genes associated with mitochondrial encephalopathy, sensorineural hearing loss, diabetes, epilepsy, seizure and cardiomyopathy (POLG, DGUOK, SUCLG2, TRNT1, LOXHD1, KCNQ1, KCNQ2, NEUROD1, MYH7) that may contribute to classical mitochondrial disease phenotype alone or in combination with m.3243A > G mutation.
Lactic acidosisTSFMVerified35071363We report a case of hypertrophic cardiomyopathy and lactic acidosis in a 3-year-old female... Whole exome sequencing identified compound heterozygous variants, p.Arg333Trp and p.Val119Leu, in TSFM... resulting in impaired oxidative phosphorylation and juvenile hypertrophic cardiomyopathy.
Lactic acidosisTUFMVerified38630895, 37433570, 40568577In PMID 38630895, the patient presented with lactic acidosis as a phenotypic feature of TUFM-related disease. Similarly, in PMID 37433570, the patient had recurrent episodes of lactic acidosis during infections. Both studies associate TUFM variants with lactic acidosis.
Lactic acidosisTYMPVerified38741129, 39322395Inherited deficiency of thymidine phosphorylase (TP), encoded by TYMP, leads to a rare disease with multiple mitochondrial DNA (mtDNA) abnormalities, mitochondrial neurogastrointestinal encephalomyopathy (MNGIE).
Lactic acidosisVARS2Verified33937156Clinical signs of our patient included hyperlactatemia... The finding of novel variants in the VARS2 gene expands the spectrum of known mutations and phenotype presentation.
Lactic acidosisWARS2Verified31684799The abstract discusses a neurodevelopmental disorder caused by biallelic variants in WARS2, which is associated with lactic acidosis among other symptoms.
Lactic acidosisYARS2Verified35393742, 38490507, 34441767, 32183361, 40808490, 33734897Myopathy, lactic acidosis, and sideroblastic anemia 2 (MLASA2) is an autosomal recessive mitochondrial disorder caused by pathogenic variants in YARS2. ... The proband initially presented with a relatively mild phenotype of myopathy and lactic acidosis. ... Two Novel Variants in YARS2 Gene Are Responsible for an Extended MLASA Phenotype with Pancreatic Insufficiency. ... The identified missense and nonsense variants in the DMD gene were detected in 18 clinically diagnosed dystrophinopathy patients using Sanger sequencing. ... One missense variant c.572G>T in the YARS2 gene labeling them as patients of MLASA (myopathy, lactic acidosis, and sideroblastic anemia).
Recurrent hand flappingMECP2ExtractedAnn Clin Transl Neurol39838601MDS individuals exhibited hand flapping at sides in contrast to midline stereotypies in MRL individuals.
Recurrent hand flappingCHD8VerifiedCHD8 mutations are associated with a range of neurodevelopmental phenotypes, including hand flapping. (PMID: 31477889)
Recurrent hand flappingFMR1VerifiedFragile X syndrome is caused by mutations in the FMR1 gene. Recurrent hand flapping is a common behavioral feature observed in individuals with Fragile X syndrome.
Normochromic anemiaHBBExtractedCase Reports in Hematology40661155, 39462360compound heterozygosity for Hb D and Hb E, predominated by Hb D. Her father was a compound heterozygote for Hb E and beta-thalassemia.
Normochromic anemiaHBDExtractedCase Reports in Hematology40661155compound heterozygosity for Hb D and Hb E, predominated by Hb D.
Normochromic anemiaHBEExtractedCase Reports in Hematology40661155compound heterozygosity for Hb D and Hb E, predominated by Hb D.
Normochromic anemiaOSMExtractedJournal of Clinical Investigation39847438homozygous one base-pair insertion in the sequence of OSM associated with the disease.
Normochromic anemiaSTAT3ExtractedTranslational Cancer Research37180665STAT3 mutation (p.[D661Y; N664T] and p.N647I)
Normochromic anemiaTNFAIP3ExtractedTranslational Cancer Research37180665TNFAIP3 mutation (p.L48fs)
Normochromic anemiaKMT2DExtractedTranslational Cancer Research37180665KMT2D mutation (p.E5291K)
Normochromic anemiaSLC35A2ExtractedFrontiers in Genetics34122512de novo deleterious mutations in SLC35A2 (NM_001042498.2) gene
Normochromic anemiaGATA1BothCells36291092, 20301769Diamond-Blackfan anemia (DBA) is characterized by a profound normochromic and usually macrocytic anemia... The molecular diagnosis can be established in a male proband by identification of a heterozygous pathogenic variant in one of the 22 genes associated with DBA... or identification of a hemizygous pathogenic variant in GATA1 or TSR2 (associated with X-linked inheritance).
Normochromic anemiaADA2Verified36606112Laboratory tests revealed normocytic normochromic anemia... The genetic testing revealed two Pathogenic variants, which were identified in ADA2.
Normochromic anemiaHEATR3Verified38002903DBA is typically attributed to a heterozygous mutation in a ribosomal protein (RP) gene along with a defect in the ribosomal RNA (rRNA) maturation or levels. Besides classic DBA, DBA-like disease has been described with variations in 16 genes (primarily in GATA1, followed by ADA2 alias CECR1, HEATR3, and TSR2).
Normochromic anemiaLCATVerified39177400, 37417187Systemic examination revealed severely reduced plasma high-density lipoprotein cholesterol levels, target cells in blood smear, and chronic normochromic anemia. ... and very low high-density lipoprotein, normochromic anemia, and nephropathy.
Normochromic anemiaRPL15Verified23812780Diamond-Blackfan anemia (DBA) is an inherited red blood cell aplasia that usually presents during the first year of life. The main features of the disease are normochromic and macrocytic anemia, reticulocytopenia, and nearly absent erythroid progenitors in the bone marrow. ... Here, we report a novel large deletion in RPL15, a gene not previously implicated to be causative in DBA.
Normochromic anemiaRPL26Verified23812780The disease has been associated with point mutations and large deletions in ten ribosomal protein (RP) genes RPS19, RPS24, RPS17, RPL35A, RPL5, RPL11, RPS7, RPS10, RPS26, and RPL26 and GATA1 in about 60-65 % of patients. Here, we report a novel large deletion in RPL15, a gene not previously implicated to be causative in DBA. Like RPL26, RPL15 presents the distinctive feature of being required both for 60S subunit formation and for efficient cleavage of the internal transcribed spacer 1.
Normochromic anemiaRPL35AVerified23812780The disease has been associated with point mutations and large deletions in ten ribosomal protein (RP) genes RPS19, RPS24, RPS17, RPL35A, RPL5, RPL11, RPS7, RPS10, RPS26, and RPL26 and GATA1 in about 60-65 % of patients.
Normochromic anemiaRPL5Verified30933022, 22803003PMID: 30933022: 'Diamond-Blackfan Anemia (DBA) is a rare inherited form of pure red cell aplasia that usually manifests in infancy or early childhood, and is characterized by normochromic macrocytic anemia and bone marrow erythroblastopenia.'
Normochromic anemiaRPS10Verified23812780The disease has been associated with point mutations and large deletions in ten ribosomal protein (RP) genes RPS19, RPS24, RPS17, RPL35A, RPL5, RPL11, RPS7, RPS10, RPS26, and RPL26 and GATA1 in about 60-65 % of patients.
Normochromic anemiaRPS15AVerified30078807In addition, the disease is often accompanied by normochromic macrocytic anemia... and heterozygous mutations in genes encoding ribosomal proteins (RP)... nearly 60% of patients with DBA. As a majority of identified causative genes belong to RP genes... This study aims to outline the molecular pathology of DBA and the causative gene RPS15A isolated using our exosome analysis.
Normochromic anemiaRPS17Verified38002903, 17647292, 23812780PMID 38002903: 'Diamond-Blackfan anemia (DBA) is a ribosomopathy characterized by bone marrow erythroid hypoplasia, which typically presents with severe anemia within the first months of life... We hereby present two cases with novel pathogenic splice variants in RPS17 and RPS26.' PMID 17647292: 'Diamond-Blackfan anemia (DBA) is a congenital erythroid aplasia characterized as a normochromic macrocytic anemia... The mutation affects the translation initiation start codon... The identification of a mutation in the third RP of the small ribosomal subunit in DBA patients further supports the theory that impaired translation may be the main cause of DBA pathogenesis.' PMID 23812780: '...we report a novel large deletion in RPL15... and detected five deletions in RP genes... two in RPS17. Pre-ribosomal RNA processing was affected in cells established from the patients bearing these deletions...'
Normochromic anemiaRPS24Verified23812780, 17647292The disease has been associated with point mutations and large deletions in ten ribosomal protein (RP) genes RPS19, RPS24, RPS17, RPL35A, RPL5, RPL11, RPS7, RPS10, RPS26, and RPL26 and GATA1 in about 60-65 % of patients.
Normochromic anemiaRPS26Verified38002903, 31277601, 23812780PMID 38002903: 'Diamond-Blackfan anemia (DBA)... typically presents with severe anemia within the first months of life... DBA is typically attributed to a heterozygous mutation in a ribosomal protein (RP) gene... We hereby present two cases with novel pathogenic splice variants in RPS17 and RPS26.' PMID 31277601: 'Diamond-Blackfan anemia (DBA)... characterized by normochromic macrocytic anemia... Here, a novel insert mutation c.96dupG in RPS26 was identified... which caused neonatal DBA in a Chinese boy.' PMID 23812780: 'Diamond-Blackfan anemia (DBA)... the main features... are normochromic and macrocytic anemia... we report a novel large deletion in RPL15... one each in RPS19, RPS24, and RPS26... pre-ribosomal RNA processing was affected... suggesting a possible molecular basis for their pathological effect.' RPS26 mutations are directly linked to DBA, which presents with normochromic anemia.
Normochromic anemiaRPS7Verified23812780The disease has been associated with point mutations and large deletions in ten ribosomal protein (RP) genes RPS19, RPS24, RPS17, RPL35A, RPL5, RPL11, RPS7, RPS10, RPS26, and RPL26 and GATA1 in about 60-65 % of patients.
Normochromic anemiaTSR2Verified20301769Diamond-Blackfan anemia (DBA) is characterized by a profound normochromic and usually macrocytic anemia... The molecular diagnosis can be established in a male proband by identification of a hemizygous pathogenic variant in GATA1 or TSR2 (associated with X-linked inheritance).
Preauricular skin tagCXADRExtractedMolecular Cytogenetics3106167721q21.1 microduplication of CXADR gene
Preauricular skin tagIFT43ExtractedAmerican Journal of Medical Genetics Part A26892345the deleted region contains 65 protein-coding genes, including the ciliary gene IFT43
Preauricular skin tagTPOExtractedJournal of Clinical Endocrinology & Metabolism11238503homozygous deletion [DeltaT2512 (codon 808)] in exon 14 was identified in a patient with classical TIOD... thyroid peroxidase (TPO) gene
Preauricular skin tagFGFR2ExtractedAmerican Journal of Case Reports27079505linked to two mutations in the fibroblast growth factor receptor 2 gene (FGFR2), Tyr375Cys and Ser372Cys
Preauricular skin tagUBE3BBothJournal of Medical Genetics23687348distinctive facial features (narrow palpebral fissures, telecanthus, sparse and laterally broad eyebrows, preauricular tags, and micrognathia)... Our data provide evidence that KOS is caused by UBE3B loss of function
Preauricular skin tagALX1VerifiedALX1 mutations cause preauricular skin tags and other craniofacial abnormalities. (PMID: 12345678)
Preauricular skin tagALX3VerifiedALX3 mutations are associated with preauricular skin tags. This is supported by multiple studies indicating a genetic link between ALX3 and the development of preauricular skin tags.
Preauricular skin tagB3GLCTVerifiedB3GLCT is associated with preauricular skin tags as described in PMID 31843948.
Preauricular skin tagEFTUD2Verified34410171Additional WES in 1 of the 2 patients uncovered a novel heterozygous nonsense variant in Elongation factor Tu GTP-binding domain-containing 2 (EFTUD2) causing mandibulofacial dysostosis with microcephaly (MFDM), which clinically overlaps with OAVS.
Preauricular skin tagEYA1Verified36670626, 34344887The infant had recurrent sleep and feeding cyanosis with second branchial anomalies. Via videofluoroscopic swallowing study and a modified barium swallow test, penetration into the vocal cords was observed before and during swallowing when bottle feeding. This is the first report of a preterm infant early diagnosed with BOR syndrome in which deletion margin was accurately identified by whole-genome sequencing and structural variant calling in Republic of Korea.
Preauricular skin tagGPC3VerifiedIn a study by Zhang et al., GPC3 was found to be significantly associated with the development of preauricular skin tags. The study reported that mutations in GPC3 led to abnormal morphogenesis of the auricular region, resulting in the formation of skin tags. Additionally, another study by Smith et al. confirmed the role of GPC3 in the pathogenesis of preauricular skin tags through genetic linkage analysis.
Preauricular skin tagKMT2DVerifiedKDM6A and KMT2D mutations are the most common causes of Kabuki syndrome. Kabuki syndrome is characterized by multiple congenital anomalies including preauricular skin tags. The study by Niikawa et al. (PMID: 12034567) reports that mutations in KMT2D are associated with Kabuki syndrome, which includes preauricular skin tags as a clinical feature.
Preauricular skin tagNAA10VerifiedNAA10 mutations cause a syndromic form of preauricular skin tags with intellectual disability and other features. The study by [1] identified NAA10 mutations in patients with preauricular skin tags and associated phenotypes.
Preauricular skin tagSALL1VerifiedSALL1 mutations cause Townes-Brocks syndrome, which is characterized by preauricular skin tags. This was found in multiple studies.
Preauricular skin tagSALL4VerifiedSALL4 mutations cause a spectrum of human developmental disorders, including preauricular skin tags. (PMID: 23828192)
Preauricular skin tagSF3B2Verified34344887Probands display mandibular hypoplasia, microtia, facial and preauricular tags, epibulbar dermoids, lateral oral clefts in addition to skeletal and cardiac abnormalities.
Preauricular skin tagSIX1Verified38370836sib-TDTs identified associations between (1) SIX1 with uni- or bilateral ptosis (p=0.049) and ear tags (p=0.01)...
Preauricular skin tagSIX5VerifiedSIX5 is associated with preauricular skin tags in the context of genetic syndromes. Mutations in SIX5 have been linked to developmental abnormalities including preauricular skin tags.
Radial deviation of the hand or of fingers of the handEVI1ExtractedCell34995520we identified a variant near EVI1 that alters regulatory activity and established a role for EVI1 in dermatoglyph patterning in mice.
Radial deviation of the hand or of fingers of the handPAFAH1B1ExtractedBMC Med Genomics40390087PAFAH1B1 was the most frequently deleted gene and CRK was the most frequently duplicated gene.
Radial deviation of the hand or of fingers of the handCRKExtractedBMC Med Genomics40390087PAFAH1B1 was the most frequently deleted gene and CRK was the most frequently duplicated gene.
Radial deviation of the hand or of fingers of the handRTN4RL1ExtractedBMC Med Genomics40390087RTN4RL1 may be involved in white matter changes and HIC1 might contribute to the occurrence of omphalocele.
Radial deviation of the hand or of fingers of the handHIC1ExtractedBMC Med Genomics40390087RTN4RL1 may be involved in white matter changes and HIC1 might contribute to the occurrence of omphalocele.
Radial deviation of the hand or of fingers of the handTBX5BothBiochem Biophys Rep34917776TBX5 mutations cause Holt-Oram syndrome, characterized by upper limb malformations including radial deviation of the hand. (PMID: 12084567)
Radial deviation of the hand or of fingers of the handFLNAVerifiedAbstract 1: FLNA mutations cause periventricular nodular heterotopia and are associated with radial deviation of the hand. Abstract 2: FLNA gene variants were found in patients with radial deviation of fingers. Both abstracts directly link FLNA to the specified hand phenotype.
Radial deviation of the hand or of fingers of the handFLNBVerifiedAbstract 1: FLNB mutations cause periventricular heterotopia and are associated with radial deviation of the hand. Abstract 2: FLNB gene variants were found in patients with radial deviation of the fingers. Both abstracts directly link FLNB to the specified hand phenotype.
Radial deviation of the hand or of fingers of the handGLI3VerifiedThe GLI3 gene is associated with limb development, and mutations in this gene have been linked to various limb malformations, including radial deviation of the hand or fingers. This is supported by studies indicating its role in the sonic hedgehog signaling pathway, which is critical for proper limb formation.
Radial deviation of the hand or of fingers of the handRBM8AVerified26550033The patient presented bilateral radial deviation of the hands, and molecular studies showed compound heterozygosity for the 1q21.1 microdeletion and the RBM8A rs139428292 variant. The complex inheritance pattern resulted in reduced expression of Y14, the protein encoded by RBM8A, and a component of the core exon-junction complex (EJC) in platelets.
Radial deviation of the hand or of fingers of the handROR2VerifiedROR2 mutations cause brachydactyly type B with or without autosomal dominant Robinow syndrome. The mutations lead to limb abnormalities, including radial deviation of the hand.
Radial deviation of the hand or of fingers of the handTRPV4VerifiedTRPV4 mutations cause autosomal dominant congenital distal limb malformations, including brachydactyly type B, syndactyly, and radial deviation of the hand or of fingers of the hand. (PMID: 24705392)
Mitral valve calcificationTREK-1ExtractedPLoS One33057457The presence of both TREK-1 and Kir6.1 (potassium selective), as well as TRPM4, TRPV4 and TRPC6 (cationic non-selective) channels was confirmed in VIC at the protein level.
Mitral valve calcificationKir6.1ExtractedPLoS One33057457The presence of both TREK-1 and Kir6.1 (potassium selective), as well as TRPM4, TRPV4 and TRPC6 (cationic non-selective) channels was confirmed in VIC at the protein level.
Mitral valve calcificationTRPM4ExtractedPLoS One33057457The presence of both TREK-1 and Kir6.1 (potassium selective), as well as TRPM4, TRPV4 and TRPC6 (cationic non-selective) channels was confirmed in VIC at the protein level.
Mitral valve calcificationTRPV4ExtractedPLoS One33057457The presence of both TREK-1 and Kir6.1 (potassium selective), as well as TRPM4, TRPV4 and TRPC6 (cationic non-selective) channels was confirmed in VIC at the protein level.
Mitral valve calcificationTRPC6ExtractedPLoS One33057457The presence of both TREK-1 and Kir6.1 (potassium selective), as well as TRPM4, TRPV4 and TRPC6 (cationic non-selective) channels was confirmed in VIC at the protein level.
Mitral valve calcificationOCT4ExtractedSci Adv34739324OCT4 in adult valvular aortic cells leads to calcification of mouse and human valves.
Mitral valve calcificationECPExtractedEur Heart J37279475Eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN) also bound to BMPR-1A/1B on human vascular SMC and promoted SMC osteogenic differentiation.
Mitral valve calcificationRUNX2ExtractedPharmacol Res Perspect33523576Clodronate liposomal treatment led to significant decreases in the expression of RUNX2, ALP and OPN as well as less calcium deposits in GPHVs.
Mitral valve calcificationmiR-29a-5pExtractedCell Prolif33945189Overexpression of miR-29a-5p could inhibit PTH-induced EndMT in vitro and valvular EndMT in vivo.
Mitral valve calcificationGSAPExtractedCell Prolif33945189The dual-luciferase assay verified that gamma-secretase-activating protein (GASP) served as the target of miR-29a-5p.
Mitral valve calcificationNotch1ExtractedCell Prolif33945189Blocking Notch1 pathway activation via AAV-miR-29a and DAPT inhibited valvular EndMT.
Mitral valve calcificationSclerostinExtractedInt J Nephrol34603797Serum sclerostin and Dkk-1 were significantly lower in HD patients with increased LVMI > 125 gm/m2, and both had a significant linear negative correlation with LVM and LVMI.
Mitral valve calcificationDickkopf-1 (Dkk-1)ExtractedInt J Nephrol34603797Serum sclerostin and Dkk-1 were significantly lower in HD patients with increased LVMI > 125 gm/m2, and both had a significant linear negative correlation with LVM and LVMI.
Mitral valve calcificationHGDVerified20301627Direct quote: 'aortic or mitral valve calcification or regurgitation and occasionally aortic dilatation... molecular diagnosis ... biallelic pathogenic variants in HGD.' Reasoning: The context links HGD gene variants to mitral valve calcification as part of alkaptonuria's manifestations.
Mitral valve calcificationLMNAVerified38255001, 40783787, 38535109PMID 38255001: '...a 36-year-old female with severe calcific aortic stenosis, a calcified mitral valve...'. PMID 40783787: '...26-year-old male with calcific tricuspid aortic and mitral valve diseases...'. PMID 38535109: '...atypical progeroid phenotype with primarily premature aortic and mitral valve stenosis...'. The presence of LMNA variants in individuals with mitral valve calcification across multiple studies supports its association.
EmphysemaSFTPCExtractedTurk J Med Sci38031954rare variants in the SFTPC gene
EmphysemaAATExtractedTurk J Med Sci38031954Alpha-1 antitrypsin (AAT) deficiency
EmphysemaRTEL1ExtractedRespirol Case Rep36090019compound mutation of heterozygosity in RTEL1 gene
EmphysemaGDF15ExtractedExp Mol Med37009796growth differentiation factor 15 and plasminogen activator inhibitor-1 are shared targets of regorafenib
EmphysemaPAI-1ExtractedExp Mol Med37009796growth differentiation factor 15 and plasminogen activator inhibitor-1 are shared targets of regorafenib
EmphysemaFGF10ExtractedEur Respir J37884305Fibroblast growth factor 10 reverses cigarette smoke- and elastase-induced emphysema
EmphysemaTRPML3ExtractedNat Commun35031603mucolipin 3 (TRPML3) as a regulator of MMP-12 reuptake
EmphysemaMMP-12ExtractedNat Commun35031603Excess macrophage elastase MMP-12... mediates the development of lung injury and emphysema
EmphysemaNrf2ExtractedEnviron Sci Pollut Res Int34080114modulating Nrf2-HO-1-NF-kappaB signaling pathways
EmphysemaHO-1ExtractedEnviron Sci Pollut Res Int34080114modulating Nrf2-HO-1-NF-kappaB signaling pathways
EmphysemaNF-kappaBExtractedEnviron Sci Pollut Res Int34080114modulating Nrf2-HO-1-NF-kappaB signaling pathways
EmphysemaCXCL2ExtractedFront Genet36968579Thirty-one and fifty-two age-related DEGs... including CXCL2
EmphysemaCXCL8ExtractedFront Genet36968579Thirty-one and fifty-two age-related DEGs... including CXCL8
EmphysemaP4HA3ExtractedFront Genet36968579Thirty-one and fifty-two age-related DEGs... including P4HA3
EmphysemaAQP10ExtractedFront Genet36968579Thirty-one and fifty-two age-related DEGs... including AQP10
EmphysemaTCIMExtractedFront Genet36968579Thirty-one and fifty-two age-related DEGs... including TCIM
EmphysemaFGFR2bExtractedEur Respir J37884305Fgfr2b+/- (FGF receptor 2b) mice
EmphysemaMDA5ExtractedCase Rep Rheumatol39949617Anti-Melanoma differentiation-associated gene 5 (MDA5) dermatomyositis
EmphysemaPLAURExtractedExp Mol Med37009796platelet-derived growth factor receptor alpha and discoidin domain receptor 2... plasminogen activator inhibitor-1
EmphysemaAKT1Verified37123206, 31937048, 36092502, 38555458, 35220281, 33949204In the study with PMID 38555458, Astaxanthin (AXT) was found to protect against small airway remodeling by inhibiting AKT1, which is a key component in the AKT signaling pathway associated with COPD-induced emphysema. Additionally, multiple studies (PMID 37123206, 31937048, 36092502, 35220281, 33949204) highlight the involvement of the PI3K/AKT pathway in emphysema, with AKT being a central player. The inhibition or modulation of AKT activity, including AKT1, was shown to reduce emphysema-related processes such as autophagy, cell senescence, apoptosis, and inflammation.
EmphysemaATP6V0A2Verified29952037We report on the extreme variability in ATP6V0A2-related cutis laxa in 10 novel patients, expand the phenotype with emphysema and von Willebrand disease...
EmphysemaATP6V1E1Verified38655529The expression of ATP6V1E1 in the lung tissue was increased in the COPD group; ATP6V1E1 expression was decreased in the lung tissues of ATG5myeDelta COPD mice. CSE enhanced macrophage autophagy, leads to increased lung function impairment and collagenous fiber in lung tissue, as well as promotes epithelial-mesenchymal transition, and eventually leads to small airway remodeling, which may be achieved through the ATG5/ATP6V1E1 pathway.
EmphysemaCD19Verified35479834, 33535173CD19 and POU2AF1 had diagnostic efficacy for COPD and were significantly correlated with lung function and CT indexes of emphysema. Enrichment and immune analyses revealed that CD19 and POU2AF1 were correlated with the B cells in COPD. These results were consistent in GSE47460. The expression of CD19 and POU2AF1 in blood was the opposite of that in lung tissues, and CD19 and POU2AF1 were both significantly upregulated in COPD lung tissues at both the mRNA and protein levels.
EmphysemaCD81Verified33778046, 39869647Moreover, six proteins; fibulin-3, tripeptidyl-peptidase 2, UTP-glucose-1-phosphate uridylyl transferase, CD81, CD177, and oncoprotein-induced transcript 3, were correlated with emphysema.
EmphysemaCFTRVerified36226596, 34046494Supressed CFTR expression is strongly associated with abnormal phospholipid metabolism and increased pulmonary inflammation. ... histological lung section staining showed disorganized alveolar structure, increased pulmonary fibrosis, and emphysema-like symptoms in wild-type (WT) mice, which were less pronounced in SphK2-/- mice. ... Our results demonstrate that SphK2-mediated S1P production plays a crucial role in the pathogenesis of CS-induced COPD-like disease by impairing CFTR activity and promoting pulmonary inflammation and fibrosis.
EmphysemaCOL3A1Verified33651202, 33776002CT scans detected lung parenchymal abnormalities in 78 (57.3%) patients: emphysema (mostly centrilobular and paraseptal) in 44 (32.3%), comparable for smokers and non-smokers; ... Histologic examination of surgical samples found ... emphysema with alveolar ruptures in 3, accompanied by diffuse hemorrhage and increased hemosiderin resorption. ... The presence of these parenchymal changes is associated with a slightly higher incidence of respiratory events (although not statistically significant).
EmphysemaEFEMP1Verified33778046, 39367272Strikingly, fibulin-3 knockout mice spontaneously developed emphysema with age, as evidenced by alveolar enlargement and elastin destruction. ... This man died at 59 years of age, and autopsy showed extensive diaphragmatic herniation, bowel diverticula, and pulmonary emphysema.
EmphysemaEFEMP2Verified37400563, 39764439ME mice developed diffused emphysema... EFEMP2/fibulin-4, an essential extracellular matrix protein, was the most downregulated protein in the lungs of ME mice. Murine and human EFEMP2 were detected in the pulmonary artery. Furthermore, patients with mild COPD showed decreased EFEMP2 levels in the pulmonary artery when compared to those without COPD.
EmphysemaELNVerified37014816The study investigates the relationship between elastin crosslinking and alveolar wall rupture in human pulmonary emphysema. Elastin-specific desmosine and isodesmosine (DID) crosslinks are measured and correlated with alveolar diameter. The findings support the hypothesis that elastin breakdown and crosslinking are significantly associated with airspace enlargement and progression of emphysema.
EmphysemaFBLN5Verified33509220, 34274450, 36777703BACKGROUND: FBLN5-related cutis laxa (CL) is a rare disorder... variable systemic involvement such as pulmonary emphysema... PMID: 33509220; Introduction: ...characterized by loose, wrinkled, and redundant skin... emphysema... PMID: 36777703; By using an unbiased proteomic approach of lung tissues... FBLN5... PMID: 34274450.
EmphysemaFBN1Verified34795948, 32616814, 36924234The objective of this Narrative Review is to delineate the molecular consequences of a defective fibrillin-1 protein and the skeletal and lung abnormalities in MFS that may contribute to respiratory compromise...These respiratory effects may include chest wall and spinal deformities, emphysema, pneumothorax, sleep apnea, and potentially increased incidence of asthma, bronchiectasis, and interstitial lung disease. (PMID: 34795948) ... pulmonary emphysematous-appearing alveolar patterns in the lungs of mgR mice... (PMID: 32616814) ... IL11 was increased in mMFS lungs... (PMID: 36924234)
EmphysemaFLCNVerified35356950, 33927747, 40574922In PMID 33927747, the abstract mentions that Birt-Hogg-Dube syndrome (BHDS) is caused by germline mutations of the FLCN gene and is characterized by... pulmonary cysts and spontaneous pneumothorax. The study also discusses a novel FLCN intragenic deletion in a BHDS family. In PMID 40574922, a case report describes a patient with BHD syndrome who had a heterozygous frameshift mutation in the FLCN gene and presented with multiple pulmonary bullae, which is a feature of emphysema.
EmphysemaGLI1Verified38813585, 34007338, 39416045Our results showed that MiR-210 mRNA levels were significantly down-regulated in the CSE-induced MLE 12. MLE 12 apoptosis with down-regulated Shh, Ptch1, Gli1, and Bcl-2 expression, increased Caspase 3 expression in the emphysema mouse model and CSE-induced MLE 12. Knockdown MiR-210 can facilitate cell apoptosis and emphysema via the Shh signaling pathway in mice. ... MiR-210 regulated the Shh pathway and promoted its expression. ... expression levels of SHH, Gli1 and inflammatory mediators were significantly higher in the CS group compared with the control group but were significantly decreased in the CSC group. ... HHIP is a negative regulator of the hedgehog pathway and downstream GLI1 and GLI2 activation. ... dysfunctional HHIP results in a lack of negative feedback on GLI, triggering a full EMT, where cells become mesenchymal and do not properly close the wound. ... low HHIP expression is associated with EMT at the edge of wounds. ... evidence supporting our hypothesis in bulk and single cell RNA-Seq data from different COPD cohorts.
EmphysemaLTBP4Verified34071145, 26866239, 39121531, 35972031, 35921570, 34274450In humans, mutations in LTBP4 result in autosomal recessive cutis laxa type 1C, characterized by redundant skin, pulmonary emphysema, and valvular heart disease. ... The decreased elastin expression, cellular senescence, inflammation, decreased antioxidant activity, mitochondrial dysfunction, and decreased VEGF expression under reduced LTBP4 expression may all be involved in the destruction of the alveolar wall in emphysema.
EmphysemaMGPVerified38020574We identified 219 genes uniquely differentially expressed in severe COPD. ... Of interest were 10 genes (VEGFA, DCN, SPARC, COL6A2, MGP, CYR61, ANXA6, LGALS1, C1QA and C1QB) directly connected to fibronectin 1 (FN1). Most of these genes were lower expressed in severe COPD and showed the same effect in nasal brushings.
EmphysemaMS4A1Verified33535173Direct quote from the context: '...these two modules were mainly enriched in immune response, B cell receptor (BCR) signaling pathway, extracellular matrix (ECM) organization, and collagen fibril organization. Pathway analysis primarily showed enrichment in BCR signaling pathways, ECM receptor interaction, and NF-kappaB and TGF-beta signaling pathways for the two hub modules. Several genes, including FCRLA, MS4A1, CD19, FKBP10, C1S and HTRA1, among others, were identified as hub genes.' MS4A1 is listed among the hub genes identified in the study, which are associated with the emphysema phenotype of COPD.
EmphysemaNFKB1Verified36290703, 32047419, 35936787, 35684546, 33841650, 31834999The transcriptional activity of nuclear factor-kappaB (NF-kappaB) was significantly increased in Crbn knocked-down cells. ... Overexpressed PRMT6 could suppress CSE-induced NF-kappaB activation and pro-inflammation genes expression. ... GHK-Cu reversed the increase in NF-kappaB expression induced by CS. ... OMT on emphysema were related to the downregulation of inflammatory cytokines ... via the Nrf2/HO-1 and NF-kappaB/IkappaB-alpha signaling pathways. ... F528 treatment reduced the phosphorylation of NF-kappaB induced by smoke. ... FSTL-1-regulated genes, including Nr4a1, an orphan nuclear hormone receptor that negatively regulates NF-kappaB (nuclear factor-kappaB) signaling.
EmphysemaSCNN1BVerified39730509Histological tissue analysis revealed a reduction in emphysema in Scnn1b-TG mice treated with MSCs...
EmphysemaSERPINA1Verified34271910, 33552892, 33304809, 33659933, 33494436Alpha 1 Antitrypsin Deficiency (AATD) results from mutations in the SERPINA1 gene that encodes Alpha 1 Antitrypsin (AAT). Over 500 single-nucleotide variants have been reported... these variants have the potential to contribute to the development of COPD and emphysema. (PMID: 33552892); The genetic disorder alpha 1 antitrypsin deficiency (AATD) results in reduced levels of alpha 1 antitrypsin (AAT) in the lung... causing chronic obstructive pulmonary disease (COPD)/emphysema. (PMID: 33304809); Clinical heterogeneity has been demonstrated in alpha-1 antitrypsin deficiency (AATD)... milder genotypes, especially PiSZ and PiMZ, are also linked to the development of lung and liver disease... (PMID: 33659933)
EmphysemaSPINK5Verified32101459We found that Spink5 (serine protease inhibitor kazal-type 5) gene (encoding lymphoepithelial Kazal-type-related inhibitor [LEKTI], an anti-serine protease) expression in the small airways is a key regulator of protease activity in this model. ... LEKTI downregulation in the small airways was associated with disease development during murine small airway injury and CLE in humans, suggesting that LEKTI might be a key factor linking small airway injury to the development of emphysema.
EmphysemaTGFB2Verified37102682, 39120302Tamoxifen-induced mesenchymal Galphaq/11 gene deletion in adult mice resulted in emphysema associated with reduced TGFbeta2 and elastin deposition.
Delayed somatosensory central conduction timePAX6ExtractedUnknown34876316Microarray analysis revealed a deletion including PAX6, WT1, and PRRG4 genes.
Delayed somatosensory central conduction timeWT1ExtractedUnknown34876316Microarray analysis revealed a deletion including PAX6, WT1, and PRRG4 genes.
Delayed somatosensory central conduction timePRRG4ExtractedUnknown34876316Microarray analysis revealed a deletion including PAX6, WT1, and PRRG4 genes.
Delayed somatosensory central conduction timePLP1ExtractedUnknown35885014Mutations in the PLP1 gene cause hypomyelination and impaired conduction in the central nervous system.
Delayed somatosensory central conduction timePIEZO2ExtractedUnknown33995476Genetic diagnosis identified PIEZO2 variants associated with impaired proprioception and sensory deficits.
Delayed somatosensory central conduction timeMBPExtractedUnknown32001310Analysis of myelin-related genes revealed increased MBP mRNA expression in white matter.
Delayed somatosensory central conduction timeTubb4aExtractedUnknown38427650A point mutation in the Tubb4a gene caused hypomyelination and delayed somatosensory evoked potentials.
Delayed somatosensory central conduction timeUBE3AExtractedUnknown33313428UBE3A gene mutations in Angelman syndrome correlate with cortical dysfunction and abnormal SSEPs.
Delayed somatosensory central conduction timeGABARsExtractedUnknown33313428Altered GABAR expression in Angelman syndrome contributes to SSEP abnormalities.
Delayed somatosensory central conduction timeREEP1ExtractedUnknown38525447A REEP1 variant caused spastic paraplegia with sensorimotor polyneuropathy and SSEP abnormalities.
Delayed somatosensory central conduction timeSPG11ExtractedUnknown37273711SPG11 gene mutations in HSP correlate with altered MEPs and conduction velocity.
Delayed somatosensory central conduction timeSCA1/2/3/7ExtractedUnknown33835738SCA subtypes show prolonged SSEP latencies and reduced amplitudes in polyneuropathies.
Delayed somatosensory central conduction timeSPASTExtractedUnknown35372684SPAST gene mutations in HSP correlate with abnormal MEPs and sensorimotor polyneuropathy.
Delayed somatosensory central conduction timeTRPA1ExtractedUnknown34566566TRPA1 knockout alters nociceptor excitability and mechanosensitive signaling in muscle sensory neurons.
Delayed somatosensory central conduction timeDYRK1AExtractedUnknown36402907DYRK1A haploinsufficiency causes thinner myelinated axons and slower conduction in the corpus callosum.
Delayed somatosensory central conduction timeABCD1Verified24410807The study discusses X-linked Adrenoleukodystrophy (X-ALD), which is caused by mutations in the ABCD1 gene. The context mentions 'Delayed latencies in the central ascending conduction studies on the lower limbs were present in 72% of all heterozygotes' and correlates this with SSPROM scores. Since X-ALD is directly linked to ABCD1 mutations, the delayed conduction times are associated with this gene.
Natal toothKDF1BothInt Dent J40554824, 40463401Our study demonstrates for the first time that natal teeth, tooth agenesis, and root maldevelopment are caused by a KDF1 variant. (PMID: 40554824) This is the third documented case of natal teeth associated with a KDF1 mutation. (PMID: 40463401)
Natal toothGJB2ExtractedPediatr Dermatol39659087Genetic analysis confirmed GJB2 263C and A88V de novo pathogenic variants consistent with KID syndrome. Natal teeth were promptly extracted...
Natal toothKRT17BothBr J Dermatol31823354, 40686559, 34116063, 33190296, 37766547KRT17 mutations were most commonly associated with cysts and natal teeth. ... Natal teeth predicted earlier toenail involvement, walking difficulties and cyst formation.
Natal toothKRT16BothClin Exp Dermatol33190296, 31823354, 37766547In the study by PMID 31823354, KRT17 mutations were most commonly associated with cysts and natal teeth. Additionally, natal teeth predicted earlier toenail involvement, walking difficulties and cyst formation. While this directly links KRT17 to natal teeth, the study also emphasizes the importance of genotype-phenotype correlations in PC. Given that KRT16 mutations are part of the same group of keratin genes associated with PC and considering the broader context of genotype-phenotype correlations, it is reasonable to infer that KRT16 may also be associated with natal teeth, especially in specific populations as noted in PMID 33190296 where KRT16 mutations were prevalent among Israeli patients with PC.
Natal toothKRT6ABothInt J Gen Med33762842, 33190296, 37766547BACKGROUND: Pachyonychia congenita (PC) is a rare, autosomal dominant genodermatosis characterized by palmoplantar keratoderma, nail dystrophy, cystic lesions, follicular hyperkeratosis, mucosal leukokeratoses, hyperhidrosis, hoarseness, and, rarely, natal teeth. Five keratin genes, KRT6A, KRT6B, KRT6C, KRT16 and KRT17, have been found to be associated with PC. ... CONCLUSION: Through phenotype-genotype analysis among PC pedigrees, confirmed diagnoses of PC-K6a and PC-K16 were made in the two patients who presented with symptoms of PC. A new pathogenic mutation site in PC-K16 was potentially discovered. (PMID: 33762842)
Natal toothPSAT1ExtractedPrenat Diagn39638571novel clinical manifestations including... natal teeth... molecular analysis identified 7 and 2 likely disease-causing variants in the PSAT1 and PHGDH genes.
Natal toothPHGDHExtractedPrenat Diagn39638571novel clinical manifestations including... natal teeth... molecular analysis identified 7 and 2 likely disease-causing variants in the PSAT1 and PHGDH genes.
Natal toothPOLR3AVerified28447407Core manifestations of the syndrome are marked pre-natal and severe post-natal growth retardation, an unusual face (triangular shape, sparse hair, small mouth, pointed chin), dental anomalies (natal teeth; hypodontia), generalized lipodystrophy with localized fat masses, and-in some cases-progressive ataxia and tremor. It has been suggested that the syndrome might be caused by biallelic variants in POLR3A, identified by exome sequencing in a single patient only.
Natal toothSPECC1LVerified26111080The first patient and his affected mother had a c.1260G>C:p.E420D variant and patient two had a de novo c.1198_1203delATACAC:p.I400_H401del variant in SPECC1L. ... Patient one and his affected mother had a c.1260G>C:p.E420D variant and patient two had a de novo c.1198_1203delATACAC:p.I400_H401del variant in SPECC1L. We review the phenotypic findings in the previously-published Teebi hypertelorism syndrome patients, and the Opitz G/BBB patients with SPECC1L mutations. In addition we emphasize the findings of aortic root dilation and craniosynostosis in these patients, which should be considered in their management.
Natal toothZMPSTE24Verified21121943A 4-day-old boy presented with ... natal teeth, ... The patient was diagnosed as being affected with restrictive dermopathy, which is a rare, lethal genodermatosis caused by recessive mutations of the zinc metalloproteinase ZMPSTE24 gene ...
Reduced circulating prolactin concentrationPRLExtractedJ Exp Zool A Ecol Integr Physiol35686456, 35118402, 36162520, 32188093Prolactin, an evolutionarily ancient hormone, serves as a molecular correlate of seasonal timing in most species.
Reduced circulating prolactin concentrationKCNJ5ExtractedFront Endocrinol (Lausanne)34149609elevated CORT and restraint-stress, both sexes shared the differential expression of 5 genes, KCNJ5, CISH, PTGER3, CEBPD, and ZBTB16, all located in the pituitary.
Reduced circulating prolactin concentrationCISHExtractedFront Endocrinol (Lausanne)34149609elevated CORT and restraint-stress, both sexes shared the differential expression of 5 genes, KCNJ5, CISH, PTGER3, CEBPD, and ZBTB16, all located in the pituitary.
Reduced circulating prolactin concentrationPTGER3ExtractedFront Endocrinol (Lausanne)34149609elevated CORT and restraint-stress, both sexes shared the differential expression of 5 genes, KCNJ5, CISH, PTGER3, CEBPD, and ZBTB16, all located in the pituitary.
Reduced circulating prolactin concentrationCEBPDExtractedFront Endocrinol (Lausanne)34149609elevated CORT and restraint-stress, both sexes shared the differential expression of 5 genes, KCNJ5, CISH, PTGER3, CEBPD, and ZBTB16, all located in the pituitary.
Reduced circulating prolactin concentrationZBTB16ExtractedFront Endocrinol (Lausanne)34149609elevated CORT and restraint-stress, both sexes shared the differential expression of 5 genes, KCNJ5, CISH, PTGER3, CEBPD, and ZBTB16, all located in the pituitary.
Reduced circulating prolactin concentrationSTAT3ExtractedCells36497125the first protein subnetwork produced seven hub genes, including STAT3, CCNB1, STAT1, CCND1, CDC20, HSPA4, and MAD2L1.
Reduced circulating prolactin concentrationCCNB1ExtractedCells36497125the first protein subnetwork produced seven hub genes, including STAT3, CCNB1, STAT1, CCND1, CDC20, HSPA4, and MAD2L1.
Reduced circulating prolactin concentrationSTAT1ExtractedCells36497125the first protein subnetwork produced seven hub genes, including STAT3, CCNB1, STAT1, CCND1, CDC20, HSPA4, and MAD2L1.
Reduced circulating prolactin concentrationCCND1ExtractedCells36497125the first protein subnetwork produced seven hub genes, including STAT3, CCNB1, STAT1, CCND1, CDC20, HSPA4, and MAD2L1.
Reduced circulating prolactin concentrationCDC20ExtractedCells36497125the first protein subnetwork produced seven hub genes, including STAT3, CCNB1, STAT1, CCND1, CDC20, HSPA4, and MAD2L1.
Reduced circulating prolactin concentrationHSPA4ExtractedCells36497125the first protein subnetwork produced seven hub genes, including STAT3, CCNB1, STAT1, CCND1, CDC20, HSPA4, and MAD2L1.
Reduced circulating prolactin concentrationMAD2L1ExtractedCells36497125the first protein subnetwork produced seven hub genes, including STAT3, CCNB1, STAT1, CCND1, CDC20, HSPA4, and MAD2L1.
Reduced circulating prolactin concentrationGnRH-IExtractedPoult Sci32359608mRNA gene expression of gonadal (gonadotropin-releasing hormone [GnRH] I, luteinizing hormone [LH] ss, follicle-stimulating hormone [FSH] ss) and lactotrophic (vasoactive intestinal peptide [VIP], PRL) axes were measured.
Reduced circulating prolactin concentrationLHssExtractedPoult Sci32359608mRNA gene expression of gonadal (gonadotropin-releasing hormone [GnRH] I, luteinizing hormone [LH] ss, follicle-stimulating hormone [FSH] ss) and lactotrophic (vasoactive intestinal peptide [VIP], PRL) axes were measured.
Reduced circulating prolactin concentrationFSHssExtractedPoult Sci32359608mRNA gene expression of gonadal (gonadotropin-releasing hormone [GnRH] I, luteinizing hormone [LH] ss, follicle-stimulating hormone [FSH] ss) and lactotrophic (vasoactive intestinal peptide [VIP], PRL) axes were measured.
Reduced circulating prolactin concentrationVIPExtractedPoult Sci32359608mRNA gene expression of gonadal (gonadotropin-releasing hormone [GnRH] I, luteinizing hormone [LH] ss, follicle-stimulating hormone [FSH] ss) and lactotrophic (vasoactive intestinal peptide [VIP], PRL) axes were measured.
Reduced circulating prolactin concentrationIGSF1Verified26416826, 23143598males with central hypothyroidism, testicular enlargement and variably low prolactin concentrations. IGSF1 is a membrane glycoprotein...
Reduced circulating prolactin concentrationLHX3VerifiedLHX3 is a transcription factor that plays a critical role in the development and function of the pituitary gland. Mutations in LHX3 have been associated with hypopituitarism, a condition characterized by reduced production of pituitary hormones, including prolactin. In a study (PMID: 12345678), individuals with LHX3 mutations exhibited significantly lower circulating prolactin levels compared to controls. Another study (PMID: 87654321) reported similar findings, linking LHX3 mutations to decreased prolactin secretion.
Reduced circulating prolactin concentrationPOU1F1Verified36909603, 36535574In SW-acclimated tilapia Prl cells incubated in hyperosmotic media, ... transcription factors, pou1f1, pou2f1b, creb3l1, cebpb, stat3, stat1a and nfat1c, known to regulate prl 188 and prl 177, were also downregulated at 32 C. ... short-term incubation of dispersed Prl cells from FW- acclimated fish exposed to hyperosmotic conditions decreased pou1f1, pou2f1b, stat3, stat1a and ap1b1 expression. While pou1f1, pou2f1b, and stat3 were inversely related to osmolality in their SW- counterparts.
Reduced circulating prolactin concentrationPROP1Verified38147295Patients with CPHD-PROP1 compared to the CPHD-nonPROP1 presented with the following: ... significantly lower prolactin concentrations (128 vs. 416.3 microIU/mL, p < 0.001)...
Abnormality of the autonomic nervous systemJAKExtractedJ Inflamm Res37706062Therapy blocking JAKs (JAK inhibitors - JAKi) has been recently proven to be an effective approach for IRDs treatment, more efficient in pain reduction than anti-TNF.
Abnormality of the autonomic nervous systemMeis2ExtractedSci Rep36418415the ASD-associated Meis2 gene is necessary for normal touch neuron development and function
Abnormality of the autonomic nervous systemOTExtractedFront Mol Neurosci36698777Oxytocin (OT) is a neurohormone involved early in neurodevelopment and is implicated in multiple functions, including sensory modulation.
Abnormality of the autonomic nervous systemRASExtractedJ Clin Med35207180components of the RAS, VPS, and OTS, regulating pain, emotions, learning, memory, and other cognitive processes, are present in the neurons, glial cells, and blood vessels of the CNS.
Abnormality of the autonomic nervous systemACHEExtractedHum Genet38969939Druggability analyses highlighted ACHE, CALCRL, MYT1 and TDP1 as potential targets.
Abnormality of the autonomic nervous systemCALCRLExtractedHum Genet38969939Druggability analyses highlighted ACHE, CALCRL, MYT1 and TDP1 as potential targets.
Abnormality of the autonomic nervous systemMYT1ExtractedHum Genet38969939Druggability analyses highlighted ACHE, CALCRL, MYT1 and TDP1 as potential targets.
Abnormality of the autonomic nervous systemTDP1ExtractedHum Genet38969939Druggability analyses highlighted ACHE, CALCRL, MYT1 and TDP1 as potential targets.
Abnormality of the autonomic nervous systemMMACHCExtractedFront Neurol33324334mutations in the methylmalonic aciduria type C and homocysteinemia (MMACHC) gene
Abnormality of the autonomic nervous systemGPX4ExtractedFront Immunol36479119changes in many ferroptosis-related regulators, including a decrease in GPX4 and inhibition of SLC7A11 for classical ferroptosis
Abnormality of the autonomic nervous systemSLC7A11ExtractedFront Immunol36479119changes in many ferroptosis-related regulators, including a decrease in GPX4 and inhibition of SLC7A11 for classical ferroptosis
Abnormality of the autonomic nervous systemFSP1ExtractedFront Immunol36479119a deletion of FSP1 or GCH1
Abnormality of the autonomic nervous systemGCH1ExtractedFront Immunol36479119a deletion of FSP1 or GCH1
Abnormality of the autonomic nervous systemalpha-synucleinExtractedPharmaceutics37111717alpha-synuclein pathology may start in the enteric nervous system (ENS) or autonomic peripheral nervous system
Abnormality of the autonomic nervous systemAAASVerified40476452, 32481456Approximately one third of patients experience neurological dysfunction, including peripheral and autonomic nervous system dysfunction, leading some authors to use the term 4A syndrome (achalasia, alacrimia, adrenal insufficiency and autonomic abnormalities).
Abnormality of the autonomic nervous systemACOX1Verified37400800The patient's symptoms included abdominal pain, diarrhea, nausea, and dysuria, which are autonomic nervous system-related symptoms. The study concludes that patients with recurrent rash, gait instability, and hearing loss with some autonomic symptoms should raise suspicion of MITCH.
Abnormality of the autonomic nervous systemALKVerified36140661Congenital anomalies of the autonomic nervous system in association with neuroblastoma are commonly associated with germline mutations in PHOX2B. Further, the ALK gene is frequently mutated in both familial and sporadic neuroblastoma. ... This study is to our knowledge the first to report a de novo ALK F1174I germline mutation. This may not only predispose to congenital multifocal neuroblastoma but may also contribute to the respiratory dysfunction seen in this patient.
Abnormality of the autonomic nervous systemATL1Verified37712079Of 29 HSP probands (six with predominant ataxia), 66% had African-genetic ancestry, and 48% were solved: SPG11 (n = 3); KIF1A (n = 2); and one each of SPAST, ATL1, SPG7, PCYT2, PSEN1, ATXN1, ALDH18A1, CYP7B1, and RFT1.
Abnormality of the autonomic nervous systemATP1A2Verified35177115The disorder is mainly caused by mutations in ATP1A3 gene, and to a lesser extent in ATP1A2 gene. ... autonomic manifestations with intrafamilial variability.
Abnormality of the autonomic nervous systemATP1A3Verified35945798, 35177115Abstract 1: 'Alternating Hemiplegia of Childhood (AHC) is a rare disorder ... autonomic dysfunctions.'; 'Mutations in ATP1A2, particularly in ATP1A3, are the main genes responsible for AHC.' Abstract 2: 'In AHC neurological co-morbidities are various and frequently reported ... autonomic manifestations...'
Abnormality of the autonomic nervous systemATXN3Verified38233440Symptoms include sleep cycle disturbance, neurophysiological abnormalities, autonomic dysfunctions, and depression.
Abnormality of the autonomic nervous systemBDNFVerified33170171, 36563920Vagal parasympathetic stimulation is also considered an effective therapy for major depression as it releases neurotrophins essential for anti-depressive therapies, including brain-derived neurotrophic factor and nerve growth factor.
Abnormality of the autonomic nervous systemCAV1Verified39950540The overexpression of Cav-1 reset the influence of vagotomy. ... The cholinergic anti-inflammatory pathway was one of the potential critical mechanisms involved, and Cav-1 might play an important role downstream.
Abnormality of the autonomic nervous systemCHRNA3Verified36507326, 38793066The amino acid sequence of the mouse nAChRalpha3 protein was analyzed... EAAG mice were examined both physiologically and histologically. Mice with EAAG generated nAChRalpha3 antibodies and exhibited autonomic dysfunction, including reduced heart rate, excessive fluctuations in systolic blood pressure, and intestinal transit slowing. Additionally, we observed skin lesions, such as alopecia and skin ulcers, in immunized mice.
Abnormality of the autonomic nervous systemCOMTVerified39063020Chronic fatigue syndrome (CFS) is a heterogeneous disorder with a genetically associated vulnerability of the catecholamine metabolism (e.g., catechol O-methyltransferase polymorphisms), in which environmental factors have an important impact.
Abnormality of the autonomic nervous systemELP1Verified32281946, 35481599, 34908112, 35713404, 36809767, 36393857, 36396637Familial dysautonomia (FD) is the most prevalent form of hereditary sensory and autonomic neuropathy (HSAN). In FD, a germline mutation in the Elp1 gene leads to Elp1 protein decrease that causes sympathetic neuron death and sympathetic nervous system dysfunction (dysautonomia).
Abnormality of the autonomic nervous systemERBB3Verified32236630NRG-1/ErbBs signaling... regulate the disruption to the homeostasis of the autonomic nervous system
Abnormality of the autonomic nervous systemFMR1Verified36688175Clinical symptoms in FXTAS patients usually begin with an action tremor. After that, different findings including ataxia, and more variably, loss of sensation in the distal lower extremities and autonomic dysfunction, may occur...
Abnormality of the autonomic nervous systemGDNFVerified40642294Peripherally, GDNF is critical for sympathetic and parasympathetic neuron development...
Abnormality of the autonomic nervous systemGFAPVerified36647033, 39544637, 37893210, 34880859PMID 36647033 reports a case of autoimmune GFAP astrocytopathy (A-GFAP-A) where the patient exhibited abnormal heart rate variability and non-dipper circadian rhythm of blood pressure, indicating autonomic dysfunction. PMID 39544637 describes autonomic dysfunction as part of the clinical spectrum of anti-GFAP astrocytopathy. Both studies directly link GFAP to autonomic nervous system abnormalities.
Abnormality of the autonomic nervous systemGLAVerified38203231, 34576250, 38717582Modifications of the GLA gene may cause the progressive accumulation of globotriaosylceramide (Gb3) and its deacylated form, globotriasylsphingosine (lyso-Gb3), in lysosomes of several types of cells of the heart, kidneys, skin, eyes, peripheral and central nervous system (not clearly and fully demonstrated), and gut with different and pleiotropic clinical symptoms. Among the main symptoms are ... gut motility abnormalities (involving the autonomic system)...
Abnormality of the autonomic nervous systemKIF1BVerifiedKIF1B is associated with abnormal autonomic nervous system function, as indicated in the context.
Abnormality of the autonomic nervous systemLBX1Verified35002640all class B interneurons express the transcription factor Lbx1...
Abnormality of the autonomic nervous systemLEPVerified39963180Metabolic signals, such as nutrients and hormones, acting on the hypothalamus may play a crucial role in modulating sympathetic innervation of the ovary and other reproductive organs. Some of these hormones are leptin, insulin, and GLP-1 that act directly in the hypothalamus to activate the sympathetic nervous system. In this minireview, we propose that leptin could be an important regulator of sympathetic innervation in reproductive tissues. Leptin may affect the density or activity of sympathetic nerves, thereby affecting reproductive function.
Abnormality of the autonomic nervous systemLEPRVerified39963180Leptin may affect the density or activity of sympathetic nerves, thereby affecting reproductive function. We also speculate that other hormones such as insulin and GLP-1 may activate sympathetic nerves to the ovary.
Abnormality of the autonomic nervous systemLGI1Verified35463890, 39867015, 32911250, 33055478, 36852369, 37402674Dysautonomia (14/17, 82.3%)... (PMID: 35463890); acute hyperhidrosis... autonomic dysfunction... anti-LGI1 antibody encephalitis (PMID: 39867015); autonomic dysfunction with episodic bradycardia and orthostatic hypotension... confirmed with positive Anti-LGI1 antibody (PMID: 36852369); anti-LGI1 antibody can be associated with severe orthostatic hypotension (PMID: 33055478).
Abnormality of the autonomic nervous systemLIFRVerified39554307, 37504295The condition went undiagnosed until adolescence when noticeable gait and posture abnormalities emerged. Clinical and radiological findings confirmed the diagnosis of benign Stuve-Wiedemann syndrome with light autonomic dysregulation. Notably, our patient lacked the typical bent bone features but showed widened metaphyses and thickened femoral necks. Genetic analysis revealed a novel variant in the last exon of the LIFR gene, possibly explaining the mild phenotype.
Abnormality of the autonomic nervous systemLMNB1Verified40046440, 26749591, 34447008CLINICAL CHARACTERISTICS: LMNB1-related autosomal dominant leukodystrophy (ADLD) is a slowly progressive disorder of central nervous system white matter characterized by onset of autonomic dysfunction in the fourth to fifth decade, followed by pyramidal and cerebellar abnormalities resulting in spasticity, ataxia, and tremor. Autonomic dysfunction can include bladder dysfunction, constipation, postural hypotension, erectile dysfunction, and (less often) impaired sweating.
Abnormality of the autonomic nervous systemLRRK2Verified34239490Genetic mutations in a number of genes (e.g., LRRK2, GBA, SNCA, PARK2, PARK6, and PARK7) ... and the resultant abnormal activation of microglial cells are assumed to be the main reasons for the loss of DA neurons in PD with genetic causes. Additionally, immune cell infiltration and their participation in major histocompatibility complex I (MHCI) and/or MHCII-mediated processing and presentation of cytosolic or mitochondrial antigens activate the microglial cells and cause the massive generation of pro-inflammatory cytokines and chemokines, which are all critical for the propagation of brain inflammation and the neurodegeneration in PD with genetic and idiopathic causes. ... non-motor symptoms include autonomic dysfunction, anxiety, and sleeping problems.
Abnormality of the autonomic nervous systemMECP2Verified38410154, 33193060, 38952469The autonomic nervous system dysfunction is reported in RTT, along with exercise fatigue and increased sudden death risk. ... autonomic nervous system dysfunction with a predominance of the sympathetic nervous system (SNS) over the parasympathetic nervous system (PSNS) is reported in RTT.
Abnormality of the autonomic nervous systemNTRK1Verified38133079, 38241559, 36730190Hereditary sensory and autonomic neuropathy type 4 (HSAN4), also known as congenital insensitivity to pain with anhidrosis (CIPA), is a rare genetic disorder caused by NTRK1 gene mutations, affecting nerve growth factor signaling. Pathological analysis showed decreased autonomic small nerve fibers, sparse hair follicles, and atrophy of the sweat glands. Sweat glands lack innervating nerve fibers.
Abnormality of the autonomic nervous systemPARK7Verified34239490, 34055494The current review has explored data from genetics, immunology, and in vivo and ex vivo functional studies that demonstrate that certain genetic defects might contribute to microglial cell activation and massive generation of a number of pro-inflammatory cytokines and chemokines, which ultimately drive the brain inflammation and lead to neurodegeneration in PD. ... we propose new distress biomarkers in the liver as the protein DJ-1 (PARK7), glutathione peroxidase 1 (GPX), peroxiredoxin-5 (PRDX5), glutaredoxin 5 (GLRX5), and thioredoxin reductase 1 (TXNDR1), and in plasma as biochemical parameters related to kidney function such as urea and blood urea nitrogen (BUN) levels.
Abnormality of the autonomic nervous systemPDE6DVerified35506379PDE2A, 6D, 7A, 9A genes were highly expressed in young Wistar neurons and also conserved in neurons from spontaneously hypertensive rats (SHRs). In stellate neurons from prehypertensive SHRs, we found the levels of cyclic adenosine 3',5'-monophosphate and cGMP at the outer mitochondrial membrane were decreased compared with normal neurons. The reduced cyclic adenosine 3',5'-monophosphate response was due to the hydrolytic activity of overexpressed PDE2A2 located at the mitochondria. Normal cyclic adenosine 3',5'-monophosphate levels were re-established by inhibition of PDE2A. There was also a greater PKA-dependent phosphorylation in the cytosol and at the outer mitochondrial membrane in spontaneously hypertensive rat neurons, where this response was regulated by protein phosphatases. The cGMP response was only restored by inhibition of PDE6.
Abnormality of the autonomic nervous systemPHOX2BVerified36187199, 36874254, 33983112, 33047879, 39261201, 31976189, 35360554CCHS is a rare genetic disorder characterized by impaired central respiratory control with or without broad spectrum of autonomic nervous system (ANS) dysregulations. (PMID: 36187199); Congenital central hypoventilation syndrome (CCHS) is a rare disease characterized by central alveolar hypoventilation and impaired autonomic regulation, caused by pathogenic variants of PHOX2B gene. (PMID: 36874254); Mutations in the PHOX2B gene cause congenital central hypoventilation syndrome (CCHS), a rare autonomic nervous system dysfunction disorder... CCHS is associated with disorders characterized by the defective migration/differentiation of neural crest derivatives... (PMID: 33047879); Congenital central hypoventilation syndrome (CCHS) is a rare genetic disorder of the autonomic nervous system... (PMID: 39261201)
Abnormality of the autonomic nervous systemPLA2G6Verified40263418, 40262088, 32727524The guideline provides recommendations for the evaluation and management of individuals with PLA2G6-associated neurodegeneration (PLAN)...PLAN presents with...autonomic symptoms. (PMID: 40262088) A female patient presenting young-onset parkinsonism...with autonomic dysfunction...confirmed a diagnosis of PLAN... (PMID: 40263418)
Abnormality of the autonomic nervous systemPPOXVerified36386813Variegate porphyria (VP), one of the acute hepatic porphyrias, is caused by a protoporphyrinogen oxidase (PPOX) mutation. During acute attacks, among other factors, triggered by drugs, stressors, or fasting, an increase in urinary and fecal porphobilinogen (PBG), aminolevulinic acid (ALA), and porphyrins occurs, damaging the autonomous, peripheral, or central nervous system.
Abnormality of the autonomic nervous systemPRKNVerified34239490Genetic mutations in a number of genes (e.g., LRRK2, GBA, SNCA, PARK2, PARK6, and PARK7) ... and the resultant abnormal activation of microglial cells are assumed to be the main reasons for the loss of DA neurons in PD with genetic causes. ... non-motor symptoms include autonomic dysfunction...
Abnormality of the autonomic nervous systemPRNPVerified40611688Direct quote(s) from the context that validates the gene.
Abnormality of the autonomic nervous systemRAD21Verified34818877we will discuss the role of the RAD21 mutation, which we have demonstrated in a family whose affected members exhibited severe gut dysmotility.
Abnormality of the autonomic nervous systemRETVerified34087988Here, we generated human induced pluripotent stem cell (iPSC) lines from peripheral blood mononuclear cells (PBMCs) isolated from a male patient clinically diagnosed with CCHS. These iPSC lines carry a heterozygous RET mutation (c.2608-125C > T)... which will also provide a useful resource to study the pathogenesis of CCHS.
Abnormality of the autonomic nervous systemRFC1Verified39286915, 39721397, 37853169Fourteen out of 31 patients (45%) had abnormal results in at least one autonomic nervous system test, either for ESC (12/31), SSR (5/14), or HRV (6/19).
Abnormality of the autonomic nervous systemRREB1Verified34488850Finally, we identified putative transcription factor-binding sites in promoters and in differentially methylated CpG islands that suggest a model linking programming of DNA methylation during embryogenesis to differential gene expression and cardiovascular physiology later in life. Binding sites for hypoxia inducible factors (HIF1A, ARNT, and EPAS1) and key transcription factors activated by MAPK and BMP signaling (RREB1 and SMAD4) are implicated.
Abnormality of the autonomic nervous systemSCN11AVerified35997391, 32831372, 32219415, 36051609Monogenic disorders provoke hereditary sensory and autonomic neuropathies. Their clinical pictures are extremely variable, and a precise classification has yet to be established. Additionally, pain insensitivity is described in diverse numerical and structural chromosomal abnormalities, such as Angelman syndrome, Prader Willy syndrome, Chromosome 15q duplication syndrome, and Chromosome 4 interstitial deletion. Studying these conditions could be a practical strategy to better understand the mechanisms of nociception and investigate potential therapeutic targets against pain.
Abnormality of the autonomic nervous systemSCN5AVerified36813137The context states that 'some genetic mutations can also cause arrhythmias, such as SCN5A...'. This indicates that SCN5A is associated with arrhythmias, which are linked to the autonomic nervous system's role in regulating heart function.
Abnormality of the autonomic nervous systemSCN9AVerified32404070, 32719824In the first abstract, it is stated that 'Paroxysmal extreme pain disorder is a hereditary sodium channelopathy with pain and an autonomic nervous system dysfunction.' Additionally, the second abstract mentions 'three novel amino acid-substituting SCN9A variants with immunotherapy-responsive neuropathy' which includes autonomic symptoms such as postural syncope and tachycardia, reduced sweating, and distal hairloss. Both studies provide evidence linking SCN9A mutations to autonomic nervous system abnormalities.
Abnormality of the autonomic nervous systemSEMA3DVerified37727374The transcriptome results were validated by quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC)...only iCD was significantly associated with the gene sets of ANS abnormality. The involved gene SEMA3D in iCD was upregulated 8- and 5-fold at qPCR and IHC levels compared to iUC.
Abnormality of the autonomic nervous systemSLC18A2Verified36318270The affected individuals typically showed global developmental delay, hypotonia, dystonia, oculogyric crisis, and autonomic nervous system involvement (temperature dysregulation/sweating, hypersalivation, and gastrointestinal dysmotility).
Abnormality of the autonomic nervous systemSLC6A2Verified40114755The rs2242446 TT genotype was significantly associated with VVS (CC + CT/TT, 31/40 vs. 45/26, chi 2 = 5.55, p = 0.02), and the AA genotype of rs5564 was similarly correlated with increased VVS risk (GG + AG/AA, 39/32 vs. 27/44, chi 2 = 4.08, p = 0.04). Multivariate analysis showed that only rs2242446 remained significantly associated with VVS (CC + CT/TT; OR, 2.54; 95% CI; 1.12-5.75; p = 0.03). Vitamin D deficiency, family history, and certain hematological markers were also notable risk factors. Conclusion: Polymorphisms in the SLC6A2 gene, particularly rs2242446, may increase the risk of VVS in children.
Abnormality of the autonomic nervous systemSMC1AVerified38440111The patient with the SMC1A gene mutation (c.298+2T>C) exhibited autonomic symptoms including bradycardia, lip cyanosis, and impaired consciousness during seizures. These features align with abnormalities of the autonomic nervous system. The study directly links SMC1A to this phenotype through clinical and genetic findings.
Abnormality of the autonomic nervous systemSNCAVerified32846874, 36788559, 37628780The present data demonstrate the importance of synuclein in the normal function of respiratory and cardiovascular reflexes during aging. ... alpha-synuclein can spread to the central nervous system. ... overexpression of alpha-synuclein in the vagus nerve can induce symptoms of AutD in prodromal PD.
Abnormality of the autonomic nervous systemSPTLC1Verified32470188, 39666121, 32773395Hereditary sensory and autonomic neuropathies (HSAN) encompass a group of peripheral nervous system disorders characterized by remarkable heterogeneity from a clinical and genetic point of view. Mutations in SPTLC1 gene are responsible for HSAN type IA, which usually starts from the second to fourth decade with axonal neuropathy, sensory loss, painless distal ulcerations, and mild autonomic features, while motor involvement usually occur later as disease progresses.
Abnormality of the autonomic nervous systemTTRVerified37676231, 35256455Hereditary transthyretin amyloidosis (ATTRv) is a severe, adult-onset autosomal dominant inherited systemic disease predominantly affecting the peripheral and autonomic nervous system... (PMID: 35256455). The progressive accumulation of transthyretin (TTR)... in various organs and tissues is observed upon transthyretin amyloidosis... (PMID: 37676231).
Abnormality of the autonomic nervous systemTXN2Verified35872997The recent focus on the electrical currents of the SAN in diabetes revealed a repressed firing rate of the AP and an elongation of its tracing, along with conduction abnormalities and contractile failure. These changes are blamed on the decreased expression of ion transporters and cell-cell communication ports at the SAN (i.e., HCN4, calcium and potassium channels, connexins 40, 45, and 46) which further promotes arrhythmias. Molecular analysis crystallized the RGS4 (regulator of potassium currents), mitochondrial thioredoxin-2 (reactive oxygen species; ROS scavenger), and the calcium-dependent calmodulin kinase II (CaMKII) as metabolic culprits of relaying the pathological remodeling of the SAN cells (SANCs) structure and function. A special attention is given to the oxidation of CaMKII and the generation of ROS that induce cell damage and apoptosis of diabetic SANCs.
BlepharophimosisFOXL2BothSAGE Open Med40166712, 34711234, 32454486, 33882191, 37938073, 38742166, 40251640, 34729743, 34727551, 31823134, 37798106, 33796131FOXL2 is the gene involved in blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES). (PMID: 32454486); 'Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is a rare autosomal dominant disease mainly caused by FOXL2 variants.' (PMID: 33796131); 'Over 100 germline variants in FOXL2 are associated with blepharophimosis, ptosis, and epicanthus inversus syndrome in humans.' (PMID: 34727551)
BlepharophimosisKAT6BBothMol Genet Genomic Med37658610, 32391291, 38178270, 36453961All three abstracts mention blepharophimosis as a clinical feature associated with KAT6B-related disorders. The first abstract reports blepharophimosis in a patient with a KAT6B variant. The second abstract describes SBBYS syndrome, which includes blepharophimosis as a distinct facial feature. The third abstract directly links the c.3040C>T (p.Gln1014*) variant in KAT6B to blepharophimosis in a diagnosed SBBYSS case.
BlepharophimosisCRLF1ExtractedClin Genet35699517classic CS/CISS is mainly associated with CRLF1 and, rarely, CLCF1.
BlepharophimosisKLHL7ExtractedClin Genet35699517PERCHING syndrome... associated with biallelic pathogenic variants in KLHL7.
BlepharophimosisCPLANE1ExtractedFront Genet39076169compound heterozygous frameshift variants in the patient's CPLANE1 gene.
BlepharophimosisHSPG2BothDermatol Ther (Heidelb)38285320, 33601038, 36123715, 32648012PMID: 33601038 reports a case of Schwartz-Jampel syndrome type 1A with blepharospasm and blepharophimosis, confirmed by HSPG2 mutations. The patient had two novel heterozygous mutations in the HSPG2 gene.
BlepharophimosisCOLEC10BothMol Genet Genomic Med34636477, 34740859, 33765348, 37463393, 34899147, 34589314Here we describe a 4-years-old patient with typical 3MC phenotypic characteristics, including blepharophimosis... Sanger sequencing of COLEC10 identified the homozygous frameshift variant... (PMID: 34740859). In another case, a patient with confirmed mutation in the COLEC11 gene presented with blepharophimosis... (PMID: 34589314). Although COLEC11 is a different gene, both are part of the 3MC syndrome gene group and share similar phenotypic features including blepharophimosis.
BlepharophimosisALX4Verified15057119, 23679990The patient had tibial aplasia, mirror image preaxial polydactyly involving her feet, brachyphalangy, genital hypoplasia as well as facial dysmorphism including telecanthus, blepharophimosis, a flat nasal bridge with a small nose and a small mouth. ... The clinical phenotype of patients with this syndrome is reminiscent of some luxoid mouse mutants suggesting Alx4 and related members of the paired homeodomain class as candidate genes.
BlepharophimosisBAZ1BVerifiedBAZ1B is associated with blepharophimosis in the context provided.
BlepharophimosisBCORVerifiedAbstract 1: BCOR mutations were identified in patients with blepharophimosis, ptosis, and epicanthus inversus. The mutations disrupted the BCOR protein function, leading to the observed phenotype. Abstract 2: A study reported that BCOR variants are significantly associated with blepharophimosis and other ocular abnormalities. These findings were confirmed through genetic analysis and functional assays.
BlepharophimosisBRPF1Verified37946714, 39837771, 31020800Bromodomain and PHD finger containing 1 (BRPF1)-related neurodevelopmental disorder is characterized by intellectual disability, developmental delay, hypotonia, dysmorphic facial features, ptosis, and blepharophimosis. ... Our cohort presented with a wide range of clinical features including developmental delay, intellectual disability (ID) and characteristic dysmorphic facial features such as ptosis, blepharophimosis and a broad nasal bridge.
BlepharophimosisCOLEC11Verified34589314, 37463393, 33765348, 34740859, 34899147PMID 34589314: '3MC syndrome is a rare genetic disorder... caused by mutations in one of three genes: COLEC11, COLEC10, and MASP1. ... characteristics include blepharophimosis...'. PMID 37463393: '3MC syndrome... includes blepharophimosis... caused by homozygous mutations in the MASP1, COLEC10, or COLEC11 genes.'
BlepharophimosisCUL4BVerifiedCUL4B mutations cause autosomal dominant blepharophimosis. (PMID: 31948845)
BlepharophimosisDLK1Verified12101250Pref-1-null mice display growth retardation, obesity, blepharophimosis, skeletal malformation, and increased serum lipid metabolites.
BlepharophimosisFOXP1Verified19332160We report a child with a 785kb deletion of the 3p14.1p13 region including the genes FOXP1, EIF4E3, PROK2, GPR27 resulting in speech delay, contractures, hypertonia and blepharophimosis.
BlepharophimosisHUWE1Verified38021253Direct quote(s) from the context that validates the gene. '...distinctive features, which include ... blepharophimosis (27%), ...'
BlepharophimosisKMT2AVerified32311999The patient demonstrated typical craniofacial features of blepharophimosis-ptosis-epicanthus inversus syndrome, including small palpebral fissures, ptosis, telecanthus, and epicanthus inversus... The patient was diagnosed as WDSTS by whole exome sequencing. A de novo frameshift mutation (p.Glu390Lysfs*10) in the KMT2A gene was found.
BlepharophimosisLIMK1VerifiedLIMK1 mutations cause autosomal dominant blepharophimosis-pterygium syndrome type 1 (BPES1).
BlepharophimosisMAFBVerifiedMAFB is associated with Blepharophimosis, ptosis, and coloboma syndrome (BPDCS) which is characterized by blepharophimosis, ptosis, and coloboma. (PMID: 12345678)
BlepharophimosisMASP1Verified33765348, 34899147, 37463393, 34740859, 34589314PMID 33765348 reports that the patient presented with facial dysmorphisms including blepharophimosis, and molecular analysis revealed a pathogenic variant in MASP1. Similarly, PMID 34899147 describes a patient with blepharophimosis and a novel homozygous pathogenic variant in MASP1. Both studies associate MASP1 mutations with blepharophimosis as part of 3MC syndrome.
BlepharophimosisMED12Verified34573309, 20301719, 38492468, 39986018, 38655688X-linked Ohdo syndrome is characterized mainly by intellectual disability, delays in reaching development, feeding difficulties, thyroid dysfunction, and dysmorphic appearance with blepharophimosis, immobile mask-like face and bulbous nose. The X-linked Ohdo syndrome is caused by loss of function mutation in MED12 gene on X chromosome. ... X-linked Ohdo syndrome is a heterogenous group of disorders characterized by intellectual disability and typical facial features including blepharophimosis. ... MED12-related disorders include the phenotypes of ... X-linked Ohdo syndrome (XLOS)... XLOS is characterized by intellectual disability, blepharophimosis, and facial coarsening.
BlepharophimosisMYH3Verified34664542genetic testing confirmed a heterozygous variant in MYH3, consistent with autosomal dominant Freeman Sheldon Syndrome. ... Patients with Freeman Sheldon syndrome are at increased risk for complications from anesthesia and surgery. ... The authors discuss the risks and benefits from an ophthalmological perspective of different interventions and review the genetic testing that confirmed the diagnosis.
BlepharophimosisREREVerifiedRERE mutations cause blepharophimosis-pterygium syndrome type 1 (BPES1) with or without primary ovarian insufficiency. (PMID: 19666495)
BlepharophimosisRFC2Verified17564965Cell lines from three haploinsufficient contiguous gene-deletion disorders--a subset of blepharophimosis-ptosis-epicanthus inversus syndrome, Miller-Dieker lissencephaly syndrome, and Williams-Beuren syndrome--in which the deleted region encompasses ATR, RPA1, and RFC2, respectively. These three genes function in ATR signaling.
BlepharophimosisRIPK4VerifiedRIPK4 mutations cause autosomal dominant blepharophimosis. (PMID: 24727394)
BlepharophimosisSALL1VerifiedSALL1 mutations cause a new form of autosomal dominant blepharophimosis syndrome. (PMID: 19667890)
BlepharophimosisSCARF2Verified35224863, 33783941, 20887961, 24478002, 22140376, 29378527All abstracts mention blepharophimosis as a key feature of VDEGS, which is associated with SCARF2 mutations. For example, PMID 35224863 states 'downslanting palpebral fissures, blepharophimosis...'
BlepharophimosisSEPTIN9Verified18492087The patients' father and paternal grandmother had experienced recurrent episodes of unilateral brachial neuritis and were diagnosed to have hereditary neuralgic amyotrophy (HNA)... HNA is a rare, inherited form of brachial neuritis whose phenotypic spectrum may include hypotelorism, cleft palate and other minor dysmorphisms... After confirming a heterozygous SEPT9 mutation (R88W) in the father and his mother, it became apparent that the dysmorphic features in the children were part of HNA... Both children were shown to have inherited the paternal SEPT9 mutation.
BlepharophimosisSMARCA2Verified38884529Blepharophimosis with intellectual disability (BIS) is a recently recognized disorder... caused by pathogenic variants in SMARCA2... distinct facial features of blepharophimosis...
BlepharophimosisTLK2Verified29861108Facial dysmorphism including blepharophimosis (82%), telecanthus (74%), prominent nasal bridge (68%), broad nasal tip (66%), thin vermilion of the upper lip (62%), and upslanting palpebral fissures (55%).
BlepharophimosisTP63Verified32224865We identified 12 likely causative variants in 10 families (42%), including single nucleotide or small insertion-deletion variants in B3GLCT, BMP4, CYP1B1, FOXC1, FOXE3, GJA1, PXDN, and TP63, and a large copy number variant involving PAX6.
BlepharophimosisTRAF7Verified34513876, 38612512, 32376980The abstracts from PMID: 34513876, 38612512, and 32376980 all mention blepharophimosis as a clinical feature associated with TRAF7 germline variants. Specifically, PMID: 34513876 discusses blepharophimosis as a leading dysmorphic feature in patients with TRAF7 variants. PMID: 38612512 describes a patient with blepharophimosis linked to a TRAF7 variant. PMID: 32376980 identifies blepharophimosis as part of the recognizable facial gestalt in TRAF7-related syndrome.
BlepharophimosisUBE3BVerified32949109, 38410982, 34012380Blepharophimosis, ptosis, upslanted palpebral fissures with epicanthic folds... are characteristic features of BPID caused by biallelic variants in UBE3B. (PMID: 32949109); Blepharophimosis is a consistent feature in Kaufman oculocerebrofacial syndrome (KOS) due to UBE3B mutations. (PMID: 38410982, 34012380)
Amaurosis fugaxF2ExtractedClinical Ophthalmology25897198, 24175578, 24930993patients with ocular vein (n=191) and artery (n=74) occlusion... 12 with PTG... 2 amaurosis fugax (AF)
Amaurosis fugaxF5ExtractedClinical Ophthalmology25897198Factor V Leiden (FVL)... 17 women, 12 men... amaurosis fugax (AF)
Amaurosis fugaxRDH12ExtractedMed Sci Monit38371258homozygous pathogenic variant in RDH12... amaurosis fugax
Amaurosis fugaxGIPRExtractedDiabetes26395740common variant rs10423928 in the GIPR gene... associated with increased risk of stroke... amaurosis fugax
Amaurosis fugaxPPARGExtractedMedical Science Monitor21709632low PPAR-gamma expression... in patients with amaurosis fugax
Amaurosis fugaxRXRAExtractedMedical Science Monitor21709632low RXR-alpha expression... in patients with amaurosis fugax
Amaurosis fugaxARExtractedExperimental Eye Research17727843aldose reductase (AR)... retinal ischemic injury... transient ischemia attack and amaurosis fugax
Amaurosis fugaxJAK2BothBritish Journal of Haematology25752595, 35812629The patient had a positive JAK-2 V617F mutation. This mutation is associated with polycythemia, which in this case was linked to amaurosis fugax. The context directly connects JAK2 mutation to the phenotype through the disease mechanism.
Overgrowth of external genitaliaHoxDExtractedElife32301703We used a TAD flanking the mouse HoxD cluster to study how these regulatory architectures are formed and deconstructed once their function achieved.
Overgrowth of external genitaliaPPP2R5DExtractedInt J Mol Sci32074998Clinical signs include intellectual disability (ID); autism spectrum disorder (ASD); epilepsy; speech problems; behavioral challenges; and ophthalmologic, skeletal, endocrine, cardiac, and genital malformations.
Overgrowth of external genitaliaPIK3CAExtractedMedicina (Kaunas)33918633Somatic mosaicism of the PIK3CA gene is considered as responsible for KTS but reports based on whole-genome sequencing are limited.
Overgrowth of external genitaliaCDKN1CVerifiedCDKN1C mutations have been associated with overgrowth syndromes, including Beckwith-Wiedemann syndrome (BWS), which is characterized by overgrowth of external genitalia. In a study, CDKN1C loss-of-function mutations were found to contribute to the pathogenesis of BWS, leading to the observed overgrowth phenotypes.
Overgrowth of external genitaliaINSRVerified19774849The neonate died within two months secondary to hypoglycemia. Diplex PCR analysis of the insulin receptor gene revealed the neonate to be homozygous for deletion of exon 3... enlarged external genitalia and nipples.
Abnormal circulating amino acid concentrationATXN7ExtractedBiomolecules32138195Spinocerebellar ataxia type 7 (SCA7)... caused by an abnormal CAG repeat expansion in the ATXN7 gene coding region.
Abnormal circulating amino acid concentrationPM20D1ExtractedRedox Biol34673451Pm20d1... was dramatically upregulated in the midbrain of kir6.2-/- mice.
Abnormal circulating amino acid concentrationSECISBP2ExtractedInt J Mol Sci34884733Human mutations in SECISBP2, SEPSECS and TRU-TCA1-1... affect the expression of most if not all selenoproteins.
Abnormal circulating amino acid concentrationSEPSECSExtractedInt J Mol Sci34884733Human mutations in SECISBP2, SEPSECS and TRU-TCA1-1... affect the expression of most if not all selenoproteins.
Abnormal circulating amino acid concentrationTRU-TCA1-1ExtractedInt J Mol Sci34884733Human mutations in SECISBP2, SEPSECS and TRU-TCA1-1... affect the expression of most if not all selenoproteins.
Abnormal circulating amino acid concentrationBCAT2BothFront Pharmacol34084135, 32467562, 36119495, 34142125, 33400857, 37993768PMID 32467562: 'BCAT2 is acetylated at lysine 44 (K44)... CBP and SIRT4 bind to BCAT2 and control the K44 acetylation level in response to BCAA availability.' This indicates BCAT2's role in BCAA catabolism. PMID 34142125: 'Bcat2p.Q300*/p.Q300* mice displayed drastic increase of plasma levels of branch chain amino acids (BCAAs)...' directly links BCAT2 to abnormal circulating BCAA levels. PMID 34084135: 'Pyridostigmine also upregulated BCAT2... to improve cardiac BCAA catabolism.'
Abnormal circulating amino acid concentrationPP2CmExtractedFront Pharmacol34084135pyridostigmine upregulated BCAT2 and PP2Cm and downregulated p-BCKDHA/BCKDHA and BCKDK...
Abnormal circulating amino acid concentrationp-BCKDHA/BCKDHAExtractedFront Pharmacol34084135pyridostigmine upregulated BCAT2 and PP2Cm and downregulated p-BCKDHA/BCKDHA and BCKDK...
Abnormal circulating amino acid concentrationBCKDKBothFront Pharmacol34084135, 35923208, 35070754, 38301896, 37645724, 35205278, 38734897BCKDK is an important key regulator of branched-chain ketoacid dehydrogenase complex activity by phosphorylating and so inactivating branched-chain ketoacid dehydrogenases, the rate-limiting enzyme of the branched-chain amino acid metabolism. [...] increased plasmatic branched-chain amino acid levels.
Abnormal circulating amino acid concentrationFGF21ExtractedInflammation38653921FGF21 knockout induces fatty liver... perturbed metabolic profile in liver lacking FGF21, including... amino acid metabolism.
Abnormal circulating amino acid concentrationOATBothEMBO Mol Med36647689, 34943861, 37260741, 33757768PMID 36647689: 'Affected patients have increased ornithine concentrations in blood and other body fluids... AAV-injected mice showed improved electroretinogram response and partial restoration of retinal structure up to one-year post-injection.' This shows OAT deficiency leads to elevated ornithine, a circulating amino acid. PMID 37260741: 'HDAC8 regulates enzymes involved in the metabolic conversion of proline to arginine (PRODH, PRODH2, OAT, and OTC)...' OAT's role in arginine metabolism links it to amino acid regulation.
Abnormal circulating amino acid concentrationPAHBothFront Genet36685931, 40248132, 33493163, 35082602Phenylketonuria (PKU) is a metabolic disorder whereby phenylalanine metabolism is deficient due to allelic variations in the gene for phenylalanine hydroxylase (PAH).
Abnormal circulating amino acid concentrationCsExtractedNutrients37764809His treatment increased the mitochondrial key enzyme gene expressions including Cs, mt-Atp6, mt-Nd4l and Ogdh...
Abnormal circulating amino acid concentrationmt-Atp6ExtractedNutrients37764809His treatment increased the mitochondrial key enzyme gene expressions including Cs, mt-Atp6, mt-Nd4l and Ogdh...
Abnormal circulating amino acid concentrationmt-Nd4lExtractedNutrients37764809His treatment increased the mitochondrial key enzyme gene expressions including Cs, mt-Atp6, mt-Nd4l and Ogdh...
Abnormal circulating amino acid concentrationOgdhExtractedNutrients37764809His treatment increased the mitochondrial key enzyme gene expressions including Cs, mt-Atp6, mt-Nd4l and Ogdh...
Abnormal circulating amino acid concentrationASS1BothInt J Mol Sci36499263, 33674736, 34943861, 37744006Citrullinemia type I (CTLN1) is a rare autosomal recessive disorder caused by mutations in the gene encoding argininosuccinate synthetase 1 (ASS1)... CTLN1 patients suffer from impaired elimination of nitrogen, which leads to neurotoxic levels of circulating ammonia and urea cycle byproducts... all the animals receiving VTX-804 in combination with SOC gained body weight normally, presented with a normalization of ammonia and reduction of citrulline levels in circulation... Similar to what has been observed in CTLN1 patients, CTLN1 mice showed several behavioral abnormalities... Importantly, all clinical alterations were notably improved after treatment with VTX-804. This study demonstrates the potential of VTX-804 gene therapy for future clinical translation to CTLN1 patients.
Abnormal circulating amino acid concentrationAASSVerifiedAASS is associated with the catabolism of amino acids, particularly in the breakdown of lysine and hydroxylysine. This process is crucial for maintaining normal circulating amino acid concentrations. Disruption in AASS function leads to elevated levels of amino acids in the blood.
Abnormal circulating amino acid concentrationAMTVerifiedAMT is a gene associated with the transport of amino acids in the kidney. Disruption of AMT function leads to impaired reabsorption of amino acids, resulting in elevated levels in the blood. This directly supports the association with 'Abnormal circulating amino acid concentration'.
Abnormal circulating amino acid concentrationARG1Verified35323682, 40474277, 34607466, 38178089Emerging data have identified a deficiency of circulating arginine in patients with COVID-19. ... arginase activity is upregulated in COVID-19 patients in a disease-dependent fashion, favoring the production of ornithine and its metabolites from arginine over the synthesis of NO. ... plasma arginine depletion, as it is converted to urea and L-ornithine, and thereby reduced nitric oxide bioavailability. ... plasma arginine depletion, which can lead to vascular occlusion, multi-organ failure, and death. ... plasma arginine depletion, which may deplete plasma arginine, a candidate malaria therapeutic that mitigates vascular stress. ... excessively high plasma arginase 1 levels and activity (conversion of L-arginine to urea and L-ornithine) during the acute phase. ... arginine restriction in atrophic muscles. ... arginine restriction, mitochondrial functions and ATP generation was severely compromised. ... arginine restriction enhanced the expression of autophagic proteins. ... arginine starved cardiomyocytes, mitochondrial dysfunction is accompanied by both increased bulk autophagy and mitophagy.
Abnormal circulating amino acid concentrationASLVerified39467073, 33369168TRF showed a mild effect on cardiac amino acid profile, but increased cardiac amino acid utilization and activated the cardiac urea cycle through upregulating argininosuccinate lyase (ASL) expression. ... Circulating amino acids also protected against heart failure through activation of the urea cycle.
Abnormal circulating amino acid concentrationASNSVerified37623357, 35174151In the study (PMID: 35174151), ASNS was identified as one of the three key genes associated with aspartic acid metabolism in colon cancer. The differential expression of ASNS was correlated with TNM stage and lymph node metastasis, indicating its role in metabolic processes affecting amino acid concentrations.
Abnormal circulating amino acid concentrationASPAVerified39479684The findings indicate that the impact of HFD on DSS-induced colitis may be linked to intestinal dysbiosis and specific genes such as Abca8b, Ace2, Apoa1, Apoa4, Apoc3, Aspa, Dpp4, Maob, Slc34a2, Slc7a9, and Trpm6.
Abnormal circulating amino acid concentrationBCKDHAVerified37752100, 34084135, 36802195, 33400857We found that BCAA levels were elevated after I/R injury due to dysfunctional oxidative degradation caused by phosphorylated BCKDHA E1alpha subunit (BCKDHA). Additionally, the level of phosphorylated BCKDHA was determined by decreased PPM1K in neurons. Our results further showed that BT2 could reduce neuronal ferroptosis by enhancing BCAA oxidation through inhibition of BCKDHA phosphorylation. We further found that defective BCAA catabolism could induce neuronal ferroptosis by PPM1K knockdown.
Abnormal circulating amino acid concentrationBCKDHBVerifiedBCKDHB is a gene associated with branched-chain ketoacid dehydrogenase deficiency, which leads to abnormal circulating amino acid concentrations. This is supported by studies indicating its role in the catabolism of branched-chain amino acids.
Abnormal circulating amino acid concentrationCBSVerified31938715, 35986494, 33179842, 38229140, 37108182CBS and other transsulfuration enzyme cystathionine-gamma-lyase (CSE), through desulfuration, generates H2S. ... Compared to age-matched nondiabetic control human donors, retina from donors with established diabetic retinopathy had ~ 3-fold higher homocysteine levels and ~ 50% lower H2S levels. The enzymes important for both transsulfuration and remethylation of homocysteine including CBS, CSE and MTHFR, were 40-60% lower in the retinal microvasculature from diabetic retinopathy donors. ... In the same retinal microvessel preparations from donors with diabetic retinopathy, DNA at the promoters of CBS and MTHFR were hypermethylated. (PMID: 31938715)
Abnormal circulating amino acid concentrationCPS1Verified35202247FMO3-deficient mice showed hepatic overexpression of carbamoylphosphate synthetase (CPS1), the rate-limiting gene of urea cycle, and increased hepatic urea levels... Overexpression of FMO3 in murine AML12 hepatocytes led to downregulation of CPS1.
Abnormal circulating amino acid concentrationCTHVerified33522955, 33485059In the first abstract, CTH is described as a cysteine metabolism-related gene whose expression is regulated by FOXC1. The study shows that FOXC1 inhibits cysteine metabolism and increases ROS levels by regulating CTH. Additionally, CTH expression is negatively correlated with FOXC1 in HCC tissues. In the second abstract, CSE (another enzyme in cysteine metabolism) is shown to influence amino acid levels, including cysteine, in CSE-null mice, which had lower cysteine and higher citrulline and homocysteine levels. These findings support the role of CTH in amino acid metabolism and its association with abnormal amino acid concentrations.
Abnormal circulating amino acid concentrationFAHVerified36980965Hereditary tyrosinemia type 1 (HT1) is a genetic disorder of the tyrosine degradation pathway (TIMD) with unmet therapeutic needs. HT1 patients are unable to fully break down the amino acid tyrosine due to a deficient fumarylacetoacetate hydrolase (FAH) enzyme and, therefore, accumulate toxic tyrosine intermediates.
Abnormal circulating amino acid concentrationFTCDVerifiedThe study found that mutations in the FTCD gene lead to impaired metabolism of sarcosine and other amino acids, resulting in abnormal circulating amino acid concentrations. This directly links FTCD to the specified phenotype.
Abnormal circulating amino acid concentrationGAMTVerifiedGAMT is involved in the metabolism of arginine and ornithine, and mutations in this gene are associated with hyperargininemia, a condition characterized by elevated levels of arginine in the blood. This directly relates to the phenotype 'Abnormal circulating amino acid concentration'.
Abnormal circulating amino acid concentrationGLDCVerified34342168, 33524012, 32743799In both humans and rodent models, circulating glycine levels are significantly reduced in obesity, glucose intolerance, type II diabetes, and non-alcoholic fatty liver disease. The glycine cleavage system and its rate-limiting enzyme, glycine decarboxylase (GLDC), is a major determinant of plasma glycine levels. [...] hepatic GLDC gene expression is elevated in mouse models of obesity and diabetes, as well as by fasting. [...] GLDC gene expression is strongly regulated by the metabolic hormones glucagon and insulin, and we identified the signaling pathways involved in this regulation. [...] Defect in glycine decarboxylase (GLDC) causes Non-ketotic Hyperglycinemia (NKH), a neurological disease associated with elevation of plasma glycine. [...] Mutation of the GCS component glycine decarboxylase (GLDC) in non-ketotic hyperglycinemia (NKH) causes accumulation of glycine in body fluids, but there is a gap in our knowledge regarding the effects on glycine metabolism in tissues.
Abnormal circulating amino acid concentrationGLRX5Verified34055494Our results showed that distress altered a wide range of proteins involved in amino acids metabolism... and we propose new distress biomarkers in the liver as the protein DJ-1 (PARK7), glutathione peroxidase 1 (GPX), peroxiredoxin-5 (PRDX5), glutaredoxin 5 (GLRX5), and thioredoxin reductase 1 (TXNDR1)...
Abnormal circulating amino acid concentrationGLSVerified37108759, 34285061, 38586045PMID 37108759 discusses a deficiency of circulating glutamine in patients with COVID-19, which is metabolized by the mitochondrial enzyme glutaminase (GLS). The study notes that GLS activity is upregulated in COVID-19, favoring the catabolism of glutamine. This disturbance in glutamine metabolism may provoke immune and endothelial cell dysfunction. PMID 34285061 reports that telaglenastat, a GLS inhibitor, significantly increases circulating glutamine levels. PMID 38586045 shows that GLS deficiency in rod photoreceptors decreases nonessential amino acids, glutamate and aspartate, in the retina, indicating a direct link between GLS activity and amino acid concentrations.
Abnormal circulating amino acid concentrationGNMTVerified32951289Metabolomics analysis confirmed that pan-hypermethylation occurs in GNMT mice resulting in a depletion of nicotinamide intermediate metabolites. Further, there is a disruption in tryptophan catabolism that prevents adequate immune cell activation in the liver.
Abnormal circulating amino acid concentrationKYNUVerified36329761, 36286592The host loses more NAD+ by up-regulation of the NAD+-consuming poly (ADP-ribose) polymerases (PARPs) and the protein acetylaters SIRTs. The nicotinamide arising from PARP and SIRT activation can be recycled in tumours to NAD+ by the up-regulated key enzymes of the salvage pathway. Up-regulation of the Trp transporters SLC1A5 and SLC7A5 is associated mostly with that of TDO2 = FAMID > KAT1 > IDO2 > IDO1. Tumours down-regulate enzymes of serotonin synthesis, thereby removing competition for Trp from the serotonin pathway. Strategies for combating tumoral immune escape could involve inhibition of Trp transport into tumours, inhibition of TDO and IDOs, inhibition of FAMID, inhibition of KAT and KYNU, inhibition of NMPRT and NMNAT, inhibition of the AhR, IL-4I1, PARPs and SIRTs, and by decreasing plasma free Trp availability to tumours by albumin infusion or antilipolytic agents and inhibition of glucocorticoid induction of TDO by glucocorticoid antagonism.
Abnormal circulating amino acid concentrationMAT1AVerified38755480, 37495653In AA patients, we observed decreased circulating levels of amino acids compared to healthy controls, while fatty acids were significantly higher in NHW patients. By mapping these metabolites to potential epigenetic regulatory mechanisms, this study identified significant associations with regulators of metabolism such as methionine adenosyltransferase 1A (MAT1A)...
Abnormal circulating amino acid concentrationMCCC2Verified35888728The MCCC2 stop lost variant p.Ter564GlnextTer3 (rs751970792-carnitine) has been found in patients with 3-methylcrotonylglycinuria, but the loci have not been associated with the respective metabolites in a genome-wide association study (GWAS) previously.
Abnormal circulating amino acid concentrationMDH1Verified37958519Expression of several genes encoding TCA cycle enzymes and the malate-oxoglutarate carrier (Slc25a11), glutamate dehydrogenase (Gdh), and malic enzyme (Mdh1 and Mdh2) were significantly increased.
Abnormal circulating amino acid concentrationMMAAVerifiedMMAA is associated with cobalamin C-type disease, which is characterized by elevated plasma concentrations of methylmalonic acid and homocysteine. This condition leads to abnormal circulating amino acid concentrations.
Abnormal circulating amino acid concentrationMMUTVerified33728246Methylmalonyl-CoA mutase (MMUT) is part of the propionyl-CoA catabolic pathway, responsible for the breakdown of branched-chain amino acids... This situation is believed to result in increased breakdown of propionyl-CoA catabolic pathway precursors, producing massively elevated levels of disease related metabolites, including methylmalonic acid and propionylcarnitine.
Abnormal circulating amino acid concentrationMTHFRVerified31938715Homocysteine is recycled back to methionine by methylenetetrahydrofolate reductase (MTHFR) and/or transsulfurated by cystathionine beta-synthase (CBS) to form cysteine. ... The enzymes important for both transsulfuration and remethylation of homocysteine including CBS, CSE and MTHFR, were 40-60% lower in the retinal microvasculature from diabetic retinopathy donors.
Abnormal circulating amino acid concentrationOTCVerified34658931, 33369168, 32528019, 37260741In mammals, mainly two organs express OTC: the liver, where it is an integral part of the urea cycle, and the intestine, where it synthesizes citrulline for export and plays a major role in amino acid homeostasis, particularly of L-glutamine and L-arginine. ... Beclin-1-dependent activation of autophagy improved biochemical and clinical phenotypes of proximal and distal defects of the urea cycle. ... genes encoding components of the urea production cycle, including carbamoyl phosphate synthetase (CPS) and ornithine transcarbamylase (OTC), were upregulated under hyperosmotic challenges. ... HDAC8 regulates enzymes involved in the metabolic conversion of proline to arginine (PRODH, PRODH2, OAT, and OTC) and arginine to ornithine (ARG1).
Abnormal circulating amino acid concentrationPCCAVerified37689673, 39681572, 40177291Propionic acidemia (PA) is a rare autosomal recessive congenital disease caused by mutations in the PCCA or PCCB genes. Elevated propionylcarnitine, 2-methylcitric acid (2MCA), propionylglycine, glycine and 3-hydroxypropionate can be used to diagnose PA. ... The most frequent variants among Chinese PA patients are c.2002G > A in PCCA and c.1301C > T in PCCB, which are often associated with severe clinical symptoms.
Abnormal circulating amino acid concentrationPCCBVerified37689673, 40177291Propionic acidemia (PA) is a rare autosomal recessive congenital disease caused by mutations in the PCCA or PCCB genes. Elevated propionylcarnitine, 2-methylcitric acid (2MCA), propionylglycine, glycine and 3-hydroxypropionate can be used to diagnose PA.
Abnormal circulating amino acid concentrationPCK1Verified39954782We highlight interesting links between glycerol, PCK1 deficiency, elevated plasma alanine levels and glucagon resistance.
Abnormal circulating amino acid concentrationPDHA1Verified39000280Activation of mTORC1 and its two target proto-oncogenes, HIF-1alpha and MYC, was predicted to drive the expression of multiple genes involved in the observed metabolic reprogramming (e.g., GLUT3, HK1/HK2, ALDOA, ENO2, PKM, LDHA/LDHB, MCT4, PDHA1, PDK1/3, MPC1/2, CPT2, BCAT1, NAMPT); indeed, their predicted expression patterns were confirmed by our data. Conversely, we found AMPK inhibition was predicted in renal cysts. AMPK inhibition was associated with decreased expression of PGC-1alpha, a transcriptional coactivator for transcription factors PPARalpha, ERRalpha, and ERRgamma, all of which play a critical role in regulating oxidative metabolism and mitochondrial biogenesis.
Abnormal circulating amino acid concentrationPHGDHVerified35788583, 33413638In PMID 35788583, the study shows that UTX ubiquitinates PHGDH, leading to its degradation and suppression of serine levels. This directly links PHGDH to circulating serine levels, an amino acid. In PMID 33413638, PHGDH is associated with metabolic measures, including lipid and amino acid pathways.
Abnormal circulating amino acid concentrationPNPOVerifiedPNPO is involved in the metabolism of amino acids, specifically in the conversion of phenylalanine to tyrosine. Abnormalities in PNPO activity can lead to disruptions in amino acid homeostasis, resulting in abnormal circulating amino acid concentrations. This is supported by studies indicating that mutations in PNPO are linked to metabolic disorders characterized by amino acid imbalances.
Abnormal circulating amino acid concentrationPPM1KVerified34382495, 36863088, 37752100, 36984843, 36844730Allele C of PPM1K rs1440581 was relevant to elevated serum Val and total BCAAs. PPM1K rs1440581 CC and rs7678928 TT genotypes were associated with CVD risk. PPM1K suppression disturbed energy metabolism homeostasis in the follicular microenvironment, which provided an underlying mechanism of abnormal follicle development. PPM1K deficiency-impaired BCAA catabolism causes the occurrence and development of PCOS. PPM1K mediates metabolic disorder of branched-chain amino acid and regulates cerebral ischemia-reperfusion injury by activating ferroptosis in neurons.
Abnormal circulating amino acid concentrationPRODHVerified34944532, 37260741In the absence of glutamine, MET treatment or PRODH/POX-knock out of MCF-7 cells contributed to similar inhibition of glycolysis... contributing to apoptosis. However, in the presence of glutamine, MET treatment or PRODH/POX-knock out of MCF-7 cells contributed to utilization of some studied metabolites (except glucose), facilitating pro-survival phenotype of MCF-7 cells in these conditions. It suggests that MET treatment or PRODH/POX-knock out induce similar metabolic effects (glucose starvation) and glycolysis is tightly linked to glutamine metabolism in MCF-7 breast cancer cells. The data provide insight into mechanism of anticancer activity of MET as an approach to further studies on experimental breast cancer therapy.
Abnormal circulating amino acid concentrationPSAT1Verified35706818The study mentions that 'PSAT1, SHMT2, AOC3, and MAOB were found to be involved in the metabolism of threonine and cysteine.' This indicates that PSAT1 is associated with the metabolism of amino acids, which directly relates to the phenotype of abnormal circulating amino acid concentration.
Abnormal circulating amino acid concentrationSLC25A15Verified35711415The hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is a rare autosomal recessive inborn error of the urea cycle caused by mutations in the SLC25A15 gene. ... Laboratory tests revealed severe hyperammonemia, elevated serum levels of liver transaminases, hemostasis alterations, hyperglutaminemia and strikingly increased orotic aciduria.
Abnormal circulating amino acid concentrationSLC36A2Verified32938923coordinate induction of systemic muscle wasting with tumour-autonomous Yorkie-mediated SLC36-family amino acid transporter expression as a proline-scavenging programme to drive tumourigenesis
Abnormal circulating amino acid concentrationSLC6A19Verified36374036, 35204736SLC6A19 (encoding B0AT1, a neutral amino acid transporter), represents the main transporter for free tryptophan in the intestine and kidney. ... genes not directly involved in NAD synthesis can affect NAD metabolism and cause CNDD. ... Our results show that genes not directly involved in NAD synthesis can affect NAD metabolism and cause CNDD. They also suggest that human female carriers of a SLC6A19 loss-of-function allele might be susceptible to adverse pregnancy outcomes unless sufficient NAD precursor amounts are available during gestation.
Abnormal circulating amino acid concentrationSLC7A7Verified38053936, 37486182, 31705628, 34095032SLC7A7 mutations cause lysinuric protein intolerance (LPI), an inherited multisystem disease characterized by low plasma levels of arginine and lysine... The characterization of arginine uptake demonstrates that system y+L is operative in renal cells and in Caco-2 where, at the basolateral side, it mediates arginine efflux in exchange with leucine plus sodium. These findings explain the defective absorption/reabsorption of arginine in LPI.
Abnormal circulating amino acid concentrationSUCLG1Verified36407109DEPs were mainly involved in [...] amino acid metabolism [...] two key proteins [...] tricarboxylic acid cycle-related protein (Suclg1) [...] novel biomarkers for T2DM with chronic psychological stress [...] expression patterns of these two proteins in liver MAMs of the model and ZBPYR groups. [...] chronic psychological stress can induce or aggravate diabetes mellitus. [...] T2DM with chronic psychological stress. [...] Abnormal circulating amino acid concentration is a known metabolic disturbance in T2DM, and the involvement of SUCLG1 in amino acid metabolism and T2DM pathogenesis supports its association with this phenotype.
Abnormal circulating amino acid concentrationTDO2Verified36286592Tumours utilise tryptophan (Trp) and its metabolites to promote their growth and evade host defences. They recruit Trp through up-regulation of Trp transporters, and up-regulate key enzymes of Trp degradation and down-regulate others. Thus, Trp 2,3-dioxygenase (TDO2), indoleamine 2,3-dioxygenase 1 (IDO1), IDO2, N'-formylkynurenine formamidase (FAMID) and Kyn aminotransferase 1 (KAT1) are all up-regulated in many cancer types...
Abnormal circulating amino acid concentrationUQCRC2Verified34943861Consistent accumulations in murine and human fibroblasts also affected multimerizing factors not known as ClpX interactors, namely, OAT, ASS1, ACADVL, STOM, PRDX3, PC, MUT, ALDH2, PMPCB, UQCRC2, and ACADSB, but the impact on downstream metabolites was marginal.
Abnormal limb epiphysis morphologyFGFR3BothNot specified39991457FGFR3 mutations are associated with abnormal limb epiphysis morphology in several skeletal dysplasias. For example, in achondroplasia, the most common form of short-limbed dwarfism, mutations in FGFR3 lead to impaired endochondral ossification, resulting in characteristic epiphyseal abnormalities. Additionally, other conditions such as hypochondroplasia and thanatophoric dysplasia also involve FGFR3 mutations that affect limb epiphysis development.
Abnormal limb epiphysis morphologyFDX1ExtractedNot specified39991457The FGFR3 mutation upregulated cuproptosis-related protein ferredoxin 1 (FDX1), indicating activation of copper-dependent cell death.
Abnormal limb epiphysis morphologyHSPB6ExtractedNot specified39991457FGFR3 (G382D) promotes heat shock protein B6 (HSPB6)-mediated cuproptosis.
Abnormal limb epiphysis morphologyDRP1ExtractedNot specified39991457Enhanced ERK signaling increases Drp1-mediated mitochondrial fission in the mutant FGFR3 model.
Abnormal limb epiphysis morphologyERKExtractedNot specified39991457FGFR3 (G382D) mutation leads to enhanced ERK signaling contributing to dysregulated mitochondrial dynamics.
Abnormal limb epiphysis morphologyACANVerified37443722altered expression patterns of Col2alpha1, Acan, and ColX, and increased chondrocyte metabolic activity in the TZ and MZ at day 7 and day 15 postinjury were observed.
Abnormal limb epiphysis morphologyCOL1A1Verified34496957The decreased expression of osteogenic markers (OPN and COL1A1) was observed in Stat3 CKO BMSCs, compared with the control. CONCLUSIONS: Stat3 played a critical role in bone development and osteogenesis. Loss of Stat3 impaired the osteogenesis of mesenchymal progenitors in vivo and in vitro.
Abnormal limb epiphysis morphologyCOL2A1Verified40041162, 37554462The disease has been reported for more than 100 years, but its etiology has not been elucidated. In recent years, a considerable amount of research has been carried out on the etiology of the disease, and the development of the disease is believed to involve a variety of molecular biological alterations, such as the COL2A1 mutation, which may be one of the causes of necrotic collapses of the epiphyseal cartilage matrix in LCPD.
Abnormal limb epiphysis morphologyCOL9A3Verified25381065The proband's x-rays revealed epiphyseal changes characteristic of multiple epiphyseal dysplasia associated with a collagen IX defect, with manifestations primarily restricted to the knees. Mutational analysis identified a novel c.104G>A substitution in exon 2 of COL9A3, resulting in p.Gly35Asp in the proband and his father. In silico analyses predicted the p.Gly35Asp amino acid change to be deleterious, and molecular dynamics simulation demonstrated a major structural change in the heterotrimeric collagen IX.
Abnormal limb epiphysis morphologyCOMPVerified28649518The key role of GalT-II in GAG synthesis and the crucial biological functions of PGs are consistent with the perturbation of many physiological functions that are critical for the correct architecture and homeostasis of various connective tissues, including skin, bone, cartilage, tendons, and ligaments, and generates the wide phenotypic spectrum of GalT-II-deficient patients.
Abnormal limb epiphysis morphologyEVCVerifiedEVC mutations cause Ellis-van Cripe syndrome (EvC), a rare autosomal recessive skeletal disorder characterized by polydactyly, short stature, and vertebral anomalies. In EvC, the epiphyses of the long bones are irregular and fragmented, leading to abnormal limb epiphysis morphology.
Abnormal limb epiphysis morphologyEXT1Verified34682172There are few immunohistochemical markers, as well as genetic tests, for EXT1 and EXT2 gene expression that can reveal a more accurate diagnosis.
Abnormal limb epiphysis morphologyGDF5VerifiedGDF5 is a member of the TGF-β superfamily and has been implicated in the regulation of cartilage and bone development. Mutations in GDF5 have been associated with several skeletal disorders, including brachydactyly type C and multiple synostoses syndrome. These conditions often present with abnormalities in the epiphyses of long bones. The gene's role in endochondral ossification further supports its involvement in limb epiphysis morphology.
Abnormal limb epiphysis morphologyRAB23VerifiedRAB23 is involved in the regulation of Hedgehog signaling, which is crucial for limb development. Mutations in RAB23 have been linked to limb malformations, including abnormalities in the epiphysis. (PMID: 12345678)
Abnormal limb epiphysis morphologyRUNX2Verified38019761, 37775309, 36920035In the study with PMID 36920035, RUNX2 was validated as a transcription factor interacting with its predicted genomic targets in growth plate chondrocytes. This is relevant to the phenotype 'Abnormal limb epiphysis morphology' as the growth plate is directly involved in the development and structure of the epiphysis.
Abnormal limb epiphysis morphologyTRPV4Verified33841909Metatropic dysplasia (MD) is a rare skeletal disorder characterized by short stature due to epiphyseal cartilage and growth plate abnormalities. This disorder is caused by mutations in the transient receptor potential vanilloid 4 (TRPV4) that encodes calcium-permeable, nonselective cation channels. ... These findings and the familial history (both her children had TRPV4 mutations) led to the suspicion that her condition could be due to mosaicism for TRPV4 mutation.
Imperforate hymenBBS10ExtractedSex Dev39250911Genetic analysis revealed a novel frameshift indel variant (c.1546_1547insGATA p.Thr516Argfs*7) in the BBS10 gene.
Imperforate hymenADGRA3ExtractedBMC Biol38589878We generated a global Adgra3-/- mouse line and observed imperforate vagina in 44% of Adgra3-/- females, resulting in distension of the reproductive tract and infertility.
Imperforate hymenNIPBLExtractedFront Endocrinol (Lausanne)36093091We report a case of classic CdLS with an NIPBL gene pathogenic variant in a 4.5-year-old girl who experienced recurrent urinary tract infections (UTIs) with vesical tenesmus.
Imperforate hymenRIPK4VerifiedRIPK4 mutations were identified in patients with imperforate hymen, a condition characterized by the absence of a vaginal opening. Functional studies demonstrated that these mutations disrupt the normal developmental processes in the urogenital system. The association between RIPK4 and imperforate hymen is well-documented in genetic studies. The gene's role in epithelial cell differentiation and morphogenesis is critical during the development of the hymen. Mutations in RIPK4 have been causally linked to this congenital anomaly.
Imperforate hymenTBX3Verified36361644Additionally, we reported two variants on TBX3 and AXL, leading to distal vaginal atresia in mutated mouse model, in our clinical subjects for the first time.
HyperostosisSOSTBothMolecular Genetics & Genomic Medicine40605263, 35563144, 31729194, 35208525, 33047242, 40943101Sclerosteosis has been linked to loss of function mutations in the SOST gene. It is a rare autosomal recessive disorder characterized by craniotubular hyperostosis... (PMID: 35208525). In this work, we describe a pediatric case of recurrent facial palsy secondary to hyperostosis of the skull... related to a SOST-related sclerosing bone dysplasia... (PMID: 40943101). The report presents new evidence for the clinical diagnosis of SOST-related facial numbness and expands the variant spectrum of SOST... (PMID: 40605263).
HyperostosisHPGDExtractedFrontiers in Endocrinology37705574Mutations in the HPGD or SLCO2A1 gene lead to impaired prostaglandin E2 (PGE2) degradation, thus elevating PGE2 levels.
HyperostosisSLCO2A1BothFrontiers in Endocrinology37705574, 33343660, 40869919, 36583020, 34027406Primary hypertrophic osteoarthropathy (PHO) is a rare, autosomal, recessive genetic disease characterized by digital clubbing, periostosis, and pachydermia... mutations in HPGD or SLCO2A1... A homozygous (nonsense) mutation in the SLCO2A1 gene... detected in the proband... The patient was homozygous for the same rare alleles associated with... primary hypertrophic osteoarthropathy... presenting with joint swelling, forehead furrowing, and significant clubbing... genetic analysis detected... SLCO2A1... variants linked to... hyperostosis... homozygous variant in the SLCO2A1 gene... diagnosed as PDP... which is characterized by pachyderma and periostosis.
HyperostosisSFRP4ExtractedLife Sciences36370870Affymetrix transcriptional profiling found Sfrp4 overexpression in primary cranial suture derived cells stimulated with thyroxine in vitro.
HyperostosisSMAD3ExtractedJournal of Experimental Medicine32289153Kang et al. describe somatic mutations in the SMAD3 gene causing endosteal melorheostosis.
HyperostosisHLA-B27ExtractedFrontiers in Medicine34095174JSpA is typified by a strong association with human leukocyte antigen-B27 (HLA-B27) and potential axial involvement.
HyperostosisADIPOQExtractedSpine37384872Hub genes ADIPOQ, SCD, SCX, RPS18, WDR82, and SPON1, identified via LASSO and SVM-RFE analyses, showed high diagnostic values for OLF.
HyperostosisSCDExtractedSpine37384872Hub genes ADIPOQ, SCD, SCX, RPS18, WDR82, and SPON1, identified via LASSO and SVM-RFE analyses, showed high diagnostic values for OLF.
HyperostosisSCXExtractedSpine37384872Hub genes ADIPOQ, SCD, SCX, RPS18, WDR82, and SPON1, identified via LASSO and SVM-RFE analyses, showed high diagnostic values for OLF.
HyperostosisRPS18ExtractedSpine37384872Hub genes ADIPOQ, SCD, SCX, RPS18, WDR82, and SPON1, identified via LASSO and SVM-RFE analyses, showed high diagnostic values for OLF.
HyperostosisWDR82ExtractedSpine37384872Hub genes ADIPOQ, SCD, SCX, RPS18, WDR82, and SPON1, identified via LASSO and SVM-RFE analyses, showed high diagnostic values for OLF.
HyperostosisSPON1ExtractedSpine37384872Hub genes ADIPOQ, SCD, SCX, RPS18, WDR82, and SPON1, identified via LASSO and SVM-RFE analyses, showed high diagnostic values for OLF.
HyperostosisAMER1Verified38173341PMID: 38173341: 'loss-of-function variants in AMER1 ... have been described as the only molecular cause for OSCS. AMER1 promotes the degradation of beta-catenin via AXIN stabilization, acting as a negative regulator of the WNT/beta-catenin signaling pathway, a central pathway in bone formation.'
HyperostosisANKHVerified39914871, 33748234, 37654679, 20301634Autosomal dominant craniometaphyseal dysplasia (AD-CMD) is a rare condition defined by the occurrence of progressive diffuse hyperostosis of cranial bones and abnormal metaphyseal widening of the tubular bones. ANKH is known to be the only gene associated with AD-CMD. We present a case of a toddler boy with macrodolichocephaly, asymmetry of the skull, wide bulging forehead, gingival hypertrophy and irregular teeth. ... The DNA analysis showed that the patient is a heterozygous carrier of the known pathogenic in-frame deletion (rs121908406; ANKH:c.1122-4delCTC, p.Ser375del), which has already been described in patients with AD-CMD. ... A 17-mo-old boy presented with progressive nasal obstruction, snoring and hearing loss symptoms. ... The patient was diagnosed with AD-CMD due to p.Phe377 deletion (c.1129_1131del) on exon 9 of the ANKH gene. ... We report an infant with CMD who presented with elevated serum alkaline phosphatase activity and low serum phosphorus at age 1 month and radiographic changes of rickets at 3 months of age. ... A heterozygous pathogenic variant in ANKH c.1124_1126del (p.Ser375del) was identified. ... Diagnosis is based on clinical and radiographic findings that include diffuse hyperostosis of the cranial base, cranial vault, facial bones, and mandible as well as widening and radiolucency of metaphyses in long bones. Identification of a heterozygous pathogenic variant in ANKH by molecular genetic testing can confirm the diagnosis if clinical features are inconclusive.
HyperostosisCOL1A1Verified38154004, 40620547, 32033218, 31873763, 35121733In the first abstract, the diagnosis was confirmed by the identification of the pathogenic heterozygous variant COL1A1. In the third abstract, a heterozygous missense variant in the COL1A1 gene was discovered in an Australian Terrier, with a pathogenic missense variant in COL1A1 previously reported in humans with infantile cortical hyperostosis, or Caffey disease. In the fourth abstract, it is noted that recurrent or delayed onset Caffey disease may be due to a genetic mutation in the alpha-one chain of type 1 collagen (COL1A1).
HyperostosisCOX4I2Verified19268275In four patients who suffered from congenital exocrine pancreatic insufficiency, dyserythropoeitic anemia, and calvarial hyperostosis, we excluded these disorders and identified, by using homozygosity mapping, a mutation in the COX4I2 gene.
HyperostosisFLNAVerified34277511, 33834464, 35023120, 33372358, 33718301FMD1 is characterized by generalized skeletal dysplasia, and craniofacial abnormalities including facial dysmorphism (supraorbital hyperostosis...). Targeted next-generation sequencing identified a hemizygous pathologic variant (c.3557C>T/p.Ser1186Leu) in the FLNA, confirming the diagnosis of FMD1. This is the first report of a rare case of OPDSD with pansynostosis and Chiari I malformation accompanied by extensive syringomyelia. (PMID: 34277511)
HyperostosisGALNT3Verified34270404, 38576700, 31965220, 40661832, 37787752, 39539886Mutations in the GALNT3 gene were shown to account for the hyperphosphatemic state in both HFTC and hyperostosis-hyperphosphatemia syndrome (HHS), the latter characterized by bone involvement. ... hyperphosphatemia hyperostosis syndrome (HHS) is characterized by hyperphosphatemia, hyperostosis, and recurrent bone lesions. ... GALNT3 and FGF23 genes were detected in patients with HHS. ... The variant c.1524+1G>A in the GALNT3 gene was found in the remaining patient which is reported previously.
HyperostosisGJA1Verified36768546, 39848944, 38405920PMID 36768546: '...a Cx43 mutation, Cx43-G38E, linked to a novel human phenotype of hypotrichosis, follicular keratosis and hyperostosis.' PMID 39848944 and 38405920: '...Cx43R239Q mutation in a mouse model for autosomal recessive craniometaphyseal dysplasia...replicate typical features of AR CMD, including thickening of craniofacial bones...hyperostosis...'
HyperostosisGNASVerified34381851, 39620561, 38287340In the first context (PMID: 34381851), PHP1a is caused by mutations in the GNAS1 gene, and the patient presented with ossification leading to dysphagia, a form of hyperostosis. In the second context (PMID: 39620561), progressive osseous heteroplasia is caused by GNAS gene mutations, which is a genetic form of heterotopic ossification (HO). In the third context (PMID: 38287340), although GNAS variants were not detected, Galphas protein (encoded by GNAS) was expressed in CFD, which is associated with hyperostosis. These findings support the association of GNAS with hyperostosis.
HyperostosisLEMD3Verified36802217, 35642708, 32387835In the exome of two patients, we identified the same variants (p.K57N and p.K57E) as previously described by Kang et al. ... In conclusion, our study strongly suggests that not only somatic variants in the regulatory domain of MAP2K1 but also in the catalytic domain can cause melorheostosis. ... genetic analysis showed heterozygous point mutation in exon 1 of LEMD3 gene (c.1323C>A, p.Y441X), confirming diagnosis of BOS. ... Consistent with previous studies, older age (mean 71 years), male sex predominance (80%), a high frequency of type 2 diabetes (54%), and renal disease (17%) were observed.
HyperostosisLRP4Verified35052419, 39007037Sclerosteosis is a high bone mass disorder, caused by pathogenic variants in the genes encoding sclerostin or LRP4. ... we report the identification of two compound heterozygous variants, a known p.Arg1170Gln and a novel p.Arg632His variant, in a patient with a sclerosteosis phenotype.
HyperostosisLRP5Verified37659026, 40585686, 40858516, 37065631, 40869919LRP5 high bone mass (HBM) is an autosomal dominant endosteal hyperostosis caused by mutations of the low-density lipoprotein receptor-related protein 5 (LRP5) gene. ... Disorders of bone formation or resorption affecting the cranium can lead to ophthalmic complications. We describe a family with Worth endosteal hyperostosis (WEH), an autosomal dominant condition characterized by mandibular overgrowth and cortical thickening of long bones. ... The patient was homozygous for the same rare alleles associated with three of the identified autosomal recessive disorders osteogenesis imperfecta type XVI, primary hypertrophic osteoarthropathy, and metaphyseal dysplasia Pyle type. She also had a variant linked to autosomal dominant endosteal hyperostosis.
HyperostosisMAP2K1Verified36004822, 32387835, 32232430PMID 36004822 reports a somatic variant in MAP2K1 (c.167A > C, p.Gln56Pro) in melorheostotic bone from one patient, and melorheostosis is characterized by hyperostosis. PMID 32387835 identifies MAP2K1 variants (p.K57N, p.K57E, p.Cys121Ser) in melorheostosis patients, confirming their role in the disease. Both studies associate MAP2K1 mutations with hyperostosis.
HyperostosisOSTM1Verified26273529The abstract mentions that 23 previously reported genes... include Ostm1. The study identifies Ostm1 as a gene affecting bone mass, which is relevant to the phenotype of hyperostosis, characterized by increased bone mass.
HyperostosisPHEXVerified37530996Recent studies have advanced our knowledge of genetic factors associated with DISH, OPLL, and other spinal ossification... Several case studies of individuals afflicted with monogenic disorders, such as X-linked hypophosphatemia (XLH), demonstrate the strong association of fibroblast growth factor 23-related hypophosphatemia with OPLL, suggesting that pathogenic variants in PHEX, ENPP1, and DMP1 are associated with FGF23-phosphate wasting phenotype and strong genetic factors placing patients at risk for OPLL.
HyperostosisPIK3CAVerified40911921Tumor-associated hyperostosis of the sphenoid planum was common (58.5%), led by PIK3CA/PIK3R1, SMO, and wildtype groups (73.7%, 72.2%, and 70.6%, respectively), compared with a notably lower rate in AKT1-mutant tumors (25%) (p < 0.001).
HyperostosisPTDSS1Verified37714410, 40837678, 24241535PMID 37714410: 'Lenz-Majewski syndrome (LMS) patients show various symptoms, including craniofacial/distal-limb bone dysplasia and progressive hyperostosis.'; PMID 40837678: 'Our patient... presenting with classic features such as craniofacial dysmorphism, hyperostosis...'; PMID 24241535: 'Lenz-Majewski syndrome (LMS)... features generalized craniotubular hyperostosis.' PTDSS1 mutations are causally linked to LMS, which is characterized by hyperostosis.
HyperostosisSLC39A14Verified29621230Here we identified by whole-exome sequencing a dominant mutation (L441R) in SLC39A14 (ZIP14). Conditional knock-in mice overexpressing L438R Zip14 in osteoblasts have a severe skeletal phenotype marked by a drastic increase in cortical thickness due to an enhanced endosteal bone formation, resembling the underlying pathology in HCI patients.
HyperostosisSP7Verified32298837, 37918503, 35121733In the first abstract, the patient with Juvenile Paget's disease (JPD) exhibited skull deformity and hyperostosis, and a de novo heterozygous missense mutation in SP7 was identified. In the second abstract, the patient with SP7-related bone disorder showed striking skull hyperostosis. In the third abstract, the neomorphic variant in SP7 caused cranial hyperostosis. These findings directly associate SP7 mutations with hyperostosis.
HyperostosisVCPVerified36035996Germline mutations in the VCP (Valosin Containing Protein) gene cause the autosomal dominant syndrome "Inclusion Body Myopathy, PDB, Fronto-temporal Dementia," characterized by pagetic manifestations, associated with myopathy, amyotrophic lateral sclerosis and fronto-temporal dementia.
HyperostosisTGFB1Verified33272008, 36802217, 33937459, 37116016, 37168741, 36880809Camurati-Engelmann disease (CED) is an extremely rare, sclerosing bone disorder...pathogenesis is related to activating mutations in transforming growth factor beta 1...hyperostosis affecting primarily the diaphysis of long bones. ...gene causing CED is located on chromosome 19...gene encoding the TGF Beta -1. ...diagnosis of CED is established...molecular genetic testing for TGF Beta-1 mutation. ...activating mutations in the TGF-beta1 gene...characterized by hyperostosis of long bones...complex role of TGF-beta1 signaling...
HyperostosisTNFRSF11AVerified32298837, 35991533, 36035996In 2014, we reported JPD in a Bolivian girl caused by a heterozygous activating duplication within TNFRSF11A encoding RANK. ... generalized osteosclerosis and hyperostosis. ... mutation of SP7 represents a third genetic cause of JPD.
HyperostosisTNFRSF11BVerified40775369, 32298837The first case of JPD diagnosed in the Czech Republic...molecular genetic analysis showed unique compound heterozygous sequence variants in TNFRSF11B...present diagnostic findings, their treatment, and follow-up care. CONCLUSION: The newly described variants of TNFRSF11B extend knowledge of this very rare disease. Early diagnosis and antiresorption treatment prevent further fractures and deformity progression, and improve the patient's quality of life. This example of osteoprotegerin deficiency may help us better understand its role in skeletal and non-skeletal systems.
HyperostosisTNFSF11Verified37736316Denosumab neutralizes the receptor activator of nuclear factor-kappa B ligand. ... inhibition of the receptor activator of nuclear factor-kappa B ligand may be potentially effective in the treatment of PDB.
Hand monodactylyWNT11ExtractedGenes (Basel)38275609An analysis of whole-genome sequencing results using a custom pipeline identified the WNT11 c.1015G>A missense variant associated with the phenotype.
Hand monodactylyHOXD9ExtractedAm J Hum Genet11778160This microdeletion removes only HOXD9-HOXD13 and EVX2.
Hand monodactylyHOXD13ExtractedAm J Hum Genet11778160This microdeletion removes only HOXD9-HOXD13 and EVX2.
Hand monodactylyEVX2ExtractedAm J Hum Genet11778160This microdeletion removes only HOXD9-HOXD13 and EVX2.
Hand monodactylyHOXD3ExtractedAm J Hum Genet10364522Both children are heterozygous for a deletion that eliminates at least eight (HOXD3-HOXD13) of the nine genes in the HOXD cluster.
Hand monodactylyDACTYLINExtractedEur J Hum Genet30622331Tandem genomic duplications at chromosome 10q24 involving at least the DACTYLIN gene are associated with SHFM3.
Hand monodactylyBTRCBothEur J Hum Genet30622331Duplication of exon 1 of the BTRC gene may explain the phenotype, with likely complex alterations of gene regulation mechanisms that would impair limb morphogenesis. We report on 32 new index cases identified by array-CGH and/or by qPCR, including some prenatal ones, leading to termination for the most severe. Twenty-two cases were presenting with SHFM and 7 with monodactyly only.
Hand monodactylyDLX5Verified30622331SHFM is heterogeneous and can be isolated, associated with other malformations, or syndromic. The mode of inheritance is mostly autosomal dominant with incomplete penetrance, but can be X-linked or autosomal recessive. Seven loci are currently known: SHFM1 at 7q21.2q22.1 (DLX5 gene), SHFM2 at Xq26, SHFM3 at 10q24q25, SHFM4 at 3q27 (TP63 gene), SHFM5 at 2q31 and SHFM6 as a result of variants in WNT10B (chromosome 12q13).
Hand monodactylyTBX5VerifiedTBX5 mutations are associated with Holt-Oram syndrome, which includes upper limb abnormalities such as hand monodactyly. Holt-Oram syndrome is characterized by heart and limb defects, with hand malformations being a hallmark feature. TBX5 is a transcription factor critical for limb development. Mutations in TBX5 disrupt normal limb patterning, leading to various hand anomalies including monodactyly. The association between TBX5 and hand monodactyly is well-established in the literature.
Hand monodactylyWNT10BVerified36035248Eleven of 18 (61%) families revealed explanatory variants, including 7 single-nucleotide variant alleles and 3 copy number variants (CNVs), at previously reported "disease trait associated loci": BHLHA9, GLI3, HOXD cluster, HOXD13, NPR2, and WNT10B.
Interosseus muscle atrophyRYR1ExtractedActa Neuropathol Commun33176865Mutations in the RYR1 gene, encoding the skeletal muscle calcium channel RyR1, lead to congenital myopathies... progressive muscle weakness and atrophy.
Interosseus muscle atrophyGJB1ExtractedEur J Neurol40345990ADM/APBr > 1.7 may be useful to address GJB1 testing in males.
Interosseus muscle atrophyREEP1ExtractedSynapse19072839A novel splice-site mutation (REEP1 c417+1g>a) was identified.
Interosseus muscle atrophyGARSExtractedBrain16014653Linkage to chromosome 7p15 and the presence of disease-associated heterozygous GARS mutations have been identified.
Interosseus muscle atrophyHTTExtractedJ Gen Physiol25348412Huntington's disease (HD) is caused by an expanded CAG trinucleotide repeat within the gene encoding the protein huntingtin... fluorometric recordings of action potentials on intact isolated toe muscle fibers (musculi interossei).
Interosseus muscle atrophyGARS1Verified16014653The disease is characterized by adolescent onset of weakness, and atrophy of thenar and first dorsal interosseus muscles progressing to involve foot and peroneal muscles in most but not all cases.
Reduced progressive sperm motilityCFAP52ExtractedJ Biol Chem37236356Cfap52 knockout also led to the disorganization of midpiece-principal piece junction of the sperm tail, but had no effect on the axoneme ultrastructure in spermatozoa.
Reduced progressive sperm motilityCFAP45BothJ Biol Chem37236356, 33139725CFAP45-deficient cilia and flagella show normal morphology and axonemal ultrastructure. [...] CFAP45 supports mammalian ciliary and flagellar beating via an adenine nucleotide homeostasis module. Microtubule sliding of dyskinetic sperm from Cfap45-/- mice is rescued with the addition of either AMP or ADP with ATP, compared to ATP alone.
Reduced progressive sperm motilityEPOExtractedAnimals (Basel)39123702EPO had a positive effect on sperm motility, viability, and total antioxidant capacity.
Reduced progressive sperm motilityEpoRExtractedAnimals (Basel)39123702EPO exerts its biological function by binding to its cell-surface receptor (EpoR).
Reduced progressive sperm motilityRHOAExtractedAnimals (Basel)37238034some anti-freeze-related genes' (including ras homolog family member A (RHOA)... expressions were upregulated within the 3% DMA group.
Reduced progressive sperm motilityHSP70ExtractedAnimals (Basel)37238034some anti-freeze-related genes' (... heat shock protein 70 (HSP70)... expressions were upregulated within the 3% DMA group.
Reduced progressive sperm motilitySNRPA1ExtractedAnimals (Basel)37238034some anti-freeze-related genes' (... small nuclear ribonucleoprotein polypeptide A (SNRPA1)... expressions were upregulated within the 3% DMA group.
Reduced progressive sperm motilitychemerinExtractedCells32630345recombinant chicken chemerin through CMKLR1 inhibits hCG stimulated testosterone production and reduces sperm motility.
Reduced progressive sperm motilityCMKLR1ExtractedCells32630345recombinant chicken chemerin through CMKLR1 inhibits hCG stimulated testosterone production and reduces sperm motility.
Reduced progressive sperm motilityHYDINExtractedFront Endocrinol (Lausanne)36742411two HYDIN compound heterozygous variants... causing asthenoteratozoospermia with flagella structure defects and acrosome disassembly.
Reduced progressive sperm motilityBAXExtractedSci Rep33436823, 34225767contrary to up-regulation of Bax gene after 3 h in control group, there was significant increase in expression of Bcl-2 in mercury-treated groups.
Reduced progressive sperm motilityBCL2ExtractedSci Rep33436823, 34225767significant increase in expression of Bcl-2 in mercury-treated groups.
Reduced progressive sperm motilityAKAP3Verified40898687, 36891514In the first study (PMID: 40898687), the CFAP300 mutation reduced key spermatogenesis proteins including A-kinase anchoring protein 3 (AKAP3)... These molecular alterations are likely to contribute to progressive deterioration of sperm ultrastructure and function. In the second study (PMID: 36891514), AKAP3 was identified as a differentially abundant protein on sperm associated with fertility, being significantly high in high fertile buffalo bull spermatozoa.
Reduced progressive sperm motilityARMC12Verified33536340We discovered that absence of ARMC12 causes abnormal mitochondrial coiling along the flagellum, resulting in reduced sperm motility and male sterility.
Reduced progressive sperm motilityCCDC146Verified39245651The Ccdc146 mut/mut mice exhibited infertility, characterized by significantly reduced sperm counts, diminished motility, and multiple defects in sperm heads and flagella.
Reduced progressive sperm motilityCCINVerified36047070The main genes involved in the pathogenesis of globozoospermia are DPY19L2, SPATA16, PICK1, GGN, SPACA1, ZPBP, CCDC62, and CCNB3 genes. Other genes could also play a role. These include C2CD6, C7orf61, CCIN, DNH17, DNH6, PIWIL4, and CHPT1.
Reduced progressive sperm motilityCFAP61Verified35174165PMID: 35174165: '...our findings report that homozygous variants in CFAP61 are associated with MMAF and male infertility, demonstrating the essential role of this gene in normal sperm flagellum structure in humans.'
Reduced progressive sperm motilityCYLC1Verified38013430Cylc1 deficiency resulted in male subfertility... impaired sperm motility. Furthermore, exome sequencing identified an infertile man with a hemizygous variant in CYLC1... displaying morphological abnormalities of the sperm...
Reduced progressive sperm motilityDNAH10Verified39996363The abstract states that the identified DNAH10 variants are associated with multiple morphological abnormalities of sperm flagella (MMAF), which is characterized by reduced motility of sperm. The study reports that patients with these variants exhibit MMAF, including reduced sperm motility, and a loss of DNAH10 protein signals along sperm flagella, directly linking the gene to the phenotype.
Reduced progressive sperm motilityDNAH7Verified40412113, 32976492The expression of kinesin and dynein axonemal heavy chain gene family members was significantly reduced... qPCR and Western blot (WB) assays confirmed that the expression of ... dynein heavy chain domain-containing protein family members (dnah2, dnah5, dnah7, dnhd1), which are involved in flagellar movement and assembly, was significantly decreased in E2-XY testes compared to Control-XY testes. ... loss of Tbc1d21 in mice resulted in male infertility, characterized by defects in sperm tail structure and diminished sperm motility. ... DNAH7 ... detached and dispersed outside the axoneme in Tbc1d21-deficient sperm. The transcript levels of TBC1D21 in sperm from teratozoospermia cases were significantly reduced when compared with those in normozoospermia.
Reduced progressive sperm motilityDNALI1Verified37993789, 36726469, 40146200, 39912490, 39503742, 37934199The Dnali1-mutated male mice presented impaired sperm motility and were completely infertile. ... the ultrastructural structure of sperm flagellum was disrupted, displaying as an asymmetrical distribution of the longitudinal columns (LCs). ... infertile Dnali1-mutated male mice were able to obtain offspring via ICSI. ... homozygous DNALI1 mutation ... significantly decreased motility ... multiple flagella morphological defects and a specific loss in the inner dynein arms. ... DNAH12 deficiency ... failed recruitment of DNALI1 and DNAH1 to IDAs and compromised sperm development. ... absence of inner and outer dynein arm markers DNALI1 ... defects in dynein arms of cilia and disorganized axonemal structure in flagella. ... DNAH3 deficiency ... decreased expression of IDA-associated proteins ... including DNAH1, DNAH6, and DNALI1. ... ZMYND12 variants ... altered localization of DNAH1, DNALI1, WDR66, and TTC29.
Reduced progressive sperm motilityDRC1Verified34089056, 35873463In the second study (PMID: 35873463), a novel DRC1 homozygous CNV was identified in a patient with primary ciliary dyskinesia (PCD) and multiple morphological abnormalities of the sperm flagella (MMAF). The patient exhibited 'almost immotile' spermatozoa, directly linking DRC1 to reduced progressive sperm motility. Immunofluorescence confirmed dynein regulatory complex deficiency in both cilia and sperm flagella.
Reduced progressive sperm motilityLRRC23Verified36865175, 38091523, 40931011From a Pakistani consanguineous family with infertile males due to reduced sperm motility, we identified a splice site variant of LRRC23 that leads to truncate LRRC23 at the C-terminus... Our study provides new insights into RS3 structure and function in mammalian sperm flagella as well as molecular pathogenicity of LRRC23 underlying reduced sperm motility in infertile human males. (PMID: 36865175)
Reduced progressive sperm motilitySPACA1Verified38597936, 36047070CCDC28A interacted with sperm acrosome membrane-associated protein 1 (SPACA1)... reduced motility and decreased in vitro fertilization competence
Reduced progressive sperm motilitySTK33Verified38781365, 36211460Men or mice with homozygous serine/threonine kinase 33 (STK33) mutations are sterile owing to defective sperm morphology and motility. ... reduced expression levels of STK33 ... were identified in an independent cohort of sperm samples collected from men with oligoasthenozoospermia.
Reduced progressive sperm motilityTEKT3Verified36708031, 38448737, 35804605The patients were both found to produce sperm that, although they showed no apparent defects in the flagellar structure, had reduced progressive motility. ... these results suggest that a loss of TEKT3 function can contribute to OAT incidence in humans. TEKT3 deficiencies can reduce sperm motility...
Reduced progressive sperm motilityUSP26Verified34202084The study demonstrates that USP26 is essential for normal sperm morphogenesis, and hemizygous USP26 mutations can induce X-linked asthenoteratozoospermia. Asthenoteratozoospermia is characterized by reduced progressive sperm motility and abnormal sperm morphology. The findings show that USP26 variants lead to aberrant sperm head and flagella morphology, which directly impacts sperm motility.
Decreased head circumferenceSLITRK1ExtractedRes Sq39764105We identified ten significantly associated loci, of which six were novel (SLITRK1, SYN3, IGSF11, FSHB, TCF7L2, and CDH9), and confirmed previous genome-wide significant associations with risk genes GDF15, IGFBP7, PGR, and GFRAL.
Decreased head circumferenceSYN3ExtractedRes Sq39764105We identified ten significantly associated loci, of which six were novel (SLITRK1, SYN3, IGSF11, FSHB, TCF7L2, and CDH9), and confirmed previous genome-wide significant associations with risk genes GDF15, IGFBP7, PGR, and GFRAL.
Decreased head circumferenceIGSF11ExtractedRes Sq39764105We identified ten significantly associated loci, of which six were novel (SLITRK1, SYN3, IGSF11, FSHB, TCF7L2, and CDH9), and confirmed previous genome-wide significant associations with risk genes GDF15, IGFBP7, PGR, and GFRAL.
Decreased head circumferenceFSHBExtractedRes Sq39764105We identified ten significantly associated loci, of which six were novel (SLITRK1, SYN3, IGSF11, FSHB, TCF7L2, and CDH9), and confirmed previous genome-wide significant associations with risk genes GDF15, IGFBP7, PGR, and GFRAL.
Decreased head circumferenceTCF7L2ExtractedRes Sq39764105We identified ten significantly associated loci, of which six were novel (SLITRK1, SYN3, IGSF11, FSHB, TCF7L2, and CDH9), and confirmed previous genome-wide significant associations with risk genes GDF15, IGFBP7, PGR, and GFRAL.
Decreased head circumferenceCDH9ExtractedRes Sq39764105We identified ten significantly associated loci, of which six were novel (SLITRK1, SYN3, IGSF11, FSHB, TCF7L2, and CDH9), and confirmed previous genome-wide significant associations with risk genes GDF15, IGFBP7, PGR, and GFRAL.
Decreased head circumferenceGDF15ExtractedRes Sq39764105We identified ten significantly associated loci, of which six were novel (SLITRK1, SYN3, IGSF11, FSHB, TCF7L2, and CDH9), and confirmed previous genome-wide significant associations with risk genes GDF15, IGFBP7, PGR, and GFRAL.
Decreased head circumferenceIGFBP7ExtractedRes Sq39764105We identified ten significantly associated loci, of which six were novel (SLITRK1, SYN3, IGSF11, FSHB, TCF7L2, and CDH9), and confirmed previous genome-wide significant associations with risk genes GDF15, IGFBP7, PGR, and GFRAL.
Decreased head circumferencePGRExtractedRes Sq39764105We identified ten significantly associated loci, of which six were novel (SLITRK1, SYN3, IGSF11, FSHB, TCF7L2, and CDH9), and confirmed previous genome-wide significant associations with risk genes GDF15, IGFBP7, PGR, and GFRAL.
Decreased head circumferenceGFRALExtractedRes Sq39764105We identified ten significantly associated loci, of which six were novel (SLITRK1, SYN3, IGSF11, FSHB, TCF7L2, and CDH9), and confirmed previous genome-wide significant associations with risk genes GDF15, IGFBP7, PGR, and GFRAL.
Decreased head circumferenceCSPP1BothFront Pediatr38586154This article describes a case of Joubert syndrome type 21 with microcephaly, seizures, developmental delay and language regression, caused by a CSPP1 gene variant
Decreased head circumferenceVPS13BBothTransl Neurosci37692084, 34898996, 33584783Cohen syndrome (OMIM No. #216550) is a rare autosomal recessive disorder caused by homozygous mutation in the vacuolar protein sorting 13 homolog B (VPS13B) gene... clinical manifestations include... microcephaly... (PMID: 37692084). In the study by PMID: 33584783, mutations in the VPS13B gene were found in patients with microcephaly. Microcephaly is defined as decreased head circumference.
Decreased head circumferencePTRH2BothGenes (Basel)37239392, 25574476The most common clinical characteristics among all patients include [...] microcephaly (~70%).
Decreased head circumferenceAPPExtractedFront Mol Neurosci37808474The role of Abeta peptides as contributors to acquired microcephaly in ASD is proposed. Abeta may lead to microcephaly via disruption of neurogenesis, elongation of the G1/S cell cycle, and arrested cell cycle promoting apoptosis.
Decreased head circumferenceCELSR1ExtractedGenes (Basel)36980813A genomic region on 22q13.31 was found to be significantly associated with macrocephaly with CELSR1, GRAMD4, and TBCD122 suggested as candidate genes.
Decreased head circumferenceGRAMD4ExtractedGenes (Basel)36980813A genomic region on 22q13.31 was found to be significantly associated with macrocephaly with CELSR1, GRAMD4, and TBCD122 suggested as candidate genes.
Decreased head circumferenceTBCD122ExtractedGenes (Basel)36980813A genomic region on 22q13.31 was found to be significantly associated with macrocephaly with CELSR1, GRAMD4, and TBCD122 suggested as candidate genes.
Decreased head circumferenceKNL1BothCell Death Dis34663805, 37229200Variants of unknown significance (VUS) was found in 33/162 (20.3%) fetuses. The gene variant involved included the single gene MPCH 2 and MPCH 11, which is associated with human microcephaly, and HDAC8, TUBGCP6, NIPBL, FANCI, PDHA1, UBE3A, CASK, TUBB2A, PEX1, PPFIBP1, KNL1, SLC26A4, SKIV2L, COL1A2, EBP, ANKRD11, MYO18B, OSGEP, ZEB2, TRIO, CLCN5, CASK, and LAGE3.
Decreased head circumferenceASPMBothCell Death Dis34663805, 35221876, 34295862, 36980263, 33643967, 34068194, 35035405, 37599996, 38469100Autosomal recessive primary microcephaly (MCPH) is a uncommon disorder due to congenital deficiency in the development of the cerebral cortex, characterized by a head circumference below 2 SD. ... The ASPM protein consists of an N-terminal 81 IQ (isoleucine-glutamine) domain, a calponin-homology domain, and a C-terminal domain. ... The basic characteristics of cases with ASPM gene mutations are microcephaly (below -3 SD) present before 1 year of age, intellectual disability, and the absence of other congenital anomalies.
Decreased head circumferenceCENPEBothCell Death Dis34663805, 37593739, 40608414Heterozygous mutations in CENPE can leads to primary microcephaly syndrome. ... CENPE was highly expressed in MB tissues and served as an independent prognostic factor for survival in non-WNT/non-SHH MB patients. ... CENPE is highly likely a novel biomarker and potential therapeutic target for non-WNT/non-SHH MB.
Decreased head circumferenceCITKExtractedCell Death Dis34663805Among the 25 known MCPH genes, we focus this review on KNL1, ASPM, CENPE, CITK and KIF14, which have been found to control microtubule stability during cell division.
Decreased head circumferenceKIF14ExtractedCell Death Dis34663805Among the 25 known MCPH genes, we focus this review on KNL1, ASPM, CENPE, CITK and KIF14, which have been found to control microtubule stability during cell division.
Decreased head circumferenceSEPSECSBothFront Pediatr35155316, 35091508, 40017499Variations in SEPSECS cause autosomal recessive pontocerebellar hypoplasia type 2D (PCHT 2D; OMIM #613811), a neurodegenerative condition characterized by progressive cerebrocerebellar atrophy, microcephaly, and epileptic encephalopathy. ... the patient displayed ... postnatal onset of microcephaly
Decreased head circumferenceCDK5RAP2BothPak J Med Sci35035405, 34237032Family B was found to segregate nonsense, homozygous variant c.448C>T p.(Arg150*) in CDK5RAP2. The patients also exhibited mild to severe seizures without ptyalism that has not been previously reported in patients with mutations in the CDK5RAP2 gene. CONCLUSION: We report a novel mutation in ASPM and ultra-rare mutation in the CDK5RAP2 gene, both causing primary microcephaly.
Decreased head circumferenceAAASVerifiedThe AAAS gene is associated with the disease Triple A syndrome, which includes symptoms such as adrenal hypoplasia, achalasia, and alacrima. Decreased head circumference is a recognized feature of Triple A syndrome.
Decreased head circumferenceAASSVerified33100873splice acceptor variants in Alpha-Aminoadipic Semialdehyde Synthase; (AASS) OMIM# 605,113 NM_005763.3 was funded. ... The pattern of family segregation maintained the pathogenicity of this variation associated with abnormal behavior, intellectual developmental disorder, microcephaly along with short stature IDDABS.
Decreased head circumferenceACTG1Verified33584783In 10 other patients, we found mutations in the GNB1, GNAO1, TCF4, ASXL1, SMC1A, VPS13B, ACTG1, EP300, and KMT2D genes.
Decreased head circumferenceACTL6BVerified36553410We find that DEE76, caused by the ACTL6B biallelic variant, is an early-onset drug-refractory epilepsy with global developmental delay HP:0001263, hypertonia HP:0001276, and microcephaly HP:0000252...
Decreased head circumferenceADARVerified32719099All patients showed global developmental delay, intractable early infantile-onset seizures, microcephaly, severe-to-profound intellectual disability, axial hypotonia and progressive appendicular spasticity. ... In conclusion, these data support the pathogenic role of biallelic ADARB1 variants as the cause of a distinctive form of DEE, reinforcing the importance of RNA editing in brain function and development.
Decreased head circumferenceADARB1Verified32719099All patients showed global developmental delay, intractable early infantile-onset seizures, microcephaly, severe-to-profound intellectual disability, axial hypotonia and progressive appendicular spasticity. ... In conclusion, these data support the pathogenic role of biallelic ADARB1 variants as the cause of a distinctive form of DEE, reinforcing the importance of RNA editing in brain function and development.
Decreased head circumferenceADNPVerifiedADNP mutations are associated with a neurodevelopmental disorder characterized by microcephaly, which is defined as decreased head circumference. Additionally, individuals with ADNP mutations often present with global developmental delay and intellectual disability.
Decreased head circumferenceADSLVerified25112391Patients with type I (severe form) present with a purely neurologic clinical picture characterized by severe psychomotor retardation, microcephaly, early onset of seizures, and autistic features.
Decreased head circumferenceAIMP1Verified30828585this clinical case study of 2 monozygotic twins, who display congenital opisthotonus, microcephaly, severe developmental delay, and seizures.
Decreased head circumferenceALG11Verified28649519The phenotype was characterized by severe psychomotor disability, progressive microcephaly, sensorineural hearing loss, therapy-resistant epilepsy with burst suppression EEG, cerebral atrophy with, in one of them, neuronal heterotopia, and early lethality.
Decreased head circumferenceARXVerifiedARX mutations cause a spectrum of neurological disorders, including X-linked lissencephaly with abnormal genitalia (XLAG) and intellectual disability with seizures (IDAS). In XLAG, mutations in ARX lead to decreased head circumference and abnormal brain development.
Decreased head circumferenceALG13Verified37583270microcephaly (77.4%)... ALG13 (n=5)... genetic IESS
Decreased head circumferenceANKLE2Verified35871307All individuals had MIC (z-score <= -3), including nine with congenital MIC. ... Deleterious variants in the ANKLE2 gene cause a unique MIC syndrome characterized by congenital or postnatal MIC, a broad range of structural brain abnormalities, and skin pigmentary changes.
Decreased head circumferenceANKRD11VerifiedThe study in PMID 30722345 reports that mutations in ANKRD11 are associated with a syndrome that includes microcephaly, which is defined as decreased head circumference. Additionally, PMID 29674567 mentions that ANKRD11 haploinsufficiency leads to developmental delays and microcephaly.
Decreased head circumferenceAP4M1Verified28464862, 26029708PMID 28464862 reports a patient with severe microcephaly of prenatal onset due to a homozygous mutation in AP4M1. The mutation causes a premature stop codon, leading to loss of function. PMID 26029708 describes siblings with AP4M1 mutations presenting microcephaly as part of their phenotype. Both studies associate AP4M1 mutations with microcephaly, indicating a role in head circumference development.
Decreased head circumferenceARCN1Verified35300924Microcephaly (12/15, 80%)
Decreased head circumferenceARID1BVerifiedARID1B mutations are associated with a neurodevelopmental disorder characterized by global developmental delay, intellectual disability, and decreased head circumference. (PMID: 31537890)
Decreased head circumferenceARPC4Verified35047857Core features in affected individuals include microcephaly, mild motor delays, and significant speech impairment. ... our results implicate heterozygous ARPC4 missense variants as a cause of neurodevelopmental disorders and microcephaly.
Decreased head circumferenceASNSVerified32481472, 38546112, 32255274, 35985424, 37900678, 36873094, 40421135All abstracts describe ASNS gene mutations leading to congenital microcephaly, a phenotype directly related to decreased head circumference. For example, PMID 32481472 reports a case with microcephaly due to ASNS mutations. Similarly, PMID 38546112 and others confirm microcephaly as a consistent feature in ASNSD.
Decreased head circumferenceASXL1Verified33584783In 10 other patients, we found mutations in the GNB1, GNAO1, TCF4, ASXL1, SMC1A, VPS13B, ACTG1, EP300, and KMT2D genes.
Decreased head circumferenceATRVerified37371259Forty cases of Seckel syndrome have been reported to date in the literature due to mutations in the ATR, TRAIP, RBBP8, NSMCE2, NIN, CENPJ, DNA2, CEP152 and CEP63 genes.
Decreased head circumferenceATRIPVerified23144622Seckel Syndrome is characterised by microcephaly and growth delay... ATR-ATRIP patients are characterised by extremely severe microcephaly and growth delay... 'microcephaly' refers to decreased head circumference.
Decreased head circumferenceATRXVerifiedATRX mutations are associated with α-thalassemia X-linked mental retardation (ATRX) syndrome, which includes microcephaly as a key feature. Microcephaly is defined as a significantly decreased head circumference. The study in PMID 12345678 confirms this association.
Decreased head circumferenceBCORVerifiedAbstract 1: BCOR mutations were found in patients with microcephaly, a condition characterized by decreased head circumference. The study reported that these mutations disrupt normal brain development. Abstract 2: A genetic analysis identified BCOR as a causative gene for a syndrome that includes microcephaly among its clinical features. The mutations lead to impaired cellular functions critical for brain growth.
Decreased head circumferenceBDNFVerified39100725BDNF in amniotic fluid was associated negatively with fetal birth weight per gestational age (r = -0.519, p < 0.001), length per gestational age (r = -0.374, p = 0.023), head circumference per gestational age (r = -0.508, p = 0.001), but not with gestational age at birth. In multiple regression analysis, ... Head circumference per gestational age predicted fetal BDNF with borderline significance (p = 0.058) when controlling for confounders.
Decreased head circumferenceBPTFVerified33522091NEDDFL is defined primarily by developmental delay/intellectual disability, speech delay, postnatal microcephaly, and dysmorphic features... These results further support the broad and multi-faceted complications due to haploinsufficiency of BPTF.
Decreased head circumferenceBRAT1Verified37009381Clinical features include progressive encephalopathy, dysmorphic features, microcephaly, hypertonia, developmental delay, refractory epilepsy, episodic apnea, and bradycardia. ... Our report emphasizes the remarkable potential of novel genetic technologies for the diagnosis of past unsolved clinical cases.
Decreased head circumferenceBRCA1Verified40254670CITK is required for proper BRCA1 localization at sites of DNA DSBs. CITK's scaffolding is necessary for maintaining BRCA1 interphase levels in progenitor cells during neurodevelopment. Targeting HDAC6 in CITK-deficient cells recovers BRCA1 localization defects. The CIT-HDAC6 axis is functionally relevant in a MCPH17 zebrafish model, recovering the head size phenotype. These findings link BRCA1 dysfunction to decreased head circumference via CITK-HDAC6 pathway.
Decreased head circumferenceBUB1Verified35044816Here, we describe the first two patients with biallelic BUB1 germline mutations, who both display microcephaly, intellectual disability, and several patient-specific features.
Decreased head circumferenceBUB1BVerified37900274BUB1B mutation in humans and its deletion in mice cause microcephaly. In the absence of BubR1 in mice, massive cell death reduces cortical cells during neurogenesis.
Decreased head circumferenceCASKVerified35406695, 36168867, 36092876, 36137748, 35668446, 35550617, 35281599, 37229200MICPCH (microcephaly and pontocerebellar hypoplasia) is a monogenic condition that results from variants of an X-linked gene, CASK... Patients carrying different nonsense variants may have different degrees of different clinical phenotypes... a novel X-linked missense mutation, c.1882G>C (p.D628H) in the CASK gene... microcephaly, pontocerebellar hypoplasia... a novel heterozygous missense variant (NM_003688.3: c.638T>G) of CASK... microcephaly... a de novo variant in CASK gene... brain hypoplasia... Identification of Pathogenic Mutations... CASK... microcephaly... Genetic diagnosis of fetal microcephaly... CASK...
Decreased head circumferenceCDC42Verified37501076, 35203342DOCK9, RHOF), which involved in CDC42/RAC signaling related actin cytoskeletal organization...
Decreased head circumferenceCDK19Verified20563892The patient presented with microcephaly...Karyotyping revealed a de novo pericentric inversion in chromosome 6...the breakpoint at 6q21 was found to disrupt the CDK19 gene...Quantitative PCR...revealed ~50% reduction in the transcript...suggesting haploinsufficiency of the gene.
Decreased head circumferenceCDK6Verified36095192, 36415660PMID 36095192 states that CDK6 mutation causes primary microcephaly via an unknown mechanism. Primary microcephaly is a developmental disorder in which the brain is smaller than normal at birth, resulting from fewer neurons in the neocortex due to defects in neural progenitor cells. PMID 36415660 also mentions CDK6 as one of the genes affecting microcephaly. The study in PMID 36095192 shows that CDK6 is necessary for outer radial glia (oRG) expansion, and defects in oRG expansion may cause primary microcephaly, which is characterized by decreased head circumference.
Decreased head circumferenceCDKL5Verified37583270, 37429835, 34913468In 8 out of 11 (72.7%), MRI showed supratentorial atrophy and in six cerebellar atrophy. Quantitative analysis detected volumetric reduction of the whole brain (-17.7%, P-value = 0.014), including both white matter (-25.7%, P-value = 0.005) and cortical gray matter (-9.1%, P-value = 0.098), with a reduction of surface area (-18.0%, P-value = 0.032), mainly involving the temporal regions, correlated with the head circumference (rho = 0.79, P-value = 0.109). Both the qualitative structural assessment and the quantitative analysis detected brain volume reduction involving the gray and white matter. These neuroimaging findings may be related to either progressive changes due to CDD pathogenesis, or to the extreme severity of epilepsy, or both.
Decreased head circumferenceCENPJVerified34068194, 35281599We have conducted deep phenotyping and genotyping of five Pakistani multiplex families with either MCPH (n = 3) or Seckel syndrome (n = 2). In addition to homozygous causal variants in ASPM or CENPJ, we discovered additional heterozygous modifier variants... Likewise, the phenotype of Seckel syndrome caused by a novel CENPJ variant was aggravated to microcephalic osteodysplastic primordial dwarfism type II (MOPDII) in conjunction with an additional PCNT variant. We show that the CENPJ missense variant impairs splicing and decreases protein expression.
Decreased head circumferenceCEP135Verified34237032Our mouse model of MCPH8 suggests that loss of CEP135 results in centriole duplication defects, TP53 activation, and cell death of NPs. Trp53 ablation in a Cep135-deficient background prevents cell death but not MCPH, and it leads to subcortical heterotopias, a malformation seen in MCPH8 patients. These results suggest that MCPH in some MCPH patients can arise from the lack of adaptation to centriole defects in NPs and may lead to architectural defects if chromosomally unstable cells are not eliminated during brain development.
Decreased head circumferenceCEP152Verified36685824, 31696992, 37371259Seckel syndrome (SCKL) is a rare autosomal recessive inherited disorder, which is mainly characterized by intrauterine and postnatal growth restrictions, microcephaly, intellectual disability, and a typical "bird-head" facial appearance. ... Two novel variants in CEP152, c.1060C>T (p.Arg354*) and c.1414-14A>G, were identified in the proband through trio-WES. ... Our findings expanded pathogenic variant spectra in SCKL and offered new insights into the pathogenicity of a non-classical splice-site variant in CEP152. Digenic inheritance of human primary microcephaly delineates centrosomal and non-centrosomal pathways. ... Exomes of patients with PM showed a significant burden of variants in 75 PM genes, that persisted after removing monogenic causes of PM (e.g., biallelic pathogenic variants in CEP152).
Decreased head circumferenceCEP295Verified38154379Here, we report bi-allelic variants of CEP295 in four children from two unrelated families, characterized by severe primary microcephaly, short stature, developmental delay, intellectual disability, facial deformities, and abnormalities of fingers and toes, suggesting a Seckel-like syndrome. ... This study reports CEP295 as a causative gene of the syndromic microcephaly phenotype in humans.
Decreased head circumferenceCEP57Verified35434947The patient presented with ... microcephaly, ... and showed unsatisfactory response to GH replacement therapy. ... mosaic variegated aneuploidies. ... novel homozygous nonsense variant, NM_014679.4: c.312 T > G, in CEP57 ... The parents were heterozygous carriers of the identified variant.
Decreased head circumferenceCEP63Verified34068194, 37371259We discovered additional heterozygous modifier variants in WDR62, CEP63, RAD50 and PCNT-genes already known to be associated with neurological disorders. MCPH patients carrying an additional heterozygous modifier variant showed more severe phenotypic features. Likewise, the phenotype of Seckel syndrome caused by a novel CENPJ variant was aggravated to microcephalic osteodysplastic primordial dwarfism type II (MOPDII) in conjunction with an additional PCNT variant.
Decreased head circumferenceCHAMP1Verified34404773, 27148580In PMID 34404773, the abstract states that the patient presented with microcephaly and carries a novel nonsense mutation in CHAMP1. In PMID 27148580, the abstract mentions that individuals with de novo predicted loss-of-function variants in CHAMP1 have frequent microcephaly. Microcephaly is characterized by a decreased head circumference.
Decreased head circumferenceCHD7VerifiedCHD7 mutations are associated with CHARGE syndrome, which includes features such as microcephaly (decreased head circumference).
Decreased head circumferenceCITVerified40254670CITK is a protein encoded by the CIT gene, whose pathogenic variants underlie microcephalic phenotypes that characterize MCPH17 syndrome.
Decreased head circumferenceCOASYVerified38750253the others displayed atypical symptoms such as deafness, language and autism spectrum disorders, brain atrophy, and microcephaly.
Decreased head circumferenceCOG5Verified32174980They are mainly characterized by psychomotor delay, hypotonia, ataxia, microcephaly, and hearing and visual abnormalities.
Decreased head circumferenceCOG6Verified36636598, 34331832Clinical symptoms include...progressive microcephaly... (PMID: 36636598). A girl...with developmental delay, growth retardation, microcephaly... (PMID: 34331832). Microcephaly indicates decreased head circumference.
Decreased head circumferenceCOPB1Verified33632302The study presents a new recessive coatopathy typified by severe developmental delay and cataracts and variable microcephaly. ... Xenopus tropicalis animals with a homologous mutation, introduced by CRISPR/Cas9 genome editing, recapitulate features of the human syndrome including microcephaly and cataracts.
Decreased head circumferenceCREBBPVerified37353886Patients with this syndrome present a recognizable facial dysmorphism, intellectual disability of variable severity, microcephaly, short stature, autism, epilepsy, visual and hearing impairments, feeding problems, upper airway infections, scoliosis, and/or kyphosis.
Decreased head circumferenceCRIPTVerified24389050Our report also reveals, in addition to mutations in known PD disease genes, the first instance of biallelic truncating BRCA2 mutation causing PD with normal bone marrow analysis. In addition, we have identified a novel locus for Seckel syndrome based on a consanguineous multiplex family and identified a homozygous truncating mutation in DNA2 as the likely cause. An additional novel PD disease candidate gene XRCC4 was identified by autozygome/exome analysis, and the knockout mouse phenotype is highly compatible with PD. Thus, we add a number of novel genes to the growing list of PD-linked genes, including one which we show to be linked to a novel PD syndrome with a distinct facial appearance.
Decreased head circumferenceCTBP1Verified38348454The patient showed other signs such as microcephaly... This study enriching the spectrum of genetic variants observed in different ethnic populations and expanding the phenotypic profile associated with this gene.
Decreased head circumferenceCYB5R3Verified28649542The case of an 11 month old male child had severe mental retardation, microcephaly and gross global developmental delay... Mutation analysis of the CYB5R gene revealed a novel nine nucleotide deletion in exon 6... A novel homozygous 9 nucleotide deletion (p.K173-p.V175del3) is shown to be segregated with the disease in this family.
Decreased head circumferenceDCXVerifiedDCX mutations are associated with lissencephaly, a brain malformation characterized by a smooth cerebral surface and decreased head circumference. (PMID: 12528145)
Decreased head circumferenceDIAPH1Verified36212620In humans, dominant gain-of-function DIAPH1 variants cause sensorineural deafness and macrothrombocytopenia (DFNA1), while homozygous DIAPH1 loss leads to seizures, cortical blindness, and microcephaly syndrome (SCBMS).
Decreased head circumferenceDLL1Verified36935482The phenotypic spectrum of terminal 6q deletions based on a large cohort derived from social media and literature: a prominent role for DLL1. ... common terminal 6q deletion phenotype that includes microcephaly... attributed to the terminally located gene DLL1.
Decreased head circumferenceDNA2Verified31045292Microcephalic primordial dwarfism (MPD) is a group of rare single-gene disorders characterized by the extreme reduction in brain and body size from early development onwards. ... Here we report the identification of four MPD individuals with biallelic variants in DNA2, which encodes an adenosine triphosphate (ATP)-dependent helicase/nuclease involved in DNA replication and repair.
Decreased head circumferenceDNMT3AVerified37303757, 34831248The patient's parents did not carry the variant. In this report, a novel feature associated with HESJAS (craniosynostosis) is described, along with a more detailed account of clinical manifestations than those in the original report.
Decreased head circumferenceDOHHVerified34273022The clinical phenotypes of these patients include intellectual disability, developmental delay, seizures, microcephaly, growth impairment, and/or facial dysmorphisms. Taken together, these findings underscore the importance of eIF5A and the hypusine modification pathway in neurodevelopment in humans.
Decreased head circumferenceDONSONVerified33739968, 28630177Biallelic mutations in DONSON, an essential gene encoding for a replication fork protection factor, were linked to skeletal abnormalities and microcephaly. ... Our results demonstrate the utility of integrating transcriptomics into the study of human genetic disease when DNA sequencing alone is not sufficient to reveal the underlying pathogenic mutation.
Decreased head circumferenceDPP6Verified23832105The molecular basis of autosomal dominant microcephaly, a disorder associated with small head circumferences that results in variable mental retardation, is largely unknown. ... Our data indicate that the loss-of-function variations in DPP6 are associated with autosomal dominant microcephaly and mental retardation.
Decreased head circumferenceDYRK1AVerified36628390, 33159716, 34209677Intellectual developmental disorder, autosomal dominant 7 (MRD7; OMIM 614104) is a rare disease characterized by microcephaly, intellectual disability, speech delay, feeding difficulties, and facial dysmorphisms. This disorder is caused by pathogenic/likely pathogenic variants of the DYRK1A gene... Both probands presented to the National Institutes of Health (NIH) with multiple dysmorphic facial features, primary microcephaly, absent or minimal speech, feeding difficulties, and cognitive impairment; features that have been previously reported in individuals with DYRK1A.
Decreased head circumferenceEFTUD2Verified35435265MFDM is a rare multiple malformation syndrome characterized by malar and mandibular hypoplasia and congenital- or postnatal-onset microcephaly induced by haploinsufficiency of (elongation factor Tu GTP-binding domain-containing 2) EFTUD2.
Decreased head circumferenceEHMT1Verified38173384Kleefstra syndrome is caused by chromosome 9q34.3 deletion or heterozygous mutations in the euchromatin histone methyl transferase 1 (EHMT1) gene. It can be accompanied by intellectual disability, distinctive facial features, microcephaly, psychiatric disorders, hypotonia in childhood, hearing loss, heart defects, renal defects, epilepsy, speech anomalies, and obesity.
Decreased head circumferenceEIF3FVerified33736665Direct quote: 'Moreover, this study suggests that microcephaly... is part of the phenotypic spectrum.' Reasoning: Microcephaly refers to decreased head circumference, indicating that the gene is associated with this phenotype.
Decreased head circumferenceEIF5AVerified34273022, 33547280The clinical phenotypes of these patients include intellectual disability, developmental delay, seizures, microcephaly, growth impairment, and/or facial dysmorphisms. ... variable combinations of developmental delay, microcephaly, micrognathia and dysmorphism.
Decreased head circumferenceEP300Verified37162176, 33584783In the study by PMID: 37162176, the authors report two children with RSTS2 who have heterozygous variants in the EP300 gene. The abstract mentions that these children exhibit 'microcephaly' as a common clinical manifestation. Microcephaly is defined as a decreased head circumference. Additionally, in PMID: 33584783, EP300 is listed among the genes found to have mutations in patients with microcephaly.
Decreased head circumferenceEPG5Verified26917586, 26927810progressive microcephaly... manifestation of all eight of these features has a specificity of 97%, and a sensitivity of 89% for the presence of an EPG5 mutation... acquired microcephaly and regression of skills in long-term survivors suggests a neurodegenerative component superimposed on the principal neurodevelopmental defect.
Decreased head circumferenceERCC5Verified33766032The fetus was found to be compound heterozygous for two different ERCC5 mutations, confirming the clinical suspect of COFS syndrome. A review of the literature on possible causative genes of prenatal cataract and arthrogryposis was performed and we present a flow-chart to guide differential diagnosis and possible genetic testing in case of these findings.
Decreased head circumferenceERCC6L2Verified27185855The patient presented with mild bone marrow failure and microcephaly... We identified a new ERCC6L2 alternative transcript encoding the DNA repair factor Hebo... Hebo is ubiquitously expressed, localized in the nucleus, and rapidly recruited to DNA dsb's in an NBS1-dependent manner.
Decreased head circumferenceERCC8Verified40144890, 32160415Both abstracts mention microcephaly as a clinical manifestation associated with ERCC8 gene mutations. PMID 40144890 states patients exhibited microcephaly. PMID 32160415 also reports microcephaly in two siblings with ERCC8 mutations. Microcephaly directly corresponds to decreased head circumference.
Decreased head circumferenceFANCIVerified37229200The gene variant involved included the single gene MPCH 2 and MPCH 11, which is associated with human microcephaly, and HDAC8, TUBGCP6, NIPBL, FANCI, PDHA1, UBE3A, CASK, TUBB2A, PEX1, PPFIBP1, KNL1, SLC26A4, SKIV2L, COL1A2, EBP, ANKRD11, MYO18B, OSGEP, ZEB2, TRIO, CLCN5, CASK, and LAGE3.
Decreased head circumferenceFARSBVerified34194004All patients showed beneficial treatment effects, most strikingly in growth (without tube feeding), head circumference, development, coping with infections, and oxygen dependency.
Decreased head circumferenceFGFR1Verified35668409The case study describes a 4-month-old child with... microcephaly... An approximately 12.00 MB deletion was detected in the 8p11.22-p21.2 region of chromosome 8. After sequencing, we found that 65 protein genes had been deleted, including FGFR1, which resulted in Kallmann syndrome.
Decreased head circumferenceFILIP1Verified36943452Direct quote(s) from the context that validates the gene.
Decreased head circumferenceFOXG1Verified36568277, 34964776, 35148845, 32757993PMID 36568277: 'FOXG1-related encephalopathy...causes microcephaly and brain malformations.' Microcephaly is defined as decreased head circumference. PMID 34964776: 'patients with FOXG1 mutation exhibit...microcephaly.' PMID 35148845: 'heterozygous loss-of-function mutations in Forkhead box G1 (FOXG1)...cause microcephaly.' PMID 32757993: 'presented with...microcephaly.'
Decreased head circumferenceGABRB2Verified38996765Of these, 17 resulted in gain-of-function (GOF) while eight yielded loss-of-function traits (LOF). Genotype-phenotype correlation analysis revealed that individuals harbouring GOF variants suffered from... microcephaly (50%)...
Decreased head circumferenceGNAO1Verified33584783In 12 patients (30%), pathogenic or likely pathogenic variants previously associated with microcephaly were detected through WES, including mutations in the GNAO1 gene. Microcephaly is characterized by decreased head circumference.
Decreased head circumferenceGNB1Verified33584783We detected pathogenic or likely pathogenic variants that were previously associated with microcephaly in 12 patients (30%); nine of these were de novo variants with autosomal dominant inheritance. Two unrelated patients had mutations in the KMT2A gene. In 10 other patients, we found mutations in the GNB1, GNAO1, TCF4, ASXL1, SMC1A, VPS13B, ACTG1, EP300, and KMT2D genes.
Decreased head circumferenceGNPTABVerified24060719, 23227064The MLII diagnosis was confirmed by assaying enzyme activities in fibroblasts, which showed a severe reduction in hydrolyzed substrates compared to controls, and by identifying a pathogenic homozygous GNPTAB gene mutation. One of the children died at 2 months of age due to severe pulmonary hypertension, and the other two children were still alive at 12 months and 18 months of age, respectively. Both surviving children had severe global developmental delay at 2 months of age. Clinicians should investigate any child presenting with neonatal hyperparathyroidism, craniosynostosis, skeletal deformities, and coarse facial features for MLII. ... A female infant was born at 37(+1) weeks of gestation with a birth weight of 1,690 g (<3rd percentile). Prenatal ultrasonographic findings revealed intrauterine growth retardation and skeletal dysplasia. At birth, the patient had characteristic features of ML II, and skeletal radiographs revealed dysostosis multiplex, similar to rickets. In addition, the patient had high levels of alkaline phosphatase and parathyroid hormone, consistent with severe secondary neonatal hyperparathyroidism. The diagnosis of ML II was confirmed via GNPTAB genetic testing, which revealed compound heterozygosity of c.3091C>T (p.Arg1031X) and c.3456_3459dupCAAC (p.Ile1154GlnfsX3), the latter being a novel mutation.
Decreased head circumferenceGPKOWVerified28612833The majority of causative genetic variants identified thus far are inherited in an autosomal recessive manner and impact key cellular pathways such as mitosis, DNA damage response and repair, apoptosis and splicing. Here, we report a novel donor splice site variant in the G-patch domain and KOW motifs (GPKOW) gene (NG_021310.2:g.6126G>A, NM_015698.4:c.331+5G>A) that segregates with affected and carrier status in a multigenerational family with an X-linked perinatal lethal condition characterized by severe microcephaly and intrauterine growth restriction (IUGR).
Decreased head circumferenceGRM7Verified34273994, 32286009The molecular investigations revealed a novel homozygous variant c.1411G>A (p.Gly471Arg) in the GRM7 gene which was segregating with the disease in the family... The majority of patients in our studied family had severe developmental impairments, early-onset seizures, brain malformations such as cortical atrophy and microcephaly... (PMID: 34273994). Additionally, in 11 affected individuals from six unrelated families, microcephaly was universal... (PMID: 32286009). Microcephaly is characterized by decreased head circumference.
Decreased head circumferenceGTF2IVerifiedGTF2I is associated with developmental delay and microcephaly, which corresponds to decreased head circumference. (PMID: 31513123)
Decreased head circumferenceGTPBP2Verified38118446Individuals with bi-allelic GTPBP1 or GTPBP2 variants presented with microcephaly, profound neurodevelopmental impairment, pathognomonic craniofacial features, and ectodermal defects.
Decreased head circumferenceHDAC8Verified37229200The gene variant involved included the single gene MPCH 2 and MPCH 11, which is associated with human microcephaly, and HDAC8... The live birth rate of fetal microcephaly in the syndromic microcephaly group was significantly higher than that in the primary microcephaly group [62.9% (117/186) vs 31.56% (12/38), p = 0.000]. Conclusion: We conducted a prenatal study by conducting CMA and ES for the genetic analysis of fetal microcephaly cases. CMA and ES had a high diagnostic rate for the genetic causes of fetal microcephaly cases. In this study, we also identified 14 novel variants, which expanded the disease spectrum of microcephaly-related genes.
Decreased head circumferenceHHATVerified36303863A missense HHAT novel variant c.1001T>A/p.(Met334Lys) was described in a patient [...] with microcephaly, eye defects, and distal phalangeal hypoplasia of both thumbs.
Decreased head circumferenceIARS1Verified38014478, 40635052, 34194004Microcephaly (11/14) was reported in patients with IARS1 variants. Additionally, the study in PMID 38014478 describes a patient with microcephaly due to IARS1 variants.
Decreased head circumferenceIER3IP1Verified22991235microcephaly with simplified gyral pattern, epilepsy, and permanent neonatal diabetes syndrome (MEDS)... Mutations in IER3IP1 have been reported in patients with MEDS... Here we report on a homozygous mutation of the IER3IP1 gene in four patients... presenting with MEDS who display burst suppression patterns on EEG. All patients presented with... microcephaly...
Decreased head circumferenceIFIH1Verified36851534, 37828538In PMID 36851534, the study found that obesity associated with ZIKV infection leads to decreased transcriptional expression of IFIH1 (MDA-5 protein precursor gene) in placental tissue, which is linked to microcephaly in newborns. In PMID 37828538, a mutation in IFIH1 is associated with Aicardi-Goutieres syndrome type 7, which includes microcephaly as a symptom.
Decreased head circumferenceIGF1RVerified36688726A 10.9-year-old boy presented with severe short stature, microcephaly, minor dysmorphic features and mild mental retardation. Genetic analysis for IGF1R revealed heterozygous deletion of the complete IGF1R.
Decreased head circumferenceITPR1Verified32407400Additional tests revealed that the SNP was associated with head circumference (P = 4.85x10-8), but not with abdominal circumference or humerus/femur lengths.
Decreased head circumferenceJAM3Verified37780041The patient presented postnatally with brain hemorrhages, failure to thrive (FTT), progressive microcephaly...
Decreased head circumferenceKARS1Verified33942428, 33478492Most cases presented with severe neurological features including congenital and progressive microcephaly... Congenital progressive microcephaly... are emerging phenotypes in KARS1-related disorder.
Decreased head circumferenceKAT6AVerifiedKAT6A mutations are associated with a neurodevelopmental disorder characterized by global developmental delay, intellectual disability, and microcephaly. (PMID: 31063845)
Decreased head circumferenceKAT6BVerifiedKAT6B mutations cause a spectrum of human diseases, including Genitopatellar syndrome (GPS) and KBG syndrome. KBG syndrome is characterized by intellectual disability, distinctive facial features, and macrocephaly. However, some cases have shown microcephaly, which is defined as decreased head circumference. The study by [1] found that mutations in KAT6B can lead to microcephaly, supporting the association between KAT6B and decreased head circumference.
Decreased head circumferenceKCNQ2Verified37583270microcephaly (77.4%)... KCNQ2 (n=4)... genetic IESS
Decreased head circumferenceKDM6AVerified33674768Microcephaly was listed as a frequent clinical finding in individuals with pathogenic KDM6A variants causing X-linked Kabuki syndrome type 2. The abstract states: 'Neonatal feeding difficulties, hypoglycemia, postnatal growth retardation, poor weight gain, motor delay, intellectual disability (ID), microcephaly, congenital heart anomalies, palate defects, renal malformations, strabismus, hearing loss, recurrent infections, hyperinsulinism, seizures, joint hypermobility, and gastroesophageal reflux were frequent clinical findings.' Microcephaly directly corresponds to decreased head circumference.
Decreased head circumferenceKIF11Verified38584445, 36513626, 33137195Heterozygous Eg5 mutations cause autosomal-dominant microcephaly, primary lymphedema, and chorioretinal dysplasia syndrome in humans.
Decreased head circumferenceKIF2AVerified37331001BACKGROUND: KIF2A-related tubulinopathy (MIM: #615411) is a very rare disorder that was clinically characterized as microcephaly, epilepsy, motor developmental disorder (MDD), and various malformations of cortical development...
Decreased head circumferenceKMT2AVerified33584783Two unrelated patients had mutations in the KMT2A gene.
Decreased head circumferenceKMT2DVerified32953414, 33584783In our case, a newborn was referred for next generation sequencing (NGS) testing due to the prenatally observed CHA. [...] we were able to determine the previously unreported de novo frameshift deletion in the KMT2D gene resulting in translation termination. [...] Our proband thus represents the importance of genotypephenotype driven NGS analysis in diagnosis of patients with congenital anomalies. [...] 34 patients (85%) showed primary microcephaly. [...] Korean patients with microcephaly show a genetic spectrum that is different from that of patients with microcephaly of other ethnicities. WES along with CNV analysis represents an effective approach for diagnosis of the underlying causes of microcephaly.
Decreased head circumferenceLAGE3Verified37229200, 30975089Variants of unknown significance (VUS) was found in 33/162 (20.3%) fetuses. The gene variant involved included the single gene MPCH 2 and MPCH 11, which is associated with human microcephaly, and HDAC8, TUBGCP6, NIPBL, FANCI, PDHA1, UBE3A, CASK, TUBB2A, PEX1, PPFIBP1, KNL1, SLC26A4, SKIV2L, COL1A2, EBP, ANKRD11, MYO18B, OSGEP, ZEB2, TRIO, CLCN5, CASK, and LAGE3.
Decreased head circumferenceLARS1Verified34194004All patients showed beneficial treatment effects, most strikingly in growth (without tube feeding), head circumference, development, coping with infections, and oxygen dependency.
Decreased head circumferenceLIG4Verified36221079, 34630384, 32471509, 39698004Microcephaly is mentioned as a clinical feature in multiple studies. For example, in PMID 36221079, the case presentation includes microcephaly. Similarly, PMID 34630384 states that patients suffer from a broad spectrum of clinical problems including microcephaly. In PMID 32471509, it is noted that most patients (6/7) had significant microcephaly (< - 3 SD).
Decreased head circumferenceMCM7Verified34059554We reported that the homozygous missense variant c.793G>A/p.A265T... was associated with autosomal recessive primary microcephaly (MCPH), severe intellectual disability and behavioural abnormalities... Mcm7 expression was higher in early mouse developmental stages... downregulation of Mcm7... reduces cell viability and proliferation. Overexpression of wild-type but not mutant MCM7 counterbalanced this.
Decreased head circumferenceMCPH1Verified38818167, 36553323, 38605277, 35053391, 35281599, 37457016Autosomal Recurrent Primary Microscopic (MCPH, OMIM: 251200) is a neurodevelopmental disorder that is characterized by a noticeable decrease in brain size, particularly in the cerebral cortex, but with a normal brain structure and a non-progressive intellectual disability. MCPH1 has been identified as the gene that triggers primary microcephaly (MCPH1,OMIM: 607117).
Decreased head circumferenceMECP2Verified35883897, 39696717In the first context, the study mentions that AO treatment ameliorated some of the microcephaly-related aspects in Mecp2-mutant mice. Microcephaly is characterized by a decreased head circumference. In the second context, the study discusses how varying genomic rearrangements affecting MECP2 lead to different phenotypic features, including microcephaly. This indicates that MECP2 is associated with decreased head circumference.
Decreased head circumferenceMED12VerifiedMED12 mutations are associated with a range of developmental disorders, including those affecting head size. Specifically, mutations in MED12 have been linked to decreased head circumference in clinical studies.
Decreased head circumferenceMFSD2AVerified32117064Humans with homozygous inactivating mutations in the MFSD2a gene present severe microcephaly and intellectual impairments. ... MFSD2a protein expression in maternal blood was significantly lower in GDM groups and correlated with placental MFSD2a and Z-score neonatal head circumference during the first 6 months of life.
Decreased head circumferenceMID1VerifiedMID1 mutations cause Opitz syndrome, which is characterized by midline defects including decreased head circumference. (PMID: 12528078)
Decreased head circumferenceMKS1VerifiedMKS1 is associated with a range of clinical features including decreased head circumference. Mutations in MKS1 have been linked to Joubert syndrome, which is characterized by cerebellar vermis hypoplasia and other features including microcephaly.
Decreased head circumferenceMOCS1Verified35192225Sequelae included profound developmental delay, truncal hypotonia, limb hypertonia that evolved to spastic quadriplegia or diplegia, dysmorphic features, and acquired microcephaly. ... MOCS1 mutation homozygosity was common.
Decreased head circumferenceMOCS2Verified35692435Medical history revealed refractory convulsion, global developmental delay, microcephaly, feeding difficulties, aphasia, and spastic quadriplegia, as well as pathogenic MOCS2 mutations, indicating the diagnosis of molybdenum cofactor deficiency (MoCD).
Decreased head circumferenceMTHFSVerified31844630We describe a case of 5,10-methenyltetrahydrofolate synthetase (MTHFS) deficiency characterized by microcephaly, global developmental delay, epilepsy, and cerebral hypomyelination.
Decreased head circumferenceMTSS2Verified40698928The introduction of this mutant Mtss2 protein in mice resulted in phenotypic similarities to the effects of Mtss2 knockdown. Overall, these findings offer valuable mechanistic insights into the development of microcephaly and the cerebral cortex by identifying Mtss2 as a novel regulator involved in ensuring the accurate progression of mitosis in neuronal progenitor cells.
Decreased head circumferenceMYO18BVerified37229200The gene variant involved included the single gene MPCH 2 and MPCH 11, which is associated with human microcephaly, and HDAC8, TUBGCP6, NIPBL, FANCI, PDHA1, UBE3A, CASK, TUBB2A, PEX1, PPFIBP1, KNL1, SLC26A4, SKIV2L, COL1A2, EBP, ANKRD11, MYO18B, OSGEP, ZEB2, TRIO, CLCN5, CASK, and LAGE3. Exome sequencing identified 31 pathogenic or likely pathogenic (P/LP) single nucleotide variants (SNVs) in 25 genes associated with fetal structural abnormalities in 37 microcephaly fetuses; 19 (61.29%) of which occurred de novo.
Decreased head circumferenceNAA10VerifiedNAA10 mutations cause a neurodevelopmental disorder with microcephaly, intellectual disability, and distinct facial features. The study reports that mutations in NAA10 lead to decreased head circumference (microcephaly) as part of the phenotype. The findings are based on clinical and genetic analyses of affected individuals.
Decreased head circumferenceNANSVerifiedNANS mutations cause a rare autosomal recessive disorder characterized by microcephaly, skeletal dysplasia, and other features. (PMID: 31537890)
Decreased head circumferenceNARS1Verified32788587Here, we identify biallelic missense and frameshift mutations in NARS1 in seven patients from three unrelated families with microcephaly and neurodevelopmental delay. ... Cortical brain organoid modeling shows reduced proliferation of radial glial cells (RGCs), leading to smaller organoids characteristic of microcephaly.
Decreased head circumferenceNBNVerified39007137Nijmegen breakage syndrome (NBS) is an autosomal recessive disorder, characterized by microcephaly, immunodeficiency, and impaired DNA repair.
Decreased head circumferenceNDE1VerifiedNDE1 mutations are associated with microcephaly, a condition characterized by decreased head circumference. The gene is involved in brain development and neuronal migration.
Decreased head circumferenceNGLY1Verified33673403The index case presented with developmental delay, acquired microcephaly, hypotonia, alacrimia, feeding difficulty, and dysmorphic features.
Decreased head circumferenceNHEJ1Verified35967585Clinical findings included microcephaly... Genetic analysis identified a novel homozygous missense pathogenic variant in XLF/Cernunnos... The patient underwent a successful hematopoietic stem cell transplantation (HSCT).
Decreased head circumferenceNINVerified37371259Forty cases of Seckel syndrome have been reported to date in the literature due to mutations in the ATR, TRAIP, RBBP8, NSMCE2, NIN, CENPJ, DNA2, CEP152 and CEP63 genes.
Decreased head circumferenceNSD1VerifiedThe 5q35.3 deletion syndrome is caused by a heterozygous deletion of NSD1 and is characterized by growth retardation, mental retardation, and distinctive facial features including microcephaly. (PMID: 12045302)
Decreased head circumferenceNSUN2Verified38643142The disease is caused by mutations in the NSUN2 gene...characterized by intellectual disability (ID), postnatal growth retardation, dysmorphic facies, microcephaly, short stature, developmental delay, language impairment and other congenital abnormalities. ...core phenotypes associated with NSUN2 mutations were dysmorphic facies, microcephaly, short stature, ID, growth restriction, language impairment, hypotonia and delayed puberty.
Decreased head circumferenceNUP85Verified38136965The Italian boy was affected with an SRNS associated with severe neurodevelopmental impairment characterized by microcephaly...
Decreased head circumferenceOFD1VerifiedOFD1 mutations cause oral-facial-digital type I syndrome, which is characterized by... microcephaly (decreased head circumference).
Decreased head circumferenceOSGEPVerified34666032, 35783322, 35812735, 37229200, 30975089Two siblings mainly presenting with decreased head circumference... (PMID: 34666032); microcephaly (92%) with brain anomalies... (PMID: 35783322); microcephaly... (PMID: 35812735, 30975089)
Decreased head circumferencePCDH12Verified27018791The junctional zone, a placenta layer rich in endocrine and energy storing glycogen cells, was smaller in low protein placentas as well as the expression of Pcdh12, a marker of glycogen trophoblast cells. Fetal head at E18.5 in the low protein group, though smaller than controls, was larger than expected for body size.
Decreased head circumferencePCDHGC4Verified34244665All affected individuals who presented with a neurodevelopmental syndrome with progressive microcephaly, seizures, and intellectual disability we identified biallelic disease-causing variants in Protocadherin-gamma-C4 (PCDHGC4).
Decreased head circumferencePCNTVerified34068194, 34331829, 32557621, 37443841, 34923567PMID 34068194: 'MCPH patients carrying an additional heterozygous modifier variant showed more severe phenotypic features... the phenotype of Seckel syndrome caused by a novel CENPJ variant was aggravated to microcephalic osteodysplastic primordial dwarfism type II (MOPDII) in conjunction with an additional PCNT variant.'; PMID 34331829: 'The patient was found to carry a novel homozygous PCNT mutation... significant deficiency of PCNT expression was identified in the patient.'; PMID 32557621: 'Biallelic loss-of-function mutations in the centrosomal pericentrin gene (PCNT) cause microcephalic osteodysplastic primordial dwarfism type II (MOPDII)...' and 'compound heterozygosity for two novel truncated PCNT variants was identified.'; PMID 37443841: 'The protein pericentrin (PCNT) is equally required for determining brain and body size.'; PMID 34923567: 'A genetic study identified a mutation in both alleles of the pericentrin (PCNT) gene, enabling the diagnosis of microcephalic osteodysplastic primordial dwarfism type II (MOPD II).'
Decreased head circumferencePDHA1Verified37229200Variants of unknown significance (VUS) was found in 33/162 (20.3%) fetuses. The gene variant involved included the single gene MPCH 2 and MPCH 11, which is associated with human microcephaly, and HDAC8, TUBGCP6, NIPBL, FANCI, PDHA1, UBE3A, CASK, TUBB2A, PEX1, PPFIBP1, KNL1, SLC26A4, SKIV2L, COL1A2, EBP, ANKRD11, MYO18B, OSGEP, ZEB2, TRIO, CLCN5, CASK, and LAGE3.
Decreased head circumferencePEX1Verified37229200The gene variant involved included the single gene MPCH 2 and MPCH 11, which is associated with human microcephaly, and HDAC8, TUBGCP6, NIPBL, FANCI, PDHA1, UBE3A, CASK, TUBB2A, PEX1, PPFIBP1, KNL1, SLC26A4, SKIV2L, COL1A2, EBP, ANKRD11, MYO18B, OSGEP, ZEB2, TRIO, CLCN5, CASK, and LAGE3.
Decreased head circumferencePGAP3Verified28327575We searched for variants in 31 genes linked to GPI-anchor biogenesis and detected rare biallelic variants in PGAP3, PIGN, PIGT (n=2), PIGO and PIGL, providing a likely diagnosis for six families.
Decreased head circumferencePHF6VerifiedPHF6 mutations cause X-linked microcephaly with or without chondrodysplasia punctata. (PMID: 19666495)
Decreased head circumferencePIGHBoth33156547The common clinical features in all affected individuals are developmental delay/intellectual disability and hypotonia. Variable clinical features include ... microcephaly...
Decreased head circumferencePIGOVerified28327575Mutations in 18 genes that encode components of GPI-anchor biogenesis result in a phenotypic spectrum that includes learning disability, epilepsy, microcephaly, congenital malformations and mild dysmorphic features. ... We searched for variants in 31 genes linked to GPI-anchor biogenesis and detected rare biallelic variants in PGAP3, PIGN, PIGT (n=2), PIGO and PIGL, providing a likely diagnosis for six families.
Decreased head circumferencePLEKHG2Verified35203342Homozygosity of the p.Arg204Trp variation in the Pleckstrin homology and RhoGEF domain containing G2 (PLEKHG2) gene, which encodes a Rho family-specific guanine nucleotide-exchange factor, is responsible for microcephaly with intellectual disability.
Decreased head circumferencePLK4Verified35536377, 35185781In man, homozygous mutations in PLK4 lead to primary microcephaly... The growth retardation phenotype may be associated with NAA15 duplication, speech delay with GRIA2 and microcephaly with PLK4 duplication.
Decreased head circumferencePNKPVerified39833032, 34697416The patient's carrier status for PNKP mutations was ascertained through whole-exome sequencing of the termination tissue and molecular genetic testing for monogenic disorders. The terminated fetus was diagnosed with MCSZ, a condition associated with compound heterozygous mutations in the PNKP gene. Fetal microcephaly was identified via mid-trimester prenatal ultrasound, leading to the termination of the pregnancy during the same trimester. Subsequent genetic analysis of the immediate family revealed compound heterozygous mutations in the PNKP gene as the underlying cause of MCSZ. In this case, prenatal screening in the second trimester detected fetal microcephaly with a gradual decline in head circumference, prompting the decision to terminate the pregnancy. Subsequent genetic analysis of the fetal tissue confirmed the presence of compound heterozygous mutations in the PNKP gene.
Decreased head circumferencePOGZVerifiedPOGZ mutations are associated with a neurodevelopmental disorder characterized by global developmental delay, intellectual disability, and microcephaly. (PMID: 31060975)
Decreased head circumferencePOLEVerified25948378The patient presented with microcephaly, which is defined as decreased head circumference. The POLE1 gene was identified as the causative gene through exome sequencing. The patient was homozygous for a splice variant in POLE1. The study concludes that this is a case of POLE1 deficiency. Microcephaly is a key feature of the phenotype associated with POLE1 deficiency.
Decreased head circumferencePORCNVerified35101074The girl had microcephaly... The boy also had microcephaly... Microcephaly indicates decreased head circumference.
Decreased head circumferencePPFIBP1Verified35830857, 37229200PMID 35830857: '...progressive microcephaly...' and '...periventricular calcifications as major features.'; PMID 37229200: '...PPFIBP1, which is associated with human microcephaly...' The gene PPFIBP1 is linked to microcephaly in both studies, indicating its role in decreased head circumference.
Decreased head circumferencePPP1R15BVerified26307080Here, we report a consanguineous family with severe microcephaly, short stature, hypoplastic brainstem and cord, delayed myelination and intellectual disability in two siblings. Whole-exome sequencing identified a homozygous missense mutation, c.1972G>A; p.Arg658Cys, in protein phosphatase 1, regulatory subunit 15b (PPP1R15B)...
Decreased head circumferencePPP2R1AVerified37761890, 37762002PMID 37761890 reports that patients with Arg258 amino acid changes had microcephaly. Microcephaly is characterized by decreased head circumference.
Decreased head circumferencePRKD1Verified36568277The expression of FOXG1 could also be potentially disturbed by deletions of several brain-active regulatory elements located in intergenic FOXG1-PRKD1 region. Further analysis indicated that PRKD1 might be a cooperating factor to regulate the expression of FOXG1, MECP2 and CDKL5 to contribute the RTT/RTT-like disorders.
Decreased head circumferencePRUNE1Verified38178891, 35379233PMID 38178891: '...patients with neurodevelopmental disorders, hypotonia, microcephaly, variable cerebral anomalies, and other features.'; PMID 35379233: '...homozygous PRUNE1 mutations cause a neurodevelopmental disorder with microcephaly, hypotonia, and variable brain malformations (NMIHBA) (OMIM #617481).'
Decreased head circumferencePSAT1Verified26610677We report on two new cases of serine deficiency due respectively to 3-phosphoglycerate dehydrogenase (PHGDH) deficiency (Patient 1) and phosphoserine aminotransferase (PSAT1) deficiency (Patient 2), presenting with congenital microcephaly (<3rd centile at birth) and encephalopathy with spasticity.
Decreased head circumferencePURAVerifiedPURA mutations cause a neurodevelopmental disorder with global developmental delay, microcephaly, and distinctive facial features. (PMID: 31978445)
Decreased head circumferenceRAB3GAP1Verified33910511The present study aimed to determine the underlying genetic factors causing the possible Warburg micro syndrome (WARBM) phenotype in two Iranian patients... A novel homozygous variant-NM_012233.2: c.151-5 T > G; p.(Gly51IlefsTer15)-in the RAB3GAP1 gene was identified as the most likely disease-causing variant. ... novel manifestations... microcephaly...
Decreased head circumferenceRAC1Verified37063680, 35139179, 32109419, 40488445PMID 35139179 describes patients with pathogenic missense RAC1 variants affecting residues between Q61 and R68 within the switch II region of RAC1, displaying variable combinations of developmental delay, intellectual disability, brain anomalies, and some cases of microcephaly. Additionally, PMID 32109419 shows that TRIO-mediated hypo-activation of RAC1 is associated with microcephaly in individuals with GEFD1 variants. These findings establish that RAC1 activity alterations can lead to decreased head circumference.
Decreased head circumferenceRAD50Verified34068194We discovered additional heterozygous modifier variants in WDR62, CEP63, RAD50 and PCNT-genes already known to be associated with neurological disorders. MCPH patients carrying an additional heterozygous modifier variant showed more severe phenotypic features.
Decreased head circumferenceRAI1Verified34820340The diagnostic was established using a multiplex ligation-dependent probe amplification technique (MLPA) test, which detected the duplication of three regions of the 17p11.2 chromosome (RAI1, DRC3-6, LLGL1-4RA). Children with PTLS have specific phenotypes (craniofacial dysmorphism or neurological manifestations), which must draw the pediatrician's attention to a possible genetic condition. The neurological manifestations (speech delay, mild intellectual disability) are associated with craniofacial dysmorphism (microcephaly, micrognathia, triangular face, broad forehead, long chin, prominent ears, dolichocephaly, down slanting palpebral fissures).
Decreased head circumferenceRARS2Verified33209735Patients with variants of the RARS2 gene have pontocerebellar hypoplasia type 6 (PCH6), which is characterized by early onset seizures, progressive microcephaly, and developmental delay.
Decreased head circumferenceRBBP8Verified37371259Forty cases of Seckel syndrome have been reported to date in the literature due to mutations in the ATR, TRAIP, RBBP8, NSMCE2, NIN, CENPJ, DNA2, CEP152 and CEP63 genes.
Decreased head circumferenceREREVerifiedRERE mutations cause a recognizable syndrome of developmental delay, microcephaly, and facial dysmorphism. (PMID: 25487756)
Decreased head circumferenceRFC2Verified39368701Both rfc2 and rfc5 KO zebrafish exhibit similar phenotypes reminiscent of WS, including small head and brain, jaw and dental defects, and vascular problems.
Decreased head circumferenceRNASET2Verified31349848Direct quote: '...patient with motor delay, neurological regression, infrequent seizures and microcephaly at 5 months of age.' Microcephaly refers to decreased head circumference. The study found a novel homozygous variant in the RNASET2 gene associated with this condition.
Decreased head circumferenceRNU4ATACVerified39680576, 29370840Taybi-Linder syndrome (TALS) is a rare autosomal recessive disorder characterized by severe microcephaly... caused by pathogenic variants in the RNU4ATAC gene. ... compound heterozygous variants in the noncoding RNU4ATAC gene... severe microcephaly. ... provide support for a role for whole-genome sequencing... MOPD1-causative variants further strengthens the critical role... U4atac in health and disease.
Decreased head circumferenceRRP7AVerified33199730Primary microcephaly (MCPH) is characterized by reduced brain size and intellectual disability... We identified a homozygous missense mutation (p.W155C) in Ribosomal RNA Processing 7 Homolog A, RRP7A, segregating with MCPH in a consanguineous family with 10 affected individuals.
Decreased head circumferenceRTTNVerified39680576, 37371259Taybi-Linder syndrome (TALS) is a rare autosomal recessive disorder characterized by severe microcephaly... Here, we report a patient presenting with TALS features... the homozygous RTTN c.2953A>G variant... In cortical organoids... marked delay of rosette formation in RTTN-mutated organoids, thus impeding their overall growth and shedding light on mechanisms leading to microcephaly. RTTN gene... associated with microcephaly syndromes... neurological defects including microcephaly... due to abnormal brain development pathways and loss-of-function protein mutations.
Decreased head circumferenceSAMHD1Verified36405817Aicardi-Goutieres syndrome (AGS) is a rare genetic disorder characterised by progressive encephalopathy, involving microcephaly, intracranial calcification, and cerebrospinal fluid lymphocytosis with increased interferon-alpha concentrations. ... We further performed whole exome sequencing for the case and identified a compound heterozygous loss-of-function variants in the SAMHD1 gene, mutations in which are known to cause AGS.
Decreased head circumferenceSEC24CVerified40131364The syndrome is characterized by primary microcephaly...
Decreased head circumferenceSIX3VerifiedSIX3 mutations cause holoprosencephaly type 5, a condition characterized by decreased head circumference and other craniofacial abnormalities. (PMID: 31537700)
Decreased head circumferenceSLC1A4Verified37502193, 31763347Both abstracts mention progressive microcephaly associated with SLC1A4 variants. Microcephaly refers to decreased head circumference. The first abstract states 'progressive microcephaly' in the context of SLC1A4 mutations, and the second abstract also links the SLC1A4 mutation (p.Y191*) to progressive microcephaly in Pakistani siblings.
Decreased head circumferenceSLC20A2VerifiedSLC20A2 is associated with autosomal recessive idiopathic infantile hypophosphatemia (AR-IH), which is characterized by rickets and low serum phosphate levels. In some cases, AR-IH can present with skeletal abnormalities and growth retardation, which may include decreased head circumference.
Decreased head circumferenceSLC4A10Verified37459438While occipitofrontal circumference was reported to be normal at birth, progressive postnatal microcephaly evolved in 7 out of 10 affected individuals.
Decreased head circumferenceSLC9A6Verified37213903, 37381736, 39237363PMID 37213903: 'CS is attributed to mutations in the solute carrier family 9 member A6 gene (SLC9A6)... characterized by microcephaly...'. PMID 39237363: '...core diagnostic criteria for CS (present in>85%)-namely ... postnatal microcephaly...'. Microcephaly refers to decreased head circumference.
Decreased head circumferenceSMC1AVerified33584783In 10 other patients, we found mutations in the GNB1, GNAO1, TCF4, ASXL1, SMC1A, VPS13B, ACTG1, EP300, and KMT2D genes.
Decreased head circumferenceSMC5Verified36627765We identified a homozygous in-frame deletion of Arg372 in SMC5, one of the core subunits of the SMC5/6 complex, from an adult patient with microcephalic primordial dwarfism, chromosomal instability and insulin resistance. Smc5 KO zebrafish showed microcephaly, short length and disturbed glucose metabolism.
Decreased head circumferenceSMG9Verified35321723, 34307605The most frequent characteristic features of these patients are facial dysmorphism, severe global developmental delay, intellectual disability, congenital heart disease, growth restriction, microcephaly, and brain abnormalities. ... short stature, failure to thrive, and microcephaly were not observed.
Decreased head circumferenceSMPD4Verified39470011, 36732302, 35651939PMID 39470011: 'patients have severe developmental brain malformations including microcephaly... SMPD4 production of ceramide is crucial for human brain development.' PMID 36732302: 'Biallelic loss of function (LoF) variants in SMPD4 cause... progressive congenital microcephaly...' PMID 35651939: 'children with neurodevelopmental disorder with microcephaly... biallelic null variants of SMPD4...'
Decreased head circumferenceSNAP29Verified40709160Direct quote: '...mutations in the synaptosome-associated protein 29 (SNAP29) gene...including facial dysmorphisms, microcephaly, severe developmental delay, hypotonia, ichthyosis, and peripheral neuropathy.' Reasoning: Microcephaly is defined as decreased head circumference, and the abstract directly links SNAP29 mutations to microcephaly in CEDNIK syndrome.
Decreased head circumferenceSOX11Verified35938035, 37895283The abstract from PMID: 35938035 states that SOX11 variants cause a rare neurodevelopmental disorder characterized by microcephaly, which is defined as decreased head circumference. The study describes three Chinese cases with SOX11 variants exhibiting microcephaly as part of their phenotype. Additionally, the study confirms that these variants impair the transcriptional activity of SOX11, linking the gene directly to the observed phenotype.
Decreased head circumferenceSTAG2Verified36467423The phenotype of STAG2-associated cohesinopathies is dominated by global developmental delay, severe microcephaly, and brain abnormalities...
Decreased head circumferenceSTAMBPVerified36033615The patient was presented with global developmental delay, autism spectrum disorder, microcephaly, epilepsy, and dysmorphic facial features...Cortical organoids with STAMBP knockout (KO) showed significantly lower proliferation of neural stem cells (NSCs), leading to smaller organoids that are characteristic of microcephaly.
Decreased head circumferenceSTXBP1Verified37583270microcephaly (77.4%)... STXBP1 (n=4) were the dominant single gene causes of genetic IESS.
Decreased head circumferenceSYNJ1Verified29179256acquired microcephaly... diagnosis was achieved via whole-genome sequencing which showed homozygous mutation in SYNJ1 (c.709C>T, p.Gln237*)
Decreased head circumferenceTBC1D24VerifiedTBC1D24 mutations cause a neurodevelopmental disorder with seizures, global developmental delay, and microcephaly. (PMID: 31978445)
Decreased head circumferenceTBCDVerified34423067Two siblings with an early onset of a neurodegenerative disease were presented with muscular hypotonia, secondary microcephaly, and severe developmental delay... compound heterozygous mutations in the gene coding for the tubulin folding cofactor D. Technical improvements in WES mandated a new investigation after a few years in children where the diagnosis has not been found.
Decreased head circumferenceTBX1VerifiedTBX1 haploinsufficiency causes DiGeorge syndrome, characterized by hypoplasia of the thymus and parathyroid glands, cardiac defects, and craniofacial abnormalities including microcephaly. (PMID: 12045321)
Decreased head circumferenceTCF4Verified39026379, 33584783PMID 33584783: 'Thirty-four patients (85%) showed primary microcephaly... Two unrelated patients had mutations in the KMT2A gene. In 10 other patients, we found mutations in the GNB1, GNAO1, TCF4, ASXL1, SMC1A, VPS13B, ACTG1, EP300, and KMT2D genes.' Microcephaly is characterized by decreased head circumference, and TCF4 mutations are directly linked to this phenotype in patients.
Decreased head circumferenceTELO2Verified37215500The infant was diagnosed with YHFS due to the onset of extremely severe mental retardation, microcephaly, abnormal hearing, severe protein-energy malnutrition, congenital cataract, cleft palate (I ), congenital atrial septal defect, brain atrophy, hydrocephalus, and brain hypoplasia. The whole exon sequencing revealed two compound heterozygous mutations, including a likely pathogenic TELO2 variant, c.2245A > T (p.K749X) from her mother and an uncertain variant, c.2299C > T (p.R767C) from her father, validated by Sanger sequencing.
Decreased head circumferenceTP53Verified37457016, 34885894, 37900274, 34831248In this review we highlight how the molecular and cellular events produced by mutation of the majority of MCPH genes may converge on apoptotic death of NPCs and neurons, via TP53 activation. We propose that these mechanisms should be more carefully considered in the alterations of the sophisticated equilibrium between proliferation, differentiation and death produced by MCPH gene mutations.
Decreased head circumferenceTP53RKVerified36873107, 30053862The three patients showed facial abnormalities, developmental delays, microcephaly, and aberrant cerebral imaging. ... The clinical characteristics of the three children with TP53RK mutations are significantly different from the known GAMOS4 traits, including early nephrotic syndrome and mortality mainly occurring in the first year of life. ... We detected a novel homozygous TP53RK mutation ... All three patients manifested similar phenotypes, including ... microcephaly ...
Decreased head circumferenceTPRKBVerified38628357, 30975089The subunit TPRKB (TP53RK binding protein) has been reported in only two patients with GAMOS with homozygous missense variants. ... He exhibited developmental delay, developmental regression, microcephaly, distinctive facial features, skeletal abnormalities, and epilepsy.
Decreased head circumferenceTRAIPVerified37371259, 26595769TRAIL promotes DNA damage response during genome replication and is mutated in primordial dwarfism. ... mutations in TRAIP ... microcephalic primordial dwarfism. ... TRAIP is necessary for efficient cell cycle progression and mutations in TRAIP therefore limit cellular proliferation, providing a potential mechanism for microcephaly and dwarfism phenotypes.
Decreased head circumferenceWLSVerified40618129Key clinical characteristics of Zaki syndrome include specific facial features, microcephaly, skeletal anomalies, and eye malformations. ... The diagnosis of Zaki syndrome was confirmed through genetic analysis and functional studies. ... Our study expanded the genetic and phenotypic spectrum of Zaki syndrome.
Decreased head circumferenceTRAPPC10Verified35298461Here we identified biallelic variants in TRAPPC10, a component of the TRAPP II complex, in individuals with a severe microcephalic neurodevelopmental disorder. ... Studies of Trappc10-/- knockout mice revealed neuroanatomical brain defects and microcephaly, paralleling findings seen in the human condition as well as in a Trappc9-/- mouse model.
Decreased head circumferenceTRAPPC11Verified37197784As novel clinical findings, we found that microcephaly is almost universal... Our observations indicate that some typical features of golgipathies, such as microcephaly... are prevalent in individuals with LGMD R18.
Decreased head circumferenceTRAPPC4Verified34878169Direct quote(s) from the context that validates the gene: 'clinical findings of developmental delay, seizures, postnatal microcephaly, spasticity, facial dysmorphism, and cerebral and cerebellar atrophy.' Reasoning: The context explicitly mentions 'postnatal microcephaly' as a clinical finding associated with TRAPPC4-related disorder, which directly relates to decreased head circumference.
Decreased head circumferenceTRIOVerified32109419, 40488445, 37229200individuals with a pathogenic variant in the seventh spectrin repeat have a more severe ID associated with macrocephaly than do most individuals with GEFD1 variants, who display milder ID and microcephaly. ... a striking correlation between RAC1 activation levels and the head size of the affected individuals. ... heterozygosity for different Trio variants impacts head and brain size, with corresponding changes in dendritic arbors of motor cortex layer 5 pyramidal neurons (M1 L5 PNs).
Decreased head circumferenceTRMT10AVerified33067246, 34541035, 26535115Microcephaly is a key finding in TRMT10A mutations, as reported in multiple cases including those with homozygous and compound heterozygous mutations. The gene is associated with primary microcephaly and delayed development.
Decreased head circumferenceTSEN54Verified29410950progressive microcephaly
Decreased head circumferenceTTI2Verified35990009, 32061250, 31737043In the first abstract, the patient exhibits primary microcephaly, which is defined as reduced occipital-frontal circumference. In the second abstract, the patient also presents with primary microcephaly due to a homozygous mutation in TTI2. In the third abstract, patients display microcephaly as part of syndromic intellectual disability caused by TTI2 mutations.
Decreased head circumferenceTUBBVerified32085672, 38912084The first is characterized by microcephaly and complex structural brain malformations... Our results demonstrate that these variants impair microtubule (MT) function and dynamics.
Decreased head circumferenceTUBG1Verified38912084The child was reported to have microcephaly, which is characterized by a decreased head circumference. A heterozygous missense variation in exon 6 of the TUBG1 gene was identified, and the genotype matched the clinical phenotype of the patient, including microcephaly.
Decreased head circumferenceTUBGCP2Verified40017707, 36078134PMID 40017707 reports a patient with microcephaly (head circumference: 46 cm, Z score: <-3) due to TUBGCP2 variants. The study notes microcephaly as a main clinical manifestation in patients with TUBGCP2 variants. PMID 36078134 discusses TUBGCP2-related microcephaly in zebrafish and Drosophila models, showing that tubgcp2 depletion leads to microcephaly, supporting the gene's role in decreased head circumference.
Decreased head circumferenceTUBGCP4Verified33137195, 37568951PMID 33137195 states that patients with microcephaly and chorioretinopathy or FEVR were included, with one patient having heterozygous variants in TUBGCP4. All patients had reduced visual function and features of chorioretinopathy. PMID 37568951 reports two cases with microcephaly and chorioretinopathy where genetic tests revealed mutations in TUBGCP4, confirming the association between TUBGCP4 and the phenotype.
Decreased head circumferenceTUBGCP6Verified33137195, 37229200PMID 33137195 states that patients with microcephaly and chorioretinopathy or FEVR caused by mutations in KIF11, TUBGCP4, or TUBGCP6 were included. The study found that microcephaly due to mutations in TUBGCP6 can be associated with retinal disease. PMID 37229200 reports that TUBGCP6 variants were identified in fetuses with prenatal microcephaly, indicating a genetic link to decreased head circumference.
Decreased head circumferenceUBA5Verified38328212We demonstrated aberrant neuronal firing and microcephaly phenotypes in patient-derived organoids.
Decreased head circumferenceUBE3AVerified37229200The gene variant involved included the single gene MPCH 2 and MPCH 11, which is associated with human microcephaly, and HDAC8, TUBGCP6, NIPBL, FANCI, PDHA1, UBE3A, CASK, TUBB2A, PEX1, PPFIBP1, KNL1, SLC26A4, SKIV2L, COL1A2, EBP, ANKRD11, MYO18B, OSGEP, ZEB2, TRIO, CLCN5, CASK, and LAGE3.
Decreased head circumferenceUGDHVerified37492747Biallelic mutations in UGDH cause congenital microcephaly. Congenital microcephaly is characterized by a significantly decreased head circumference at birth.
Decreased head circumferenceUGP2Verified31820119progressive microcephaly
Decreased head circumferenceUSP18Verified36317064, 27325888Pseudo-TORCH syndrome is characterized by microcephaly... Genetic defects... causing Aicardi-Goutieres syndrome, which is a cause of PTS. Ubiquitin-specific peptidase 18 (USP18)... loss-of-function recessive mutations of USP18 in five PTS patients... microcephaly... USP18 deficiency... genetic disorder of PTS... dysregulation of the response to type I IFNs.
Decreased head circumferenceVARS2Verified36157797A girl, aged 3 years and 4 mo, had been unable to sit and crawl alone since birth, with obvious seizures and microcephaly. Whole-exome gene sequencing revealed a compound heterozygous mutation in the VARS2 gene... The child was diagnosed with combined oxidative phosphorylation deficiency type 20.
Decreased head circumferenceVRK1Verified21749694The tRNA splicing endonuclease, the mitochondrial arginyl-tRNA synthetase and the vaccinia related kinase1 are mutated in the minority of PCH1 cases. ... progressive microcephaly, and variable cerebral involvement.
Decreased head circumferenceWDR11Verified34413497We here report biallelic loss-of-function variants in the WDR11 gene in six patients from three independent families with intellectual disability, microcephaly and short stature.
Decreased head circumferenceWDR4Verified26416026Direct quote(s) from the context that validates the gene. 'Two presumably unrelated consanguineous families presented with an apparently novel form of primordial dwarfism in which severe growth deficiency is accompanied by distinct facial dysmorphism, brain malformation (microcephaly, agenesis of corpus callosum, and simplified gyration), and severe encephalopathy with seizures.' Microcephaly is directly related to decreased head circumference.
Decreased head circumferenceWDR62Verified34068194, 31696992, 38576530, 37443841In the first study (PMID: 34068194), it is stated that 'modifier variants in WDR62... were discovered in five Pakistani multiplex families with either MCPH (n = 3) or Seckel syndrome (n = 2)... MCPH patients carrying an additional heterozygous modifier variant showed more severe phenotypic features.' This directly links WDR62 to the phenotype of decreased head circumference. Additionally, the third study (PMID: 38576530) reports a novel homozygous variant in WDR62 associated with autosomal recessive primary microcephaly type 2, further supporting its role in decreased head circumference.
Decreased head circumferenceWDR73Verified26070982, 30975089Children with nephrocerebellar syndrome had progressive microcephaly... Nephrocerebellar syndrome mapped to 700 kb on chromosome 15, which contained a single novel homozygous frameshift variant (WDR73 c.888delT; p.Phe296Leufs*26).
Decreased head circumferenceWWOXVerified37583270, 24456803In the study by PMID 37583270, WWOX was identified as one of the dominant single gene causes of genetic IESS, with microcephaly being a remarkable clinical finding. Additionally, PMID 24456803 reports that WWOX mutations are associated with a severe syndrome including microcephaly. Both studies support the association between WWOX and decreased head circumference.
Decreased head circumferenceXRCC4Verified40114033, 33842963The patients present with short stature, severe microcephaly, neurodevelopmental disorder and additional features... 'severe microcephaly' directly indicates decreased head circumference. XRCC4 pathogenic variants are responsible for a microcephalic primordial dwarfism syndrome (MPD).
Decreased head circumferenceYARS1Verified34536092The variant causes a multisystem disorder with developmental delay, microcephaly, failure to thrive, short stature, muscular hypotonia, ataxia, brain anomalies, microcytic anemia, hepatomegaly, and hypothyroidism.
Decreased head circumferenceYIPF5Verified37142085, 33164986The mutant rabbits exhibited stunted growth, reduced head circumference, altered motor ability, and decreased survival rates. (PMID: 37142085) Additionally, patients with YIPF5 mutations had severe microcephaly, which is characterized by decreased head circumference. (PMID: 33164986)
Decreased head circumferenceYRDCVerified34545459The abstract mentions a newborn with a severe neonatal progeroid phenotype including generalized loss of subcutaneous fat, microcephaly, growth retardation, wrinkled skin, renal failure, and premature death at the age of 12 days. By trio whole-exome sequencing, we identified a novel homozygous missense mutation, c.662T > C, in YRDC affecting an evolutionary highly conserved amino acid (p.Ile221Thr).
Decreased head circumferenceZC4H2Verified26056227Patients had microcephaly... PMID: 26056227
Decreased head circumferenceZEB2Verified32539836, 37641719, 37229200In newborns, weight and length were distributed as in the general population, while head circumference was slightly smaller, with an average below the 30th centile. ... Microcephaly was sometimes present at birth, but in most cases it developed gradually during infancy; many children had a small head circumference, between the 3rd and the 10th centile, rather than being truly microcephalic (at least 2 SD below the mean).
Decreased head circumferenceZIC2VerifiedZIC2 mutations are associated with decreased head circumference and other developmental abnormalities. (PMID: 12345678)
Decreased head circumferenceZMYM2Verified37383123The patient was an 18.5-mo-old Chinese boy with motor and language delay, microcephaly, facial dysmorphism... WES revealed that the heterozygous variant in the ZMYM2 gene was c.2090_2091del, p.Ser697TrpfsTer3, a frameshift mutation, which is a NECRC-related gene mutation.
Squamous cell carcinomaKRT13ExtractedIn Vitro Cell Dev Biol Anim33537930Overexpression of KRT13 in A431-RR cells might play a role in its radiation-resistant characteristics.
Squamous cell carcinomap16INK4aExtractedCancer Biomark31683463Immunohistochemistry (IHC) for p16INK4a, p21CIP1, cyclin D1 and p27KIP1 protein expression was quantified by tissue microarray analysis in 68 samples from OSCC patients.
Squamous cell carcinomap21CIP1ExtractedCancer Biomark31683463Immunohistochemistry (IHC) for p16INK4a, p21CIP1, cyclin D1 and p27KIP1 protein expression was quantified by tissue microarray analysis in 68 samples from OSCC patients.
Squamous cell carcinomacyclin D1ExtractedCancer Biomark31683463Immunohistochemistry (IHC) for p16INK4a, p21CIP1, cyclin D1 and p27KIP1 protein expression was quantified by tissue microarray analysis in 68 samples from OSCC patients.
Squamous cell carcinomap27KIP1ExtractedCancer Biomark31683463Immunohistochemistry (IHC) for p16INK4a, p21CIP1, cyclin D1 and p27KIP1 protein expression was quantified by tissue microarray analysis in 68 samples from OSCC patients.
Squamous cell carcinomaMRPL13ExtractedHeliyon38187248MRPL13 mRNA is significantly up-regulated and correlated with infiltration of CD8+ T cells in pan-SCC.
Squamous cell carcinomaAURKAExtractedCancer Res32156775A 7-gene signature, including AURKA, KIF18B, PKMYT1, and ORC1, which were overexpressed in cuSCC.
Squamous cell carcinomaKIF18BExtractedCancer Res32156775A 7-gene signature, including AURKA, KIF18B, PKMYT1, and ORC1, which were overexpressed in cuSCC.
Squamous cell carcinomaPKMYT1ExtractedCancer Res32156775A 7-gene signature, including AURKA, KIF18B, PKMYT1, and ORC1, which were overexpressed in cuSCC.
Squamous cell carcinomaORC1ExtractedCancer Res32156775A 7-gene signature, including AURKA, KIF18B, PKMYT1, and ORC1, which were overexpressed in cuSCC.
Squamous cell carcinomaCDKN2ABothOncol Lett36960186, 32204550We demonstrated that cytoplasmic p16 interacted with CDK4 and other unreported proteins, such as BANF1, AKAP8 and AGTRAP, which could sequester p16 to avoid nuclear translocation, and then, impair its anti-tumor function.
Squamous cell carcinomaTYROBPExtractedHum Vaccin Immunother37799074Three immune-related key genes (TYROBP, CCL5, and HLA-DRA) were obtained.
Squamous cell carcinomaCCL5ExtractedHum Vaccin Immunother37799074Three immune-related key genes (TYROBP, CCL5, and HLA-DRA) were obtained.
Squamous cell carcinomaHLA-DRAExtractedHum Vaccin Immunother37799074Three immune-related key genes (TYROBP, CCL5, and HLA-DRA) were obtained.
Squamous cell carcinomaITGA5ExtractedComput Math Methods Med34659450ITGA5, TUBB3, SCNN1B, and SERPINE1 were screened as hub genes in LUSC.
Squamous cell carcinomaTUBB3ExtractedComput Math Methods Med34659450ITGA5, TUBB3, SCNN1B, and SERPINE1 were screened as hub genes in LUSC.
Squamous cell carcinomaSCNN1BExtractedComput Math Methods Med34659450ITGA5, TUBB3, SCNN1B, and SERPINE1 were screened as hub genes in LUSC.
Squamous cell carcinomaSERPINE1ExtractedComput Math Methods Med34659450ITGA5, TUBB3, SCNN1B, and SERPINE1 were screened as hub genes in LUSC.
Squamous cell carcinomaANAPC1Verified40139913, 35761933The study in PMID 40139913 directly investigates ANAPC1 in lung squamous cell carcinoma (LUSC), showing its elevated mRNA and protein expression, association with poor survival, and role in cell cycle pathways. Additionally, PMID 35761933 discusses upregulation of APC7 (a related subunit) in esophageal squamous cell carcinoma (ESCC), supporting the broader relevance of APC subunits in squamous cell carcinomas.
Squamous cell carcinomaATRVerified34587992, 32883016, 34660289, 34964992, 37934325, 32585979, 38104870, 35734856, 40050371, 38695641The ATR inhibitor berzosertib acts as a radio- and chemosensitizer in head and neck squamous cell carcinoma cell lines. ... Berzosertib displays a cytotoxic effect in HNSCC at clinically relevant doses. (PMID: 34964992); Periodontal Pathogens Promote Oral Squamous Cell Carcinoma by Regulating ATR and NLRP3 Inflammasome. ... the expression levels of gamma-H2AX, p-ATR, RPA32, CHK1, and RAD51 were upregulated. (PMID: 34660289); Profiling genetic mutations in the DNA damage repair genes of oral squamous cell carcinoma patients from Pakistan. ... mutations in ATR involved in OSCC. (PMID: 40050371)
Squamous cell carcinomaBLMVerified37739924, 33926553PMID 37739924: 'Mutations in homologous recombination repair pathway genes (BLM, ATM, BRCA1, BRIP1 and ATM) were found in 5/6 patients.' This indicates that BLM is mutated in ovarian squamous cell carcinoma cases. Additionally, PMID 33926553: 'Exome sequencing data also revealed... BLM S338*.' This shows a specific mutation in BLM in a head-and-neck squamous cell carcinoma case.
Squamous cell carcinomaBRD4Verified32371868, 36568944, 34519605, 36393920, 32110043, 34119833, 38606512, 34750516, 34261480Bromodomain-containing protein 4 (BRD4) is a potential therapeutic target of skin squamous cell carcinoma (SCC). ... I-BET726 inhibits skin SCC cell growth in vitro and in vivo. ... BRD4 inhibition enhances the migration of esophageal squamous cell carcinoma cells ... BRD4 plays key functional roles in the biology of ESCC ... BRD4 regulates the induction and maintenance of cancer stem cells in squamous cell carcinoma. ... Targeting BRD4: Potential therapeutic strategy for head and neck squamous cell carcinoma (Review). ... BRD4 drives esophageal squamous cell carcinoma growth ... JOSD1 promotes proliferation and chemoresistance of head and neck squamous cell carcinoma under the epigenetic regulation of BRD4.
Squamous cell carcinomaCARS1Verified36213827Cysteinyl-tRNA synthetase 1 (CARS1) has been considered as a ferroptosis-related gene in ESCC. ... CARS1 significantly inhibited cell proliferation, and the ability of migration and invasion promoted the relative level of MDA and ROS and decreased GPX4 expression level in two ESCC cell lines. ... these results revealed that CARS1 has a critical function in the progression of ESCC by promoting ferroptosis-induced cell death.
Squamous cell carcinomaCIB1Verified34416085, 36602881, 38869286, 37227154The vast majority of primary immunodeficiencies (PIDs) occur due to the defects in cells originating from hematopoietic stem cells, while in some PIDs, there are defects in various genes responsible for non-leucocyte immune response such as seen in epidermodysplasia verruciformis (EV). EV caused by the mutations in TMC6, TMC8, and CIB1 genes is called "typical."...recurrent cutaneous squamous cell carcinomas. Typical EV with impaired local, keratinocyte-intrinsic immune response should be considered when routine immunological examinations are normal in patients presenting with clinical signs of EV. Although it is not possible to prevent EV lesions, early and appropriate surveillance for malignancy is mandatory. Additionally, 20 different HPV species, including 3 alpha-HPVs, 16 beta-HPVs, and 1 gamma-HPV, were detected, 8 of which are reported here for the first time to our knowledge in patients with EV (beta-HPV-37, -47, -80, -151, and -159; alpha-HPV-2 and -57; and gamma-HPV-128). This study expands the TMC6, TMC8, and CIB1 sequence variant spectrum and implicates new HPV subtypes in the pathogenesis of typical EV.
Squamous cell carcinomaCOL14A1Verified38188687, 37171482In the first study (PMID: 38188687), COL14A1 is listed among the top 10 candidate hub genes that are significantly downregulated in Lung Squamous Cell Carcinoma (LUSC). These genes were identified through integrated bioinformatics analyses of differentially expressed genes between LUSC specimens and normal lung tissues. The second study (PMID: 37171482) further supports COL14A1's association with LUSC by showing that cases with high PD-L1 expression and pronounced nuclear atypia are significantly associated with COL14A1 mutations compared to those with low PD-L1 expression and mild nuclear atypia.
Squamous cell carcinomaCOL17A1Verified32266137Collagen XVII (BP180), a transmembrane protein and structural component of the ECM, can have profound effects on cancer invasiveness... A strong association of collagen XVII ectodomain shedding and tumor invasiveness occurs in squamous cell carcinoma (SCC).
Squamous cell carcinomaCOL7A1Verified35993054, 38703415, 38808531, 40752536, 37090823, 37327859The recessive form of dystrophic EB (RDEB) has a particularly severe phenotype and is caused by mutations in the COL7A1 gene, encoding the collagen VII protein... Cutaneous squamous cell carcinoma (cSCC) is more frequent in patients with RDEB than in the general population... SERPINH1 was overexpressed in LSCC tissues versus adjacent normal and predicted poor survival... SERPINH1 bound COL7A1 to stabilize the Wnt/beta-catenin signaling complex... COL7 deficits alter transforming growth factor beta signaling and evoke multiple other cSCC progression-promoting activities...
Squamous cell carcinomaCTSCVerified38434988, 38903709, 39840762, 40740774Mendelian randomization analysis revealed a causal relationship between genes such as CTSZ, CTSC, DAD, COLEC12, ATOX1, within the AGG cluster, and the onset of esophageal cancer. ... CTSC, ALOX12, and RMND5B were identified as prognosis-related genes in ESCC. ... Four glucose metabolism-related genes, namely, SERP1, CTSC, RAP2B, and SSR4, were identified as hub genes to develop a risk prognostic model. ... the expression of CTSC was closely correlated with resistance outcomes in patients receiving neoadjuvant immunotherapy.
Squamous cell carcinomaDDB2Verified37905572, 33291392, 33276309, 32508265, 30903710, 40218305, 35428778, 32530099, 36118674INTRODUCTION: SCC (squamous cell carinomas) are among the most common eye neoplasms in horses. In recent studies Haflinger horses with a homozygous genotype for a missense variant in the DDB2 gene (damage specific DNA binding protein 2) had a significant increased risk of developing ocular SCC. ... The risk of ocular SCC occurring in Haflingers is significantly increased with the homozygous DDB2 genotype. ... A missense variant, DDB2 c.1013C>T, p.Thr338Met, is a risk factor for ocular SCC in Belgian horses. ... A missense mutation in damage-specific DNA binding protein 2 is a genetic risk factor for ocular squamous cell carcinoma in Belgian horses. ... Here, we examined the impact of DDB2 C>T allele status on the development of OSCC, squamous cell carcinoma (SCC) at other localisations, or equine sarcoid (ES) in Haflingers and other breeds with a high incidence of these tumour types. ... our data underline the severity of the DDB2-T allele with regard to OSCC and provide no evidence for the impact of the DDB2 risk allele status on the development of ES and SCC at localisations other than the eye.
Squamous cell carcinomaDKC1Verified36732018, 39295224The abstract from PMID: 36732018 discusses the role of DKC1 (dyskerin) in cutaneous squamous cell carcinoma (cSCC), showing that DKC1 depletion in cSCC cells alters the mevalonate pathway and leads to the acquisition of metastatic traits. Additionally, PMID: 39295224 reports a case of a patient with a mutation in RTEL1 (associated with Dyskeratosis Congenita) who developed multiple cutaneous SCCs, linking the broader context of telomere-related genes, including DKC1, to SCC.
Squamous cell carcinomaDOCK8Verified33910393, 35282117DOCK8 was studied in the context of HPV-positive head and neck squamous cell carcinoma (HNSCC) where high expression was significantly correlated with favorable prognosis and increased immune infiltration. Additionally, in esophageal squamous cell carcinoma (ESCC), high expression of DOCK8 was associated with poorer survival.
Squamous cell carcinomaERCC2Verified37082048, 36632298, 33868488, 32377720, 33714009, 36552043, 36632296ERCC2 and XPD gene alterations can cause defective DNA repair efficiency which ultimately leads to genomic instability and carcinogenesis. ... The aim of the study was to evaluate the expression of XPD and XPG gene polymorphism in oral squamous cell carcinoma cases. ... Among the polymorphisms that are often significantly associated with HNSCC risk are: ... XPD Lys751Gln, ... ERCC2 A35931C, Asp312Asn, ERCC5 rs1047768 and rs17655 with HNSCC prognosis. ... Aberrations in DDR signals are implicated in the response to HNSCC chemotherapy and can be exploited as novel therapeutic targets, sensitive/effective non-invasive biomarkers as well as for the design of novel clinical trials.
Squamous cell carcinomaERCC4Verified36996606, 40076972, 40908315In the study with PMID 40076972, it was found that the TP53-Q331* mutation enhances TSCC chemoresistance through an ID2-mediated NER pathway, which involves upregulation of nucleotide excision repair (NER) pathway-related genes ERCC4 and ERCC8. This directly links ERCC4 to the biological process in squamous cell carcinoma.
Squamous cell carcinomaERCC5Verified36632296, 38726002, 36803971In PMID 36632296, ERCC5 rs1047768 and rs17655 polymorphisms were discussed in relation to HNSCC prognosis with conflicting results. In PMID 38726002, ERCC5 (BIVM-ERCC5) was identified as a differential gene between response and non-response groups to neoadjuvant immunochemotherapy in ESCC. In PMID 36803971, ERCC5 was part of a 5-DDRG prediction signature for ESCC prognosis.
Squamous cell carcinomaFERMT1Verified38982038, 34814915, 40806555, 40044983Kindler syndrome (KS) is a rare genodermatosis resulting from loss-of-function mutations in FERMT1, the gene that encodes Kindlin-1. KS patients have a high propensity to develop aggressive and metastatic cutaneous squamous cell carcinoma (cSCC). Here we show in non-KS-associated patients that elevation of FERMT1 expression is increased in actinic keratoses compared to normal skin, with a further increase in cSCC supporting a pro-tumorigenic role in this population. In contrast, we show that loss of Kindlin-1 leads to increased SCC tumor growth in vivo and in 3D spheroids, which was associated with the development of a hypoxic tumor environment and increased glycolysis. The metalloproteinase Mmp13 was upregulated in Kindlin-1-depleted tumors, and increased expression of MMP13 was responsible for driving increased invasion of the Kindlin-1-depleted SCC cells. These results provide evidence that Kindlin-1 loss in SCC can promote invasion through the upregulation of MMP13, and offer novel insights into how Kindlin-1 loss leads to the development of a hypoxic environment that is permissive for tumor growth.
Squamous cell carcinomaGATA1Verified40259045, 38169528The study investigates the role of KDM4C and its interaction with GATA1 in regulating heme metabolism and tumor progression in HNSCC. ... Immunohistochemical analysis of HNSCC patient samples revealed high KDM4C and GATA1 expression correlated with advanced clinical stages and poor survival outcomes. ... the two CAF types differentially affect cisplatin sensitivity and the underlying molecular mechanism. ... IGFBP3 expression was promoted by GATA-binding protein 1 (GATA1), a transcription factor targeted by miR-876-3p, which was enriched only in CAF-P-derived EV. ... there was a positive correlation between IGFBP3 and GATA1 expression and cisplatin sensitivity in OSCC tissues from patients.
Squamous cell carcinomaGJB2Verified34291047Connexin26 (Cx26) is specifically expressed in human skin tissue and can transmit radiation-induced damage signals. The study found that human skin squamous cell carcinoma cells (A431 cells) expressed significantly more Cx26 and were more sensitive to radiation compared to normal human keratinocytes (HaCaT cells). Knockdown of Cx26 in A431 cells decreased radiosensitivity and altered the expression of key proteins in the MAPK and NF-kappaB signaling pathways.
Squamous cell carcinomaGJB6Verified32537823, 34291047The probe ID of these 11 genes was retrieved by Affymetrix using the NetAffx Query algorithm. The protein-protein interaction (PPI) network and Kaplan-Meier curve were used to find associations among the genes' expression data. We found that among these 11 genes, nine genes, CCNA1, MMP3, FLRT3, GJB6, ZFR2, PITX2, SYCP2, MEI1, and UGT8 were significant (p < .05). A survival plot was drawn between the p value and gene expression. This study helped us find the nine significant genes which play vital roles in HNSCC along with their key pathways and their interaction with other genes in the PPI network.
Squamous cell carcinomaGTF2E2Verified34853466The general transcription factor IIE subunit beta (GTF2E2) is crucial for physiological and pathological functions, but its roles in the aggression and recurrence of ESCC remain ambiguous. In this study, we found that GTF2E2 was highly expressed in ESCC samples, and elevated GTF2E2 expression predicted early recurrence after surgery for ESCC patients. High expression of GTF2E2 associated with more aggressive clinic features and poor prognosis.
Squamous cell carcinomaIL7Verified38554147Here, we show that IL7 in combination with radiotherapy (RT) is effective in activating CD8 + T-cells for reducing tumor growth. Our studies were conducted using both human papillomavirus related and unrelated orthotopic HNSCC murine models.
Squamous cell carcinomaING1Verified35117725, 32831651In general, p33ING1 expression was restricted to only the cytoplasm for all cancers, whereas it was found in the nucleus of renal clear cells, ovarian and colorectal cancers. Among them, p33ING1 was expressed in more than half of squamous cell carcinomas derived from the esophagus and cervix... p33ING1b expression is correlated to acetylation of p53 at lysine 382 residue... p33ING1b and SIR2 are potentially attractive therapeutic targets.
Squamous cell carcinomaKRT14Verified33149622, 31994197, 32705284, 36406169, 40394426, 38859848, 33142242, 35279544The results revealed that the DEGs were mainly involved in pathways related to p63 transcription factor network and validated transcriptional factor targeting TAp63, etc. Based on the analysis, we finally identified DSG3 and KRT14 as potential biomarkers for distinguishing between LUAD and LUSC. These results suggested that DSG3 and KRT14 could have the potential to play an important role in NSCLC patients, as diagnostic markers. At the same time, DSG3 or KRT14 indicated a worse prognosis in LUSC patients, which were associated with pathways relevant to the TRAIL signaling pathway and TNF receptor signaling pathway according to bioinformatic analysis. (PMID: 33149622); HPV16 is sufficient to induce squamous cell carcinoma specifically in the tongue base in transgenic mice... The lesions maintained expression of CK14 (KRT14) and the HPV16 E6 and E7 oncogenes, and displayed deregulated cell proliferation and up-regulation of p16INK4A. (PMID: 31994197); Involvement of RNase 7 in the malignant potential of oral squamous cell carcinoma cells... The expression level of K14 was significantly higher in the siRNA-OSCC cells compared to the OSCC cells. (PMID: 32705284); Primary epididymis squamous cell carcinoma in a CB6F1-Tg rasH2 mouse... The tumor cells were positive for cytokeratin AE1/AE3 and cytokeratin 14 and negative for cytokeratin 5, p63, uroplakin III, vimentin, desmin, and alphaSMA. (PMID: 36406169); Establishment and characterization of patient-derived tongue squamous cell carcinoma cell lines... confirmed by Keratin-14 staining. (PMID: 40394426); KIF2C is a critical regulator for malignant progression of head and neck squamous cell carcinoma... Downstream genes such as PDGFA, EGFR, TP63, SNAI2, KRT5, and KRT14 were found to be down-regulated... (PMID: 38859848); Molecular homology between canine spontaneous oral squamous cell carcinomas and human head-and-neck squamous cell carcinomas... identified selective upregulation of KRT14 and KRT17 in COSCC. (PMID: 33142242); Oral basaloid squamous-cell carcinoma... immunohistochemical analysis revealed positivity for AE1/AE3, CK 5, CK 14, p63 and Ki67 (>80%), but negativity for CK7, S-100 and alpha-SMA. (PMID: 35279544)
Squamous cell carcinomaKRT5Verified35673812, 38611634, 37212698, 34150027, 36094593, 38001588Keratin 5 (K5) is an immunohistochemical marker of squamous differentiation. The study found that clone SP27 showed significantly higher analytical sensitivity for K5 in lung cancer specimens, and KRT5 mRNA was expressed in 71% of adenocarcinomas. In another study, the combination of AGR2 and KRT5 reliably distinguished SCC from ADC with high accuracy. Additionally, KRT5 was part of a 10-gene panel for characterizing circulating tumor cells in esophageal squamous cell carcinoma, indicating its relevance to SCC.
Squamous cell carcinomaLAMA3Verified40628792, 32767748, 38305336, 33168804, 31889588, 32954225, 40234833, 36313206LAMA3 expression was 2.4-fold higher in ESCC tumor tissues than in adjacent normal tissues (p < 0.001). High LAMA3 levels were associated with worse overall survival and disease-free survival (p < 0.05). Knockdown of LAMA3 suppressed cell proliferation by 57% (p < 0.001), migration by 49% (p < 0.001), and invasion by 47% (p < 0.001).Pathway enrichment analysis indicated involvement of LAMA3 and its co-expressed genes in cell adhesion, extracellular matrix organization, and the PI3K-AKT pathway. In summary, our results demonstrate that LAMA3 is a major promoter of ESCC progression and a potential biomarker and therapeutic target.
Squamous cell carcinomaLAMB3Verified39111076, 36415640, 36081907, 39256753, 38957320, 38473784PMID:39111076: 'Laminin subunit beta 3 (LAMB3)... plays a vital role in regulating cell proliferation, migration, and cell cycle in certain diseases. Previous studies have indicated that LAMB3 is highly expressed in numerous tumorous... conditions, including... squamous cell carcinoma of the skin...'. PMID:36415640: 'Decreased Expression of LAMB3 Is Associated with Esophageal Cancer Stem Cell Formation... LAMB3 expression was decreased in YM-1 spheres suggesting LAMB3 association with sphere formation.' PMID:39256753: 'seven key BMRGs (BGN, LAMB3, SPARC, MMP1, LUM, COL4A1, and NELL2)... diagnostic nomogram for ESCC.' PMID:38957320: 'genetic markers involved in ECM remodeling including LAMB3... significantly increased in tumors of younger vs. older patients.'
Squamous cell carcinomaLAMC2Verified36284634, 38989468, 39595099, 34612783, 32860673, 35506252, 36396303, 38803944, 32277532LAMC2 was expressed at high level in LSCC tissues and associated with poor prognosis. ... LAMC2 overexpression increased TU177 cell viability, proliferation ability, promoted cell cycle, cell migration, and invasion capacity. ... LAMC2 was overexpressed in LSCC and correlated with poor prognosis. ... NSUN2 was significantly upregulated in HNSCC tissues compared to normal tissues and was associated with poor prognosis. ... LAMC2 identified as a key downstream target. ... lncRNA CASC9 promotes the malignancy of OSCC cells by sponging miR-545-3p to enhance LAMC2 expression. ... BBOX1-AS1 promotes the malignant phenotype of OSCC cells via the upregulation of LAMC2 expression by targeting miR-3940-3p. ... LAMC2 expression was significantly increased in HNSC, and LAMC2 was obviously correlated with an adverse prognosis for patients. ... increased LAMC2 expression was significantly associated with lymph node metastasis, tumour-node-metastasis stages and tumour status. ... higher LAMC2 expression was found to be significantly associated with OS/PFS/DSS. ... LAMC2-CD44 and immune resistance. ... high expression of LAMC2 was significantly correlated with poor survival of HNSCC patients.
Squamous cell carcinomaLMNAVerified32517491This report outlines the case of two biological sisters with LMNA-associated FPLD who developed hypopharyngeal squamous cell carcinoma in the absence of any other risk factors for head and neck cancer.
Squamous cell carcinomaMC1RVerified36329591, 38534742, 38034848PMID 36329591 directly states that MC1R is highly expressed in esophageal squamous cell carcinoma, with significant overexpression in cancer tissues compared to adjacent tissues (P < 0.05). Immunohistochemistry confirmed elevated MC1R in tumor samples. The study concludes MC1R may serve as a biomarker for this cancer type.
Squamous cell carcinomaMMP1Verified33954053, 36545225, 35426219, 38495954, 34495460, 36081670, 34301206, 35756415, 31977248, 35444950PMID 33954053: 'High expression of the SPP1, SERPINE1 and Matrix metalloproteinases 1 (MMP1) genes was connected to worse prognosis in patients with LSCC... Inhibition of SPP1, SERPINE1 and MMP1 suppressed cell proliferation, invasion and migration.' PMID 35426219: 'MMP1 was proved to promote cell growth, migration, and phosphorylation of AKT in vitro and to promote liver metastasis in vivo.' PMID 36081670: 'MMP1 and MMP12 were noticeably increased in ESCC specimens...' PMID 34301206: 'Seven hub genes... including MMP1...' PMID 35756415: 'LINC01116... regulating the derepression of matrix metalloproteinase 1 (MMP1).' PMID 31977248: 'MMP1 may be a novel biomarker for immunotherapy, and prognostic judgment of patients with cervical cancer.' PMID 35444950: 'High matrix metalloproteinase-1 (MMP1) expression was found that have a great graft advantage in xenografts...'
Squamous cell carcinomaMVDVerified38898137LRG1, SDR16C5, PIP4K2C and MVD proteins were selected for immunohistochemical analysis in HPV-positive and -negative OPSCC tissue samples. These protein s expression levels were compared with clinicopathological parameters and patient survival to investigate their clinical relevance.
Squamous cell carcinomaNLRP1Verified36293159, 36246601, 36960186, 38684755, 35574984, 37889986, 34600420, 40593496In human keratinocytes and skin, NLRP1 is the central inflammasome sensor activated by cellular perturbation induced, for example, by UVB radiation. UVB represents the main inducer of skin cancer, which is the most common type of malignancy in humans. Recent evidence demonstrates that activation of NLRP1 in human skin supports the development of cutaneous squamous cell carcinomas (cSCCs) by inducing skin inflammation. In contrast, the NLRP1 inflammasome pathway is restrained in established cSCCs, suggesting that, at this stage, the protein complex has a tumor suppressor role.
Squamous cell carcinomaNTHL1Verified40499530, 36685880In the first abstract, LINC02562 is shown to promote lung cancer progression by regulating NTHL1-dependent DNA damage repair mechanisms. Lung squamous cell carcinoma (LUSC) is specifically mentioned as a cancer type where LINC02562 is highly expressed and interacts with NTHL1. In the second abstract, NTHL1 is part of a 12-CRGs signature associated with head and neck squamous cell carcinoma (HNSC) prognosis and immune status. Both studies directly link NTHL1 to squamous cell carcinoma subtypes.
Squamous cell carcinomaNUTM1Verified34333275, 36040068, 37819236, 37131839, 32873880, 37119804, 33222286NUT carcinoma (NC) is a rare subtype of squamous cell carcinoma defined by NUTM1 rearrangements encoding NUT fusion oncoproteins (the most frequent fusion partner being BRD4) that carries a very poor prognosis, with most patients dying in under 1 year. ... NC is an aggressive squamous carcinoma defined by the BRD4-NUT fusion oncoprotein. ... The fusion causes the formation of large hyperacetylated genomic regions or megadomains, mis-regulation of c-MYC, and an aggressive carcinoma of squamous cell origin.
Squamous cell carcinomaRECQL4Verified37456212, 33628589, 40963872, 37132629Abstract 1: 'A novel germline pathogenic variant was identified in the RECQL4 gene of the family. RECQL4 is a known protein in DNA repair and replication. Considering its effect on other types of SCC, it may play an important role in SCC initiation and progression in the breast.' Abstract 2: 'RECQL4 was highly expressed in tumor tissues... and positively correlated with poor differentiation, enhanced invasion, and metastasis... RECQL4 depletion induced G0/G1 phase arrest and cellular senescence.' Abstract 3: 'ESCC exhibited amplifications of MCL1, RECQL4...'. Abstract 4: 'Twenty-one patients (10.5%) had a total of 22 PGVs... most common MUTYH, WNR, or RECQL4.'
Squamous cell carcinomaRSPO1Verified38864442, 35854363, 31917882, 40963872, 34309520RSPO1-mutated keratinocytes from PPK skin displayed impaired differentiation and EMT-like phenotype, with SCC specimens showing increased proliferation and dedifferentiation markers. RSPO1-mutated fibroblasts exhibited cancer-associated properties, promoting SCC development. RSPO1 is linked to SCC susceptibility in 46XX disorder of sexual development.
Squamous cell carcinomaSASH1Verified32547092, 32905855, 37504303SASH1 Suppresses the Proliferation and Invasion of Human Skin Squamous Cell Carcinoma Cells via Inhibiting Akt Cascade. The expression levels of SASH1 mRNA and protein were greatly reduced in cSCC cells. The overexpression of SASH1 inhibited the viability and invasion of cSCC cells, while its knockdown induced the viability and invasion of cSCC cells. Paired like homeodomain 1 and SAM and SH3 domain-containing 1 were selected to be further explored... statistical analysis indicated their close associations with patient prognosis. In vitro experiments demonstrated the inhibitory effect of... SAM and SH3 domain-containing 1 on HNSCC progression. Interactions of piRNAs with the mRNA of Candidate Genes in Esophageal Squamous Cell Carcinoma... piRNAs bind only to the mRNAs of nine candidate ESCC genes: AURKA, BMP7, GCOM1, ERCC1, MTHFR, SASH1, SIX4, SULT1A1, and TP53.
Squamous cell carcinomaSLC17A9Verified37818081The abstract states that SLC17A9 up-regulation was significantly correlated with overall survival in LUAD and LUSC (P < 0.05). Additionally, SLC17A9 expression was negatively associated with overall survival and positively related to most LUSC immune cells and immunoinhibitor (20/23), particularly immuno A2aR, PD-1, and CTLA-4 (P < 0.001).
Squamous cell carcinomaSLX4Verified38832974, 35929646, 38432114In PMID 38832974, SLX4 (c.2786C > T) is mentioned as one of the most frequent mutation sites in esophageal squamous cell cancer (ESCC) with 6.5% frequency. In PMID 35929646, SLX4/FANCP is associated with germline and somatic mutation burden in squamous cell carcinomas of head and neck and lung. In PMID 38432114, SLX4 mutations are identified as predictors of shorter overall survival in cervical cancer patients.
Squamous cell carcinomaSMARCAD1Verified35592705, 35212137Both studies report associations between SMARCAD1 mutations and cutaneous squamous cell carcinoma (cSCC). PMID 35592705 notes a family history of cSCC in Basan syndrome, while PMID 35212137 directly links SMARCAD1 variants to cSCC in Huriez syndrome.
Squamous cell carcinomaSTAT1Verified38706215, 35686499, 36560800, 39497541, 32685473, 38166970, 31709529, 34559306In the study by PMID 38706215, it was found that USP39 knockdown inhibited the expression of STAT1 mRNA in HNSCC cells, indicating a direct role of STAT1 in HNSCC. Additionally, PMID 39497541 showed that STAT1 negatively regulates LHPP expression in ESCC, highlighting its involvement in ESCC progression. PMID 32685473 demonstrated that BRCA1 overexpression upregulates STAT1, contributing to CCRT resistance in CSCC. These findings collectively support the association of STAT1 with squamous cell carcinoma.
Squamous cell carcinomaSTAT4Verified39337665, 35686499, 33361747, 37256972, 36444617, 32010142The T allele of STAT4 rs7574865 significantly increases the likelihood of LSCC occurrence by 1.4-fold... The G allele of rs10181656 is significantly associated with various clinical characteristics of LSCC... Additionally, we found that the decreased Th1 cells' function is associated with ER stress... Gain-of-function variants in STAT4 caused DPM in the families that we studied... STAT4 mediates resistance to HNSCC metastasis
Squamous cell carcinomaTERCVerified36033580, 40072633, 31837325, 34436017TERC has a significant impact on the proliferation and migration of oral squamous cell carcinoma cells. ... TERC under the minimally invasive treatment of digital technology has little effect on the proliferation and migration of oral squamous cell carcinoma cells. ... lncRNA TINCR ... promoted methylation in the promoter regions of Myc (N-MYC, L-MYC, and c-MYC) and TERC genes, inhibiting the proliferation, migration, and invasion of CSCC cells. ... TERC and TERRA, mainly in the LUSC subtype. ... Amplification of 3q26 locus ... includes TERC. ...
Squamous cell carcinomaTERTVerified35225554, 40307280, 39091884, 34667860, 32404253, 34650187, 31960186, 40758763, 36096049The present study demonstrates that TERT promoter mutations with UV signatures are frequent in ocular surface squamous cell carcinoma. ... The average frequency of TERT promotor mutation was 46.1% ... TERT promoter mutations could be considered as biomarkers assisting in risk stratification and prognostic prediction. ... TERT gene alterations, mainly TERT promoter mutations (14/15 cases, 93%) featured significantly in HPV-independent carcinomas.
Squamous cell carcinomaTINF2Verified39578854, 33736925, 39661387PMID 33736925 reports a case of squamous cell carcinoma of the tongue in a 5-year-old girl with dyskeratosis congenita caused by an autosomal dominant type 3 TINF2 mutation. This directly links TINF2 to squamous cell carcinoma. Additionally, PMID 39661387 shows that individuals with AR/XLR TBDs, including TINF2 mutations, have a significantly higher risk of head and neck squamous cell carcinomas.
Squamous cell carcinomaTMC6Verified36705400, 33818984, 39001899Aggressive Squamous Cell Carcinoma in a Case of Epidermodysplasia Verruciformis Carrying a TMC6 Splice-site Mutation. ... Epidermodysplasia verruciformis is a rare genodermatosis associated with mutations in the EVER1/TMC6 and EVER2/TMC8 genes. ... The development of squamous cell carcinoma and melanoma are frankly lower concerning CEV.
Squamous cell carcinomaTMC8Verified37183530, 40196225, 37029240, 33981360, 35008199, 34790351, 38869286, 33818984, 36170758, 34416085TMC8 was identified as one of five prognostic genes in laryngeal squamous cell carcinoma (LSCC) and was part of a risk model associated with tryptophan metabolism. Additionally, TMC8 was found to be upregulated in head and neck squamous cell cancer (HNSC) and associated with improved prognosis. In the context of Epstein-Barr virus-associated epithelial cancers, TMC8 was significantly upregulated in EBV-positive tumor tissues. Furthermore, mutations in TMC8 are linked to epidermodysplasia verruciformis, which is characterized by a high risk of progression to squamous cell carcinoma.
Squamous cell carcinomaTNFRSF10BVerified33737574, 37976123, 36522309, 31731196, 38679518In this study, we observed the distinct genomic and expression alterations of nine genes involved in cell death in 55% HNSCC tissues, which were associated with HPV status, tumor staging, and anatomic locations. ... A panel of HPV(+) HNSCC lines showed abundant TRAILR2 and IAP1 protein expression... The death agonistic TRAILR2 antibody alone showed no cell inhibitory effects, whereas its combination with birinapant and/or TRAIL protein demonstrated additive or synergistic effects. ... 159 genes involved in necroptosis pathways were acquired from the KEGG database, of which most showed significant differences between two groups in terms of genomic, transcriptional and methylation alterations. In particular, ... TNFRSF10B were significantly associated with the survival (p < 0.05) and were used to construct the necroptosis signature... TRAIL death receptors in several squamous and adenocarcinoma NSCLC cell lines... TRAIL receptor expression levels also correlated with markers of angiogenesis and neutrophil infiltration in lung squamous carcinoma and adenocarcinoma. ... CMSP enhanced the TRAIL-induced apoptosis in ESCC cells by upregulating the expression of DR4 and DR5 via the p38 MAPK signalling pathway. ... The expression of the TRAIL gene increased 5-fold in HNO97 cells on treatment with L acidophilus and S mutans, which further increased to ~17-fold with both species present.
Squamous cell carcinomaTYMSVerified37682862, 33256074, 35117403, 39835116, 40256022, 36731178TYMS is involved in the malignant process of multiple cancers, and has gained much attention as a cancer treatment target. ... Our study indicated a novel and effective regulatory capacity of TYMS in the cell proliferation of ESCC by relieving oxidative stress through activating expression of Nrf2 and Nrf2-dependent antioxidant enzymes genes. ... TS exhibited a strong specific and stable nuclear immunoreactivity in all specimens including MEC, BC, TEC, and SEC when compared with p63. ... CAPs in the ESCC TME were found to be highly heterogeneous, and we identified six pericyte subtypes: ... c5_TYMS, ... which have commonality in a part of their functions, and each of them has a major function to play, by having different strengths of interaction with different components in the TME. ... Both IFNalpha2b and 5-FU, when administered individually or in combination, effectively suppress the proliferation and migration of Cal27 tumor cells, induce cell apoptosis and arrest cell cycle. ... detection of HPV in CTCs from patients with non-metastatic SCCA is feasible and appears to be a sensitive diagnostic method.
Squamous cell carcinomaXPAVerified36118674, 33714009, 36866916Compared with the controls, cases had statistically significantly lower protein expression levels of XPA (P < 0.001) and lower mRNA expression levels of XPA and XPB (P = 0.005 and 0.001, respectively). ... the sensitivity of the expanded model with protein and mRNA expression levels, in addition to demographic variables, on HNSCCs risk was significantly improved. ... HNSCC patients at diagnosis exhibited deregulated DDR-related parameters and higher levels of oxidative stress and abasic sites compared with HC ... nucleotide excision repair (NER; ERCC1, ERCC2/XPD, XPA, XPC) and base excision repair (APEX1, XRCC1) genes were downregulated in patients versus HC. ... A novel XPA splice-site mutation identified in a 4-year-old Filipino girl with xeroderma pigmentosum and squamous cell carcinoma were confirmed by whole-exome sequencing and skin biopsy, respectively.
Squamous cell carcinomaXPCVerified39409898, 35902966, 38672576, 33714009, 37798436, 40052589Xeroderma Pigmentosum Type C (XP-C) primary skin fibroblasts overexpress HGF and promote Squamous Cell Carcinoma (SCC) invasion... The use of inhibitors of the activation of the HGF/SF pathway counteracted the effects of XP fibroblasts on the growth of cancer cells. (PMID: 39409898); A 7-year-old Turkish male... with a novel homozygous c.2250 + 1G>A splice site mutation of the XPC gene... with recurrent facial squamous cell carcinoma lesions. (PMID: 35902966); XPC Protects against Carcinogen-Induced Histologic Progression to Lung Squamous Cell Carcinoma... (PMID: 38672576); Genetic variability in XPC c.2815A>C... associated with outcome of head and neck squamous cell carcinoma patients. (PMID: 37798436); Immune checkpoint inhibitors for children with xeroderma pigmentosum and advanced cutaneous squamous cell carcinoma... (PMID: 40052589)
Malignant neoplasm of the central nervous systemLMNAExtractedCancer Research34530169We identify three nuclear lamin genes (LMNA, LMNB1, and LMNB2) that are significantly upregulated in glioma tissues compared with normal brain tissues.
Malignant neoplasm of the central nervous systemLMNB1ExtractedCancer Research34530169Elevated expressions of LMNB1, LMNB2, and LMNA in glioma cells are highly associated with the rapid progression of the disease.
Malignant neoplasm of the central nervous systemLMNB2ExtractedCancer Research34530169The repression of glioma cell growth by lamin knockdown is mediated by the pRb-mediated G1-S inhibition.
Malignant neoplasm of the central nervous systemTRPC6ExtractedJournal of Neuro-Oncology38097166The HadVCi score was (-0.2526673*TRPC6) + ...
Malignant neoplasm of the central nervous systemRNF207ExtractedJournal of Neuro-Oncology38097166The HadVCi score was ... (-0.2244276*RNF207) + ...
Malignant neoplasm of the central nervous systemSEC31BExtractedJournal of Neuro-Oncology38097166The HadVCi score was ... (-0.0894468*SEC31B) + ...
Malignant neoplasm of the central nervous systemZCRB1ExtractedJournal of Neuro-Oncology38097166The HadVCi score was ... (-0.0190214*ZCRB1) + ...
Malignant neoplasm of the central nervous systemDNPH1ExtractedJournal of Neuro-Oncology38097166The HadVCi score was ... (-0.017122*DNPH1) + ...
Malignant neoplasm of the central nervous systemCCDC34ExtractedJournal of Neuro-Oncology38097166The HadVCi score was ... (0.0495818*CCDC34) + ...
Malignant neoplasm of the central nervous systemPURGExtractedJournal of Neuro-Oncology38097166The HadVCi score was ... (0.1196349*PURG) + ...
Malignant neoplasm of the central nervous systemLILRA5ExtractedJournal of Neuro-Oncology38097166The HadVCi score was ... (0.1778997*LILRA5).
Malignant neoplasm of the central nervous systemSMARCB1BothJournal of Neurosurgery39586083, 33762087, 37969088, 32192808, 31707588, 34777208, 38639853, 38062114, 40376705The identification of SMARCB1 inactivation in pediatric malignant rhabdoid tumors provided the first example that the SWI/SNF complex may act as a tumor suppressor. It is now estimated at least 20% of all human tumors contain mutations in the subunits of the SWI/SNF complex. This review summarizes the central nervous system tumors with alterations in the SWI/SNF complex genes. Atypical teratoid/rabdoid tumor (AT/RT) is a highly aggressive embryonal tumor genetically characterized by bi-allelic inactivation of SMARCB1, and immunohistochemically shows complete absence of nuclear expression of its protein product INI1. A small subset of AT/RT show retained INI1 expression but defects in another SWI/SNF complex gene SMARCA4. Embryonal tumors with medulloblastoma, pineoblastoma, or primitive neuroectodermal morphology but loss of INI1 expression are now classified as AT/RT. Cribriform neuroepithelial tumor (CRINET) is an intra or para-ventricular tumor that has similar SMARCB1 alterations as AT/RT but generally has a benign clinical course. Besides AT/RT and CRINET, compete loss of nuclear INI1 expression has also been reported in poorly differentiated chordoma and intracranial myxoid sarcoma within the central nervous system. Families with non-truncating SMARCB1 mutations are prone to develop schwannomatosis and a range of developmental syndromes. The schwannomas in these patients usually demonstrate a mosaic INI1 staining pattern suggestive of partial residual protein function. Finally, clear cell meningioma is a WHO grade II variant meningioma characterized by bi-allelic inactivation of the SMARCE1 gene and immunohistochemically show loss of its protein product BAF57 expression in tumor cell nuclei.
Malignant neoplasm of the central nervous systemPRAMEF12ExtractedOncology Reports38913622PRAMEF12 knockdown inhibited cell proliferation, induced apoptosis and resulted in induction of S-phase cell cycle arrest.
Malignant neoplasm of the central nervous systemCD79BExtractedCancer Letters40593136Risk model revealed 5 genes (CD79B, STXBP4, DDHD1, FKBP1B and TRAM2) was related with overall survival (OS) of GBM patients.
Malignant neoplasm of the central nervous systemSTXBP4ExtractedCancer Letters40593136Risk model revealed 5 genes (CD79B, STXBP4, DDHD1, FKBP1B and TRAM2) was related with overall survival (OS) of GBM patients.
Malignant neoplasm of the central nervous systemDDHD1ExtractedCancer Letters40593136Risk model revealed 5 genes (CD79B, STXBP4, DDHD1, FKBP1B and TRAM2) was related with overall survival (OS) of GBM patients.
Malignant neoplasm of the central nervous systemFKBP1BExtractedCancer Letters40593136Risk model revealed 5 genes (CD79B, STXBP4, DDHD1, FKBP1B and TRAM2) was related with overall survival (OS) of GBM patients.
Malignant neoplasm of the central nervous systemTRAM2ExtractedCancer Letters40593136Risk model revealed 5 genes (CD79B, STXBP4, DDHD1, FKBP1B and TRAM2) was related with overall survival (OS) of GBM patients.
Malignant neoplasm of the central nervous systemALKVerified39924713, 38139220, 36768562, 33960745, 32681571ALK-positive histiocytosis... excluded known histiocytic subtypes... (PMID: 39924713). Germline variants in CPGs... like ALK... (PMID: 38139220). ALK inhibitors... central nervous system metastasis... (PMID: 36768562). Characteristics of central nervous system progression... crizotinib or alectinib... (PMID: 33960745). Congenital tumors... fusions involving the MET, ALK and NTRK genes... (PMID: 32681571).
Malignant neoplasm of the central nervous systemAPCVerified39756803, 38139220The abstract from PMID: 39756803 mentions that APC is a WNT signal transduction molecule abundantly expressed in the central nervous system and that truncation mutations of the APC gene are responsible for FAP, which is associated with brain tumors. Additionally, the abstract from PMID: 38139220 reports that APC is one of the cancer predisposition genes found to have germline variants in pediatric patients with central nervous system tumors.
Malignant neoplasm of the central nervous systemASCL1Verified33755378, 35501487Protein expression of proneural marker ASCL1 (enriched in SHH-1B) and glial markers OLIG2 and GFAP (absent in SHH-2) as well as global mRNA expression patterns differed, but all subgroups were characterized by overexpression of SHH as well as Notch pathway members. In a Drosophila model, knockdown of Snr1 (the fly homologue of SMARCB1) in hedgehog activated cells not only altered hedgehog signaling, but also caused aberrant Notch signaling and formation of tumor-like structures. Finally, on survival analysis, molecular subgroup and age of onset (but not ASCL1 staining status) were independently associated with overall survival, older patients (> 3 years) harboring SHH-1B experiencing relatively favorable outcome.
Malignant neoplasm of the central nervous systemATMVerified33268695, 34199532, 35301087PMID 33268695 discusses ATM activation in the context of DNA damage response (DDR) in glioblastoma cells. PMID 35301087 highlights ATM-dependent signaling in glioblastoma's DNA damage response and temozolomide resistance. Both studies associate ATM with malignant central nervous system tumors.
Malignant neoplasm of the central nervous systemBDNFVerified39648800, 36831557Activation of intracellular signaling pathways such as the mitogen-activated protein kinase pathway, phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin pathway, and phospholipase C gamma pathway by BDNF can all potentially enhance the growth, survival, proliferation, and migration of cancer cells, influencing cancer development. The loss of BDNF and its receptor, tropomyosin receptor kinase B, in signaling pathways is also associated with increased susceptibility to brain and heart diseases.
Malignant neoplasm of the central nervous systemBMPR1AVerified36271359, 33116227The new classification model was validated in further groups of patients from the CGGA database (n = 291) and the Cancer Genome Atlas (n = 625). A new glioma grade (HB grade) based on histopathology and BMP2 expression can predict the prognosis of glioma patients, with BMPR1B and BMPR2 expression indicating a different prognosis in different types of gliomas. The higher the concentration of BMP2, the better the prognosis of patients.
Malignant neoplasm of the central nervous systemBRAFVerified37851071, 33042847, 36077798, 34301805BRAF alterations are most commonly missense mutations or aberrant fusions. These mutations are observed in numerous primary central nervous system tumors as well as metastases. (PMID: 33042847); The i-ID system provides reliable integrated diagnosis of adult malignant CNS tumors. (PMID: 37851071); Sequencing of a central nervous system tumor demonstrates cancer transmission in an organ transplant. (PMID: 34301805)
Malignant neoplasm of the central nervous systemBRD4Verified36711038, 38365636, 36934287, 37190167, 33643826, 35755286The study in PMID 36711038 shows that BRD4 is highly expressed in glioblastoma multiforme (GBM) tumor tissues compared to normal tissues and is associated with poor prognosis. Additionally, BRD4 expression correlates with immune infiltration and tumor purity in GBM. PMID 38365636 demonstrates that MZ1, a BRD4 inhibitor, reduces GBM cell proliferation and tumor size in xenograft models. PMID 36934287 reports a CNS embryonal tumor with a BRD4-LEUTX fusion, indicating BRD4's role in a specific subtype of central nervous system tumors. PMID 37190167 and 33643826 link BRD4 to medulloblastoma progression and Hedgehog pathway inhibition, further supporting its association with central nervous system malignancies.
Malignant neoplasm of the central nervous systemCASZ1Verified36243768The neural crest lineage regulatory transcription factors (TFs) form a core regulatory circuitry (CRC) in neuroblastoma (NB) to specify a noradrenergic tumor phenotype. ... In NB tumor cells, the CASZ1 tumor suppressor is silenced while CRC components are highly expressed. ... Our study identifies that the restored CASZ1 forms a negative feedback regulatory circuit with the established NB CRC to induce noradrenergic neuronal differentiation of NB.
Malignant neoplasm of the central nervous systemCDKN1AVerified40952624, 36714975In PMID 40952624, PL induced G2/M phase arrest via up-regulation of CDKN1A/p21. In PMID 36714975, CDKN1A rs3176334 [T/C] showed homozygous polymorphic genotype in high-grade astrocytomas (p = .039). Both studies link CDKN1A to CNS malignancies.
Malignant neoplasm of the central nervous systemCDKN2AVerified37851071, 34301805, 37947008The 2021 World Health Organization (WHO) classification of central nervous system (CNS) tumors uses an integrated approach involving histopathology and molecular profiling... For suspected glioma, genotyping for IDH1/2, TERT SNV, and CDKN2A copy number alteration was routinely performed... Assessment of IDH1/2, TERT, H3F3AK27M, BRAFV600E, and CDKN2A alterations with i-ID and permanent genomic analysis was concordant in 100%, 100%, 100%, 100%, and 96.4%, respectively. Combination with FS and intraoperative genotyping assay improved diagnostic accuracy in gliomas. Overall, i-ID matched with p-ID in 80/82 (97.6%) patients with glioma and 18/19 (94.7%) with PCNSL. Homozygous deletion of cyclin-dependent kinase inhibitor 2a (CDKN2A) has been associated with an adverse prognosis in IDH-mutant gliomas, supratentorial ependymomas, meningiomas, and MPNST. In this study, we examined the value of p16 protein immunohistochemistry as a rapid and cost-effective screening tool for a homozygous CDKN2A deletion. Deleterious mutations... and a chromosomal deletion spanning the CDKN2A/B genes, were shared between the recipients' lesions.
Malignant neoplasm of the central nervous systemCDKN2BVerified34301805, 40075786, 35203456The study found that a chromosomal deletion spanning the CDKN2A/B genes was shared between the recipients' lesions, indicating a link to the transmitted cancer. Additionally, the latest WHO classification assigns grade 3 meningiomas based on criteria that include a homozygous CDKN2A and/or CDKN2B deletion. The presence of CDKN2A/B homozygous deletion is also an independent predictor of poor prognosis in IDH-mutant gliomas, associated with malignant progression.
Malignant neoplasm of the central nervous systemCDKN2CVerified33193598Collectively, this systematic analysis of DNA sequencing data revealed that some key genes including NF1, NF2, and CDKN2C and Hippo signaling pathway were associated with spinal schwannoma, which may help improve our understanding about the genomic landscape of spinal schwannoma.
Malignant neoplasm of the central nervous systemCHEK2Verified38139220Our study found that 27% of pediatric patients with CNS tumors have a germline variant in some of the known CPGs, like ALK, APC, CHEK2, ELP1, MLH1, MSH2, NF1, NF2 and TP53.
Malignant neoplasm of the central nervous systemDICER1Verified38455248, 36534424, 32291395, 37508972, 36737790The 2021 World Health Organization classification for brain tumors introduced several new entities and categories.Tumors of uncertain differentiation are a new subcategory that includes... the Primary intracranial sarcoma, DICER1-mutant. ...DICER1-associated central nervous system sarcoma (DCS). DCS is a high-grade malignancy predominantly affecting pediatric patients. ...Biallelic DICER1 variants were identified in all cases, ...DICER1-mutant, in a patient with a germline DICER1 variant.
Malignant neoplasm of the central nervous systemELP1Verified38139220, 39816537, 38962751Our study found that 27% of pediatric patients with CNS tumors have a germline variant in some of the known CPGs, like ALK, APC, CHEK2, ELP1, MLH1, MSH2, NF1, NF2 and TP53. ... Medulloblastoma (MB) is a highly malignant childhood brain tumor. ... Our study identified 14 valid germline variants that met our criteria, with these variants being detected in the genes APC, BRCA2, PTCH1, PTCH2, ELP1, and SUFU. ... ELP1 pathogenic variants (PV) have been recently identified as the most frequent variants predisposing to Sonic Hedgehog (SHH) medulloblastomas (MB);
Malignant neoplasm of the central nervous systemERBB2Verified39888615The cohort included 274 patients (272 [99.3%]) with ERBB2-positive metastatic breast cancer (MBC) and CNS disease... Both OS and CNS-related death were significantly correlated with the pattern of presentation... On multivariable modeling for CNS-related death, LMD (hazard ratio, 1.87; 95% CI, 1.19-2.93; P = .007) and treatment with whole-brain radiotherapy (hazard ratio, 1.71; 95% CI, 1.13-2.58; P = .01) were associated with CNS-related death. Conclusions and Relevance: In this cohort study, 55.2% of deaths among patients with ERBB2+ breast cancer and brain metastasis were due to CNS-related causes.
Malignant neoplasm of the central nervous systemGABRDVerified33969375, 33718116In the first study (PMID: 33969375), the authors identified GABRD as one of four SAPs correlated with the prognosis of LGG patients. They also found that GABRD was up-regulated in LGG patients with seizures, suggesting a link to glioma pathogenesis. In the second study (PMID: 33718116), GABRD was identified as one of 11 core molecules in GBM, with its expression levels significantly related to survival. Both studies associate GABRD with central nervous system malignancies.
Malignant neoplasm of the central nervous systemGDNFVerified33585220Through immunohistochemical studies, markers that enhance GB invasiveness have been shown to be expressed in the peritumoral area of the brain, such as Transforming Growth Factor alpha (TGF-alpha), Stromal Sell-Derived Factor 1 (SDF1/CXCL12), Sphingosine-1-Phosphate (S1P) and Neurotrophic Factor Derived from the Glial cell line (GDNF), contributing to the increase in tumor mass.
Malignant neoplasm of the central nervous systemGPC4Verified36686480The PPI network identified 11 BM genes from the DEGs: SPARCL1, GPC3, LAMA1, SDC4, GPC4, ADAMTS8, LAMA2, LAMC3, SMOC1, LUM and THBS2. Based on the complex correlation between these 11 genes and immune infiltration, a risk model was established to predict PAs invasiveness.
Malignant neoplasm of the central nervous systemGPR161Verified32056145, 39816537In the first study (PMID: 32056145), GPR161 was one of seven medulloblastoma predisposition genes investigated using a candidate gene approach. The second study (PMID: 39816537) included GPR161 among ten susceptibility genes of interest for analysis in an Asian cohort. Medulloblastoma is a malignant embryonal tumor of the cerebellum, classified as a malignant neoplasm of the central nervous system.
Malignant neoplasm of the central nervous systemHSPG2Verified32509446Five stromal signatures indicated poor prognosis which including HSPG2... Five stromal signature correlated with poor prognosis also provide a strong predictor of gliomas patient outcome.
Malignant neoplasm of the central nervous systemIDH1Verified37851071, 36575552, 36673007, 35855126, 31914945, 36203303The 2021 World Health Organization (WHO) classification of central nervous system (CNS) tumors uses an integrated approach involving histopathology and molecular profiling... For suspected glioma, genotyping for IDH1/2, TERT SNV, and CDKN2A copy number alteration was routinely performed... Assessment of IDH1/2... with i-ID and permanent genomic analysis was concordant in 100%... Overall, i-ID matched with p-ID in 80/82 (97.6%) patients with glioma... IDH mutant (10%) and IDH wild-type tumors (90%) are two different entities... All IDH mutant diffuse astrocytic tumors are considered in a single type 'astrocytoma IDH mutant'... Quantitative evaluation of T2-mapping relaxation times shows significant differences regarding the IDH-status in WHO grade II and III gliomas... IDH-mutant astrocytomas... in the spinal cord.
Malignant neoplasm of the central nervous systemKEAP1Verified39407193Modulation of Nrf2/ARE and downstream activities in a Keap1-dependant manner, with the aid of plant-derived secondary metabolites exhibits promise in the management of brain tumors.
Malignant neoplasm of the central nervous systemKIF1BVerified37564981The patient... identified a novel heterozygous germline mutation of the KIF1B gene (c.3331_3332del; p.Asn1111Glnfs*21), which is only present in the girl and not the other family members. This family is notable by the early age of onset of multiple neural crest tumors associated with a high propensity for malignancy and metastatic spread. The presence of concomitant mutations in two susceptibility genes for neural crest tumors poses the question of their respective roles in the development of tumors in this family.
Malignant neoplasm of the central nervous systemKRASVerified37360159In elderly WHO5 GBM patients, KMT5B (p = 0.082), KRAS (p = 0.1) and PPM1D (p = 0.055) were each associated with overall survival (OS). Among them, KRAS and PPM1D were found to be prognostic features unique to WHO5 elderly GBM patients.
Malignant neoplasm of the central nervous systemLIN28BVerified37341142, 35945579, 34771690Expression of protein lin-28 homolog B (LIN28B)... is associated with worse survival in this disease. ... LIN28B knockdown in G3-MB-patient-derived cell lines leads to a significant reduction in cell viability and proliferation in vitro and in prolonged survival of mice with orthotopic tumors. ... LIN28B, promoting proliferation and suppression of neuroblast differentiation.
Malignant neoplasm of the central nervous systemLMO1Verified34938970, 35280742, 37183825High LMO1 expression was associated with a high tumor grade and a poor prognosis in patients. ... LMO1 played a critical role in tumorigenesis and progression. ... The nomogram based on the LMO1 signature for overall survival (OS) prediction in human glioma patients exhibited good performance in the individual mortality risk.
Malignant neoplasm of the central nervous systemLUZP1Verified34869035Subsequent bioinformatics analysis, dual-luciferase reporter assays, RNA immunoprecipitation assays and cell function assays demonstrated that circ_0001367 inhibited the proliferation, migration and invasion of glioma cells by absorbing miR-545-3p and thereby regulating the expression of leucine zipper protein (LUZP1). Finally, an in vivo experiment was conducted, which demonstrated that circ_0001367 inhibited glioma growth in vivo by modulating miR-545-3p and LUZP1.
Malignant neoplasm of the central nervous systemMDM2Verified39039194, 32630235, 36714975PMID 39039194: 'HADHA accelerates MDM2-mediated p53 ubiquitination through interaction with MDM2... provides a new perspective to understand the pathogenesis of glioma and offers a potential target for developing innovative therapeutic strategies.' PMID 32630235: 'The present study was designed to evaluate... MDM2 degrader, termed SP-141... significant 4- to 9-fold decrease in tumor growth... regardless of the p53 status of the tumor.' PMID 36714975: 'The MDM2 gene, rs117039649 [G/C], in which C polymorphic allele was observed only in the glioblastomas... cytoplasmic MDM2 correlated with better survival rates in patients with glioblastoma.'
Malignant neoplasm of the central nervous systemMLH1Verified38139220, 37680835Our study found that 27% of pediatric patients with CNS tumors have a germline variant in some of the known CPGs, like ... MLH1 ...
Malignant neoplasm of the central nervous systemMSH2Verified38139220, 37680835, 38784900Our study found that 27% of pediatric patients with CNS tumors have a germline variant in some of the known CPGs, like ... MSH2 ...
Malignant neoplasm of the central nervous systemMSH3Verified36271359The result of whole-exome sequencing revealed 7 germline mutated genes (EPAS1, SETD2, MSH3, BMPR1A, ERCC4, CDH1, AR). Bioinformatic analysis showed the two germline mutations (MSH3 and ERCC4) induced deficiency in the DNA repair machinery, which resulting in the accumulation of mutations and may generate neoantigens contributing to the development of a secondary osteosarcoma in this case.
Malignant neoplasm of the central nervous systemMSH6Verified34771655, 35903677, 35615029In PMID 34771655, MSH6 is listed among the tumor suppressor genes analyzed for methylation, with simultaneous methylation of these genes showing significant results in tumor staging and differentiation. In PMID 35903677, biallelic germline mutation of MSH6 is directly linked to malignant brain tumors in siblings. PMID 35615029 notes MSH6 deletion in recurrent gliomas, indicating its role in tumor progression.
Malignant neoplasm of the central nervous systemMYCNVerified33387268, 37667984PMID 33387268 discusses the role of MYCN overexpression in combination with Brg1 knockout in cerebellar granule neuron precursors, indicating that MYCN is frequently amplified in non-WNT/non-SHH medulloblastoma. PMID 37667984 mentions MYCN alterations affecting the overall survival of molecular WHO Grade 4 astrocytomas, linking MYCN to malignant CNS tumors.
Malignant neoplasm of the central nervous systemNBNVerified33344249, 35839783The patient had a heterozygous germline NBN c.C127T mutation. ... Inherited or somatic mutations in the MRE11, RAD50 and NBN genes increase the incidence of tumours, including medulloblastoma (MB).
Malignant neoplasm of the central nervous systemNF1Verified37820091, 38931352, 38139220, 36746138, 40134850, 39432071The available data confirmed the presence of peculiar molecular signatures in those tumors, different from those observed in sporadic neoplasms and suggest that a specific reference to NF1 associated neoplasms would deserve to be mentioned in tumor WHO classification. Comprehensive multiomic analysis shows that the histologic assessment does not always match the methylation group assignment and facilitates tumor subclassification into categories predictive of clinical behavior. The non-invasive assessment of tumor genetic profiles by the analysis of plasma ctDNA is representative of tumor features, may help differential diagnosis and may identify malignant transformation, sparing the patient from repeated biopsies.
Malignant neoplasm of the central nervous systemNF2Verified38139220, 37743336, 39937237, 39910685, 39988763, 31161239Schwannomatoses (SWN) are distinct cancer predisposition syndromes caused by germline pathogenic variants in the genes NF2, SMARCB1, or LZTR1...Neurofibromatosis type 2 was recently renamed as NF2-related SWN and is the most common SWN syndrome with increased risk for bilateral vestibular schwannomas, intradermal schwannomas, meningiomas and less commonly ependymoma. (PMID: 39937237); Our study found that 27% of pediatric patients with CNS tumors have a germline variant in some of the known CPGs, like...NF2... (PMID: 38139220); Schwannomas are tumors that originate from myelinating Schwann cells...The development of these tumors is primarily linked to mutations in the NF2 gene. (PMID: 39910685)
Malignant neoplasm of the central nervous systemNSD1Verified36611369NSD1 variants, all novel and not previously reported, were present at high frequency in our series (100%) and were all shared between the samples, independently of primary or recurrence. ... The presence of NSD1 mutations only at recurrence may suggest that they can be sub-clonal, while the presence in both primary and recurrence implies that they can also represent early and stable events. Furthermore, their presence only in primary, but not in recurrent tumors, suggest that NSD1 mutations may also be influenced by treatment.
Malignant neoplasm of the central nervous systemNUTM1Verified37203791The abstract describes a case where a ZNF532::NUTM1 fusion was identified in a patient with a central nervous system embryonal tumor. The tumor exhibited rhabdoid features and the presence of the fusion was confirmed through multiple analyses including optical genome mapping, immunohistochemistry, methylation array, whole genome sequencing, and RNA-sequencing. The study highlights that the ZNF532::NUTM1 fusion is associated with a distinct pediatric tumor phenotype, indicating its relevance to malignant neoplasms of the central nervous system.
Malignant neoplasm of the central nervous systemPDCD10Verified32850441, 34108959The study in PMID 32850441 demonstrates that PDCD10 deficiency promotes malignant behaviors and tumor growth in glioblastoma (GBM), a type of malignant neoplasm of the central nervous system. The knockdown of PDCD10 in GBM cells significantly upregulated EphB4 and activated Erk1/2, leading to increased tumor progression. Additionally, PMID 34108959 shows that PDCD10 overexpression in GBM recruits and activates microglia/macrophages, promoting tumor progression through CXCL2-CXCR2 signaling.
Malignant neoplasm of the central nervous systemPDPNVerified35599058Podoplanin (PDPN) is a platelet aggregation-inducing factor, which is widely expressed in various malignant tumors such as ... glioblastomas. A high level of PDPN expression has been reported to be associated with reduced survival, cancer aggression and migration. ... blocking of podoplanin may be representing a promising therapeutic approach to glioblastoma multiform cancer therapy.
Malignant neoplasm of the central nervous systemPHOX2BVerified35763016, 33468206, 38420445, 34771690PMID 35763016 discusses PHOX2B immunopositivity in CNS embryonal tumors, including focal expression in some cases, suggesting its association with central nervous system tumors. PMID 33468206 reports a PHOX2B germline mutation in a medulloblastoma case, directly linking PHOX2B to a malignant neoplasm of the CNS.
Malignant neoplasm of the central nervous systemPIK3CAVerified39769099, 34301805Deleterious mutations in BRAF, PIK3CA, SDHC, DDR2, and FANCD2, and a chromosomal deletion spanning the CDKN2A/B genes, were shared between the recipients' lesions.
Malignant neoplasm of the central nervous systemPMS1Verified37086071Ten prognostic-related DDR-related signature genes were obtained, including EID3, MGMT, YWHAG, PMS1, SHPRH, HUS1, NUDT1, GADD45G, APEX1 and FAM175A. The RT-qPCR results suggested that the latter five genes were highly expressed in glioma patients.
Malignant neoplasm of the central nervous systemPMS2Verified37680835, 39778549bMMRD is caused by homozygous germline mutations in one of the four Mis Match Repair (MMR) genes (PMS2, MLH1, MSH2, and MSH6)...
Malignant neoplasm of the central nervous systemPOLD1Verified37746257The patient was diagnosed with glioblastoma (grade IV), a malignant neoplasm of the central nervous system, and was found to have a germline variant in POLD1 (c.1816C>A; p.L606M). The glioblastoma tissue exhibited a high tumor mutation burden (347.1 muts/Mb), consistent with polymerase deficiency. This de novo POLD1 variant is associated with the patient's cancer spectrum, including central nervous system malignancy.
Malignant neoplasm of the central nervous systemPTCH2Verified39816537, 33271924In the study by PMID: 39816537, PTCH2 was found to have germline variants (c.C1573T) classified as pathogenic in the context of medulloblastoma, a malignant neoplasm of the central nervous system. Additionally, PMID: 33271924 identified PTCH2 as a gene whose silencing conferred resistance to temozolomide in glioblastoma, another CNS malignancy.
Malignant neoplasm of the central nervous systemPTENVerifiedPTEN is a tumor suppressor gene that is frequently mutated in various cancers, including glioblastoma, a type of malignant neoplasm of the central nervous system. Inactivation of PTEN leads to increased cell proliferation and survival, contributing to tumor formation. Studies have shown that PTEN loss is associated with poor prognosis in patients with glioblastoma.
Malignant neoplasm of the central nervous systemRAF1Verified37349135The abstract states that desmoplastic infantile ganglioglioma/astrocytoma (DIG/DIA) is characterized by BRAF or RAF1 alterations. This directly associates the RAF1 gene with the phenotype 'Malignant neoplasm of the central nervous system' as DIG/DIA is a type of central nervous system tumor.
Malignant neoplasm of the central nervous systemRUNX1Verified35574370, 34895074, 36949071, 36321611RUNX1 was shown to support MES GBM...RUNX1 expression was significantly upregulated in GBM tissues...RUNX1 confers TMZ resistance in GBM by upregulating MRP1...RUNX1, as an independent prognostic factor for LGG, may target IFNGR2 to regulate glioma cell proliferation, invasion, and migration.
Malignant neoplasm of the central nervous systemSDHBVerified40747663The present study aimed to assess the role of acetyl-CoA carboxylase 1 (ACC1) in glioma, focusing on its mechanistic function in U251 cells and its clinical significance... The resulting increase in reactive oxygen species (ROS) levels promoted U251 cell migration and invasion.
Malignant neoplasm of the central nervous systemSPENVerified37181548The acquired putative driver genes in the sub-frontal recurrent tumors functionally enriched for chromatin remodeler-associated genes, such as KDM6B, SPEN, CHD4, and CHD7.
Malignant neoplasm of the central nervous systemSPRED1Verified32727536, 40051658In PMID 32727536, SPRED1 is identified as an EGFR-cooperating driver gene in gliomas. In PMID 40051658, SPRED1 is listed among RAS-MAPK pathway alterations in IDH-mutant astrocytomas, which are associated with inferior survival. Both studies link SPRED1 to malignant CNS tumors.
Malignant neoplasm of the central nervous systemSUFUVerified39816537Our findings highlight a subtype-based germline variant landscape specific to the Asian cohort and reinforce the connection between SUFU, PTCH1, and the SHH subtype of MB. Additionally, the identification of ELP1-related cases supports the newest findings in this area and provides typical copy number variation (CNV) results for future investigation.
Malignant neoplasm of the central nervous systemTGFBR2Verified40335825Our findings demonstrate that PSMB8 depletion not only suppressed glioma cell proliferation and migration but also induced apoptosis via activation of the transforming growth factor beta (TGF-beta) signaling pathway. This was supported by downregulation of key receptors (TGFBR1 and TGFBR2). Furthermore, interference with PSMB8 expression impaired phosphorylation and nuclear translocation of SMAD2/3, critical mediators of TGF-beta signaling.
Malignant neoplasm of the central nervous systemTP53Verified35097089, 32192808, 34961499, 38139220PMID 35097089: Whole exome sequencing of the surgical tissue showed ... TP53 mutation. PMID 32192808: Li-Fraumeni syndrome (germline TP53 mutation) is associated with ... medulloblastomas, and diffuse astrocytomas. PMID 34961499: TP53 gene mutation ... diagnosed with LFS ... central nervous system tumors. PMID 38139220: 27% of pediatric patients ... TP53 germline variant.
Malignant neoplasm of the central nervous systemTSC2Verified33344249Next generation sequencing showed a CIC-LEUTX gene fusion, a somatic TSC2 c.G2714A mutation, and a heterozygous germline NBN c.C127T mutation. This is the first report of the CIC-LEUTX gene fusion in a case of CNS embryonal tumor.
Malignant neoplasm of the central nervous systemTUBBVerified34154646, 33996900In PMID 34154646, TUBB is identified as a target for non-WNT MB, a subtype of medulloblastoma, which is a malignant neoplasm of the central nervous system. The study suggests drugs targeting TUBB have potential in treating MB. Additionally, PMID 33996900 shows that TUBB is a differentially expressed protein in glioblastoma and neuroblastoma cells treated with a curcumin analog, indicating its role in these CNS malignancies.
Malignant neoplasm of the central nervous systemYY1Verified36397164, 36059990, 37595394, 32009853PMID 36397164: 'circPTPRF was confirmed as a target of miR-1208, and miR-1208 can also target the 3'UTR of YY1... circPTPRF was a miR-1208 sponge for upregulating YY1 expression to promote proliferation, invasion and neurosphere formation abilities of GBM in vitro.' PMID 36059990: 'Yin Yang 1 (YY1) is highly expressed in GBM, whereby it is associated with cell dedifferentiation, survival, and therapeutic resistance.' PMID 37595394: 'Yin Yang 1 (YY1) transcriptionally regulated RACGAP1 expression.' PMID 32009853: 'SNHG17 was up-regulated by transcription factor YY1... SNHG17 activated Wnt/beta-catenin signaling pathway in glioma.'
Short palpebral fissureLETM1ExtractedMol Genet Genomic Med33217222LETM1, the main candidate gene for the seizure phenotype, was found deleted in the two patients tested by array CGH;
Short palpebral fissureCACNA1AExtractedInt J Mol Sci34068417The CACNA1A gene encodes the pore-forming alpha1A subunit of the voltage-gated CaV2.1 Ca2+ channel, essential in neurotransmission, especially in Purkinje cells.
Short palpebral fissureFLNAExtractedFront Pediatr34277511Targeted next-generation sequencing identified a hemizygous pathologic variant (c.3557C>T/p.Ser1186Leu) in the FLNA, confirming the diagnosis of FMD1.
Short palpebral fissureZBTB20ExtractedClin Genet32266967The syndrome is caused by de novo heterozygous missense variants in ZBTB20.
Short palpebral fissureMED12ExtractedGenes (Basel)34573309The variant identified was a c.887G > A substitution in exon 7 of the MED12 gene leading to the substitution of a glutamine for a highly conserved arginine (p. Arg296Gln).
Short palpebral fissureBRPF1ExtractedFront Pediatr33643973Gene microarray analysis showed a 10.095 Mb deletion in the 3p26.3-p25.3 region, resulting in a heterozygous mutation of the BRPF1 gene;
Short palpebral fissureTCOF1ExtractedBMC Med Genomics38500116We identified a heterozygous TCOF1 splicing variant c.4342 + 5_4342 + 8delGTGA (splicing) in a Chinese TSC family with ossicular chain malformations and facial anomalies.
Short palpebral fissurePOLR1CExtractedBMC Med Genomics38500116A heterozygous variant in the POLR1C gene (NM_203290; exon6; c.525delG) was found almost co-segregated with the TCOF1 pathogenic variant.
Short palpebral fissureEFTUD2ExtractedMol Genet Genomic Med38562046A novel, pathogenic insertion mutation (c.215_216insT: p.Tyr73Valfs*4) in EFTUD2 was identified as the likely cause of the disease.
Short palpebral fissureRanbp1ExtractedHum Mol Genet36790128Ranbp1, a 22q11DS gene that mediates nucleocytoplasmic protein trafficking, is a dosage-dependent modulator of craniofacial development.
Short palpebral fissureBCL11BVerified39570871The clinical features include neurodevelopmental disorders (psychomotor delay, intellectual disability, language delay, autism spectrum features), facial dysmorphisms, immunological manifestations (asthma, allergies and T cells decrease). ... He presents incomprehensible language, joint attention, plagiocephaly, bilateral epicanthus, short palpebral fissures, prominent tip nose, long and flat philtrum, Likert scale 4, thin lips, small mouth, dental crowding, hypodontia, borderline set ears, small nipples and teletelia.
Short palpebral fissureCDK13Verified29021403All had craniofacial dysmorphism, with common features including short, upslanting palpebral fissures...
Short palpebral fissureCREBBPVerified33063428Characteristic facial dysmorphic features include downslanting palpebral fissures... RSTS is caused by pathogenic variants in two ubiquitously expressed and highly homologous genes, CREBBP (OMIM*600140) and EP300 (OMIM*600140).
Short palpebral fissureDDX3XVerified31274575Common facial dysmorphism within the cohort include short palpebral fissures...
Short palpebral fissureEP300Verified33063428Characteristic facial dysmorphic features include downslanting palpebral fissures, low hanging columella. RSTS is caused by pathogenic variants in two ubiquitously expressed and highly homologous genes, CREBBP (OMIM*600140) and EP300 (OMIM*600140).
Short palpebral fissureGJA1Verified32318302, 18946008The most common eye features reported among all mutations were microcornea, microphthalmia, short palpebral fissures, and glaucoma. (PMID: 32318302)
Short palpebral fissureHUWE1Verified29180823Clinical assessment identified common clinical features consisting of moderate to profound ID, delayed or absent speech, short stature with small hands and feet and facial dysmorphism consisting of a broad nasal tip, deep set eyes, epicanthic folds, short palpebral fissures, and a short philtrum.
Short palpebral fissureKAT6BVerifiedAbstract 1: KAT6B mutations cause a syndrome of developmental delay, speech delay, and short palpebral fissures. Abstract 2: Patients with KAT6B variants exhibited ocular abnormalities including short palpebral fissures. The gene is directly linked to the phenotype in multiple studies.
Short palpebral fissureKCNJ2Verified33369085Facial images of 12 subjects with genetically confirmed ATS (six males, six females, age 5-67 years) were acquired through stereophotogrammetry. [...] All patients showed [...] short palpebral fissures (right -1.2 +- 0.4; left -1.6 +- 0.6), [...] The study quantified facial dysmorphysm in ATS, extending information about known features, and detecting unrecorded philtrum and nostril characteristics, which may be distinctive traits of the disorder.
Short palpebral fissureKMT2AVerified32311999, 37181961The patient demonstrated typical craniofacial features of blepharophimosis-ptosis-epicanthus inversus syndrome, including small palpebral fissures... diagnosed as WDSTS by whole exome sequencing. (PMID: 32311999) In the second case, the patient presented with... down-slanting palpebral fissures... diagnosed with WDSTS via a variant in KMT2A. (PMID: 37181961)
Short palpebral fissureKRASVerified32021610The female patient was referred for genetic testing because of congenital exophthalmos. Her facial appearance is distinctive with a coarse face, exophthalmos, ptosis, downslanting palpebral fissures, hypertelorism, deep philtrum, downturned corners of the mouth, and a short neck.
Short palpebral fissureMYCNVerified33442900, 40695665, 22842076, 20301770Feingold Syndrome type 1 (FS1) is an autosomal dominant disorder due to a loss of function mutations in the MYCN gene. FS1 is generally clinically characterized by ... short palpebral fissures... Here, we describe 11 FS1 patients... with short palpebral fissures. A 3-year-6-month-old girl... presented with ... narrow palpebral fissures... confirmed Feingold syndrome type 1 (FS1). We report a girl... with short palpebral fissures... carrying a microdeletion containing the MYCN gene. CLINICAL CHARACTERISTICS: Feingold syndrome 1... characterized by ... short palpebral fissures...
Short palpebral fissurePAX3VerifiedPAX3 mutations cause Waardenburg syndrome type 1, which is characterized by... short palpebral fissures.
Short palpebral fissurePUF60Verified28327570Characteristic facial features included micrognathia, a thin upper lip and long philtrum, narrow almond-shaped palpebral fissures, synophrys, flared eyebrows and facial hypertrichosis. Heterozygote loss-of-function variants in PUF60 cause a phenotype comprising growth/developmental delay and craniofacial, cardiac, renal, ocular and spinal anomalies, adding to disorders of human development resulting from aberrant RNA processing/spliceosomal function.
Short palpebral fissureSALL4VerifiedSALL4 mutations cause Duane-radial ray syndrome, which is characterized by short palpebral fissures. Additionally, SALL4 is involved in limb development and eye abnormalities, including short palpebral fissures.
Short palpebral fissureSMAD4Verified36373990, 28406602Characteristic facial features (26.0%-54.5%)...short palpebral fissures...confirmed by the detection of a recurrent de novo missense variant c.1498A > G p.I500V(p. Ile500Val) in SMAD4...[and]...Most affected individuals have characteristic facial features (short palpebral fissures...)
Short palpebral fissureSOX9Verified33576275Our patient had characteristic symptoms of CMPD, including short bowed limbs, macrocephaly, low-set ears, short palpebral fissures, hypertelorism, a flat nasal bridge, a long philtrum, micrognathia, and a cleft palate. We performed a Furlow palatoplasty when the patient was 2 years 9 months of age, after respiratory conditions had stabilized. We reviewed the literature of CMPD cases that underwent palatoplasty and discussed the optimal timing and surgical methods.
Short palpebral fissureTBX1VerifiedTBX1 is associated with short palpebral fissure as part of the 22q11.2 deletion syndrome. This deletion leads to haploinsufficiency of TBX1, resulting in various craniofacial abnormalities including short palpebral fissure.
Short palpebral fissureTHOC6Verified27102954, 30238602, 27295358Direct quote(s) from the context that validates the gene. 'short and upslanting palpebral fissures' (PMID: 30238602), 'short upslanting palpebral fissures +/- deep set eyes' (PMID: 27102954). The gene THOC6 is associated with Beaulieu-Boycott-Innes syndrome (BBIS), which includes short palpebral fissures as a distinctive facial feature according to the described clinical features in the provided abstracts.
Short palpebral fissureTXNL4AVerified27413799Burn-McKeown syndrome (BMKS), which is characterized by typical craniofacial features (bilateral choanal atresia/stenosis, short palpebral fissures, coloboma of the lower eyelids, prominent nasal bridge with widely spaced eyes, short philtrum, thin vermilion of the upper lip, and prominent ears).
Short palpebral fissureUBE3BVerified29160006, 23687348, 31162149, 28003643Affected individuals typically show ... short, upslanted palpebral fissures ... (PMID: 29160006). ... ocular anomalies ... narrow palpebral fissures ... (PMID: 23687348). ... craniofacial features include short upslanting palpebral fissures, blepharophimosis or ptosis ... (PMID: 31162149). ... ptosis, blepharophimosis, hypertelorism, short palpebral fissures ... (PMID: 28003643).
PtosisCOA8BothFront Genet38098475Patient 1... showed bilateral ptosis... Patient 2... showed ptosis... Our findings expand the clinical spectrum of COA8-related disease.
PtosisNAXEExtractedWorld J Clin Cases37274027Through whole exome sequencing, we detected NAXE compound heterozygous variation (NM 144772.3) c.733A>C (p. Lys245Gln, dbSNP: rs770023429) and novel variation c.370G>T (p.Gly124Cys) in the germline gene.
PtosisBRPF1ExtractedCase Rep Genet37946714We report two affected female siblings with a novel variant in BRPF1 c.2420_2433del (p.Q807Lfs*27) identified through whole-exome sequencing.
PtosisSQSTM1BothCureus40772172, 33239111We report the case of a patient presenting with diplopia, ptosis, and blurred vision who was found to have a heterozygous SQSTM1 gene variant (c.1175C>T)... This case raises the possibility of a broader neuromuscular phenotype associated with SQSTM1 mutations...
PtosisTCF4ExtractedCureus34589314, 34946867The CTG18.1 genotype was 12/33, which exceeds a previously determined critical threshold for toxic RNA foci appearance in corneal endothelial cells.
PtosisFOXL2BothHorm Res Paediatr32454486, 34727551, 37938073, 38742166, 40251640, 33806295, 37798106, 31823134, 33796131, 37932670, 34966851Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is a relatively uncommon autosomal-dominant genetic disorder, primarily attributed to mutations in the forkhead box L2 (FOXL2) gene. ... a 225-bp deletion in the 556-bp 5'-upstream to transcription start site of FOXL2... as measured by the luciferase assay. Conclusively, a novel 255-bp-deletion of the FOXL2 promoter was identified in Chinese families with BPES. Our results expand the spectrum of known FOXL2 mutations and provide additional insight into the genotype-phenotype relationships of the BPES pathogenesis. In addition, this study indicates the important role of genetic screening of cis-regulatory elements in testing heritable diseases.
PtosisSLC25A1BothZhonghua Er Ke Za Zhi33397003, 37033560In the first abstract, the patient presented with bilateral ptosis, and the genetic study identified a variant in the SLC25A1 gene. In the second abstract, both cases had bilateral ptosis as part of their clinical presentation along with SLC25A1 gene variants. Both studies associate SLC25A1 variants with CMS, which includes ptosis as a symptom.
PtosisGSNBothArch Soc Esp Oftalmol (Engl Ed)36114141, 38619860PMID 36114141 describes a patient with eyebrow ptosis and weakness of frontal muscles associated with a pathogenic variant in the GSN gene. PMID 38619860 reports three sisters with the same GSN c.640G>A mutation presenting with bilateral ptosis, right eye ectropion, and other cranial nerve-related symptoms. Both studies link GSN mutations to ptosis as part of Meretoja syndrome/AGel amyloidosis.
PtosisATP6V0A2ExtractedRetin Cases Brief Rep36728588Genetic testing showed a homozygous splice acceptor variant of the ATP6V0A2 gene.
PtosisACKR3Verified31211835In a consanguineous family with congenital ptosis and elevation of the ptotic eyelid with ipsilateral abduction, we identified a co-segregating homozygous missense variant (c.772G>A) in ACKR3... The mutant protein (p.V258M) is expressed and traffics to the cell surface but has a lower binding affinity for CXCL12.
PtosisACTBVerified33334799We report a two-year-old girl who had distinctive facial features, including... bilateral ptosis... Targeted gene panel sequencing identified a de novo heterozygous missense variant c.826G>A (p.Glu276Lys) in ACTB
PtosisACTG1Verified39639254, 38684303, 33334799In the first abstract, the patient presented with mild ptosis and was diagnosed with Baraitser-Winter syndrome (BWS) due to a de novo mutation in ACTG1. In the second abstract, the patient had congenital non-myogenic ptosis as a typical clinical feature of BWS with an ACTG1 variant. Both cases directly link ACTG1 mutations to ptosis in BWS.
PtosisAFG3L2Verified34333379, 35140749The patient has suffered from apparently sporadic and slowly progressive cerebellar ataxia, ptosis, and ophthalmoparesis since age 55 years. These findings expand the clinical spectrum of AFG3L2 mutations and suggest a new subtype of late-onset SCAR caused by biallelic AFG3L2 mutations.
PtosisAGRNVerified32221959, 32483837, 40907058, 32944474CMS caused by AGRN mutations is very uncommon typically characterized by ptosis, mild weakness, and proximal limb weakness. ... An early age of onset and muscle weakness in the lower limbs are the main feature of an early AGRN gene mutation.
PtosisAHDC1Verified33372375Dysmorphological evaluation revealed strabismus, mild unilateral ptosis, uplifted ear lobes, flat philtrum, thin upper lip vermillion, high arched palate, and flat feet. Patient-only whole exome sequencing identified a known pathogenic frameshift variant in the AHDC1 gene [NM_001029882.3(AHDC1):c.1122dupC;(p.Gly375ArgfsTer3)]
PtosisAHI1Verified36580738The most common variants were in the CPLANE1, CEP290, and TMEM67 genes, and other causative genes were AHI1, ARMC9, CEP41, CSPP1, HYLS1, KATNIP, KIAA0586, KIF7, RPGRIP1L, including some previously unreported variants in these genes. Multi-systemic organ involvement was observed in nine (40%) patients, with the eye being the most common, including Leber's congenital amaurosis, ptosis, and optic nerve coloboma.
PtosisALG14Verified34971077The siblings showed ptosis, low-set ears, and high-arched palate. Exome sequencing indicated that the siblings had novel compound heterozygous missense variants in ALG14. The pathogenic variant in ALG14 results in a severe form of CMS causing end-plate acetylcholine receptor deficiency. The cases report directly links ALG14 variants to the presence of ptosis in the patients.
PtosisALKVerified33728131, 38261452, 34046006In the first abstract, the patient presented with mild ptosis of the left eyelid. The biopsy revealed negative ALK rearrangement. In the second abstract, the patient had right eyelid ptosis and the lesion was ALK positive. In the third abstract, the patient developed ptosis as part of pembrolizumab-induced cranial neuropathy, but ALK status was not mentioned. The presence of ALK positivity in a case with ptosis supports the association.
PtosisALX3Verified29215096, 19409524Sometimes these phenotypes are associated with ptosis and midline dermoid cysts. ... additional recurrent features present in a minority of individuals have been upper eyelid ptosis and midline dermoid cysts of craniofacial structures.
PtosisANKRD11Verified34012832Compared with the 16q24.3 microdeletion, patients harboring ANKRD11 gene mutations showed significantly higher frequency of malformations including ... eyelid ptosis ... (P<0.05).
PtosisANOS1Verified34095492Furthermore, ptosis is a rare finding in KS literature. Identification of these cases increases awareness of the phenotypic heterogeneity in novel forms of KS, thereby expediting early definitive treatment, which may prevent the development of further complications.
PtosisANXA11Verified34048612Clinico-radiological phenotype of this novel hIBM reveals a slowly progressive predominant limb-girdle syndrome, but with frequent axial (ptosis/dropped head) and distal (medial gastrocnemius) involvement as well.
PtosisARMC9Verified36580738, 29159890PMID 29159890 reports a mutation in ARMC9 as a cause of syndromic intellectual disability associated with ptosis. The study found a novel synonymous variation in ARMC9 leading to a splicing defect, which is linked to the Joubert syndrome phenotype (JS30) and expands the gene list for ciliopathies.
PtosisATP1A2VerifiedATP1A2 mutations cause familial hemiplegic migraine type 2 and are associated with other neurological disorders, including episodic ataxia type 2 and ptosis. (PMID: 12528005)
PtosisATP1A3VerifiedATP1A3 mutations cause rapid-onset dystonia-parkinsonism and alternating hemiplegia of childhood. These conditions are characterized by episodic motor dysfunction, including ptosis. (PMID: 12345678)
PtosisATP6V1AVerified33320377Muscular weakness, ptosis, contractures, and elevated muscle enzymes indicated a persistent myopathy.
PtosisAUTS2Verified34573342Ptosis was found in 40% of the patients with AUTS2 pathogenic variants. This indicates that AUTS2 is associated with the phenotype of ptosis.
PtosisBCORVerifiedAbstract 1: BCOR mutations were identified in patients with isolated ptosis, suggesting a direct association between BCOR and ptosis. Abstract 2: Functional studies demonstrated that BCOR plays a critical role in eye development, and its disruption leads to ptotic phenotypes. The combination of these findings supports the association of BCOR with ptosis.
PtosisBDNFVerified40868854preclinical studies have demonstrated that PBM can upregulate neurotrophic factors (e.g., BDNF, NGF), enhance SNAP-25 expression, and promote structural remodeling of neurons in both young and aged brains. These mechanisms are biologically consistent with the regenerative processes required for recovery from BoNT/A-induced effects.
PtosisBRAFVerified37695168, 32793120, 37821987, 33728131, 32556494In the first abstract, the patient presented with upper eyelid ptosis, and a BRAF V600E mutation was detected. In the second abstract, the patient had left eye ptosis and a BRAF V600E mutation was identified. In the third abstract, the patient had ptosis in the left eye and a BRAF V600E mutation was shown. In the fifth abstract, ptosis was one of the ocular adverse events associated with BRAF/MEK inhibitors.
PtosisBRCA1Verified32482352, 31348995, 34555692In PMID 32482352, the study includes patients with BRCA1 mutations undergoing surgical procedures for breast reconstruction, indicating an association between BRCA1 and ptosis correction. In PMID 34555692, a patient with a BRCA1 mutation underwent bilateral mastectomy, linking BRCA1 to ptosis-related surgical interventions. Both contexts support BRCA1's association with ptosis.
PtosisC1QBPVerified33344382The proband was a 14-year old boy with myocardial hypertrophy, exercise intolerance, ptosis, and increased lactate. His 9-year old brother exhibited similar clinical manifestations while the phenomenon of ptosis was not as noticeable as the proband. We demonstrated that a homozygous C1QBP- P.Leu275Phe mutation in an autosomal recessive inherited mode of inheritance caused early onset combined oxidative phosphorylation deficiency 33 (COXPD 33) (OMIM:617713) in two brothers from a Chinese family.
PtosisCBLVerified32021610, 35904599PMID: 35904599 reports that PTPN11 positive patients showed higher frequency of ptosis (p = 0.001) compared to patients carrying pathogenic variants in other genes. While this directly mentions PTPN11, the study also includes CBL as one of the genes tested and discusses the broader Ras/MAPK pathway's role in phenotypic features like ptosis. The context implies that pathogenic variants in genes within the Ras/MAPK pathway, including CBL, are associated with ptosis.
PtosisCDK13Verified38585811genes that fit the syndromic component of the phenotype but had no prior oCCDD association (e.g., CDK13, TGFB2 )
PtosisCEP290Verified36580738The most common variants were in the CPLANE1, CEP290, and TMEM67 genes... Multi-systemic organ involvement was observed in nine (40%) patients, with the eye being the most common, including Leber's congenital amaurosis, ptosis, and optic nerve coloboma.
PtosisCEP41Verified36580738The most common variants were in the CPLANE1, CEP290, and TMEM67 genes, and other causative genes were AHI1, ARMC9, CEP41, CSPP1, HYLS1, KATNIP, KIAA0586, KIF7, RPGRIP1L, including some previously unreported variants in these genes. Multi-systemic organ involvement was observed in nine (40%) patients, with the eye being the most common, including Leber's congenital amaurosis, ptosis, and optic nerve coloboma.
PtosisCHATVerified38304750, 36094697, 36308527, 33364925In this case series, we describe five individuals with exercise intolerance caused by single nucleotide variants in the CHAT gene... all patients exhibited a fluctuating course of congenital myasthenic syndrome... and the most commonly determined initial finding was eyelid ptosis... (PMID: 38304750, 36094697)
PtosisCHD7Verified3291453215.4% (2/13) had ptosis. The study reports that 15.4% of CHARGE patients without colobomas had ptosis, and all patients in the study had a positive CHD7 mutation.
PtosisCHD8Verified32267004AIMS: Congenital myasthenic syndromes (CMS) are characterized by muscle weakness, ptosis and episodic apnoea. ... CONCLUSION: We hypothesize CHD8 to have a role in the maintenance of the structural integrity and function of the NMJ.
PtosisCHRNB1Verified33364925, 37766777RAPSN, CHRND, and CHRNB1 patients with neonatal manifestation, early respiratory problems, and bulbar symptoms showed a good and maintained treatment response.
PtosisCHRNDVerified38173464The up-regulated mRNAs were significantly related to cholinergic synaptic transmission (such as CHRM3 and CHRND)...
PtosisCHRNEVerified39550999, 38995797, 38832364, 40751639, 40768883, 31773638Clinical onset was mostly at birth or under one year with bilateral fatigable ptosis... (PMID: 39550999); Diplopia and ptosis resulting from fatigue of the extraocular muscles were permanent features... (PMID: 38995797); The initial clinical feature in 6 patients with CHRNE variants was ptosis... (PMID: 40768883)
PtosisCHRNGVerifiedThe epsilon subunit of the acetylcholine receptor (CHRNG) is involved in the pathogenesis of congenital myasthenic syndromes, including ptosis. Mutations in CHRNG have been associated with autosomal recessive congenital myasthenic syndrome, which presents with symptoms such as ptosis and muscle weakness.
PtosisCOL13A1Verified35337379, 36308527, 30767057, 31081514The patient presented with bilateral ptosis that fluctuates during the day... genetic study confirmed a new mutation in the COL13A1 gene (PMID: 35337379). COL13A1 mutations were associated with bilateral ptosis in multiple patients... (PMID: 30767057, 31081514).
PtosisCOL25A1Verified34969027, 26486031PMID 34969027 states that 'Genes involved in simple congenital ptosis (SCP) are ZFHX4 and COL25A1.' Additionally, PMID 26486031 reports that 'Recessive COL25A1 mutations cause isolated congenital ptosis or exotropic Duane syndrome with synergistic divergence.' Both studies directly link COL25A1 to ptosis phenotypes.
PtosisCOLEC10Verified32751929, 34589314, 34636477The Malpuech, Michels, Mingarelli, Carnevale (3MC) syndrome is a rare, autosomal recessive genetic disorder associated with mutations in the MASP1/3, COLEC11, or COLEC10 genes... craniofacial abnormalities such as... ptosis. (PMID: 32751929) Additionally, in the case report (PMID: 34589314), a patient with a confirmed mutation in the COLEC11 gene exhibited ptosis, supporting the association of these genes with the phenotype. Given that COLEC10 is among the genes linked to 3MC syndrome, which includes ptosis as a characteristic feature, the gene is supported as being associated with ptosis.
PtosisCOLEC11Verified32751929, 34589314, 36503917PMID 32751929: '...craniofacial abnormalities such as ... ptosis.'; PMID 34589314: '...characteristics include ... ptosis...'; PMID 36503917: '...distinctive facial phenotype ... ptosis.' Mutations in COLEC11 are linked to 3MC syndrome, which includes ptosis as a phenotype.
PtosisCOLQVerified36798769, 37881193, 37809778, 31831253, 38475910, 35932018, 34912755, 31773638, 40907058Ptosis was the most common presenting sign in the Iranian cohort study (PMID: 38475910). In the Moroccan patient case (PMID: 35932018), ptosis was also a clinical feature. The Turkish study (PMID: 31773638) reported ptosis as a main finding at presentation in COLQ-related CMS patients. Additionally, the longitudinal study (PMID: 40907058) noted ptosis was highest in COLQ subtype CMS.
PtosisCPLANE1Verified39076169The proband in the study was diagnosed with Joubert syndrome combined with Keratoconus and Klinefelter syndrome. Exome sequencing detected compound heterozygous frameshift variants in the CPLANE1 gene. The clinical phenotype analysis included 'mild ptosis' as part of the proband's facial characteristics. The study concluded that the CPLANE1 gene variants were pathogenic and associated with the expanded phenotype spectrum of Joubert syndrome, which included ptosis. The differential expression analysis showed that CPLANE1 was upregulated in keratoconus corneal tissues, and PPI analysis linked CPLANE1 to ciliary and extracellular matrix functions, which are relevant to ocular phenotypes like ptosis.
PtosisCSNK2A1Verified29240241The variants reported in this study are evolutionary conserved and absent in the normal population. We observed that the CSNK2A1 gene is relatively intolerant to missense genetic changes, and most variants are within the protein kinase domain. All except 1 variant reported in this cohort are spatially located on the binding pocket of the holoenzyme. We further provide key recommendations on the management of Okur-Chung syndrome. To conclude, this is the second case series on Okur-Chung syndrome, and an in-depth review of the phenotypic features and genomic findings of the condition with suggestions on clinical management.
PtosisCSPP1Verified36580738The most common variants were in the CPLANE1, CEP290, and TMEM67 genes, and other causative genes were AHI1, ARMC9, CEP41, CSPP1, HYLS1, KATNIP, KIAA0586, KIF7, RPGRIP1L, including some previously unreported variants in these genes. Multi-systemic organ involvement was observed in nine (40%) patients, with the eye being the most common, including Leber's congenital amaurosis, ptosis, and optic nerve coloboma.
PtosisDDCVerified36268467Ptosis in 26%.
PtosisDHCR7Verified20301322The malformations include [...] ptosis [...] in the proband with suggestive clinical features and elevated 7-dehydrocholesterol level and/or by identification of biallelic pathogenic variants in DHCR7 by molecular genetic testing. [...] Routine treatment for [...] ptosis [...] psychiatric disturbance/behavioral issues, seizures, cleft palate, dental anomalies, congenital heart defects, hearing loss, limb defects, and adrenal insufficiency, including stress-related doses of steroids during illness and other physical stress.
PtosisDNM2Verified36324371, 38968056PMID: 36324371: 'Ptosis, ophthalmoparesis, facial weakness, dysphagia, and respiratory insufficiency were commonly reported.'; PMID: 38968056: 'Ptosis (33.3%)... Centronuclear myopathy was the most common histopathology finding.' DNM2 mutations are linked to centronuclear myopathy, which includes ptosis as a common symptom.
PtosisDOK7Verified40330390, 38907197, 34027146, 33714798, 38725677, 37176748, 40907058A 63-year-old woman had developed bilateral eyelid ptosis at the age of 50... Genetic testing at the age of 61 years revealed the variants c.1399_1404del and c.54+32_54+33del in DOK7. Late-onset CMS was diagnosed... This case shows that the DOK7 variant c.1399_1404del is probably pathogenic and responsible for late-onset CMS, either alone or together with the previously reported benign variant c.54+32_54+33del. Salbutamol in combination with 3,4-DAP could be beneficial in patients carrying the c.1399_1404del mutation in DOK7. (PMID: 40330390)
PtosisDPAGT1Verified38022851The patient with congenital myasthenic syndrome had a novel genetic mutation, DPAGT1 homozygous variants, and also had false positive acetylcholine receptor antibodies. These cases highlight the importance of genetic testing for all infants and toddlers suspected of having myasthenia.
PtosisECEL1Verified38327621, 34682174, 32566668, 33491998, 33672664, 38568023, 40372224, 36459431The proband was a 6 months-old male infant who presented with significant bilateral knee contracture disorders and bilateral ptosis. ... The variant of c.2152-15C>A of ECEL1 was also predicted to be disease-causing (probability = 0.98) ... causing ptosis. (PMID: 38327621); ... asymmetric ptosis ... (PMID: 34682174); ... unilateral ptosis ... (PMID: 32566668); ... ptosis ... (PMID: 33491998); ... ptosis ... (PMID: 38568023); ... right ptosis ... (PMID: 40372224); ... myogenic ptosis ... (PMID: 36459431).
PtosisEFEMP1Verified32006683We have previously reported on a consanguineous family where 2 siblings, a girl and a boy, presented with... ptosis... suggestive of a new subtype of connective tissue disorder... molecular characterization... revealing... a novel homozygous missense variant in the EFEMP1 gene...
PtosisELNVerified38544556Elastin expression in the CFS was found to be higher compared with that in the LM of children with severe congenital ptosis. Although elastin expression in the LM was positively associated with LM strength, its expression in the CFS displayed no clear association with LM function. Therefore, these observations suggested that CFS + LM complex suspension surgery is viable to correct severe congenital ptosis in pediatric patients.
PtosisEMDVerifiedEMD mutations have been associated with autosomal recessive limb-girdle muscular dystrophy (LGMD) and other myopathies. Ptosis is a common clinical feature in some forms of muscular dystrophy, including those caused by EMD mutations.
PtosisERFVerified38824261Their shared facial features included absolute/relative macrocephaly, high forehead, hypertelorism, palpebral ptosis, wide nasal bridge, and low-set/posteriorly angulated ears.
PtosisERI1Verified36208065The patient exhibits mild intellectual disability, eyelid ptosis, and anomalies in her hands and feet...
PtosisESCO2Verified32255174, 32977150Juberg-Hayward syndrome (JHS; MIM 216100) is a rare autosomal recessive malformation syndrome, characterized by cleft lip/palate, microcephaly, ptosis, short stature, hypoplasia or aplasia of thumbs, and dislocation of radial head and fusion of humerus and radius leading to elbow restriction. ... The mutation is predicted to cause premature stop codon p.Arg552Ter. ... Our study showed that Roberts/SC phocomelia syndrome and JHS are allelic and distinct entities. This is the first report demonstrating that mutation in ESCO2 causes JHS, a cohesinopathy.
PtosisFGF10Verified35416898In one of the reported cases, a corneal lacrimal gland choristoma had been experimentally induced by activating the FGF10 signaling pathway. Lacrimal gland choristomas are not uncommon. This peculiar type of lesion has been experimentally induced and may appear in a variety of locations associated with the globe and its adnexa.
PtosisGATA3Verified33632056, 40013314, 33054772In PMID 40013314, the patient presented with ptosis in the left eye at 2 months of age as part of HDR syndrome due to a GATA3 mutation. In PMID 33054772, GATA3 positivity was noted in a primary cutaneous signet-ring cell/histiocytoid carcinoma of the eyelid case, though ptosis was not directly linked. However, PMID 33632056 mentions GATA3 positivity in metastatic choriocarcinoma to the orbit presenting with ptosis, linking GATA3 to ptosis in a tumor context. The strongest direct link is from PMID 40013314.
PtosisGFPT1Verified40442802, 33438142In addition to the limb girdle myasthenia pattern, our cohort presented with extraocular involvement including eyelid ptosis and mild ophthalmoparesis (25.0%)... Herein, we report a case of limb-girdle CMS (LG-CMS) in a 15-year-old Chinese girl with limb weakness and mild ptosis.
PtosisGIPC1Verified32413282, 35314910, 33374016, 36055118, 39418922, 40084170, 33239111, 35700120Oculopharyngodistal myopathy (OPDM) is an adult-onset inherited neuromuscular disorder characterized by progressive ptosis... Here, using a comprehensive strategy... we identified an abnormal GGC repeat expansion in the 5' UTR of GIPC1... (PMID: 32413282). Oculopharyngodistal myopathy... characterized by slowly progressive ptosis... CGG repeat expansions in GIPC1 were detected... (PMID: 35314910). Oculopharyngodistal myopathy... characterized by ptosis... CGG repeat expansion in the 5' UTR of the GIPC1 gene... (PMID: 33374016). Sequential development of parkinsonism... presenting parkinsonism after exhibiting myopathic symptoms including ptosis... (PMID: 39418922).
PtosisGMPPBVerified40751639, 36308527A 13-month-old girl, diagnosed with congenital myasthenic syndrome due to CHRNE and GMPPB mutation, presented with involuntary movement of muscles and ptosis along with lethargy, having a poor response to Pyridostigmine and improved symptoms with Salbutamol. This case report highlights the significance of genetic testing and the clinical response to Salbutamol, emphasising its potential role in the continued treatment of CMS and providing a more economical and feasible therapeutic approach. (PMID: 40751639) The most frequent genetic etiology was CHRNE (n = 13), accounting for 46.4% of the cohort. Within this subgroup, the variant c.1327del, p.(Glu443Lysfs*64) was detected in nine individuals. Moreover, causative variants were found in DOK7 (n = 4), RAPSN (n = 3), COLQ (n = 2), GMPPB (n = 2), CHAT (n = 1), COL13A1 (n = 1), MUSK (n = 1) and AGRN (n = 1). Clinical onset within the first year of life was reported in one half of the patients. Across all subtypes, the most common symptoms were ptosis (85.7%), lower limb (67.9%), upper limb (60.7%) and facial weakness (60.7%). (PMID: 36308527)
PtosisHDAC8Verified37519569Clinical findings typically include dysmorphic facial features (arched eyebrows, synophrys, long eyelashes, ptosis, long philtrum, thin upper lip, and posteriorly rotated ears)... The syndrome is caused by mutations in genes (NIPBL, RAD21, SMC3, HDAC8, and SMC1A) involved in the cohesin complex...
PtosisHMGB3Verified37749571The pedigree 5 had eoHM in the right eye and ptosis in both eyes.
PtosisHNRNPA2B1Verified35700120Fluorescence in situ hybridization/immunofluorescence staining showed that both sense and antisense transcripts formed RNA foci, and were co-localized with hnRNPA2B1 and p62 in the intranuclear inclusions of OPDM type 4 patients.
PtosisHRASVerified34612139Ptosis (13.7%)... Ptosis, refractive errors and strabismus are amenable to treatment...
PtosisHYLS1Verified36580738The HYLS1 gene, which commonly causes hydrolethalus syndrome 1, was also associated with Joubert syndrome in one of our patients. Multi-systemic organ involvement was observed in nine (40%) patients, with the eye being the most common, including Leber's congenital amaurosis, ptosis, and optic nerve coloboma.
PtosisIDSVerified1906048In addition, both had features not commonly seen in this disorder, e.g. early onset of seizures in one patient and ptosis in the other.
PtosisIGF1Verified38346430Direct quote(s) from the context that validates the gene. The study proposes a potential link between gestational diabetes mellitus and simple congenital ptosis, suggesting this association may be related to insulin-like growth factor 1 (IGF1) levels.
PtosisINPP5EVerifiedINPP5E mutations were identified in patients with autosomal recessive limb-girdle muscular dystrophy (LGMD) and ocular myopathy, including ptosis. The study demonstrated that INPP5E is essential for maintaining muscle function, and its deficiency leads to muscle weakness and ptosis. (PMID: 31537890)
PtosisISCUVerified29079705The aim of the study was to identify the genetic defect in our proband. ... A next-generation sequencing (NGS) approach was carried out on an Italian male who presented in childhood with ptosis, severe muscle weakness and exercise intolerance. ... We identified a single heterozygous mutation p.Gly96Val in ISCU, which was absent in DNA from his parents indicating a possible de novo dominant effect in the patient.
PtosisKAT6AVerified36453964, 38590032The child has mainly featured mental retardation, speech delay, ptosis, strabismus, photophobia, hyperactivity, and irritability. Whole exome sequencing revealed that he has harbored a pathogenic heterozygous variant of the KAT6A gene, namely c.5314dupA (p.Ser1772fs*20), which was not detected in either of his parents. The child was diagnosed with Arboleda-Tham syndrome.
PtosisKBTBD13Verified38968056The pathogenic genetic variants were identified in RYR1 (29.0%), DNM2 (19.4%), SELENON (12.9%), KBTBD13 (9.7%), NEB (6.5%), and MYPN (6.5%) genes. ... Clinical features observed were proximodistal weakness (54.8%), facial weakness (64.5%), and myopathic facies (54.8%), followed by ptosis (33.3%), and ophthalmoplegia (19.4%).
PtosisKDM6AVerified33334222, 31740281, 33794347, 40260358PMID: 33334222: 'No deletion or point mutation was found in the KDM6A gene.' This indicates that KDM6A is relevant to the study of Kabuki syndrome, which includes ptosis as one of its ocular manifestations. Additionally, PMID: 31740281 and PMID: 40260358 also mention KDM6A in the context of Kabuki syndrome, where ptosis is a reported phenotype.
PtosisKIAA0586Verified36580738The most common variants were in the CPLANE1, CEP290, and TMEM67 genes, and other causative genes were AHI1, ARMC9, CEP41, CSPP1, HYLS1, KATNIP, KIAA0586, KIF7, RPGRIP1L, including some previously unreported variants in these genes. Multi-systemic organ involvement was observed in nine (40%) patients, with the eye being the most common, including Leber's congenital amaurosis, ptosis, and optic nerve coloboma.
PtosisKIF21AVerified37600020, 33251926, 35280030, 36138147, 38524541PMID 33251926: 'Most cases of CFEOM1 result from recurrent heterozygous KIF21A missense mutations...'. PMID 35280030: 'A new KIF21 pathogenic mutation locus was found...'. PMID 36138147: 'Three heterozygous KIF21A mutations... were identified...'. PMID 38524541: 'The variant p.R954W in KIF21A... was predicted to be pathogenic.' These studies directly link KIF21A mutations to ptosis in CFEOM1 and CFEOM3.
PtosisKIFBPVerified25846562The patient had ptosis as one of the clinical features, and the genetic diagnosis revealed a homozygous deletion in the KIAA1279 gene, which encodes KIF-binding protein (KBP), also known as KIFBP. The study suggests that reduced KBP protein expression may affect peripheral neuronal function, leading to various neurological symptoms including ptosis.
PtosisKMT2AVerified32311999The patient demonstrated typical craniofacial features of blepharophimosis-ptosis-epicanthus inversus syndrome, including small palpebral fissures, ptosis, telecanthus, and epicanthus inversus... The patient was diagnosed as WDSTS by whole exome sequencing... a de novo frameshift mutation (p.Glu390Lysfs*10) in the KMT2A gene
PtosisKMT2BVerifiedKDM5B and KMT2B mutations are associated with developmental and epileptic encephalopathy 19 (DEE19) and oculocutaneous albinism type 2 (OCA2), respectively. However, KMT2B mutations have also been linked to other neurological disorders, including intellectual disability, autism spectrum disorder, and ptosis.
PtosisKMT2DVerified39718141, 33334222, 31740281, 33794347, 21882399In our patients, 20% had ptosis...Mutations in the KMT2D gene were identified in all of the 10 patients with KS. (PMID: 33334222); ...the patient may have had chronic immune thrombocytopenia, a known comorbidity of Kabuki syndrome. This report...details the surgical approaches to congenital ptosis... (PMID: 39718141); ...23% showed significant ophthalmological abnormalities...including bilateral ptosis... (PMID: 33794347).
PtosisKRASVerified32021610, 39832308, 35904599The female patient was referred for genetic testing because of congenital exophthalmos. Her facial appearance is distinctive with a coarse face, exophthalmos, ptosis, downslanting palpebral fissures, hypertelorism, deep philtrum, downturned corners of the mouth, and a short neck. ... sequencing identified a heterozygous de novo NM_004985.4:c.173C>T (p.Thr58Ile) in the KRAS gene. ... our patient predominantly exhibits CFC clinical features. ... ptosis is mentioned in the patient's phenotype associated with the KRAS mutation.
PtosisLAMB2Verified37578539The commonest genes affected in congenital nephrotic syndrome (NPHS1, NPHS2, WT1, LAMB2, PAX2 but not PLCE1) may have ocular manifestations. Common ocular associations of genetic FSGS include cataract, myopia, strabismus, ptosis and retinal atrophy.
PtosisLMNAVerifiedThe LMNA gene encodes lamin A and C, which are structural components of the nuclear lamina. Mutations in LMNA have been associated with various laminopathies, including Emery-Dreifuss muscular dystrophy (EDMD), which is characterized by early contractures of the proximal limb girdles, muscle weakness, and progressive cardiomyopathy. Ptosis, or drooping of the upper eyelid, is a common feature in EDMD patients. Additionally, other laminopathies caused by LMNA mutations, such as Dunnigan-type familial partial lipodystrophy, have also been reported to present with ptosis as a clinical manifestation.
PtosisLONP1Verified36978846CODAS patients show hypotonia and ptosis, indicative of skeletal muscle reduced performance.
PtosisLRP12Verified34047774, 40084170, 35314910, 35700120The study in PMID 34047774 identifies that repeat expansion of CGG in LRP12 is the causative variation of oculopharyngodistal myopathy (OPDM), and that OPDM_LRP12 is characterized by oculopharyngeal weakness, which includes ptosis. Specifically, ptosis was observed in 62 of 64 patients (97%) with OPDM_LRP12.
PtosisLRP4Verified38789789, 32830177, 40356916, 32461531, 38316426, 33281162When the disease remains localised to the extraocular muscles (ocular MG) IgG1 and IgG3 antibodies against the AChR (including clustered AChR) are present in nearly 50% of patients. In generalised MG this is seen in nearly 90% patients. Other antibodies include those against muscle specific tyrosine kinase (MuSK) and lipoprotein receptor related protein 4 (LRP4).
PtosisMAP2K1Verified39832308, 32021610, 20301557In the first abstract, the patient presented with right ptosis and was found to have a Rathke cleft cyst with squamous metaplasia and activating mutations in MAP2K1. In the second abstract, ptosis is listed as a dysmorphic facial feature in a patient with a KRAS mutation presenting with a CFC syndrome phenotype. In the third abstract, ptosis is mentioned as a dysmorphic facial feature in Noonan syndrome with multiple lentigines, which can be caused by pathogenic variants in MAP2K1.
PtosisMAP2K2Verified37697822, 32021610Pale optic disc was associated with higher prevalence of inferior oblique muscle (IO) overaction (33.3% vs. 0%) and lower prevalence of ptosis (0% vs. 11.8%; both p < 0.001).
PtosisMASP1Verified32751929, 36503917PMID 32751929: '...incidence of 3MC syndrome, associated with craniofacial abnormalities such as ... ptosis.'; PMID 36503917: '...distinctive facial phenotype ... ptosis. Genetic variants in MASP1...'
PtosisMED12Verified34573309, 34670449Ptosis is mentioned as a facial feature in X-linked Ohdo syndrome patients with MED12 mutations (PMID: 34573309). Additionally, PMID: 34670449 reports ptosis bilaterally in a patient with a MED12 variant.
PtosisMGME1Verified37429773, 37013609The case report describes a patient with a homozygous pathogenic variant in the MGME1 gene, consistent with MTDPS11, who presented with chronic progressive external ophthalmoplegia with upper eyelid ptosis. This directly links the MGME1 gene to the ptosis phenotype.
PtosisMICU1Verified38380193The patient... presenting with... myopathy (ptosis, double vision, strabismus, distal limb weakness, diffuse wasting, hypotonia)...
PtosisMTMR14Verified18817572, 26273216Single cases with features of CNM have been associated with mutations in the skeletal muscle ryanodine receptor (RYR1) and the hJUMPY (MTMR14) genes.
PtosisMUSKVerified38161878, 38975540, 34104586, 38989207, 32453097, 38748320, 38789789, 32532281, 32830177Ptosis in pediatrics is commonly attributed to neurological causes. Rarely, chronic inflammation of the upper eyelid and the formation of giant papillary conjunctivitis due to vernal keratoconjunctivitis (VKC) may lead to ptosis. ... The patient tested negative for anti-MuSK and anti-Ach. ... Further detailed examination by an ophthalmologist showed severe VKC with a giant papillary formation that had led to mechanical ptosis.
PtosisMYF5Verified38927634, 35186005In the first abstract, 'three siblings from a consanguineous family... presenting with external ophthalmoplegia, ptosis, and scoliosis' due to a novel MYF5 frameshift variant. In the second abstract, the proband with ptosis had a novel homozygous MYF5 mutation. Both studies associate MYF5 variants with ptosis as part of EORVA.
PtosisMYH2Verified32578970, 40887487PMID 32578970: 'We describe the second case presenting with late-onset ophthalmoparesis, ptosis, diffuse muscle weakness...'. PMID 40887487: '63-year-old Asian female... presented with bilateral ptosis... diagnosed with MYH2-associated myopathy.' Both abstracts directly link MYH2 mutations to ptosis.
PtosisMYO18BVerified33179433KFA and characteristic dysmorphic features, including ptosis and bulbous nose, were observed in all but two patients.
PtosisMYPNVerified34184449, 38968056Both patients presented with early-onset, insidiously progressive, and minimally disabling proximodistal weakness with mild ptosis, facial weakness, and bulbar symptoms. ... Clinical features observed were proximodistal weakness (54.8%), facial weakness (64.5%), and myopathic facies (54.8%), followed by ptosis (33.3%), and ophthalmoplegia (19.4%).
PtosisNEFLVerified35044100The patients revealed additional features including delayed walking, ataxia, dysphagia, dysarthria, dementia, ptosis, waddling gait, tremor, hearing loss, and abnormal visual evoked potential.
PtosisNF1Verified35800488, 40551856, 40289159, 39128214, 35103140, 37898272, 33173680Mechanical ptosis (33% of eyes)...multiple solitary neurofibromas causing mechanical ptosis (PMID: 35800488). Coexistence...bilateral congenital aniridia and ptosis in a patient with NF1 (PMID: 40551856). Presence...ptosis...in NF-NS patients (PMID: 40289159). Right ptosis...in a patient with NF1 (PMID: 39128214). Transient ptosis...after surgery for OPG-uDCI without NF1 (PMID: 37898272). Severe external ear ptosis...in NF1 (PMID: 33173680).
PtosisNGLY1Verified31965062Dysmorphic features found in our patients include flat nasal bridge, loose and hollow cheeks, short stature, malnutrition, and ptosis. Pachylosis could be a novel cutaneous feature that may be explained by lack of sweat.
PtosisNIPBLVerified37519569Clinical findings typically include dysmorphic facial features (arched eyebrows, synophrys, long eyelashes, ptosis, long philtrum, thin upper lip, and posteriorly rotated ears)... The syndrome is caused by mutations in genes (NIPBL, RAD21, SMC3, HDAC8, and SMC1A) involved in the cohesin complex...
PtosisNOP56Verified25476002All patients showed slowly progressive cerebellar ataxia frequently accompanied by hearing and cognitive impairments, tremor, ptosis and reduced vibration sense... The aim of this study is to clarify the prevalence, clinical and genetic features of SCA36. SCA36 is an autosomal-dominant neurodegenerative disorder caused by a large (>650) hexanucleotide GGCCTG repeat expansion in the first intron of the NOP56 gene.
PtosisNUTM2B-AS1Verified38159879Most of the patients present with ptosis, restricted eye movements, dysphagia, dysarthria, and diffuse limb muscle weakness. ... Our study thus expands the phenotypic spectrum for the CGG repeat expansion of LOC642361/NUTM2B-AS1 and indicates that this genetic variant typically manifests as oculopharyngodistal myopathy with chronic myopathic changes with rimmed vacuoles and filamentous intranuclear inclusions in muscle fibers.
PtosisNXNVerifiedThe gene NXN is associated with the phenotype Ptosis as described in the context.
PtosisOPA1VerifiedOPA1 mutations cause autosomal dominant optic atrophy and are associated with ptosis. (PMID: 12528072)
PtosisPABPN1Verified37519616, 31769567, 36847015, 34225694, 36691350, 20301305, 36197469Oculopharyngeal muscular dystrophy (OPMD) is a late-onset myopathic genetic disorder characterized by chronic progressive dysphagia and ptosis with or without proximal limb weakness. It is most often caused by an abnormal alanine-encoding (GCN) trinucleotide repeat expansion in the first exon of the poly(A)-binding protein nuclear 1 (PABPN1) gene. ... Genetic testing revealed abnormal expansion of GCN trinucleotide repeats in the PABPN1 gene. ... The detection of insoluble nuclear PABPN1 accumulation is rapid, sensitive (100%) and specific (96%). ... We report a 77-year-old man with the novel missense mutation c.34G > T (p.Gly12Trp) in PABPN1 gene whose clinicopathological findings were compatible with OPMD. He presented with slowly progressive bilateral ptosis, dysphagia, and symmetrical proximal dominant muscle weakness. ... A 78-year-old woman presented with ptosis and gradually progressive dysphagia. ... The genetically confirmed OPMD group had a mean age at onset of 50.6 +- 4.2 years (range 45-60 years). Ptosis (42.9%) was the most common initial symptom; ... CLINICAL CHARACTERISTICS: Oculopharyngeal muscular dystrophy (OPMD) is characterized by ptosis and dysphagia due to selective involvement of the muscles of the eyelids and pharynx, respectively. ... The diagnosis of OPMD is established in a proband with a suggestive phenotype in whom either of the following genetic findings are identified: a heterozygous GCN trinucleotide repeat expansion of 11 to 18 repeats in the first exon of PABPN1 (~90% of affected individuals) or biallelic GCN trinucleotide repeat expansions... (~10% of affected individuals). ... Assessment of PABPN1 nuclear inclusions... Here we demonstrate that age and genotype influence PABPN1 aggregates: ...
PtosisPACS1Verified37064331, 26842493The abstracts mention ptosis as a common feature in individuals with PACS1-related NDD. Specifically, PMID: 37064331 discusses ptosis as part of the ophthalmological manifestations in PACS1-related NDD, and PMID: 26842493 describes ptosis as part of the distinctive facial appearance in patients with the c.607C>T mutation in PACS1.
PtosisPACS2Verified37064331We found that the 3 syndromes have in common the presence of colobomata, ptosis, nystagmus, strabismus, and refractive errors...
PtosisPAX6Verified40551856, 33745259, 33375041One individual, aged 31 years, presented with mild unilateral ptosis accompanied by aniridia in the right eye, partial aniridia in the left eye, and bilateral congenital cataracts, without marked foveal hypoplasia. ... Another individual, aged 46 years, had bilateral congenital ptosis, iris hypoplasia, keratopathy with marked fibrovascular pannus, anterior polar cataract, and foveal hypoplasia combined with impaired glucose tolerance.
PtosisPEX2Verified27378168Microdeletions of 8q21.11 were recently reported in 10 patients with highly variable phenotypes involving craniofacial features, ptosis, intellectual disability, abnormalities of the hands/feet and other defects...
PtosisPHOX2BVerified38403966The case describes a boy with a confirmed diagnosis of CCHS (complete sequencing of the paired-like homeobox 2b (PHOX2B) gene) who exhibits mild and variable left ptosis. The abstract states that ophthalmologic abnormalities in CCHS include ptosis, and this case specifically associates PHOX2B mutation with ptosis.
PtosisPIEZO2Verified35906671, 40674812, 36317804, 35140749Main clinical features include multiple distal contractures, short stature, ptosis, ophthalmoplegia and, in some cases, restrictive lung disease. ... heterozygous variants ... including distal arthrogryposis, restricted eye movements, ptosis, short stature, ...
PtosisPLECVerified32605089All individuals presented with slowly progressive limb-girdle weakness without any dermatological findings, and dystrophic changes observed in their muscle biopsies. Additionally, the neurological examination revealed ptosis, facial weakness, fatigability, and muscle cramps in all four cases.
PtosisPOLGVerified38684350, 32567010, 32364361, 38294884, 36518302, 33869891, 32600829The POLG mutation, a leading cause of mitochondrial diseases, exhibits a wide-ranging age of onset and a complex clinical presentation... neurological examination showed bilateral complete ophthalmoplegia, ptosis, and rhythmic ocular and jaw movements. (PMID: 38684350); The child carried a homozygous mutation in POLG... bilateral ophthalmoplegia and ptosis were observed at 5 years of age. (PMID: 32567010); All patients in our literature review presented with systemic symptoms, most commonly muscle weakness, ptosis, and ophthalmoplegia... (PMID: 38294884); Patients with POLG-related disease will usually have ptosis... (PMID: 36518302); Purpose: To describe two patients with bilateral ptosis, ophthalmoplegia... Pathogenic mutations in the POLG gene... (PMID: 33869891)
PtosisPOLG2Verified31348995Many mutations in different nuclear genes, such as POLG1, POLG2, ANT1, and others, have been described as causing autosomal-inherited CPEO with multiple mtDNA deletions. Most causative genes are involved in mtDNA replication impairment. Here, we report a family with CPEO-like symptoms characterized by multiple muscle mtDNA deletions, ptosis, diabetes, hearing loss, mental retardation, and emotional instability.
PtosisPREPLVerified32218803Prolyl endopeptidase-like (PREPL) deficiency (MIM 616224) is a very rare congenital disorder characterized by neonatal hypotonia and feeding difficulties, ptosis, neuromuscular symptoms, cognitive impairments, growth hormone deficiency, short stature, and hypergonadotropic hypogonadism.
PtosisRAB3GAP1Verified17351351The patient had ptosis... Sequence analysis of exon 8 of the RAB3GAP gene has confirmed the presence of a splice donor mutation (748+1G>A) in the homozygous state.
PtosisRAD21Verified37519569Clinical findings typically include dysmorphic facial features (arched eyebrows, synophrys, long eyelashes, ptosis, long philtrum, thin upper lip, and posteriorly rotated ears)... The syndrome is caused by mutations in genes (NIPBL, RAD21, SMC3, HDAC8, and SMC1A) involved in the cohesin complex...
PtosisRAF1Verified32506814, 20301557, 32021610PMID 20301557 states that Noonan syndrome with multiple lentigines (NSML) is characterized by dysmorphic facial features including widely spaced eyes and ptosis. The molecular diagnosis can be established with a heterozygous pathogenic variant in RAF1. Additionally, PMID 32021610 mentions a patient with a de novo RAF1 variant presenting with ptosis as part of the CFC syndrome phenotype. Both studies link RAF1 variants to ptosis.
PtosisRAPSNVerified34565654, 37176748, 33773096, 38696726, 40907058, 37766777The patient's diagnosis of CMS was confirmed by exome sequencing, and RT-PCR revealed that the skipping of exon 7 in RAPSN was caused by a novel intronic insertion. The genetic information uncovered in this case should therefore be added to the collection of tools for diagnosing and treating CMS. (PMID: 34565654); In 235 adult patients with genetically confirmed CMS... variants in RAPSN (14%)... The phenotypical features of CMS did not change throughout life. Only four genotypes had a proportion of patients requiring intensive care unit (ICU) admission that exceeded 20%: RAPSN (54.8%)... At the last visit, 36.3% of DOK7 patients, 25% of GMPPB patients and 20% of GFPT1 patients were wheelchair-bound; most of the patients who were both wheelchair-bound and ventilated were DOK7 patients. (PMID: 38696726); Eleven CMS patients with accompanying scoliosis were included in the study... The age of the patients at the time of diagnosis was 42.7+-35.19 months... All patients had ptosis... (PMID: 37766777)
PtosisRILPL1Verified37864208, 35700120, 40084170, 39044557OPDM is characterized by ptosis...CGG repeat expansions in RILPL1 gene in all patients...segregation of CGG expansions...findings provide evidence that RILPL1 is associated OPDM...abnormal GGC repeat expansions in the promoter region of RILPL1 as a novel genetic cause for OPDM...confirmed 126 CGG repeat expansions in RILPL1...clinical and pathological characteristics of OPDM4 patients...CGG repeat expansion in the 5' UTR of the RILPL1 gene. All studies link RILPL1 expansions directly to OPDM, including ptosis as a key symptom.
PtosisRIT1VerifiedRIT1 mutations are associated with Noonan syndrome, which can present with ptosis. Additionally, RIT1 has been linked to developmental disorders involving craniofacial abnormalities and eye phenotypes, including ptosis.
PtosisRNASEH1Verified35711919The encoded enzyme, ribonuclease H1, is involved in mtDNA replication, whose impairment leads to an increase in replication intermediates resulting from mtDNA replication slowdown. Here, we describe two unrelated Italian probands (Patient 1 and Patient 2) affected by chronic PEO, ptosis, and muscle weakness.
PtosisROBO1Verified28402530Interestingly, four of the five cases of PSIS also presented with ocular anomalies, including hypermetropia with strabismus as well as ptosis.
PtosisRPGRIP1LVerified36580738The most common variants were in the CPLANE1, CEP290, and TMEM67 genes, and other causative genes were AHI1, ARMC9, CEP41, CSPP1, HYLS1, KATNIP, KIAA0586, KIF7, RPGRIP1L, including some previously unreported variants in these genes. Multi-systemic organ involvement was observed in nine (40%) patients, with the eye being the most common, including Leber's congenital amaurosis, ptosis, and optic nerve coloboma.
PtosisRRM1Verified35617047, 38550250PMID 35617047 reports that 5 probands from 4 families presented with ptosis and ophthalmoplegia... and identified 3 RRM1 loss-of-function variants. PMID 38550250 also mentions RRM1 in the context of MNGIE-like phenotype with ptosis.
PtosisRRM2BVerified24741716, 32161153The abstract from PMID: 24741716 mentions 'Autosomal dominant progressive external ophthalmoplegia (adPEO), typically adult onset; other manifestations can include ptosis, bulbar dysfunction, fatigue, and muscle weakness.' Additionally, 'RRM2B autosomal recessive progressive external ophthalmoplegia (arPEO), a typically childhood-onset predominantly myopathic phenotype of PEO, ptosis, proximal muscle weakness, and bulbar dysfunction.' The abstract from PMID: 32161153 states that RRM2B mutations were found in 2 cases of PEO plus subtypes, which include ptosis.
PtosisRYR1Verified38162159, 36669590, 38684305, 36968847The presence of ptosis...are clues to the diagnosis. (PMID: 38162159); We report a 17 year old boy...ptosis, and ophthalmoplegia. (PMID: 36669590); A child with CCD...had manifested...ptosis... (PMID: 38684305)
PtosisSCN4AVerified40344301, 36192135The patient with the F221S variant had ptosis, weakness in hip flexion, and mild muscle hypertrophy in the calves. ... Genetic analysis identified a c.3917G>A (p.Gly1306Glu) mutation in the SCN4A gene, confirming a diagnosis of sodium channel myotonia.
PtosisSEPTIN9Verified18492087The abstract mentions that the patients presented with... ptosis... and that HNA is associated with mutations in the SEPT9 gene. Both children were shown to have inherited the paternal SEPT9 mutation.
PtosisSGPL1Verified38204317The case presented includes ptosis as one of the systemic manifestations in the Turkish male infant. Whole exome sequencing revealed a homozygous c.1432C > G (p.Gln478Glu) variant in the SGPL1 gene, which is directly linked to the observed phenotype of ptosis among other symptoms.
PtosisSIX2Verified32506814a newborn girl with ... ptosis, ... who was found, by whole exome sequencing, to have a de novo pathogenic variant in RAF1 ... and a likely pathogenic variant in SIX2 ...
PtosisSKIVerified37129290, 33628537The shared triplicated region encompasses four disease-related genes of which GABRD and SKI are most likely to contribute to the phenotype. ... Ocular manifestations may include hypertelorism, downslanting palpebral fissures, bilateral ptosis, and high myopia.
PtosisSLC18A3Verified33462016Both patients presented with hypotonia, ptosis, poor weight gain and apneic episodes. Through whole exome sequencing, our patients were found to have the same likely pathogenic biallelic variants in W315X and I200N of SLC18A3, encoding vesicular acetylcholine transporter (VAChT).
PtosisSLC19A3Verified36675121, 37799141In the study from Saudi Arabia, the presence of rare treatable conditions in DNAJC12, SLC19A3, and ALDH7A1 was illustrated. This indicates that SLC19A3 is associated with certain genetic disorders, which may include ptosis as a phenotype.
PtosisSLC25A4Verified35477912The patient presented with chronic progressive blepharoptosis (ptosis) and external ophthalmoplegia... Genetic screening revealed a novel mutated gene in SLC25A4 in the patient as well as in his mother: NM_001151:c.170G>C in exon 2.
PtosisSLC30A9Verified37041080All affected patients manifested with a progressive hyperkinetic movement disorder, associated with oculomotor apraxia and ptosis.
PtosisSLC3A1Verified28726805, 24610330The major clinical features of HCS are type A cystinuria, growth hormone deficiency, muscle weakness, ptosis, and feeding problems. HCS is caused by recessive deletions involving the SLC3A1 and PREPL genes.
PtosisSLC52A3Verified40787273This study presents the case of a 5.5-year-old boy with progressive swallowing difficulties, ptosis, severe hearing loss, and a progressive speech disorder. Remarkably, he showed a significant response to high-dose riboflavin supplementation. Subsequent genetic testing confirmed the diagnosis. Whole exome sequencing identified a homozygous missense variant, [c.239G>A; (p.Gly80Asp)], in the SLC52A3, consistent with BVVL 1. It is essential to remember that BVVL is a set of sensorineural hearing loss and a variety of cranial nerve palsies.
PtosisSLC5A7Verified36840359Background: Congenital myasthenic syndromes (CMSs) are characterized by hypotonia, episodic apnea, muscle weakness, ptosis and generalized fatigability. CMS type 20 (CMS20) is a rare disorder caused by variants in SLC5A7. In contrast to most other CMSs, CMS20 is also associated with neurodevelopmental disorders (NDDs).
PtosisSMARCA2Verified35762114Surgical correction of ptosis may be indicated for NCBRS patients. This report may help further delineate the phenotype of this condition, which may allow for more rapid identification of those affected and provide incentive for additional studies.
PtosisSMC1AVerified34729759, 37519569The child has exhibited developmental delay, microcephaly, ptosis, micrognathia, and low ear setting, and was suspected as CdLS. ... a hemizygous C.3500T>C (p.ile1167thr) of the SMC1A gene was predicted to underlay the clinical manifestations of the patient.
PtosisSMC3Verified37519569Clinical findings typically include dysmorphic facial features (arched eyebrows, synophrys, long eyelashes, ptosis, long philtrum, thin upper lip, and posteriorly rotated ears)... The syndrome is caused by mutations in genes (NIPBL, RAD21, SMC3, HDAC8, and SMC1A) involved in the cohesin complex...
PtosisSNAP25Verified40868854The context mentions that preclinical studies have demonstrated that PBM can upregulate neurotrophic factors (e.g., BDNF, NGF), enhance SNAP-25 expression, and promote structural remodeling of neurons in both young and aged brains. This indicates that SNAP25 is associated with the processes discussed, which are relevant to the recovery from BoNT/A-induced effects, including complications like ptosis.
PtosisSPECC1LVerified32807111, 26111080PMID 32807111: 'ocular alterations such as ptosis... in patients with Dup22q11.2, optic nerve coloboma and dysplasia in optic nerve... it is proposed that deregulation of the SPECC1L gene could be implicated in the development of ocular coloboma.' PMID 26111080: 'missense mutations in SPECC1L... associated with oblique facial clefting and Opitz G/BBB syndrome... ptosis...'
PtosisSPRVerified40243727Two consanguineous North African and Middle Eastern families are reported with multiple affected individuals presenting with developmental delay, ataxia, hypotonia, fatigue, and ptosis, or parkinsonism and cognitive impairment. Exome sequencing revealed a novel homozygous SPR c.560A>G (p.Glu187Gly) mutation that segregates with disease.
PtosisSTAC3Verified36030003, 37626540The Bailey-Bloch congenital myopathy, also known as Native American myopathy (NAM), is an autosomal recessive congenital myopathy ... characterized by congenital weakness and arthrogryposis, cleft palate, ptosis, short stature, kyphoscoliosis, talipes deformities, and susceptibility to malignant hyperthermia (MH) triggered by anesthesia. NAM is linked to STAC3 gene ... Here, we present seven patients from the Comoros Islands ... diagnosed with STAC3 related congenital myopathy and having the recurrent variant identified in the Lumbee people. ... these are the first descriptions of CMYP13 in Brazil. In both patients, we found the previously described pathogenic missense variant p.Trp284Ser in homozygosity.
PtosisSURF1Verified33042241Direct quote(s) from the context that validates the gene. The abstract mentions that the child presented with ptosis as part of her extraneurological manifestations, and the muscle biopsy revealed evidence of mitochondrial respiratory chain defect involving complex IV and SURF1 mutation.
PtosisTHVerified37011980, 34435630The initial symptom of the very severe patient was motor delay. Clinical symptoms of the very severe patient included ... ptosis (2 cases)...
PtosisSZT2Verified33681650hypotonia and distinctive facial dysmorphism, including a high forehead and to a lesser extent ptosis and down-slanting palpebral fissures, were present in the majority.
PtosisTAMM41Verified35321494We report three unrelated individuals with mitochondrial disease that share clinical features, including... ptosis. Whole exome and genome sequencing identified compound heterozygous variants in TAMM41 in each proband.
PtosisTBK1Verified38152653The genetic analyses revealed two heterozygous variants, in the SOD1 (OMIM*147450) and the TBK1 (OMIM*604834) genes respectively, and furthermore mitochondrial DNA (mtDNA) sequencing identified the homoplasmic m.14484T>C variant usually associated with Leber's Hereditary Optic Neuropathy (LHON). We discuss how all these variants may synergically impinge on mitochondrial function, possibly contributing to the pathogenic mechanisms which might ultimately lead to the neurodegenerative process, shaping the clinical ALS phenotype enriched by adjunctive clinical features.
PtosisTENM3Verified35397152The patient exhibited long philtrum, large ears, bilateral ptosis, and nystagmus. Ophthalmic tests showed that he had microcornea, iris and choroidal coloboma. The patient presented with global developmental delay (GDD).
PtosisTFAP2BVerified20301285Typical facial features are depressed nasal bridge and broad flat nasal tip, widely spaced eyes, downslanted palpebral fissures, mild ptosis, short philtrum with prominent philtral ridges with an upward pointing vermilion border resulting in a triangular mouth, and thickened (patulous) everted lips. The diagnosis of Char syndrome is established in a proband with suggestive clinical findings and/or a heterozygous pathogenic variant in TFAP2B identified by molecular genetic testing.
PtosisTGFB2Verified38585811genes that fit the syndromic component of the phenotype but had no prior oCCDD association (e.g., CDK13, TGFB2 )
PtosisTGIF1Verified35140749, 15912188The proband was an 8-year-old boy presenting a typical solitary median maxillary central incisor with a range of other phenotypic anomalies, including ptosis. SNP array revealed a 14.3 Mbp heterozygous deletion at chromosome 18p11.32-p11.21 in the proband but not in the unaffected parents. WGS further confirmed the identified deletion. 194 genes were involved in the chromosome region. Among them, 12 genes had been shown to be associated with diseases, including TGIF1, a reported SMMCI gene.
PtosisTK2Verified34484922, 35094997, 35280287, 32161153, 38599303PMID 34484922: Thymidine Kinase 2 Deficiency-Induced Adult-Onset Ptosis and Proximal Weakness. PMID 35094997: Clinical presentation typically includes... limb myopathy with ptosis... in the late-onset form. PMID 38599303: A patient with adult-onset TK2d presented with ptosis... Treatment improved outcomes.
PtosisTMEM67Verified36580738The most common variants were in the CPLANE1, CEP290, and TMEM67 genes, and other causative genes were AHI1, ARMC9, CEP41, CSPP1, HYLS1, KATNIP, KIAA0586, KIF7, RPGRIP1L, including some previously unreported variants in these genes. Multi-systemic organ involvement was observed in nine (40%) patients, with the eye being the most common, including Leber's congenital amaurosis, ptosis, and optic nerve coloboma.
PtosisTOP3AVerified37013609The majority of patients have a consistent clinical phenotype characterised by bilateral ptosis, ophthalmoplegia, myopathy and axonal sensory-motor neuropathy.
PtosisTTNVerified32830177, 33642484, 39574984, 32536668, 40062097, 34433744In the case of atypical MG, measurement of anti-striated muscle antibody or muscle biopsy should be considered. ... positive for anti-titin antibody and anti-Kv1.4 antibody. ... diagnosed as sporadic late-onset nemaline myopathy (SLONM) with MG, and treated by tacrolimus. ... patient developed MG crisis following a 10-year history of intermittent double vision with ptosis, and a 7-year history of dropped head. ... positive for anti-MuSK, anti-Lrp4, and anti-titin antibodies. ... positive for anti-striated muscle (>1:2560) and anti-titin (>2.71) antibodies, suggesting irMG or a paraneoplastic syndrome, ... positive for anti-titin antibody and anti-Kv1.4 antibody. ... positive for anti-titin antibody titer 11.51 ... positive for anti-titin antibody titer 15.13 ...
PtosisTP63Verified33933124A new finding of eyelid ptosis or eyelash ptosis was demonstrated in 11 subjects (37%), mostly associated with TP63 or EDA1 genes variants.
PtosisTPM3Verified35688744Physical assessment revealed bilateral ptosis and facial paresis, with high arched palate and retrognathia; global hypotonia and diffuse axial weakness, including neck and upper and lower limb girdle and foot dorsiflexion weakness.
PtosisTRAF7Verified34513876, 37067385PMID 34513876: '...characterized by neurodevelopmental delay, ptosis, cardiac defects, limb anomalies, and dysmorphic features.'; PMID 37067385: '...features of individuals harboring these variants are characterized by neurodevelopmental delay, ptosis, cardiac defects, limb anomalies, and dysmorphic features.' Both abstracts directly mention ptosis as a phenotype associated with TRAF7 variants.
PtosisTUBB2BVerifiedTUBB2B mutations cause autosomal dominant congenital fibrosis of the eyelid (MIM 136600) and autosomal dominant congenital ptosis with microphthalmia (MIM 117210).
PtosisTUBB3Verified31302631, 34652576, 35765833, 32573066, 40073207, 36494820, 33251926, 34435630All abstracts mention TUBB3 mutations in the context of ptosis. For example, PMID 31302631 states the father had bilateral ptosis and the children had right eye elevation deficiency. PMID 34652576 describes individuals presenting at birth with ptosis. PMID 32573066 reports a patient with severe bilateral palpebral ptosis. PMID 36494820 notes TUBB3 variants in patients with CFEOM, which includes ptosis. These studies directly link TUBB3 to ptosis phenotypes.
PtosisTUBB6Verified35140749, 29016863A TUBB6 mutation is associated with autosomal dominant non-progressive congenital facial palsy, bilateral ptosis and velopharyngeal dysfunction. ... the phenotype characterized by congenital non-progressive bilateral facial palsy and congenital velopharyngeal dysfunction presenting with varying degrees of hypomimia, rhinophonia, impaired gag reflex and bilateral ptosis.
PtosisTWIST1Verified35944701, 39994540Heterozygous loss of function mutations in TWIST1 cause Saethre-Chotzen syndrome, which is characterized by craniosynostosis, facial asymmetry, ptosis, strabismus, and distinctive ear appearance. ... Conditional inactivation of Twist1 using these drivers leads to disorganized extraocular muscles that cannot be reliably identified as specific muscles. ... Strabismus in individuals with TWIST1 mutations may therefore be caused by abnormalities in extraocular muscle development and secondary abnormalities in innervation and tendon formation.
PtosisTWNKVerified35011763, 37316776, 35792653, 32161153, 39409059PMID: 35011763: 'Ptosis and PEO (92% and 80%) were the most common findings.'; PMID: 37316776: 'Chronic progressive bilateral ptosis and ophthalmoplegia... diagnosed with CPEO caused by a novel mutation in PEO/TWNK'; PMID: 35792653: 'Parkinsonian features... in patients harboring variants in... TWNK'; PMID: 32161153: 'TWNK (n=8)... associated with progressive external ophthalmoplegia and ptosis'; PMID: 39409059: 'TWNK gene... associated with progressive external ophthalmoplegia and ptosis. The studies directly link TWNK mutations to ptosis in PEO/PEO-plus syndromes, confirming its role.
PtosisTYMPVerified36072350, 32849836, 33825174, 32914088, 33533561, 36192783, 34170051Ptosis is a key feature of MNGIE, and the disease is caused by mutations in the TYMP gene. For example, the abstract from PMID: 36072350 states, 'Key features of the disease include ... ptosis, ...' and 'MNGIE is caused by mutations in the gene-encoding thymidine phosphorylase (TP; previously known as endothelial cell growth factor 1).'
PtosisU2AF2Verified34112922The patient showed global developmental delay, intellectual disability, epilepsy, short stature, microcephaly, facial dysmorphism, intermittent exotropia, bilateral ptosis, muscle hypotonia and thin corpus callosum, indicating that U2AF2-related disorder could include systemic dysmorphisms, epilepsy and brain malformation along with global developmental delay.
PtosisUBE3BVerified32949109, 38410982, 34012380, 23200864PMID: 32949109: 'Patients presented with the characteristic features of the syndrome including blepharophimosis, ptosis, upslanted palpebral fissures with epicanthic folds...'. PMID: 38410982: 'Blepharophimosis, telecanthus, ptosis, intellectual disability and abnormal lipid profile were similar to those found in previously reported KOS patients.' PMID: 34012380: 'distinctive facial features... including blepharophimosis, ptosis, telecanthus...'. All three PMIDs directly associate UBE3B mutations with ptosis as part of the clinical phenotype.
PtosisUBR7Verified33340455In seven individuals with intellectual disability, epilepsy, ptosis, hypothyroidism, and genital anomalies, we uncovered bi-allelic variants in UBR7. Their phenotype differs significantly from that of Johanson-Blizzard syndrome (JBS)...
PtosisVAMP1Verified38531369, 33631708Patient 1 had fatigable ptosis... confirmed the presence of a homozygous loss of function VAMP1 mutations in all three patients... (PMID: 33631708). The 8-year-old boy with... ptosis... genetic analysis revealed a homozygous missense variant in the VAMP1 gene (PMID: 38531369).
PtosisWT1Verified37578539, 32446308The commonest genes affected in congenital nephrotic syndrome (NPHS1, NPHS2, WT1, LAMB2, PAX2 but not PLCE1) may have ocular manifestations. ... Common ocular associations of genetic FSGS include cataract, myopia, strabismus, ptosis and retinal atrophy.
PtosisZBTB20Verified32071410, 39129839Facial features were similar with macrocephaly, prominent forehead, downslanting palpebral fissures, ptosis, and large ears. (PMID: 32071410) and 'recognizable facial phenotype including deep set eyes, ptosis, narrow and frequently downslanting palpebral fissures, and depressed nasal bridge.' (PMID: 39129839)
PtosisZC4H2Verified37519288, 35121145Common eye manifestations of the syndrome reported in the literature include ptosis, strabismus, and oculomotor apraxia. The overall incidence of these manifestations is 56%.
PtosisZFHX4Verified34461323, 32962661, 34969027PMID 34461323 describes a patient with a ZFHX4 mutation presenting with ptosis. PMID 32962661 reports a missense alteration in ZFHX4 in a child with congenital ptosis. PMID 34969027 directly links ZFHX4 to simple congenital ptosis.
PtosisZIC1Verified23679990The clinical phenotype of the three 3q deleted patients included multiple congenital anomalies and peculiar facial appearance, related to the localization and extension of each deletion. In particular, phenotypes resulted from the variable combination of three recognizable patterns: DWM (with incomplete penetrance); blepharophimosis, ptosis, and epicanthus inversus syndrome; and Wisconsin syndrome (WS), recently mapped to 3q.
PtosisZMIZ1Verified39658964, 31833199The most common ophthalmic finding was ptosis (35%). Refractive error was common (myopia in 20%, hyperopia in 12%). Other findings included strabismus (12%) and amblyopia (16%).
PtosisZNF407Verified24907849Direct quote(s) from the context that validates the gene. 'dysmorphic features including bilateral ptosis and epicanthic folds, synophrys, midface hypoplasia, downturned mouth corners, thin upper vermillion border and prominent ears, bilateral 5th finger camptodactyly, bilateral short 4th metatarsal bones, and limited knee mobility bilaterally.' The gene ZNF407 is associated with a syndrome that includes ptosis as one of the dysmorphic features.
PtosisZNF462Verified39287049, 35198003, 32543299, 33975400, 35182807, 40105472Weiss-Kruszka syndrome (WKS) is a rare genetic disorder characterized by metopic ridging, ptosis, arched eyebrows, down slanting palpebral fissures, abnormalities in the corpus callosum, cardiac malformations, and variable neurodevelopmental delay... Our study reviewed nine patients from seven unrelated families and identified seven novel heterozygous ZNF462 variants through exome sequencing. (PMID: 39287049); This study aims to explore the clinical characteristics and genetic basis of a patient with unilateral ptosis... identified a heterozygous nonsense variant c.6431C > A (p.Ser2144*) in the ZNF462 gene... (PMID: 35198003); We presented a case of an infant... bilateral palpebral ptosis... identification of a novel mutation c.3306dup; p.(Gln1103Thrfs*10) in ZNF462. (PMID: 32543299); Weiss-Kruszka syndrome (WSKA)... characteristic craniofacial features, ptosis... identified a novel de novo heterozygous nonsense variant, c.4185del; p.(Met1396Ter) in ZNF462. (PMID: 33975400); Weiss-Kruszka syndrome is... craniofacial features, ptosis... Here we report the first case of Weiss-Kruszka syndrome... associated to a de novo 9q31.1q31.3 microdeletion showing an acute lymphoblastic leukemia. (PMID: 35182807); Clinical and Molecular Landscape of Weiss-Kruszka Syndrome... heavily arched eyebrows, mild bilateral ptosis... identified a de novo splicing variant, c.6833-2A > T, in the ZNF462 gene. (PMID: 40105472)
Abnormality of the pulmonary veinsLamin A/CExtractedUnknown32144494Pulmonary vein isolation treats symptomatic AF in a patient with Lamin A/C mutation
Abnormality of the pulmonary veinsTG2ExtractedUnknown32116663Role of TG2-Mediated SERCA2 Serotonylation on Hypoxic Pulmonary Vein Remodeling
Abnormality of the pulmonary veinsSERCA2ExtractedUnknown32116663Role of TG2-Mediated SERCA2 Serotonylation on Hypoxic Pulmonary Vein Remodeling
Abnormality of the pulmonary veinsFOXF1BothUnknown34325731, 31662342, 33832123, 39497128, 34315444, 32987465, 36969329, 39393900, 32386508, 36980834Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a fatal congenital lung disorder strongly associated with genomic alterations in the Forkhead box F1 (FOXF1) gene and its regulatory region. [...] the misalignment of pulmonary veins adjacent to the pulmonary arterioles, which were consistent with ACDMPV. [...] the alteration in the FOXF1 gene, led us to conclude the definitive diagnosis of alveolar capillary dysplasia.
Abnormality of the pulmonary veinsEIF2AK4BothUnknown32461209, 38232988, 39502262, 36400028PVOD may also be associated with a mutation in the EIF2AK4 gene in heritable forms of disease. ... Mutations in the eukaryotic translation initiation factor 2 alpha kinase 4 (EIF2AK4) gene have been linked to the development of PVOD, with the worst prognosis seen in homozygous mutation carriers. ... Hereditary PVOD is caused by biallelic variants of the EIF2AK4 gene. ... The discovery of biallelic mutations in the eukaryotic translation initiation factor 2 alpha kinase 4 (EIF2AK4) gene in heritable PCH and PVOD greatly advanced our understanding of the overlapping nature of these conditions.
Abnormality of the pulmonary veinsCCDC40BothUnknown35518361Of the 72 fetuses that underwent CNV-seq and WES, 11 (15.3%) had positive genetic results, eight had definitive pathogenic variants, and three had likely pathogenic variants. The diagnostic genetic variant rate identified using WES was 11.1% (8/72), in which primary ciliary dyskinesia (PCD)-associated gene mutations (CCDC40, CCDC114, DNAH5, DNAH11, and ARMC4) accounted for the vast majority (n = 5). Other diagnostic genetic variants, such as KMT2D and FOXC1, have been rarely reported in heterotaxy cases, although they have been verified to play roles in congenital heart disease. ... Consistent with the results of a previous study, intracardiac anomalies were more severe in patients with right atrial isomerism than in those with left atrial isomerism (LAI) and mainly manifested as atrial situs inversus, bilateral right atrial appendages, abnormal pulmonary venous connection, single ventricles or single atria, and pulmonary stenosis or atresia.
Abnormality of the pulmonary veinsCCDC114ExtractedUnknown35518361PCD-associated gene mutations (CCDC40, CCDC114, DNAH5, DNAH11, and ARMC4) accounted for the vast majority (n = 5)
Abnormality of the pulmonary veinsDNAH5BothUnknown35518361Of the 72 fetuses that underwent CNV-seq and WES, 11 (15.3%) had positive genetic results, eight had definitive pathogenic variants, and three had likely pathogenic variants. The diagnostic genetic variant rate identified using WES was 11.1% (8/72), in which primary ciliary dyskinesia (PCD)-associated gene mutations (CCDC40, CCDC114, DNAH5, DNAH11, and ARMC4) accounted for the vast majority (n = 5). Other diagnostic genetic variants, such as KMT2D and FOXC1, have been rarely reported in heterotaxy cases, although they have been verified to play roles in congenital heart disease. Consistent with the results of a previous study, intracardiac anomalies were more severe in patients with right atrial isomerism than in those with left atrial isomerism (LAI) and mainly manifested as atrial situs inversus, bilateral right atrial appendages, abnormal pulmonary venous connection, single ventricles or single atria, and pulmonary stenosis or atresia.
Abnormality of the pulmonary veinsDNAH11BothUnknown35518361In 18 fetuses diagnosed with LAI, the main intracardiac anomalies were bilateral left atrial appendages. Of the 72 fetuses that underwent CNV-seq and WES, 11 (15.3%) had positive genetic results, eight had definitive pathogenic variants, and three had likely pathogenic variants. The diagnostic genetic variant rate identified using WES was 11.1% (8/72), in which primary ciliary dyskinesia (PCD)-associated gene mutations (CCDC40, CCDC114, DNAH5, DNAH11, and ARMC4) accounted for the vast majority (n = 5). Other diagnostic genetic variants, such as KMT2D and FOXC1, have been rarely reported in heterotaxy cases, although they have been verified to play roles in congenital heart disease.
Abnormality of the pulmonary veinsARMC4ExtractedUnknown35518361PCD-associated gene mutations (CCDC40, CCDC114, DNAH5, DNAH11, and ARMC4) accounted for the vast majority (n = 5)
Abnormality of the pulmonary veinsKMT2DExtractedUnknown35518361Other diagnostic genetic variants, such as KMT2D and FOXC1, have been rarely reported in heterotaxy cases
Abnormality of the pulmonary veinsFOXC1ExtractedUnknown35518361Other diagnostic genetic variants, such as KMT2D and FOXC1, have been rarely reported in heterotaxy cases
Abnormality of the pulmonary veinsPIK3CAExtractedUnknown35626846Pulmonary Vein Stenosis Associated with Germline PIK3CA Mutation
Abnormality of the pulmonary veinsJAG1ExtractedUnknown36157644Alagille syndrome associated with total anomalous pulmonary venous connection and severe xanthomas: A case report
Abnormality of the pulmonary veinsTBX4ExtractedUnknown40008593Primary Pulmonary Hypoplasia With Congenital Alveolar Dysplasia Associated With TBX4 Gene Deletion
Abnormality of the pulmonary veinsMESP2Verified22711292We propose overexpression of three genes, ADAMTSL3, MESP1, and MESP2 as a potential mechanism for cardiac and vessel malformations associated with tetrasomy 15q. Finally, we believe cardiac defects with this genetic syndrome are a poor prognostic finding associated with high mortality.
Abnormality of the pulmonary veinsMYRFVerified40819034MYRF gene mutations can lead to the development of Cardio-Urogenital Syndrome (CUGS), characterized by congenital heart disease, abnormalities in the internal and external reproductive organs, and ocular anomalies. CUGS can manifest with various types of congenital heart diseases, such as ... Pulmonary Vein Anomalies et al.
Abnormality of the pulmonary veinsTBX5Verified35514310The present findings extended the phenotypic cardiac defects associated with HOS; to the best of our knowledge, this is the first association of mixed-type TAPVR with TBX5. Prior to the current analysis, the molecular association of TAPVR with HOS had never been documented; hence, this is the first genetic investigation to report the association between TAPVR and HOS.
HepatitisAPOBEC/AIDExtractedMol Ther Nucleic Acids37187708CRISPRa regulation of APOBEC/AID genes for targeting hepatitis B virus.
HepatitisHBxExtractedHepatol Int32770306HBV X gene (HBx) mutants emerged during antiviral therapy and increase cccDNA levels.
HepatitisRAD51AP1ExtractedHeliyon39850418RAD51AP1 was identified as a specific key gene linked to the progression of HBV-associated HCC.
HepatitisCCND1ExtractedBiochem Biophys Rep40697521CCND1 gene mRNA levels and promoter methylation were measured in patients with CHB-related LF/LC.
HepatitisESR2ExtractedBiochem Genet38245888ESR2 gene polymorphisms rs3020449 and rs2978381 were associated with CHB, LC, and HCC susceptibility.
HepatitisESR1ExtractedStem Cell Res Ther37775797Polymorphisms in ESR1 gene are related to HCC susceptibility among people carrying chronic hepatitis B.
HepatitisCD73ExtractedStem Cell Res Ther37775797CD73 mediates the therapeutic effects of endometrial regenerative cells in Con A-induced hepatitis.
HepatitisRRM2ExtractedCells35883690R2 (RRM2) gene expression is critical for HBV replication via ERE-R2-box interaction.
HepatitisBIRC5ExtractedBiochem Biophys Rep40697521Higher expression of BIRC5 was associated with worse survival in breast cancer patients.
HepatitisCASP3ExtractedBiochem Biophys Rep40697521Higher expression of CASP3 was associated with worse survival in breast cancer patients.
HepatitisCCNA2ExtractedBiochem Biophys Rep40697521Higher expression of CCNA2 was associated with worse survival in breast cancer patients.
HepatitisCCNE1ExtractedBiochem Biophys Rep40697521Higher expression of CCNE1 was associated with worse survival in breast cancer patients.
HepatitisCXCL8ExtractedBiochem Biophys Rep40697521Higher expression of CXCL8 was associated with worse survival in breast cancer patients.
HepatitisCYCSExtractedBiochem Biophys Rep40697521Higher expression of CYCS was associated with worse survival in breast cancer patients.
HepatitisAIREVerified34217342, 36974230In the first study, several less common phenotypes, such as autoimmune hepatitis, were observed in patients. Additionally, different AIRE mutations that were observed have expanded the genetic spectrum, which will help with future understanding of the molecular pathogenesis of APS1. In the second study, the patient was diagnosed with APS1 and had positive autoantibodies, and genetic testing detected a novel pathogenic homozygous AIRE mutation. The patient presented with autoimmune hepatitis as one of the clinical manifestations.
HepatitisAKR1D1Verified35774985The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the differentially expressed genes (DEGs), such as ... aldo-keto reductase family 1 member D1 (akr1d1)... indicated that ... hepatitis C... was one of the main metabolic pathways altered by SJ supplementation when compared with the HC group.
HepatitisAPCVerified32486480, 35961146, 31630500, 34540977, 40348604The PM of APC gene increases in chronic hepatitis C patients and can affect patients' response to antiviral therapy. Additionally, alterations in the Wnt/APC/beta-catenin pathway could represent a shared pathogenic mechanism in Hepatocellular Carcinoma (HCC) and gastrointestinal malignancies, which are associated with Hepatitis.
HepatitisATP7AVerified34819411, 33129558The incidence of copper-associated hepatitis in Labrador retriever in Japan has not been examined. This study examined the genotype frequencies of ATP7B:c.4358G>A, a mutation responsible for copper-associated hepatitis, and ATP7A:c.980C>T, a modifier of this disease... Based on the genotyping results, the risk of copper-associated hepatitis in the study population was 0.80% in males and 1.05% in females. Variants in ATP7A and ATP7B modulate hepatic copper levels in Labrador retrievers and Dobermans.
HepatitisATP7BVerified34819411, 33590415, 37926771The incidence of copper-associated hepatitis in Labrador retriever in Japan has not been examined. This study examined the genotype frequencies of ATP7B:c.4358G>A, a mutation responsible for copper-associated hepatitis... The gene frequency was 0.107 for ATP7B:c.4358A. ... the risk of copper-associated hepatitis in the study population was 0.80% in males and 1.05% in females. Wilson's disease (WD) is a rare genetic disorder inherited as an autosomal recessive trait. The signs and symptoms of this disease are related to dysfunctional ATP7B protein which leads to copper accumulation and cellular damage. The organs that are most commonly affected by WD are the liver and brain. ... All 11 dogs with CuCh that underwent genetic testing were homozygous negative for the COMMD1 deletion and ATP7A variant but homozygous positive (n = 7) or heterozygous (n = 4) for the ATP7B variant.
HepatitisAXIN1Verified40344393, 35166233, 32294900, 40423574The study in PMID 40344393 found mutations in AXIN1 among Mongolian HCC patients, with CCND1 expression significantly upregulated in tumors with CTNNB1 and AXIN1 mutations. Hepatitis virus infections were significantly associated with these mutations. Additionally, PMID 35166233 highlights that loss-of-function mutations of AXIN1 occur in approximately 35% of human HCC samples, linking it to deregulated Wnt/beta-catenin signaling, a key pathway in HCC development often associated with hepatitis.
HepatitisBLNKVerified37593735the expression levels of some classical molecules associated with distinct signaling pathways-including HLA-B, HLA-DRB5, BLNK, BLK, IL4R, SCIMP, JUN, CEBPB, NDFIP1, and TXNIP-were significantly reduced in corresponding subsets of PBMCs from the NR group relative to those of the HR group.
HepatitisBTKVerified38899330, 40815495, 37150651, 35283317, 37528444, 39006388The abstracts discuss the association between Bruton tyrosine kinase (BTK) inhibitors and hepatitis B virus (HBV) reactivation, which is a form of hepatitis. For example, PMID 38899330 states that BTK inhibitors are linked to HBV reactivation in patients with hematologic malignancies. Similarly, PMID 40815495 and 37150651 describe cases where BTK inhibitor use led to HBV reactivation, resulting in hepatitis. These studies directly connect BTK inhibitors to hepatitis through HBV reactivation.
HepatitisC1SVerified38061333, 35964089In the MR analysis, genetically predicted levels of complement C1q C chain (C1QC) were positively associated with the risk of autoimmune hepatitis (odds ratio 1.125, 95% confidence interval 1.018-1.244)... Additionally, C1S (0.111, 0.018-0.672) were significantly associated with the risk of hepatocellular carcinoma. Proteins from the complement regulatory networks and various liver disease-related proteins share common biological processes.
HepatitisC4BVerified32557728Components of the classical and lectin pathways, including complement factors C2, C4b, and C4d, as well as complement factor I (CFI) and C5, were reduced in AH patients compared to healthy persons.
HepatitisCASP8Verified32050950, 40672613, 35746675, 36518852In the study on Yinchenhao decoction, CASP8 was identified as a target involved in the treatment of hepatitis C, with the decoction potentially influencing pathways like the TNF signaling pathway. Additionally, in the context of hepatitis B, CASP8 expression was found to be negatively associated with viral DNA load. These findings suggest a role for CASP8 in hepatitis-related processes.
HepatitisCD3EVerified40143948, 35593496, 34218795In the study (PMID: 34218795), CD3E was identified as one of the hub genes associated with immune infiltration in hepatocellular carcinoma (HCC), which is often caused by chronic liver infections such as hepatitis. The expression levels of CD3E were decreased in cancer tissues and correlated with CD8+ T cell infiltration. Additionally, in PMID: 35593496, CD3+ T cells were found to be involved in hepatocyte damage in swine infected with hepatitis E virus (HEV), a zoonotic agent related to hepatitis. These findings support the association of CD3E with hepatitis-related immune responses.
HepatitisCD40LGVerified34440067, 34988689, 37305442, 36738524, 34551597CD40-CD40L is a key receptor-ligand signaling pair involved in the adaptive immune response and pathogenesis of autoimmune diseases...TNFR1-/- mice showed much less intra-parenchymal infiltrates, hepatocellular necrosis, and perivascular clusters upon CD40 mAb activation than their wild type littermates. ...blocking CD40-CD40L signaling, but not ICOS-ICOSL signaling, specifically inhibits B-cell activation and IgG production. ...IL-15-producing splenic B cells...IFNgamma and CD40L/CD40 signaling were indispensable for the expression of IL-15 in B cells...HBV may impair TFH cell function by enhancing inhibitory regulatory T-cell activity. ...the NLRP3 inflammasome...regulating downstream CD40-CD40L signaling.
HepatitisCIITAVerified38741238, 32103629Both abstracts support the association of CIITA with hepatitis. PMID 38741238 shows CIITA inhibits HBV replication in hepatocytes and HCC cells, reducing HBV DNA and antigen levels. PMID 32103629 identifies CIITA genetic variants linked to chronic HBV infection risk in Han Chinese population.
HepatitisCLEC7AVerified33312564, 31606552, 34896749Candidalysin enhances ethanol-induced liver disease independently of the beta-glucan receptor C-type lectin domain family 7 member A (CLEC7A) on bone marrow-derived cells... Candidalysin is associated with liver disease severity and mortality in patients with alcoholic hepatitis.
HepatitisCOG8Verified33960418, 28619360The patient showed elevated serum liver enzymes and interface hepatitis with mild lobular activity. The parents were heterozygous carriers of each variant.
HepatitisCTNNB1Verified40344393, 37158967, 40725188, 34319157, 35509137, 33918222, 31505100beta-catenin accumulation was observed in tumors with CTNNB1 mutations (D32N/Y, S33C/Y, S34V, S37P, T41A, and S45P). ... Hepatitis virus infections were significantly associated with these mutations (p < 0.01), suggesting a link between viral infection and genetic alterations in HCC development. ... Targeting ER stress/PKA/GSK-3beta/beta-catenin pathway as a potential novel strategy for hepatitis C virus-infected patients. ... Wnt/beta-catenin signaling Regulates Hepatitis B Virus cccDNA Levels. ... beta-Catenin Signaling Regulates the In Vivo Distribution of Hepatitis B Virus Biosynthesis across the Liver Lobule. ... Selective effect of beta-catenin on nuclear receptor-dependent hepatitis B virus transcription and replication. ... Additional Inhibition of Wnt/beta-catenin Signaling by Metformin in DAA Treatments as a Novel Therapeutic Strategy for HCV-Infected Patients. ... Deficiency of canonical Wnt/beta-catenin signalling in hepatic dendritic cells triggers autoimmune hepatitis.
HepatitisCYP7A1Verified33657087, 36699093, 36950015, 34198609In the context of cholestatic hepatitis, CYP7A1 is mentioned as a key target of quercetin, an active component of Hypericum japonicum, indicating its involvement in the disease process. Additionally, quercetin 7-rhamnoside (Q7R) was shown to decrease CYP7A1 levels, further linking it to cholestatic hepatitis. Polygoni Multiflori Radix (PM) was found to upregulate CYP7A1, contributing to cholestasis. These findings collectively support the association of CYP7A1 with hepatitis.
HepatitisCYP7B1Verified39952566, 38418983, 37620226The study shows that liver specific CYP7B1 overexpression attenuates early Western diet-induced MASLD progression, indicating its role in preventing liver toxicity and hepatotoxicity associated with MASLD, which is a form of hepatitis. The data suggests that maintaining normal mitochondrial cholesterol metabolism with hepatic CYP7B1 expression prevents oxysterol-driven liver toxicity, thus attenuating MASLD progression.
HepatitisFASVerified36969885, 32890764, 35129072, 32482709The expression of CD8, Fas, FasL, and Caspase-8 expression as well as apoptotic markers was enhanced in the Epstein-Barr virus hepatitis group relative to the controls (p<0.05).
HepatitisFASLGVerified33506011, 36620830, 36969885, 32209020, 33824856Fas/FasL and complement activation are associated with Chronic Active Epstein-Barr Virus Hepatitis. ... The expression of CD8, Fas, FasL, and Caspase-8 expression as well as apoptotic markers was enhanced in the Epstein-Barr virus hepatitis group relative to the controls (p<0.05).
HepatitisFOXP3Verified39117877, 36857742, 34820942, 32743104, 35580072, 36635631, 37875903, 38173532The IL28B rs12979860 T > C and FOXP3 rs2232365 A > G polymorphisms significantly affect DAA treatment response in HCV Egyptian patients. Lower levels of IL-28B along with higher levels of FOXP3 are linked to poor response. (PMID: 39117877); Polymorphisms in the FOXP3 gene are associated with the presence of antinuclear antibodies in chronic hepatitis C. (PMID: 32743104); FOXP3 was found to be significantly upregulated in CHB with HBeAg(+) compared to spontaneously cleared HBV infection. (PMID: 35580072); CTLA4+CD4+CXCR5-FOXP3+ T cells associate with unfavorable outcome in patients with chronic HBV infection. (PMID: 36635631); IL-21 modulates balance between regulatory T cells and T-helper 17 cells in chronic hepatitis B virus infection through FOXP3. (PMID: 37875903)
HepatitisGNASVerified35052777, 38756592In the study (PMID: 38756592), GNAS was identified as a pivotal target within the PPI network of YGJ-CH. YGJ attenuated liver inflammation and inhibited GNAS/STAT3 signaling in vivo. Overexpression of GNAS was further verified to highlight its critical role in YGJ treatment for chronic hepatitis.
HepatitisGPR35Verified38407233In the context of liver ischemia-reperfusion injury (IRI), the study demonstrates that CXCL17, upregulated by YAP/TEAD1 signaling, recruits MDSCs via binding with GPR35 during liver IRI. This indicates a direct association between GPR35 and the pathological process of liver IRI, which can lead to acute liver dysfunction and hepatitis.
HepatitisGUSBVerified40272894We successfully employed Ox-GUS to visualize GUS activity in real-time in mouse models of ... autoimmune hepatitis, and inflammatory bowel disease...
HepatitisHBBVerified35420168By short time-series expression miner and functional analysis, aquaporin 1 (AQP1), dystroglycan 1 (DAG1), and hemoglobin subunit beta (HBB) were identified as potential biomarkers. Immunohistochemical analysis revealed that the expression levels of AQP1, DAG1, and HBB were upregulated in the three groups.
HepatitisIFIH1Verified38102741, 36743960Our research shows that DHX58 rs2074158-G allele [...] and IFIH1 rs10930046-C allele (additive model: adjusted OR = 1.26, 95% CI [1.07-1.49], P = 0.005) were associated with chronic hepatitis C (CHC). [...] IFIH1 rs10930046, DHX58 rs2074158, age, ALT, and AST levels were all independent predictors of CHC.
HepatitisIGHG2Verified38561745Glycomic analysis indicated an elevated level of fucosylated N-glycans, especially a progressive increase in fucosylation levels on IgA1 and IgG2 determined by glycoproteomic analysis.
HepatitisIGKCVerified33585012, 40570050PMID 33585012 reports that IGKC is upregulated in advanced cirrhosis patients with HCV compared to controls. This indicates a potential role of IGKC in the pathogenesis of HCV-related liver disease.
HepatitisIL12AVerified32554051, 32723283, 37565510, 36656054, 37195820A allele, AA and AG genotypes of IL-12A rs568408 were more represented in the chronic HBV infection group compared to the control group, and they were associated with 1.65-, 2.58- and 3.13-fold risks of developing this infection, respectively. Gene-gene interaction analysis showed that subjects carrying the IL-12A rs568408AA/AG and IL-12B rs3212227AA genotypes had a 3.16-fold increased risk of chronic HBV infection. This study suggested that IL-12A rs568408 and gene-gene interactions of IL-12A rs568408 and IL-12B rs3212227 contributed to the outcome of chronic HBV infection, meanwhile indicating their usefulness as a predictive and diagnostic biomarker of chronic HBV infection. Additionally, the IL-12A (G/A) and IL-12B (A/C) polymorphisms were found to be significant in chronic hepatitis C, with IL-12A GA and AA genotypes showing higher frequencies in patient groups. The IL-12A rs568408 AG/AA genotypes were independently associated with an increased risk to develop liver cirrhosis in male patients. The meta-analysis confirmed that IL-12A rs568408 was associated with an increased risk of HBV infection across different populations.
HepatitisIL17FVerified39873997, 34369380, 34190694, 33435354, 39200991The study identifies a significant association between IL-17F rs763780 polymorphisms and a higher risk of HCC in Egyptian patients with chronic hepatitis C. ... Our findings suggest that A allele and AA genotype at IL-17F rs763780 (A7488G) locus, might be associated with increased risk of C/HCC among patients with hepatitis B virus infection. ... IL-17A and IL-17F are critical cytokines involved in inflammatory processes.
HepatitisIL17RAVerified36172147, 38519059, 34130335, 33431762, 40686026, 34980743The role of IL-17RA is upregulated in patients with hepatitis B virus/hepatitis C virus (HBV/HCV) infections... (PMID: 34130335). Additionally, a case of autoimmune hepatitis (AIH) during treatment with brodalumab, an anti-IL-17RA antibody, was reported (PMID: 33431762, 34980743). Furthermore, IL-17RA methylation changes were observed in hepatitis B virus reactivation patients (PMID: 40686026).
HepatitisIL18BPVerified32285199, 34066709, 35665232, 40170380A patient with autosomal recessive complete IL-18BP deficiency was shown to have FVH following HAV infection. ... genetic variations in host factors such as ... IL-18 binding protein (IL-18BP) have been linked to hepatitis A severity. ... HBeAg-negative chronic hepatitis patients were characterized as having the highest interleukin 18 binding protein (IL-18BP) levels.
HepatitisIL21RVerified32351297, 37875903, 38508431, 38849082In PMID 37875903, IL-21R levels in PBMCs from CHB were higher than those from IT patients. IL-21 and IL-21R levels were linked to Th17 cell promotion and Treg inhibition, relevant to hepatitis. In PMID 38508431, BSF increased IL-21R expression on B-cells, affecting HBV. In PMID 38849082, blocking IL-21R restored ConA-induced ALI, showing its role in liver inflammation.
HepatitisIRF5Verified40898263, 34589288, 39893238, 39045132, 36016428In PMID 40898263, IRF5 was highlighted as a key HSG in both the colocalization and pan-cancer analyses. In PMID 34589288, administration of LNP-encapsulated siRNA against Irf5 reduced its expression in macrophages and ameliorated liver injury. In PMID 39045132, IFNalpha was regulated by IFNAR or IRF5 in E11-induced hepatitis. In PMID 36016428, 17beta-oestradiol elevated interferon regulatory factor 5, contributing to an antiviral state against HCV.
HepatitisITCHVerified36286484, 35044214, 36338154PMID 36286484: 'ITCH binds directly to the carboxy-terminal half of pX... CRISPR deletion or siRNA knockdown of ITCH... impaired the release of eHAV... overexpression of wild-type ITCH rescued release...'. PMID 35044214: 'HCV-induced ROS/JNK activation promoted Itch phosphorylation... siRNA knockdown of Itch reduced extracellular HCV infectivity... polyubiquitylation of VPS4A...'. Both studies show ITCH's role in hepatitis virus release.
HepatitisKRT18Verified33306505, 31811953, 33156105, 39023658, 33043565Keratin-18 (K18) is a promising biomarker for predicting histological severity of AH, defining the type of hepatocyte death (necrosis vs apoptosis), predicting 90-day mortality, and predicting the response to corticosteroid therapy in severe AH. The authors conclude that K18 is diagnostic, prognostic, and may be a theragnostic marker for prednisolone therapy. Serum level of keratin 18 and amount of hepatocyte death and liver disease severity than for other biomarkers (AST, ALT, and the AST:ALT ratio). Serum levels of K18 might be used to identify patients with severe AH at risk for death. Elevated serum CK-18 levels at admission were linked to a higher risk of death or liver transplantation during follow-up. M65 levels > 305 U/L, identified in the training cohort, facilitated the noninvasive detection of incomplete histological remission.
HepatitisMST1Verified40393543, 38697356, 34113355, 34129887, 37312627, 36478861The expressions of Nrf2 and MST1 were increased, and the levels of cleaved caspase-9 and interleukin (IL)-1beta were decreased after melatonin treatment. ... In the liver of CVB3-infected mice, the expression of Nrf2 and MST1 was increased. ... RASSF4 in the liver interacts with MST1 to inhibit YAP nuclear translocation through the Hippo pathway. ... In AH samples, RNA-seq analysis and immunohistochemistry of total liver and microdissected hepatocytes revealed marked downregulation of the Hippo pathway, demonstrated by lower levels of active MST1 kinase and abnormal activation of YAP in hepatocytes. ... Hepatic expression signatures in HBsAg-transgenic mice correlated with YAP responses, cell cycle control, DNA damage and spindle events. Suppression and inactivation of MST1/2 led to the loss of YAP phosphorylation and the induction of BMI1 expression in vivo and in vitro.
HepatitisPI4KAVerified39688508Phosphatidylinositol-4-kinase type III alpha (PI4KIIIalpha)... interacts with the hepatitis C virus non-structural 5 A protein (NS5A) to produce phosphoinositol-4-phosphate (PI4P)... Patients with hepatitis C virus infection in the liver have been associated with increased levels of PI4P at the endoplasmic reticulum. A crucial element of these replication organelles is PI4KIIIalpha.
HepatitisPIK3R1Verified35359864, 37504922, 36188529, 40956833PMID 35359864 states that PIK3R1 was selected as one of the top 5 closely related targets to celastrol in autoimmune hepatitis. Celastrol administration significantly ameliorated hepatitis by reducing PI3K phosphorylation, which is associated with PIK3R1.
HepatitisRFX5Verified35291486, 37008925In the first study (PMID: 35291486), RFX5 was identified as a possible regulator of IER3-related TF in the context of hepatocellular carcinoma (HCC). HCC is a severe outcome of chronic liver diseases, including hepatitis. The second study (PMID: 37008925) found that RFX5 is one of the potential transcription factors associated with the Turquoise module linked to immune response in non-alcoholic steatohepatitis (NASH), which is an advanced form of non-alcoholic fatty liver disease (NAFLD) and can progress to liver cirrhosis and HCC. Both studies associate RFX5 with liver-related diseases, supporting its role in hepatitis-related conditions.
HepatitisSEMA4DVerified33646067CD100 is an important immune semaphorin that is a secreted and membrane bound protein involved in infectious diseases. ... HBV-ACLF patients had lower plasma sCD100 and higher mCD100 level on CD14+ monocytes compared with asymptomatic HBV carriers, chronic hepatitis B patients, and controls. ... The current data indicated that severe inflammation induced sCD100/mCD100 imbalance to inactivate CD14+ monocytes response, which might be beneficial for the survival of HBV-ACLF patients.
HepatitisSERPINA1Verified38487736, 33116457, 33585096The study in PMID 38487736 discusses the confirmation of Alpha 1-Antitrypsin (A1AT) deficiency through genotyping, specifically mentioning the detection of S and Z alleles in liver transplant cases with PASD/A1AT-positive globules. Alpha-1 antitrypsin is encoded by the SERPINA1 gene, and the presence of these alleles is directly linked to the deficiency causing hepatic issues, including hepatitis. Additionally, PMID 33585096 presents a case of liver cirrhosis in a patient with the SERPINA1 ZZ phenotype, further associating the gene with liver disease progression, including hepatitis.
HepatitisSLC25A15Verified35928244, 39086438In the first study (PMID: 35928244), SLC25A15 (Slc25a15) was upregulated in response to acupuncture treatment in a liver damage model, indicating its involvement in mitochondrial function and liver health. In the second study (PMID: 39086438), mutations in SLC25A15 were directly linked to HHH syndrome, which manifests with hepatitis among other symptoms. The disruption of ORNT1 function due to SLC25A15 mutations leads to metabolic imbalances that cause liver failure and hepatitis.
HepatitisSTAT1Verified38231631, 33850522, 34199353, 40101098, 33137361, 35267462, 38308318The phosphorylation of STAT1 in HepG2.2.15 cells resistant to IFNalpha-2b was significantly decreased, and the expression level of 2',5'-oligoadenylate synthetase 1 was downregulated. Decreased phosphorylation of STAT1 in the JAK-STAT signaling pathway a contributor to the development of resistance to IFN-alpha in HBV. (PMID: 33850522); Kaempferol, Sesamin, and Quercetin decisively contributed to the cell growth and proliferation by affecting STAT1, interleukin-6, and CXCL10 proteins. (PMID: 40101098); gemcitabine activates STAT1 phosphorylation... which triggers activation of interferon-sensitive response element (ISRE) and transcription of interferon-stimulated genes (ISGs). (PMID: 33137361); STAT1 and STAT3 are expressed and activated in HCC and tumor infiltrating immune cells... suggesting increased immunological tolerance. (PMID: 35267462); Tet2 interacted with Stat1, inhibiting the expression of proinflammatory factors and suppressing liver regeneration. (PMID: 38308318)
HepatitisSYKVerified36568669, 32205992, 32512905, 33638929, 37229242, 34411785, 32251678, 36618328SYK is expressed in non-hematopoietic cells and effectively regulates various non-immune biological responses as well. In this review, we mainly summary the role of SYK in different liver diseases. Robust SYK expression has been discovered in hepatocytes, hepatic stellate cells, as well as Kupffer cells, which participates in the regulation of numerous signal transduction in various liver diseases (e.g. hepatitis, liver fibrosis and hepatocellular carcinoma).
HepatitisTCF3Verified31421377Previously, the following four epithelial-mesenchymal transition-related genes were considered to be significantly influential: E-cadherin (CDH1), inhibitor of DNA binding 2 (ID2), matrix metalloproteinase 9 (MMP9), and transcription factor 3 (TCF3). A prognostic prediction model, NRISK4 = (-0.333 x [CDH1] - 0.400 x [ID2] + 0.339 x [MMP9] + 0.387 x [TCF3]) was constructed, but from patients with HCC with predominantly hepatitis B virus infection. We therefore aim to validate if this model also fits patients with HCC and hepatitis C virus (HCV) infection.
HepatitisTCF4Verified32486480, 36076262, 38469563, 40931030The effect of p22 on TCF/beta-catenin transcription was dose dependent and inhibited by dominant-negative TCF4. HBV p22 activated synthetic and native Wnt target gene promoter reporters, and TCF/beta-catenin target gene expression in vivo. Importantly, HBV p22 activated Wnt signaling on its own and in addition to Wnt or beta-catenin induced Wnt signaling. Furthermore, HBV p22 elevated TCF/beta-catenin transcription above constitutive activation in colon cancer cells due to mutations in downstream genes of the Wnt pathway, namely APC and CTNNB1. Collectively, our data identifies a previously unappreciated role for the HBV pre-core protein p22 in elevating Wnt signaling. Understanding the molecular mechanisms of p22 activity will provide insight into how Wnt signaling is fine-tuned in cancer.
HepatitisTNFSF15Verified32674433On the other hand, we observed the activation of several T helper 1 (Th1)- and T helper 2 (Th2)-cytokines (IFN-gamma, IL-2, IL-8, IL-12p40, IL-15, TGF-beta4, TNF-SF-15 and t-BET), without being able to control the viral replication due to the high concentration of viral particles in some organs, principally in the gut. One possible role of these cytokines is contributing to the control of inflammation and cell protection of intestinal cells, principally during the early activation of immune responses. However, the fact that these responses are not mature enough to control the viral infection means that more studies need to be carried out to elucidate this topic.
HepatitisTP53Verified35070964, 38201266, 40344393, 37125127, 39601371, 35117817, 37304923, 36298868PMID 38201266: 'H2O2 upregulated p53 levels... E6AP, an E3 ligase, induced the ubiquitin-dependent proteasomal degradation of HCV Core in a p53-dependent manner.'; PMID 40344393: 'p53 overexpression in tumors with TP53 mutations... Hepatitis virus infections were significantly associated with these mutations.'; PMID 37125127: 'TP53 gene also interacts with different HCV proteins... TP53 mRNA was notably upregulated in HCV patients.'; PMID 39601371: 'USP14 upregulation downregulated MDM2 and promoted P53 deubiquitination to delay the invasion of hepatitis B virus and the development of hepatitis.'; PMID 35117817: 'TP53 249Ser mutation may be a high risk factor of HBV-related HCC recurrence.'; PMID 37304923: 'silencing of the p53 tumour suppressor gene... HCC formation... hepatitis viruses'; PMID 36298868: 'p53 downregulates HBx via E6AP-mediated proteasomal degradation in HBV replication.'
HepatitisTRAF3IP2Verified35490666Transcriptome analysis showed that the "TNF signaling pathway" and "IL-17 signaling pathway" had the highest enrichment of differentially expressed genes (DEGs). Then, TNF/IL-17/PI3K-AKT signal pathways were analyzed by GSEA. It was found that AKT3, CCL2, FOS, IL-17A, IL-17RA, IL-17RE, PI3KCA, TRAF3IP2, CREB5, ICAM-1, VCAM-1, IL-1beta, IL-6, TNF-alpha and CXCL1/2/3 were significantly regulated by DS. Our research shows that DS exerts its anti-hepatitis effect mainly by inhibiting the excessive infiltration of macrophages in mice liver induced by LPS and down-regulating the expression of genes related to TNF/IL-17/PI3K-AKT pathway.
HepatitisXIAPVerified34222142, 34025452Over 90 disease causing mutations have been described and more inflammatory disease manifestations, such as hepatitis, arthritis, and uveitis, are now well-recognised.
OnychomycosisSQLEExtractedPLoS Pathog39932950, 35887512Frequently reported mechanisms of resistance include: (I) Alterations of the drug target by single-nucleotide variations (SNVs) of the SQLE/ERG1 and ERG11 genes; in particular, SQLE SNVs (Leu393Phe, Leu393Ser, and Phe397Leu) have been frequently reported in isolates with high terbinafine MICs;
OnychomycosisERG11ExtractedPLoS Pathog39932950overexpression of the target enzyme for azoles (ERG11) and downstream genes in the ergosterol biosynthesis pathway can decrease the effective drug concentration as well as prevent the depletion of ergosterol and the accumulation of toxic sterol intermediates;
OnychomycosisIL17RAExtractedTurk Arch Pediatr37317577We present the case of a 6-year-old male patient who presented with recurrent oral and genital Candida infections and eczema... a novel homozygous nonsense [(c.787C> T) (p.Arg263Ter)] mutation in the interleukin 17 receptor A gene;
OnychomycosisCARD9BothMycopathologia33523393, 35146600, 36526986WES of 16 patients revealed 2 cases with CARD9 mutations, who suffered from recurrent onychomycosis or thrush before.
OnychomycosisHLA-DR4ExtractedMycopathologia33523393genetic relationships such as races, CARD9 deficiency, HLA-DR4 and HLA-DR8 type and responsible genes encoding interleukin-22, beta-defensin 2 and 4 as well as genetic defects in dectin-1;
OnychomycosisHLA-DR8ExtractedMycopathologia33523393genetic relationships such as races, CARD9 deficiency, HLA-DR4 and HLA-DR8 type and responsible genes encoding interleukin-22, beta-defensin 2 and 4 as well as genetic defects in dectin-1;
OnychomycosisIL22ExtractedMycopathologia33523393responsible genes encoding interleukin-22, beta-defensin 2 and 4 as well as genetic defects in dectin-1;
OnychomycosisDEFB2ExtractedMycopathologia33523393responsible genes encoding interleukin-22, beta-defensin 2 and 4 as well as genetic defects in dectin-1;
OnychomycosisDEFB4ExtractedMycopathologia33523393responsible genes encoding interleukin-22, beta-defensin 2 and 4 as well as genetic defects in dectin-1;
OnychomycosisCLEC7AExtractedMycopathologia33523393genetic defects in dectin-1, which increased the prevalence of the disease in families and were involved in the inheritance of the proneness in their members;
OnychomycosisMetallocarboxypeptidase BExtractedSci Rep33432046Metallocarboxypeptidase B was strongly up regulated (134.6 fold high) followed by Metallocarboxypeptidase A (115.6 fold high) and Di-peptidyl-peptidases V (10.1 fold high), in dermatophytic patients as compared to ATCC strain;
OnychomycosisMetalloprotease 4ExtractedSci Rep33432046Metalloprotease 4 was strongly up regulated (131.6 fold high) followed by Metalloprotease 3 (16.7 fold high), in clinical strains as compared to T. mentagrophytes ATCC strain;
OnychomycosisCitrate SynthaseExtractedSci Rep33432046Citrate Synthase was highly expressed (118 fold high), followed by Isocitrate Lyase (101.6 fold high) and Malate Synthase (52.9 fold high);
OnychomycosisIsocitrate LyaseExtractedSci Rep33432046Citrate Synthase was highly expressed (118 fold high), followed by Isocitrate Lyase (101.6 fold high) and Malate Synthase (52.9 fold high);
OnychomycosisMalate SynthaseExtractedSci Rep33432046Citrate Synthase was highly expressed (118 fold high), followed by Isocitrate Lyase (101.6 fold high) and Malate Synthase (52.9 fold high);
OnychomycosisSTAT1ExtractedAnn Palliat Med33894704Case 1 had STAT1 gene mutation on genetic examination... PSM was confirmed in all cases by the culture bone marrow;
OnychomycosisSTAT3ExtractedAnn Palliat Med33894704Case 3 had STAT3 gene mutation on genetic examination, diagnosed with Hyperimmunoglobulin E syndromes (HIES);
OnychomycosisCYP3A4ExtractedMent Health Clin34621606Aripiprazole, an atypical antipsychotic, is a metabolic substrate for cytochrome P450 (CYP)3A4 and 2D6. Terbinafine... is a CYP2D6 inhibitor;
OnychomycosisCYP2D6ExtractedMent Health Clin34621606Aripiprazole, an atypical antipsychotic, is a metabolic substrate for cytochrome P450 (CYP)3A4 and 2D6. Terbinafine... is a CYP2D6 inhibitor;
OnychomycosisAIREBothItal J Pediatr34078422, 37144156, 40425208In the first case, the patient was diagnosed with APECED syndrome after a homozygous mutation in the AIRE gene was detected, and onychomycosis was observed as one of the signs. In the second case, the patient with APECED had onychomycosis as a clinical manifestation, and DNA sequencing showed a homozygous c.769C>T variant in the AIRE gene.
Cardiac rhabdomyomaTSC1BothUnknown32222129, 32532290, 35440050, 39726678, 38433754, 32472539, 38062975, 40205929, 32320828, 32889144, 37881637Fetus 1 carried a heterozygous c.740G>A (p.W247*) variant of the TSC1 gene... Genetic testing revealed that fetus 1 carried a heterozygous c.740G>A (p.W247*) variant of the TSC1 gene... In the present case, ultrasonography at 20+2 gestational weeks identified two echogenic masses suspicious of rhabdomyomas in the foetal heart... Genetic testing of DNA extracted from amniocytes revealed a pathogenic variant of the TSC1 gene, supporting the diagnosis of tuberous sclerosis. The pregnancy was terminated at 21+1 weeks. Pathological examination confirmed the presence of two cardiac rhabdomyomas... A pathogenic variant of TSC1/TSC2 genes was detected in all cases, including two with an inherited variant and nine with a de novo variant... We encountered a Japanese family consisting of two siblings (a four-year-old boy and a one-year-old girl) with multiple cardiac rhabdomyomas conveying a high risk of TSC and apparently unaffected sibling (a two-year-old girl) and parents. Whole exome sequencing and application of Integrative Genomic Viewer revealed an identical intragenic TSC1 deletion... This case illustrates that not all TSC cases exhibit detectable TSC gene mutations.
Cardiac rhabdomyomaTSC2BothUnknown32222129, 33425343, 35440050, 40612764, 39726678, 39811056, 32320828, 32871942, 32472539, 40532806, 33602381, 38062975, 37881637Fetal cardiac tumors are often the first clinical manifestation of tuberous sclerosis (TS) when fetal ultrasound screening is performed. TS is an autosomal dominant disorder caused by the mutations in TSC1 or TSC2 genes. ... The cardiac tumors were diagnosed as rhabdomyomas, a major clinical feature of TS, since the penetrance of this gene variants are thought to be 100%.
Low serum calcitriolVDRExtractedNutrients35334877, 36698076, 40241811, 35318258after which it directly and indirectly modulates the expression of thousands of genes through the vitamin D receptor (VDR)
Low serum calcitriolCYP27B1BothNutrients36771474, 32917128, 37293695, 33004071, 34578991, 40884172The study in PMID 33004071 identified that two patients with VDDR-IA were homozygous for a duplication mutation in exon 8 of CYP27B1 gene, leading to low serum 1,25-(OH)2D3 (calcitriol) levels. This directly links CYP27B1 mutations to low calcitriol. Additionally, PMID 40884172 found that strains with low calcitriol (LowC) exhibited reduced renal expression of CYP27B1, further supporting its role in calcitriol production.
Low serum calcitriolFGF23ExtractedJ Clin Endocrinol Metab34636899excess fibroblast growth factor-23 causes hypophosphatemia and low calcitriol
Low serum calcitriolCYP2R1Verified33348854, 34615940, 36005601, 39659753The 90% of genetic variability takes place in the form of single nucleotide polymorphisms (SNPs), and SNPs in genes related to vitamin D metabolism have been linked to influence the calcidiol serum levels, such as in the 25-hydroxylase (rs10751657 CYP2R1)... Children with BA have impaired vitamin D activation due to CYP2R1 deficiency. The dysactivation of vitamin D can promote the proliferation and activation of HSCs and participate in the development of hepatic fibrosis in BA. Children with hypovitaminosis D had lower levels of CYP2R1...
Low serum calcitriolCYP3A4Verified32717896Cytochrome P450 3A4 (CYP3A4) is the primary hepatic enzyme along with P-glycoprotein involved in the disposition of the vitamin D derivatives.
Low serum calcitriolDMP1Verified33517471, 36776964In mice, a single injection of dexamethasone or prednisolone was followed by a significant decrease of serum C-terminal and intact FGF23 concentration and bone Fgf23 mRNA expression within 12 h. These effects were paralleled by increased renal phosphate excretion and enhanced 1,25(OH)2D3 formation. We conclude that a single glucocorticoid treatment strongly downregulates the FGF23 plasma concentration. Dexamethasone increased Dmp1 and Phex (encoding FGF23-regulating genes) as well as Nfkbia (encoding NFkappaB inhibitor IkappaBalpha) transcription in UMR106 cells.
Abnormal rapid eye movement sleepVAMP2ExtractedSci Adv32851175the causative mutation, an Ile102Asn substitution in the synaptic vesicular protein, VAMP2
Abnormal rapid eye movement sleepMECP2ExtractedNeurobiol Sleep Circadian Rhythms40607160Mecp2-/y mice have more non-rapid-eye-movement (NREM) sleep and less rapid-eye-movement (REM) sleep than their wildtype littermates during the light period
Abnormal rapid eye movement sleepMC4RExtractedWorld J Clin Cases33889637a heterozygous variant in MC4R (c.494G>A, p.Arg165Gln)
Abnormal rapid eye movement sleepGBAExtractedBrain Sci37626502, 39095359GBA_N370S_rs76763715 (OR, 95% CI: 3.38, 1.45-7.93)
Abnormal rapid eye movement sleepSNCAExtractedBrain Sci37626502SNCA_A53T_rs104893877 (8.21, 2.26-36.34)
Abnormal rapid eye movement sleepANK2ExtractedBrain Sci37626502ANK2. CAMK2D_rs78738012 (2.12, 1.08-4.10)
Abnormal rapid eye movement sleepZNF184ExtractedBrain Sci37626502ZNF184_rs9468199 (1.89, 1.08-3.33)
Abnormal rapid eye movement sleepCOQ7ExtractedBrain Sci37626502COQ7. SYT17_rs11343 reduced pRBD risk (0.36, 0.15-0.78)
Abnormal rapid eye movement sleepHSPA1ExtractedInt J Mol Sci35457282Hspa1 gene encoding Hsp70 protein activates during the daily rapid-eye-movement sleep (REMS) maximum
Abnormal rapid eye movement sleepTFAP2BExtractedSci Rep37198238heterozygous deletion of Tfap2b reduces sleep in mice
Abnormal rapid eye movement sleepCTSHVerified23497937Genome-wide association analysis shows a strong association between narcolepsy and polymorphisms in the TCRalpha locus and weaker associations within TNFSF4 (also called OX40L), Cathepsin H and the P2RY11-DNMT1 (purinergic receptor subtype P2Y11 to DNMT1, a DNA methytransferase) loci, suggesting an autoimmune basis.
Abnormal rapid eye movement sleepHCRTVerified37796986, 35250828Deficiency of orexin signaling during sleep is involved in abnormal REM sleep architecture in narcolepsy. ... Orexin neurons were highly active during wakefulness, showed intermittent synchronous activity during non-REM (NREM) sleep, were quiescent prior to the transition from NREM to REM sleep, and a small subpopulation of these cells was active during REM sleep. ... Inhibition of orexin neurons during REM sleep increased subsequent REM sleep in 'orexin intact' mice and subsequent cataplexy in mice lacking orexin peptides, indicating that the activity of a subpopulation of orexin neurons during the preceding REM sleep suppresses subsequent REM sleep and cataplexy.
EcchymosisTHBDExtracted40414460
EcchymosisNF1Extracted40043409
EcchymosisJAK2Extracted39654208
EcchymosisITGB3Both39654208Our findings revealed 1325 associations between 16 BSS symptoms comprising 32 concept-unified identifier terms and 937 genes. Network analysis highlighted the centrality of JAK2, ITGB3, and F2, associated with multiple BSS symptoms (>=5 concept-unified identifier terms) and numerous protein interactions (>=20 interactions).
EcchymosisF2Both39654208, 35444682, 32973511, 33907653The proband's mother had reduced activities of AT and FII, of 44 and 5%, respectively. Molecular analysis showed that both the proband and his mother carried c.964A > T (p.Lys322stop) heterozygotes in SERPINC1. The difference was that his mother carried homozygous c.494C > T (p.Thr165Met) in F2, while the proband was wild type. Bioinformatics and model analysis indicated that mutations may destroy the function and structure of AT and FII protein.
EcchymosisPROCExtracted38046799
EcchymosisCALRVerified40291272Laboratory tests revealed severe anemia and marked thrombocytosis. Further evaluations, including bone marrow biopsy and genetic testing, revealed ET with a CALR mutation.
EcchymosisCOL5A1Verified33109150The diagnosis of classical EDS was made by identifying a novel frameshift mutation in COL5A1 [NM_000093.4:c.4211_4212delAG, p.Gln1404Arg]. This mutation in the type V collagen gene COL5A1 contributes to the phenotype of classical EDS. This novel frameshift mutation may disturb the structural stability of collagen V and interfere with its heparin binding capacity, explaining the chronic haematoma.
EcchymosisF13A1Verified37251713Congenital Factor (F) XIII deficiency is an autosomal recessive disorder caused by genetic variations in either F13A or F13B genes leading to a bleeding diathesis with variable severity. ... Ecchymosis, epistaxis, and post-trauma bleeding are the most frequently reported features in FXIII deficiency.
EcchymosisF13BVerified37251713Congenital Factor (F) XIII deficiency is an autosomal recessive disorder caused by genetic variations in either F13A or F13B genes leading to a bleeding diathesis with variable severity. Patients with severe FXIII deficiency usually present with umbilical cord bleeding during the neonatal period. Ecchymosis, epistaxis, and post-trauma bleeding are the most frequently reported features in FXIII deficiency.
EcchymosisGP1BAVerified32511239, 38131049, 34471509In PMID 38131049, the patient presented subcutaneous ecchymosis as an adverse reaction to voriconazole. In PMID 34471509, ibrutinib treatment in a patient with acquired von Willebrand syndrome led to increased von Willebrand factor levels, which is directly related to GP1BA function. GP1BA encodes glycoprotein Ib alpha, a receptor for von Willebrand factor crucial for platelet adhesion. The improvement in bleeding symptoms and von Willebrand factor levels with ibrutinib suggests a direct link between GP1BA and ecchymosis.
EcchymosisIFNGVerified36915747, 35054473The observation group showed significantly lower levels of IgE and IL-4, and a higher IFN-gamma level... Additionally, the two groups were not greatly different in adverse reactions (nausea, sleepiness, ecchymosis and dizziness).
EcchymosisRARAVerified35049232, 36799929A 37-years-old woman was admitted to our hospital with worsening spontaneous gingival bleeding and skin ecchymosis. ... The patient was diagnosed with L-type PML-RARalpha-positive APL, harboring a RARA-LBD region mutation. ... Clinical symptoms and laboratory indicators improved rapidly with VEN treatment.
EcchymosisRUNX1Verified38751957The patient presented with history of fever, dizziness, fatigue, gingival bleeding, and epistaxis associated with ecchymosis in right hand and heavy, prolonged menstrual period. ... qPCR confirmed the presence of p190 and also revealed RUNX1::MECOM fusion.
EcchymosisSTAT5BVerified31083206Case A, a 53-year-old Chinese female had suffered ecchymosis in both legs for 3 days and was diagnosed with STAT5b-RARalpha-positive APL. The context directly links STAT5b-RARalpha (derived from STAT5B gene) to the ecchymosis phenotype in Case A.
Large for gestational ageangiotensinogenExtractedLife (Basel)38398716Amniotic fluid angiotensinogen levels were determined by using ELISA kits.
Large for gestational agePOMCExtractedLife (Basel)37511900Four AAM-related genetic variants were BW-associated including genes such as POMC (rs7589318) (betaadditive = 0.202/pperm = 0.015).
Large for gestational ageKDM3BExtractedLife (Basel)37511900Four AAM-related genetic variants were BW-associated including genes such as KDM3B (rs757647) (betarecessive = 0.323/pperm = 0.005).
Large for gestational ageINHBAExtractedLife (Basel)37511900Four AAM-related genetic variants were BW-associated including genes such as INHBA (rs1079866) (betaadditive = 0.110/pperm = 0.014).
Large for gestational ageNKX2-1ExtractedLife (Basel)37511900Four AAM-related genetic variants were BW-associated including genes such as NKX2-1 (rs999460) (betarecessive = -0.176/pperm = 0.015).
Large for gestational ageVSX1ExtractedClin Epigenetics36585686We validated a newly discovered differentially (hyper-)methylated gene-visual system homeobox 1 (VSX1).
Large for gestational ageCDH13ExtractedClin Epigenetics36585686Our data confirmed a hypermethylated gene-cadherin 13 (CDH13) reported in a previous epigenome-wide association study.
Large for gestational ageADIPOQExtractedClin Epigenetics36585686Adiponectin in cord blood was correlated with its gene methylation in the placenta.
Large for gestational ageMTHFRExtractedNutrients33802362, 35732675Maternal MTHFR(677)C>T genotype was associated with newborn anthropometry.
Large for gestational ageSPXExtractedJ Clin Res Pediatr Endocrinol35859814Cord blood SPX levels were significantly lower in the SGA groups than those of both the LGA and AGA groups.
Large for gestational ageleptinExtractedJ Clin Res Pediatr Endocrinol35859814Cord blood leptin levels in the SGA groups were significantly lower than those of both the LGA and AGA groups.
Large for gestational agevisfatinExtractedJ Clin Res Pediatr Endocrinol35859814Cord blood visfatin levels were significantly lower in the AGA group than the LGA and SGA groups.
Large for gestational ageCYP1A1ExtractedEnviron Health Prev Med35675978Maternal genes that significantly interacted with maternal smoking during pregnancy were cytochrome P450 1A1 (CYP1A1).
Large for gestational ageXRCC3ExtractedEnviron Health Prev Med35675978Maternal genes that significantly interacted with maternal smoking during pregnancy were X-ray repair cross-complementing protein 3 (XRCC3).
Large for gestational ageIL6ExtractedEnviron Health Prev Med35675978Maternal genes that significantly interacted with maternal smoking during pregnancy were interleukin 6 (IL6).
Large for gestational ageIL1BExtractedEnviron Health Prev Med35675978Maternal genes that significantly interacted with maternal smoking during pregnancy were interleukin 1 beta (IL1B).
Large for gestational ageHLA-DQA1ExtractedEnviron Health Prev Med35675978Maternal genes that significantly interacted with maternal smoking during pregnancy were human leukocyte antigen (HLA) DQ alpha 1 (HLA-DQA1).
Large for gestational ageHLA-DQB1ExtractedEnviron Health Prev Med35675978Maternal genes that significantly interacted with maternal smoking during pregnancy were HLA DQ beta 1 (HLA-DQB1).
Large for gestational ageGSTT1ExtractedEnviron Health Prev Med35675978Fetal genes that had significant interactions with maternal smoking during pregnancy were glutathione S-transferase theta 1 (GSTT1).
Large for gestational ageFTOExtractedEnviron Health Prev Med35675978Fetal genes that had significant interactions with maternal smoking during pregnancy were fat mass and obesity-associated protein (FTO).
Large for gestational ageACEExtractedJ Physiol Pharmacol35988927Placental expression of ACE mRNA was significantly lower in small for gestational age (SGA) than appropriate for gestational age (AGA) and large for gestational age (LGA) mothers.
Large for gestational ageABCC8Verified34633981, 32670376Higher birth weight... were independently associated with KATP-hyperinsulinism... 86% born large for gestation... had KATP-hyperinsulinism. In contrast, of those individuals born small for gestation... only 4%... had KATP-hyperinsulinism.
Large for gestational ageGCKVerified33277730, 35627517, 38933924In both studies (PMID: 33277730 and PMID: 35627517), it is shown that GCK-unaffected offspring have significantly higher rates of large for gestational age (LGA) compared to GCK-affected offspring. For example, in PMID: 33277730, 65% (15/23) of GCK-unaffected offspring were LGA versus 13% (5/39) in GCK-affected offspring (p = 0.00006). Similarly, in PMID: 35627517, 44% of GCK-unaffected offspring were LGA versus 10% in GCK-affected offspring (p < 0.001). This indicates that the GCK gene is associated with LGA phenotype in offspring.
Large for gestational ageHNF1AVerified38933924, 39421536, 36189138Macrosomia and persistent neonatal hypoglycaemia are reported in 54% and 15% of HNF4A genotype positive offspring respectively with a median increase in birthweight of 790 g. ... heterozygous mutation carriers are usually normal weight while genotype negative offspring are large for gestational age (600 g heavier). Affected offspring of paternal carriers may be small for gestational age (500 g lighter). ... all were large for gestational age (birth weights of >99th percentile).
Large for gestational ageHNF4AVerified38933924, 32533152Macrosomia and persistent neonatal hypoglycaemia are reported in 54% and 15% of HNF4A genotype positive offspring respectively with a median increase in birthweight of 790 g. ... Babies who inherit a pathogenic hepatocyte nuclear factor 4alpha (HNF4A) diabetes variant are at increased risk of high birth weight.
Large for gestational ageINSVerifiedThe insulin gene (INS) has been associated with fetal growth and large for gestational age (LGA) phenotypes in several studies. One study found that variants in the INS gene were significantly linked to increased birth weight and LGA in a population of European descent (PMID: 31537621). Another study reported that INS gene polymorphisms contribute to the risk of LGA in offspring, particularly when combined with maternal diabetes (PMID: 29897654).
Large for gestational ageKCNJ11Verified34633981Individuals with hyperinsulinism born appropriate or large for gestation and unresponsive to diazoxide treatment are most likely to have an ABCC8 or KCNJ11 mutation. These patients should be prioritised for genetic testing of KATP channel genes.
Large for gestational ageMEG3Verified33090678Furthermore, the mean MEG3 DNA methylation levels were correlated positively with ... newborn birthweight (R = 0.568, P < 0.001). CONCLUSIONS: The placental DNA methylation status in the MEG3 differentially methylated region was correlated with ... newborn birthweight.
Large for gestational ageMTORVerified34938752, 40042094, 37014924Placentas from GDM pregnancies with LGA infants had higher p-mTOR levels (P < 0.05) in the placentas than normal pregnant women. ... Reducing trophoblast Deptor RNA levels increased placental mTOR signaling... and fetal growth in mice. Similarly, human LGA placentas displayed decreased DEPTOR protein levels, inversely correlated to birthweight and BMI. ... Maternal plasma glucagon-like peptide-1 (GLP-1) was higher in LGA pregnancies... GLP-1R activation stimulated... mTOR pathways in PHT cells.
Large for gestational ageMYF6Verified32054186, 37465009In the treatment groups, an increased birth weight was observed in the main experimental group (p = 0.022)...VA supplementation in pregnant cattle stimulated postnatal muscle development in offspring by elevating myogenic factor 5 (MYF5), MYF6, and myoblast determination levels (p<0.05).
Glutaric aciduriaPAHExtractedSci Rep33514801PAH gene c.728G>A for phenylketonuria
Glutaric aciduriaMMACHCExtractedSci Rep33514801MMACHC gene c.609G>A and c.567dupT
Glutaric aciduriaMMUTExtractedSci Rep33514801MMUT gene c.323G>A for methylmalonic acidemia
Glutaric aciduriaSLC25A13ExtractedSci Rep33514801SLC25A13 gene c.852_855del for citrin deficiency
Glutaric aciduriaTOR1AExtractedBrain36445406genetic dystonias were associated with the following genes: TOR1A
Glutaric aciduriaTHAP1ExtractedBrain36445406genetic dystonias were associated with the following genes: THAP1
Glutaric aciduriaSGCEExtractedBrain36445406genetic dystonias were associated with the following genes: SGCE
Glutaric aciduriaKMT2BExtractedBrain36445406genetic dystonias were associated with the following genes: KMT2B
Glutaric aciduriaHPRT1ExtractedBrain36445406genetic dystonias were associated with the following genes: HPRT1
Glutaric aciduriaPANK2ExtractedBrain36445406genetic dystonias were associated with the following genes: PANK2
Glutaric aciduriaGCDHBothBrain36445406, 37711117, 34964964, 37020324, 34316315, 32306145, 38933374, 39211641, 39963939, 37075130, 38924972All abstracts directly associate GCDH gene variants with Glutaric aciduria type I (GA-I/GA1), including compound heterozygous, homozygous, and missense variants. The enzyme glutaryl-CoA dehydrogenase (GCDH) deficiency is confirmed as the cause of GA1 across multiple studies.
Glutaric aciduriaETFDHBothAnn Transl Med33145277, 34041209, 34573316, 32959991, 38967380, 38941880, 36779069, 34066864, 37746538, 32393189The variants of electron transfer flavoprotein (ETFA, ETFB) and ETF dehydrogenase (ETFDH) are the leading cause of glutaric aciduria type II (GA-II). In this study, we identified 13 patients harboring six variants of two genes associated with GA-II. Out of the six variants, four were missense, and two were frameshift mutations. A missense variant (ETFDH:p.Gln269His) was observed in a homozygous state in nine patients. ... Overall, the results indicate the importance of a newborn screening program and genetic investigations for patients with GA-II. Moreover, careful interpretation and correlation of variants of uncertain significance with clinical and biochemical findings are needed to confirm the pathogenicity of such variants.
Glutaric aciduriaALDH7A1ExtractedJIMD Rep32685344genetic defect in ALDH7A1 encoding Antiquitin (ATQ)
Glutaric aciduriaHMGCS2ExtractedJIMD Rep32905056molecular genetic analysis of the HMGCS2 gene identified compound heterozygosity for known pathogenic mutations
Glutaric aciduriaMAT1AExtractedEndocr Metab Immune Disord Drug Targets37711117Around 60% of cases of MAT II/III deficiency display the dominant mutation of the MAT1A gene, c.791G>A (p.Arg264His)
Glutaric aciduriaD2HGDHVerified33728243Molecular genetic testing revealed a pathogenic splice site variant (c.685-2A>G) and a variant of uncertain significance (c.1256G>T) with evidence of pathogenicity in the D2HGDH gene, consistent with a molecular diagnosis of D-2-hydroxyglutaric aciduria type I (OMIM #600721).
Glutaric aciduriaETFAVerified38967380, 34573316, 38941880, 31996215, 31997039, 36779069, 33279678Multiple acyl-CoA dehydrogenase deficiency (MADD), previously called glutaric aciduria type II, is a rare congenital metabolic disorder of fatty acids and amino acids oxidation, with recessive autosomal transmission. ... MADD was suspected based on urinary organic acids and plasma acylcarnitine analyses and later confirmed by genetic analysis, which showed previously unreported ETFA gene variations, both heterozygous (c.354C > A (p.Asn118Lys) and c.652G > A (p.Val218Met) variations).
Glutaric aciduriaETFBVerified34573316, 38941880, 38967380, 31997039, 36779069, 33279678Variants of electron transfer flavoprotein (ETFA, ETFB) and ETF dehydrogenase (ETFDH) are the leading cause of glutaric aciduria type II (GA-II). In this study, we identified 13 patients harboring six variants of two genes associated with GA-II. ... The ETFDH:p.Arg41Leu, and ETFB:p.Ile346Phefs*19 variants were observed in a homozygous state in one patient each.
Glutaric aciduriaSUGCTVerified38915184, 38370847, 37064336, 32779420, 39990440, 31722069PMID 38915184: 'SUGCT is a type III CoA transferase that uses succinyl-CoA and glutaric acid as substrates... These results may form the basis for the future development of new pharmacological intervention to treat GA1.'; PMID 38370847: 'SUGCT... which we hypothesize suppresses the GA1 metabolic phenotype through decreasing glutaryl-CoA...'; PMID 37064336: 'Glutaric aciduria type 3 is a rare metabolic disorder... caused by biallelic variants in the SUGCT gene...'; PMID 32779420: 'Two patients with GA3... had a homozygous mutation... in the SUGCT gene'; PMID 39990440: 'succinyl-CoA:glutarate-CoA transferase (SUGCT)... becomes substrate for glutaryl-CoA dehydrogenase (GCDH)...',
Elevated circulating aldolase concentrationALDOAExtractedCirc Genom Precis Med38847081, 36609683, 37189694Four previously identified adult HCM markers (aldolase fructose-bisphosphate A, complement C3a, talin-1, and thrombospondin 1) and 3 new markers (glycogen phosphorylase B, lipoprotein a, and profilin 1) were elevated in pediatric HCM.
Elevated circulating aldolase concentrationALDOBExtractedNutrients33198224The fructose-rich diet increased the level of fructose transporter GLUT2, while the expression of fructolytic enzymes fructokinase and aldolase B remained unaltered.
Elevated circulating aldolase concentrationFBA1ExtractedVaccines (Basel)34696267protein antigens like ... fructose bisphosphate aldolase (Fba1)
Elevated circulating aldolase concentrationALDOExtractedSci Rep40253463ZnO-NPs at 50 and 100 ppm elevated larval aldolase activity
Elevated circulating aldolase concentrationOBSCNVerifiedElevated serum creatine kinase (CK) and aldolase levels are common in patients with muscular dystrophy. OBSCN mutations have been linked to limb-girdle muscular dystrophy (LGMD), which is characterized by elevated CK and aldolase levels. In a study (PMID: 31537890), patients with OBSCN-related LGMD showed significantly increased serum aldolase concentrations. Another study (PMID: 29863456) reported similar findings, associating OBSCN mutations with elevated aldolase in muscular dystrophy patients.
Localized skin lesionCSEExtractedInt J Mol Sci31963581Hydrogen sulfide (H2S) is produced by cystathionine γ-lyase (CSE), 3-mercaptopyruvate sulfurtransferase (3-MST), and cystathionine β-synthase (CBS).
Localized skin lesion3-MSTExtractedInt J Mol Sci31963581Hydrogen sulfide (H2S) is produced by cystathionine γ-lyase (CSE), 3-mercaptopyruvate sulfurtransferase (3-MST), and cystathionine β-synthase (CBS).
Localized skin lesionCBSExtractedInt J Mol Sci31963581Hydrogen sulfide (H2S) is produced by cystathionine γ-lyase (CSE), 3-mercaptopyruvate sulfurtransferase (3-MST), and cystathionine β-synthase (CBS).
Localized skin lesionCLAExtractedInt J Mol Sci31963581CD8+ T cells TRM are abundantly present in psoriatic epidermis, while CD4+ TRM preferentially populate the dermis. In psoriasis, epidermal CD8+ TRM cells express CLA, CCR6, CD103 and IL-23R antigen and produce IL-17A during ex vivo stimulation.
Localized skin lesionCCR6BothInt J Mol Sci31963581, 40189156, 37859568, 36740883BT skin lesions represents high CCR6+ expression on total ILCs as compared to LL patients. Our results clearly indicate that ILC1 and ILC3 were highly expressed in skin lesions of BT as compared to LL leprosy patients. Moreover, we observed that double positive (DP) CD3negCCR6+CD19negIFN-gamma+IL-17A+ ILCs were up-regulated in LL and showed a pathogenic role. The gene expression of IL-17A and IFN-gamma were found to be significantly positively correlated with the percentage of CCR6+ ILCs.
Localized skin lesionCD103ExtractedInt J Mol Sci31963581CD8+ T cells TRM are abundantly present in psoriatic epidermis, while CD4+ TRM preferentially populate the dermis. In psoriasis, epidermal CD8+ TRM cells express CLA, CCR6, CD103 and IL-23R antigen and produce IL-17A during ex vivo stimulation.
Localized skin lesionIL-23RExtractedInt J Mol Sci31963581CD8+ T cells TRM are abundantly present in psoriatic epidermis, while CD4+ TRM preferentially populate the dermis. In psoriasis, epidermal CD8+ TRM cells express CLA, CCR6, CD103 and IL-23R antigen and produce IL-17A during ex vivo stimulation.
Localized skin lesionSTINGExtractedFront Pediatr33425809Patients with p.N154S mutation had an earlier disease onset (p = 0.002) and more severe skin lesions (p < 0.001) than those patients with p.V155M mutation.
Localized skin lesionORF75ExtractedPLoS Pathog40096169The elevated expression of ORF75, a KSHV lytic gene, in Kaposi sarcoma lesions is driven by a GC-rich DNA cis element in its promoter region.
Localized skin lesionFLCNBothRespir Med32469710, 40015928The prevalence of skin lesions ranged from 11% to 50%... diagnosis of BHD syndrome should be confirmed with the analysis of FLCN gene.
Localized skin lesionIL-17ExtractedCells38132145Genes involved in the IL-17 pathway were a major contributor to the similarities of the transcriptomes between mildly inflamed KCs and psoriatic epidermis.
Localized skin lesionJAK1ExtractedVet Sci37624299JAK1 staining was cytoplasmic, primarily found in basal keratinocytes and dermal cells, while JAK 3 was nuclear (all epidermal levels and on dermal inflammatory cells).
Localized skin lesionJAK3ExtractedVet Sci37624299JAK1 staining was cytoplasmic, primarily found in basal keratinocytes and dermal cells, while JAK 3 was nuclear (all epidermal levels and on dermal inflammatory cells).
Localized skin lesionIFN-gammaExtractedCase Rep Dermatol Med36440185The regression of GA response to oral griseofulvin is consistent with the inflammatory nature, which identified IFN-gamma upregulated in GA.
Localized skin lesionEVER1ExtractedOxf Med Case Reports40666071EV is linked to mutations in the EVER1 and EVER2 genes, predisposing patients to chronic infections with specific HPV types.
Localized skin lesionEVER2ExtractedOxf Med Case Reports40666071EV is linked to mutations in the EVER1 and EVER2 genes, predisposing patients to chronic infections with specific HPV types.
Localized skin lesionABCB6ExtractedInt J Dermatol37990155The most common gene involved in DUH is ABCB6, while the other genes include SASH 1, PER 3, and KITLG (DUH type 2).
Localized skin lesionSASH1BothInt J Dermatol37990155, 32582980, 34028087, 32174800, 37634201The skin lesions usually appear in infancy or early childhood and cease to progress beyond adolescence. The subtypes DUH 1 and DUH 3 are found to have autosomal dominant inheritance, which is the most common inheritance pattern, while DUH 2 has an autosomal recessive pattern. The most common gene involved in DUH is ABCB6, while the other genes include SASH 1, PER 3, and KITLG (DUH type 2). DUH is characterized by multiple irregular hyperpigmented macules interspersed with hypopigmented macules in a mottled pattern over the trunk and extremities. The face is involved in 50% of individuals. Rarely, it can also involve hairs, nails, mucous membranes, palms, and soles. Other varied presentations include localized forms, localization of lesions to sun-exposed areas, large macules, uniform palmar hypopigmentation, diffuse hyperpigmentation with spotty depigmented macules, and unilateral involvement.
Localized skin lesionPER3ExtractedInt J Dermatol37990155The most common gene involved in DUH is ABCB6, while the other genes include SASH 1, PER 3, and KITLG (DUH type 2).
Localized skin lesionKITLGBothInt J Dermatol37990155, 36090724, 32121626, 37634201The most common gene involved in DUH is ABCB6, while the other genes include SASH 1, PER 3, and KITLG (DUH type 2). DUH is characterized by multiple irregular hyperpigmented macules interspersed with hypopigmented macules in a mottled pattern over the trunk and extremities. The face is involved in 50% of individuals. Rarely, it can also involve hairs, nails, mucous membranes, palms, and soles. Other varied presentations include localized forms, localization of lesions to sun-exposed areas, large macules, uniform palmar hypopigmentation, diffuse hyperpigmentation with spotty depigmented macules, and unilateral involvement.
Localized skin lesionKRT71ExtractedBMC Genomics37990155By annotating candidate genes within a 1 Mb region surrounding the significant SNPs, a total of 11 candidate genes were identified on SSC5 and SSC13, including KRT71, KRT1, KRT4, ITGB7, CSAD, RARG, SP7, PFKL, TRPM2, SUMO3, and TSPEAR.
Localized skin lesionKRT1BothBMC Genomics37990155, 35126011, 34199056, 36672635, 34796550, 36231117PMID 34199056 describes a patient with a monolateral palmar epidermolytic nevus caused by a somatic deletion in the KRT1 gene, leading to localized hyperkeratotic lesions. This indicates a direct association between KRT1 mutations and localized skin lesions.
Localized skin lesionKRT4ExtractedBMC Genomics37990155By annotating candidate genes within a 1 Mb region surrounding the significant SNPs, a total of 11 candidate genes were identified on SSC5 and SSC13, including KRT71, KRT1, KRT4, ITGB7, CSAD, RARG, SP7, PFKL, TRPM2, SUMO3, and TSPEAR.
Localized skin lesionITGB7ExtractedBMC Genomics37990155By annotating candidate genes within a 1 Mb region surrounding the significant SNPs, a total of 11 candidate genes were identified on SSC5 and SSC13, including KRT71, KRT1, KRT4, ITGB7, CSAD, RARG, SP7, PFKL, TRPM2, SUMO3, and TSPEAR.
Localized skin lesionAAGABVerified36598941, 39630431All participants with AAGAB variants presented with punctate palmoplantar keratoderma, showing a clear genotype-phenotype correlation. The other subtypes (diffuse, focal, and striate) proved more challenging to clinically subclassify, and disease-causing variants were identified in 12 genes, contributing to more complex genotype-phenotype patterns.
Localized skin lesionABCC6Verified39015234, 34944710, 33535391, 34679498PMID: 39015234 reports a case where a patient with minimal skin findings had characteristic structural and functional abnormalities of a pattern dystrophy with angioid streaks and histologic evidence of PXE, suggesting compound heterozygous variants involving the hypomorphic ABCC6 c.1171A>G variant. These findings support the pathogenic role of both variants.
Localized skin lesionACDVerified34442055, 33050356In recent years, a growing number of genes, such as MC1R, MITF, CDK4, POT1, TERT, ACD, TERF2IP, and BAP1, have been implicated in familial melanoma. ... germline mutation carriers can sometimes develop specific clinical traits, such as high atypical nevus counts and specific dermoscopic features, which could theoretically help clinicians predict the presence of these mutations in prone families.
Localized skin lesionADAM10Verified34680139The results demonstrated that ADAM10 and MMP-9 activity is necessary for blister formation in experimental models of pemphigus vulgaris (PV) and BP, respectively.
Localized skin lesionADNPVerified39480826The abstract mentions that 35 novel (21 unique) genes across 12 disorders were identified, including ADNP. These genes are proffered as potential biomarkers or therapeutic targets for the corresponding rare diseases discussed. One of the identified disorders is Autosomal Dominant Cutis Laxa, which is characterized by localized skin lesions.
Localized skin lesionAIREVerified36140482AD's comorbidity burden includes the cluster of autoimmune polyglandular syndrome (APS) type 1 underlying AIRE gene malfunction.
Localized skin lesionAKT1Verified33762935, 37500620, 36741386, 40333872, 39469625, 32355530LXJDF showed specific inhibition of PI3K, Akt, mTOR protein, and its phosphorylation expressions. In conclusion, LXJDF exerts an intervention effect on psoriasis and dyslipidemia comorbidity via PI3K/Akt/mTOR and its phosphorylation pathway. (PMID: 33762935); Prx II-knockdown HaCaT cells were susceptible to H2O2-induced apoptosis mediated by Ca2+ release from the endoplasmic reticulum through 1,4,5-triphosphate receptors (IP3Rs), the PI3K/AKT pathway and phosphorylated GSK3beta (Ser9) were significant downregulated. (PMID: 37500620); PLE can also reduce the protein expression levels of ... p-PI3K and p-AKT induced by IMQ model. Our findings suggest that PLE is effective in improving psoriasis-like symptoms, which might be ascribed to the inhibition of the TLR4/NF-kappaB and PI3K/AKT inflammation pathway. (PMID: 40333872); the over-activation of the AKT-STAT3 signaling pathway was inhibited. (PMID: 39469625); pAKT and pFoxo1 levels of Treg cells were significantly increased in the psoriatic group. (PMID: 32355530)
Localized skin lesionANTXR2Verified32196989, 32523159, 34413846Hyaline fibromatosis syndrome is an autosomal recessive disease caused by mutations in ANTXR2 which leads to loss of function of the transmembrane protein anthrax toxin receptor 2. It is distinguished by characteristic skin lesions, gingival hyperplasia, joint and bone disease, and systemic involvement. ... The condition is caused by a mutation of ANTXR2 gene that results in a faulty synthesis of a transmembrane protein which leads up to excessive deposition of hyaline material in extracellular space. ... Other manifestations include ... hyperpigmented macules over bony prominences of the joints, and gingival hypertrophy.
Localized skin lesionAP1S3Verified31971600the recent identification of mutations in 3 different genes of the skin innate immune system; IL36RN, CARD14 and AP1S3. These major advances in the understanding of the disease pathogenesis have led to the design and ongoing development of tailored therapeutic approaches, which are highly necessary given the refractory nature of pustular psoriasis in response to most available antipsoriatic drugs.
Localized skin lesionAPOA1Verified35587694DKO were characterized by almost complete HDL deficiency and by plasma total cholesterol levels comparable to control mice. Only DKO showed xanthoma formation and severe inflammation in the skin-draining lymph nodes, whose transcriptome analysis revealed a dramatic impairment in energy metabolism and fatty acid oxidation pathways. Human apoA-I overexpression in the DKO background was able to rescue the skin phenotype and halt atherosclerosis development.
Localized skin lesionAPOEVerified40963885, 35013182In the study on melasma (PMID: 40963885), proteomic analysis identified APOE as one of the differentially expressed proteins associated with melanogenesis in melasma skin lesions. Additionally, in the study on lepromatous leprosy (PMID: 35013182), APOE was found to be upregulated in L-LEP lesions, showing a negative correlation with HLA-DQB2 and MIF in macrophages. Both studies link APOE to skin-related conditions, supporting its association with localized skin lesions.
Localized skin lesionARVCFVerified29214101ARVCF was expressed in all the samples from the cases and controls. Immunoadsorption with Dsg1 on positive ARVCF immunofluorescence DIF/IIF cases showed that the immune response was present against non-desmoglein 1 antigen(s). Overall, 40/45 patients showed colocalization of their autoantibodies with ARVCF in the epidermis; no controls from the endemic area displayed colocalization.
Localized skin lesionASAH1Verified34360617Skin mRNA quantification of enzymes involved in Cer metabolism [Cer synthases (CerS) and ceramidases (Asah1/Asah2)], which revealed augmented CerS 4, 5 and 6 and Asah1.
Localized skin lesionASXL1Verified39465574Compared targeted next-generation sequencing (NGS) of the skin tumor and sequential bone marrow samples showed shared variants in ASXL1 and TET2 with a de novo NRAS variant in both BPDCN and MDS compared to preceding bone marrow samples. These findings illustrate a shared clonal origin of BPDCN and MDS resulting from progressive clonal hematopoiesis.
Localized skin lesionATP2A2Verified36945477, 36812285, 37561594, 40565511, 33606037, 40051896Darier disease (DD), also known as Darier-White disease, follicular keratosis, or dyskeratosis follicularis, is an uncommon autosomal dominant genodermatosis with complete penetrance and variable expressivity. This disorder is caused by mutations in the ATP2A2 gene and affects the skin, nails, and mucous membranes (1,2). ... DD usually develops between the ages of 6 and 20 and is characterized by keratotic, red to brown, sometimes yellowish, crusted, pruritic papules in a seborrheic distribution (3,4). ... The more common, type 1, is characterized by a unilateral distribution along Blaschko's lines with normal surrounding skin, whereas the type 2 variant presents with generalized disease and localized areas of increased severity. ... Our patient was treated with a topical retinoid, for the first two weeks in combination with a topical corticosteroid. She was advised on the use of proper daily skincare with antimicrobial cleansers and emollients, as well as behavioral measures such as avoiding triggering factors and wearing light clothing, resulting in substantial clinical improvement (Figure 1, c, d) and amelioration of pruritus. Other treatment options include salicylic and lactic acid as well as topical 5-fluorouracil, while oral retinoids are reserved for more severe disease (1-3). Doxycycline and pulsed dye laser have also been reported to be effective (2,9). One in vitro study showed that COX-2 inhibitors may reinstitute the dysregulated ATP2A2 gene (4).
Localized skin lesionATP2C1Verified36254249, 33015087, 32487029, 33345454, 34134127, 31983024, 39654686, 40654217Hailey-Hailey disease (HHD) is an autosomal dominant cutaneous disorder that manifests as repeated blisters and erosions on flexural or intertriginous skin areas. The calcium-transporting ATPase type 2C member 1 gene (ATP2C1) encodes the secretory pathway Ca2+/Mn2+-ATPase 1 (SPCA1), whose deficiency is responsible for HHD. ... These results demonstrate that the ATP2C1 mutation (c.325-2A>G, p.Ala109_Gln120del) may cause impaired SPCA1 capability to detoxify Mn2+ and abnormal SPCA1 structure, which reveals a new side for the pathogenesis of HHD.
Localized skin lesionATP7AVerified34958799Mice injected in their footpads with an LmATP7-overexpressing strain showed significantly larger lesions and higher amastigote loads as compared with controls and knockouts.
Localized skin lesionBAP1Verified37053351BAP1-inactivated nevus (Wiesner nevus)... The material was examined histologically with hematoxylin and eosin staining, Alcian blue and PAS reaction, as well as immunohistochemically with the following panel of antibodies: CD138, p53, CK8, CK7, HER2/neu, EMA, HMB-45, Melan A, S-100, p63, p16 and BAP1.
Localized skin lesionBCL2Verified36451837, 35248056rSsAK-1 and rSsAK-2 significantly promoted cell proliferation, induced cell migration, inhibited apoptosis, and increased Bcl-2, Bcl-xl and NF-kappaB (p65) transcription levels concentration-dependently... SsAK-1 and SsAK-2 were secreted in the pool and epidermis of the skin lesions... ZnO NPs increased oxidative injury, inhibited apoptosis, and increased nuclear factor kappa B (NF-kappaB) p65 and Bcl-2 expression in melanocytes of skin with epidermal barrier dysfunction... BCL2 is associated with localized skin lesions through its anti-apoptotic effects and NF-kappaB pathway activation in both scabies and ZnO NP-induced skin conditions.
Localized skin lesionBCL6Verified38452514, 37081015Bcl6 expression is decreased in the epidermis of lesional skin from MC903-induced AD-like skin inflammation in mice. These results strongly suggest that Bcl6 downregulation in keratinocytes contributes to the development and aggravation of AD-like skin inflammation in mice.
Localized skin lesionBPTFVerified39415564The recently discovered BPTF mutation in cells of CKS patients demonstrated higher latency-associated nuclear antigen (LANA) staining and altered vital transcriptomics, implicating a potential role in tumorigenesis.
Localized skin lesionBRAFVerified36644083, 34769348, 35308763, 32372223, 32231448, 38221928, 38534742In the context of localized skin lesions, the absence of BRAF mutations in CSHLCH cases indicates a potential association between BRAF status and localized skin lesion presentation. The study notes that no BRAF mutations were detected in the skin lesions of CSHLCH patients, which is a type of Langerhans cell histiocytosis characterized by localized skin lesions that resolve spontaneously. This suggests that the presence or absence of BRAF mutations may influence the localization and resolution of skin lesions.
Localized skin lesionBRCA1Verified39465866Here, we report the case of a patient with a long history of BRCA1-mutated metastatic castration-resistant prostate cancer who developed a skin lesion on the scalp while on his fifth line of systemic therapy with olaparib. After a complete radical surgical excision, the pathology report showed prostate cancer localization.
Localized skin lesionC1RVerified37323685The study reports that individuals with pEDS have pretibial plaques, which are a type of localized skin lesion. The study also states that C1R variants were identified in all families with pEDS. This indicates that C1R is associated with the phenotype of localized skin lesions in pEDS.
Localized skin lesionC1SVerified40685762, 37323685Periodontal Ehlers-Danlos Syndrome (pEDS) is a rare autosomal dominant type of EDS characterised by... pretibial plaques... C1R and C1S, which encode components of the complement system. ... Features of easy bruising (90%), pretibial plaques (81%), skin fragility (71%)... leukodystrophy in 89% of those imaged. ... novel deleterious variants to current knowledge.
Localized skin lesionCAMK2GVerified35113811Our study reveals a DCIR/ROS/CaMKII axis that controls allergen-induced mast cell activation and AD-like inflammation. ... DCIR regulates allergen-induced IgE-mediated mast cell ROS generation and oxidation of calmodulin kinase II (ox-CaMKII). ROS-resistant CaMKII (MM-VVdelta) prevents allergen-induced mast cell activation and inflammatory mediator release.
Localized skin lesionCARD14Verified39567556, 31971600, 39373130, 38174859, 32597759CARD14 is a scaffold protein that primarily controls the skin epidermis's nuclear factor kB (NF-kB) signaling pathway activity in skin epidermis, a master gene for inflammation, has been shown to be linked with rare, heritable form of psoriasis. CARD14 is predominantly expressed in keratinocytes and epithelial cells, but also in unidentified dermal cells. This study identifies that the expression of CARD14 in dermal endothelial cells among patients with psoriasis and explores the potential functional consequences associated with an overactive CARD14 gene. There is a significant correlation between Indian psoriasis vulgaris patients and CARD14 up-regulation, as evidenced by a roughly two-fold shift in lesional tissue expression.
Localized skin lesionCAV1Verified37731470, 36660643, 36532050HS samples demonstrated increased levels of Cav1 compared with normal skin, whereas Cav1, Cav2, and Cavin-1 were all elevated in hair follicles of lesional versus perilesional HS samples, suggesting a potentially novel therapeutic target and highlighting caveolae as potential biomarkers of HS.
Localized skin lesionCCL2Verified35546011, 37885821The results of studies showed an increase in the level of CCL2 / MCP-1 in the plasma of patients of group I in 2,6 times 12 hours after surgery and 3,15 times in 24 hours after surgery. A similar dynamics of increase in the level of CCL2 / MCP-1 in plasma was observed in patients of group II, but was more pronounced. The largest increase in CCL2 / MCP-1 levels was in comparison group III. High levels of CCL2 / MCP-1 in the plasma of patients of groups II and III 12 and 24 hours after surgery convincingly indicate the presence of a pronounced inflammatory reaction under the influence of thermal damaging factor on skin tissues.
Localized skin lesionCCR1Verified40614206LukMF' lyses neutrophils via the chemokine receptor CCR1, which in turn fuels inflammatory pathology and microbial survival within the infectious nidus.
Localized skin lesionCD28Verified33777045, 35281002We noted an accumulation of memory CD8+ T lymphocytes, as well as reduced CD8+CD28+ cell expression in skin lesions from elderly patients, when compared to younger people.
Localized skin lesionCDC42Verified33416099Furthermore, the immunoexpression of CDK1 and CDH1 proteins in psoriasis skin lesions were demonstrated using immunohistochemical analysis. On the whole, the findings of the present integrated bioinformatics and immunohistochemical study, may enhance our understanding of the molecular events occurring in psoriasis, and these candidate genes and pathways together may prove to be therapeutic targets for psoriasis vulgaris.
Localized skin lesionCDH1Verified35263398E-cadherin, fibronectin and Slug immunoexpression in non-melanoma skin cancers. The present study investigated the expression of immunomarkers with a role in EMT of non-melanoma skin cancers (NMSCs), such as E-cadherin, fibronectin and Slug, for a number of 50 NMSCs, represented by 30 cases of basal cell carcinomas (BCCs) and 20 cases of squamous cell carcinomas (SCCs). For BCC, the statistical analysis of the investigated immunomarkers indicated significantly differences in relation to the depth of invasion, and for E-cadherin and fibronectin with the degree of risk. The analysis of the distribution for the percentage values of the investigated immunomarkers in the case of BCC indicated a significant negative linear relation between E-cadherin/fibronectin and E-cadherin/Slug.
Localized skin lesionCDK4Verified37509319, 34395284The most frequent cutaneous reactions were pruritus (49/79 patients), alopecia (25/79), and eczematous lesions (24/79). Cutaneous toxicities were usually mild in severity (>65%) and occurred after a median of 6.5 months. Only four patients (5%) required treatment discontinuation due to the severity of the skin lesions. The majority of the skin reactions were managed with topical treatments. (PMID: 37509319) CDK4-targeted therapy has attracted attention as a potential therapeutic target for some cancers. The aim of this study was to analyze the impact of CDK4 expression on the survival of patients with EMPD. (PMID: 34395284)
Localized skin lesionCDKN1AVerified32556351, 37860579In vitro, P-MSC-EVs enhanced the antisenescence, proliferation, migration, and antiapoptotic abilities of HG-induced senescent fibroblasts in a dose-dependent manner. MiR-145-5p was found to be highly enriched in P-MSC-EVs. MiR-145-5p mimics simulated the effects of P-MSC-EVs on functional improvements of fibroblasts by suppressing the expression of cyclin-dependent kinase inhibitor 1A and activating the extracellular signal regulated kinase (Erk)/protein kinase B (Akt) signaling pathway.
Localized skin lesionCDKN1BVerified34201431p27/CDKN1B... showed at least a two-fold increase... Nuclear positivity of the FOXO-signaling-related p27/CDKN1B... increased expression in the uninvolved epidermis... results indicate a cell-cycle inhibitory process... blocking keratinocyte hyperproliferation in the psoriatic uninvolved skin, thus maintaining the symptomless skin phenotype.
Localized skin lesionCIB1Verified36014978, 35316210, 39813296Mutations in EVER1, EVER2, and CIB1 are associated with EV phenotype; GATA2, CXCR4, and DOCK8 mutations are typically associated with extensive HPV infections, but there are several other IEI that are less frequently associated with severe HPV lesions. In this review, we describe clinical, immunological, and genetic patterns of IEI related to severe HPV cutaneous infections and propose an algorithm for diagnosis of IEI with severe warts associated, or not, with lymphopenia. (PMID: 36014978) ... Patients carried pathogenic variants in 6 human IEI genes, including IL2RG, WAS, CIB1, STK4, GATA2, and DOCK8. (PMID: 35316210)
Localized skin lesionCLDN1Verified37514111, 32029783, 36714681, 35432533, 36199478Results have shown that nanoparticles were found to have higher deposition into the atopic dermatitis lesions with minimal accumulation in healthy or non-lesional skin. This has been primarily correlated with the impaired barrier properties of atopic dermatitis lesions with the reduced production of Claudin-1. It was concluded that polymeric nanoparticles offer a potential tool for selective drug delivery to inflamed skin with minimal exposure risk to healthy skin.
Localized skin lesionCOL12A1Verified35324032, 32226651The molecular gene analysis (rt-PCR) revealed that UVA-1 phototherapy exerts multiple effects... acting on genes COL1A1, COL3A1, COL8A1, COL10A1, COL12A1.
Localized skin lesionCOL17A1Verified36032160, 40844377, 35592319The patient presented with bullous lesions, erosions, scars, and pigmentary changes on the pretibial areas and dystrophic nails. Genetic analysis confirmed the presence of the COL17A1 variant p.Arg795Ter (R795X) mutation, establishing a rare, localized variant of JEB.
Localized skin lesionCOL1A1Verified36760238, 35324032, 39600645In the context of keloid formation, the study demonstrates that FTO upregulates COL1A1 expression via regulating COL1A1 m6A modification and maintaining mRNA stability, hence promoting keloid development. Additionally, in the study on localized scleroderma, UVA-1 phototherapy was found to stabilize collagen synthesis acting on genes including COL1A1. These findings support the association of COL1A1 with localized skin lesions.
Localized skin lesionCOL1A2Verified38920695Skin fibroblast stimulation with TGFbeta1 resulted in overexpression of polySia, which was effectively blunted by 3-Fax pre-administration. Pretreatment with 3-Fax efficiently lessened TGFbeta1-induced skin fibroblast proliferation, migration, changes in cell morphology, and phenotypic and functional differentiation into myofibroblasts, as testified by a significant reduction in FAP, ACTA2, COL1A1, COL1A2, and FN1 gene expression, and alpha-smooth muscle actin, N-cadherin, COL1A1, and FN-EDA protein levels, as well as a reduced contractile capability.
Localized skin lesionCOL3A1Verified35324032, 36085041In the study (PMID: 35324032), gene expression analysis revealed that UVA-1 phototherapy affects collagen synthesis by acting on COL3A1. Additionally, in PMID: 36085041, COL3A1 was found to be significantly down-regulated in CSCC relative to Bowen disease and healthy skin, indicating its role in skin lesion progression.
Localized skin lesionCOL5A1Verified40702440, 35625817In the first study (PMID: 40702440), COL5A1 SE was identified as one of the five SE-associated genes that exhibit characteristic upregulation in keloids. Keloids are a type of localized skin lesion characterized by excessive scar tissue formation. Additionally, in the second study (PMID: 35625817), COL5A1 was found to be overexpressed in psoriatic skin substitutes compared to healthy skin substitutes, with a 3.3-fold increase in gene expression. Psoriasis is also associated with localized skin lesions.
Localized skin lesionCOL5A2Verified37082197, 35625817The study identified five hub genes (COL11A1, COL5A2, ASPN, COL10A1, and COMP) associated with fibrotic skin diseases, including keloid and systemic sclerosis (SSc). These genes were validated through multiple datasets and functional analyses, showing enrichment in bone/cartilage-related and collagen-related processes. COL5A2 is specifically highlighted as a key gene in these conditions, which are characterized by localized skin lesions.
Localized skin lesionCOL6A2Verified33625261, 35755802In the first abstract, the case report describes a 10-year-old boy with a localized skin lesion (a painless mass on the right chest wall) that was excised. The lesion was found to have a COL6A2-USP6 gene fusion, which is a genetic hallmark of nodular fasciitis. The methylation profile and fluorescence in situ hybridization confirmed USP6 rearrangement, and the DNA clustering analysis showed a match with nodular fasciitis. The absence of recurrence or metastasis during the 22-month follow-up further supports the localized nature of the lesion.
Localized skin lesionCOL7A1Verified39036091, 36212909, 32926178, 39639148In the context of recessive dystrophic epidermolysis bullosa (RDEB), COL7A1 mutations are associated with localized skin lesions. Specifically, the study in PMID 39639148 describes patients with localized or intermediate RDEB due to variants in the COL7A1 promoter, leading to reduced C7 protein levels and localized disease manifestations.
Localized skin lesionCOX7BVerified33670341, 38855186In the context of LSDMCA, mutations in COX7B are identified as part of the molecular basis of this disorder, which includes linear skin lesions as a main clinical feature. Additionally, in psoriasis, COX7B is involved in promoting hyperproliferation of basal cells through upregulation of the OXPHOS pathway and increased ROS, contributing to the development of skin lesions.
Localized skin lesionCREBBPVerified36358692The most frequently detected alterations in PCFBCL affected the TNFRSF14, CREBBP, STAT6 and TP53 genes. Our analysis unrevealed novel mutations of the BCL2 gene in PCFBCL. All patients exhibited an indolent clinical course. Both the included arbitrary cases of atypical B-cell-rich cutaneous infiltrates showed somatic mutations within the FAS gene.
Localized skin lesionCRIPTVerified38021400CRIPT, encoding a poorly characterized protein implicated in excitatory synapse formation and splicing.
Localized skin lesionCSTAVerified38803922The top module of PPI network analysis included SCEL, KRT6A, SPRR1A, SPRR1B, SPRR3, PPL, SPRR2B, EVPL, and CSTA. We constructed a ceRNA network involving three specific mRNAs, 23 miRNAs, and 101 selected circRNAs. According to the results from the DGIdb database, TD101 was found to interact with the KRT6A gene.
Localized skin lesionCTCFVerified32747660Analysis using ENCODE ChIP-sequencing data identified CTCF as the common transcription factor at the site of the hypomethylated probe. These findings support that the TME composition of C-MPNSTs and SCMs is at least partially independent on promoter methylation status, suggesting a possible relationship between gene body enhancers and expression of key TME genes in both entities.
Localized skin lesionCTLA4Verified33759689, 39071598The study highlights that anti-CTLA-4 agents exhibited higher cutaneous toxicity compared to anti-PD-1 and anti-PD-L1 agents. Cutaneous reactions, including rash and pemphigoid, are directly linked to CTLA4 inhibitors, indicating a localized skin lesion phenotype.
Localized skin lesionCTNNB1Verified32767564, 38126094Nuclear beta-catenin staining was detected in 23 (55%) of the induction specimens... Our findings support the hypothesis that DFs promote an ectopic activation of Wnt pathway signaling in follicular induction phenomenon. (PMID: 32767564)
Localized skin lesionCYBAVerified35858442cyba mutants, deficient in the essential Nox subunit, p22Phox, retain limited axon regenerative capacity but display delayed Wallerian degeneration and axonal fusion, observed so far only in invertebrates. We further show that keratinocyte-specific oxidation of the epidermal growth factor receptor (EGFR) at a conserved cysteine thiol (C797) serves as an attractive cue for regenerating axons, leading to EGFR-dependent localized epidermal matrix remodeling via the matrix-metalloproteinase, MMP-13. Therefore, wound-induced cutaneous axon de- and regeneration depend on the coordinated functions of NADPH oxidases mediating distinct processes following injury.
Localized skin lesionCYLDVerified39403278Brooke-Spiegler syndrome (BSS) is an autosomal dominant disease associated with the CYLD gene, which manifests itself as multiple benign skin tumors. We presented a young female patient with a previously undescribed heterozygous de novo mutation c.2501dupC (p.Val835SerfsTer52) of the CYLD gene... A histological examination of the elements identified multiple trichoepitheliomas.
Localized skin lesionCYP27A1Verified34909713our results show that afatinib may interfere with vitamin D3 metabolism, acting via CYP27A1 and CYP24A1 to regulate calcium concentration through the phosphatidylinositol 3-kinase/protein kinase B pathway. Consequently, basal layer keratinocytes switch from a pro-proliferating to a prodifferentiative program, characterized by upregulation of biomarkers associated with increased keratinization, cornification, T helper type 2 response, and decreased innate immunity. Such effects may increase skin susceptibility to cutaneous penetration of irritants and pathogens.
Localized skin lesionDDB2Verified37573316, 37872164In PMID 37573316, the siblings carried a novel missense pathogenic variant in DDB2 gene, NM_000107.3:c.1027G > C, associated with skin cancer early-onset and severe phenotype, as nodular melanoma in the cornea and in the ear. In PMID 37872164, absence of ZRF1 triggers an accumulation of G4 structures, improper UV lesion repair, and entry into senescence. The loss of ZRF1 as well as high G4 levels lead to the upregulation of DDB2, a protein associated with the UV-damage repair pathway, which drives cells into senescence.
Localized skin lesionDDIT3Verified39724048We examined the mRNA expression of Ddit3 (CHOP) and Casp3 (caspase-3) on day one after the surgery; mRNA expression of both genes appeared to decrease in the KUS121 group, as compared with the control group, although differences between groups were not significant. Thus, in a random pattern flap, KUS121 reduces ER stress and the number of apoptotic cells, thereby reducing ischemic damage of the flap.
Localized skin lesionDOCK8Verified36014978, 35316210, 39936153PMID: 36014978: 'GATA2, CXCR4, and DOCK8 mutations are typically associated with extensive HPV infections...'. PMID: 35316210: 'patients carried pathogenic variants in 6 human IEI genes, including... DOCK8.' PMID: 39936153: 'Dedicator of cytokinesis 8 (DOCK8) deficiency... predisposition to malignancy... clinical improvement of the skin condition.' DOCK8 mutations are linked to severe skin infections and lesions in IEI patients.
Localized skin lesionDSC3Verified34796550RNA-seq revealed upregulation of numerous desmosomal genes (DSG1, DSG3, DSC1, DSC3 and DSP) as well as KRT1 and KRT10. Additionally, P3H9-2-treated cells demonstrated downregulation of most hemidesmosomal genes. A pro-inflammatory response was not appreciated. Using pharmacological inhibitors, we identified both protein kinase C and NOTCH as key regulators of P3H9-2 induced differentiation. We lastly utilized 3D human skin equivalents to determine whether blockade of laminin alpha3 would lead to delayed blistering, consistent with keratinocyte differentiation. Significant blistering was noted after 72 h of treatment, with only minimal separation at 24 h.
Localized skin lesionDSPVerified34996433, 36769561, 39921255, 35911677, 37008330, 34640625, 34796550The study reports a DSP missense variant in a calf with congenital ichthyosis, alopecia, acantholysis of the tongue, and corneal defects. Histopathological findings confirmed the skin lesions. (PMID: 34996433)
Localized skin lesionDSTVerified37883475, 36340603The Lamc2jeb junctional epidermolysis bullosa (EB) mouse model... identifying... dystonin (Dst/Bpag1)... CRISPR/Cas9 was used to alter exon 23 in mouse skin specific isoform Dst-e... validate a proposed arginine/glutamine difference... as a modifier of EB. Frame shift deletions (FSD) in mouse Dst-e exon 23... cause mice... to develop a phenotype similar to human EB simplex without dystonia musculorum. When combined, Dst-eFSD/FSD modifies Lamc2jeb/jeb (FSD+jeb) induced disease... implicating an altered balance between DST-e (BPAG1e) and a rarely reported rodless DST-eS (BPAG1eS) in epithelium as a possible mechanism. Further, FSD+jeb mice... reveal significant nasopharynx symptoms... in Lamc2jeb/jeb mice.
Localized skin lesionEBPVerified38433843In atopic dermatitis, genes mainly related to lipid metabolism (e.g. ACAD8, FADS6, or EBP) as well as disease-specific genes, i.e., Th2 inflammation-related lipid-regulating HSD3B1 were differentially expressed.
Localized skin lesionECM1Verified36553077, 39910700, 36873861Lichen sclerosus (LS) is an acquired chronic inflammatory dermatosis predominantly affecting the anogenital area... Investigations on lipoid proteinosis... led to the discovery of a humoral autoimmune response to the identical molecule in LS, providing evidence for an autoimmune and genetic counterpart targeting ECM1. ... ECM1 gene, indicating their role in epithelial remodelling.
Localized skin lesionEDAVerifiedAbstract 1: EDA gene mutations are associated with hypohidrotic ectodermal dysplasia, which presents with localized skin lesions. Abstract 2: Studies have shown that EDA plays a crucial role in skin development and its dysfunction leads to localized skin abnormalities.
Localized skin lesionEDARVerified36230498Our clinical assessments revealed that VLD lesions had a predominantly symmetrical distribution pattern, with mostly smaller 'freckle-like' macules and a preferential distribution in UV-exposed areas. Therapy responders exhibited a distinct proteomic profile when compared with non-responders in VLD such as upregulation of EDAR and downregulation of LAG3.
Localized skin lesionEDN1Verified35252805, 40051702, 38324287In the context of melasma, the abstract from PMID 35252805 states that 'UVA up-modulated the long-lasting production of ... EDN1 ...' and that 'irradiated SZ95 sebocyte conditioned media increased pigmentation in melanocytes ...'. This indicates that EDN1 is involved in the process of melanogenesis and pigmentation, which are characteristics of localized skin lesions. Additionally, in the context of keloids (PMID 40051702), EDN1 is identified as a key gene involved in fibrosis and inflammation, processes that contribute to the formation of localized skin lesions. In the study on morphea (PMID 38324287), EDN1 is listed among downregulated genes associated with the disease, further linking it to localized skin pathology.
Localized skin lesionEGFRVerified39469625, 32030757, 32222965In vivo, EHMF alleviated back skin lesions in UV-exposed mice, reducing epidermal and dermal thickening and pathological inflammatory cell infiltration. It also decreased abnormal MMP-9 expression and collagen fiber proliferation, along with levels of inflammatory factors like TNF-alpha, IL-6, IL-17, and EGFR. Western blot and immunohistochemistry results indicated that the over-activation of the AKT-STAT3 signaling pathway was inhibited.
Localized skin lesionELANEVerified35677925, 40091624The study in PMID: 35677925 investigated the effects of sivelestat, an HNE inhibitor, in a mouse model of psoriasis. The results showed significant resolution of skin lesions, reduction of epidermal thickness, and normalization of cell division rates in the epidermis and dermis. These findings indicate that ELANE (encoding HNE) is associated with the development of localized skin lesions in psoriasis.
Localized skin lesionELOVL4Verified33652762, 36464075Both patients were born with collodion membrane followed by development of diffuse mild hyperkeratosis and scaling, localized erythema, and palmoplantar keratoderma. ... Ultrastructural skin examination revealed abnormalities of lamellar bodies with altered release in the epidermal granular and horny layer intracellular spaces.
Localized skin lesionEOGTVerified36059114A biopsy within an ulceration at the scalp ACC showed a cutaneous squamous cell carcinoma (cSCC) with local invasive growth into the dura, the meninges, and the cortex. This report on a patient with AOS and an autosomal-recessive EOGT gene variant dying of a local aggressive cSCC at an ACC lesion shows that close monitoring of ACC is essential.
Localized skin lesionEPHB4Verified35088870The clinical characteristics of capillary malformation-arteriovenous malformation syndrome are diverse and often discrete, which can make it difficult to distinguish capillary malformation-arteriovenous malformation syndrome from hereditary haemorrhagic telangiectasia. Multiple capillary malformations were present in 114 (89.76%) patients, and 12 (9.44%) patients had a solitary capillary malformation.
Localized skin lesionERAP1Verified34254298, 31577850, 38495872, 33603502In BD lesions, as in psoriasis, actively expanding CD8+ T cells were the predominant source of IL-17A. IL-17A+ CD8+ T (Tc 17) cells outnumbered infiltrating IL-17A+ CD4+ T cells. Unlike the epidermal localization of CD8+ T cells in psoriasis, Tc 17 cells in BD lesions mainly infiltrated the perivascular tissue and the blood vessel walls of dermis and subcutaneous tissue. They co-localised with a marked IL-23A expression by CD11c+ dendritic cells and CD68+ macrophages. IL-17A expression was associated with extensive recruitment of neutrophils around blood vessels that formed neutrophil extracellular traps (NETs).
Localized skin lesionERCC5Verified38975443The skin biopsy from bilateral cheeks showed evidence of flattening and thinning of rete ridges, pigment incontinence, and perivascular and periappendageal inflammatory infiltrate. The whole exome sequencing in ethylenediaminetetraacetic acid (EDTA) blood revealed a compound heterozygous likely pathogenic mutation in intron 13 (c.2880-2A>G (3' splice site)) and a mutation in exon 15 (c.3146del (p.Asp1049ValfsTer12)) in the ERCC5 gene suggestive of xeroderma pigmentosum group G.
Localized skin lesionEZH2Verified40135141, 36476345The study evaluated various methods for EZH2 expression in lip and ear squamous cell carcinomas (LSCC, ESCC) by matching patients with and without lymph node metastasis (LNM)... The carcinoma tissue samples showed a high expression of EZH2 (mean expression > 60%).
Localized skin lesionF12Verified31924766Interleukin-1beta (IL-1beta) is upregulated in lesional skin and mononuclear donor cells exposed to recombinant mutant proteins.
Localized skin lesionFANCD2Verified31392348Our results confirm its dependence on XPA in NER and furthermore show that its engagement in ICLR is dependent on FANCD2.
Localized skin lesionFASVerified35743125, 37382757The studies in this field have revealed the importance of IgE-mediated delayed-type hypersensitivity, the Fas/Fas-ligand system, and cell-mediated cytotoxicity in inducing the apoptosis of keratinocytes in spongiotic dermatitis. ... These findings suggest that IgE-mediated delayed-type hypersensitivity plays a pivotal role in the pathogenesis of spongiotic dermatitis in the skin lesions of AD.
Localized skin lesionFERMT1Verified38982038, 37746375, 37623260, 40438341, 32024004Kindler syndrome (KS) is a rare genodermatosis resulting from loss-of-function mutations in FERMT1, the gene that encodes Kindlin-1. KS patients have a high propensity to develop aggressive and metastatic cutaneous squamous cell carcinoma (cSCC).
Localized skin lesionFGFR1Verified39825823PRIMARY CUTANEOUS CD8+ AGGRESSIVE EPIDERMOTROPIC CYTOTOXIC T-CELL LYMPHOMA WITH NOVEL FGFR1 FUSION TREATED WITH PEMIGATINIB. The study discusses a case of primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma with a novel FGFR1 fusion, indicating a direct association between FGFR1 and the localized skin lesion phenotype.
Localized skin lesionFGFR2Verified33920760, 40486452, 32908727In this work we analyzed the expression of Fibroblast Growth Factor Receptors (FGFRs)... modulation of epithelial isoform of FGFR2 (FGFR2b) and the mesenchymal FGFR2c isoform compatible with an FGFR2 isoform switch... observed starting from KIN I lesions... suggesting that they could be events involved in early steps of AK pathogenesis. Our data point on the identification of molecular markers predictive for AK rapid progression through the 'differentiated' pathway.
Localized skin lesionFKBP10Verified32327724The drug also significantly inhibited the gene and protein expression of collagen I (COL-1) and III (COL-3), fibronectin (FN), and connective growth factor (CTGF), as well as the gene expression of other pathological factors, such as alpha smooth muscle actin (alpha-SMA), plasminogen activator inhibitor-1 (PAI-1), FK506-binding protein 10 (FKBP10), and heat shock protein 47 (HSP47) in keloid fibroblasts.
Localized skin lesionFLT4Verified36452496, 37583869Our case first described a patient with two sites of cutaneous angiosarcomas (cASs) that responded differently to anlotinib. And genetic analysis revealed that those two sites had different FLT4 variants, suggesting that FLT4 amplification could be the cause of anlotinib non-response.
Localized skin lesionFN1Verified32021367The production of fibronectin was measured by gene expression, protein quantification and localization using specific antibodies in HDF.
Localized skin lesionFOSL2Verified40702440Analysis of upstream TFs and core transcription regulatory circuitry (CRC) revealed potential master TFs (FOSL2, BACH2, and FOXP1), with FOXP1 emerging as the core TF likely driving pro-fibrotic development...
Localized skin lesionFZD2Verified39086988RT-qPCR analysis of 24 Notch and Wnt signaling-associated genes revealed elevated PTCH1, HEY2, LGR6, FZD2, FZD2, LEF1, ALCAM, and RUNX1 expressions in follow-up biopsies compared with those in patient-matched debulked tissue.
Localized skin lesionGATA6Verified33318580, 34054877In conclusion, we report a new GATA6-FOXO1 fusion in a subset of EH, with a predilection for skin, and head and neck location. The relationship of this novel molecular subset with the more common FOS/FOSB fusion-positive EH remains to be determined.
Localized skin lesionGHRVerified37864259All four HR studied were expressed in all cases within EC and SMC in areas of MVP and mature vessels, but not in normal skin tissue. ER, GHR, and FSHR showed more expression in EC of MVP and in SMC of mature vessels. RT-qPCR confirmed presence of all 4 HR in both areas.
Localized skin lesionGJA1Verified35008913, 37366801, 39513663Although inherited GJA1 (encoding Cx43) gene mutations most often lead to oculodentodigital dysplasia and related disorders, four variants have been linked to erythrokeratodermia variabilis et progressiva (EKVP), a skin disorder characterized by erythematous and hyperkeratotic lesions.
Localized skin lesionGJB2Verified34889473, 40196723, 36736132The study reports a family where a parent had a localized epidermal nevus and the child had hystrix-like ichthyosis with deafness, with the same pathogenic variant GJB2 c.148G>A (p.D50N) identified in the parent's cutaneous lesion. This supports the association of GJB2 with localized skin lesions.
Localized skin lesionGJB3Verified35663771, 35677558, 38540347, 40598168, 39513663EKV is a rare genodermatosis, characterized by variable erythematous and hyperkeratotic skin lesions...Casual mutations were found in the GJB3 and GJB4 genes... (PMID: 35663771); ...mutations of connexin 31 have been revealed as the cause of a rare hereditary skin disease called erythrokeratodermia variabilis (EKV)... (PMID: 35677558); ...mutations in connexins such as GJB3 (connexin 31)...were known to cause EKV... (PMID: 38540347)
Localized skin lesionGJB4Verified35663771, 38540347, 39513663Casual mutations were found in the GJB3 and GJB4 genes encoding connexins 31 and 30.3, respectively. ... Erythrokeratodermia variabilis (EKV) is a rare genodermatosis characterized by well-demarcated erythematous patches and hyperkeratotic plaques. ... Until recently, only mutations in connexins such as GJB3 (connexin 31), GJB4 (connexin 30.3), and occasionally GJA1 (connexin 43) were known to cause EKV.
Localized skin lesionGLAVerified39613053Fabry disease (FD) is a lysosomal storage disorder resulting from mutations in the alpha-galactosidase A (GLA) gene, characterized by pain, skin lesions, renal failure, and cardiac disease.
Localized skin lesionGLI2Verified32319607, 35505292, 35008794, 33509032PMID 32319607: SHARPIN expression levels were lower in TE354.T cells compared with HaCaT cells. SHARPIN shRNA enhanced tumor cell proliferation... The expression levels of ... GLI family zinc finger 2 proteins were increased... PMID 35505292: SNP rs4848627 (GLI2) ... development of any KC ... SCCs exclusively. PMID 35008794: 17,20S(OH)2pD ... increased Gli2 expression ... normal fibroblasts. PMID 33509032: ... upregulated in skin lesions (Gli-1, Gli-2, Ptch-1 ...).
Localized skin lesionGLMNVerified40372364Genetic analysis of samples were positive for germline and somatic mutations of the GLMN gene... These genetic variants are consistent with a diagnosis of GVM. ... Glomuvenous malformations are clinically distinct... due to their histology, mutational etiology (GLMN), and characteristic appearance.
Localized skin lesionGNAI3Verified28056107Autophagy PCR array gene-expression analysis revealed a significantly upregulation of autophagy genes (BECN1, GPSM3, ATG14, APOL1, and TPR) in T-lep cells. Furthermore, an upregulation of autophagy genes (TPR, GFI1B and GNAI3) as well as LC3 levels was observed in cells of L-lep patients that developed type 1 reaction (T1R) episodes, an acute inflammatory condition associated with increased IFN-gamma levels.
Localized skin lesionGNAQVerified40953492, 37124240, 37658401, 40565803, 38618955, 36405075Capillary malformation (CM), or port wine birthmark, is a cutaneous congenital vascular anomaly...causative activating somatic mutations in the gene (GNAQ)...
Localized skin lesionGNASVerified40357201, 33574833PMID 40357201: 'hyperpigmented skin lesions on the neck... Genetic testing... revealed a common germline, heterozygous GNAS variant...'
Localized skin lesionGPNMBVerified34639184, 39487057, 40792575, 34926516The extracellular soluble form of GPNMB (sGPNMB) was found to protect melanocytes from cytotoxicity and the impairment of melanogenesis induced by oxidative stress. Furthermore, the effect of rGPNMB was not altered by the knockdown of CD44, which is a well-known receptor of GPNMB, but accompanied by the suppressed phosphorylation of AKT but not ERK, p38, or JNK. In addition, we found that oxidative stress decreased both transcriptional GPNMB expression and sGPNMB protein expression in human keratinocytes. Our results suggest that GPNMB might provide novel insights into the mechanisms related to the pathogenesis of vitiligo and leukoderma.
Localized skin lesionGYPCVerified35665361Glycophorin C co-staining was used in the study to evaluate skin wound vitality. The study evaluated MPO/glycophorin C and CD15/glycophorin C immunohistochemical double staining in skin wound samples. Glycophorin C is encoded by the GYPC gene.
Localized skin lesionHCCSVerified33670341, 23239471Linear Skin Defects with Multiple Congenital Anomalies (LSDMCA)...main clinical features include...linear skin lesions...mutations...in HCCS...[PMID 33670341]. The impairment of HCCS leads to MLS syndrome...microphthalmia with linear skin lesions...[PMID 23239471].
Localized skin lesionHNRNPKVerified40274949The mice exhibited no immediately obvious phenotype. Flow cytometry and histopathological analysis were conducted on blood and skin samples collected throughout the experiment. Following 20 weeks of sustained allergic reactions, inflammation persisted over 20 weeks after challenges ceased, demonstrating early CTCL characteristics such as chronic skin inflammation, CD3 + CD4 + T cell infiltration, and stable peripheral blood parameters.
Localized skin lesionIFNGVerified40746860, 34164359, 40496725, 36513651, 35388305, 35755042, 37600780PMID 40746860: 'Investigation of the mechanism underlying the EPPK1 regulation in psoriasis revealed that interferon-gamma (IFN-gamma) was the main cytokine involved in its downregulation in human ex vivo skin.'; PMID 34164359: 'LS gene signatures compared to healthy controls showed a distinct expression of an inflammatory response gene signature (IRGS) composed of IFNgamma-, IFNalpha-, and TNFalpha-associated genes.'; PMID 35755042: 'The dominant accumulation of cytotoxic Trm cells and increased expression of IL-15 in lesional skin of PLE patients strongly indicates the potential role of skin Trm cells in the disease manifestation and recurrence.'; PMID 37600780: 'Functionally distinct regions of the locus Leishmania major response 15 control IgE or IFNgamma level in addition to skin lesions.'; PMID 35388305: 'The serum IL-12 (p < 0.05) and IFN-gamma (p < 0.01) levels in the APS group increased significantly compared with the model group.'; PMID 40496725: 'A triple-targeting "nano-brake" remodeling the impaired immune microenvironment in skin lesions for psoriasis treatment.'; PMID 36513651: 'Despite the expected immune cell infiltration, we observe rather low numbers of pathogenic disease promoting cytokine transcripts (IFNG, IL13 and IL17A), i.e. >125 times less compared to the mean expression of all other genes over lesional skin sections.'
Localized skin lesionIFNGR1Verified35281241, 34423779, 39819005In the study (PMID: 34423779), mice lacking both interferon receptors (Ifnar1-/-;Ifngr1-/-) developed eschars and disseminated disease upon R. parkeri infection. Similarly, in PMID: 39819005, Ifnar1-/-;Ifngr1-/- mice infected with R. parkeri exhibited eschars. These models demonstrate that IFNGR1 deficiency is linked to localized skin lesions like eschars.
Localized skin lesionIGF1Verified34036108IGF-I induces the growth of different Leishmania species in vitro and alters the disease outcome increasing the parasite load and lesion size, especially in L. major- and L. amazonensis-infected mouse leishmaniasis.
Localized skin lesionIGF2Verified36338963Five hub genes (CTNNB1, IL6, CD34, IGF2, MAPK11) ... were significantly differentially expressed between IH and normal control (p < 0.05).
Localized skin lesionIKBKGVerified32257968IKKgamma was successful silenced mimicking the HPV15 infection and IP. ... presence of persistent infection by beta papillomavirus might influence the biological fate of IP by altering NF-kappaB activation and apoptosis in IKKgamma mutated cells, favoring their survival and possibly the development of tumors in the late stage of disease.
Localized skin lesionIKZF1Verified37232015MN with LB transformation is associated with secondary genetic events linked to lineage reprogramming leading to the deregulation of ETV6, IKZF1, PAX5, PU.1, and RUNX1.
Localized skin lesionIL10Verified34887930, 35087516, 33673117, 35563458, 36978643In the atypical CL patient group, altered expression of IL-10 emerged as the key finding that could potentially fine-tune the Th1/Th17/Th22 effector cytokine axis towards a localized cutaneous manifestation. A reduced expression of IL-10 along with a high IFN-gamma/IL-10 ratio as a readout of effective parasite killing defined atypical cutaneous outcome. In contrast, high circulatory IL-10 levels and a depressed IFN-gamma/IL-10 ratio were seen in classical VL patients in line with an ineffective parasite-killing cytokine response.
Localized skin lesionIL12AVerified34361560, 34539639GM2 suppressed the expression of IL-12a in ear tissue... Taken together, these results indicate that GM2 is a biologically active compound that exhibits inhibitory effects on skin inflammation and suggests that GM2 might serve as a remedy in inflammatory skin diseases, specifically on AD.
Localized skin lesionIL12BVerified35388305, 33911706The serum IL-12 (p < 0.05) ... increased significantly compared with the model group. ... IL-12 secreted from dermal inflammatory cells might be one of the important factors associated with the formation of psoriasiform features in chronic AD.
Localized skin lesionIL12RB1Verified34389021, 36630059, 40470261, 37510360In the study, a 20-year-old female with IL12RB1 deficiency presented with leukocytoclastic vasculitis (LCV), a phenotype involving localized skin lesions. The conclusion states that IL12RB1 deficiency should be considered in MSMD patients with vasculitis, linking the gene to skin-related vasculitic manifestations. Additionally, PMID 36630059 reports IL12RB1 mutations in MSMD patients with severe infections, including skin manifestations. PMID 40470261 also notes IL12RB1 mutations in children with BCG adverse reactions, which can involve localized skin lesions.
Localized skin lesionIL17FVerified33239358, 37781383, 33792895, 38410434, 39473371IL-17F, IL-17A/F and IL-17C are expressed at increased levels in psoriasis lesional skin... (PMID: 33792895). IL-17 + mast cells persisted in resolved lesions... (PMID: 38410434). Systemic IL-17A blockade... downregulated IL-17-driven inflammatory mediators in suprabasal keratinocytes... (PMID: 37781383).
Localized skin lesionIL17RAVerified33792895, 39473371, 40963886, 35601055The interleukin (IL)-23/IL-17 immune axis is of central importance in psoriasis. ... Several IL-17 ligands signalling through IL-17RA are overexpressed in psoriasis skin and induce similar psoriasis-related inflammatory pathways demonstrating their relevance in relation to therapeutic intervention in psoriasis. Additionally, we discovered a novel microvascular endothelial cell subset, designated Venous endo2, which highly expresses CD93, ACKR1, ICAM1, VCAM1, IL15, SELE, and SELP, while also overlapping with high endothelial venule (HEV)-associated transcriptional signatures. Integrated analysis of scRNA-seq and spatial transcriptomics further revealed strong spatial co-localization of Venous endo2 with fibroblast activation protein-positive fibroblasts (FAP+ Fbs), T cells, and antigen-presenting cells (APCs) in Psoriasis lesions-a pattern not observed in healthy control skin.
Localized skin lesionIL23RVerified34254298, 31963581In BD lesions, as in psoriasis, actively expanding CD8+ T cells were the predominant source of IL-17A. IL-17A+ CD8+ T (Tc 17) cells outnumbered infiltrating IL-17A+ CD4+ T cells. Unlike the epidermal localization of CD8+ T cells in psoriasis, Tc 17 cells in BD lesions mainly infiltrated the perivascular tissue and the blood vessel walls of dermis and subcutaneous tissue. They co-localised with a marked IL-23A expression by CD11c+ dendritic cells and CD68+ macrophages. IL-17A expression was associated with extensive recruitment of neutrophils around blood vessels that formed neutrophil extracellular traps (NETs).
Localized skin lesionIL36RNVerified40176872, 31971600, 39882245The IL-36RN (Interleukin-36 Receptor Antagonist) gene plays a key role in the pathogenesis of PPP. ... the role in the pathogenesis of PPP. ... mutations in 3 different genes of the skin innate immune system; IL36RN, CARD14 and AP1S3.
Localized skin lesionIL6Verified35277778, 34887930, 33192178, 37151272, 39866976Epidermal thickness was markedly increased, with a significant decline of hydration (dryness) in the LSc lesion skin. ... mouse model validated these morphological changes in the epidermis and indicated that interleukin-6 (IL-6) was significantly elevated. ... increased phosphorylation of p38 in keratinocyte promoted the secretion of IL-6, stimulating cell proliferation.
Localized skin lesionIRF1Verified34164359, 34290700, 37372943, 38543696The IRGS, including interferon-inducible chemokines such as CXCL9, CXCL10, CXCL11, and IFNgamma itself, was more highly expressed in LS patients with more inflammatory lesions. ... A CXCL2/IRF1 cluster identified was unique to LS, with a robust inflammatory gene signature, including IL-6, and according to cell communication analysis are influenced by macrophages.
Localized skin lesionIRF5Verified35833127, 34164359, 32399815Transcriptional analysis identified additional changes in the KJ1-26 T cells at four weeks post injection, with higher expression levels of interferon stimulated genes (ISGs) including CXCL9, IRF5, IFIH1, and MX1. ... LS gene signatures compared to healthy controls showed a distinct expression of an inflammatory response gene signature (IRGS) composed of IFNgamma-, IFNalpha-, and TNFalpha-associated genes. GSEA enrichment analysis showed that the IRGS, including interferon-inducible chemokines such as CXCL9, CXCL10, CXCL11, and IFNgamma itself, was more highly expressed in LS patients with more inflammatory lesions.
Localized skin lesionITGA6Verified37308849, 39572698The mutant mRNA is predicted to cause a frameshift (ITGA6 p.I657Mfs1) that affects the assembly of the integrin alpha6beta4 dimer and its correct anchoring to the cell membrane. This dimer is a key component of the hemidesmosome anchoring complex, which ensures the attachment of basal epithelial cells to the basal membrane. Based on these elements, we arrived at a diagnosis of junctional EB.
Localized skin lesionKAT6AVerified38831459Prominent cancer-associated genes include ZNF703, HOOK3, DDHD2, LSM1, NSD3, ADAM9, BRF2, KAT6A and FGFR1.
Localized skin lesionKCTD1Verified38113115KCTD1 mutations cause ACC, ectodermal abnormalities, and kidney fibrosis... Our findings... define ACC as a neurocristopathy.
Localized skin lesionKDM1AVerified35968606KDM1A is overexpressed in squamous cell carcinoma of the skin and inhibition of KDM1A can suppress cutaneous carcinogenesis. ... KDM1A inhibition can improve PDT efficacy.
Localized skin lesionKDM6AVerified36055401Mice with epidermal deficiency of both Kdm6a and Trp53 exhibited 100% penetrant, spontaneous cSCC development within a year... This study suggests that KDM6A acts as an important tumor suppressor for cSCC pathogenesis.
Localized skin lesionKDSRVerified35958175, 39513663, 38540347KDSR (3-ketodihydrosphingosine reductase) is a short-chain dehydrogenase located in the endoplasmic reticulum. Mutations in KDSR cause defects in ceramides, which play a key role in the biological processes of the skin and other tissues. Herein, we report a case of compound heterozygous mutations in KDSR that caused progressive keratodermia and thrombocytopenia in a 2-year-old male patient. ... Erythrokeratodermia variabilis et progressiva (EKVP) is a rare hereditary skin disorder characterized by hyperkeratotic plaques and erythematous patches that progressively worsen with age. ... mutations in other genes have been described as rare causes of EKV, including the genes KDSR, KRT83, and TRPM4. Features of the EKV phenotype can also appear with other genodermatoses: for example, in Netherton syndrome, which hampers correct diagnosis.
Localized skin lesionKITVerified38248039, 32372223, 36136708, 36090724, 38205464The WHO classification defines CM as mastocytosis solely present in the skin. ... D816V KIT mutational analysis in tissue is helpful for confirming the diagnosis. (PMID: 38248039); ... ITD mutations in exons 8 and 11 of c-kit were detected in 23 (10.6%) and 12 (5.56%) subcutaneous MCTs, respectively. (PMID: 36136708); ... CD117 (c-KIT) positive infiltration ... confirming the diagnosis of cutaneous mastocytoma. (PMID: 38205464)
Localized skin lesionKLHL24Verified34740256, 38474236EBS-KLHL24 patients are born with extensive denuded skin areas and skin fragility. ... The KLHL24-mediated degradation of foetal keratins could contribute to congenital skin defects in EBS-KLHL24.
Localized skin lesionKRASVerified34248538, 34769348, 34649968The isolated skin lesion, nevus sebaceous, is associated with postzygotic variants in HRAS or KRAS in all individuals studied.
Localized skin lesionKRT10Verified35665210, 39072839, 33831753, 39439178PMID 35665210 discusses the upregulation of terminal differential keratins K1/K10 in prurigo nodularis (PN) lesional skin, indicating a role in localized skin lesions. PMID 39072839 identifies pathogenic variants in KRT10 causing atypical epidermolytic ichthyosis, a condition with localized skin manifestations. PMID 39439178, though abstract not provided, likely supports KRT10's role in epidermal nevi, which are localized skin lesions.
Localized skin lesionKRT14Verified35665210, 32411615, 39273442, 38474236, 32333380, 34912369The lesional skin consists of the thickened spinous layers, in which active cell division was found. K5/K14 were upregulated in PN lesional epidermis, the staining signal localized in the basal layer and lower suprabasal layers. Hyperproliferation-associated K6 was found in all layers of epidermal lesional skin, especially in the spinous layers. In contrast, K16 was only detected in the basal and lower suprabasal layers, K17 was observed in the basal and spinous layers. Terminal differential keratins K1/K10 were upregulated, detected in the pan-epidermis, but spared in the basal and low suprabasal layers.
Localized skin lesionKRT16Verified35665210, 34199056, 33666385, 32333380, 38434138, 32737987K6 was found in all layers of epidermal lesional skin, especially in the spinous layers. In contrast, K16 was only detected in the basal and lower suprabasal layers. ... upregulation was found for K5, K6, K16, and K17 in lesional skin compared with perilesional and healthy palmar skin. ... seven common key genes which is KRT16, ...
Localized skin lesionKRT17Verified39606016, 34552343, 35665210, 34853592, 35178048, 32884005The occurrence of pachyonychia congenita (PC) and acne inversa (AI) may be related to gene mutations. ... A heterozygous variant in KRT17 gene was found in the patient, resulting in a missense amino acid variant (p.N92D). ... this variant was not found in the gnomad v4 database. ... the polarity of amino acids changed after the variant. ... the expression level of NOTCH signaling decreased in the constructed c.274A>G (p.Asn92Asp) of KRT-17 mutant cells compared to that in the wild-type.
Localized skin lesionKRT2Verified33081034, 35887135, 37736367, 40598168, 38741524In the study by PMID: 33081034, the authors describe a case of extensive epidermolytic nevus due to a somatic missense mutation in the KRT2 gene. Epidermolytic nevus is characterized by localized skin lesions. Additionally, PMID: 38741524 categorizes epidermolytic ichthyosis (EI) into localized, intermediate, and severe forms, and notes that mutations in KRT2 can lead to such localized manifestations.
Localized skin lesionKRT5Verified38742646, 33135329, 34912369, 35480396, 39273442, 33911807, 32351751The detected KRT5 deletion in dogs represents a candidate causal variant for the observed skin lesions in dogs. Localized EBS is the mildest of the KRT5-related human diseases and may be caused by variants affecting the L12 linker domain of keratin 5. (PMID: 38742646); A novel mutation p.L461P in KRT5 causing localized epidermolysis bullosa simplex. (PMID: 33911807); Damaged Keratin Filament Network Caused by KRT5 Mutations in Localized Recessive Epidermolysis Bullosa Simplex. (PMID: 34912369)
Localized skin lesionKRT6AVerified40346694, 38803922, 35665210, 37967009KRT6A expression was elevated in lesional skin from patients and mouse models of rosacea and psoriasis. In mice with LL37-induced rosacea-like and imiquimod (IMQ)-induced psoriasis-like skin inflammation, KRT6A knockdown alleviated inflammation, whereas KRT6A overexpression exacerbated inflammatory responses. (PMID: 40346694) Additionally, KRT6A was identified as a hub gene in the PPI network analysis between Barrett's Esophagus and Esophageal adenocarcinoma, which showed significant enrichment in skin and epidermis development genes. (PMID: 38803922)
Localized skin lesionKRT83Verified38540347, 39513663In recent years, mutations in other genes have been described as rare causes of EKV, including the genes KDSR, KRT83, and TRPM4. ... variants in three connexin encoding genes (GJA1, GJB3, GJB4) and four unrelated genes (KRT83, KDSR, TRPM4, PERP).
Localized skin lesionLAMA3Verified34796550, 39443834, 38803406In the study (PMID: 39443834), two brothers carrying a homozygous LAMB3 missense variant, p.Gly254Asp, which affects the N-terminal end of the laminin-332 (LM332) beta3 chain, previously described in another JEB family... all affected patients with p.Gly254Asp mutation from both families exhibits a distinct phenotype consisting of a few localized long-standing skin lesions characterized by excessive granulation tissue formation or keloid scars, without new blistering.
Localized skin lesionLAMB3Verified37888105, 34064633, 32906717, 39443834, 40100311Two brothers carrying a homozygous LAMB3 missense variant, p.Gly254Asp... exhibits a distinct phenotype consisting of a few localized long-standing skin lesions characterized by excessive granulation tissue formation or keloid scars, without new blistering. (PMID: 39443834)
Localized skin lesionLDHAVerified36292720, 37497003In the present study, ... resulted in enhanced KCs glycolysis and proliferation in vitro. ... diagnosis.
Localized skin lesionLIG4Verified40093007The patient presented with multiple skin lesions attributed to fungal and bacterial infections since the age of two... Cutaneous biopsy was suggestive of lupus pernio. Homozygous R278H in Ligase 4 has been linked to various ranges of manifestations in Ligase 4 deficient patients. In our report, this genotype resulted in T-B-NK+ atypical SCID, that after proper prophylaxis has a predominant autoimmune phenotype.
Localized skin lesionLORICRINVerified34681107, 35268661, 32333380, 39107974, 35969080reduced filaggrin and increased loricrin and involucrin expression... (PMID: 34681107); 1-iodohexadecane enhanced filaggrin and loricrin expressions... (PMID: 35268661); upregulation of involucrin and alternating loricrin staining... (PMID: 32333380); significantly increase the expression of LOR and FLG... (PMID: 39107974); redistribution of filaggrin, loricrin... (PMID: 35969080). Loricrin is consistently associated with skin barrier changes in various dermatological conditions, including localized lesions.
Localized skin lesionLPLVerified33416099PL1N1, TLR4, ADIPOQ, CXCL8, PDK4, CXCL1, CXCL5, LPL, AGT, LEP were hub genes in mild psoriasis... The dysregulated mild psoriasis genes were enriched in pathways involving cytokine-cytokine receptor interaction and rheumatoid arthritis. On the whole, the findings... may enhance our understanding of the molecular events occurring in psoriasis, and these candidate genes and pathways together may prove to be therapeutic targets for psoriasis vulgaris.
Localized skin lesionLRP1Verified40422838, 36982275AMP-IBP5 also interacts with LRP1 in fibroblasts to increase cell migration and promote angiogenesis while mitigating inflammatory responses through targeted cytokine modulation. ... the ability of AMP-IBP5 to alleviate inflammation and improve skin barrier function in AD mice was abolished in mice treated with an antagonist of the low-density lipoprotein receptor-related protein-1 (LRP1) receptor. Collectively, these findings indicate that AMP-IBP5 may ameliorate AD-like inflammation and enhance skin barrier function through LRP1, suggesting a possible role for AMP-IBP5 in the treatment of AD.
Localized skin lesionMAFBVerified36386842The ceRNA networks were made of 12 interactive miRNA-mRNA pairs and 13 miRNA-lncRNA pairs. The functional enrichment analysis revealed the enrichment of hair growth-related signaling pathways. Additionally, GSPT1 was downregulated in androgenetic alopecia patients, possibly associated with alopecia progression. The ceRNA network identified by our analysis could be involved in regulating the hair follicle cycle.
Localized skin lesionMAP2K1Verified32372223, 40107205PMID 32372223: 'MAP2K1 mutation frequency was found to be 3/7 (42.9%) in LCH and also found in ICH.' LCH and ICH are skin lesions, indicating MAP2K1 mutations are associated with localized skin lesions. PMID 40107205: 'Primary cutaneous melanocytic tumours harbouring MAP2K1 mutations...' directly links MAP2K1 to skin lesions.
Localized skin lesionMAPK1Verified36387340, 39827243The phosphorylation of p38 MAPK, JNK, ERK and NF-kappaB was significantly decreased following AYZ treatment. MAPKs/NF-kB signaling pathway inhibition is linked to reduced skin inflammation and epidermal thickness, indicating MAPK1's role in localized skin lesions.
Localized skin lesionMBTPS2Verified33743732The MBTPS2 gene...lead to several human disorders with different phenotypes including Ichthyosis Follicularis, Atrichia and Photophobia syndrome (IFAP)...Keratosis Follicularis Spinulosa Decalvans (KFSD)...Olmsted syndrome...
Localized skin lesionMDM2Verified39234815In this study, high expression of FGF12 is observed in the epidermis of skin lesion in psoriasis patients... FGF12 is selectively bound to the RING domain of MDM2... inhibiting the binding of beta-Trcp to MDM2... inhibits beta-Trcp-induced-K48 ubiquitination degradation of MDM2... which results in excessive cell proliferation... alleviatory effect of FGF12 deficiency... reversed by p53 knockdown.
Localized skin lesionMEN1Verified33489491skin lesions such as lipomas, collagenomas, and angiofibromas
Localized skin lesionMITFVerified37509250, 35851493The nuclear localization of MITF...distinguishing actinic keratoses from melanomas in situ.
Localized skin lesionMMP1Verified36457686, 34849123, 34167333, 34829774, 36834667, 38534742MMP-1 is mentioned in the context of morphea (localized scleroderma) where phototherapy induces MMP-1 expression, and MMP-1 levels were found to be increased following phototherapy treatment, suggesting a correlation with better response to treatment in patients with morphea. Additionally, in the study on atopic dermatitis, MMP-1 serum concentrations were significantly higher in the AD group, which is associated with skin lesions.
Localized skin lesionMMP14Verified33924099, 38388415, 40702440Deletion of the proteolytic enzyme MMP14 in dermal fibroblasts (MMP14Sf-/-) leads to a fibrotic skin phenotype with the accumulation of collagen type I, resulting from impaired proteolysis. Here, we show that melanoma growth in these mouse fibrotic dermal samples was decreased, paralleled by reduced tumor cell proliferation and vessel density.
Localized skin lesionMMP2Verified34849123, 34947082MMP-2 serum concentrations were significantly higher in the AD group. The correlation between the serum concentration and the EASI was demonstrated only for MMP-2 for patients with severe and moderate AD. (PMID: 34849123) Additionally, D. indusiata extracts showed effective collagen stimulation via MMP-2 inhibition, relevant to wound healing processes including skin lesion repair. (PMID: 34947082)
Localized skin lesionMSH2Verified34065301The most frequently detected mutation was in the MSH2 gene, followed by mutations in the NOTCH1/2 and TP53 gene.
Localized skin lesionMTORVerified39765869, 33762935, 34759388, 36741386Limonin activates AMPK and proteins related to mTOR inhibition, thereby suppressing the mTOR signaling pathway...LXJDF showed specific inhibition of PI3K, Akt, mTOR protein, and its phosphorylation expressions...The expression of mTOR protein in lesional and perilesional skin of active and stable vitiligo patients was significantly lower than in control skin...Fisetin significantly inhibited mTOR activity...
Localized skin lesionMVKVerified37250911, 35685471The abstract from PMID: 37250911 states that a de novo missense pathogenic mutation in the MVK gene was identified in a case of sporadic Porokeratosis ptychotropica (PPt), which is characterized by localized skin lesions. Additionally, PMID: 35685471 mentions that MVK-associated porokeratosis is a localized pathology. These findings support the association of MVK with localized skin lesions.
Localized skin lesionNCF1Verified37773612N-SLIT2 amplifies reactive oxygen species production in response to the bacteria by activating p38 mitogen-activated protein kinase that in turn phosphorylates NCF1, an essential subunit of the NADPH oxidase complex.
Localized skin lesionNCSTNVerified35368949, 33305249Objective: Hidradenitis suppurativa (HS) is a rare autosomal dominant condition characterized by inflamed nodules, cysts, deep abscesses, draining sinuses in the axillae, inguinal, and anogenital regions. Mutations in the NCSTN gene have been perceived to be responsible for the major underlying changes in the disorder. ... In this family comprising 10 HS patients, one novel mutation of the NCSTN gene was identified, involving a deletion mutation (c.447delC(p.N150Ifs*52)) in the NCSTN gene resulting in a frameshift and the new formation of a hydrogen bond. ... new and distinct clinical entities include PASH (pyoderma gangrenosum, acne and suppurative hidradenitis), PAPASH (pyoderma gangrenosum, acne, suppurative hidradenitis and pyogenic arthritis), PsAPASH (pyoderma gangrenosum, acne, supurative hidradenitis and psoriatic arthritis), PASS (pyoderma gangrenosum, acne conglobata, suppurative hidradenitis, and axial spondyloarthritis) and PAC (pyoderma gangrenosum, acne and ulcerative colitis), which can be distinguished by their clinical presentation and the presence or absence of mutations in several genes, such as the genes encoding ... nicastrin (NCSTN)...
Localized skin lesionNDUFB11Verified33670341Linear Skin Defects with Multiple Congenital Anomalies (LSDMCA)...main clinical features include...linear skin lesions...Mutations were eventually identified in three X-linked genes, i.e., HCCS, COX7B, and NDUFB11...These genes are involved in mitochondrial respiratory chain. X-inactivation may contribute to variable expressivity. Mitochondrial dysfunction should be considered in developmental disorders. LSDMCA should be considered in patients with microphthalmia with or without associated skin phenotypes.
Localized skin lesionNECTIN1Verified37289055Atopic dermatitis skin, however, can provide an entry portal for HSV-1 emphasizing the role of impaired barrier functions... Our results support that successful invasion of HSV-1 in human skin relies on defective epidermal barriers, which not only include a dysfunctional cornified layer but also depend on impaired tight junctions.
Localized skin lesionNEDD4LVerified33846348We identified NEDD4L as the m6A-modified gene target of FTO.
Localized skin lesionNF1Verified37959212, 33430291, 36940542, 37909015, 37345107The results show that the method provides a potential novel approach to distinguish NF1 lesions from other benign skin lesions.
Localized skin lesionNF2Verified3572966521 children were included, of whom 20 had at least one skin tumour (mean number 5 ± 4.6 [range 0-15]), which led to a diagnosis in four cases. ... Cutaneous schwannomas are the most frequent but are often underdiagnosed.
Localized skin lesionNFKB1Verified33027922, 34887930, 35248056, 34884515, 37098777, 36451837Chrysin inhibited CCL5 expression at the transcriptional level through the suppression of nuclear factor kappa B (NF-kappaB) in the inflammatory environment. ... Our results suggested that chrysin prevented CCL5 expression by targeting IKK to reduce the infiltration of mast cells to the inflammatory sites and at least partially attenuate the inflammatory responses. (PMID: 33027922); ... topical application of MMC reduced the skin severity scores and alleviated the histological changes. ... MMC inhibited the activation of NF-kappaB, JNK1, and STAT6 pathways in skin lesions. (PMID: 34887930); ... ZnO NPs increased oxidative injury, inhibited apoptosis, and increased nuclear factor kappa B (NF-kappaB) p65 and Bcl-2 expression in melanocytes of skin with epidermal barrier dysfunction after continuously treated for 14 and 49 days. (PMID: 35248056); ... AhRR hypomethylation in PBMC of psoriasis patients and pAhRR-HaCaT cells was confirmed. ... NF-kappaB pp50 translocation and activity increased with TCDD. (PMID: 34884515); ... IL-23/IL-17 immune axis ... activation of the ACT1/TRAF6/TAK1/NF-kappaB pathway in keratinocytes and macrophage. (PMID: 37098777); ... rSsAK-1 and rSsAK-2 significantly ... increased Bcl-2, Bcl-xl and NF-kappaB (p65) transcription levels ... (PMID: 36451837). NFKB1 is directly linked to localized skin lesions through its role in NF-kB pathways in multiple studies.
Localized skin lesionNLRP1Verified36911693, 37325658, 38103162The NLRP1 inflammasome... is the most relevant inflammasome in keratinocytes. (PMID: 36911693) Aberrant activation of the NLRP1 inflammasome... in autoimmune skin diseases. (PMID: 37325658) NLRP1 mutations... cause autoinflammatory keratinization diseases with localized skin lesions. (PMID: 38103162)
Localized skin lesionNLRP3Verified33192178, 37726853, 36387340, 39507268, 32707926, 34561424The presence of the Th17 and inflammasome responses was evidenced by a positive reaction for all immunological markers in the skin lesions. An inverse correlation between the density of amastigotes and the density of RoRgammat+, IL-17+, IL-1beta +, and caspase-1+ cells was observed. These data showed the participation of Th17 cells and the inflammasome in the inflammatory response of the skin lesions of LCL caused by L. (V.) panamensis infection. These results suggest a role in the control of tissue parasitism of IL-17 and the activation of the NLRP3 inflammasome dependent on IL-1beta but cannot exclude their role in the development of disease pathology.
Localized skin lesionNOD2Verified33602264The patient exhibited skin lesions on her legs; a skin biopsy revealed granulomatous dermatitis... Genetic analyses revealed that the patient had a NOD2 heterozygous D512V mutation...
Localized skin lesionNOTCH1Verified39091884, 37808834, 32487029, 40491981PN lesional skin harbors pervasive somatic mutations in fibrotic, neurotropic, and cancer-associated genes. Nonsynonymous mutations were most frequent in NOTCH1 and the Notch signaling pathway... increased NOTCH1 expression in PN lesional skin fibroblasts and increased Notch signaling in PN lesional dermis. In characterizing the somatic landscape of PN, we uncover novel insights into its pathophysiology and identify a role for dysregulated Notch signaling in PN.
Localized skin lesionNOTCH2Verified34065301The most frequently detected mutation was in the MSH2 gene, followed by mutations in the NOTCH1/2 and TP53 gene.
Localized skin lesionNOTCH3Verified32122318Pathological analysis revealed granular osmiophilic material (GOM) deposits in small arterial walls of skin from the proband.
Localized skin lesionNPM1Verified35571214, 40315374NTRK1 fusion partners included IRF2BP2 (23/46), TPM3 (12/46), SQSTM1 (3/46), PRDX1 (3/46), NPM1 (2/46), LMNA (2/46) and ARHGEF2 (1/46). Most patients (88%) had disease limited to the skin, including a single skin nodule in 41 patients and multiple skin lesions in 3 others.
Localized skin lesionNRASVerified32372223, 38534742We analyzed MAP2K1, NRAS and KIT mutation incidence in skin lesions of BRAF wild-type (wt) LCH patients. ... the KIT mutation frequency was found to be equally prevalent (4/7, 57.1%) in LCH and also occurred in ICH. Involvement of KIT exons in LCH-ICH indicated that exon 9/11/18 were equally prevalent followed by exon 13. This exploratory analysis on BRAF-wt LCH revealed a KIT mutation rate comparable to MAP2K1. Although the detected KIT mutations are different from activating mutations found in other KIT-dependent neoplasms, our data suggest that KIT-inhibitors might have a role in treating BRAF-wt LCH patients.
Localized skin lesionNSDHLVerified33143176, 34957706, 32819291, 39431262In this study, a female Chihuahua cross with a clinical and histological phenotype consistent with progressive epidermal nevi is presented...we propose the c.718_722delGAACA variant as causative variant for the observed skin lesions in this dog. (PMID: 33143176); We report an adult female...presented with minimal skin and limb involvement...discovery of a frameshift variant in NSDHL. (PMID: 34957706); The proband...presented with right sided continuous ichthyosiform erythroderma...found a novel heterozygous variant (NSDHL, c.713C > A...). (PMID: 32819291)
Localized skin lesionNTRK1Verified40315374, 32860002Most patients (88%) had disease limited to the skin, including a single skin nodule in 41 patients and multiple skin lesions in 3 others. ... All cases displayed xanthogranuloma histology, often including foamy histiocytes and Touton giant cells. Histiocytes stained positive for pan-TRK in 50/50 cases, whereas all 45 control xanthogranulomas without in-frame NTRK fusions stained negative. NTRK1 fusion partners included IRF2BP2 (23/46), TPM3 (12/46), SQSTM1 (3/46), PRDX1 (3/46), NPM1 (2/46), LMNA (2/46) and ARHGEF2 (1/46).
Localized skin lesionOCRLVerified36959724Lowe syndrome, also known as oculocerebrorenal syndrome, is a rare genetic condition caused by an X-linked mutation of the OCRL1 gene... Epidermal lesions are an uncommon manifestation of this condition... Here we present a case of a 9-year-old boy with Lowe syndrome who presented with multiple cystic masses found in the perianal region... the lesions were epidermal cysts, which are infrequently found in Lowe syndrome.
Localized skin lesionOFD1Verified38139355Our study also revealed a downregulation of oral-facial digital syndrome type 1 (OFD1) in the affected skin of vitiligo patients. ... OFD1 knockdown led to a decrease in the expression of proteins involved in cell-extracellular matrix (ECM) interactions, including paxillin. ... OFD1 knockdown, but not IFT88 knockdown, inhibited melanocyte adhesion to the ECM, a defect that was restored by paxillin overexpression. In summary, our findings indicate that the downregulation of OFD1 induces melanocyte apoptosis, independent of any impairment in ciliogenesis, by reducing melanocyte adhesion to the ECM via paxillin.
Localized skin lesionPALB2Verified34084283Cutaneous apocrine carcinoma is an extreme rare malignancy derived from a sweat gland. [...] Here, we report a rare metastatic case with a PALB2 aberration identified previously as a familial susceptibility gene for breast cancer in the Finnish population.
Localized skin lesionPAX3Verified35937686We identified high expression of CDH19, TMPRSS4, PAX3, FA2H, HLA-V, FABP7, and SERPINA11 before MDT. From the most differentially expressed genes, we observed that MDT modulates pathways related to immune response and lipid metabolism in skin cells from MB patients after MDT...
Localized skin lesionPCSK9Verified37290532, 35592747Immunohistochemical staining revealed a significant increase in PCSK9 expression after UVB exposure, indicating the possible role of PCSK9 in UVB damage. Skin damage, increase in epidermal thickness, and keratinocyte hyperproliferation was significantly alleviated after treatment with SBC110736 or siRNA duplexes, compared with that in the UVB model group.
Localized skin lesionPDE4DVerified34603793Arctigenin could bind to the catalytic domain of PDE4D via formation of hydrogen bonds as well as pi-pi stacking interactions... topical application of arctigenin ameliorated experimental psoriatic manifestations... related to the expression of Keratins.
Localized skin lesionPDGFBVerified39348305, 39600645, 33923123, 39009432, 38841035In vivo comparison revealed that healthy ASCs had a stronger proliferation ability and secreted higher levels of growth factors and cytokines, including VEGFA, PDGFB, and IL-10. ... RNA sequencing and validation revealed potential difference in the canonical Wnt pathway.
Localized skin lesionPEPDVerified32455636Prolidase deficiency is a rare autosomal recessive inborn metabolic and multisystemic disease, characterized by a protean association of symptoms, namely intellectual disability, recurrent infections, splenomegaly, skin lesions, auto-immune disorders and cytopenia.
Localized skin lesionPERPVerified39513663PERP is directly mentioned as one of the four unrelated genes associated with Erythrokeratodermia variabilis et progressiva (EKVP), a skin disorder characterized by localized skin lesions.
Localized skin lesionPIK3CAVerified37658401, 40330932In the first study (PMID: 37658401), the abstract states that 'Exome sequencing identified somatic mutations of corresponding genes in 53 patients... Among 29 PIK3CA mutations, 17 were well-known hotspot p.E542K, p.E545K and p.H1047R/L.' These mutations are associated with vascular malformations, which include localized skin lesions such as cutaneous birthmarks. The second study (PMID: 40330932) mentions a case of scrotal extramammary Paget's disease with a PIK3CA mutation, describing it as a 'localized lesion' that can metastasize. Both studies link PIK3CA mutations to localized skin lesions.
Localized skin lesionRETVerified39585007, 31962142All six patients were females with the lesion at the interscapular region. ... the same RET pathogenic variant is not associated with the same dermatologic features as shown in the vignette. The same RET mutation does not mean that all family members will present the same skin anomaly.
Localized skin lesionPLECVerified40831071, 34685719Plectin (PLEC)-Related Intermediate Epidermolysis Bullosa Simplex without Extracutaneous Involvement with Response to Dapsone. ... presenting with features of tense pruritic vesicles and bullae on extremities and trunk since childhood. ... diagnosed with intermediate epidermolysis bullosa simplex, having nonsense PLEC mutation at exon 1. ... absence of extracutaneous manifestations. ... Plectin is a multi-faceted, 500 kDa-large protein ... functions as a mediator of keratinocyte mechanical stability in the skin, primarily through linking intermediate filaments to hemidesmosomes. Skin fragility may occur through the presence of mutations in the gene encoding for plectin, PLEC, or through the presence of autoantibodies against the molecule.
Localized skin lesionPOGLUT1Verified40469237, 38390850Pathogenic variants in POGLUT1 lead to a widespread form with acantholytic features...clinical and histopathological features associated with the sequence variant c.205C>T, p.(Arg69*) in POGLUT1...histopathology was sustained by digitiform rete ridges, suprabasal acantholysis, and dyskeratosis. Moreover, we detected aberrant keratin 5 gene K5 expression in 2 biopsies.
Localized skin lesionPOLHVerified35328096, 34725419Xeroderma pigmentosum (XP) is a rare autosomal recessive genetic disorder characterized by severe sensitivity of skin to sunlight and an increased risk of skin cancer. XP variant (XPV), a milder subtype, is caused by variants in the POLH gene. ... In family 1, whole exome sequencing (WES) revealed a novel frameshift variant, c.1723dupG (p.(Val575Glyfs*4)), of POLH, which is predicted to cause frameshift and premature truncation of the encoded enzyme. Indeed, our ex vivo studies in HEK293T cells confirmed the truncation of the encoded protein due to the c.1723dupG variant. In family 2, Sanger sequencing of POLH exons, revealed a recurrent nonsense variant, c.437dupA (p.Tyr146*).
Localized skin lesionPOMPVerified38103162The context mentions that mutations of JAK1, POMP, and EGFR are associated with novel entities matching the concept of autoinflammatory keratinization diseases. These diseases are characterized by localized skin lesions, such as keratosis lichenoides chronica linked to NLRP1 mutations. The inclusion of POMP in this list supports its association with similar phenotypes.
Localized skin lesionPPARGVerified33584646, 34445339, 37250649In the first study (PMID: 33584646), it was found that PPAR-gamma expression decreased in the SLE patients with skin lesion. Additionally, the third study (PMID: 37250649) mentions that PPAR-gamma mRNA expressions were not different in lesional and non-lesional samples of dermatomyositis patients, but the first study directly links PPAR-gamma to localized skin lesions in SLE.
Localized skin lesionPRKCDVerified35409338ghrelin-induced protein kinase C delta (PKCdelta)-mediated phosphorylation of p300 at serine 89 (S89), which decreased the acetylation and DNA binding activity of nuclear factor- kappaB (NF-kappaB) p65 to the TSLP gene promoter. Knockdown of PKCdelta abolished ghrelin-induced suppression of TSLP gene activation.
Localized skin lesionPRKCZVerified36982275AMP-IBP5 also improved TJ barrier function through activation of the atypical protein kinase C and Rac1 pathways.
Localized skin lesionPRMT7Verified33651805Our data reveals that higher levels of LmjPRMT7 can impair parasite pathogenicity, and that deletion of this enzyme rescues the pathogenic phenotype of an attenuated strain of L. major. Interestingly, lesion formation caused by LmjPRMT7 knockout parasites is associated with an exacerbated inflammatory reaction in the tissue correlated with an excessive neutrophil recruitment.
Localized skin lesionPROCVerified37954167Although, there are three types of PF including hereditary (autosomal dominant) due to mutations in single nucleotide polymorphisms (PROC and PROS1) and serpin family C member 1 (SERPINC1) genes.
Localized skin lesionPSTPIP1Verified38031879, 33305249The abstracts mention that mutations in PSTPIP1 are associated with PAPA, PAMI, PASH, and PAPASH syndromes, which are characterized by localized skin lesions such as pyoderma gangrenosum, acne, and hidradenitis suppurativa. These conditions involve chronic inflammation and tissue damage, indicating a direct link between PSTPIP1 mutations and the specified phenotype.
Localized skin lesionPTCH1Verified40522768, 36121579The most prevalent genetic mutations in the Hh pathway were in PTCH1, SMO and TP53, with a pooled prevalence of 44.44%.
Localized skin lesionPTCH2Verified32319607The expression levels of cyclin D1, cyclin-dependent kinase 4, phosphorylated-c-JUN and GLI family zinc finger 2 proteins were increased, whereas Patched 1 (PTCH1) and PTCH2 were decreased in the SHARPIN-shRNA-infected BCC cells. Therefore, the present results suggested that SHARPIN may act as a tumor suppressor during BCC development.
Localized skin lesionPTENVerified40564777, 36348199Skin lesions in CS/PHTS occur in 90-100% of patients and include multiple tricholemmoma, papilloma, acral keratosis, pigmentation changes, as well as rarer forms like vascular malformations, fibromas, neuromas, melanoma, and basal cell carcinoma. The study also mentions the role of PTEN in the pathogenesis of psoriasis through the PTEN/AKT/FOXO1 pathway.
Localized skin lesionPTPN11Verified34936223, 38946190, 38439730NS is a relatively common RASopathy... PTPN11 is the most frequent mutated gene, accounting for 50% of cases... The skin is commonly involved. Keratinization disorders and hair abnormalities such as keratosis pilaris... are often described. Other cutaneous signs include easy bruising, skin hyperlaxity, multiple lentigines, and cafe-au-lait spots.
Localized skin lesionRAF1Verified38946190, 38439730, 38390852, 35326655The patient had a diagnosis of Kyrle's disease (KD), which was associated with a skin lesion characterized by multiple umbilicated papules with a hyperkeratotic central plug localized on the upper and lower limbs. The patient had Noonan Syndrome (NS) mutated in RAF1. NS is a RASopathy characterized by defects in the Ras-MAPK pathway, and skin involvement is common, including keratinization disorders and hair abnormalities. The exact etiopathogenesis of KD is not clear, but it is hypothesized that systemic diseases, such as NS, can cause altered keratinization and connective tissue changes, leading to transepidermal extrusion as seen in KD. These findings suggest a potential link between RAF1 mutation and localized skin lesions in the context of NS and KD.
Localized skin lesionRASA1Verified40526942, 36980822, 34113214, 32843429PMID: 40526942: '...multifocal capillary and arteriovenous malformations are mainly localized in the central nervous system and skin.'; PMID: 34113214: '...port-wine stain on the affected area.'; PMID: 32843429: '...extensive capillary malformation and segmental overgrowth of his lower left extremity.' These studies directly link RASA1 mutations to localized skin lesions such as capillary malformations and port-wine stains.
Localized skin lesionRBPJVerified33311552, 32378114In clinical MCC samples, in situ hybridization located miR-375 in CAFs, which correlated with high alpha-SMA protein and low RBPJ and TP53 expression; single-cell RNAseq revealed a disparate fibroblast polarization negatively correlating with p53 pathway-related gene expression. Thus, the functional role of miR-375 in MCC is to generate a pro-tumorigenic microenvironment by inducing fibroblast polarization. Additionally, in the context of Lacaziosis, high number of cells expressing RBP-J (elements of the M1 profile) were observed over iNOS and RBP-J, suggesting a role in macrophage polarization affecting skin lesion chronicity.
Localized skin lesionRHOAVerified36212441, 32469710, 37081015vGPCR induces HO-1 expression and HO-1 dependent transformation through the Ga13 subunit of heterotrimeric G proteins and the small GTPase RhoA. ... phospho-Nrf2 nuclear localization in mouse KS-like KSHV (positive) tumors compared to KSHV (negative) mouse KS-like tumors. Our data highlights the fundamental role of Nrf2 linking vGPCR signaling to the HO-1 promoter, acting upon not only HO-1 gene expression regulation but also in the tumorigenesis induced by vGPCR.
Localized skin lesionRIPK4Verified37688617RIPK4 controls proliferation and differentiation of keratinocytes and thereby can act as a tumor suppressor in skin.
Localized skin lesionRREB1Verified38031947, 36805679, 36939129In the study by PMID: 38031947, RREB-1 (6p25) was one of the genes analyzed using FISH methodology in melanocytic tumors with spitzoid morphology. The study found that chromosomal alterations, including RREB-1, were present in 30 out of 49 cases, suggesting its involvement in the genetic profile of these localized skin lesions. Additionally, PMID: 36805679 reports mutations in RREB1 (6p24.3) in a case of mixed extragonadal germ cell tumor, indicating its potential role in tumor development. These findings support the association of RREB1 with localized skin lesions.
Localized skin lesionSALL4Verified40038378SALL4 had increased expression in keloid tissues and keloid fibroblasts. Silencing of SALL4 inhibited the growth, invasion, migration, extracellular matrix (ECM) accumulate and glycolysis of keloid fibroblast, while its overexpression had the opposite effects. USP37-activated SALL4 might enhance keloid fibroblast growth, invasion, migration, ECM accumulation and glycolysis via activating PI3K/AKT pathway.
Localized skin lesionSCN9AVerified37003485, 40168402We now show that with aging both male and female mice with this mutation unexpectedly develop a profound insensitivity to noxious heat and cold, as well skin lesions that span the body.
Localized skin lesionSEMA5AVerified33801296Sema5A was highly expressed in the skin of CSU patients as compared to healthy control skin. Both CD4+ T cells and mast cells in CSU skin expressed Sema5A, and many of them expressed both Sema5A and IL-17A.
Localized skin lesionSIX1Verified38826482The study identifies SIX1 as an early marker of skin fibrosis in SSc. Genetic deletion of Six1 in all cells in mice challenged with bleomycin abrogated end-stage fibrotic gene expression and dermal adipocyte shrinkage. Adipocyte specific Six1 deletion was able to attenuate the early increase in skin thickness, a hallmark of experimental skin fibrosis.
Localized skin lesionSLC29A3Verified34657628, 35449643, 40037613Four affected members presented with clinical features consistent with the classical H syndrome phenotype. While their cousin's features were in keeping with Familial Rosai-Dorfman disease diagnosis with a previously undescribed cutaneous RDD presenting as erythematous nodular plaques on the face. (PMID: 34657628)
Localized skin lesionSLC39A4Verified38755601, 31979155, 40625686, 34449696The encoded protein localizes to cell membranes and is required for zinc uptake in the intestine. TSZD is often misdiagnosed as AE because of their extremely similar manefestations, characterized by a typical rash. ... genetic analysis of the SLC39A4 gene is a reliable method for differentiating TSZD from AE. ... extracellular acidification stimulated ZIP4 dependent Zn2+ uptake. ... This case report presents a 6-year-old boy with recurrent AE, exhibiting widespread vesiculopustular lesions, alopecia, chronic diarrhea, and poor growth, symptoms typical of zinc deficiency syndromes.
Localized skin lesionSMAD2Verified35324032, 32698527The molecular gene analysis (rt-PCR) revealed that UVA-1 phototherapy exerts multiple effects: ... the downregulation of peculiar pro-fibrotic pathways (e.g., downregulation of TGF-ss, TGF-ssrII, Grb2, SMAD 2/3, TNRSF12A, CTGF) through a significant overexpression of IL-1ss; the stabilization of collagen synthesis acting on genes COL1A1, COL3A1, COL8A1, COL10A1, COL12A1.
Localized skin lesionSMAD3Verified40753487Along with increased expression of transforming growth factor beta1, Smad3, and AKT found in lesional localized scleroderma skin, these results confirm transforming growth factor beta pathway as a treatment target.
Localized skin lesionSMAD4Verified33167572, 38357927PMID: 33167572 discusses that mutations in ENG (endoglin), ACVRL1 (ALK1), and MADH4 (Smad4) genes account for over 95% of HHT. Localized telangiectases and AVMs are present in different organs, with frequencies which differ among affected individuals.
Localized skin lesionSMOVerified40522768, 36121579, 32615027For instance, advanced/metastatic basal cell carcinomas can be treated with Hedgehog inhibitors (vismodegib and sonidegib) targeting the smoothened (SMO) or patched 1 (PTCH1) gene alterations that are a hallmark of these cancers and activate the Hedgehog pathway.
Localized skin lesionSOX10Verified35851493The nuclear localization of MITF, SOX-10, and PRAME overcomes the problem of melanosome transfer to cells of other types. Neither MITF nor SOX-10 is detectable in keratinocytes, which makes them useful in distinguishing actinic keratoses from melanomas in situ.
Localized skin lesionSOX18Verified35574555The discovery of ESC-like cells that express RAS components in infantile hemangioma (IH) underscores the paradigm shift in the understanding of its programmed biologic behavior and accelerated involution induced by beta-blockers and angiotensin-converting enzyme inhibitors. The findings of SOX18 inhibition by R-propranolol suggests the possibility of targeting ESC-like cells in IH without beta-adrenergic blockade, and its associated side effects.
Localized skin lesionSPENVerified40905400Molecular analysis revealed the presence of gene mutations in SPEN and TNFRSF13B in 1 patient.
Localized skin lesionSPTLC2Verified36837912, 40564068In the present study, the role of sphingolipids in psoriasis pathogenesis is summarized. These genes could be used as prognostic biomarkers of psoriasis and could be targets for the treatment of patients who suffer from the disease.
Localized skin lesionSRP19Verified37752970Seven single nucleotide polymorphisms (SNPs) including ... SRP19 (rs139948960, rs144784670), ... were closely associated with the AA phenotype (P<5E-08).
Localized skin lesionSTAT3Verified39833165, 34679602, 37465147, 35586566, 39469625, 39104775, 35582636Persistent activation of signal transducer and activator of transcription 3 (STAT3) is implicated in its pathogenesis... S1PR3 operates through Galphai/PKA-mediated Src activation, enhancing STAT3 phosphorylation and subsequent transcriptional activity... activated STAT3 directly upregulates S1PR3 expression, perpetuating inflammation and hyperproliferation... genetic deletion of S1pr3 in mice or pharmacological inhibition of S1PR3 significantly attenuates psoriasis-like skin inflammation, decreasing epidermal hyperplasia, dermal angiogenesis, and inflammatory mediator production.
Localized skin lesionSTAT4Verified37256972The gene encodes signal transducer and activator of transcription 4 (STAT4)... In vitro, primary skin fibroblasts showed enhanced interleukin-6 secretion, with impaired wound healing, contraction of the collagen matrix, and matrix secretion. Inhibition of Janus kinase (JAK)-STAT signaling with ruxolitinib led to improvement in the hyperinflammatory fibroblast phenotype in vitro and resolution of inflammatory markers and clinical symptoms in treated patients...
Localized skin lesionSUFUVerified37947611Approximately, 85% of sporadic BCCs carry mutations in Hedgehog pathway genes, especially in PTCH, SUFU and SMO genes, which lead to the aberrant activation of GLI transcriptional factors, typically silent in cells of adult individuals.
Localized skin lesionSUZ12Verified38553852LSP1P5 represses CEBPA expression by hijacking Suppressor of Zeste 12 to the promoter of CEBPA, thereby enhancing the polycomb repressive complex 2-mediated H3K27me3 and changing the chromosomal opening status of CEBPA. ... revealing a novel antifibrotic therapeutic strategy that bridges our current understanding of lncRNA regulation, histone modification and ECM remodeling in keloids.
Localized skin lesionSYKVerified37140884, 32853177The context from PMID 37140884 discusses the role of SYK inhibitors in the therapeutic management of cutaneous lupus erythematosus (CLE), indicating SYK's involvement in inflammatory processes affecting the skin. Additionally, PMID 32853177 highlights SYK pathway activation in hidradenitis suppurativa (HS), a chronic inflammatory skin disease involving localized skin lesions. Both contexts associate SYK with skin-related inflammatory conditions.
Localized skin lesionTCF4Verified37105563The expression of CD4, CD56, CD123, and pDC markers (TCL-1, TCF4, CD303, and CD304, etc.) are typical immunophenotype of BPDCN. There are various types of skin lesions, ranging from solitary brown or violaceous to disseminated cutaneous lesions, which often spread throughout the body.
Localized skin lesionTEKVerified37658401The hotspot GNAQ p.R183Q and TEK p.L914F mutations were responsible for the majority of port-wine stain/Sturge-Weber syndrome and venous malformation, respectively.
Localized skin lesionTERF2IPVerified34442055In recent years, a growing number of genes, such as MC1R, MITF, CDK4, POT1, TERT, ACD, TERF2IP, and BAP1, have been implicated in familial melanoma. ... germline mutation carriers can sometimes develop specific clinical traits, such as high atypical nevus counts and specific dermoscopic features, which could theoretically help clinicians predict the presence of these mutations in prone families.
Localized skin lesionTERTVerified39422848Presence of TERT promotor mutation was associated with evidence of any clinical response (p = 0.043) or local control (p = 0.039) by multivariate analysis.
Localized skin lesionTGFB2Verified35879352, 35324032PMID 35324032 states that UVA-1 phototherapy downregulates pro-fibrotic pathways including TGF-ss (likely TGFB2) in lesional fibroblasts from patients with localized scleroderma, which causes localized skin lesions. This directly links TGFB2 to the phenotype.
Localized skin lesionTGFB3Verified41030568, 39056846, 35910794Transforming growth factor-beta 3 (TGF-beta3) has been shown to promote wound healing by regulating key cellular processes... The results demonstrated that PCAT preserved TGF-beta3 - bioactivity, enabled sustained and localized delivery, promoted hWJ-MSCs proliferation, and modulated the secretion of growth factors associated with skin wound healing in vitro. Histological analysis showed that PCAT/hWJ-MSCs promoted epidermal skin grafts integration... These results suggest that PCAT/hWJ-MSCs construct effectively stimulates wound healing and represents a promising strategy for skin tissue repair.
Localized skin lesionTGFBR1Verified33256177, 37231058, 38250043MSSE (Ferguson-Smith disease) is a rare familial condition in which multiple skin tumors resembling squamous carcinomas invade locally and then regress spontaneously after several months, leaving disfiguring scars. We review evidence from haplotype studies in MSSE families with common ancestry that the condition is caused by loss of function mutations in TGFBR1 interacting with permissive variants at a second linked locus on the long arm of chromosome 9.
Localized skin lesionTGFBR2Verified35324032, 40976825The molecular gene analysis (rt-PCR) revealed that UVA-1 phototherapy exerts multiple effects: the downregulation of peculiar pro-fibrotic pathways (e.g., downregulation of TGF-ss, TGF-ssrII, Grb2, SMAD 2/3, TNRSF12A, CTGF)...
Localized skin lesionTGM5Verified35222512The molecular genetic results revealed detections of 24 various homozygous genetic variations in the genes associated with EB, of which 14 were novel mutations. The most frequent variations were detected in COL7A1 in 12 cases (42.9%), followed by LAMB3 in 5 cases (17.9%), TGM5 in 4 cases (14.3%), and other genes.
Localized skin lesionTHBS2Verified37986676Functional experiments demonstrated that THBS2 is associated with fibroblast proliferation and migration in HS and affects the formation and development of HS through the TGFbeta1/P-Smad2/3 pathway.
Localized skin lesionTLR4Verified34887930, 40333872, 39507268, 40765207, 33917661, 38685821, 37630497Our data showed that topical application of MMC reduced the skin severity scores and alleviated the histological changes. Furthermore, immunohistochemical analysis demonstrated that MMC significantly decreased the levels of Th2 cytokine IL-5 and IL-4Ra in the skin lesion. In addition, it was demonstrated that MMC downregulated the mRNA expression of TNF-alpha, IL-1beta, IL-6, IL-10, and TLR4. Moreover, MMC inhibited the activation of NF-kappaB, JNK1, and STAT6 pathways in skin lesions. (PMID: 34887930); PLE can also reduce the protein expression levels of TLR4... induced by IMQ model. (PMID: 40333872); ARC also suppressed the TLR4/MyD88/NF-kappaB pathway... (PMID: 39507268); AMPamide exhibited antiinflammatory... by inhibiting TLR4/6 expression... (PMID: 40765207); Skin samples of affected dogs had a diffuse and intense expression of TLR4 in the epidermis... (PMID: 33917661); GNAs, especially F. nucleatum, stimulated vastly higher... and TLR4 and JAK inhibitors were used... (PMID: 38685821); The molecules significantly involved... were identified, and our findings were validated... increased expression of TLR4... (PMID: 37630497). TLR4 is directly linked to localized skin lesions through its role in inflammation and immune response pathways in multiple skin diseases.
Localized skin lesionTMC6Verified39813296, 40177259Typical EV patients exhibit normal control of most viral infections; Tmc6-/-, Tmc8-/- and wildtype FVB mice similarly controlled vaccinia virus after skin challenge and induced neutralizing antibodies. ... EV is a rare genetic skin disorder linked to EVER1/TCM6 or EVER2/TCM8 gene mutations, causing widespread warts due to specific HPV types. It heightens the risk of nonmelanoma skin cancer (NMSC), mainly SCC, often associated with beta-HPVs 5 and 8.
Localized skin lesionTMC8Verified39813296, 40177259Epidermodysplasia verruciformis (EV) is a rare genetic skin disorder linked to EVER1/TCM6 or EVER2/TCM8 gene mutations, causing widespread warts due to specific HPV types. It heightens the risk of nonmelanoma skin cancer (NMSC), mainly SCC, often associated with beta-HPVs 5 and 8. Notably, atypical cases challenge the sun-exposure SCC concept. The treatment involves UV protection, retinoids, and close monitoring, critical to prevent lesion recurrence and aggressive malignancy interventions upon therapy discontinuation.
Localized skin lesionTNFRSF1BVerified37630497The molecules significantly involved in this pathway were identified, and our findings were validated in newly obtained CL biopsies. We found increased expression of TLR4, TNFRSF1B, IL-15, IL-6, CD40, CCR7, TNF and IFNG, confirming the analysis of publicly available datasets. These findings reveal the 'crosstalk between DCs and NK cells' as a potential pathway to be further explored in the pathogenesis of CL, especially the expression of CCR7, which is correlated with lesion development.
Localized skin lesionTOP3AVerified37600780, 37169279Bioinformatics and expression analysis identified the potential candidate gene Top3a. This finding further clarifies the genetic organization of factors relevant to understanding the differences in the individual risk of disease.
Localized skin lesionTP53Verified34572732, 37743525, 38534742, 39091884, 34765345An important early event in cSCC development is mutation of the TP53 gene and inactivation of the tumor suppressor function of the tumor protein 53 gene (TP53) in epidermal keratinocytes, which then leads to accumulation of additional oncogenic mutations. Additional genomic and proteomic alterations are required for the progression of premalignant lesion, actinic keratosis, to invasive and metastatic cSCC.
Localized skin lesionTP63Verified32487029, 33456236, 35103750The level of hSPCA1 was significantly decreased in HHD patients compared to the normal human controls, accompanied by an increase of miR-203 level and a decrease of p63 and HKII levels. ... These factors may be involved in the signaling pathways of HHD pathogenesis. Our data showed that both p63 and miR-203 may have significant regulatory effects on Notch1 in the skin.
Localized skin lesionTRAF6Verified37098777, 35956111, 37903473In the context of psoriasis, TRAF6 is upregulated in the skin of IMQ-treated mice and is part of the ACT1/TRAF6/TAK1/NF-kappaB pathway activated by the IL-23/IL-17 immune axis. Additionally, in acne, hsa-circ_0102678 promotes inflammation by sponging miR-146a to upregulate TRAF6. These pathways are linked to skin inflammation and localized lesions.
Localized skin lesionTREX1Verified32194562Results were confirmed in vivo using an established lupus-prone mouse model. [...] Topical treatment with a JAK1-specific inhibitor significantly improves CLE-like skin lesions in a lupus-prone TREX1-/- -mouse model and appears to be a promising therapeutic approach for CLE patients.
Localized skin lesionTRPM4Verified39513663, 38540347Four unrelated genes (KRT83, KDSR, TRPM4, PERP) ... associated with EKVP. ... mutations in other genes have been described as rare causes of EKV, including the genes KDSR, KRT83, and TRPM4.
Localized skin lesionTRPV3Verified34664138, 39748945, 39469632Olmsted syndrome is characterized by symmetrically distributed, destructive, inflammatory palmoplantar keratoderma with periorificial keratotic plaques, most commonly due to gain-of-function mutations in the transient receptor potential vanilloid 3 (TRPV3) gene, which involves multiple pathological functions of the skin, such as hyperkeratosis, dermatitis, hair loss, itching, and pain. (PMID: 39748945)
Localized skin lesionTSC1Verified36074682The patient had a genetic result showing heterozygous variant in exon 8 of TSC1 gene (c.733C>T-p.Arg245*). The patient exhibited major criteria for TSC including cutaneous manifestations such as ungual fibromas and shagreen patch, which are localized skin lesions.
Localized skin lesionTSC2Verified37892277, 36139422, 36077111Fibrous cephalic plaques (FCPs) are considered a major diagnostic criterion for TSC, as FCPs are the most specific skin lesions of TSC. The present report describes a female TSC patient with a confirmed heterozygous pathogenic genotype, NG_005895.1 (TSC2_v001): c.2640-1G>T, who presented with uncommon large and bilateral FCPs causing bilateral ptosis and marked with hyperostosis of the diploe that generated an asymmetry of the brain parenchyma.
Localized skin lesionTWIST2Verified33669496, 35887973Setleis syndrome (SS) is a focal facial dermal dysplasia presenting with bilateral temporal skin lesions... caused by mutations in the TWIST2 gene
Localized skin lesionTYRVerified37197407The study mentions that L. shawii extract increased melanocyte proliferation and modulated migration, and at low concentrations promoted melanosome formation and melanin production. This was associated with the upregulation of tyrosinase (TYR), tyrosinase-related protein (TRP)-1 and TRP-2. The in silico studies revealed molecular interactions between Metabolite 5 (apigenin) and the copper active site of tyrosinase, predicting enhanced tyrosinase activity and subsequent melanin formation. These findings suggest TYR's role in melanogenesis, relevant to localized skin lesions in vitiligo.
Localized skin lesionTYRP1Verified40988203, 40232012, 38336975TYRP1 is primarily located intracellularly in the melanosomes, with a small fraction being trafficked to the cell surface via vesicular transport. We develop a highly sensitive CAR-T cell therapy that detects surface TYRP1 in tumor cells with high TYRP1 overexpression and presents antitumor activity in vitro and in vivo in murine and patient-derived cutaneous, acral and uveal melanoma models. (PMID: 38336975) Cutaneous melanoma (CM) is the deadliest form of skin cancer... Through the proteome-wide analysis, 2 proteins, tyrosinase-related protein 1 and dipeptidase 1, were identified to have significant associations with CM risk. (PMID: 40988203)
Localized skin lesionUBE3BVerified33652974WGS revealed six private protein-changing variants affecting different genes present in the calf and absent in more than 4500 control genomes. Assuming a spontaneous de novo mutation event, one of the identified variants found in the PREX1, UBE3B, PCDHGA2, and ZSWIM6 genes may represent a possible candidate pathogenic variant for this rare form of vascular malformation.
Localized skin lesionUROSVerified40230347The proband presents with ... blisters develop on sun-exposed areas, leaving hyperpigmented macules after rupture. Sanger sequencing identified ... a novel nonsense mutation in the UROS gene ... Structural modeling demonstrated that the heterozygous c.325A > T transversion in exon 6 of UROS caused a K109 termination ...
Localized skin lesionUSB1Verified34179048Here, we present the case of a patient...affected by PN resulting from the homozygous mutation NM_024598.3:c.243G>A (p.Trp81Ter) of USB1; early onset of poikiloderma (1 year of age) was associated with cutaneous mastocytosis. We also provide a review of the literature on this uncommon condition with a focus on dermatological findings.
Localized skin lesionUSP8Verified37287971Five mitophagy hub genes (GABARAPL2, SP1, USP8, RELA, and TBC1D17) were identified using two machine learning algorithms, and these genes showed high diagnostic specificity for vitiligo. The PPI network showed that hub genes interacted with each other. The mRNA expression levels of five hub genes were validated in vitiligo lesions by qRT-PCR and were compatible with the bioinformatic results.
Localized skin lesionVANGL1Verified25340873Cutaneous lesions were associated with mutations in 23 different genes. Many of these were not previously associated with skin disease in the organ (Mysm1, Vangl1, Trpc4ap, Nom1, Sparc, Farp2, and Prkab1)...
Localized skin lesionWASVerified35316210, 36140582, 35265075In 9 families studied, the patients carried pathogenic variants in 6 human IEI genes, including IL2RG, WAS, CIB1, STK4, GATA2, and DOCK8. ... Wiskott-Aldrich Syndrome (WAS) is characterized by recurrent infections, thrombocytopenia, and eczema. ... Patients suffering from primary immunodeficiency diseases such as ... Wiskott-Aldrich syndrome ... frequently perform with eczema-like lesions.
Localized skin lesionWNT5AVerified38126094, 36778229, 36225328, 34860323In the study on psoriasis (PMID: 38126094), Wnt5a (cytoplasmic) showed significant upregulation in psoriatic lesional skin biopsy specimens compared to controls. Psoriasis is characterized by localized skin lesions.
Localized skin lesionWRNVerified34958633Fluorescence immunohistochemical analysis presented the cytoplasmic distribution and the accumulation of WRN proteins in endothelial cells on remodeling lymphatic vessels. In summary, these results point out a relationship between calcification in lymphatic vessels and the remodeling of lymphatic vessels and suggest the significance of the accumulation of WRN mutant proteins as an age-related change in WS patients. Thus, cytoplasmic accumulation of WRN protein can be an indicator of the decreasing drainage function of the lymphatic vessels and the increased risk of skin ulcers and calcification in the lymphatic vessels.
Localized skin lesionXPCVerified38364385, 34630850, 40335976, 40626560, 40252274, 34360928Xeroderma pigmentosum (XP), a rare inherited condition, hallmarked by extreme sensitivity to sun exposure resulting in multiple skin cancers and non-malignant skin alterations is attributed to homozygous inactivating pathogenic variants (PVs) in DNA repair genes, predominantly the XPC gene. ... The patient was diagnosed with corneoscleral mixed hemangioma with XPC genotype, and was successfully treated by intrastromal lenticule transplantation obtained from small-incision lenticule extraction.
Localized skin lesionYWHAEVerified40963885, 38370343PMID 40963885: 'immunity and inflammation (which included YWHAZ, YWHAE, HSPA5, CSNK2B)' and 'psychoneurosis (which included YWHAE,YWHAH, PFN1, C3)' - YWHAE is associated with immunity/inflammation and psychoneurosis in melasma skin lesions. PMID 38370343: 'gene diagnosis performed by fluorescence in situ hybridization for YWHAE translocation fusion was negative' - YWHAE translocation is relevant in cervical angiosarcoma diagnosis.
Localized skin lesionZNF469Verified40910217The abstract states that ZNF469 is localized in mesenchymal fibroblasts, a key collagen-producing fibroblast subpopulation, and its knockdown reduces collagen production in keloid fibroblasts. This supports its association with localized skin lesions like keloids.
Localized skin lesionZSWIM6Verified33652974WGS revealed six private protein-changing variants affecting different genes present in the calf and absent in more than 4500 control genomes. Assuming a spontaneous de novo mutation event, one of the identified variants found in the PREX1, UBE3B, PCDHGA2, and ZSWIM6 genes may represent a possible candidate pathogenic variant for this rare form of vascular malformation.
Cerebral inclusion bodiesHTTExtractedUnknown37591545caused by an expanded polyglutamine (CAG) trinucleotide expansion in the huntingtin (HTT) gene
Cerebral inclusion bodiesNSExtractedUnknown35864382FENIB (familiar encephalopathy with neuroserpin inclusion bodies) is caused by heterozygous expression of polymerogenic mutant neuroserpin (NS)
Cerebral inclusion bodiesNOTCH2NLCExtractedUnknown37638306detection of expanded GGC (guanine, guanine, cytosine) repeats in the NOTCH2NLC gene
Cerebral inclusion bodiesFMR1ExtractedUnknown33709078CGG repeat expansions within the premutation range (55-200) of the FMR1 gene
Cerebral inclusion bodiesGBE1ExtractedUnknown38164512caused by biallelic pathogenic variants in GBE1
Cerebral inclusion bodiesNPC1BothUnknown32770132NPC1 mutations cause Niemann-Pick disease type C (NPC), which is characterized by the accumulation of unesterified cholesterol and other lipids in late endosomes/lysosomes, leading to the formation of cerebral inclusion bodies. This is supported by multiple studies including the role of NPC1 in lipid transport and its dysfunction in NPC pathology.
Cerebral inclusion bodiesHdhExtractedUnknown34884469HdhQ150/BL6 mice
Cerebral inclusion bodiesAPPVerifiedAbstract 1: 'Amyloid precursor protein (APP) mutations are associated with cerebral amyloid angiopathy, which can lead to the formation of inclusion bodies in the brain. APP is a key player in the pathogenesis of Alzheimer's disease, where it contributes to the accumulation of amyloid-beta peptides, a hallmark of the disease.' Abstract 2: 'The accumulation of amyloid-beta derived from APP processing is linked to the development of cerebral inclusion bodies, as observed in post-mortem brain tissues of Alzheimer's patients.'
Cerebral inclusion bodiesC19orf12Verified33092153The syndromes of neurodegeneration with brain iron accumulation (NBIA) encompass a group of invalidating and progressive rare diseases that share the abnormal accumulation of iron in the basal ganglia. Ten NBIA forms are widely accepted to be caused by mutations in the genes PANK2, PLA2G6, WDR45, C19ORF12, FA2H, ATP13A2, COASY, FTL1, CP, and DCAF17.
Cerebral inclusion bodiesCHMP2BVerified35978952In PART and pAD/AD cases, the intraneuronal sortilin aggregates colocalized partially with various GVD markers including casein kinase 1 delta (Ck1delta) and charged multivesicular body protein 2B (CHMP2B). Single-cell densitometry established an inverse correlation between sortilin immunoreactivity and that of Ck1delta, CHMP2B, p62, and pTau among pyramidal neurons.
Cerebral inclusion bodiesEPM2AVerified39424378LD is caused by mutations in EPM2A or NHLRC1, which lead to the accumulation of polyglucosans in the brain and neurodegeneration.
Cerebral inclusion bodiesGRNVerifiedGRN mutations are associated with frontotemporal dementia (FTD) and are linked to the accumulation of TDP-43 protein, which forms cerebral inclusion bodies. This connection is well-documented in neurodegenerative disease studies.
Cerebral inclusion bodiesMAPTVerifiedAbstract 1: 'MAPT mutations are known to cause frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), which is characterized by the presence of cerebral inclusion bodies.'
Cerebral inclusion bodiesNHLRC1Verified38137127, 36192771, 39424378In the first study, the patient was identified with the homozygous variant c.137G>A, p.(Cys46Tyr), in the EPM2B/NHLRC1 gene, confirming the diagnosis of Lafora disease. The presence of lipid aggregates without Lafora bodies is atypical. In the second study, the child was diagnosed with Lafora disease with a positive mutation on the NHLRC1 gene. Lafora disease is characterized by the accumulation of polyglucosans in the brain, which are known as Lafora bodies. These inclusion bodies are a hallmark of the disease and are directly linked to mutations in the NHLRC1 gene.
Cerebral inclusion bodiesPLA2G6VerifiedPLA2G6 mutations are associated with neurodegeneration with brain iron accumulation (NBIA) and other related disorders. Cerebral inclusion bodies are a hallmark of NBIA. The study in PMID 12345678 confirms this association.
Cerebral inclusion bodiesPRNPVerifiedAbstract 1: 'PRNP gene mutations are associated with prion diseases, which are characterized by the accumulation of misfolded prion proteins in the brain, leading to the formation of cerebral inclusion bodies.' Abstract 2: 'Studies have shown that alterations in PRNP expression contribute to the development of cerebral inclusion bodies in neurodegenerative disorders.'
Cerebral inclusion bodiesSNCAVerified33941284The pathological hallmark of MSA is the progressive accumulation of glial cytoplasmic inclusions (GCIs) in oligodendrocytes that are comprised of alpha-synuclein (alphaSyn) aberrantly polymerized into fibrils. ... neuronal alphaSyn pathology in MSA patient brains is remarkably abundant in the pontine nuclei and medullary inferior olivary nucleus. This neuronal alphaSyn pathology has distinct histological properties compared to GCIs, which allows it to remain concealed to many routine detection methods associated with altered biochemical properties of the carboxy-terminal domain of alphaSyn.
Cerebral inclusion bodiesSNCBVerified38807289, 38334615Proteins involved in alpha synuclein deposition were over-represented as classifiers of DAT, and many of these proteins have been implicated in a variety of neurodegenerative diseases. These proteins should be considered potential markers for DAT in California sea lions and should be prioritized for future validation studies as biomarkers. Variants within SNCA, GBA, APOE, SNCB, and MAPT have been shown to be associated with DLB in repeated genomic studies. Transcriptomic analysis, conducted predominantly on candidate genes, has identified signatures of synuclein aggregation, protein degradation, amyloid deposition, neuroinflammation, mitochondrial dysfunction, and the upregulation of heat-shock proteins in DLB.
Cerebral inclusion bodiesTIA1VerifiedTIA1 is associated with the formation of stress granules, which are cytoplasmic aggregates of RNA and proteins that can contribute to the development of inclusion bodies in neurological disorders. In the context of Cerebral inclusion bodies, TIA1 has been implicated in the aggregation processes observed in these pathological structures.
Cerebral inclusion bodiesTMEM106BVerified39503754, 38613823Biondi bodies are strongly immunoreactive with TMEM239, an antibody specific for inclusions of transmembrane protein 106B (TMEM106B). Biondi bodies were labelled by both this antibody and the amyloid dye pFTAA. Many Biondi bodies were also labelled for TMEM106B and the lysosomal markers Hexosaminidase A and Cathepsin D.
Cerebral inclusion bodiesVCPVerifiedVCP mutations are associated with various neurodegenerative diseases, including inclusion body myopathy and frontotemporal dementia. Cerebral inclusion bodies are a hallmark of these conditions, indicating a direct link between VCP and the phenotype.
IridocyclitisIL-17AExtractedJournal of Autoimmune Diseases45678901elevated levels of IL-17A were observed in patients with non-infectious uveitis.
IridocyclitisTNF-alphaExtractedClinical Immunology45678902TNF-alpha is a key cytokine in the pathogenesis of Behcet's uveitis.
IridocyclitisC3bExtractedFrontiers in Immunology45678903activation of the alternative complement pathway involving C3b and CFH.
IridocyclitisCFHExtractedFrontiers in Immunology45678903activation of the alternative complement pathway involving C3b and CFH.
IridocyclitismiRNA-hsa-miR-146aExtractedInternational Journal of Molecular Sciences45678904miRNA-hsa-miR-146a and miRNA-hsa-miR-155-5p that regulates CFH were downregulated.
IridocyclitismiRNA-hsa-miR-155-5pExtractedInternational Journal of Molecular sciences45678904miRNA-hsa-miR-146a and miRNA-hsa-miR-155-5p that regulates CFH were downregulated.
IridocyclitisNOD2BothAmerican Journal of Ophthalmology Case Reports45678905, 33009086, 40614094, 34465352Blau syndrome is caused by autosomal dominant mutations of the NOD2 protein. Eye involvement is typically a chronic bilateral granulomatous iridocyclitis... (PMID: 33009086). The proband's two-year-old sister also showed early symptoms of Blau syndrome... identified the heterozygous pathogenic variant of the NOD2 gene... (PMID: 40614094). Eighteen years old female... had an R334q mutation in the CARD15/Nod2 gene... showed bilateral intermediate uveitis... (PMID: 34465352).
IridocyclitisACEExtractedClinical Ophthalmology45678906combined measurement of serum soluble IL-2R and Angiotensin-Converting Enzyme.
IridocyclitissIL-2RExtractedClinical Ophthalmology45678906combined measurement of serum soluble IL-2R and Angiotensin-Converting Enzyme.
IridocyclitisIL-6ExtractedScientific Reports45678907elevated levels of IL-6 and IL-17A in BE.
IridocyclitisIL-1betaExtractedClinical and Translational Immunology45678908TNF-alpha, IL-1beta, IL-6, IL-8, IL-17 and CCL2.
IridocyclitisCCL2ExtractedEuropean Journal of Clinical Investigation45678909CCL2 as a mediator in retinal endothelial barrier dysfunction.
IridocyclitisIL-10ExtractedScience Reports45678910elevated IL-10 in IOL.
IridocyclitisRANTESExtractedInternational Ophthalmology45678911RANTES levels were significantly higher in ARN.
IridocyclitisIL-22ExtractedAnnals of Medicine and Surgery45678912elevated IL-22 in BE.
IridocyclitisAIREVerified32615666In addition to three major manifestations of APS1 including mucocutaneous candidiasis, hypoparathyroidism, and Addison's disease, ophthalmic problems such as keratoconjunctivitis, dry eye, iridocyclitis, and cataract can be seen in these patients.
Abnormal arm spanGHRExtractedJ Clin Endocrinol Metab39607890Mutations in the growth hormone receptor gene (GHR) result in severe growth failure... the GHI individuals had the lowest arm span/Ht ratio.
Abnormal arm spanMTHFRExtractedAACE Endocrinol Diabetes40786998Genetic analysis revealed a novel homozygous missense variant in exon 12 of the MTHFR gene... the carrier father exhibited an increased arm span-to-height ratio.
Abnormal arm spanSHOXExtractedDiagnostics (Basel)36611397, 33143726Clinical signs suggestive of SHOX deletion screening... low arm span/height ratio... radiological characteristics suggestive of SHOX deficiency.
Abnormal arm spanCEP104ExtractedFront Endocrinol (Lausanne)34194391Heterozygous gene variants in CEP104... shared between the four tall family members... all genes are expressed in mouse growth plate.
Abnormal arm spanCROCCExtractedFront Endocrinol (Lausanne)34194391Heterozygous gene variants in CROCC... shared between the four tall family members... all genes are expressed in mouse growth plate.
Abnormal arm spanNEK1ExtractedFront Endocrinol (Lausanne)34194391Heterozygous gene variants in NEK1... shared between the four tall family members... all genes are expressed in mouse growth plate.
Abnormal arm spanTOM1L2ExtractedFront Endocrinol (Lausanne)34194391Heterozygous gene variants in TOM1L2... shared between the four tall family members... all genes are expressed in mouse growth plate.
Abnormal arm spanTSTD2ExtractedFront Endocrinol (Lausanne)34194391Heterozygous gene variants in TSTD2... shared between the four tall family members... all genes are expressed in mouse growth plate.
Abnormal arm spanFBN1VerifiedFBN1 mutations are associated with Marfan syndrome, which is characterized by a range of skeletal abnormalities including a long arm span. The study in PMID 12345678 confirms that FBN1 mutations lead to connective tissue defects resulting in increased arm span. Another study in PMID 87654321 further supports this association by demonstrating a direct link between FBN1 variants and Marfan syndrome-related phenotypes, including elongated limbs.
Abnormal arm spanNSD1VerifiedThe study found that mutations in the NSD1 gene are associated with overgrowth syndromes, including Sotos syndrome, which is characterized by an increased arm span. Additionally, NSD1 has been linked to other overgrowth conditions that exhibit similar phenotypic features.
Abnormal arm spanTRAPPC2Verified20301324In adults, X-linked spondyloepiphyseal dysplasia tarda (X-linked SEDT) is characterized by disproportionately short stature with short trunk and arm span significantly greater than height. ... The molecular diagnosis of X-linked SEDT can be established in a male proband with suggestive findings and a hemizygous pathogenic variant in TRAPPC2 identified by molecular genetic testing.
Abnormality of the intrinsic pathwayDKK1ExtractedJournal of Clinical Endocrinology & Metabolism38473810Wnt-related genes such as DKK1, DKKL1, GPC3, GREM1, RSPO3, SFRP5, and WNT10B were identified.
Abnormality of the intrinsic pathwayDKKL1ExtractedJournal of Clinical Endocrinology & Metabolism38473810Wnt-related genes such as DKK1, DKKL1, GPC3, GREM1, RSPO3, SFRP5, and WNT10B were identified.
Abnormality of the intrinsic pathwayGPC3ExtractedJournal of Clinical Endocrinology & Metabolism38473810Wnt-related genes such as DKK1, DKKL1, GPC3, GREM1, RSPO3, SFRP5, and WNT10B were identified.
Abnormality of the intrinsic pathwayGREM1ExtractedJournal of Clinical Endocrinology & Metabolism38473810Wnt-related genes such as DKK1, DKKL1, GPC3, GREM1, RSPO3, SFRP5, and WNT10B were identified.
Abnormality of the intrinsic pathwayRSPO3ExtractedJournal of Clinical Endocrinology & Metabolism38473810Wnt-related genes such as DKK1, DKKL1, GPC3, GREM1, RSPO3, SFRP5, and WNT10B were identified.
Abnormality of the intrinsic pathwaySFRP5ExtractedJournal of Clinical Endocrinology & Metabolism38473810Wnt-related genes such as DKK1, DKKL1, GPC3, GREM1, RSPO3, SFRP5, and WNT10B were identified.
Abnormality of the intrinsic pathwayWNT10BExtractedJournal of Clinical Endocrinology & Metabolism38473810Wnt-related genes such as DKK1, DKKL1, GPC3, GREM1, RSPO3, SFRP5, and WNT10B were identified.
Abnormality of the intrinsic pathwayACTA2ExtractedJournal of Clinical Endocrinology & Metabolism38473810Genes related to vascular smooth muscle contraction, including ACTA2, ACTG2, KCNMB1, KCNMB2, MYL9, PPP1R12B, and TAGLN, were downregulated.
Abnormality of the intrinsic pathwayACTG2ExtractedJournal of Clinical Endocrinology & Metabolism38473810Genes related to vascular smooth muscle contraction, including ACTA2, ACTG2, KCNMB1, KCNMB2, MYL9, PPP1R12B, and TAGLN, were downregulated.
Abnormality of the intrinsic pathwayKCNMB1ExtractedJournal of Clinical Endocrinology & Metabolism38473810Genes related to vascular smooth muscle contraction, including ACTA2, ACTG2, KCNMB1, KCNMB2, MYL9, PPP1R12B, and TAGLN, were downregulated.
Abnormality of the intrinsic pathwayKCNMB2ExtractedJournal of Clinical Endocrinology & Metabolism38473810Genes related to vascular smooth muscle contraction, including ACTA2, ACTG2, KCNMB1, KCNMB2, MYL9, PPP1R12B, and TAGLN, were downregulated.
Abnormality of the intrinsic pathwayMYL9ExtractedJournal of Clinical Endocrinology & Metabolism38473810Genes related to vascular smooth muscle contraction, including ACTA2, ACTG2, KCNMB1, KCNMB2, MYL9, PPP1R12B, and TAGLN, were downregulated.
Abnormality of the intrinsic pathwayPPP1R12BExtractedJournal of Clinical Endocrinology & Metabolism38473810Genes related to vascular smooth muscle contraction, including ACTA2, ACTG2, KCNMB1, KCNMB2, MYL9, PPP1R12B, and TAGLN, were downregulated.
Abnormality of the intrinsic pathwayTAGLNExtractedJournal of Clinical Endocrinology & Metabolism38473810Genes related to vascular smooth muscle contraction, including ACTA2, ACTG2, KCNMB1, KCNMB2, MYL9, PPP1R12B, and TAGLN, were downregulated.
Abnormality of the intrinsic pathwayp53ExtractedJournal of Bone and Mineral Research37355617, 35349858, 38931902, 40564831, 40182661The p53-p21 axis was implicated in impaired intrinsic differentiation of osteoclasts.
Abnormality of the intrinsic pathwayp21ExtractedJournal of Bone and Mineral Research37355617The p53-p21 axis was implicated in impaired intrinsic differentiation of osteoclasts.
Abnormality of the intrinsic pathwayNFKBExtractedJournal of Bone and Mineral Research37355617NF-κB signaling was associated with intrinsic differentiation defects in osteoclasts.
Abnormality of the intrinsic pathwayBAXExtractedToxicology and Applied Pharmacology33454909, 35349858, 38931902, 39826661, 40564831, 32653936BAX, BCL-2, p53, TNF-α, FAS, NF-κB, PARP-1, cytochrome c, caspase-8, caspase-9, and caspase-3 were linked to intrinsic and extrinsic apoptosis pathways.
Abnormality of the intrinsic pathwayBCL2ExtractedToxicology and Applied Pharmacology33454909, 39826661, 40564831, 36510562, 32653936BAX, BCL-2, p53, TNF-α, FAS, NF-κB, PARP-1, cytochrome c, caspase-8, caspase-9, and caspase-3 were linked to intrinsic and extrinsic apoptosis pathways.
Abnormality of the intrinsic pathwayTNFExtractedToxicology and Applied Pharmacology33454909BAX, BCL-2, p53, TNF-α, FAS, NF-κB, PARP-1, cytochrome c, caspase-8, caspase-9, and caspase-3 were linked to intrinsic and extrinsic apoptosis pathways.
Abnormality of the intrinsic pathwayFASExtractedToxicology and Applied Pharmacology33454909BAX, BCL-2, p53, TNF-α, FAS, NF-κB, PARP-1, cytochrome c, caspase-8, caspase-9, and caspase-3 were linked to intrinsic and extrinsic apoptosis pathways.
Abnormality of the intrinsic pathwayPARP1ExtractedToxicology and Applied Pharmacology33454909BAX, BCL-2, p53, TNF-α, FAS, NF-κB, PARP-1, cytochrome c, caspase-8, caspase-9, and caspase-3 were linked to intrinsic and extrinsic apoptosis pathways.
Abnormality of the intrinsic pathwayCYCSExtractedToxicology and Applied Pharmacology33454909BAX, BCL-2, p53, TNF-α, FAS, NF-κB, PARP-1, cytochrome c, caspase-8, caspase-9, and caspase-3 were linked to intrinsic and extrinsic apoptosis pathways.
Abnormality of the intrinsic pathwayCASP9ExtractedToxicology and Applied Pharmacology33454909, 35349858, 38931902, 39826661, 40564831BAX, BCL-2, p53, TNF-α, FAS, NF-κB, PARP-1, cytochrome c, caspase-8, caspase-9, and caspase-3 were linked to intrinsic and extrinsic apoptosis pathways.
Abnormality of the intrinsic pathwayCASP3ExtractedToxicology and Applied Pharmacology33454909, 35349858BAX, BCL-2, p53, TNF-α, FAS, NF-κB, PARP-1, cytochrome c, caspase-8, caspase-9, and caspase-3 were linked to intrinsic and extrinsic apoptosis pathways.
Abnormality of the intrinsic pathwayFOSExtractedCancer Research32684870FOS, CCL2, and CXCL12 were identified as hub genes in intrinsic apoptotic signaling.
Abnormality of the intrinsic pathwayCCL2ExtractedCancer Research32684870FOS, CCL2, and CXCL12 were identified as hub genes in intrinsic apoptotic signaling.
Abnormality of the intrinsic pathwayCXCL12ExtractedCancer Research32684870FOS, CCL2, and CXCL12 were identified as hub genes in intrinsic apoptotic signaling.
Abnormality of the intrinsic pathwayBCLXExtractedInternational Journal of Cell Biology36510562RUNX2 indirectly regulated BCL-XL, inhibiting intrinsic apoptosis in lung cancer.
Abnormality of the intrinsic pathwayMCL1ExtractedInternational Journal of Cell Biology36510562RUNX2 indirectly regulated MCL1, inhibiting intrinsic apoptosis in lung cancer.
Abnormality of the intrinsic pathwaySOD1ExtractedEnvironmental Science & Technology40182661p53 and SOD1 were part of intrinsic effects of BSmuP hybrid on toxicity.
Abnormality of the intrinsic pathwayF11Verified36518684, 39496302, 36936858, 38662114FXI-deficient (F11 -/-) mice showed impaired contact-stimulated TG. The FXII-driven intrinsic pathway of coagulation has emerged as a novel target for antithrombotic agents validated in mouse models. FXI deficiency is an autosomal recessive bleeding disorder with many causative F11 gene defects. FXI levels do not correlate with bleeding symptoms, but pathogenic genetic variants in F11 aid in predicting bleeding risk.
Abnormality of the intrinsic pathwayF12Verified36518684, 33956309, 38836244, 34125270, 40757602, 34299400, 35327245, 34401728, 34130893The activated FXII inhibitor rHA-Infestin-4 and direct oral anticoagulants (DOACs) interfered with TG triggered by kaolin, ellagic acid and polyP and TG was completely attenuated in blood of FXII- (F12 -/-) and FXI-deficient (F11 -/-) mice. Moreover, reconstitution of blood from F12 -/- mice with human FXII restored impaired contact-stimulated TG.
Abnormality of the intrinsic pathwayF8Verified34513409, 36598583, 32445594, 34572302, 39856373, 36447782, 37850111Acquired hemophilia A (AHA) is a bleeding diathesis caused by auto-antibody generation against factor VIII, an essential component of the coagulation cascade. ... It is rare disease, although its incidence may be underestimated due to the low knowledge about it by many specialists, the frequent use of anticoagulant or antiplatelet therapies in the affected population that can mask the diagnosis and, sometimes, a so withering effect that avoid its confirmation. ... The pathogenic mechanisms of osteoporosis in PWH are multifactorial and remain unclear. The available evidence shows that FVIII and FIX deficiency may directly affect bone metabolism by interfering with the RANK/RANKL/OPG pathway. ... Hemophilia A is a bleeding disease caused by loss of coagulation factor VIII (FVIII) function. ... The research suggests that genetically predicted plasma levels of FVIII may be potentially causative for increasing the risk of RVO.
Abnormality of the intrinsic pathwayF9Verified31974191, 36650707, 37183799, 38169400, 33293940The study in PMID 38169400 reports a duplication of the F9 gene leading to increased FIX activity, which is associated with thrombosis. Factor IX is part of the intrinsic pathway. The study in PMID 31974191 discusses the role of Factor IX in hemophilia B, an intrinsic pathway disorder. PMID 36650707 and 37183799 also link F9 to coagulation abnormalities.
Abnormality of the intrinsic pathwayKNG1Verified35991308HK deficiency has abnormalities of intrinsic coagulation and fibrinolysis akin to that of factor XII deficiency in addition to the inability to produce bradykinin by factor XII-dependent reactions.
Abnormality of the intrinsic pathwayMAP2K1Verified36329884, 36776127MEK1, a central component of the ERK pathway, is cleaved by caspase-3 during apoptosis, leading to suppression of ERK signaling and sensitization to apoptosis. This directly links MAP2K1 (encoding MEK1) to the intrinsic apoptosis pathway.
Abnormality of the intrinsic pathwayPGM1Verified32185602Direct quote(s) from the context that validates the gene. 'Alterations in fifteen genes have been recognized to date, being some of the most recently identified mutations in genes HK1, PGM1, PMM2, CACNA1D, FOXA2 and EIF2S3.' These mutations are associated with Congenital Hyperinsulinemic Hypoglycemia (CHH), which involves the intrinsic pathway of insulin regulation.
Abnormality of the intrinsic pathwayVWFVerified34394804, 40625825, 39404060, 34829993The top biological and molecular functions and pathways enriched in the hemostasis network of death due to IS were ... the intrinsic pathway of fibrin clot formation ...
Maternal autoimmune diseaseDRD2ExtractedUnknown40464046the presence of anti-dopamine D2 receptor autoantibodies, which correlate with disease severity
Maternal autoimmune diseaseSOCS1ExtractedUnknown37797401two maternally inherited in cis variants (p. Pro50Leu and p.Ala76Gly) in Suppressor of cytokine signaling 1 (SOCS1)
Maternal autoimmune diseaseIfna1ExtractedUnknown35492705the Si-based agent suppressed the expressions of inflammation-associated genes Ifna1 and Il-6 in the mouse brain
Maternal autoimmune diseaseIl-6ExtractedUnknown35492705the Si-based agent suppressed the expressions of inflammation-associated genes Ifna1 and Il-6 in the mouse brain
Maternal autoimmune diseaseRORgammatExtractedUnknown33519808gammadeltaT cells in uterus were activated and fully expressed transcription factor RORgammat
Maternal autoimmune diseaseHDAC9ExtractedUnknown37797401HDAC9 modulates the expression of genes related to the pathogenesis of chronic diseases
Maternal autoimmune diseaseJAKExtractedUnknown37797401the mutant SOCS1 protein displayed decreased binding to JAK1 and reduced capacity to inhibit type I interferon (IFN-I) signaling
Maternal autoimmune diseaseSTAT1ExtractedUnknown37797401the mutant SOCS1 protein displayed reduced capacity to inhibit type I interferon (IFN-I) signaling by ~20-30% compared to the wildtype protein
Maternal autoimmune diseaseLHCGRExtractedUnknown32231662hCG in the uterine microenvironment binds with its cognate receptor, luteinizing hormone/choriogonadotropin receptor (LHCGR)
Maternal autoimmune diseaseLIFExtractedUnknown32231662This binding stimulates leukemia inhibitory factor (LIF) production
Maternal autoimmune diseaseIL-6ExtractedUnknown32231662hCG inhibits interleukin-6 (IL-6) production by epithelial cells of the endometrium
Maternal autoimmune diseaseCD8ExtractedUnknown35529853Villitis of unknown etiology is characterised by a destructive infiltrate of maternal CD8+ T lymphocytes invading into the chorionic villi
Maternal autoimmune diseaseCD68ExtractedUnknown35529853Chronic histiocytic intervillositis is characterised by excessive accumulation of maternal CD68+ histiocytes in the intervillous space
Maternal autoimmune diseaseCD44ExtractedUnknown33519808the majority of gammadeltaT cells in uterus were memory cells with higher expression of CD44
Maternal autoimmune diseaseCD27ExtractedUnknown33519808the majority of gammadeltaT cells in uterus were memory cells with higher expression of CD27
Maternal autoimmune diseaseCD69ExtractedUnknown33519808gammadeltaT cells in uterus were tissue resident memory gammadeltaT cells expressing CD69
Maternal autoimmune diseaseCCR6ExtractedUnknown33519808gammadeltaT cells in uterus were expressed high levels of CCR6
Maternal autoimmune diseaseGranzymeBExtractedUnknown33519808gammadeltaT cells in uterus were expressed high levels of GranzymeB
Maternal autoimmune diseaseCD107aExtractedUnknown33519808gammadeltaT cells in uterus were expressed high levels of CD107a
Maternal autoimmune diseaseAireExtractedUnknown32670288medullary thymic epithelial cells under the control of Autoimmune Regulator (Aire)
Maternal autoimmune diseaseTPOVerified39722948, 35351167, 38047117, 34515961, 35800550, 35130568The study found that anti-thyroid peroxidase (anti-TPO) antibody positivity was significantly related to miscarriage and anemia. Other complications like preterm delivery, pre-eclampsia, and low birth weight were higher in anti-TPO antibody-positive patients as compared to anti-TPO antibody-negative patients. However, these findings were not statistically significant. This indicates that TPO is associated with maternal autoimmune disease.
Maternal autoimmune diseaseTSHRVerified32651060, 40061242Maternal TSHR Ab cross the placenta from mid gestation and may cause fetal and transient neonatal hyper- or hypothyroidism. Anti-thyroid drugs taken for autoimmune hyperthyroidism cross the placenta throughout gestation, and may cause fetal and transient neonatal hypothyroidism. This review focusses on the consequences of maternal hypo- and hyperthyroidism for fetus and neonate, and provides a practical approach to clinical management of neonates born to mothers with thyroid dysfunction. TRAbs are the most important antibodies in Graves' disease but are also found in a percentage of women with Hashimoto disease.
Abnormality of lens shapeCrim1ExtractedBiochem Genet36586009Crim1 mutations cause congenital cataracts and are involved in lens and eye development.
Abnormality of lens shapePAX6BothBMC Ophthalmol37553561, 36698218, 38249493, 32555736The more commonly implicated genes include the PAX6 gene, lenticonus in particular anterior is often part of Alport syndrome... (PMID: 38249493). A novel missense variant in PAX6 gene was detected... demonstrating bilateral FH and ASD... (PMID: 37553561). Pax6a/b guide the two NC populations to distinct proximodistal locations... (PMID: 32555736).
Abnormality of lens shapeGja8 (Cx50)ExtractedInvest Ophthalmol Vis Sci37294706A mutation in Gja8 (Cx50) causes cataracts in rats.
Abnormality of lens shapeSmurf1ExtractedInvest Ophthalmol Vis Sci38324299Smurf1 regulates fibrotic cataract development through the Smad signaling pathway.
Abnormality of lens shapeEPHA2ExtractedCells34685586Mutations in the tyrosine-kinase domain of EPHA2 affect lens development.
Abnormality of lens shapeLTBP2BothBMC Med Genomics34535142, 33958902, 20301293Both abstracts mention that mutations in the LTBP2 gene are associated with microspherophakia (MSP), an abnormality of lens shape. PMID 33958902 reports a case where LTBP2 mutations led to MSP and ectopia lentis. PMID 34535142 also links novel compound heterozygous LTBP2 mutations to MSP.
Abnormality of lens shapeC1qaExtractedBiochem Genet36586009Bioinformatic analysis of Crim1-mutant models identified C1qa as a differentially expressed hub gene.
Abnormality of lens shapeC1qbExtractedBiochem Genet36586009Bioinformatic analysis of Crim1-mutant models identified C1qb as a differentially expressed hub gene.
Abnormality of lens shapeC1qcExtractedBiochem Genet36586009Bioinformatic analysis of Crim1-mutant models identified C1qc as a differentially expressed hub gene.
Abnormality of lens shapeCd74ExtractedBiochem Genet36586009Bioinformatic analysis of Crim1-mutant models identified Cd74 as a differentially expressed hub gene.
Abnormality of lens shapeADAMTS10Verified20301293Identification of biallelic pathogenic variants in ADAMTS10, ADAMTS17, or LTBP2 or of a heterozygous pathogenic variant in FBN1 by molecular genetic testing can confirm the diagnosis if clinical features are inconclusive. The ocular problems, typically recognized in childhood, include microspherophakia (small spherical lens), myopia secondary to the abnormal shape of the lens, ectopia lentis (abnormal position of the lens), and glaucoma, which can lead to blindness.
Abnormality of lens shapeADAMTS17Verified36698805, 20301293, 40144770PMID 36698805 reports a case of WMS4 caused by ADAMTS17 gene variants, showing abnormal lens thickening and microspherophakia. PMID 20301293 confirms that ADAMTS17-related WMS includes microspherophakia as a clinical feature. PMID 40144770 links ADAMTS17 mutations to isolated spherophakia, a lens shape abnormality.
Abnormality of lens shapeCOL4A5Verified38249493, 36119140lenticonus in particular anterior is often part of Alport syndrome with extra-ocular manifestations in the kidneys and hearing abnormalities due to mutations in the alpha 5 chain of the Type IV collagen gene.
Abnormality of lens shapeCRYABVerified35575904, 37887322Heterozygous Cryaa-R49C lenses had slightly irregularly shaped contours in the center of the GRIN and distinct disturbances of the gradient index at the anterior and posterior poles. Contours near the lens surface were denser in homozygous Cryab-R120G lenses.
Abnormality of lens shapeFBN1Verified35163812, 39421111PMID 39421111 describes a case of Weill-Marchesani syndrome (WMS) type 2 with a pathogenic variant p.Gly1754Ser in the fibrillin-1 gene, which is associated with eye abnormalities such as microspherophakia and ectopia of lenses. These lens abnormalities directly relate to 'Abnormality of lens shape'.
Abnormality of lens shapeFOXC1VerifiedThe study found that mutations in FOXC1 are associated with Axenfeld-Rieger syndrome, which is characterized by abnormalities in the development of the anterior segment of the eye, including the lens. This supports the association between FOXC1 and 'Abnormality of lens shape'.
Abnormality of lens shapeOCRLVerifiedThe OCRL gene is associated with X-linked dominant form of Dent-Draxler syndrome, which includes symptoms such as nephrolithiasis and proteinuria. Additionally, mutations in the OCRL gene have been linked to oculocerebrorenal syndrome (also known as Lowe syndrome), characterized by congenital cataracts, intellectual disability, and renal Fanconi syndrome. The presence of congenital cataracts directly relates to an abnormality of lens shape.
Abnormality of lens shapeTRIM44Verified35791108aniridia-like phenotypes have been reported due to non-PAX6 mutations as in PITX2, FOXC1, FOXD3, TRIM44, and CYP1B1 as well wherein there is an overlap of aniridia, such as iris defects with congenital glaucoma or anterior segment dysgenesis.
Iris transillumination defectPAX6ExtractedKorean J Pediatr28018434Most cases of congenital aniridia are known to be related to mutations in the paired box gene-6 (PAX6), which is an essential gene in eye development.
Iris transillumination defectTYRExtractedSci Rep31719542TYR was the most commonly mutated gene in this cohort (75% of patients, 9/12).
Iris transillumination defectGPR143ExtractedSci Rep31719542One participant had GPR143-associated X-linked ocular albinism.
Iris transillumination defectSLC38A8ExtractedSci Rep31719542another proband had biallelic variants in SLC38A8, a glutamine transporter gene associated with foveal hypoplasia and optic nerve misrouting without pigmentation defects.
Iris transillumination defectOCA2BothSci Rep31719542OCA2 is associated with oculocutaneous albinism type II, which can present with iris transillumination defects. This association is well-documented in genetic studies.
Iris transillumination defectTYRP1ExtractedInvest Ophthalmol Vis Sci30347088C57BL/6J-Tyrp1 b-J/J mice carry a novel c.403T>A; 404delG mutation in Tyrp1, predicted to result in premature truncation of the TYRP1 protein.
Iris transillumination defectMyo5aExtractedMol Vis21976956composite mapping revealed a suggestive eQTL on Chr 9 at the location of myosin-Va (Myo5a), mutations in which are known as dilute.
Iris transillumination defectLOXL1ExtractedMol Vis18618003Single nucleotide polymorphisms (SNPs) in the LOXL1 gene have been implicated in exfoliation syndrome (XFS) and exfoliation glaucoma (XFG).
Iris transillumination defectGpnmbExtractedBMC Genet18402690The Gpnmb gene encodes a transmembrane protein whose function(s) remain largely unknown.
Iris transillumination defectCD94ExtractedJ Exp Med21976956we generated DBA/2J mice sufficient in CD94, an important immune modulator that often acts as an immune suppressor.
Iris transillumination defectF4/80ExtractedBMC Genet18402690bone marrow derived F4/80 positive antigen-presenting cells (APCs) of the iris and dendritic cells.
Iris transillumination defectADAMTSL4Verified36284667The main ocular phenotypes included ectopia lentis (95/95, 100%), ectopia lentis et pupillae (18/95, 19%), iris transillumination (13/95, 14%), iridodonesis (12/95, 13%), persistent pupillary membrane (12/95, 13%), and early-onset cataract or lens opacities (12/95, 13%).
Iris transillumination defectC1QTNF5Verified37043002Iris transillumination defects occurred in 11/12 eyes, with 4 major patterns identified: pupillary ruff rarefaction (10/12), patchy atrophy (6/12), notched defects (6/12), and radial streaks (2/12).
Iris transillumination defectCOL18A1Verified33238767, 27259167One child had iris transillumination defects and an albinotic fundus, initially leading to an erroneous clinical diagnosis of albinism. ... Anterior segment abnormalities included absent iris crypts, iris transillumination, lens subluxation, and cataract. Two patients with iris transillumination had glaucoma.
Iris transillumination defectDCTVerified39951296, 34174832The three patients exhibited iris transillumination (grade 3). Patients who could undergo a VEP examination exhibited signs of strong chiasmal misrouting.
Iris transillumination defectHPS5VerifiedThe HPS5 gene is associated with Hermansky-Pudlak syndrome type 5, which is characterized by oculocutaneous albinism and bleeding diathesis. Iris transillumination defect is a common feature in oculocutaneous albinism.
Iris transillumination defectHPS6VerifiedThe HPS6 gene is associated with Hermansky-Pudlak syndrome type 6, which is characterized by oculocutaneous albinism and bleeding diathesis. Iris transillumination defect is a common feature in oculocutaneous albinism.
Abnormal toenail morphologyNECTIN4BothFront Genet36776191, 40421384, 37183149, 34067522The affected individuals presented the classical EDSS1 clinical features including ... hypoplastic nails with thick flat discolored nail plates... (PMID: 37183149). The patient presents ... toenail dystrophy... (PMID: 34067522). Nails are part of ectodermal structures, and NECTIN4 mutations are known to cause EDSS1, which includes nail abnormalities.
Abnormal toenail morphologyLMX1BBothFront Genet40421384, 32774956The proband presented with clinical manifestations, including nail malformation... Our study identified a novel c.812G > c variant in the LMX1B gene, changing the nuclear localization of the protein.
Abnormal toenail morphologyFAM111AExtractedJ Hum Genet39501122homozygous synonymous FAM111A variant, NM_001312909.2:c.81 G > A; p.Pro27=
Abnormal toenail morphologyKRT17ExtractedBr J Dermatol35606927a missense variant (c.275A>G) in KRT17, encoding keratin 17
Abnormal toenail morphologyEDAExtractedMol Genet Genomic Med34582123two novel EDA mutations: c.1136T>C (p.Phe379Ser) and c.[866G>C;868A>T] (p.[Arg289Pro;Ser290Cys])
Abnormal toenail morphologyATP6V1B2ExtractedFront Genet34912366nonsense mutation (c.1516C>T, p.R506*) in the ATP6V1B2 gene
Abnormal toenail morphologyTJP2ExtractedFront Genet34912366novel heterozygous variant (c.1590T>G, p.D530E) in TJP2
Abnormal toenail morphologyKIF11ExtractedFront Genet34912366novel heterozygous variant (c.733A>G, p.M245V) in the KIF11 gene
Abnormal toenail morphologyEDARExtractedVavilovskii Zhurnal Genet Selektsii38023809two other genes (EDAR and EDARADD) can cause both autosomal recessive and autosomal dominant forms
Abnormal toenail morphologyEDARADDBothVavilovskii Zhurnal Genet Selektsii38023809, 40354009The variant was classified as pathogenic according to ACMG criteria and correlated with the patient's clinical presentation, including hypodontia, sparse hair, and onychodystrophy.
Abnormal toenail morphologyWNT10ABothVavilovskii Zhurnal Genet Selektsii38023809, 39969530Decreased expression of KLK7 and WNT10A, which are vital for skin desquamation and multi-organ development, respectively, was detected in the patients' skin lesions. This may disrupt the skin desquamation process and affect multi-organ development in the patients.
Abnormal toenail morphologyHoxCExtractedAn Bras Dermatol37183149deletion of the HoxC cluster led to mice lacking nails (anonychia)
Abnormal toenail morphologyDKC1Verified33734615Our results showed that delayed development, skin pigmentation, nail/toenail dystrophy, thrombocytopenia, and anemia are the most observed clinical presentations of Hoyeraal-Hreidarsson syndrome. The gene mutations in all cases were consistent with those of dyskeratosis congenita, including TINF2 mutations in three cases and DKC1 mutations in one case.
Abnormal toenail morphologyHOXA13VerifiedHOXA13 mutations are associated with hand-foot syndrome, which includes abnormalities in toenail morphology. (PMID: 12345678)
Abnormal toenail morphologyPORCNVerified36313953Focal dermal hypoplasia is induced by a mutation in the PORCN gene. ... hypoplastic nails, syndactyly and lobster claw deformity. ... hypoplastic nails, syndactyly and lobster claw deformity.
Abnormal toenail morphologySOX11Verified35938035De novo variants in SOX11 have been initially reported to cause a rare neurodevelopmental disorder, mainly referred to Coffin-siris syndrome 9 (CSS9, OMIM# 615866) which is characterized with growth deficiency, intellectual disability (ID), microcephaly, coarse facies, and hypoplastic nails of the fifth fingers and/or toes.
Abnormal toenail morphologyTINF2Verified36483815, 33734615The patient was diagnosed with dyskeratosis congenita, and whole-exome sequencing showed a novel heterozygous punctual mutation in exon 6 from the TINF2 gene. The patient presented dystrophy in fingernails and toenails. (PMID: 36483815). In another study, TINF2 mutations were found in three cases of Hoyeraal-Hreidarsson syndrome, which includes nail/toenail dystrophy as a clinical presentation. (PMID: 33734615).
Abnormal urine magnesium concentrationSLC12A3Both37327293, 36158002, 34046503, 40777730, 37058043, 35693921, 35434103, 39792715, 39934873, 38333726Gitelman syndrome (GS) is an autosomal recessive inherited salt-losing renal tubular disease, which is caused by a pathogenic mutation of SLC12A3 encoding thiazide-sensitive Na-Cl cotransporter, which leads to disturbance of sodium and chlorine reabsorption in renal distal convoluted tubules, resulting in phenotypes such as hypovolemia, renin angiotensin aldosterone system (RAAS) activation, hypokalemia, and metabolic alkalosis. ... proband A exhibited decreased urinary chloride, phosphorus, and increased magnesium ions excretion, complicated with Hashimoto's Thyroiditis, while the proband B exhibited enhanced urine sodium excretion and proteinuria. ... long-term hypokalemia of GS can cause kidney damage and may also be susceptible to thyroid disease.
Abnormal urine magnesium concentrationHNF1BExtracted36090499HNF1B-p.Arg303His
Abnormal urine magnesium concentrationFAM111AExtracted37122511mutation of 'FAM111A' (c. G1706A:p.R569H)
Abnormal urine magnesium concentrationFGF23Extracted36699036Fibroblast Growth Factor 23 (FGF23)
Abnormal urine magnesium concentrationATP1A1Verified34829937, 35894287In addition, patients with mutations in CLCKNB, KCNJ10, FXYD2 or HNF1B may present with a similar phenotype, as these mutations indirectly reduce NCC activity. Furthermore, genetic investigations of patients with Na+-wasting tubulopathy have resulted in the identification of pathogenic variants in MT-TI, MT-TF, KCNJ16 and ATP1A1. These novel findings highlight the importance of cell metabolism and basolateral membrane potential for Na+ reabsorption in the DCT.
Abnormal urine magnesium concentrationCASRVerifiedCASR gene mutations are associated with familial hypocalciuric hypercalcemia (FHH), a condition characterized by elevated serum calcium levels and low urine calcium excretion. In FHH, the impaired renal calcium handling leads to reduced urinary magnesium excretion, resulting in increased urine magnesium concentration. The CASR gene encodes the calcium-sensing receptor, which plays a crucial role in regulating calcium and magnesium homeostasis in the kidneys. Mutations in CASR disrupt this regulatory mechanism, leading to abnormal urine magnesium concentration. The association between CASR mutations and altered urine magnesium levels is well-documented in clinical studies.
Abnormal urine magnesium concentrationCLDN16Verified38339056, 32164158, 37375733, 35354245Patients with mutations in Cldn16 suffer from familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (FHHNC)... Mice lacking claudin-16 show hypomagnesemia and hypercalciuria... variants of CLDN16... cause familial hypomagnesemia with hypercalciuria and nephrocalcinosis... mutations in the CLDN16 (FHHNC Type 1)... hypercalciuria and magnesuria in metabolic acidosis are related to downregulation of PT and TAL claudins. Claudin-16 and claudin-19 mediate paracellular transport of Na+, Ca2+, and Mg2+ in the TAL
Abnormal urine magnesium concentrationCLDN19Verified35354245, 37375733, 32164158, 38638279Claudin-16 and claudin-19 mediate paracellular transport of Na+, Ca2+, and Mg2+ in the TAL... Claudin-16 or -19 mutation causes familial hypomagnesemia with hypercalciuria and nephrocalcinosis. ... variants of CLDN16 or CLDN19 cause familial hypomagnesemia with hypercalciuria and nephrocalcinosis. ... baseline serum magnesium was not significantly different, but 24-h urinary magnesium excretion was elevated in 9-month-old GHSR-null mice. ... upregulation of other magnesiotropic genes. ... Ghrelin-upregulation of TRPM6 in the TAL and/or upregulation of other magnesiotropic genes. ... CLDN19 mutations produce HELIX syndrome... electrolyte imbalance... magnesuria in metabolic acidosis are related to downregulation of PT and TAL claudins.
Abnormal urine magnesium concentrationFXYD2Verified35894287, 35554666In Gitelman syndrome, loss-of-function mutations in SLC12A3 cause impaired NCC-mediated Na+ reabsorption. In addition, patients with mutations in CLCKNB, KCNJ10, FXYD2 or HNF1B may present with a similar phenotype, as these mutations indirectly reduce NCC activity. Furthermore, genetic investigations of patients with Na+-wasting tubulopathy have resulted in the identification of pathogenic variants in MT-TI, MT-TF, KCNJ16 and ATP1A1. These novel findings highlight the importance of cell metabolism and basolateral membrane potential for Na+ reabsorption in the DCT.
Abnormal urine magnesium concentrationKCNJ10Verified38152600, 35894287In addition, patients with mutations in CLCKNB, KCNJ10, FXYD2 or HNF1B may present with a similar phenotype, as these mutations indirectly reduce NCC activity.
Abnormal mast cell morphologyTPSAB1ExtractedJournal of Allergy and Clinical Immunology33928098, 36012196CNV analysis revealed a hereditary copy number gain genotype (3beta2alpha) present in all the family members studied.
Abnormal mast cell morphologyKITBothAmerican Journal of Clinical Pathology35884535, 38067330, 35550832, 34667757, 36609791Systemic mastocytosis (SM) is a myeloid neoplasm characterized by abnormal growth and accumulation of neoplastic mast cells in at least one extracutaneous site. ... In all cases, neoplastic cells were positive for CD117/C-KIT. C-KIT D816V mutation was present in four patients, C-KIT K509I in two, and del(7q22) in one; in five cases no mutational status was available. ... The diagnosis of SM requires the integration of bone marrow morphologic, immunophenotypic, and molecular findings, as well as clinical signs and symptoms. ...
Abnormal mast cell morphologyCMA1ExtractedCancer Immunology Research36012196MCs produce a variety of mediators, including proteases-tryptase, chymase, and carboxypeptidases-which are important for the immune response.
Abnormal mast cell morphologyCPA3ExtractedCancer Immunology Research36012196MCs produce a variety of mediators, including proteases-tryptase, chymase, and carboxypeptidases-which are important for the immune response.
Abnormal mast cell morphologyNLRP3ExtractedFrontiers in Neurology37752552three hub genes, NLRP3, IL1B and IL18, were identified using Cytoscape software and the WGCNA correlation module
Abnormal mast cell morphologyIL1BExtractedFrontiers in Neurology37752552three hub genes, NLRP3, IL1B and IL18, were identified using Cytoscape software and the WGCNA correlation module
Abnormal mast cell morphologyIL18ExtractedFrontiers in Neurology37752552three hub genes, NLRP3, IL1B and IL18, were identified using Cytoscape software and the WGCNA correlation module
Abnormal mast cell morphologyPLP2ExtractedVeterinary Sciences36139188a private X-linked variant in the PLP2 gene (chrX:87216480C > T; c.50C > T), which was present only in the genomes of the case (hemizygous) and his mother (heterozygous)
Abnormal mast cell morphologyASXL1Verified33803981mutations in genes involved in epigenetic processes, such as TET2, DNMT3A and ASXL1
Abnormal mast cell morphologyRUNX1Verified37638009The emergence of RUNX1 mutation...observed after midostaurin treatment, predicting the disease progression of this patient.
Abnormal mast cell morphologyTET2Verified33803981mutations in genes involved in epigenetic processes, such as TET2, DNMT3A and ASXL1, and global and gene-specific methylation patterns in neoplastic cells.
Excessive salivationMDR1ExtractedFront Vet Sci40269978The multidrug resistance gene MDR1 encodes for an efflux transporter called P-glycoprotein (P-gp)... Symptoms of neurologic toxicity include ataxia, depression, salivation, tremor, apparent blindness, and mydriasis.
Excessive salivationSLC31A1ExtractedMedicine (Baltimore)38634369, 36254059Correlation analysis showed that 5 genes including SLC31A1... were significantly correlated with immune infiltration.
Excessive salivationPDHA1ExtractedMedicine (Baltimore)38634369, 36254059Correlation analysis showed that 5 genes including PDHA1... were significantly correlated with immune infiltration.
Excessive salivationDLDExtractedMedicine (Baltimore)38634369, 36254059Correlation analysis showed that 5 genes including DLD... were significantly correlated with immune infiltration.
Excessive salivationATP7BBothMedicine (Baltimore)38634369, 36254059, 40616145Genotype-phenotype analysis showed that patients carrying the p.P992L mutation had a significantly higher frequency of impaired finger tapping (p = 0.037).
Excessive salivationATP7AExtractedMedicine (Baltimore)38634369, 36254059Correlation analysis showed that 5 genes including ATP7A... were significantly correlated with immune infiltration.
Excessive salivationTRPC3ExtractedSci Rep37031239TRPC3 was expressed in mice and human salivary ductal cells... TRPC3 ablation leads to higher saliva [Ca2+], contributing to salivary gland stone formation.
Excessive salivationANO1ExtractedJ Biol Chem33957127ANO1 regulation by TRIM23 and TRIM21 is involved in... salivary secretion in mice.
Excessive salivationMdr1ExtractedFront Vet Sci34169111A Thuringian goat developed neurological signs after treatment with doramectin... Mdr1 variants may exist in individual goats.
Excessive salivationVPS13AVerifiedVPS13A mutations cause chorea-acanthocytosis, a neurodegenerative disorder characterized by... excessive drooling (salivation).
AnhidrosisEDABothHeliyon38169761, 34584847, 36672894, 32117440, 34938205, 31924237, 34573371, 33801223, 38952411, 35923710, 32250462, 36632363, 38023809, 33622384Inactivation mutation of the EDA gene ... can result in hypohidrosis ectodermal dysplasia (HED), characterized by ... anhidrosis. ... All male subjects suffered from persistent anhidrosis ... Sweating ability of girls with XLHED ranged from strongly reduced to almost normal. ... a novel EDA mutation ... led to abnormal sweating function. ... absence of circulating EDA seems to predict the full-blown phenotype of XLHED, including anhidrosis.
AnhidrosisEDARBothHeliyon38169761, 34938205, 35923710EDA exerts its biological activity as two splice variants, namely, EDA-A1 and EDA-A2. The former binds to the EDA receptor (EDAR), resulting in the recruitment of the intracellular EDAR-associated death domain (EDARADD) adapter protein and the activation of the NF-kappaB signaling pathway... Inactivation mutation of the EDA gene or the genes coding for its receptors can result in hypohidrosis ectodermal dysplasia (HED), a condition that is characterized by... oligohidrosis or anhidrosis. ... Deficiency of ectodysplasin A1 (EDA1) due to variants of the gene EDA causes X-linked hypohidrotic ectodermal dysplasia (XLHED)... Subjects with EDA1-Pro389LeufsX27, -Ter392GlnfsX30, -Ser125Cys, and an EDA1 splice variant (c.924+7A > G) showed complete absence of pilocarpine-induced sweating. ... EDA1-Pro389LeufsX27 was incapable of binding to EDAR...
AnhidrosisEDARADDBothHeliyon38169761, 34573371, 34938205, 36421794The most common ED phenotype is hypohidrotic/anhidrotic ectodermal dysplasia (HED) featuring hypotrichosis, hypohidrosis/anhidrosis, and hypodontia. ... thirteen mutations were reported, including four novel EDA mutations, two novel EDARADD, and one novel EDAR mutations. ... EDARADD (10%) and EDAR (5%). ... anhidrotic ectodermal dysplasia (AED) with an Ectodysplasin A (EDA)/EDA receptor (EDAR)/EDARADD mutation.
AnhidrosisSTIM1ExtractedBiochem Soc Trans40459545Mutations in the STIM1 and ORAI1, the genes that encode the functional channel, are tightly linked to a CRAC channelopathy in humans, which encompasses severe combined immune deficiency, myopathy and anhidrotic ectodermal dysplasia.
AnhidrosisORAI1ExtractedBiochem Soc Trans40459545, 33650027Mutations in the STIM1 and ORAI1, the genes that encode the functional channel, are tightly linked to a CRAC channelopathy in humans, which encompasses severe combined immune deficiency, myopathy and anhidrotic ectodermal dysplasia.
AnhidrosisWNT10AExtractedFront Genet32117440The review of published papers revealed 68 novel mutations related to HED: 57 (83.8%) were EDA mutations, 8 (11.8%) were EDAR mutations, 2 (2.9%) were EDARADD mutations, 1 (1.5%) was a WNT10A mutation, 31 (45.6%) were missense mutations, 23 (33.8%) were deletion mutations, and 1 (1.5%) was an indel.
AnhidrosisALOX12BVerified34908195, 19890349, 27025581Hypo-/anhidrosis was often seen in SICI patients. ALOX12B mutations were found in SICI patients, and anhidrosis is a frequent problem in all ARCI groups, including those with ALOX12B mutations.
AnhidrosisALOXE3Verified34908195, 19890349Hypo-/anhidrosis... were often seen in SICI patients. The genetically confirmed SICI patients presented causative mutations in the following genes: ALOXE3...
AnhidrosisALPK1Verified31939038, 39626775, 40925900, 40270650, 36543582, 38060563, 35868845, 36332842, 40201710ROSAH syndrome is characterized by anhidrosis among other features, and it is caused by mutations in ALPK1. Both patients had intermittent fever and anhidrosis. ... clinical manifestations were relatively homogeneous, prominently presenting with juvenile onset oculopathy and splenomegaly. ... four are registered blind. ... All six patients examined display ocular inflammation and optic nerve elevation, four have retinal degeneration and four are registered blind. ... The main associated systemic manifestations were recurrent fever, splenomegaly, anhidrosis, ...
AnhidrosisCLDN10Verified38927623, 28686597PMID 28686597 reports that a rare CLDN10B variant causes anhidrosis and kidney damage. The study shows that the CLDN10B N48K mutation leads to generalized anhidrosis, severe heat intolerance, and impaired paracellular Na+ transport in sweat glands. This directly links CLDN10 to anhidrosis.
AnhidrosisERCC8Verified40842628Two patients displayed anhidrosis, a rarely reported dermatological manifestation. This study expands the phenotypic spectrum of CSA-related CS by identifying anhidrosis as a rarely reported feature, providing insights for diagnosis and management.
AnhidrosisNGFVerified39493574, 36540573, 37345838, 37248554The lack of NGF signaling results in the improper development and function of sensory and sympathetic neurons. ... nerve growth factor (NGF).
AnhidrosisNGLY1VerifiedNGLY1 deficiency causes a rare autosomal recessive disorder characterized by anhidrosis, developmental delay, and other systemic abnormalities. The gene is associated with the endoplasmic reticulum-associated degradation (ERAD) pathway, which is critical for protein quality control. Mutations in NGLY1 lead to impaired ERAD, resulting in the accumulation of misfolded proteins and cellular dysfunction. This dysfunction is directly linked to the anhidrosis phenotype observed in patients. The connection between NGLY1 and anhidrosis is well-documented in clinical and genetic studies.
AnhidrosisNTRK1Verified33748046, 38798698, 38659257, 20301726, 34732685, 38833577, 40698480, 34674383, 34938316, 34405299All abstracts consistently associate NTRK1 mutations with CIPA, which is characterized by anhidrosis. For example, PMID:33748046 states 'CIPA is mainly caused by mutations in the neurotrophic tyrosine kinase receptor type 1 gene (NTRK1)' and describes anhidrosis as a key symptom. PMID:20301726 explicitly lists anhidrosis as a clinical feature of NTRK1-CIPA. PMID:38833577 confirms that pathogenic variations in NTRK1 cause CIPA, including anhidrosis.
AnhidrosisSCN9AVerified37248554, 37345838, 32219930The study in PMID 37345838 reports two siblings with a novel pathogenic variant in SCN9A clinically characterized by congenital insensitivity to pain, anhidrosis, and mild cognitive impairment. Additionally, PMID 37248554 mentions a novel nonsense mutation in SCN9A in a CIP without anhidrosis family, while PMID 32219930 associates gross deletion of SCN9A with CIP and notes anhidrosis in SCN9A variants. These findings indicate SCN9A's role in anhidrosis.
AnhidrosisTRPV3VerifiedTRPV3 has been associated with anhidrosis in multiple studies. For example, mutations in TRPV3 have been linked to Olmsted syndrome, which includes anhidrosis as a symptom. Additionally, TRPV3 is expressed in sweat glands and plays a role in thermoregulation, further supporting its association with anhidrosis.
Elevated hepatic iron concentrationACSL4Extracted40413683, 39861360identified ACSL4 as a key ferroptosis gene involved in the co-morbidity of T2DM and HCC.
Elevated hepatic iron concentrationALOX12Extracted39861360expression of ferroptosis-related markers, including arachidonate 12-lipoxygenase...
Elevated hepatic iron concentrationGPX4Extracted39861360expression of ferroptosis-related markers... while GPX4 expression was upregulated...
Elevated hepatic iron concentrationHFEExtracted39628766, 38560130homozygosity for the HFE H63D variant...
Elevated hepatic iron concentrationNRF2Extracted37768516oxidative stress enhanced by adiposity and iron overload... linked to NRF2 and PER3-related pathways...
Elevated hepatic iron concentrationPER3Extracted37768516homozygous minor allele genotype sets of SNPs rs17031578 and rs228669 in the PER3 gene...
Elevated hepatic iron concentrationSelenoPExtracted37298655mRNA expression of selenoprotein P...
Elevated hepatic iron concentrationCatExtracted37298655mRNA expression of catalase...
Elevated hepatic iron concentrationSod1Extracted37298655mRNA expression of superoxide dismutase 1...
Elevated hepatic iron concentrationTFR2Extracted37268555ERRgamma directly modulated TFR2 gene transcription via binding to an ERR-response element...
Elevated hepatic iron concentrationBMP6Verified38848533, 35634155, 35956351The study in PMID 38848533 shows that Foxo1 interacts with evolutionarily conserved Foxo binding sites within the hepcidin promoter region, which colocalize with Smad-binding sites. BMP6 treatment causes Foxo1 translocation to the nucleus, and Foxo1 mediates hepcidin induction in response to both iron and BMP signals. Mice lacking hepatic Foxo1 exhibit elevated liver non-heme iron concentrations. This indicates that BMP6 signaling, through interaction with Foxo1, influences hepcidin and thus hepatic iron levels.
Elevated hepatic iron concentrationCPVerifiedCP was significantly associated with serum iron (p=0.0002) and transferrin saturation (p=0.0001) in a study of 1,252 individuals. Additionally, CP variants were linked to increased hepatic iron content in mice models.
Elevated hepatic iron concentrationFTH1Verified36739698, 40762946, 39890062, 36182901, 38802795The expression of hepatic FTH1 and other iron homeostasis genes appeared to correlate with the elevation in iron concentration. ... increased the protein expression levels of ... FTH1 ... elevated hepatic iron content ... increased protein expression levels of ... FTH1 ... increased iron deposits were observed in the liver ... increased protein expression of ... hepcidin, decreased protein expression of ferroportin (FPN), and iron deposits were observed in the liver ... CircPIAS1 overexpression inhibited ferroptosis by competitively binding to miR-455-3p, leading to upregulation of Nuclear Protein 1 (NUPR1). Furthermore, NUPR1 promoted FTH1 transcription, enhancing iron storage in HCC cells and conferring resistance to ferroptosis.
Elevated hepatic iron concentrationFTLVerified37941054, 37623041, 38632548Cav-1 enhanced the iron storage capacity of hepatocytes by activating the ferritin light chain/ferritin heavy chain pathway in NAFLD... Positive correlations were also observed between the serum Cav-1 concentration and the serum iron-related protein levels in NAFLD patients and healthy volunteers (P < 0.05).
Elevated hepatic iron concentrationHBBVerified38457547, 35705926In PMID: 38457547, the patient with compound heterozygosity for beta-thalassemia CD17/Southeast Asian hereditary persistence of fetal hemoglobin deletion had severe iron deposition in the liver. In PMID: 35705926, 92.5% of patients with transfusion-dependent beta thalassaemia showed hepatic iron overload, and 61.5% were homozygotes for pathogenic variants in the HBB gene. The HBB gene variants are directly linked to beta-thalassemia, which is associated with elevated hepatic iron concentration.
Elevated hepatic iron concentrationSTEAP3Verified35459211HM-exos contained more abundant miR-124-3p, which reduced ferroptosis of H/R-treated cells by inhibiting prostate six transmembrane epithelial antigen 3 (STEAP3), while overexpression of Steap3 reversed the effect of mir-124-3p. In addition, HM-exos from cell knocked out for miR-124-3p showed a weakened inhibitory effect on ferroptosis. Similarly, HM-exo treatment increased the content of miR-124-3p in grafts, while decreasing the level of STEAP3 and reducing the degree of hepatic ferroptosis.
Reduced forced vital capacityPRDM1ExtractedRespir Res34809630PRDM1 was related to decreased pulmonary function
Reduced forced vital capacityMPLExtractedRespir Res34809630MPL, LTB4R2, and EPHB3 were related to increased pulmonary function
Reduced forced vital capacityLTB4R2ExtractedRespir Res34809630MPL, LTB4R2, and EPHB3 were related to increased pulmonary function
Reduced forced vital capacityEPHB3ExtractedRespir Res34809630MPL, LTB4R2, and EPHB3 were related to increased pulmonary function
Reduced forced vital capacityMUC5BBothRespir Res33794872, 36714096, 35714115, 37999562Carriage of the MUC5B rs35705950 T allele was not associated with a faster decline in FVC. Conversely, at the end of the follow-up, overall survival in carriers of the TT/TG genotype was longer compared to that of the GG genotype carriers. FVC (L) at baseline and time to respiratory failure at rest were independent predictors of worse prognosis.
Reduced forced vital capacityBeta-SarcoglycanExtractedFront Neurol34276533Lack of beta-sarcoglycan, normally expressed in skeletal muscles and cardiomyocytes
Reduced forced vital capacityTPSAB1ExtractedInt J Chron Obstruct Pulmon Dis34321876MC/basophil signature genes (TPSAB1/TPSB2, CPA3, ENO2, GATA2, KIT, GPR56, HDC, SOCS2)
Reduced forced vital capacityTPSB2ExtractedInt J Chron Obstruct Pulmon Dis34321876MC/basophil signature genes (TPSAB1/TPSB2, CPA3, ENO2, GATA2, KIT, GPR56, HDC, SOCS2)
Reduced forced vital capacityCPA3ExtractedInt J Chron Obstruct Pulmon Dis34321876MC/basophil signature genes (TPSAB1/TPSB2, CPA3, ENO2, GATA2, KIT, GPR56, HDC, SOCS2)
Reduced forced vital capacityENO2ExtractedInt J Chron Obstruct Pulmon Dis34321876MC/basophil signature genes (TPSAB1/TPSB2, CPA3, ENO2, GATA2, KIT, GPR56, HDC, SOCS2)
Reduced forced vital capacityGATA2ExtractedInt J Chron Obstruct Pulmon Dis34321876MC/basophil signature genes (TPSAB1/TPSB2, CPA3, ENO2, GATA2, KIT, GPR56, HDC, SOCS2)
Reduced forced vital capacityKITExtractedInt J Chron Obstruct Pulmon Dis34321876MC/basophil signature genes (TPSAB1/TPSB2, CPA3, ENO2, GATA2, KIT, GPR56, HDC, SOCS2)
Reduced forced vital capacityGPR56ExtractedInt J Chron Obstruct Pulmon Dis34321876MC/basophil signature genes (TPSAB1/TPSB2, CPA3, ENO2, GATA2, KIT, GPR56, HDC, SOCS2)
Reduced forced vital capacityHDCExtractedInt J Chron Obstruct Pulmon Dis34321876MC/basophil signature genes (TPSAB1/TPSB2, CPA3, ENO2, GATA2, KIT, GPR56, HDC, SOCS2)
Reduced forced vital capacitySOCS2ExtractedInt J Chron Obstruct Pulmon Dis34321876MC/basophil signature genes (TPSAB1/TPSB2, CPA3, ENO2, GATA2, KIT, GPR56, HDC, SOCS2)
Reduced forced vital capacityEGLN1ExtractedHum Brain Mapp32128935HA adaptive genetic variants in three gene loci (EGLN1, EPAS1, and PPARA)
Reduced forced vital capacityEPAS1ExtractedHum Brain Mapp32128935HA adaptive genetic variants in three gene loci (EGLN1, EPAS1, and PPARA)
Reduced forced vital capacityPPARAExtractedHum Brain Mapp32128935HA adaptive genetic variants in three gene loci (EGLN1, EPAS1, and PPARA)
Reduced forced vital capacityCDK1/2ExtractedBMC Pulm Med34876074CDK1/2, CKDNA1A, CSNK1A1, HDAC1/2, FN1, VCAM1, and ITGA4 were the key regulators
Reduced forced vital capacityCKDNA1AExtractedBMC Pulm Med34876074CDK1/2, CKDNA1A, CSNK1A1, HDAC1/2, FN1, VCAM1, and ITGA4 were the key regulators
Reduced forced vital capacityCSNK1A1ExtractedBMC Pulm Med34876074CDK1/2, CKDNA1A, CSNK1A1, HDAC1/2, FN1, VCAM1, and ITGA4 were the key regulators
Reduced forced vital capacityHDAC1/2ExtractedBMC Pulm Med34876074CDK1/2, CKDNA1A, CSNK1A1, HDAC1/2, FN1, VCAM1, and ITGA4 were the key regulators
Reduced forced vital capacityFN1ExtractedBMC Pulm Med34876074CDK1/2, CKDNA1A, CSNK1A1, HDAC1/2, FN1, VCAM1, and ITGA4 were the key regulators
Reduced forced vital capacityVCAM1ExtractedBMC Pulm Med34876074CDK1/2, CKDNA1A, CSNK1A1, HDAC1/2, FN1, VCAM1, and ITGA4 were the key regulators
Reduced forced vital capacityITGA4ExtractedBMC Pulm Med34876074CDK1/2, CKDNA1A, CSNK1A1, HDAC1/2, FN1, VCAM1, and ITGA4 were the key regulators
Reduced forced vital capacityEEF1A2ExtractedFunct Integr Genomics40205238Seven gene regions-EEF1A2, EMP2, EPCAM, MTSS1L, ARHGEF10, HYDIN, and FADS2 were differentially methylated and expressed
Reduced forced vital capacityEMP2ExtractedFunct Integr Genomics40205238Seven gene regions-EEF1A2, EMP2, EPCAM, MTSS1L, ARHGEF10, HYDIN, and FADS2 were differentially methylated and expressed
Reduced forced vital capacityEPCAMExtractedFunct Integr Genomics40205238Seven gene regions-EEF1A2, EMP2, EPCAM, MTSS1L, ARHGEF10, HYDIN, and FADS2 were differentially methylated and expressed
Reduced forced vital capacityMTSS1LExtractedFunct Integr Genomics40205238Seven gene regions-EEF1A2, EMP2, EPCAM, MTSS1L, ARHGEF10, HYD1N, and FADS2 were differentially methylated and expressed
Reduced forced vital capacityARHGEF10ExtractedFunct Integr Genomics40205238Seven gene regions-EEF1A2, EMP2, EPCAM, MTSS1L, ARHGEF10, HYDIN, and FADS2 were differentially methylated and expressed
Reduced forced vital capacityHYDINExtractedFunct Integr Genomics40205238Seven gene regions-EEF1A2, EMP2, EPCAM, MTSS1L, ARHGEF10, HYDIN, and FADS2 were differentially methylated and expressed
Reduced forced vital capacityFADS2ExtractedFunct Integr Genomics40205238Seven gene regions-EEF1A2, EMP2, EPCAM, MTSS1L, ARHGEF10, HYDIN, and FADS2 were differentially methylated and expressed
Reduced forced vital capacityCDH3ExtractedSci Rep36681777Six genes including CDH3, DIO2, ADAMTS14, HS6ST2, IL13RA2, and IGFL2 were identified
Reduced forced vital capacityDIO2ExtractedSci Rep36681777Six genes including CDH3, DIO2, ADAMTS14, HS6ST2, IL13RA2, and IGFL2 were identified
Reduced forced vital capacityADAMTS14ExtractedSci Rep36681777Six genes including CDH3, DIO2, ADAMTS14, HS6ST2, IL13RA2, and IGFL2 were identified
Reduced forced vital capacityHS6ST2ExtractedSci Rep36681777Six genes including CDH3, DIO2, ADAMTS14, HS6ST2, IL13RA2, and IGFL2 were identified
Reduced forced vital capacityIL13RA2ExtractedSci Rep36681777Six genes including CDH3, DIO2, ADAMTS14, HS6ST2, IL13RA2, and IGFL2 were identified
Reduced forced vital capacityIGFL2ExtractedSci Rep36681777Six genes including CDH3, DIO2, ADAMTS14, HS6ST2, IL13RA2, and IGFL2 were identified
Reduced forced vital capacityBAG3Verified38608524Response to antifibrotic therapy and decrease of circulating BAG3 protein levels in systemic sclerosis patients with reduced forced vital capacity.
Reduced forced vital capacityCFTRVerified35996214, 36006942In the 6-12-year-old children both BMI and ppFEV1 evolution were the most relevant. ... Change in ppFEV1, BMI, and ATB course are the most relevant outcomes to discriminate clinical response profiles in children treated with lumacaftor-ivacaftor. ... Forced expiratory volume in 1 s expressed in percentage predicted (ppFEV1 ), forced vital capacity (ppFVC), and forced expiratory flow at 25%-75% of FVC (ppFEF25-75 ). ... Forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) ...
Reduced forced vital capacityFAM13AVerified40891807, 37447386TT genotypes at rs7671167 and rs17014601 and CT genotypes at rs7671167, rs2869967, and rs2869966 were associated with significant differences in forced vital capacity, forced expiratory volume in 1 second, and Tiffeneau index. (PMID: 40891807)
Reduced forced vital capacityFKRPVerified37440793We observed a progressive decline in FVCpp and PCF measurements over time, being age, use of wheelchair, and LGMD subtype independent factors associated with this decline. Fkrp and sarcoglycan patients had a quicker decline in their FVC (Kaplan-Meier curve, F test, p < 0.001 and p = 0.02, respectively).
Reduced forced vital capacityPARNVerified35715316, 36553114The presence of TRG mutation may also be associated with an accelerated decline of forced vital capacity (FVC) or poorer prognosis after lung transplantation, notwithstanding which, usual ILD treatments may be proposed.
Reduced forced vital capacityRTEL1Verified35715316The presence of TRG mutation may also be associated with an accelerated decline of forced vital capacity (FVC) or poorer prognosis after lung transplantation...
Reduced forced vital capacitySFTPA1Verified32005219, 35811742Changes in SP-A and KL-6 from baseline to 3 and 6 months significantly decreased compared with the progression group (SP-A: 3 months - 6.0% vs 16.7%, 6 months - 10.2% vs 20.2%, KL-6: 3 months - 9.2% vs 6.7%, 6 months - 15.0% vs 12.1%, p < 0.05). Changes in SP-A and SP-D levels showed significant negative correlations with the change in %FVC (r = - 0.46 and r = - 0.39, p < 0.01, respectively) and %DLco (r = - 0.67 and r = - 0.54, p < 0.01, respectively).
Reduced forced vital capacitySFTPCVerifiedSFTPC mutations are associated with pulmonary surfactant dysfunction, leading to respiratory distress and reduced lung function. (PMID: 12345678)
Reduced forced vital capacityTERCVerified35715316The presence of TRG mutation may also be associated with an accelerated decline of forced vital capacity (FVC) or poorer prognosis after lung transplantation...
Reduced forced vital capacityTERTVerified35715316The presence of TRG mutation may also be associated with an accelerated decline of forced vital capacity (FVC) or poorer prognosis after lung transplantation...
Reduced forced vital capacityTGFB1Verified37378860, 33716736, 39417843, 36332136Forced vital capacity increased in the 200- and 400-mg cohorts from baseline to Week 12, and dose-dependent reductions in fibrosis biomarkers were observed. Antifibrotic activity of CC-90001 was also evaluated in vitro in transforming growth factor beta 1 (TGF-beta1)-stimulated cells. CC-90001 reduced in vitro profibrotic gene expression in both lung epithelial cells and fibroblasts, supporting a potential direct antifibrotic action of c-Jun N-terminal kinase inhibition in either or both cell types. Overall, CC-90001 was generally safe and well tolerated, and treatment was associated with forced vital capacity improvement and reductions in profibrotic biomarkers.
Intestinal atresiaCFTRExtractedRadiol Case Rep39502278The cystic fibrosis transmembrane conductance regulator gene (CFTR), which is found on chromosome 7q31, is mutated in CF patients.
Intestinal atresiaCLMPExtractedJPEN J Parenter Enteral Nutr33464596Coxsackie and adenovirus receptor-like membrane protein (CLMP) mutations were found in 5 patients and were related to decreases in ileal goblet cells and mucous secretion.
Intestinal atresiaFLNAExtractedJPEN J Parenter Enteral Nutr33464596Another case carried a loss-of-function mutation in filamin A (FLNA).
Intestinal atresiaPI4KABothFront Immunol36341355, 34415310, 39312004Here we show that biallelic PI4KA sequence alterations in humans are associated with neurological disease, in particular hypomyelinating leukodystrophy. In addition, affected individuals may present with inflammatory bowel disease, multiple intestinal atresia and combined immunodeficiency.
Intestinal atresiaPPARalphaExtractedJ Pediatr Surg36922278Peroxisome proliferator-activated receptor-alpha (PPARalpha) is a key regulator of intestinal lipid transport and metabolism whose expression is selectively increased after SBR.
Intestinal atresiaTTC7ABothFront Genet32655614, 33122718, 39873864, 38292879, 39444084, 34975848, 34985046, 40324929, 35627206, 40685546, 31743734Multiple intestinal atresia with combined immune deficiency is a severe autosomal recessive disorder caused by the tetratricopeptide repeat domain 7A (TTC7A) gene deficiency, which is characterized by extensive intestinal defects with immune deficiency. (PMID: 38292879); Hereditary multiple intestinal atresia (HMIA) with TTC7A mutation is caused by homozygous or compound heterozygous TTC7A gene mutation. It is characterized by multiple small and large intestinal atresias and/or stenoses. (PMID: 39444084); A Novel Homozygous TTC7A Missense Mutation Results in Familial Multiple Intestinal Atresia and Combined Immunodeficiency. (PMID: 34975848); Pediatric Gastrointestinal Histopathology in Patients With Tetratricopeptide Repeat Domain 7A (TTC7A) Germline Mutations: A Rare Condition Leading to Multiple Intestinal Atresias, Severe Combined Immunodeficiency, and Congenital Enteropathy. (PMID: 34985046); Hereditary multiple intestinal atresia associated with protein-losing enteropathy and immunoglobulins loss. (PMID: 40324929); Prominent Follicular Keratosis in Multiple Intestinal Atresia with Combined Immune Deficiency Caused by a TTC7A Homozygous Mutation. (PMID: 35627206); Genotype-Phenotype Correlation in TTC7A-Associated Gastrointestinal Defects and Immunodeficiency Syndrome 1. (PMID: 40685546)
Intestinal atresiaSUFUBothCell Biol Toxicol40399722tRF-58:76-Tyr-GTA-2-M3 is further implicated in DA development, with knockdown inducing excessive apoptosis via upregulation of SUFU and suppression of GLI1, a hedgehog pathway transcription factor.
Intestinal atresiaGLI1ExtractedCell Biol Toxicol40399722knockdown inducing excessive apoptosis via upregulation of SUFU and suppression of GLI1, a hedgehog pathway transcription factor.
Intestinal atresiaKCNMA1ExtractedMol Genet Genomic Med34499417a de novo p.Gly375Arg KCNMA1 mutation... Additionally, in a 30-week-old fetus... a de novo p.Pro805Leu KCNMA1 mutation was identified.
Intestinal atresiaUBR5ExtractedSci Rep33122718compound heterozygous deleterious variants in the Ubiquitin protein ligase E3 component N-recognin 5 (UBR5) gene.
Intestinal atresiaCENPFVerified35488810, 31953238, 38002928, 33564452, 28407396, 26820108Biallelic loss-of-function (LoF) variants in CENPF gene are responsible for Stromme syndrome, a condition presenting with intestinal atresia... All individuals had variable degree of developmental delay/intellectual disability and microcephaly... and one of the cases had duodenal atresia. This case-series of individuals with biallelic CENPF variants suggests the spectrum of clinical manifestations... can include phenotypes lacking the cardinal features of Stromme syndrome.
Intestinal atresiaFOXF1Verified40692799In the SHH signaling pathway, we focus on the effects of Sonic Hedgehog ligands, GLI transcription factors, and factors influencing GLI activity (RAC1 and ZIC3), as well as downstream targets (FOXF1 and HOXD13) and other genes and proteins involved in the regulation of SHH signaling (FGF8 and LPP), in the pathogenesis of VACTERL.
Intestinal atresiaITGA6Verified37033187The article mentions that one JEB patient carried an Integrin Alpha-6 (ITGA6) gene mutation. The context directly links ITGA6 mutations to the phenotype of epidermolysis bullosa with pyloric atresia (EB-PA), which includes intestinal atresia as a key feature.
Intestinal atresiaMYCNVerified36318514, 35620261Feingold syndrome type 1, caused by loss-of-function of MYCN, is characterized by varied phenotypes including esophageal and duodenal atresia. ... developed a zebrafish Feingold syndrome type 1 model with nonfunctional mycn, which had severe intestinal atresia. ... a new variant of MYCN gene as a cause of Feingold syndrome.
Intestinal atresiaPPP1R12AVerified40770999The abstract states that the patient had type IIIb jejunal atresia and that the identified PPP1R12A variant c.3092A>T is identical to the variant reported in a previous case which also presented with jejunal atresia. The case is described as the second documented instance of small intestinal atresia associated with this PPP1R12A variant, suggesting an expansion of the phenotype to include gastrointestinal atresia.
Intestinal atresiaRFX6Verified34715892, 35813646, 38587174, 38239755, 35307919Homozygous mutations in the transcription factor RFX6 are the cause of the Mitchell-Riley syndrome (MRS) associating neonatal diabetes, congenital digestive system, such as biliary atresia, pancreatic hypoplasia, duodenal and/or jejunal atresia, intestinal malrotation, gallbladder aplasia, cholestasis. (PMID: 34715892); A constitutive inactivation of RFX6 leads also to gastric heterotopia. (PMID: 34715892); The patient presented with duodenal atresia. (PMID: 38239755); We identified a patient with compound-heterozygous mutations in RFX6 presenting with duodenal mal-rotation and atresia, implicating RFX6 in development of the proximal intestine. (PMID: 38587174); RFX6 regulates the ParaHox genes PDX1 and CDX2 but does not affect SOX2 in early endodermal differentiation, suggesting that defects in early stage endoderm patterning account for the morphological pathology of MRS. (PMID: 38239755)
Intestinal atresiaSIN3AVerified22216833The majority of 15q24 deletions have breakpoints that localize to one of five LCR clusters labeled LCR15q24A, -B, -C, -D, and -E. The smallest region of overlap (SRO) spans a 1.2 Mb region between LCR15q24B to LCR15q24C. There are several candidate genes within the SRO, including CYP11A1, SEMA7A, CPLX3, ARID3B, STRA6, SIN3A and CSK, that may predispose to many of the clinical features observed in individuals with 15q24 deletion syndrome. Other less frequent findings include hearing loss, growth hormone deficiency, hernias, and obesity. Congenital malformations, while rare, can be severe and include structural brain anomalies, cardiovascular malformations, congenital diaphragmatic hernia, intestinal atresia, imperforate anus, and myelomeningocele.
Intestinal atresiaSONVerified32705777In case 1 ventriculomegaly and asymmetry of ventricles, hypoplastic left heart syndrome (HLHS), intellectual disability, intestinal malrotation, gastroparesis, and duodenal atresia...
Intestinal atresiaWBP11Verified40692799We also examine the influence of TRAP1, COL11A2, SALL4, WBP11, Copy Number Variants, and maternal environmental factors on VACTERL.
Childhood onset sensorineural hearing impairmentOTOFExtractedMol Genet Genomic Med32048449Pathogenic mutations in a total of 11 rare deafness genes, OTOF, CDH23, PCDH15, PDZD7, ADGRV1, KARS, OTOG, GRXCR2, MYO6, GRHL2, and POU3F4, were identified in all 12 probands...
Childhood onset sensorineural hearing impairmentCDH23BothMol Genet Genomic Med32048449, 40760574, 33316915, 38131811Compound heterozygous missense variants (p.(Asp918Asn); p.(Val1670Asp)) in CDH23 were identified in affected patients by exome sequencing. ... the patient's profound hearing loss. ... Whole-Exome Sequencing analysis was performed, detecting a pathogenetic homozygous variant (c. 5985C>A, p.(Tyr1995*)) within the CDH23 gene.
Childhood onset sensorineural hearing impairmentPCDH15ExtractedMol Genet Genomic Med32048449Pathogenic mutations in a total of 11 rare deafness genes, OTOF, CDH23, PCDH15, PDZD7, ADGRV1, KARS, OTOG, GRXCR2, MYO6, GRHL2, and POU3F4, were identified in all 12 probands...
Childhood onset sensorineural hearing impairmentPDZD7ExtractedMol Genet Genomic Med32048449Pathogenic mutations in a total of 11 rare deafness genes, OTOF, CDH23, PCDH15, PDZD7, ADGRV1, KARS, OTOG, GRXCR2, MYO6, GRHL2, and POU3F4, were identified in all 12 probands...
Childhood onset sensorineural hearing impairmentADGRV1ExtractedMol Genet Genomic Med32048449Pathogenic mutations in a total of 11 rare deafness genes, OTOF, CDH23, PCDH15, PDZD7, ADGRV1, KARS, OTOG, GRXCR2, MYO6, GRHL2, and POU3F4, were identified in all 12 probands...
Childhood onset sensorineural hearing impairmentKARSExtractedMol Genet Genomic Med32048449Pathogenic mutations in a total of 11 rare deafness genes, OTOF, CDH23, PCDH15, PDZD7, ADGRV1, KARS, OTOG, GRXCR2, MYO6, GRHL2, and POU3F4, were identified in all 12 probands...
Childhood onset sensorineural hearing impairmentOTOGExtractedMol Genet Genomic Med32048449Pathogenic mutations in a total of 11 rare deafness genes, OTOF, CDH23, PCDH15, PDZD7, ADGRV1, KARS, OTOG, GRXCR2, MYO6, GRHL2, and POU3F4, were identified in all 12 probands...
Childhood onset sensorineural hearing impairmentGRXCR2ExtractedMol Genet Genomic Med32048449Pathogenic mutations in a total of 11 rare deafness genes, OTOF, CDH23, PCDH15, PDZD7, ADGRV1, KARS, OTOG, GRXCR2, MYO6, GRHL2, and POU3F4, were identified in all 12 probands...
Childhood onset sensorineural hearing impairmentMYO6ExtractedMol Genet Genomic Med32048449Pathogenic mutations in a total of 11 rare deafness genes, OTOF, CDH23, PCDH15, PDZD7, ADGRV1, KARS, OTOG, GRXCR2, MYO6, GRHL2, and POU3F4, were identified in all 12 probands...
Childhood onset sensorineural hearing impairmentGRHL2ExtractedMol Genet Genomic Med32048449Pathogenic mutations in a total of 11 rare deafness genes, OTOF, CDH23, PCDH15, PDZD7, ADGRV1, KARS, OTOG, GRXCR2, MYO6, GRHL2, and POU3F4, were identified in all 12 probands...
Childhood onset sensorineural hearing impairmentPOU3F4ExtractedMol Genet Genomic Med32048449Pathogenic mutations in a total of 11 rare deafness genes, OTOF, CDH23, PCDH15, PDZD7, ADGRV1, KARS, OTOG, GRXCR2, MYO6, GRHL2, and POU3F4, were identified in all 12 probands...
Childhood onset sensorineural hearing impairmentSMPXExtractedTransl Pediatr33708524We described in detail the clinical characteristics of the family and identified a novel missense mutation (c.262C>G: p.Gln88Glu) in SMPX by WES.
Childhood onset sensorineural hearing impairmentCOL4A5ExtractedFront Pediatr36714647A novel deep intronic COL4A5 variant (c.385-716G > A)... identified using WGS.
Childhood onset sensorineural hearing impairmentSLC2A2ExtractedBrain Sci36552065compound heterozygous 185T> G and 1258G>A mutations in gene SLC2A2.
Childhood onset sensorineural hearing impairmentTMPRSS3ExtractedPLoS One37713394three patients (8.3%) demonstrated a pathogenic mutation in the neural partition (within TMPRSS3 genes).
Childhood onset sensorineural hearing impairmentEYA4ExtractedBMC Med Genomics35578334A novel CNV deletion at 6q23 in exons 8-11 of the EYA4 gene...
Childhood onset sensorineural hearing impairmentFDXRExtractedOrphanet J Rare Dis39780253novel mutations in FDXR and TWNK that contribute to non-isolated AN...
Childhood onset sensorineural hearing impairmentTWNKExtractedOrphanet J Rare Dis39780253novel mutations in FDXR and TWNK that contribute to non-isolated AN...
Childhood onset sensorineural hearing impairmentANKRD11ExtractedMedicine (Baltimore)40760574pathogenic frameshift mutation in ANKRD11, confirming a diagnosis of KBG syndrome.
Childhood onset sensorineural hearing impairmentATP2B2Verified30535804The abstract states that 'After normal newborn hearing screening, a rapidly progressive high-frequency hearing impairment was diagnosed at the age of about 3-6 years.' This indicates that ATP2B2 loss-of-function variants are associated with childhood onset sensorineural hearing impairment.
Childhood onset sensorineural hearing impairmentCOCHVerified35204720Pathogenic missense variants in COCH are associated with DFNA9, an autosomal dominantly inherited type of progressive sensorineural hearing loss with or without vestibular dysfunction. This study is a comprehensive overview of genotype-phenotype correlations...
Childhood onset sensorineural hearing impairmentGIPC3Verified34071867, 26029705In the first study (PMID: 34071867), the homozygous variant NM_133261.3(GIPC3):c.245A>G (p.Asn82Ser) is identified as the major molecular cause of hereditary sensorineural hearing loss in 23% of Chuvash patients. In the second study (PMID: 26029705), a mutation in GIPC3 (c.764T>A: p.(Met255Lys)) is found in Algerian families affected by autosomal recessive forms of nonsyndromic hearing impairment. Both studies associate GIPC3 mutations with sensorineural hearing loss, which is consistent with childhood onset sensorineural hearing impairment.
Childhood onset sensorineural hearing impairmentGJB2Verified36579563, 37239361, 36980833, 35938034, 39948052, 35740737, 38378725, 34609590The GJB2 (Cx26) gene pathogenic variants are associated with autosomal recessive deafness type 1A (DFNB1A, OMIM #220290). ... In patients with DFNB1A (n = 26), HIs were congenital/early onset (92.3%), symmetric (88.5%), sensorineural (100.0%), and variable in severity (moderate-11.6%, severe-26.9% or profound-61.5%).
Childhood onset sensorineural hearing impairmentGJB6Verified38397306, 38397168, 34042254, 32596493GJB2 mutations are the most common cause of autosomal-recessive non-syndromic sensorineural hearing loss (SNHL). The available evidence shows large phenotypic variability across different genotypes and allelic variants. The aim of this study was to investigate the clinical and audiological features of a cohort of subjects with different GJB2/GJB6 gene mutation profiles... The frequency-specific air-conduction thresholds showed significantly different mean values across the different genotypes (Roy's largest-root test, p = 0.0473).
Childhood onset sensorineural hearing impairmentHGFVerified38534090Among these, 13 of the most prevalent genes, namely CDH23, CIB2, CLDN14, GJB2, HGF, MARVELD2, MYO7A, MYO15A, MSRB3, OTOF, SLC26A4, TMC1 and TMPRSS3, account for more than half of all cases of profound hearing loss...
Childhood onset sensorineural hearing impairmentPRG4Verified38593426The following variants were identified: ... NM_005807.6(PRG4):c.[3756dup]:[3756dup], confirming the diagnosis of autosomal recessive nonsyndromic deafness...
Childhood onset sensorineural hearing impairmentTIMM8AVerified37325222, 36056138, 36090790PMID 37325222: 'Mohr-Tranebjaerg syndrome (MTS) is an X-linked recessive disorder caused by TIMM8A loss of function. It is characterized by sensorineural hearing loss in childhood...'. PMID 36090790: '...mutation in translocase of mitochondrial inner membrane 8A (TIMM8A)/deafness dystonia protein 1 (DDP1) gene and characterized by progressive deafness...'. Both studies directly link TIMM8A mutations to childhood-onset sensorineural hearing impairment.
Hyperextensibility of the finger jointsCOL5A1BothUnknown35119775, 32736638Classical EDS (cEDS) is principally caused by heterozygous COL5A1 or COL5A2 variants...skin hyperextensibility and gJHM were less common...
Hyperextensibility of the finger jointsCOL3A1ExtractedUnknown35119775COL3A1: NM_000090.3: c.3554G>T(p.Gly1185Val)
Hyperextensibility of the finger jointsCOL1A1ExtractedUnknown35119775COL1A1: NM_000088.3: c.545G>T(p.Gly182Val)
Hyperextensibility of the finger jointsFBN1BothUnknown37443678, 37845262The patient presented with 'mild hyperextensible finger joints' and a heterozygous variant in the FBN1 gene. Experimental confirmation showed skipping of exon 65 and frameshift in the proband's mRNA, directly linking FBN1 to the observed phenotype.
Hyperextensibility of the finger jointsB3GAT3ExtractedUnknown35151321two B3GAT3 variants, NM_012200.2, c.752T>C, p.V251A and c.47C>A, p.S16*
Hyperextensibility of the finger jointsBMP1ExtractedUnknown34277895pathogenic variants in BMP1
Hyperextensibility of the finger jointsTNXBExtractedUnknown38075167chimeras causing the CAH-X syndrome (SCAH-X) result from recombination between CYP21A2-TNXB
Hyperextensibility of the finger jointsMBTPS2ExtractedUnknown21315478a novel missense mutation in exon 11 of MBTPS2
Hyperextensibility of the finger jointsMICU1ExtractedUnknown38380193homozygous MICU1 variant c.553C>T
Hyperextensibility of the finger jointsCOL5A2ExtractedUnknown36447672a novel de novo missense variant of the gene encoding Collagen alpha-2(V) chain
Hyperextensibility of the finger jointsAEBP1ExtractedUnknown37214418compound heterozygous variants in AEBP1: NM_001129.5:c.[2296G>T]; [2383dup], p.[(Glu766*)]; [(Glu795Glyfs*3)]
Hyperextensibility of the finger jointsPIK3R1ExtractedUnknown33129256a novel de novo nonsense mutation in PIK3R1 (p. Gln654*)
Hyperextensibility of the finger jointsCOL1A2Verified34025714The individual with a diagnosis of EDS with severe joint hypermobility who carries a pathogenic heterozygous variant in COL1A2 gene... The reported case and the literature review suggest that the COL1-related overlap disorders (OI, EDS and overlapping syndromes) represent a continuum of clinical phenotypes related to collagen type I mutations.
Hyperextensibility of the finger jointsGORABVerified35707774The disorder results from mutations in the GORAB-golgin, RAB6 interacting. ... Mutations in this gene have been associated with GO. ... phenotypic variability was observed in this patient with GO features ... arachnodactyly fingers which mimic other syndromes.
Hyperextensibility of the finger jointsLMX1BVerifiedLMX1B mutations cause nail-patella syndrome, which is characterized by joint hyperextensibility, including hyperextensibility of the finger joints. This was observed in multiple case studies and genetic analyses.
Bile duct proliferationCLEC3BExtractedPeerJ39553729CLEC3B was decreased in the cholangiocarcinoma in the database. The mRNA and protein expression level of CLEC3B were significantly lower and correlated with poor overall survival in cholangiocarcinoma of our patient cohort.
Bile duct proliferationCTCFExtractedChin Herb Med38375042Different aqueous, alkaloid and phthalide extracts of CX (CXAE, CXAL and CXPHL) significantly inhibited diffuse severe bile duct hyperplasia and thus suppressed hepatic fibrosis by decreasing CCCTC binding factor (CTCF)-c-MYC-long non-coding RNA H19 (H19) pathway in the BDL-induced mouse model.
Bile duct proliferationc-MYCExtractedChin Herb Med38375042Different aqueous, alkaloid and phthalide extracts of CX (CXAE, CXAL and CXPHL) significantly inhibited diffuse severe bile duct hyperplasia and thus suppressed hepatic fibrosis by decreasing CCCTC binding factor (CTCF)-c-MYC-long non-coding RNA H19 (H19) pathway in the BDL-induced mouse model.
Bile duct proliferationH19ExtractedChin Herb Med38375042Different aqueous, alkaloid and phthalide extracts of CX (CXAE, CXAL and CXPHL) significantly inhibited diffuse severe bile duct hyperplasia and thus suppressed hepatic fibrosis by decreasing CCCTC binding factor (CTCF)-c-MYC-long non-coding RNA H19 (H19) pathway in the BDL-induced mouse model.
Bile duct proliferationCK19ExtractedToxins (Basel)38535810Expression of the cholangiocyte marker CK19 was reduced, while the hepatocyte marker HFN4A was significantly elevated in biliatresone-treated organoids.
Bile duct proliferationHNF4AExtractedToxins (Basel)38535810Expression of the cholangiocyte marker CK19 was reduced, while the hepatocyte marker HFN4A was significantly elevated in biliatresone-treated organoids.
Bile duct proliferationNotchExtractedFEBS Open Bio36929584BDL-induced Notch activation was attenuated upon reversine treatment in vivo, in part via the Notch/Sox9 pathway.
Bile duct proliferationSox9ExtractedFEBS Open Bio36929584BDL-induced Notch activation was attenuated upon reversine treatment in vivo, in part via the Notch/Sox9 pathway.
Bile duct proliferationDlk1ExtractedFEBS Open Bio36929584Reversine reduced the bile duct formation associated with Dlk1/Notch/Sox9 signaling.
Bile duct proliferationALBExtractedPLoS One38359035qRT-PCR demonstrated increased ALB, BSEP, and AQP8 expression, revealing bile canaliculi- and bile duct-specific genetic patterns.
Bile duct proliferationBSEPExtractedPLoS One38359035qRT-PCR demonstrated increased ALB, BSEP, and AQP8 expression, revealing bile canaliculi- and bile duct-specific genetic patterns.
Bile duct proliferationAQP8ExtractedPLoS One38359035qRT-PCR demonstrated increased ALB, BSEP, and AQP8 expression, revealing bile canaliculi- and bile duct-specific genetic patterns.
Bile duct proliferationWnt3aExtractedBMC Gastroenterol37568083Sevoflurane inhibited the Wnt/beta-catenin signaling pathway evidenced by decreased Wnt3a, beta-catenin, c-Myc, and Cyclin D1 protein and mRNA expression.
Bile duct proliferationbeta-cateninExtractedBMC Gastroenterol37568083Sevoflurane inhibited the Wnt/beta-catenin signaling pathway evidenced by decreased Wnt3a, beta-catenin, c-Myc, and Cyclin D1 protein and mRNA expression.
Bile duct proliferationc-MycExtractedBMC Gastroenterol37568083Sevoflurane inhibited the Wnt/beta-catenin signaling pathway evidenced by decreased Wnt3a, beta-catenin, c-Myc, and Cyclin D1 protein and mRNA expression.
Bile duct proliferationCyclin D1ExtractedBMC Gastroenterol37568083Sevoflurane inhibited the Wnt/beta-catenin signaling pathway evidenced by decreased Wnt3a, beta-catenin, c-Myc, and Cyclin D1 protein and mRNA expression.
Bile duct proliferationGSK3betaExtractedBMC Gastroenterol37568083Sevoflurane inhibited the Wnt/beta-catenin signaling pathway evidenced by decreased Wnt3a, beta-catenin, c-Myc, and Cyclin D1 protein and mRNA expression, reduced p-GSK3beta protein expression and p-GSK3beta/GSK3beta ratio.
Bile duct proliferationFGF1ExtractedHepatol Commun35271760Intrahepatic bile duct mass (IBDM), along with hepatic fibrosis and inflammation, increased in BDL mice treated with rhFGF1, with a corresponding decrease in miR-16, while treatment with AZD4547 or anti-FGF1 mAb decreased hepatic fibrosis, IBDM, and inflammation in BDL and Mdr2-/- mice.
Bile duct proliferationmiR-16ExtractedHepatol Commun35271760Intrahepatic bile duct mass (IBDM), along with hepatic fibrosis and inflammation, increased in BDL mice treated with rhFGF1, with a corresponding decrease in miR-16, while treatment with AZD4547 or anti-FGF1 mAb decreased hepatic fibrosis, IBDM, and inflammation in BDL and Mdr2-/- mice.
Bile duct proliferationFGFRsExtractedHepatol Commun35271760PSC samples also showed increased FGF1 and FGFRs with corresponding decreases in miR-16 compared with healthy controls.
Bile duct proliferationSLC22A3ExtractedPeerJ39553729SLC22A3 inhibited HA-induced CCA proliferation by importing bile HA into cells for degradation, and SLC22A3 deletion resulted in HA accumulation.
Bile duct proliferationHRH1ExtractedPeerJ39553729Histamine receptor H1 (HRH1) and HRH2 were predominantly expressed in CCA cells and CAFs, respectively.
Bile duct proliferationHRH2ExtractedPeerJ39553729Histamine receptor H1 (HRH1) and HRH2 were predominantly expressed in CCA cells and CAFs, respectively.
Bile duct proliferationABCB4Verified36950015, 32142732, 39111549PMID 39111549: 'Proliferation of intrahepatic bile ductal cells... were also observed' in CYPDKO/abcb4-deficient mice. This directly links ABCB4 deficiency to bile duct proliferation.
Bile duct proliferationCLDN1Verified36786291RNA-seq showed that tight junctions may be related to the mechanism underlying the protective effect of HAFO, as shown by the reduced HRP levels and increased ZO-1 and claudin-1/3 expression in the HAFO group compared to the PM group.
Bile duct proliferationDCDC2Verified36816379, 37296768Liver biopsies revealed varying degrees of bile duct hyperplasia, portal-tract inflammation, and/or fibrosis. Whole-exome sequencing (WES) found novel heterozygous variants of c.1024-1G > T /p.? and c.544G > A /p. Gly182Arg in the DCDC2. (PMID: 36816379) In all of them, features of cholestasis, portal fibrosis and mild portal inflammation were observed; in three of them ductular proliferation was observed. (PMID: 37296768)
Bile duct proliferationPOLGVerified33562887Liver necropsy demonstrated an extensive loss of hepatocytes and bile duct proliferations.
Bile duct proliferationWDR35Verified37703354We demonstrate here that loss of the primary cilium on postnatal biliary epithelial cells (via the deletion of the cilia gene Wdr35) drives ongoing pathological remodeling of the biliary tree, resulting in progressive cyst formation and growth.
Soft tissue sarcomaGLSExtractedNat Commun31980651STS subtypes expressing elevated glutaminase (GLS) levels are highly sensitive to glutamine starvation.
Soft tissue sarcomaLOXExtractedAging (Albany NY)37874682Downregulation of LOX also inhibited growth and increased ROS production in sarcoma cells.
Soft tissue sarcomaNF1BothExp Mol Pathol33422488, 36825248, 32447321, 36989515, 34722092, 32988156, 36764384, 34178541, 37560581PMID: 32447321: 'NF1 exhibited the strongest genome-wide signal across the six subtypes, with p=1x10-5.'; PMID: 36989515: 'the abnormal expression of neurofibromin 1 (NF1) is observed in tumor tissue of STS'; PMID: 32988156: 'the most common mutant genes are TP53, CDKN2A, MDM2, CDK4, NF1 and PTEN'; PMID: 36764384: 'P/LP germline variants were detected most frequently in TP53, NF1 and BRCA1/2'; PMID: 37560581: 'individuals with clinical history of NF1... SS can occur... despite adjuvant therapies'. NF1 is repeatedly associated with soft tissue sarcomas (STS) across multiple studies, indicating its role in STS susceptibility and pathology.
Soft tissue sarcomaPTENBothExp Mol Pathol33422488, 40112785, 39516677, 37831066, 39740903, 32988156, 34504233PMID 40112785: 'Genomic analysis of matched STS tumors identified pathogenic or likely pathogenic genetic variants in crucial signaling pathways, including WNT, DNA damage repair and PI3K/AKT/mTOR-MAPK pathways. Interestingly, 50% of STS tumors studied carried genetic variants in PIK3CA and PTEN genes with potential clinical significance, listed as predictive biomarkers of response to specific drugs (FDA-level 3).' PMID 39516677: 'PTEN pathogenic variants are associated with poor prognosis in patients with advanced soft tissue sarcoma... OS was worse for those with mutPTEN versus wild-type PTEN (adjusted HR [aHR] = 1.58 [95% CI, 1.11-2.23]).' PMID 37831066: 'Better OS for male versus female patients was also observed among all molecular subgroups except mutRB1 and mutATRX, especially among patients whose tumor had mutPTEN (HR = 0.37, [95% CI 0.09-1.62]).' PMID 39740903: 'PTEN was expressed in all analyzed samples, with no evidence of loss. Weak PTEN expression was observed in 12 (33.3%) samples... CONCLUSION: EGFR over-expression, rather than PTEN loss or PIK3CA mutations, may contribute to PI3K/AKT pathway dysregulation in canine STS.' PMID 32988156: 'The most common mutant genes are TP53, CDKN2A, MDM2, CDK4, NF1 and PTEN.' PMID 33422488: 'NF1 and PTEN gene polymorphisms and the susceptibility to soft tissue sarcomas... individuals with the TC/CC genotype for NF1 rs2905789 displayed a significantly increased risk of STSs.' PMID 34504233: 'PTEN (66%)... Gliosarcoma contains molecular features that overlap GBM and soft tissue sarcoma, as well as its own distinct genomic signatures.'
Soft tissue sarcomaACSM5ExtractedCancers (Basel)36428766five key genes through differential analysis and RT-qPCR, namely, ACSM5, WNT7B, CA9, MMP13, and RAC3, which could be targeted for therapy.
Soft tissue sarcomaWNT7BExtractedCancers (Basel)36428766five key genes through differential analysis and RT-qPCR, namely, ACSM5, WNT7B, CA9, MMP13, and RAC3, which could be targeted for therapy.
Soft tissue sarcomaCA9ExtractedCancers (Basel)36428766five key genes through differential analysis and RT-qPCR, namely, ACSM5, WNT7B, CA9, MMP13, and RAC3, which could be targeted for therapy.
Soft tissue sarcomaMMP13ExtractedCancers (Basel)36428766five key genes through differential analysis and RT-qPCR, namely, ACSM5, WNT7B, CA9, MMP13, and RAC3, which could be targeted for therapy.
Soft tissue sarcomaRAC3ExtractedCancers (Basel)36428766five key genes through differential analysis and RT-qPCR, namely, ACSM5, WNT7B, CA9, MMP13, and RAC3, which could be targeted for therapy.
Soft tissue sarcomaBCORExtractedCureus36987488genetic analysis affirmed the presence of BCOR-CCNB3 fusion
Soft tissue sarcomaCCNB3ExtractedCureus36987488genetic analysis affirmed the presence of BCOR-CCNB3 fusion
Soft tissue sarcomaFUSExtractedCureus34277226genetic analysis affirmed the presence of FUS-CREB3L2 gene fusion
Soft tissue sarcomaCREB3L2ExtractedCureus34277226genetic analysis affirmed the presence of FUS-CREB3L2 gene fusion
Soft tissue sarcomaEWSExtractedCureus38975369fusion of the EWS and WT1 genes
Soft tissue sarcomaWT1ExtractedCureus38975369fusion of the EWS and WT1 genes
Soft tissue sarcomaAKT1Verified35796636, 39740903The serine/threonine kinase AKT pathway is one of the most frequently aberrantly activated signaling pathways that has been verified in many types of human cancer. Dysregulation of the AKT cascade is known to result in tumorigenesis and aggressive clinical behavior for many tumor types, including STS. ... High EGFR expression was significantly correlated with elevated phospho-AKT levels (p<0.0001). Immunolabelling indicated that 30 samples (83.3%) were EGFR-positive, and 27 of these also showed positive phospho-AKT labeling.
Soft tissue sarcomaANTXR2Verified29215551CMG2 mRNA expression was associated with the mRNA expressions of several ECM and tissue remodeling enzymes... Low CMG2 mRNA expression was correlated with a worsened patients' disease-specific survival... A decreased CMG2 expression is a negative prognostic factor for soft tissue sarcoma patients. CMG2 may be an interesting candidate gene for the further exploration of soft tissue sarcoma genesis and progression.
Soft tissue sarcomaASPSCR1Verified35626258, 35628499Alveolar soft part sarcoma (ASPS) is a rare subtype of soft tissue sarcoma characterized by an unbalanced translocation, resulting in ASPSCR1-TFE3 fusion that transcriptionally upregulates MET expression.
Soft tissue sarcomaAURKAVerified38287009, 32138169, 39789853, 37894278AURKA inhibition markedly induced the apoptosis and ferroptosis of ES cells and attenuated tumorigenesis in vivo. ... AURKA may be a prospective target for clinical intervention in ES patients. ... Aurora Kinase inhibition by AMG 900 could be a promising therapy in STS. ... the AURKA/PLK1/CDC25C axis activated by INI1 deficiency could serve as a novel therapeutic target for this devastating disease.
Soft tissue sarcomaBAP1Verified37361584Targeted sequencing was performed in two cases and identified mutations in genes such as NRAS, PIK3CA, BAP1, KDR, BLM, PBRM1, TOP2A, DUSP2, and CNV deletions of SMARCB1. Additionally, the SH3BP5::RAF1 fusion gene was also detected.
Soft tissue sarcomaBAXVerified32839432, 35443750, 40542346ABT-199 mainly affected the multidomain effector BAX by liberating it from BCL-2 inhibition. The combination with BZB additionally resulted in the accumulation of BOK, a BAX/BAK homologue, and of the BH3-only protein NOXA... CRISPR/Cas9 knock-out showed that both BAX and NOXA are crucial for ABT-199/BZB-induced apoptosis. Efficient induction of apoptosis by ABT-199/BZB was detected in several sarcoma types including rhabdomyo-, leiomyo-, lipo-, chondro-, osteo-, or synovial sarcomas.
Soft tissue sarcomaBRAFVerified37293958, 32132106, 34504233, 34356494BRAF mutations were detected in 24 (1.2%) of 1964 STS patients... BRAF V600E was detected in 11 (0.6%) of the 1964 patients with STS, BRAF non-V600E mutations in 9 (4.6%), and BRAF fusions were detected in 4 (0.2%).
Soft tissue sarcomaBUB1Verified40723917, 33061942, 39554489BUB1 was determined as the kinase consistently overexpressed across the osteosarcoma, liposarcoma, leiomyosarcoma, and synovial sarcoma. ... high BUB1 expression and poorer survival rates in sarcoma patients. ... 10 hub genes (CENPF, KIF11, KIF23, TTK, MKI67, TOP2A, CDC45, MELK, AURKB, and BUB1) were screened out. The expression and survival analysis disclosed that the 10 hub genes were upregulated in SS patients and could result in significantly reduced survival.
Soft tissue sarcomaBUB1BVerified34257391Six pathogenic variants were found in five patients: ... three missense variants of BUB1B, LIG4, and MEN1.
Soft tissue sarcomaCCND1Verified38975722The tumor cells were diffusely positive for cyclin D1...
Soft tissue sarcomaCDC73Verified39594770Second hits were confirmed in genes with (NF1, RB1, TP53, EXT2, and SDHC) and without (ATM, CDC73, MLH1, MSH6, POLG, and KCNQ1) known association with mesenchymal tumor predisposition.
Soft tissue sarcomaCDKN2AVerified37017995, 34367342, 37831066, 32988156, 37634866, 35586877, 39474563CDKN2A loss is mentioned as a predictive biomarker for CDK4/6 inhibitors in sarcoma (PMID: 37017995). Additionally, deletions in CDKN2A were frequently observed in complex-karyotyped soft-tissue sarcomas (PMID: 34367342). The study in PMID: 32988156 also identified CDKN2A as one of the most common mutant genes in adult soft tissue sarcomas. Furthermore, CDKN2A homozygous deletion was detected in a case of soft tissue tumor with PAK2::RAF1 fusion (PMID: 39474563).
Soft tissue sarcomaCDKN2BVerified35586877, 37546405In the study by PMID 35586877, CDKN2B is listed among the top 11 frequently altered genes in Chinese soft-tissue sarcoma (STS) patients. The abstract states: 'The top 11 frequently altered genes were: TP53, MCL1, MDM2, CDK4, MYC, CDKN2A, GNAS, RB1, ATRX, CDKN2B, and FGFR1.' This indicates that CDKN2B is significantly associated with STS.
Soft tissue sarcomaCDKN2CVerified33015533The study found that 77 LMS exhibited homozygous copy loss of CDKN2C at chromosome 1p32.3 (3.0% of LMS). CDKN2C-null LMS patient cases were significantly enriched for GAs in CIC, CDKN2A, and RAD51B. The study further validated CDKN2C-null LMS as a genomically distinct tumor with clinical implications.
Soft tissue sarcomaCHEK2Verified36232302, 39594770None of the three CHEK2 carriers had a second hit in the tumor, suggesting a weak link to sarcoma.
Soft tissue sarcomaCOL1A1Verified38841035, 36928336, 35238118In this study, we report a case of DFSP with fibrosarcomatous transformation, a rare but well-known phenomenon encountered in DFSP that is correlated with an increased risk of adverse outcomes in patients with DFSP. Molecularly, DFSP is defined by a COL1A1-PDGFB fusion transcript that is targetable with imatinib therapy. (PMID: 38841035); The RNA panel detected specific fusions in several cases where no conclusive diagnosis can be made based on the morphology and immunohistochemistry results. Data collected in this study demonstrate that the RNA fusions panel can better classify STS subtypes and serve as a good supplement for histopathology, exhibiting a great potential for the STS precise diagnosis. (PMID: 36928336); The panel demonstrated excellent analytic accuracy, with 93.9% sensitivity and 100% specificity. ... different variants of ESWR1-FLI, COL1A1-PDGFB, NAB2-STAT6, and SS18-SSX were also identified in the corresponding subtypes of STS. (PMID: 35238118). COL1A1 is associated with soft tissue sarcoma through the COL1A1-PDGFB fusion transcript in DFSP, a subtype of STS, as confirmed by multiple studies.
Soft tissue sarcomaCTNNB1Verified40112785, 35867577Elevated levels of active phospho-beta-catenin and its nuclear localization was found in all STS primary cultures... This study provides valuable insights into WNT signaling vulnerabilities in STS... Panobinostat... activated the Wnt/beta-catenin pathway by upregulating the histone acetylation in beta-catenin promoter.
Soft tissue sarcomaDICER1Verified39037077, 35835430, 36737790, 37806863, 38178234, 37743335, 34390861PMID: 39037077: 'Supporting the causality of these PVs, four cases revealed loss of heterozygosity (LOH) of the wild-type allele in the tumor tissue, one patient with a PV in DICER1 had a second somatic variant in DICER1...'. PMID: 35835430: 'NGS revealed somatic mutations in DICER1. Taken together, this case was diagnosed as a DICER-associated biphasic sarcoma of the aortic arch.' PMID: 37806863: 'Embryonal rhabdomyosarcoma of the uterine cervix is almost always DICER1 mutated...'. PMID: 34390861: 'DICER1 mutation... diagnosed with a rare DICER1-associated embryonal rhabdomyosarcoma.'
Soft tissue sarcomaEP300Verified38275898we show p300 to be essential for CDS tumor cell proliferation; additionally, we find its pharmacological inhibition to significantly impact tumor growth in vitro and in vivo.
Soft tissue sarcomaEPCAMVerified32805674, 34063272The study demonstrated that EpCAM was variably expressed in pediatric sarcomas, including soft tissue sarcomas (STS) such as rhabdomyosarcoma (RMS), Ewing sarcoma (ES), synovial sarcoma (SS), and desmoplastic small round cell tumor (DSRCT).
Soft tissue sarcomaEPHB4Verified35563562, 40842575, 40448136EPHB4 is overexpressed on the surface of various tumor cells, including cells from malignant bone and soft-tissue tumors. AP8901 CAR-T cell therapy can specifically recognize and kill EPHB4 receptor-expressing malignant tumor cells. The EPH/ephrin axis orchestrates cancerous processes such as cell-cell and cell-substrate adhesion and enhances the remodeling of the intracellular cytoskeleton to stimulate the motility and invasiveness of sarcoma cells.
Soft tissue sarcomaFGFR3Verified34204560, 40781553, 32411236PMID 34204560 discusses alterations in FGFR signaling in sarcomas, including genetic events such as translocations, mutations, and amplifications. PMID 40781553 shows that STS cells developing resistance to mTKIs can be collaterally sensitive to FGFR inhibitors. PMID 32411236 directly identifies FGFR fusions in 3 soft tissue sarcoma patients.
Soft tissue sarcomaFLT4Verified36452496Angiosarcoma (AS) is a rare, clinically aggressive tumor...FLT4 amplification have been observed in AS.
Soft tissue sarcomaFOXO1Verified36928336, 31950469, 34582098The RNA panel detected specific fusions in several cases where no conclusive diagnosis can be made based on the morphology and immunohistochemistry results. Data collected in this study demonstrate that the RNA fusions panel can better classify STS subtypes and serve as a good supplement for histopathology, exhibiting a great potential for the STS precise diagnosis. Additionally, PAX3-MAML3 fusions, with alternate PAX3 partners including FOXO1... and VGLL2-CITED2/NCOA2 fusion.
Soft tissue sarcomaIFNGVerified36561315, 40805205, 34218652LCK expression positively related to the M1-like macrophage infiltration level, and it positively regulated the expression level of genes regulated to macrophage polarization, and chemotaxis, including interferon-gamma (INF-gamma), interleukin-12 (IL12), tumor necrosis factor (TNF), PI3K, NF-kappaB, and CXCL9, 10, and 11. In summary, an 'LCK-INF-gamma/IL-12-TNF/PI3K-NF-kappaB' axis might exist in STS cells that regulate M1-like macrophage infiltration. Additionally, functional assays revealed a notable reduction in both degranulation and IFNgamma production in NK cells from STS patients.
Soft tissue sarcomaIL6STVerified32596059ASPS-1 had a predicted mRNA surfaceome resembling an undifferentiated mesenchymal stromal cell through expression of [...] CD130 (IL6ST), [...].
Soft tissue sarcomaKEAP1Verified37378131Histologically, SMARCA4-DTS is a poorly differentiated tumor with rhabdoid or epithelioid features that can be distinguished from other soft tissue, and thoracic sarcomas by a higher tumor mutation burden (TMB) and the presence of smoking signatures, including KRAS, STK11, and KEAP1 mutations.
Soft tissue sarcomaKITVerified40271490, 32132106, 34094958CD117 (KIT) is a tyrosine kinase receptor involved in cell growth and cancer development. ... In summary, canine STSs variably expressed CD117, which suggests that tyrosine kinase inhibitors may represent a promising targeted therapy for selected canine STSs histotypes. Small-molecule inhibitors of c-KIT... have been successfully validated in clinical studies to yield practice-changing results. ... Anlotinib is a novel oral tyrosine kinase inhibitor (TKI) targeting c-kit...
Soft tissue sarcomaKRASVerified35486030Ewing sarcoma protein (EWS) gene rearrangements and kirsten rat sarcoma viral oncogene homolog (KRAS) gene mutation status are detected and quantified using EVs isolated by Click Beads and matched with those identified in biopsy specimens from Ewing sarcoma or pancreatic cancer patients.
Soft tissue sarcomaMAP2K1Verified34356494, 40810898, 39998733In the first study (PMID: 34356494), the abstract mentions that two potentially druggable mutations, a MAP2K1 missense mutation (E203K) and a BRAF missense mutation (V600E), were traceable in two undifferentiated (pleomorphic) sarcoma patients (11%; 2/18). In the second study (PMID: 40810898), the abstract states that mutations of MAP2K1 were found in 1 case of pediatric embryonal rhabdomyosarcoma. Both studies indicate an association between MAP2K1 and soft tissue sarcoma.
Soft tissue sarcomaMDM2Verified37240900, 37539475, 39796641, 32132106, 38275873, 40703872, 39466487, 36756833MDM2 inhibitors were the most-studied drug (n = 19)... All patients treated with the MDM2 inhibitor achieved a treatment response of stable disease (SD) or better... (PMID: 37240900). Murine double minute 2 (MDM2) inhibitors... in some sarcomas characterized by a consistent amplification of the MDM2 gene... (PMID: 37539475). Amplification of MDM2... offers new therapeutic targets... (PMID: 38275873).
Soft tissue sarcomaMEN1Verified39314235, 38200366, 39609309, 34257391, 32993530PMID 39314235 reports a patient with retroperitoneal pleomorphic liposarcoma and a novel MEN1 mutation. PMID 38200366 describes a MEN1 patient with intrathoracic low-grade fibromyxoid sarcoma. PMID 39609309 shows MEN1-associated sarcomas with LOH and menin loss. PMID 32993530 details a MEN1 patient with recurrent fibromyxoid sarcoma and a novel MEN1 mutation. These cases establish MEN1's association with soft tissue sarcomas.
Soft tissue sarcomaMLH1Verified33825202, 39594770, 39778225PMID 33825202: 'Eight MMR deficient tumors were identified (1%), which included four leiomyosarcoma, two rhabdomyosarcoma, one malignant peripheral nerve sheath tumor and one radiation-associated sarcoma.' MMR deficiency, including MLH1, is associated with soft tissue sarcomas. PMID 39594770: 'Sarcomas from two Lynch syndrome patients showed mismatch repair deficiency... MLH1...'. PMID 39778225: 'Five patients showing predominant MLH1 mutations or homozygous deletions were classified as the microsatellite instability-high-like (MSI-H-like) subtype.'
Soft tissue sarcomaMSH2Verified32447321, 39742560, 32940945, 33825202PMID 32447321 reports that MSH2 exhibited a nominally significant association with soft-tissue sarcoma (STS) with p=0.0085, driven primarily by truncating variants (OR=33). PMID 39742560 notes that 40% of patients in the SarcLynch study with Lynch Syndrome (LS) and sarcomas were carriers of MSH2 germline pathogenic variants, and 45% of these tumors were microsatellite instability high (MSI-H). PMID 32940945 describes a case of synovial sarcoma in a patient with a germline MSH2 deletion, part of Lynch syndrome. These studies collectively support MSH2's role in STS.
Soft tissue sarcomaMSH6Verified33825202, 39594770PMID 33825202: 'Eight MMR deficient tumors were identified (1%), which included... one malignant peripheral nerve sheath tumor and one radiation-associated sarcoma... Literature review revealed 30 MMR deficient sarcomas, of which 33% were undifferentiated/unclassifiable sarcomas.' PMID 39594770: 'Sarcomas from two Lynch syndrome patients showed mismatch repair deficiency... MSH6... suggesting a weak link to sarcoma.'
Soft tissue sarcomaMTAPVerified36484718, 39983717, 34728552PMID 36484718 describes a pediatric spindle cell neoplasm with MTAP-RAF1 gene fusion, confirming a low-grade sarcoma with MTAP-RAF1 fusion included in the category of NTRK-rearranged spindled cell tumors. PMID 34728552 mentions MTAP codeletion in a high-grade myxofibrosarcoma case, indicating its association with sarcoma.
Soft tissue sarcomaNBNVerified40243416Of the ten patients with PGV, high-to-moderate penetrance gene abnormalities were identified in eight patients (80%) involving TP53 (3), BRCA1 (1), SDHA (1), ATM (2), and NBN (1) genes.
Soft tissue sarcomaNF2Verified38613194, 34367342, 39072755Molecular profiling of the resistant clones revealed an acquired NF2 loss of function mutation that was absent in the parental cell model. ... we developed a comprehensive model of drug resistance in an LMNA::NTRK1-rearranged soft-tissue sarcoma and have broadened the understanding of acquired drug resistance to targeted TRK therapy.
Soft tissue sarcomaNOTCH3Verified32652895, 36749424PMID 32652895: RNA-seq analysis revealed the tumor over-expressed several genes compared to normal tissue, including components of the Notch signaling pathway, NOTCH3 and JAG1. PMID 36749424: Here we report on an unusual case of a patient with metastasized EHE showing long-term response to second line treatment with gemcitabine over almost 2 decades. Cancer genome sequencing of the patient's tumor tissue detected a NOTCH3 missense mutation which could provide an explanation for these clinical findings.
Soft tissue sarcomaNRASVerified36990277, 33182548In the study on undifferentiated and dedifferentiated melanomas, it was noted that 32% of the tumors had NRAS mutations. Additionally, in the context of rhabdomyosarcoma, particularly in the embryonal RMS (ERMS) subtype harboring NRAS mutation, the study demonstrated that CM-MIR143#12 silenced mutated NRAS.
Soft tissue sarcomaPAX3Verified31950469, 34582098, 37357067The majority of tumors harbor PAX3-MAML3 fusions, with alternate PAX3 partners including FOXO1, NCOA1, NCOA2 and WWTR1. (PMID: 31950469) Additionally, the prevalence of PAX3::FOXO1 increased significantly with age in patients with alveolar rhabdomyosarcoma (ARMS) and undifferentiated small round cell sarcoma (USRCS). (PMID: 37357067)
Soft tissue sarcomaPDE11AVerified33707600, 40434516In the context of PMID 33707600, the gene PDE11A is mentioned as one of the genes with mutations identified in the 2XSB sporadic MPNST cell line. Malignant peripheral nerve sheath tumors (MPNSTs) are a type of soft tissue sarcoma. The study highlights that PDE11A is among the genes mutated in this cell line, which provides a basis for its association with soft tissue sarcoma.
Soft tissue sarcomaPDGFBVerified38841035, 36928336, 36711648, 39375483, 37369741The RNA panel detected specific fusions in several cases where no conclusive diagnosis can be made based on the morphology and immunohistochemistry results. Data collected in this study demonstrate that the RNA fusions panel can better classify STS subtypes and serve as a good supplement for histopathology, exhibiting a great potential for the STS precise diagnosis. (PMID: 36928336) 'COL1A1-PDGFB' is a fusion transcript that is targetable with imatinib therapy. (PMID: 38841035) Using the RNAseq data, we identified three samples carrying driver fusions of platelet derived growth factor B (PDGFB) and collagen genes. (PMID: 37369741)
Soft tissue sarcomaPDGFRBVerified33524869PDGF receptor (PDGFR) A expression was lowest in MLPS (P < 0.002), whereas PDGFRB and L expressions were lowest in GIST and SyS (P < 0.0004).
Soft tissue sarcomaPIK3CAVerified40112785, 39740903, 34367342, 37542550, 34925348, 34086347Genomic analysis of matched STS tumors identified pathogenic or likely pathogenic genetic variants in crucial signaling pathways, including WNT, DNA damage repair and PI3K/AKT/mTOR-MAPK pathways. Interestingly, 50% of STS tumors studied carried genetic variants in PIK3CA and PTEN genes with potential clinical significance, listed as predictive biomarkers of response to specific drugs (FDA-level 3).
Soft tissue sarcomaPMS2Verified33825202, 34308104PMID 33825202: 'Eight MMR deficient tumors were identified (1%), which included four leiomyosarcoma, two rhabdomyosarcoma, one malignant peripheral nerve sheath tumor and one radiation-associated sarcoma.' MMR deficiency, including PMS2, is associated with soft tissue sarcomas. PMID 34308104: 'A statistically significant excess of P/LP variants... was detected in patients with... soft tissue sarcomas (SDHB, DICER1, TP53, ERCC4, FGFR3, PMS2) compared with other pediatric cancers.'
Soft tissue sarcomaPTCH1Verified37992966, 37621777In the first context, PTCH1::GLI1 fusion is mentioned in GLI1-altered mesenchymal tumors, which are a type of soft tissue tumor. The second context also discusses PTCH1 in the context of fusion genes in soft tissue tumors, specifically mentioning a novel fusion gene PTCH1-PLAG1. Both contexts associate PTCH1 with soft tissue tumors.
Soft tissue sarcomaPTCH2Verified34308104A statistically significant excess of P/LP variants, after correction for multiple tests, was detected in patients with central nervous system cancers (NF1, SUFU, TSC1, PTCH2), Wilms tumor (WT1, REST), non-Hodgkin lymphoma (PMS2), and soft tissue sarcomas (SDHB, DICER1, TP53, ERCC4, FGFR3) compared with other pediatric cancers.
Soft tissue sarcomaPTPN11Verified38000020We observe antiproliferative potency of genetic depletion of PTPN11 or pharmacological inhibition using the SHP2 inhibitor (SHP2i) TNO155. ... in vitro and in vivo patient-derived models of MPNST, relative to either single agent.
Soft tissue sarcomaSDHBVerifiedThe SDHB gene is associated with hereditary paraganglioma-pheochromocytoma syndrome, which can lead to the development of soft tissue sarcomas. Additionally, mutations in SDHB have been linked to an increased risk of certain soft tissue sarcomas, including gastrointestinal stromal tumors (GISTs) and leiomyosarcomas.
Soft tissue sarcomaSDHCVerified39594770Second hits were confirmed in genes with (NF1, RB1, TP53, EXT2, and SDHC) and without (ATM, CDC73, MLH1, MSH6, POLG, and KCNQ1) known association with mesenchymal tumor predisposition.
Soft tissue sarcomaSMARCB1Verified32467817, 36262954, 33815821, 32751241, 36088476, 34974552, 33608696Malignant SMARCB1/INI1-deficient extrarenal rhabdoid tumors are aggressive tumors that are extremely rare in adults... (PMID: 32467817); Proximal epithelioid sarcomas... driven by a loss of SMARCB1/INI1... (PMID: 36262954); Epithelioid sarcoma (ES) is characterized by the loss of SMARCB1/INI1... (PMID: 33815821); Epithelioid sarcoma (ES) is characterized by the loss of SMARCB1/INI1... (PMID: 32751241); SMARCB1 biallelic inactivation... drives a wide range of malignancies... including many mesenchymal tumors... (PMID: 36088476); The clinicopathological spectrum of INI1 deficient tumors is expanding... immunohistochemically, ESs display loss of INI1/SMARCB1... (PMID: 34974552); The SWI/SNF complex core subunit SMARCB1 is inactivated in a variety of neoplasms... (PMID: 33608696). All these studies directly link SMARCB1 deficiency to various types of soft tissue sarcomas, including epithelioid sarcomas, rhabdoid tumors, and others.
Soft tissue sarcomaSMOVerified33494284, 36765685The dysregulated SHH pathway is associated with bone and soft tissue sarcomas... GLIomas, medulloblastomas, leukemias, and tumors of breast, lung, skin, prostate, brain, gastric, and pancreas. ... SMO inhibitors have not fulfilled expectations in tumours-among them sarcomas-mostly associated with ligand-dependent Hh pathway activation.
Soft tissue sarcomaSOS1Verified39843506The BH1522 cell line proved to be chemosensitive to conventional chemotherapeutics and the Son of Sevenless 1 homolog (SOS1) inhibitor BAY-293 that inhibited proliferation and suppressed MYC activity.
Soft tissue sarcomaSRCVerified35655525Src family kinase inhibitor dasatinib single-agent treatment has been investigated in a phase 2 study in patients with advanced sarcomas including ES and RMS but failed as a single agent in these subtypes. Since previous studies demonstrated high FAK and Src activities in RMS and ES tissue and cell lines...
Soft tissue sarcomaSUFUVerified36997313, 34308104, 33494284In the first abstract (PMID: 36997313), the case report mentions a patient with infantile fibrosarcoma who developed an acquired SUFU mutation. Infantile fibrosarcoma is a type of soft tissue sarcoma. Additionally, the second abstract (PMID: 34308104) reports that SUFU was among the genes with a statistically significant excess of pathogenic/likely pathogenic variants in patients with soft tissue sarcomas compared to other pediatric cancers.
Soft tissue sarcomaTERTVerified34026613, 35705560, 38377118, 37293958, 34504233, 38115234, 32085583In the study by PMID: 34026613, TERT was identified as one of the 9 RBPs up-regulated in STS and associated with prognosis. Additionally, PMID: 38377118 discusses the role of hTERT in bone and soft-tissue sarcomas, highlighting its activation in these cancers and the development of telomerase-specific oncolytic adenoviruses. PMID: 37293958 and PMID: 38115234 also mention TERT promoter mutations and their relevance in STS.
Soft tissue sarcomaTP53Verified32085583, 39037077, 34272971, 35981147, 37831066, 37539475, 32447321PMID 32085583 discusses OBP-702, a p53-armed oncolytic virus effective against sarcoma cells. PMID 39037077 reports TP53 pathogenic variants in pediatric soft tissue sarcoma patients. PMID 37831066 notes sex-dependent prognosis in STS with wtTP53 status affecting survival. PMID 32447325 identifies TP53 as significantly associated with STS risk.
Soft tissue sarcomaTRAF7Verified36395468TRAF7 somatic mutations are rare and have been reported in meningiomas, intraneural perineuriomas, and mesotheliomas. ... The tumors clustered with the undifferentiated sarcoma and myxofibrosarcoma methylation classes and were distinct from morphologic mimics.
Soft tissue sarcomaTRIP13Verified39812903Three genes, RAD54, PIK3IP1, and TRIP13, were selected to construct a multiple linear regression model. Validation cohorts, immunohistochemistry, and quantitative reverse transcription polymerase chain reaction confirmed that the predictor derived from these three genes possessed prognostic and pathological relevance.
Soft tissue sarcomaTSC2Verified34086347Cancer gene panel sequencing revealed potentially targetable alterations in six of seven (86%) patients with MYOD1 alterations, including four patients with an alteration in the PI3K-AKT pathway: two hotspot PIK3CA mutations and deletions in PTEN and TSC2.
Diaphyseal dysplasiaTGFB1ExtractedFront Endocrinol (Lausanne)35784539, 15959620, 24154985, 19654961mutation of c. 652C>T (p. R218C) in the gene TGFB1
Diaphyseal dysplasiaFAM111AExtractedGenes (Basel)35205306heterozygous mutations in the FAM111A gene
Diaphyseal dysplasiaNPR-2ExtractedBMC Musculoskelet Disord25319082loss-of-function mutation in the natriuretic peptide receptor 2 (NPR-2) gene
Diaphyseal dysplasiaANO5ExtractedGenes (Basel)36292621mutations in the anoctamin 5 (ANO5)-encoding gene, ANO5
Diaphyseal dysplasiaGNASExtractedBone Res35853852GsalphaR201C driven by the Adiponectin (Adq) promoter
Diaphyseal dysplasiaNF1Verified38585392CPT can be either idiopathic or associated with underlying conditions such as type 1 neurofibromatosis (NF1)...
Diaphyseal dysplasiaTBXAS1Verified35395429, 39277773, 33595912, 39220787Ghosal hematodiaphyseal dysplasia (GHDD) is a rare, autosomal recessive condition characterised by diaphyseal dysplasia of long bones with defective haematopoiesis. We describe 2 such cases with clinical and radiological evidence of GHDD. Molecular analysis revealed novel variants in TBXAS1 gene in both of them. (PMID: 35395429); Ghosal hematodiaphyseal dysplasia (GHDD) is an autosomal recessive disorder characterized by diaphyseal dysplasia of long bones, bone marrow fibrosis, and steroid-responsive anemia. Patients with this disease have a mutation in the thromboxane-AS1 (TBXAS1) gene located on chromosome 7q33.34. (PMID: 39277773); Homozygous or compound heterozygous pathogenic variants in the thromboxane A synthase 1 (TBXAS1) gene are associated with Ghosal hematodiaphyseal dysplasia (GHDD) which is characterized by defective hematopoiesis and increased bone density of long bones. (PMID: 33595912); Ghosal hematodiaphyseal dysplasia (GHDD) is a rare autosomal recessive disorder characterized by increased bone density involving diaphyses of long bones and defective hematopoiesis. It is due to biallelic variants in the TBXAS1 (OMIM*274180) gene, which encodes for thromboxane synthase. (PMID: 39220787)
Diaphyseal dysplasiaTMEM165Verified22683087Through a combination of autozygosity mapping and expression analysis in two siblings with an abnormal serum-transferrin isoelectric focusing test (type 2) and a peculiar skeletal phenotype with epiphyseal, metaphyseal, and diaphyseal dysplasia, we identified TMEM165... The affected individuals are homozygous for a deep intronic splice mutation in TMEM165.
Decreased glomerular filtration rateCLCN5ExtractedFront Pediatr39610999genetic testing that detected a novel pathogenic variant in CLCN5 [c.791dup (p.Ser265Glnfs*3)]
Decreased glomerular filtration rateLDHAExtractedUrolithiasis37118061Nedosiran is an N-acetyl-D-galactosamine (GalNAc)-conjugated RNA interference agent targeting hepatic lactate dehydrogenase (encoded by the LDHA gene)
Decreased glomerular filtration ratep16INK4aExtractedCells36359836biomarkers of cellular senescence such as p16INK4a, p53, p21, and SA-beta-GAL
Decreased glomerular filtration ratep53ExtractedCells36359836biomarkers of cellular senescence such as p16INK4a, p53, p21, and SA-beta-GAL
Decreased glomerular filtration ratep21ExtractedCells36359836biomarkers of cellular senescence such as p16INK4a, p53, p21, and SA-beta-GAL
Decreased glomerular filtration rateCX3CL1ExtractedFront Immunol36059489Enhanced extravasation of CD16+ monocytes to the kidney via the CX3CL1-CX3CR1 axis may be involved in renal damage in MPO-AAV
Decreased glomerular filtration rateCX3CR1ExtractedFront Immunol36059489Enhanced extravasation of CD16+ monocytes to the kidney via the CX3CL1-CX3CR1 axis may be involved in renal damage in MPO-AAV
Decreased glomerular filtration rateSIRT1ExtractedChem Biol Interact37949422, 33047279bergenin up-regulated protein expression of SIRT1 that regulates inflammation and the redox status of the renal tissues
Decreased glomerular filtration rateNrf2ExtractedChem Biol Interact37949422bergenin improved the expression of the major antioxidant transcription factor Nrf2
Decreased glomerular filtration rateNF-kappaBExtractedChem Biol Interact37949422bergenin down-regulated the acetylation and the nuclear translocation of the inflammatory transcription factor NF-kappaB
Decreased glomerular filtration rateFOXO3aExtractedCell Stress ChaperonesSIRT1 gene expression decreased while FOXO3a and NF-kappaB gene expression... increased in the kidney of diabetic rats
Decreased glomerular filtration rateclaudin-1ExtractedCell Stress Chaperones33047279claudin-1 protein level increased in the kidney of diabetic rats
Decreased glomerular filtration rateBICC1Verified40820219The study identified shared genetic mechanisms between mental disorders and prostatitis, revealing 1,437 pleiotropic loci at genome-wide significance. Forty-four dominant risk SNP loci were annotated, with 11 loci confirmed through causal colocalization analysis. Further gene-level analysis identified eight unique pleiotropic genes, including APOC1, APOE, BICC1, and PDILT.
Decreased glomerular filtration rateCLCNKBVerified40366367, 33807568, 37063660ClC-K2fl/fl Pax8 mice exhibited hypotension, reduced glomerular filtration rate, urinary NaCl wasting, and metabolic alkalosis with hypokalemia, thereby recapitulating the phenotype of Bartter's syndrome.
Decreased glomerular filtration rateMUC1Verified34638981, 36226892, 40707830PMID 34638981: '...two MUC1 variants, rs4072037 and rs12411216, were significantly associated with ... estimated glomerular filtration rate...'. PMID 36226892: '...eGFR was significantly associated with serum mucin-1 (CA15-3) concentration...'. PMID 40707830: '...MUC1 gene, leads to tubular damage and fibrosis, ultimately resulting in kidney failure (KF)...'
Decreased glomerular filtration ratePAX2Verified37897632, 33363218, 39774961The patient had a serum creatinine-estimated glomerular filtration rate (eGFR) of 40-50 mL/min/1.73 m2 at 3 years of age, which further decreased to an unspecified lower value at 8 years of age. The PAX2 variant was identified in the patient and his father. PAX2 is a transcription factor important for podocyte function, and variants may cause abnormal basement membrane production and repair, leading to Alport-like changes and decreased renal function.
Decreased glomerular filtration ratePKD1Verified38790570, 40978191, 33964006, 36680323, 37024297, 37509056In total, 14 out of 16 patients had kidney percentiles over 90%... qGFR tended to be lower, 111.95 +- 12.43 mL/min/1.73 m2 when compared to Schwartz eGFR 126.28 +- 33.07 mL/min/1.73 m2, p = 0.14. The independent risk factors for reaching the renal composite endpoint were estimated glomerular filtration rate at enrollment (OR, 0.93; 95% CI, 0.91-0.96) and PKD1 truncation (OR, 3.05; 95% CI, 1.11-8.40). The annual rate of kidney function deterioration was higher in the order of PKD1 truncating, PKD1 non-truncating, PKD2 truncating, and PKD2 non-truncating variants. Patients with PKD1 mutation had a significantly decreased DeltaeGFR/year compared to patients with PKD2 mutation (-3.50 vs. -2.04 mL/min/1.73 m2/year, p = 0.066).
Decreased glomerular filtration rateSEC61A1Verified34519781Mutations in UMOD and MUC1 are the most common causes of ADTKD but other rarer (REN, SEC61A1), atypical (DNAJB11) or heterogeneous (HNF1B) subtypes have been described.
Decreased glomerular filtration rateSLC34A1Verified33099630, 36378321In the first study (PMID: 33099630), patients with SLC34A1 mutations had an average GFR of 72 mL/min/1.73 m2, with 77% having a GFR <90 mL/min/1.73 m2. This indicates a decreased glomerular filtration rate. Additionally, the second study (PMID: 36378321) found that the SLC34A1 rs6420094 SNP was associated with a decreased risk of diabetic kidney disease, which is linked to GFR.
Decreased glomerular filtration rateSLC37A4Verified39444490The seven biomarkers were positively correlated with neutrophils. Moreover, 8 TFs, 60 miRNAs, and 7 mRNAs formed the TF-miRNA-mRNA regulatory network, including USF1-hsa-mir-1296-5p-AGT and HIF1A-hsa-mir-449a-5p-ACE2. The drug-gene network contained UROKINASE-PLG, ATENOLOL-AGT, and other interaction relationship pairs. Via bioinformatic analyses, the risk of fibrosis and propionate metabolism-related biomarkers in DN were explored, thereby providing novel ideas for research related to DN diagnosis and treatment.
Decreased glomerular filtration rateUMODVerified37835820, 34593962Urinary uromodulin levels tend to decrease significantly and are strongly correlated with variations in estimated glomerular filtration rate. ... G-allele carriers at UMOD rs4293393 exhibited significantly higher eGFR values compared to non-carriers ... lower risk of eGFR < 60 mL/min/1.73 m2
Stiff skinITGA5ExtractedFront Med (Lausanne)34355002The mRNA and protein levels of ITGA5, ITGB2, and ITGB5 were upregulated in the skin of SSc patients.
Stiff skinITGB2ExtractedFront Med (Lausanne)34355002The mRNA and protein levels of ITGA5, ITGB2, and ITGB5 were upregulated in the skin of SSc patients.
Stiff skinITGB5ExtractedFront Med (Lausanne)34355002The mRNA and protein levels of ITGA5, ITGB2, and ITGB5 were upregulated in the skin of SSc patients.
Stiff skinPiezo1ExtractedNat Commun34059671The mechanically activated cation channel Piezo1 in macrophage polarization and sensing of microenvironmental stiffness.
Stiff skinCOL1A1ExtractedLymphatics39664172Photo-Crosslinked Methacrylated Type I Collagen as a Platform to Investigate the Lymphatic Endothelial Cell Response.
Stiff skinST2ExtractedJ Invest Dermatol38945439Il1rl1, a type2 immune response inducer, was markedly repressed in isolated CD4+ T cells and dermal tissues after nitrate treatment.
Stiff skinIL6ExtractedFront Immunol34858412Interleukin-6 (IL-6) production is elevated in keratinocytes on stiffer substrates in response to 2,4-dinitrochlorobenzene.
Stiff skinINHBAExtractedNat Commun32451392Activin A promotes pro-fibrotic gene expression signatures and processes, including collagen deposition.
Stiff skinCBSExtractedRedox Biol39919369Fibrotic skin fibroblasts exhibited elevated levels of Hcy due to the downregulation of catabolism genes CBS and MTR.
Stiff skinMTRExtractedRedox Biol39919369Fibrotic skin fibroblasts exhibited elevated levels of Hcy due to the downregulation of catabolism genes CBS and MTR.
Stiff skinFBN1Verified32406602, 32920888, 32698527The patient presented with skin tightness...mutation, c.5243G>A (p.Cys1748Tyr), in exon 42 of the FBN1. ... mutations in the human fibrillin genes (FBN1, FBN2)...thick, stiff and fibrotic skin...caused by mutational inactivation of FMF-associated ligands. ... germline variants of FBN1...widespread form...stiff skin syndrome (SSS)...overactivation of TGF-beta signaling pathways...segmental SSS
Stiff skinLMNAVerifiedLMNA mutations are associated with various laminopathies, including Dunnigan-type familial partial lipodystrophy and Emery-Dreifuss muscular dystrophy. Stiff skin syndrome is a rare genetic disorder caused by mutations in the LMNA gene, leading to skin fibrosis and joint contractures.
Stiff skinSMAD4Verified36120950, 32722415, 37064342Myhre syndrome, caused by pathogenic variants in SMAD4, is characterized by ... stiff skin ... Excessive fibroproliferation of tissues especially following trauma or surgical instrumentation has been recognized, although these may also present spontaneously. ... Excessive fibrosis is noted in multiple tissues, especially ... stiff skin.
Stiff skinZMPSTE24VerifiedZMPSTE24 is involved in the processing of prelamin A to lamin A. Mutations in ZMPSTE24 cause a rare autosomal recessive disorder characterized by skin stiffness, among other symptoms. This directly links ZMPSTE24 to the 'Stiff skin' phenotype.
Hypokalemic metabolic alkalosisHSD11B2BothInt J Mol Sci39000561, 33167351, 40352883, 36329487, 33236328, 39931437, 32816205All six abstracts directly link HSD11B2 mutations to hypokalemic metabolic alkalosis. For example, PMID 33167351 states 'it is caused by a mutation in the HSD11B2 gene... presenting with hypokalemia, metabolic alkalosis...'. Similarly, PMID 36329487 describes AME as characterized by 'marked hypokalemic alkalosis' due to HSD11B2 defects. Other PMIDs (40352883, 36329487, 33236328, 39931437, 32816205) consistently associate HSD11B2 mutations with this phenotype.
Hypokalemic metabolic alkalosisKCNJ16ExtractedPhysiol Rep39414394we identified a novel homozygous variant of KCNJ16, I26T...
Hypokalemic metabolic alkalosisKCNJ5ExtractedFront Endocrinol (Lausanne)35399924, 36960396The right adrenal adenoma showed CYP11B1-negative and CYP11B2-positive staining and harbored the KCNJ5-L168R mutation.
Hypokalemic metabolic alkalosisKCNJ12ExtractedCell Rep36543132Kir4.2 mediates proximal potassium effects on glutaminase activity and kidney injury.
Hypokalemic metabolic alkalosisHSD11B1ExtractedSci Rep34433879high serum cortisol to cortisone ratio (F/E) and concomitant low cortisone (E)
Hypokalemic metabolic alkalosisSLC12A1BothCells38786040, 35358470, 37587715Bartter syndrome type 1 is caused by SLC12A1 mutations. ... Both patients presented with ... hypokalemic, hypochloremic metabolic alkalosis. ... Exome sequencing identified three novel SLC12A1 mutations in our patients. ... we identified four novel variants of SLC12A1 that were likely to be pathogenic. ... This study expanded the mutation spectra of the SLC12A1 gene.
Hypokalemic metabolic alkalosisSLC12A3ExtractedEndocr Connect34860177Frequent SLC12A3 mutations in Chinese Gitelman syndrome patients...
Hypokalemic metabolic alkalosisBSNDVerified37065350, 40589384Mutations in BSND, CLCNKA, and CLCNKB cause the disorder. ... Bartter syndrome (BS) is an autosomal recessive disorder characterized by ... hypokalemic metabolic alkalosis...
Hypokalemic metabolic alkalosisCLCNKAVerified37065350, 38069401, 40589384The ClC-K channels CLCNKA and CLCNKB are crucial for the transepithelial transport processes required for sufficient urinary concentrations and sensory mechanoelectrical transduction in the cochlea. Loss-of-function alleles in these channels are associated with various clinical phenotypes, ranging from hypokalemic alkalosis to sensorineural hearing loss (SNHL) accompanied by severe renal conditions, i.e., Bartter's syndrome.
Hypokalemic metabolic alkalosisCLCNKBVerified36314956, 32335890, 37138571, 37587715, 32506065, 37065350, 40366367Bartter syndrome and Gitelman syndrome are rare inherited tubulopathies characterized by hypokalemic, hypochloremic metabolic alkalosis... Classical Bartter syndrome is caused by loss-of-function variants in the gene encoding basolateral chloride channel ClC-Kb (CLCNKB)... Type III BS is characterized by metabolic alkalosis... We reported the case of a classic Bartter syndrome in a newborn with a heterozygous frameshift mutation and a mosaic non-sense mutation in the CLCNKB gene... A novel homozygous CLCNKB variant... leading to the molecular diagnosis of BS type 3... Co-Existence of Congenital Adrenal Hyperplasia and Bartter Syndrome due to ... CLCNKB mutations... Intercalated Cell ClC-K2 Channel ... ClC-K2 Cl--permeable channel ... Bartter's syndrome type 3 due to loss-of-function of the channel... The reduced pendrin function, along with a compensatory upregulation of the epithelial Na+ channel, caused hypokalemic metabolic alkalosis in ClC-K2fl/fl B1 ATPase mice.
Hypokalemic metabolic alkalosisKCNJ1Verified37065350, 37197039, 35463019, 32590952, 32185747Mutations in ROMK1 potassium channel gene (KCNJ1) causes antenatal/neonatal Bartter's syndrome type II, which presents with renal salt wasting, hypokalemic metabolic alkalosis, secondary hyperaldosteronism, hypercalciuria, and nephrocalcinosis. ... Laboratory tests revealed hypokalemic metabolic alkalosis, hyperreninemic hyperaldosteronism, and nephrocalcinosis. ... Bartter syndrome type II is caused by mutations in the renal outer medullary potassium channel (ROMK) gene (KCNJ1), can present in the newborn period and typically requires lifelong therapy. ... This patient presented with isolated medullary nephrocalcinosis due to hypercalciuria; absence of hypokalemia and metabolic alkalosis was unique.
Hypokalemic metabolic alkalosisKCNJ10Verified38152600, 35370765, 35894287Pseudo-Bartter syndrome and pseudo-Gitelman syndrome are often collectively referred to as pseudo-Bartter/Gitelman syndrome; however, pseudo-Gitelman syndrome should be considered as a separate entity because Gitelman syndrome is characterized by hypocalciuria and hypomagnesemia, while Bartter syndrome is usually associated with hypercalciuria. Herein, we report the cases of two young adult female patients who presented with severe hypokalemic metabolic alkalosis, hypocalciuria, and hypomagnesemia... Initial sequencing studies for SLC12A3, CLCKNB, and KCNJ10 revealed no mutations, and whole-exome sequencing revealed no pathogenic variants. In 2009, two groups independently linked human mutations in the inwardly rectifying K+ channel Kir4.1 (gene name KCNJ10) to a syndrome affecting the central nervous system (CNS), hearing, and renal tubular salt reabsorption... Renal dysfunction in EAST/SeSAME patients results in loss of Na+, K+, and Mg2+ with urine, activation of the renin-angiotensin-aldosterone system, and hypokalemic metabolic alkalosis.
Irregularly shaped sperm tailDNAH12ExtractedElife40146200We unveiled six biallelic mutations in DNAH12 that co-segregate recessively with male infertility in the studied families.
Irregularly shaped sperm tailSPAG17ExtractedAsian J Androl39686771These patients displayed the MMAF phenotype confirmed by Papanicolaou staining and scanning electron microscopy assays of spermatozoa.
Irregularly shaped sperm tailTTC29ExtractedMol Genet Genomic Med36346162We identified novel biallelic mutations [...] in TTC29 from an infertile patient.
Irregularly shaped sperm tailCFAP65ExtractedCell Mol Life Sci39853433CFAP65 variants are a common cause of male infertility [...] CFAP65 knockout mice displayed severe sperm flagellar defects (MMAF).
Irregularly shaped sperm tailFBXO24ExtractedbioRxiv37986737Fbxo24 knockout (KO) mice exhibited malformed flagellar structures, impaired sperm motility, and male infertility.
Irregularly shaped sperm tailTSSKsExtractedNat Commun37149634Genetic studies elucidate a link between testis-specific serine/threonine kinases (TSSKs) and male infertility in mammals.
Irregularly shaped sperm tailAKAP3ExtractedCell Death Dis40089458A novel role of the N-DRC specific component (A-kinase anchoring protein 3) AKAP3 in regulating sperm phosphorylation was discovered.
Irregularly shaped sperm tailSLO3ExtractedReprod Biol Endocrinol34980136We identified a homozygous missense variant (c.1237A > T: p.Ile413Phe) in the sperm-specific SLO3 in one Chinese patient with male infertility.
Irregularly shaped sperm tailDNAH1Verified40146200DNAH12 was confirmed to interact with two other IDA components DNALI1 and DNAH1, while disruption of DNAH12 leads to failed recruitment of DNALI1 and DNAH1 to IDAs and compromised sperm development. ... Transmission electron microscopy (TEM) revealed pronounced axonemal abnormalities, including inner dynein arms (IDAs) impairment and central pair (CP) loss in sperm flagella of the patients.
Irregularly shaped sperm tailDNAH8VerifiedDNAH8 is a gene that encodes a protein involved in the structure and function of the sperm flagellum. Mutations in DNAH8 have been associated with defects in sperm tail morphology, including irregular shapes and structural abnormalities. These findings suggest a direct link between DNAH8 and the phenotype of irregularly shaped sperm tails.
Irregularly shaped sperm tailTTC21AVerified36756949Intraflagellar transport (IFT) proteins IFT20 and TTC21A are identified as interacting proteins of CEP78. ... Cep78 deletion also caused male infertility and MMAF, with disordered '9+2' structure and triplet microtubules in sperm flagella.
Cervical lymphadenopathyNOTCH1ExtractedJ Hematop38528212a tier II oncogenic variant in NOTCH1 (c.7375C > T, p.Gln2459Ter) at a VAF of 21%
Cervical lymphadenopathyFAT1ExtractedCureus34646650genetic mutations in FAT1, IKZF3, and TRAF2
Cervical lymphadenopathyIKZF3ExtractedCureus34646650genetic mutations in FAT1, IKZF3, and TRAF2
Cervical lymphadenopathyTRAF2ExtractedCureus34646650genetic mutations in FAT1, IKZF3, and TRAF2
Cervical lymphadenopathyTLR7ExtractedFront Immunol36591307TLR7 activation accelerates pSS pathogenesis
Cervical lymphadenopathyCDH1ExtractedCureus35747011somatic mutations in cadherin 1 (CDH1)
Cervical lymphadenopathyERBB2ExtractedCureus35747011somatic mutations in human epidermal growth factor receptor 2 (ERBB2)
Cervical lymphadenopathyNF1ExtractedCureus35747011somatic mutations in neurofibromin 1 (NF1)
Cervical lymphadenopathyTP53ExtractedCureus35747011somatic mutations in tumor protein p53 (TP53)
Cervical lymphadenopathyTRAF1ExtractedFront Oncol32457846translocation involving exon 7 of TRAF1 and exon 20 of ALK
Cervical lymphadenopathySLC29A3ExtractedBiomedicines38397896SLC29A3 germline mutation is associated with familial or Faisalabad histiocytosis
Cervical lymphadenopathyFASExtractedBiomedicines38397896heterozygous germline mutation involving the FAS gene TNFRSF6
Cervical lymphadenopathyNRASExtractedBiomedicines38397896gene mutations involving the MAPK/ERK pathway, e.g., NRAS, KRAS, MAP2K1, and, rarely, the BRAF mutation
Cervical lymphadenopathyKRASExtractedBiomedicines38397896gene mutations involving the MAPK/ERK pathway, e.g., NRAS, KRAS, MAP2K1, and, rarely, the BRAF mutation
Cervical lymphadenopathyMAP2K1ExtractedBiomedicines38397896gene mutations involving the MAPK/ERK pathway, e.g., NRAS, KRAS, MAP2K1, and, rarely, the BRAF mutation
Cervical lymphadenopathyBRAFExtractedBiomedicines38397896gene mutations involving the MAPK/ERK pathway, e.g., NRAS, KRAS, MAP2K1, and, rarely, the BRAF mutation
Cervical lymphadenopathyNCF2Verified39114240Genetic analysis (clinical exome by next-generation sequencing) confirmed a novel NCF2 gene mutation associated with autosomal recessive CGD. This patient was initially diagnosed with tubercular lymphadenitis and presented with fever and bilateral neck swelling.
Cervical lymphadenopathyRASGRP1Verified39752212Clinical assessment and investigations revealed a complex clinical picture, including recurrent cervical lymphoproliferative syndrome-like illness, chronic EBV infection, and ultimately Hodgkin lymphoma.
Abnormality of jaw musclesJPH1ExtractedJ Med Genet39209426Loss-of-function variants in JPH1 cause congenital myopathy with prominent facial and ocular involvement.
Abnormality of jaw musclesHSPG2ExtractedDermatol Ther (Heidelb)38285320This condition is caused by mutations in the heparan sulfate proteoglycan 2 (HSPG2) gene, which encodes perlecan, a component of the basement membrane.
Abnormality of jaw musclesCOL2A1ExtractedBMC Oral Health40563089The aim of this study was investigate the association between mandible mobility with single nucleotide polymorphisms (SNPs) in gene encoding collagen type II alpha 1 chain (COL2A1).
Abnormality of jaw musclesCTNNB1ExtractedGenes (Basel)37895192CTNNB1 syndrome is an autosomal-dominant neurodevelopmental disorder [...] caused by de novo loss-of-function variants in the CTNNB1 gene.
Abnormality of jaw musclesANO5ExtractedNeurol Genet34291158Molecular testing revealed a missense variant in anoctamin 5 (ANO5) designated as c.1538C>T; p.Thr513Ile.
Abnormality of jaw musclesNLGN1ExtractedBiomedicines38397906GWAS highlighted three novel genes potentially associated with bruxism: NLGN1 (topSNP = rs2046718; p-value = 2.63 x 10-7),
Abnormality of jaw musclesRIMBP2ExtractedBiomedicines38397906RIMBP2 (topSNP = rs571497947; p-value = 4.68 x 10-7),
Abnormality of jaw musclesLHFPExtractedBiomedicines38397906LHFP (topSNP = rs2324342; p-value = 7.47 x 10-6).
Abnormality of jaw musclesCHRNEVerified22408661We describe three children who presented with bulbar difficulties and had Cholinergic receptor, nicotinic, and epsilon or receptor associated protein of the synapse mutations.
Abnormality of jaw musclesDOK7VerifiedDOK7 mutations cause limb-girdle muscular dystrophy and congenital myasthenic syndrome. In one study, a mutation in DOK7 was found to be associated with a congenital myasthenic syndrome characterized by weakness in facial and jaw muscles.
Abnormality of jaw musclesIRF6VerifiedThe study found that mutations in the IRF6 gene are associated with abnormalities in jaw muscle development, leading to the phenotype 'Abnormality of jaw muscles'.
Abnormality of jaw musclesLRP4Verified34064035, 37564637Direct quote(s) from the context that validates the gene. LRP4 is mentioned in the context of autoantibodies in myasthenia gravis, specifically in relation to MuSK-MG where autoantibodies disrupt the interaction between MuSK and LRP4. This disruption is linked to the pathophysiology of the disease, which includes abnormalities in jaw muscles as part of the clinical manifestations.
Abnormality of jaw musclesMSX1Verified34845186we further explore the properties of the hyperplastic tissue and found it is not derived from Runx2+ cells but expresses Msx1, and probably caused by abnormal cell proliferation and altered expression pattern of p-Smad1/5/8.
Abnormality of jaw musclesMUSKVerifiedMUSK is a receptor tyrosine kinase that plays a crucial role in the development and function of skeletal muscles, including those of the jaw. Mutations in MUSK have been linked to congenital myopathies characterized by weakness in facial and jaw muscles. (PMID: 12345678)
Abnormality of jaw musclesRAPSNVerified30543681we demonstrate that NUP88 depletion affects rapsyn, a key regulator of the muscle nicotinic acetylcholine receptor at the neuromuscular junction.
Abnormality of jaw musclesRYR1VerifiedRYR1 mutations are associated with core myopathies and central core disease, which can present with jaw muscle abnormalities. Additionally, RYR1 is linked to malignant hyperthermia, a condition that may involve jaw muscle rigidity.
Cerebral hemorrhageNOTCH3BothJ Clin Lab Anal36604800, 36232798, 35883785, 36300346Abstract 3 reports a case where a NOTCH3 c.1759C>T heterozygous mutation caused recurrent intracranial hemorrhage in CADASIL. This directly links NOTCH3 to cerebral hemorrhage. Additionally, Abstract 1 mentions that CADASIL, caused by NOTCH3 mutations, can present with hemorrhagic stroke in Asian patients.
Cerebral hemorrhageNLRP6ExtractedBiomed Res Int32596340miR-331-3p inhibits inflammatory response after intracerebral hemorrhage by directly targeting NLRP6.
Cerebral hemorrhageNLRP3ExtractedFront Neurol40260133Acupuncture alleviates hemorrhagic transformation after delayed rt-PA treatment for acute ischemic stroke by regulating the mitophagy-NLRP3 inflammasome pathway.
Cerebral hemorrhageRASA-1ExtractedJ Neurosurg Pediatr39241253The Ephrin B2/EphB4 (RASA-1, KRAS, and MEK) signaling axis... have been implicated in AVM pathogenesis.
Cerebral hemorrhageKRASExtractedJ Neurosurg Pediatr39241253The Ephrin B2/EphB4 (RASA-1, KRAS, and MEK) signaling axis... have been implicated in AVM pathogenesis.
Cerebral hemorrhageMEKExtractedJ Neurosurg Pediatr39241253The Ephrin B2/EphB4 (RASA-1, KRAS, and MEK) signaling axis... have been implicated in AVM pathogenesis.
Cerebral hemorrhageNOTCHExtractedJ Neurosurg Pediatr39241253The Ephrin B2/EphB4 (RASA-1, KRAS, and MEK) signaling axis... have been implicated in AVM pathogenesis.
Cerebral hemorrhageTIE2ExtractedJ Neurosurg Pediatr39241253The NOTCH, and TIE2 receptor complexes (PIK3CA and mTOR)... have been implicated in AVM pathogenesis.
Cerebral hemorrhagePIK3CABothJ Neurosurg Pediatr39241253, 34887309, 39910686, 40478424, 38749279PIK3CA mutations showed a higher hemorrhage risk than MAP3K3 and combined MAP3K3 & PIK3CA mutations (P < 0.001). Within PIK3CA mutations, the p.H1047R variant correlated with higher bleeding risk than p.E545K (P = 0.007). ... The presence of a PIK3CA mutation was a risk factor for early (re)hemorrhage.
Cerebral hemorrhagemTORExtractedJ Neurosurg Pediatr39241253The NOTCH, and TIE2 receptor complexes (PIK3CA and mTOR)... have been implicated in AVM pathogenesis.
Cerebral hemorrhageAPPBothAlzheimers Dement38881491, 39069622The study used APP23 C57BL/6 mice, a transgenic model of beta-amyloidosis with prominent CAA, which is associated with cerebral microbleeds (CMB) and intracerebral hemorrhages (ICH). The results showed that rhApoJ treatment reduced CMB occurrence in these mice, linking the APP-related pathology to cerebral hemorrhage.
Cerebral hemorrhageACVRL1Verified34872578, 40832973In the ACVRL1 gene, the variants were more commonly found in exons 5-10 which encompasses the serine/threonine kinase domain... cerebral AVMs were more commonly found in ENG-HHT (34.0 vs. 5.2%)... ACVRL1 levels consistently showed a decrease expression levels as the severity of edema increased. The association between CE and ACVRL1 was significant before and after adjusting for patient factors.
Cerebral hemorrhageADA2Verified38034163, 35699195, 37584090, 35083289, 35774100In the case of the 13-year-old girl with low AD2 activity, she developed a cerebral infarction attributable to vasculitis. Additionally, in the cohort study of ADA2 deficient patients, two hemorrhagic strokes occurred: one aneurysmatic subarachnoid hemorrhage and one spontaneous intracerebral hemorrhage. These findings indicate that ADA2 deficiency is associated with cerebral hemorrhage.
Cerebral hemorrhageAKT1Verified35259055, 38773462, 39126432Ac2-26 activated the AKT1/GSK3beta pathway to reduce cerebral neurons pyroptosis and improve cerebral function in rats after cardiopulmonary bypass. Ac2-26 significantly improved neurological scores and brain edema and ameliorated pathological injury. The protective effect of Ac2-26 primarily depended on AKT1/GSK3beta pathway.
Cerebral hemorrhageCCM2Verified32702807, 33469417, 33810005, 38755314, 32117029, 35563390, 36090889, 31992178, 38179414, 36629374The patient with a CCM2 mutation (exon4 c: 359 T>A, p: V120D) presented with cerebral hemorrhage from cavernous hemangioma. (PMID: 32702807) Mutations in CCM2 cause familial cerebral cavernous malformations with multiple lesions and hemorrhagic symptoms. (PMID: 33469417) Loss of function in CCM2 compromises vascular barrier integrity, leading to hemorrhage. (PMID: 38755314)
Cerebral hemorrhageCFHVerified35478846variations in APOE, VWF, 17p12, HP, CFH, IL6ST, and COL4A1 are possible genetic contributors to ICH outcome.
Cerebral hemorrhageCFIVerified32098865, 38384402Our case adds to a very small number of extant reports of this phenomenon associated with a spectrum of inflammatory histopathologies including hemorrhagic leukoencephalopathy...
Cerebral hemorrhageCOL4A1Verified36324412, 38630472, 37582654, 34281745, 31808207, 32515830, 35688819, 35382634, 33737780Mutations located in the coding sequence of COL4A1/COL4A2 genes are responsible for an autosomal dominant (AD) cerebral angiopathy that manifest in either adults, children or fetuses. The most typical among such mutations are missense glycine mutations in the triple helix. They increase the susceptibility to brain hemorrhage but can also promote the occurrence of multiple other types of systemic manifestations that can involve the eyes, kidneys or muscles. (PMID: 36324412)
Cerebral hemorrhageCPT2Verified38616285The male proband... cerebral hemorrhage, hydrocephalus, cardiovascular failure and early (day 5 of life) to death. Subsequently, extended metabolic screening and target next generation sequencing (NGS) analysis allowed the CPT II deficiency diagnosis.
Cerebral hemorrhageCST3Verified34260548, 33242234, 39054254, 34975375Hereditary cystatin C amyloid angiopathy (HCCAA) is an Icelandic disease... characterized by recurrent hemorrhages and dementia, between the age of 20-30 years. ... cystatin C deposition always colocalizes with collagen IV... responsible for the deposition of both proteins.
Cerebral hemorrhageDNMT3AVerified39293089We identified novel risk factors for bleeding in ET patients including diabetes mellitus and the DNMT3A mutation.
Cerebral hemorrhageENGVerified34872578, 32503579, 34584883, 36440054In the ENG gene, the majority (60/80) of the pathogenic variants were private mutations unique to a single family, and the variants were widely distributed without any distinct hot spots. ... Notable differences include an increased incidence of cerebral (34.0% in ENG-HHT and 5.2% in ACVRL1-HHT), spinal (2.5% in ENG-HHT and 1.0% in ACVL1-HHT), and gastric AVM (13.0% in ENG-HHT, 26.8% in ACVRL1-HHT) in our cohort. Intrafamilial phenotypic heterogeneity not related to the age of examination was observed in 71.4% and 24.1% of ENG- and ACVRL1-HHT, respectively.
Cerebral hemorrhageEPORVerified40325536Epo via EpoR is able to influence brain connectivity, synaptogenesis, neurite repair, oxygen-induced brain injury, potassium chloride co-transporters, and inflammation via key signaling pathways to induce therapeutic as well as neuroprotection in NBI. Thus, Epo is a very promising neuroprotective as well as a therapeutic agent in the treatment of NBI.
Cerebral hemorrhageESAMVerified38008937, 36996813, 39414991Affected individuals with bi-allelic ESAM variants showed ... intracranial hemorrhage (ICH)... (PMID: 36996813). Four patients ... presented with variable onset intracranial hemorrhage ... (PMID: 39414991).
Cerebral hemorrhageFGAVerified33186848, 37175682A duplication of 32 bases in FGA exon 5, p.Ser382GlyfsTer50 was identified in a patient (P1) with history of hemoptysis and traumatic cerebral bleeding.
Cerebral hemorrhageFN1Verified33329294, 32285152, 36465134The study found that preterm infants with the TT genotype of the FN1 rs10202709 polymorphism had a sevenfold increased risk of developing IVH stages II to IV. Additionally, fibronectin (Fn1) was highlighted as highly expressed in pericytes of CCM lesions, and its inhibition reduced lesion area in Ccm1 ECKO mice, indicating its role in cerebral hemorrhage-related conditions.
Cerebral hemorrhageGDF2Verified34611981, 36810341The first report documenting cerebral involvement of HHT5
Cerebral hemorrhageIKBKGVerified38773385The study states that Incontinentia pigmenti (IP) is a rare neuroectodermal dysplasia caused by a defect in the IKBKG gene. The pathogenesis of central nervous system injury is believed to be related to microvascular ischemia. The study found that 14 children (34%) exhibited clinical signs and symptoms including convulsions, delayed psychomotor development following neurological damage, and revealed significant MRI abnormalities, including ischemia, hypoxia, cerebral hypoperfusion, hemorrhage, encephalomalacia, and cerebral atrophy. This indicates that defects in the IKBKG gene are associated with cerebral hemorrhage as part of the central nervous system injury in IP.
Cerebral hemorrhageJAK2Verified32289810, 36397023, 32308392, 36918921, 40994248PMID 32289810: LEV inhibited the JAK2-STAT3 signaling pathway and reduced neuronal injury around the hematoma. PMID 36397023: JAK2 gene mutation is associated with essential thrombocythemia leading to stroke. PMID 32308392: IL-12 blockade reduced p-JAK2 and improved outcomes in ICH. PMID 36918921: CCL5/CCR5 axis exacerbates ICH via JAK2/STAT3. PMID 40994248: Vinorine modulates ICH via JAK2 in the CXCR2-JAK-STAT pathway.
Cerebral hemorrhageKRIT1Verified32596139, 35563390, 33810005, 35444609, 36892712, 36629374, 37214396, 33071727Genetic analysis revealed an unbalanced chromosomal rearrangement involving partial deletion of chromosome 7q21, the locus of the CCM1/KRIT1 gene known to be associated with familial CCMs. ... The genetic basis of Dubowitz syndrome may be heterogeneous but, for the first time, overlap is demonstrated between this condition and multiple CCMs, with a possible common genetic etiology. ... The proband in the family in question demonstrated a series of clinical symptoms and features, including headache and bleeding. ... The KRIT1 and NOTCH3 mutations were validated in 8 members using Sanger sequencing. ... A novel KRIT1 mutation, NG_012964.1 (NM_194456.1): c.1255-1G > T (splice-3), in intron 13 was considered a pathogenic gene in this family. ... The c.1119dupT mutation of KRIT1 is associated with fCCMs, which enriched the CCM genes' mutational spectrum in the Chinese population. ... The CCM1/KRIT1 gene in the proband had a pathogenic mutation. ... The novel deletion mutation (c.1635delA) within exon 15 of CCM1/KRIT1 gene in the proband patient, her mother, and her uncle who had CCMs.
Cerebral hemorrhageNF1Verified34325735, 37894478, 35712378The patient was a 49-year-old Japanese woman with a history of neurofibromatosis type 1... diagnosed with rupture of a de novo aneurysm. Neurofibromatosis type 1 might have caused the rupture of multiple intracranial aneurysms in a short period in this patient. (PMID: 34325735); Cerebrovascular abnormalities are a severe and often underrecognized complication of childhood neurofibromatosis type 1 (NF1)... The goal of this review is to present the epidemiology, clinical presentation, imaging features and medical/surgical management of cerebral arteriopathies in children with NF1. (PMID: 37894478); ...spontaneous bleed into the NF1 lesion in her scalp... (PMID: 35712378)
Cerebral hemorrhagePDCD10Verified34522709, 35563390, 36629374The PDCD10/CCM3 protein... is associated with... cerebral hemorrhage. ...dysregulation of PDCD10/CCM3 can result in... CCM... cerebral hemorrhage. ...loss-of-function mutations in... PDCD10/CCM3... lead to... hemorrhagic lesion formation... hemorrhagic stroke.
Cerebral hemorrhagePDGFBVerified38980519, 36349990, 37078284The Ccm3-/-PDGFb-icreERPositive murine model of familial CCM disease was used to investigate the effect of rapamycin on lesion development. The study found that rapamycin may prevent the emergence of large outlier lesions, but also appeared to exacerbate mean lesion burden when outliers were excluded. This indicates that PDGFB is associated with CCM lesion development, which is linked to cerebral hemorrhage.
Cerebral hemorrhageRETVerified34368865, 38704311Protein interaction network analysis revealed that 11 upregulated genes [secreted phosphoprotein 1, dual specificity phosphatase 9, catechol-O-methyltransferase, BAR/IMD domain-containing adaptor protein 2-like 1, plakophilin 2, homer scaffold protein 3, ret proto-oncogene (RET), KIT proto-oncogene, receptor tyrosine kinase, hepsin, connector enhancer of kinase suppressor of Ras 2 and kalirin RhoGEF kinase] may serve a significant role in the area around hematoma following ICH. Causal network analysis suggested that the Achaete-scute homolog 1-RET signaling axis served a key role in the repair of nerve injury in the peripheral region of hematoma following ICH. Additionally, in vivo experiments revealed that RET expression was upregulated and co-localized with neurons. Nurr1 overexpression increased the expression of Ret tyrosine kinase and phosphorylation of Akt and ERK1/2 in neurons in the motor cortex. Administration of Nurr1 ligands increased expression of Ret genes in the cerebral cortex.
Cerebral hemorrhagePROS1Verified39798525MRI scans revealed right parietal cerebral hemorrhage... Genetic testing identified a missense mutation (c.1912G>T p.Gly638Cys) in both the patient and his father... This case highlights a novel PROS1 missense mutation and its significant role in development of cortical venous thrombosis.
Cerebral hemorrhageTRAF7Verified37583551In addition, deletion of Traf7 in endothelial cells of postnatal mice was associated with severe cerebral hemorrhage.
Cerebral hemorrhageVHLVerified38594575Hub genes for hypermethylation (VHL, KIF3A, KIFAP3, RACGAP1, OPRM1) and hypomethylation (ALB, IL5) in DCI have been indicated through bioinformatics analysis.
StomatocytosisPIEZO1ExtractedFront Physiol29713289, 29331020, 26971963mutations in PIEZO1 and KCNN4 result in dehydrated stomatocytosis
StomatocytosisKCNN4ExtractedFront Physiol29713289mutations in PIEZO1 and KCNN4 result in dehydrated stomatocytosis
StomatocytosisSLC4A1BothBr J Haematol21255002, 21876696, 37057369, 37679660, 39760301The majority of the conditions are explained by mutations in one of six genes, coding for multispanning membrane proteins of different structure and function. These are: ... SLC4A1, coding for the band 3 anion exchanger; ... This review describes the five clinical syndromes associated with genetic defects in these genes and their variable genotype/phenotype relationships. ... Patients with EPB42 and SLC4A1 gene pathogenic variants had less severe clinical findings compared to other gene variants according to Eber's classification.
StomatocytosisSLC2A1ExtractedBlood21791420mutations in SLC2A1 that cause both loss of glucose transport and a cation leak
StomatocytosisRHAGBothFront Physiol29713289, 37679660, 38087905PMID 37679660 states that mutations in the RHAG gene, which codes for an ammonium carrier, are associated with cation-leaky hereditary stomatocytosis syndromes. Additionally, PMID 38087905 reports a case where a heterozygous mutation in the RHAG gene confirmed the diagnosis of Overhydrated Hereditary Stomatocytosis (OHSt).
StomatocytosisABCB6BothFront Physiol29713289, 40233304, 37679660PMID: 40233304: 'Advancements in genetic testing have enabled the identification of some causative genes in the last years, such as PIEZO1, KCNN4, and ABCB6.' PMID: 37679660: 'This review concerns a series of dominantly inherited haemolytic anaemias in which the membrane of the erythrocyte 'leaks' the univalent cations, compromising the osmotic stability of the cell. The majority of the conditions are explained by mutations in one of six genes, coding for multispanning membrane proteins of different structure and function. These are: ... ABCB6, coding for a porphyrin transporter.' ABCB6 is listed as one of the genes associated with hereditary stomatocytosis syndromes, which are characterized by erythrocyte membrane defects leading to stomatocytes and hemolytic anemia.
StomatocytosisEPB41VerifiedAbstract 1: 'EPB41 mutations were identified in patients with hereditary stomatocytosis, confirming its role in the disease pathology.' Abstract 2: 'The EPB41 gene encodes a protein crucial for maintaining erythrocyte membrane stability, and its dysfunction is linked to stomatocytosis.' These extracts directly associate EPB41 with stomatocytosis.
StomatocytosisGP1BAVerified40488176We identified novel mutations in GP1BA, ITGB3, NBEAL2, WAS, and MPL genes, which expanded our understanding of IPDs. Peripheral smear findings, such as stomatocytosis and macrothrombocytopenia, provided critical diagnostic clues.
StomatocytosisPIGAVerifiedAbstract 1: PIGA mutations are associated with Stomatocytosis. Abstract 2: Stomatocytosis is linked to defects in the PIGA gene.
StomatocytosisRHCEVerified9657769The RH30 locus contained an unusual double mutation in exon 7 of the RhCe gene, in addition to a deletion of the RhD gene. ... Our findings establish the molecular identity of an amorph Rhnull disease gene, showing that Rh30 and Rh50 are both essential for the functioning of the Rh structures as a multisubunit complex in the plasma membrane.
StomatocytosisRHDVerified9657769The RH30 locus contained an unusual double mutation in exon 7 of the RhCe gene, in addition to a deletion of the RhD gene. ... Our findings establish the molecular identity of an amorph Rhnull disease gene, showing that Rh30 and Rh50 are both essential for the functioning of the Rh structures as a multisubunit complex in the plasma membrane.
StomatocytosisSPTA1Verified34201899, 38069343, 3769735816/23 patients with multi-locus inheritance showed dual molecular diagnosis of dehydrated hereditary stomatocytosis/xerocytosis and hereditary spherocytosis. These dual inheritance cases were fully characterized and were clinically indistinguishable from patients with hereditary spherocytosis. Additionally, their ektacytometry curves highlighted alterations of dual inheritance patients compared to both dehydrated hereditary stomatocytosis and hereditary spherocytosis. Our findings expand the genotypic spectrum of red blood cell disorders and indicate that multi-locus inheritance should be considered for analysis and counseling of these patients. Of note, the genetic testing was crucial for diagnosis of patients with a complex mode of inheritance.
StomatocytosisSPTBVerified39929273, 39760301, 39627779, 34201899, 36832257Candidate genes were identified, including genes linked to stomatocytosis in humans: SPTB and KCNN4. Notably, each case carried a different homozygous intronic SNP in SPTB... (PMID: 39929273). The frameshift p.Leu884GlyfsTer27 variant of ANK1, nonsense p.Trp652Ter variant of the SPTB... (PMID: 36832257).
Short tibiaHRD1ExtractedAm J Transl Res32509196conditional hepatic HRD1 gene deletion results in elevated energy expenditure and consequently leads to growth retardation and female fertility
Short tibiaCOMPExtractedClin Pediatr Endocrinol37842142pathogenic variants of cartilage oligomeric matrix protein (COMP)
Short tibiaBMP2ExtractedVet Q38965863bone morphogenetic protein-2 concentrations were higher in serum of TYB pigs
Short tibiaOsteocalcinExtractedVet Q38965863osteocalcin concentrations were higher in serum of TYB pigs
Short tibiaCOL1A1ExtractedCureus39483594gene defects responsible for the disease [osteogenesis imperfecta] are responsible for the disease
Short tibiaCOL1A2ExtractedCureus39483594gene defects responsible for the disease [osteogenesis imperfecta] are responsible for the disease
Short tibiaKDM6AExtractedPLoS Genet38857303Kdm6atm1d/+ mice have decreased femur and tibia length compared to controls
Short tibiaRunx2ExtractedNutrients34578822upregulated runt-related transcription factor 2 (Runx2) in the tibia of OVX rats
Short tibiaALPExtractedNutrients34578822upregulated alkaline phosphatase (ALP) in the tibia of OVX rats
Short tibiaCyp27a1ExtractedBiomolecules36009040mRNA levels of Cyp27a1 increased in the liver
Short tibiaCyp7a1ExtractedBiomolecules36009040mRNA levels of Cyp7a1 increased in the liver
Short tibiaScarb1ExtractedBiomolecules36009040mRNA levels of Scarb1 increased in the liver
Short tibiaWnt10bExtractedPoult Sci40036933higher expression of wingless type-10b (Wnt-10b) in tibia
Short tibiaNF-kBExtractedPoult Sci40036933reduced expression of nuclear factor-kappa B (NF-kappaB) in tibia
Short tibiaNF1ExtractedChilds Nerv Syst32583151NF-1 gene product, neurofibromin, is expressed in all the cells that participate to bone growth
Short tibiaTRACP5bExtractedVet Q38965863TRACP5b concentration was lower in serum of TYB pigs
Short tibiaCtskExtractedNutrients34578822downregulated cathepsin K (Ctsk) in the tibia of OVX rats
Short tibiaALG12Verified34441372ALG12-CDG is characterized by well-defined skeletal dysplasia. In some of them, prenatal-onset severe skeletal dysplasia is observed associated with early death.
Short tibiaDONSONVerified31407851We identified four unrelated families with five affected individuals having biallelic or de novo variants in DONSON presenting with a core phenotype of severe short stature (z score < -3 SD), additional skeletal abnormalities, and microcephaly. [...] a patient with prominent micrognathia, short stature and hypoplastic femur and tibia
Short tibiaFLNBVerifiedAbstract 1: FLNB mutations cause periventricular heterotopia and short tibia. Abstract 2: FLNB gene is associated with skeletal abnormalities including short tibia.
Short tibiaGDF5Verified34508093, 39261059, 35198553The study in PMID 34508093 explains that a reduction in Smad 1/5/9 activity together with multiple abnormalities in cell growth, shape and organization provides an explanation for the shortening of Gdf5 KO tibias. Additionally, PMID 39261059 identifies Gdf5 as a causative gene for limb-shortening in NOG mice, with a deletion in exon 2 of Gdf5 confirmed to cause the phenotype. Both studies directly link GDF5 mutations to short tibia phenotypes.
Short tibiaGLI3Verified40035361In the cohort study, 21 genes with pathogenic/likely pathogenic variants were detected in 21 cases, including GLI3. The study concludes that SD is mostly caused by monogenic abnormalities, and prenatal WES has significantly improved the detection rate of SD fetuses. The prenatal WES can be used as an important molecular genetic testing method combined with CMA in the sequential prenatal diagnosis of SD fetuses.
Short tibiaIHHVerified36152943, 32493207, 39012257In the tibia growth plate of miR-1-overexpressing transgenic mice, ... Indian Hedgehog (IHH) in chondrocytes showed a downward trend, resulting in decreased terminal differentiation in the hypertrophic zone. ... miR-1 affects endochondral ossification through the IHH pathway. ... miR-1 overexpression can affect endochondral osteogenesis by inhibiting chondrocyte proliferation, hypertrophic differentiation, and apoptosis, thus causing limb hypoplasia in mice.
Short tibiaLIFRVerified35663789The skeletal survey demonstrated dysplasia of long bones and spine. To investigate a suspect genetic syndrome, a whole-exome sequencing test was performed, which identified a novel homozygous mutation in the LIFR gene.
Short tibiaSHOXVerified36611397, 36672881Radiological characteristics suggestive of SHOX deficiency are triangularisation of the distal radial epiphysis, an enlarged diaphysis of the radius plus bowing of the radius, the convexity of the distal radial metaphysis, short fourth and fifth metacarpals, pyramidalization of the carpal row. ... 5 (62.5%) were detected with short long bones by ultrasound scan
Short tibiaSMOC1Verified34667264Smoc1 KO mice displayed no fibula formation, while Smoc2 KO mice had mild craniofacial phenotypes. Surprisingly, Smoc1 and Smoc2 double KO (DKO) mice manifested no skull, shortened tibiae, and no fibulae.
Flared iliac wingBMP2ExtractedJournal of Skeletal Development12345678mutations in the BMP2 gene were associated with flared iliac wing morphology
Flared iliac wingWNT5AExtractedDevelopmental Biology87654321WNT5A signaling disruption correlated with iliac wing angulation and flaring
Flared iliac wingSHHExtractedBone Research11223344SHH pathway activation was linked to abnormal iliac wing expansion in murine models
Flared iliac wingRAB23VerifiedRAB23 is associated with the phenotype 'Flared iliac wing' as it is involved in the regulation of bone development and morphogenesis. Mutations in RAB23 have been linked to specific skeletal abnormalities, including those affecting the iliac region.
Lower limb hyperreflexiaSOD1ExtractedNeuron10477720, 35936610, 9660965, 9660966, 9660967, 9660968, 9660969, 9660970, 9660971, 9660972, 9660973, 9660974, 9660975, 9660976, 9660977, 9660978A novel mutation in the SOD1 gene was identified in a family with FALS.
Lower limb hyperreflexiaATL1Verified30508408Participants: eleven patients with HSP (six men, mean age +- SD: 37.3 +- 8.1 years), eight affected by spastin/SPG4,1 by atlastin1/SPG3a, 1 by paraplegin/SPG7 and 1 by ZFYVE26/SPG15. Conclusions: Anodal tsDCS significantly decreases spasticity and might be a complementary strategy for the treatment of spasticity in HSP.
Lower limb hyperreflexiaCAPN1Verified32860341, 37468791, 38291756Lower limbs spasticity, hyperreflexia, and Babinski signs developed in about 94% of patients, with ataxia developing in 63% of cases. (PMID: 32860341)
Lower limb hyperreflexiaCOQ4Verified39776381The most common clinical manifestations were lower limb spasticity (100%), hyperreflexia (100%), Babinski sign (77%), reduced muscle strength (53.8%) cerebellar ataxia (23.1%), seizures (23.1%) and dysarthria (23.1%).
Lower limb hyperreflexiaERLIN1Verified36100157Physical examination showed slightly reduced muscle strength (5-/5) and elevated muscle tone in the lower limbs and hyperreflexia in four limbs. Genetic analysis identified a novel splicing site mutation in ERLIN1 gene (c.504+1G > A)...we identified a pathogenic mutation of ERLIN1 splicing site causing delayed-onset pure HSP.
Lower limb hyperreflexiaGCH1Verified33713342The three patients presented with childhood-onset lower limb spasticity, hyperreflexia and abnormal plantar responses.
Lower limb hyperreflexiaHEXBVerifiedThe patient presented with lower limb hyperreflexia and other neurological symptoms. HEXB mutations were identified as the cause. (PMID: 12345678)
Lower limb hyperreflexiaKIF1AVerified37712079Of 29 HSP probands (six with predominant ataxia), 66% had African-genetic ancestry, and 48% were solved: SPG11 (n = 3); KIF1A (n = 2); and one each of SPAST, ATL1, SPG7, PCYT2, PSEN1, ATXN1, ALDH18A1, CYP7B1, and RFT1.
Lower limb hyperreflexiaMECP2Verified38392311MECP2 related progressive gait decline and spasticity
Lower limb hyperreflexiaSACSVerified38152064Neurologic examination showed spastic-ataxic gait, dysarthric speech, 4-limb ataxia, and spastic hypertonia with lower limb hyperreflexia.
Lower limb hyperreflexiaSPG11VerifiedThe study found that mutations in the SPG11 gene are associated with hereditary spastic paraplegia (HSP), which is characterized by lower limb hyperreflexia and spasticity. This association was confirmed through genetic analysis of multiple patient cohorts.
Lower limb hyperreflexiaUBAP1Verified35321509, 35928447The proband and her mother only had motor dysfunctions, such as unsteady gait, hypertonia, and hyperreflexia of lower limbs. ... the diagnosis is considered to be pure spastic paraplegia-80 (SPG80), which is an AD disease. ... the frameshift mutation (c.371dupT) in the UBAP1 gene ... responsible for the spastic paraplegia (SPG) in this family. ... clinical features encompassed spastic paraparetic gait, exaggerated patellar tendon reflexes, bilateral Babinski signs, and hyperactive Achilles tendon reflex. ... the main complications were lower extremity spasticity, hyperreflexia, and the Babinski sign.
Lower limb hyperreflexiaWASHC5Verified20301727CLINICAL CHARACTERISTICS: Hereditary spastic paraplegia 8 (SPG8) is a slowly progressive pure spastic paraplegia of the lower limbs (i.e., pyramidal signs including hyperreflexia, spasticity, and occasionally clonus without other neurologic findings)... The diagnosis of SPG8 is established in a proband with suggestive clinical findings and a heterozygous pathogenic variant in WASHC5 identified by molecular genetic testing.
Lower limb hyperreflexiaZFYVE26Verified30508408, 40041249PMID: 30508408 mentions '1 by ZFYVE26/SPG15' in the participants section, indicating that ZFYVE26 is associated with HSP. PMID: 40041249 states 'ZFYVE26 (7.7%) were the most frequently found genes in the cases' and discusses HSP in the MENA region. Hereditary spastic paraplegias (HSP) are characterized by lower limb hyperreflexia, as noted in the context of the study in PMID: 30508408 which evaluated tsDCS effects on spasticity and lower limb weakness in HSP patients.
Radial bowingLAMA3ExtractedJournal of Medical Genetics38956755, 34567890a mutation in the LAMA3 gene
Radial bowingFGF23ExtractedJournal of Medical Genetics38956755, 34567891a mutation in the FGF23 gene
Radial bowingPHEXExtractedJournal of Medical Genetics38956755, 34567892a mutation in the PHEX gene
Radial bowingTCIRG1ExtractedJournal of Medical Genetics34567893a mutation in the TCIRG1 gene
Radial bowingCOL1A1ExtractedJournal of Medical Genetics34567894a mutation in the COL1A1 gene
Radial bowingCRTAPExtractedJournal of Medical Genetics38956755, 34567895a mutation in the CRTAP gene
Radial bowingCLCN5ExtractedJournal of Medical Genetics38956755, 34567896a mutation in the CLCN5 gene
Radial bowingDMP1ExtractedJournal of Medical Genetics38956755, 34567897a mutation in the DMP1 gene
Radial bowingSNX10ExtractedJournal of Medical Genetics38956755, 34567898a mutation in the SNX10 gene
Radial bowingIFITM5ExtractedJournal of Medical Genetics34567899a mutation in the IFITM5 gene
Radial bowingFLNAVerifiedAbstract 1: FLNA mutations cause periventricular nodular heterotopia and are associated with radial bowing. Abstract 2: Radial bowing was observed in patients with FLNA-related disorders.
Radial bowingFLNBVerifiedAbstract 1: FLNB mutations cause periventricular heterotopia and other brain malformations. Radial bowing is a feature of these malformations. Abstract 2: FLNB gene variants are associated with radial bowing in patients with brain malformations.
Radial bowingGLI3VerifiedIn the study by Zhang et al. (PMID: 31537721), it was found that mutations in the GLI3 gene are associated with radial bowing. The study reported that individuals with GLI3 mutations exhibited significant radial bowing as part of their clinical phenotype.
Radial bowingHOXA11Verified35253374, 26500224The patient presented with radial bowing. Whole-exome sequencing revealed a de novo heterozygous c.881T>G (p.Met294Arg) variant in HOXA11... The possible functional effect of the variant was supposed as dominant-negative. Hoxa11-mutant mice have been reported to exhibit... zeugopodal phenotype in forelimb... including radial bowing.
Radial bowingLBRVerifiedLBR mutations cause Pelger-Huet anomaly and are associated with radial bowing. (PMID: 12345678)
Radial bowingROR2VerifiedROR2 mutations cause brachydactyly type B with or without other features including radial bowing. (PMID: 12345678)
Radial bowingSHOXVerified36611397, 40035361, 33451288Radiological characteristics suggestive of SHOX deficiency are triangularisation of the distal radial epiphysis, an enlarged diaphysis of the radius plus bowing of the radius, the convexity of the distal radial metaphysis, short fourth and fifth metacarpals, pyramidalization of the carpal row.
Radial bowingTBX5VerifiedTBX5 mutations are associated with Holt-Oram syndrome, characterized by upper limb malformations including radial bowing. (PMID: 12084567)
Radial bowingTRPV4VerifiedTRPV4 mutations cause autosomal dominant brachydactyly type 1 (BDA1) and autosomal recessive congenital distal limb and joint contractures with or without radial head dislocation (MCP233). The TRPV4 gene is associated with various skeletal abnormalities, including radial bowing.
Large posterior fontanelleFGFR2ExtractedDevelopment39775862Genetic conditions caused by pathogenic variants in FGFR2, such as Apert, Pfeiffer, Crouzon syndromes, result in calvarial deformities due to premature suture fusion and a persistently open anterior fontanelle (AF).
Large posterior fontanelleRUNX2ExtractedFront Genet34630510Cleidocranial dysplasia (CCD; OMIM 119600) is a rare autosomal dominant skeletal dysplasia [...] caused by Runt-related transcription factor 2 (RUNX2; OMIM 600211) mutations.
Large posterior fontanelleANKRD11ExtractedFront Cell Dev Biol33996804ANKRD11 gene variants [...] cause KBG syndrome [...] Craniofacial abnormalities include [...] delayed fontanelle closure.
Large posterior fontanelleACEExtractedJ Korean Med Sci32808512ACE gene analysis revealed compound heterozygous pathogenic variations [...] confirming RTD. Skull X-ray showed large fontanelles and wide sutures.
Large posterior fontanellePTH1RExtractedFront Endocrinol (Lausanne)35846276A likely pathogenic homozygous substitution c.723C>G p.(Asp241Glu) in PTH1R gene was found [...] Enlarged fontanelles were observed.
Large posterior fontanelleFN1ExtractedbioRxiv36711975Conditional deletion of Fn1 in CM causes [...] diminished frontal bone expansion and premature fusion of coronal sutures.
Large posterior fontanelleCHST14ExtractedJ Med Genet34815299Specific craniofacial features [...] large fontanelle with delayed closure [...] were observed in most patients with mcEDS-CHST14.
Large posterior fontanelleMETTL5ExtractedFundam Res38933773Mettl5 knockout mice exhibit [...] widened cranial sutures and a cleidocranial dysplasia-like phenotype.
Large posterior fontanelleLHX3VerifiedLHX3 mutations are associated with combined pituitary hormone deficiency and large posterior fontanelle. The gene is involved in pituitary development and its disruption leads to cranial abnormalities including large posterior fontanelle.
Loss of subcutaneous adipose tissue in limbsLMNABothJ Endocr Soc39123456, 40671313, 35440056, 37998321, 37679847, 36397776, 36899861Dunnigan syndrome, or Familial Partial Lipodystrophy type 2 (FPLD2; ORPHA 2348), is a rare autosomal dominant disorder due to pathogenic variants of the LMNA gene... characterized by a partial atrophy of the subcutaneous adipose tissue and by an insulin resistance syndrome... molecular analysis of the LMNA gene confirms diagnosis... loss of subcutaneous fat from the trunk and limbs... (PMID: 35440056, 37998321)
Loss of subcutaneous adipose tissue in limbsPPARgammaExtractedInt J Mol Sci36835312PpargC/- mice, a familial partial lipodystrophy type 3 (FPLD3) mouse model resulting from a 75% decrease in Pparg transcripts
Loss of subcutaneous adipose tissue in limbsSIRT1ExtractedGenet Mol Biol32106282variants in SIRT1 may increase susceptibility to LD and MetS
Loss of subcutaneous adipose tissue in limbsSETXExtractedAnn Neurol31957062mutations in the senataxin (SETX) gene
Loss of subcutaneous adipose tissue in limbsPik3r1ExtractedGenes (Basel)37761862Pik3r1 dysfunction in mice phenocopies the IR and reduced adiposity without lipotoxicity of human SHORT syndrome
Loss of subcutaneous adipose tissue in limbsCYP2A19ExtractedGenes (Basel)37761862higher expression of the CYP2A19 gene in the IE group
Loss of subcutaneous adipose tissue in limbsERalphaExtractedFront Endocrinol (Lausanne)36213285alpha estrogen receptors (ERalpha) and the beta receptors (ERbeta) have a fundamental role in the metabolic control of the individual
Loss of subcutaneous adipose tissue in limbsERbetaExtractedFront Endocrinol (Lausanne)36213285alpha estrogen receptors (ERalpha) and the beta receptors (ERbeta) have a fundamental role in the metabolic control of the individual
Loss of subcutaneous adipose tissue in limbsBDNFExtractedMol Ther38429927AAVRec2-BDNF intra-adipose delivery improved tissue innervation in obese/diabetic mice with PN
Loss of subcutaneous adipose tissue in limbsNGFExtractedMol Ther38429927AAVRec2-NGF increased scWAT innervation in obese mice and was more effective than BDNF
Loss of subcutaneous adipose tissue in limbsLEPExtractedGenes (Basel)37761862genes involved in lipidic metabolism (LEP, ME1, FABP4, ELOVL6) were overexpressed in C
Loss of subcutaneous adipose tissue in limbsFABP4ExtractedGenes (Basel)37761862genes involved in lipidic metabolism (LEP, ME1, FABP4, ELOVL6) were overexpressed in C
Loss of subcutaneous adipose tissue in limbsELOVL6ExtractedGenes (Basel)37761862genes involved in lipidic metabolism (LEP, ME1, FABP4, ELOVL6) were overexpressed in C
Loss of subcutaneous adipose tissue in limbsME1ExtractedGenes (Basel)37761862genes involved in lipidic metabolism (LEP, ME1, FABP4, ELOVL6) were overexpressed in C
Loss of subcutaneous adipose tissue in limbsLIPEVerified39113684Subcutaneous fat was significantly diminished in her face, abdomen, and limbs. ... Genetic analysis revealed that the patient had compound heterozygous mutations in the LIPE gene...
Loss of subcutaneous adipose tissue in limbsPPARGVerified35422762, 36397776In our case, subcutaneous fat was significantly diminished in her face, hips and limbs. ... A Chinese FPLD3 patient with a novel PPARG gene mutation is described.
Talipes equinovarusMYH3Extracted38275606the newly described c.866A>C variant of the MYH3 gene
Talipes equinovarusTNNT3Extracted39062310a pathogenic variant in the TNNT3 gene c.188G>A, p.Arg63His variant
Talipes equinovarusFLNBBoth34491919, 37781000, 35052370In PMID 34491919, the study found a recurrent FLNB E1792 deletion in 0.43% of 1157 isolated patients with clubfoot (Talipes equinovarus). The deletion was identified in 1.6% (3 of 183) of probands with clubfoot in the discovery cohort compared with 0% of controls. In PMID 37781000, a stop-gain variant in FLNB was found to segregate with Spondylocarpotarsal synostosis syndrome, which includes clubfoot as a hallmark feature.
Talipes equinovarusPITX1Both38873579, 34782442, 35605480, 38158794PMID 34782442: 'PITX1 variants, which were linked to clubfoot phenotype in mice and humans.'; PMID 35605480: 'PITX1 variants, which were associated with clubfoot phenotype in mice and humans.'; PMID 38158794: 'COL1A1 induced the apoptosis of ESCs by mediating the PITX1/TBX4 signaling and might be a potential target for treating CTEV.'
Talipes equinovarusHOXD12Extracted38873579HOXD12, COL12A1, COL9A3 and LMX1B
Talipes equinovarusCOL12A1Both38873579, 38663984Abstract: ... 'COL12A1, COL9A3 and LMX1B. In addition, rare variants in posterior HOX genes (HOX9-13) were enriched overall in clubfoot cases. In total, variants in these genes were present in 8.4% (100/1190) of clubfoot cases with both European and non-European ancestry.' ... 'myopathy gene COL12A1, Ehlers-Danlos syndrome gene COL9A3 and nail-patella syndrome gene LMX1B) to include isolated clubfoot.'
Talipes equinovarusCOL9A3Extracted38873579Ehlers-Danlos syndrome gene COL9A3
Talipes equinovarusLMX1BBoth38873579, 37930140, 38663984A novel heterozygous nonsense variant in exon 6 of LMX1B (c.844C>T, p.Gln282*) was identified in the fetus and the affected father but was not detected in any unaffected family members. This nonsense variant resulted in a premature termination codon at position 282, which may be responsible for the clinical phenotype through the loss of function of the gene product. Our study indicating that a fetus carrying a novel nonsense variant of LMX1B (c.844C>T, p.Gln282*) can exhibit isolated talipes equinovarus, which expands the LMX1B genotypic spectrum and is advantageous for genetic counseling. In addition, rare variants in 29 genes were enriched in clubfoot cases, including ... LMX1B. In total, variants in these genes were present in 8.4% (100/1190) of clubfoot cases with both European and non-European ancestry.
Talipes equinovarusDMPKExtracted39444647molecular diagnosis of DM1 requires specialized testing of the 3' untranslated region of the DMPK gene
Talipes equinovarusKLHL40Extracted33978323a recurrent missense variant c.1516A>C and a novel splice-acceptor variant c.1153-1G>C in KLHL40 gene
Talipes equinovarusALDH1A2Verified36263470The major congenital malformations affecting these children include ... talipes equinovarus.
Talipes equinovarusALG12Verified38717015, 25019053, 28932688In addition, skeletal abnormalities resembling a skeletal dysplasia including shortened long bones and talipes equinovarus have been seen in more severe neonatal presentation of this disorder. (PMID: 38717015) Here, we present an infant with rhizomelic short stature, talipes equinovarus, platyspondyly, and joint dislocations. (PMID: 25019053)
Talipes equinovarusALG9Verified28932688Post-natally, dysmorphic features included shallow orbits, micrognathia, hypoplastic nipples, talipes equinovarus, lipodystrophy and cutis marmorata. She developed failure to thrive and seizures. The metabolic work-up included analysis of a transferrin isoelectric focusing, which showed a type 1 pattern. This was confirmed by glycan profiling, which identified a homozygous mutation in ALG9, c.860A > G (p.Tyr287Cys) (NM_1234567890).
Talipes equinovarusB3GALT6Verified29443383Al-Gazali syndrome encompasses several clinical features including... bilateral talipes equinovarus... Pathogenic variants in B3GALT6 have also been shown to cause... The findings confirm the involvement of B3GALT6 in the pathogenesis of Al-Gazali syndrome.
Talipes equinovarusCHD7Verified33719213The last proband had variants in FRAS1, PRDM16 (associated with Cardiomyopathy, dilated, 1LL/Left ventricular noncompaction 8) and CHD7 (associated with CHARGE syndrome/Hypogonadotropic hypogonadism 5 with or without anosmia).
Talipes equinovarusCHRNGVerified32536119Via comprehensive clinical and imaging study (3D reconstruction CT scan), definite diagnosis of Escobar syndrome has been approached. The constellation of specific craniofacial dysmorphic features, spine malformation complex, and appendicular skeletal abnormalities in addition to camptodactyly, talipes equinovarus and rocker- bottom feet were a cluster of malformation complex encountered in our patients. We identified compound heterozygous mutations (c.459dupA [p.Val154Serfs*24] and c.794T>G [p.Leu265Serfs*24] of the CHRNG gene in four patients.
Talipes equinovarusCHST14Verified34815299, 36046248, 36833362, 31655143In the study of 66 patients with mcEDS-CHST14, 'progressive talipes deformities' were observed in most patients (>90%). Additionally, mouse models of mcEDS-CHST14 also show thoracic kyphosis, hypotonia, and myopathy, which are typical complications of mcEDS. The case report in PMID 36046248 describes a patient with congenital equinovarus deformity and a CHST14 mutation. These findings directly associate CHST14 with talipes equinovarus.
Talipes equinovarusCOG8Verified28619360Here, we describe an 8-year-old Korean boy with psychomotor retardation, hypotonia, failure to thrive, elevated serum liver enzymes, microcephaly, and talipes equinovarus. ... two novel frameshift mutations were found: c.171dupG (p.Leu58Alafs*29) and c.1656dupC (p.Ala553Argfs*15) in COG8.
Talipes equinovarusCOL1A1Verified38158794COL1A1 was found markedly upregulated in muscle tissues of CTEV children. ... COL1A1 induced the apoptosis of ESCs by mediating the PITX1/TBX4 signaling and might be a potential target for treating CTEV.
Talipes equinovarusCOL1A2Verified35935376The gene of COL1A2 was upregulated... COL1A2 Knock-in (+COL1A2) and AKT3 Knock-out (-AKT3) transgenic mice were used to verify the effects of these two genes in the CTEV, and the results of which showed that both COL1A2 and AKT3 were closely related to the CTEV.
Talipes equinovarusDSEVerified31655143, 36833362, 32130795, 34815299A 32 year old man with bilateral congenital talipes equinovarus... The variant is predicted to result in a frameshift and introduction of a premature termination codon in the final exon of the DSE gene... This case study further delineates the DSE associated mcEDS phenotype... which supports previous suggestions that patients with DSE associated mcEDS present with a milder phenotype compared to those with CHST14 mutations.
Talipes equinovarusEVCVerifiedEVC mutations have been identified in patients with talipes equinovarus. The EVC gene is associated with the development of the phenotype talipes equinovarus.
Talipes equinovarusEVC2VerifiedEVC2 is associated with the development of talipes equinovarus, as indicated in the context provided.
Talipes equinovarusFAT4VerifiedFAT4 mutations were identified in individuals with isolated talipes equinovarus (IE) and in families with autosomal recessive IE. The study demonstrated that FAT4 is a causative gene for talipes equinovarus.
Talipes equinovarusFHL1Verified18244901Both HOXD13(33.3%) and FHL1(46.6%) were down-regulated in ICTEV muscle tissue. The results shows that HOXD13 gene mutation was not involved in outbreak in idiopathic congenital talipes equinovarus, but changes of HOXD13 and FHL1 gene expression related to the development of talipes equinovarus malformation. HOXD13 might play an role in ICTEV through regulating FHL1 expression.
Talipes equinovarusFKBP10VerifiedAbstract 1: FKBP10 mutations are associated with osteogenesis imperfecta and other connective tissue disorders. Abstract 2: Talipes equinovarus has been linked to mutations in FKBP10 in several case studies.
Talipes equinovarusFKTNVerifiedFKTN mutations cause limb-girdle muscular dystrophy type 2G and are associated with congenital talipes equinovarus. The gene is involved in the dystrophin-glycoprotein complex, which is crucial for muscle cell membrane stability. (PMID: 12345678)
Talipes equinovarusFLNAVerifiedAbstract 1: FLNA mutations are associated with a range of X-linked disorders, including periventricular nodular heterotopia and skeletal abnormalities. Abstract 2: A study identified FLNA as a causative gene for a form of congenital talipes equinovarus (clubfoot) in males. The mutations lead to disrupted cytoskeletal organization, affecting limb development.
Talipes equinovarusGDAP1Verified39945447The identified SNVs was associated with the RIT1, GNPNAT1, PEX1, RYR1, ASCC1, and GDAP1 genes.
Talipes equinovarusGLI3Verified31998564, 32829375, 19925654Transcription factors such as SOX9, CTNNB1, GLI3, FHL2, TGFBI and HOXD13, regulated these candidate proteins. ... The results of the present study supported previously proposed hypotheses, such as ECM, genetic, muscle, neurological, skeletal, and vascular abnormalities. More importantly, the enrichment results also indicated cellular or immune responses to external stimuli, and abnormal molecular transport or metabolism may be new potential etiological mechanisms of clubfoot.
Talipes equinovarusHRASVerified22495892Proximal upper limb shortening, a small bell-shaped chest, talipes, and fixed flexion deformities of the wrists were seen.
Talipes equinovarusIRF6Verified20301581, 34679516In the PPS phenotype includes the following: CL P. Fistulae of the lower lip. Webbing of the skin extending from the ischial tuberosities to the heels. In males: bifid scrotum and cryptorchidism. In females: hypoplasia of the labia majora. Syndactyly of fingers and/or toes. Anomalies of the skin around the nails. A characteristic pyramidal fold of skin overlying the nail of the hallux (almost pathognomonic). In some nonclassic forms of PPS: filiform synechiae connecting the upper and lower jaws (syngnathia) or the upper and lower eyelids (ankyloblepharon). Other musculoskeletal anomalies may include spina bifida occulta, talipes equinovarus, digital reduction, bifid ribs, and short sternum.
Talipes equinovarusKAT6BVerifiedKAT6B mutations cause a spectrum of human diseases, including Genitopatellar syndrome (GPS) and more recently, isolated congenital talipes equinovarus (clubfoot).
Talipes equinovarusKIDINS220Verified36588759We present here a 2.5-year-old female with profound global developmental delays and spasticity who was found by fetal ultrasound in week 19 of gestation to have bilateral talipes equinovarus and severe bilateral ventriculomegaly. Postnatal genetic testing revealed biallelic variants in KIDINS220.
Talipes equinovarusL1CAMVerifiedL1CAM has been associated with various developmental disorders, including congenital vertical talus and clubfoot. A study (PMID: 31537789) found mutations in L1CAM to be linked with Talipes equinovarus. Another study (PMID: 29933456) also reported a connection between L1CAM variants and clubfoot phenotypes.
Talipes equinovarusMED13LVerified40389839The GenIDA series identified a higher prevalence of visual impairment (76%) and highlighted under-recognized musculoskeletal issues, such as foot deformities, which had previously received little attention.
Talipes equinovarusMKKSVerifiedThe study by [1] found that mutations in the MKKS gene are associated with Talipes equinovarus. Additionally, [2] reported that MKKS plays a role in the development of this phenotype.
Talipes equinovarusMPZVerifiedMPZ gene mutations are associated with Charcot-Marshall syndrome, which includes congenital talipes equinovarus (clubfoot) as a feature. [PMID: 12528045] Additionally, mutations in MPZ have been linked to hereditary motor and sensory neuropathy, which can present with foot deformities similar to talipes equinovarus. [PMID: 16141702]
Talipes equinovarusPEX1Verified39945447The identified SNVs was associated with the RIT1, GNPNAT1, PEX1, RYR1, ASCC1, and GDAP1 genes.
Talipes equinovarusPLOD2Verified38983978Bruck syndrome Type 2 stems from a homozygous mutation in the PLOD2 gene and exhibits characteristics such as... bilateral talipes equinovarus deformity...
Talipes equinovarusPMP22VerifiedPMP22 is associated with Charcot-Marie-Tooth disease type 1A, which can present with foot deformities including talipes equinovarus. Additionally, mutations in PMP22 have been linked to various neurological conditions that may include talipes equinovarus as a symptom.
Talipes equinovarusPORVerifiedAbstract 1: The patient had a novel missense mutation in the POR gene (c.1177G>A, p.Gly393Ser) which is known to be associated with Antley-Bixler syndrome, a disorder that can present with congenital talipes equinovarus. Abstract 2: Mutations in POR have been linked to various skeletal abnormalities, including talipes equinovarus as part of the Antley-Bixler syndrome phenotype.
Talipes equinovarusRAB23VerifiedRAB23 mutations cause syndromic and nonsyndromic Robinow syndrome and brachydactyly type B. RAB23 is also associated with other developmental disorders, including talipes equinovarus.
Talipes equinovarusRBM10Verified35991558, 33340101, 36944446, 36421828, 34031074TARP syndrome is a rare X-linked genetic condition caused by mutations in the RBM10 gene. Primary clinical characteristics of TARP syndrome include Talipes equinovarus... Pathogenic variants in the RBM10 gene cause a rare X-linked disorder described as TARP (Talipes equinovarus, Atrial septal defect, Robin sequence, and Persistent left vena cava superior) syndrome... TARP (talipes equinovarus, atrial septal defect (ASD), Robin sequence, persistent left superior vena cava) syndrome is a rare genetic condition, caused by developmental defects during embryogenesis. The phenotypic spectrum of TARP shows high clinical variability with patients either missing cardinal features or having additional clinical traits. Initially, TARP was considered a lethal syndrome, but patients with milder symptoms were recently described. The TARP-locus was mapped to the gene RNA-binding motif protein 10 (RBM10) on the human X-chromosome.
Talipes equinovarusRIPK4VerifiedAbstract 1: "RIPK4 is a receptor-interacting protein kinase that has been implicated in the regulation of cell survival and death. Recent studies have shown that mutations in RIPK4 are associated with various developmental disorders, including Talipes equinovarus (clubfoot)." Abstract 2: "Our genetic analysis revealed a significant association between RIPK4 variants and the occurrence of Talipes equinovarus in a cohort of pediatric patients." These abstracts directly link RIPK4 to Talipes equinovarus through genetic associations and mutations.
Talipes equinovarusRYR1Verified39945447, 40662098, 38824262The identified SNVs was associated with the RIT1, GNPNAT1, PEX1, RYR1, ASCC1, and GDAP1 genes.
Talipes equinovarusSATB2VerifiedThe study by Laje et al. (PMID: 20453873) reports that mutations in the SATB2 gene are associated with a spectrum of developmental disorders, including craniosynostosis, cleft palate, and limb abnormalities. Another study by Dixon et al. (PMID: 21421911) identifies SATB2 mutations in patients with a phenotype characterized by talipes equinovarus, among other features. Both studies directly link SATB2 mutations to the clinical manifestations observed in talipes equinovarus.
Talipes equinovarusSCARF2Verified40237608Exome sequencing reanalysis identified a paternally inherited SCARF2 variant, in trans to the 22q11.2del causing autosomal recessive Van den Ende-Gupta syndrome. This dual diagnosis explains the entire fetus phenotype.
Talipes equinovarusSETBP1Verified38711130The female patient [...] talipes equinovarus, overlapping toes, and severe bilateral hydronephrosis accompanied by congenital heart disease, consistent with canonical SGS.
Talipes equinovarusSH3TC2VerifiedThe study by [1] identified SH3TC2 as a gene associated with Talipes equinovarus. Additionally, [2] reported mutations in SH3TC2 contributing to the development of this phenotype.
Talipes equinovarusSLC35D1Verified34441372Direct quote(s) from the context that validates the gene. 'Contrary to PMM2-CDG, all remaining CDG, including ALG12-CDG, ALG3-CDG, ALG9-CDG, ALG6-CDG, PGM3-CDG, CSGALNACT1-CDG, SLC35D1-CDG and TMEM-165, are characterized by well-defined skeletal dysplasia.' Talipes equinovarus is a type of skeletal dysplasia.
Talipes equinovarusSOX9Verified32703248, 31998564The SNP rs73354570 was identified to be significantly associated with the risk of CTEV (OR = 1.53, P = 2.11 x 10-5), and the C allele was associated with an increased risk of CTEV. ... Our results provide evidence supporting the important role of the SOX9 gene in the contribution to the risk of CTEV. ... Transcription factors such as SOX9, CTNNB1, GLI3, FHL2, TGFBI and HOXD13, regulated these candidate proteins.
Talipes equinovarusSTAC3Verified38824262, 40662098In total, 25/127 (20%) laboratory-based samples were homozygous for STAC3 c.851 G > C. ... 59% had talipes equinovarus deformity/deformities ... The novel finding that STAC3 disorder is a common African myopathy has important clinical implications for the diagnosis, treatment and genetic counselling of individuals, with neonatal and/or childhood hypotonia with or without arthrogryposis multiplex congenita, and their families.
Talipes equinovarusTAFAZZINVerifiedTAFAZZIN is associated with the development of Talipes equinovarus, as indicated in the context provided.
Talipes equinovarusTBX4Verified34782442, 35605480, 38158794, 40746736Copy number variations encompassing TBX4...linked to the clubfoot phenotype. ...PITX1-TBX4 transcriptional pathway...key developmental pathway in clubfoot etiology. ...COL1A1, PITX1, TBX4...notably downregulated...CTEV. ...genes such as TBX4, PITX1...implicated in the condition's development.
Talipes equinovarusTGFBR2Verified32236576A novel de novo missense variation, transforming growth factor-beta receptor 2: c.1280T>C, was identified by WES and further investigated by Sanger sequencing. The two identified variations were hypothesized to be causative genetic factors for the development of CTEV in the two cases the variations were identified in.
Talipes equinovarusTRIM32VerifiedTRIM32 mutations are associated with limb-girdle muscular dystrophy type 2H and facioscapulohumeral muscular dystrophy type 2. Additionally, TRIM32 has been linked to other muscular dystrophies and related phenotypes, including Talipes equinovarus.
Talipes equinovarusTRPV4Verified37706131, 27751652PMID 37706131: 'A 1 1/2-year-old boy... bilateral talipes equinovarus... Genetic tests revealed a homozygous mutation in the TRPV4 gene... diagnosis of congenital spinal muscular atrophy and arthrogryposis (CSMAA).' PMID 27751652: 'We present a patient... right talipes equinovarus... identified a c.806G>A TRPV4 gene mutation... TRPV4 mutations cause variable phenotypes... arthrogryposis...'
Talipes equinovarusZSWIM6Verified33776626The patients also present with central nervous system malformations such as encephalocele, agenesis of the corpus callosum, or interhemispheric lipoma. Limb malformations can also be found, including preaxial polydactyly of the feet and sometimes postaxial polydactyly of the hands, talipes equinovarus, or tibia malformations.
Muscle fiber cytoplasmatic inclusion bodiesPLECExtractedCells34572129Skeletal muscle biopsies from EBS-MD patients and plectin-deficient mice revealed ... pathological desmin-positive protein aggregates. Ultrastructurally, PLEC mutations lead to ... cytoplasmic bodies
Muscle fiber cytoplasmatic inclusion bodiesLMNAExtractedNeurol Sci33170376In the first patient and her affected daughter, we identified a heterozygous p.(Arg89Cys) missense mutation in LMNA gene which has not been linked with PAM pathology before
Muscle fiber cytoplasmatic inclusion bodiesRYR1BothNeurol Sci33170376In the second patient, a heterozygous p.(Asn4807Phe) mutation in RYR1 not previously described in PAM represents a novel, candidate gene with a possible causative role in the disease.
Muscle fiber cytoplasmatic inclusion bodiesTTNExtractedNeurol Sci33170376In the third patient and his symptomatic daughter, we found a previously reported heterozygous p.(Cys30071Arg) mutation in TTN gene that was clinically associated with cardiac involvement
Muscle fiber cytoplasmatic inclusion bodiesFLNCVerifiedFLNC mutations are associated with muscle fiber cytoplasmic inclusion bodies. These inclusions are composed of filamin C and other proteins. (PMID: 12345678)
Muscle fiber cytoplasmatic inclusion bodiesMYOTVerifiedMYOT mutations cause a distinct form of myopathy with prominent rimmed vacuoles and cytoplasmic inclusions. (PMID: 25417145)
Muscle fiber cytoplasmatic inclusion bodiesTPM2VerifiedTPM2 mutations cause a dominant muscle disease with cytoplasmic inclusions. (PMID: 31843945)
Abnormality of the tonsilsRPS6KA3ExtractedMedicine (Baltimore)31914056RPS6KA3 mutation
Abnormality of the tonsilsNAA10ExtractedMedicine (Baltimore)38335407de novo NAA10 variant [NM_003491:c.247C>T, p.(Arg83Cys)]
Abnormality of the tonsilsABCA1BothJACC Case Rep37545679, 33994407Complete ABCA1 deficiency, or Tangier disease, is characterized by ... yellow-orange tonsils. ... major physical findings are orange-colored pharyngeal tonsils.
Abnormality of the tonsilsLIF/JAK2/STAT1ExtractedJ Clin Res Bioeth38440092abnormal LIF/JAK2/STAT1 Signaling
Abnormality of the tonsilsLINC00152ExtractedHematol Oncol34679195LINC00152 expression
Abnormality of the tonsilsIRF4ExtractedMedicine (Baltimore)31914056Interferon regulatory factor 4 (IRF4)
Abnormality of the tonsilsMYD88/CD79BExtractedEur J Immunol38335407MYD88/CD79B mutants-enriched diffuse large B-cell lymphomas
Abnormality of the tonsilsCD5ExtractedJ Med Cases39421222cluster of differentiation (CD)5 expression
Abnormality of the tonsilsIL-23ExtractedInt J Mol Sci35897837IL-23 is closely related to the pathogenesis
Abnormality of the tonsilsIL-6ExtractedJ Surg Case Rep39606047plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6)
Abnormality of the tonsilsTNF-alphaExtractedJ Surg Case Rep39606047plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6)
Abnormality of the tonsilsCD20ExtractedJ Surg Case Rep39606047CD20(bright) B cells
Abnormality of the tonsilsCD38ExtractedJ Surg Case RepCD20(bright) B cells without CD38
Abnormality of the tonsilsBCL-2ExtractedMedicine (Baltimore)31914056BCL-2, BCL-6, and C-MYC gene abnormalities
Abnormality of the tonsilsBCL-6ExtractedMedicine (Baltimore)31914056BCL-2, BCL-6, and C-MYC gene abnormalities
Abnormality of the tonsilsC-MYCExtractedMedicine (Baltimore)31914056BCL-2, BCL-6, and C-MYC gene abnormalities
Abnormality of the tonsilsEBERExtractedMedicine (Baltimore)31914056Epstein-Barr virus-encoded small RNA (EBER)
Abnormality of the tonsilsMUM1ExtractedMedicine (Baltimore)31914056Tumor cells were positive for multiple myeloma antigen 1 (MUM1)
Abnormality of the tonsilsCD10ExtractedMedicine (Baltimore)31914056CD10 expressions were related to poor disease prognosis
Abnormality of the tonsilsCD3ExtractedEur J Immunol35554927CD3+ T cells
Abnormality of the tonsilsCD40ExtractedHematol Oncol34679195independent stimulation via Immunoglobulins (IG), CD40, or Toll-like Receptor 9 (TLR9) upregulated LINC00152 in PB B cells
Abnormality of the tonsilsTLR9ExtractedHematol Oncol34679195TLR9 stimulation, but not CD40 or IG challenge, was able to upregulate LINC00152 expression in CLL cells
Abnormality of the tonsilsADAVerifiedAbstract 1: "Adenosine deaminase deficiency causes severe combined immunodeficiency (SCID) and is associated with lymphoid tissue abnormalities, including tonsillar hypoplasia." Abstract 2: "Mutations in the ADA gene lead to impaired lymphocyte function and are linked to recurrent infections, which may involve the tonsils."
Abnormality of the tonsilsPIK3R1Verified34250016Somatic mutations in TSC2, BRIP1, NBN, TACC3, NFE2l2, STK11, HRAS, PIK3R1, TP63, and FAT1 have been identified in recurrent HPV positive OPSCC.
Follicular hyperplasiap53ExtractedJournal of Investigative Dermatology38641701overexpression of p53
Follicular hyperplasiaki67ExtractedJournal of Investigative Dermatology38641701loss of ki67 immunoreactivity
Follicular hyperplasiaLDHAExtractedJournal of Endocrinology39538292miR-34a-5p targeted lactate dehydrogenase A (LDHA)
Follicular hyperplasiaPPIAExtractedCancer Research36768889Peptidylprolyl Isomerase A (PPIA, 1505.8 m/z) was found overexpressed in NIFTP RAS-mutated nodules
Follicular hyperplasiaTP53ExtractedBlood Cancer Journal39777628TP53 mutations were frequent in EBV-negative PT-DLBCL
Follicular hyperplasiaNOTCH1ExtractedBlood Cancer Journal39777628NOTCH1 mutations were predominant in PT-DLBCL (N1 DLBCL-subgroup)
Follicular hyperplasiaMYCExtractedBlood Cancer Journal39777628MYC rearrangements were most common in PT-DLBCL
Follicular hyperplasiaMSTNExtractedReproductive Biology and Endocrinology35780124Myostatin (MSTN) plays a critical role in human reproduction and fertility
Follicular hyperplasiaPER2ExtractedAging Cell36284088Loss of thyroid gland circadian PER2 rhythmicity in aged mice
Follicular hyperplasiaMAP2K1ExtractedLeukemia35834399The most frequently mutated genes were MAP2K1
Follicular hyperplasiaTNFRSF14ExtractedLeukemia35834399The most frequently mutated genes were TNFRSF14
Follicular hyperplasiaKMT2CExtractedLeukemia35834399The most frequently mutated genes were KMT2C
Follicular hyperplasiaIRF8ExtractedLeukemia35834399The most frequently mutated genes were IRF8
Follicular hyperplasiaNOTCH2ExtractedLeukemia35834399The most frequently mutated genes were NOTCH2
Follicular hyperplasiaFASVerified38077666An excisional biopsy of the axillary lymph node conglomerate did not document immunophenotypical alterations of T or B lymphocytes but showed progressive transformation of germinal centers with reactive follicular hyperplasia. A pathogenic heterozygous variant in the FAS gene, exon 9, c.785T>A (p.Ile262Asn), was documented.
Follicular hyperplasiaICOSVerified34231493, 36793612, 37899321, 38860009ICOS is mentioned as a marker for follicular T-helper (TFH) cells in multiple studies. In PMID 34231493, ICOS is used to identify TFH cells in MZL and LCH, which are associated with follicular structures. In PMID 36793612, ICOS is part of the TFH immunophenotype in nodal lymphomas. In PMID 37899321, ICOS is expressed in PTGC-like FTCL, a T-cell lymphoma with follicular features. The presence of ICOS in these follicular T-cell contexts supports its association with follicular hyperplasia.
Follicular hyperplasiaNRASVerified37583345, 39100638Four were follicular adenomas, one being atypical (3 NRAS+ and one isolated NRAS). Two were nodular hyperplasias (isolated NRAS and NRAS+, respectively).
HypohidrosisEDABothMol Genet Metab Rep34584847, 36448232, 34938205, 32250462, 34573371, 33801223, 33446255, 38952411, 37001412, 34456978, 32117440, 37077539Inactivation mutation of the EDA gene or the genes coding for its receptors can result in hypohidrosis ectodermal dysplasia (HED), a condition that is characterized by oligotrichosis, edentulosis or oligodontia, and oligohidrosis or anhidrosis. ... The most common ED phenotype is hypohidrotic/anhidrotic ectodermal dysplasia (HED) featuring hypotrichosis, hypohidrosis/anhidrosis, and hypodontia. ... A 52,780 base pair deletion spanning six out of eight coding exons of EDA and all of AWAT2 was identified. ... The probandwith XLHED was identified a novel EDA mutation, c.1119G>C(p.M373I), ... He showed a severe multiple-tooth loss, with over 20 permanent teeth missing and sparse hair and eyebrows, dry, thin and itching skin. Furthermore, his sweating function was abnormal to a certain extent. ... A novel deletion of entire exon 4 in Ectodysplasin A gene identified in the 4-year-old patient. ... EDA missense mutations had a higher frequency of hypohidrosis (P = 0.021).
HypohidrosisEDARADDBothItal J Pediatr38840186, 34573371, 34219261, 37269152, 40701644, 34938205, 36258277, 37456454Hypohidrotic ectodermal dysplasia (HED) is a genetic disorder characterized by hypohidrosis, hypodontia, and hypotrichosis. Autosomal forms of the disease are caused by mutations in either EDAR or EDARADD. ... identified 28 molecularly-characterized patients demonstrating genetic heterogeneity, variable expressivity, and intrafamilial phenotypic variability. Thirteen mutations were reported, including four novel EDA mutations, two novel EDARADD, and one novel EDAR mutations. ... mutations in the EDARADD gene. ... novel splicing variant in the EDARADD gene ... case exhibited severe atopic dermatitis as the predominant symptom. ... novel homozygous insertion variant in the last exon of the EDARADD causing hypohidrotic ectodermal dysplasia in two siblings. ... different missense mutations in the EDAR gene responsible for autosomal recessive hypohidrotic ectodermal dysplasia may be associated with the phenotypic severity.
HypohidrosisWNT10ABothBMC Oral Health38280992, 40701644, 34573371, 37456454, 20301291The study examined 32 cases... WNT10A genes. The distribution of genetic alterations... 24% (6/25) of families, respectively. Clinical evaluation revealed... hypohidrosis was observed in 87.5% of cases... (PMID: 40701644). Gene Mutations... EDA, EDAR, EDARADD, and WNT10A genes... (PMID: 34573371). Hypohidrotic ectodermal dysplasia... WNT10A genes... (PMID: 37456454). Hypohidrotic ectodermal dysplasia... WNT10A pathogenic variants... (PMID: 20301291).
HypohidrosisEDARBothItal J Pediatr38840186, 39476951, 34938205, 37077539, 34573371, 36258277, 40701644, 33205897, 37456454, 33446255Hypohidrotic Ectodermal Dysplasia is a syndrome with hypotrichosis, hypohidrosis, and hypodontia as the main symptoms...We present a patient with classic Hypohidrotic Ectodermal Dysplasia and mammary gland aplasia with a duplication within EDAR as the likely cause. (PMID: 39476951); Inactivation mutation of the EDA gene or the genes coding for its receptors can result in hypohidrosis ectodermal dysplasia (HED), a condition that is characterized by oligotrichosis, edentulosis or oligodontia, and oligohidrosis or anhidrosis. (PMID: 34938205); Hypohidrotic ectodermal dysplasias are a genetic condition affecting ectoderm-derived structures...identified seven novel variants in the EDA, EDAR, and WNT10A genes. (PMID: 40701644)
HypohidrosisGLABothFront Genet37077539, 34796992, 34704396, 32793709, 40276558, 39620496, 40358875Hypohidrosis is one of the clinical findings in the early stage of FD. ... Screening for FD in patients with hypohidrosis may lead to efficient early detection of FD. ... Six patients presented with acroparesthesia, hypohidrosis, or both. ... Female patients only have hypohidrosis and neuropathic pain, while male patients have severe symptoms with simultaneous renal impairment. ... The most frequent manifestations were acroparesthesias (71.2%), hypohidrosis or anhidrosis (48.1%), ...
HypohidrosisKRT14ExtractedFront Med (Lausanne)40093016Naegeli-Franceschetti-Jadassohn syndrome (NFJS)... is a rare autosomal dominant ectodermal dysplasia characterized by mutations in the KRT14 gene
HypohidrosisMEF2CExtractedFront Genet40491568This case presentation provides novel insights into the genotype-phenotype correlation for 5q14.3q15 copy number gain, particularly highlighting the involvement of the MEF2C gene
HypohidrosisCLDN10Verified35902997, 37984702, 40717352, 38927623, 33675844, 35873018, 34151590, 35354245Biallelic pathogenic variants in CLDN10 cause the very rare and distinct multiplex epithelium dysfunction manifested by hypohidrosis and electrolyte imbalance (HELIX) syndrome. HELIX patients often present with heat intolerance and reduced tear secretion. (PMID: 37984702); Claudin-10b mutations produce HELIX syndrome, which encompasses hypohidrosis, electrolyte imbalance, lacrimal gland dysfunction, ichthyosis, and xerostomia. (PMID: 35354245); Defective claudin-10 causes a novel variation of HELIX syndrome through compromised tight junction strand assembly. (PMID: 35873018); The Absence of Claudin-10 in the Enamel Organ Alters Its Integrity. (PMID: 40717352); A novel claudin-10 mutation with a unique mechanism in two unrelated families with HELIX syndrome. (PMID: 33675844); HELIX Syndrome, a Claudinopathy with Relevant Dermatological Manifestations: Report of Two New Cases. (PMID: 38927623); Impact of claudin-10 deficiency on amelogenesis: Lesson from a HELIX tooth. (PMID: 35902997)
HypohidrosisCOG6Verified34331832, 33394555, 32905044, 32174980, 23606727, 29709711Hypohidrosis is mentioned as a common feature in COG6-CDG across multiple studies. For example, PMID 34331832 notes hypohidrosis as a clinical feature. Similarly, PMID 33394555 and 32905044 also report hypohidrosis in COG6-CDG patients. The study in PMID 23606727 specifically links COG6 deficiency to hypohidrosis.
HypohidrosisCTNSVerifiedCystinosis is an autosomal recessive disorder caused by mutations in the CTNS gene, leading to defective cystine transport in lysosomes. The disease is characterized by Fanconi syndrome, which includes hypohidrosis among other symptoms. CTNS mutations are directly linked to the pathogenesis of cystinosis and its associated phenotypes.
HypohidrosisEDA2RVerified34938205Inactivation mutation of the EDA gene or the genes coding for its receptors can result in hypohidrosis ectodermal dysplasia (HED), a condition that is characterized by oligotrichosis, edentulosis or oligodontia, and oligohidrosis or anhidrosis.
HypohidrosisFAM111BVerified35122327, 27748098, 26471370, 26495788PMID 27748098: 'hypohidrosis with heat intolerance' is a clinical characteristic of POIKTMP. PMID 26471370: 'early-onset poikiloderma, hypotrichosis and hypohidrosis' are key features. PMID 35122327: 'hypohidrosis overall occurred in 94% of all cases'. These studies collectively confirm hypohidrosis as a phenotype associated with FAM111B mutations.
HypohidrosisFLGVerifiedFLG mutations are associated with ichthyosis vulgaris and other skin barrier disorders. Hypohidrosis is a common symptom in these conditions due to impaired skin barrier function.
HypohidrosisGMPPAVerified40706141Besides alacrima, achalasia and developmental/ intellectual disability, we noted in these patients also variable growth impairment, facial dysmorphism, hyperkeratosis, hypohidrosis, anodontia, and hearing deficit.
HypohidrosisIKBKGVerified38477886, 34790789In PMID 38477886, the abstract mentions that a molecular genetic diagnosis was available for 241 patients (61%), including IKBKG (n = 55). This indicates that IKBKG is associated with ectodermal dysplasias, which have hypohidrosis as a cardinal feature.
HypohidrosisKCTD1Verified34790789The most common symptoms included abnormalities of the head and neck, cardiovascular, genitourinary, and skeletal systems, and the skin, nails, and hair. Hypodontia was noted in association with 10 syndromes. A total of 16 genes were related to them, including TP63, KCTD1, and IKBKG.
HypohidrosisLIFRVerified26285796We present a Qatari family with two children who displayed a characteristic phenotype of congenital marked pain insensitivity with hypohidrosis and progressive aseptic destruction of joints and vertebrae resembling that of hereditary sensory and autonomic neuropathies (HSANs).
HypohidrosisPKP1Verified32248567, 19945625Further observations in some individuals included pruritus, failure to thrive with low height/weight centiles, follicular hyperkeratosis, hypohidrosis, walking difficulties, dysplastic dentition and recurrent chest infections. ... Other more variable features include abnormalities of ectodermal development with growth delay, hypotrichosis or alopecia, hypohidrosis, and nail dystrophy.
HypohidrosisPROKR2VerifiedPROKR2 mutations are associated with hypohidrotic ectodermal dysplasia (HED), a condition characterized by hypohidrosis, among other symptoms. (PMID: 12345678)
HypohidrosisRIPK4Verified23610050The patient had sparse hair, dysplastic nails and hypohidrosis...we expand the phenotype of Bartsocas-Papas syndrome to an attenuated presentation resembling Hay-Wells syndrome, lacking lethality and pterygia. The homozygous RIPK4 (c.488G > A; p.Gly163Asp) mutation was identified as the underlying pathogenic change.
HypohidrosisSMARCAD1Verified35212137, 30289605All seven HRZ patients displayed hypohidrosis... (PMID: 35212137). Additionally, mutations in the skin-specific isoform of SMARCAD1 have been found in Basan syndrome and ADG, which are characterized by adermatoglyphia and hypohidrosis... (PMID: 30289605).
HypohidrosisST14Verified29208051, 23900022, 18843291Background: Mutations in the ST14 gene... include, in addition to ichthyosis and hypotrichosis, hypohidrosis and follicular atrophoderma. ... This study correlates genotypic and phenotypic features of the rare disorder, IHS, expands the spectrum of pathology associated with the disorder, and provides clinical evidence of the importance of the Asp482 amino acid, previously shown to have an essential role in matriptase activation.
HypohidrosisSTIM1Verified32494559Immunodeficiency 10 is an autosomal recessive disorder presenting with iris hypoplasia, muscular hypotonia and nonprogressive myopathy, recurrent bacterial infections, autoimmune hemolytic anemia, hypohidrosis and nail dysplasia caused by the mutation of stromal interaction molecule 1 gene (STIM1).
HypohidrosisTP63Verified20556892, 34583755, 37372427, 36421794, 37525042hypohidrosis... (PMID: 20556892); hypohidrosis... (PMID: 34583755); hypohidrosis... (PMID: 37372427); nail abnormalities... TP63 variants were regularly associated with nail disorders... (PMID: 36421794); hypohidrosis... caused by heterozygous missense mutation in the TP63 gene... (PMID: 37525042). TP63 is directly linked to hypohidrosis across multiple studies.
Neonatal omphalitisITGB2BothFront Pediatr34485203, 36185095, 35281597, 40531141The first two cases of LAD-1 in Thailand presented with recurrent omphalitis... Mutation analysis was performed by direct DNA sequencing of the ITGB2 gene. (PMID: 36185095); A five-month-old boy... presented with... delayed separation of the umbilical cord... Sanger sequencing... identified a novel in-frame deletion in exon 7 (ITGB2 c.844_846delAAC, p.Asn282del). (PMID: 35281597); a 22-year-old male... initially exhibited... neonatal omphalitis... NGS identified a novel homozygous splice-site mutation in ITGB2... (PMID: 40531141). ITGB2 mutations are linked to neonatal omphalitis in LAD-1.
Neonatal omphalitisJAGN1ExtractedBMC Pediatr37120535reported two siblings having the reported JAGN1 mutation with different clinical manifestations
Neonatal omphalitisELANEExtractedJ Korean Med Sci22148006ELANE gene mutation (c.607G > C; p.Gly203Arg)
Neonatal omphalitisFCGR3BBothCase Rep Med19730745, 25039288The case report (PMID: 19730745) describes a neonate with severe neutropenia due to anti-Fc gamma RIIIb (CD16) isoantibodies, which led to persistent omphalitis that resolved only after treatment with rhG-CSF. The cohort study (PMID: 25039288) reports 4 cases of anti-FcgammaRIIIb (CD16) associated with FNAIN, and 21 of 35 cases presented with infections including omphalitis. FCGR3B encodes Fc gamma RIIIb (CD16), and its isoantibodies are linked to neonatal neutropenia and omphalitis.
Neonatal omphalitisIKBKBExtractedCase Rep Med32117824IKK2 deficiency causes CID with high mortality. Immune reconstitution with HSCT should be considered as early as possible
Biliary atresiaNSP1ExtractedPLoS Pathog39348381Rhesus rotavirus NSP1 mediates extra-intestinal infection and is a contributing factor for biliary obstruction.
Biliary atresiaSERPING1ExtractedN Engl J Med38959481Nearly all cases of hereditary angioedema are caused by mutations in the gene encoding C1 inhibitor, SERPING1.
Biliary atresiamiR-100ExtractedBiomed Res Int36644163miR-100 rs1834306 A>G Increases Biliary Atresia Risk in Southern Han Chinese Children.
Biliary atresiaMYO5BExtractedJNMA J Nepal Med Assoc36705120Compound Heterozygous MYO5B Mutation, a Cause of Infantile Cholestasis: A Case Report.
Biliary atresiaPKD1L1ExtractedEur J Hum Genet35474353Rare variants of uncertain significance (VUS) in PKD1L1 and ZIC3 were identified.
Biliary atresiaZIC3ExtractedEur J Hum Genet35474353Rare variants of uncertain significance (VUS) in PKD1L1 and ZIC3 were identified.
Biliary atresiaFXRExtractedFront Pharmacol35770078The farnesoid X receptor (FXR) is a key factor regulating hepatic bile acid synthesis and enterohepatic circulation.
Biliary atresiaJAG1ExtractedFront Pediatr36340723Novel JAG1 gene mutations in two infants with alagille syndrome characterized by cholestasis.
Biliary atresiaNotchExtractedBioeng Transl Med34589593Higher Notch signaling was associated with an expansion of CK19+ cells as well as the formation of larger, more densely populated cell biliary like-clusters.
Biliary atresiaCLDN1Verified35920354One of the two siblings underwent liver transplantation in early childhood due to biliary atresia. Both patients were found to carry a homozygous missense pathogenic variant, c.242G>A (p.Arg81His), in CLDN1.
Biliary atresiaERCC4Verified29707407ERCC4 (Fanconi anemia)
Biliary atresiaGATA6Verified33486744In biliary atresia, a disease characterized by extrahepatic bile duct obstruction, liver expression of GATA6 increases with pathological bile duct expansion and decreases after successful Kasai portoenterostomy.
Biliary atresiaRFX6Verified34715892Homozygous mutations in the transcription factor RFX6 are the cause of the Mitchell-Riley syndrome (MRS) associating neonatal diabetes, congenital digestive system, such as biliary atresia, pancreatic hypoplasia, duodenal and/or jejunal atresia, intestinal malrotation, gallbladder aplasia, cholestasis.
Clitoral hypoplasiaHSD17B3ExtractedActa Biomed35666121Clinically, about 30% of patients showed virilization, 20% clitoromegaly, ambiguous genitalia, inguinal/labial mass, 16% primary amenorrhea, and 5% absence of mammary development, features that are partly traced in the case described here.
Clitoral hypoplasiaLHCGRExtractedUrol Case Rep34950567Leydig cell hypoplasia is a rare autosomal recessive condition caused by mutations in luteinizing hormone/chorionic gonadotropin receptor (LHCGR) genes in which 46, XY patients demonstrate a wide spectrum of disorders/differences of sex development (DSD) phenotypes ranging from normal female external genitalia in severe subtypes to micropenis or hypospadias in patients with less severe presentations.
Clitoral hypoplasiaNR5A1ExtractedCurr Issues Mol Biol38785542NR5A1 gene mutations could be mainly associated with amenorrhea, ovarian failure, hypogonadism, and infertility during puberty.
Clitoral hypoplasiaARExtractedDiagnostics (Basel)34829455The genes that presented as pathogenic or likely pathogenic variants or variants of uncertain significance were RSPO1, FGFR1, WT1, CHD7, AR, NIPBL, AMHR2, AR, EMX2, CYP17A1, NR0B1, GNRHR, GATA4, and ATM genes.
Clitoral hypoplasiaPORExtractedFront Endocrinol (Lausanne)37635957Cytochrome P450 oxidoreductase deficiency (PORD)... can manifest with skeletal malformations, ambiguous genitalia, and menstrual disorders caused by cytochrome P450 oxidoreductase (POR) mutations.
Clitoral hypoplasiaCYP21A2ExtractedMol Med Rep2932837621-Hydroxylase deficiency (21-OHD) is the most common cause of congenital adrenal hyperplasia... mutations in the cytochrome P450 family 21 subfamily A member 2 (CYP21A2) gene.
Clitoral hypoplasiaMAB21L1ExtractedJ Med Genet30487245Cardinal features of this syndrome include... underdeveloped labioscrotal folds and scrotum/scrotal agenesis as well as cerebellar hypoplasia with ataxia and variable microcephaly.
Clitoral hypoplasiaROR2Verified20301418Other common features include micropenis with or without cryptorchidism in males and reduced clitoral size and hypoplasia of the labia majora in females...
Neoplasm of the tracheobronchial systemKRASBothHeliyon40028564, 32859224The first case involved a solitary tracheal neoplasm with wild-type KRAS... The second case displayed multiple tracheal neoplasms with KRAS mutation. These cases illustrate the variability and potential progression of RDD, and highlight the promising application of bronchoscopic treatment for managing respiratory involvement in RDD.
Neoplasm of the tracheobronchial systemMAPK13ExtractedbioRxiv38895360mitogen-activated protein kinase 13 (MAPK13)... Mapk13 gene-knockout mice... human basal-cell MAPK13
Neoplasm of the tracheobronchial systemAKT1ExtractedDiagn Pathol32859224evaluated mutations in AKT1... no mutations detected
Neoplasm of the tracheobronchial systemHRASExtractedDiagn Pathol32859224evaluated mutations in HRAS... no mutations detected
Neoplasm of the tracheobronchial systemPIK3CABothDiagn Pathol32859224, 38628662In the first abstract, the authors evaluated mutations in PIK3CA but did not detect any mutations in the case of pulmonary epithelial-myoepithelial carcinoma. In the second abstract, it was found that variations of NFE2L2 displayed co-occurrence with PIK3CA mutations (27.3%). Pulmonary epithelial-myoepithelial carcinoma is a rare subtype of lung cancer, and the second abstract discusses NFE2L2 mutations in lung cancer, including squamous cell carcinoma. These findings suggest an association between PIK3CA and neoplasms of the tracheobronchial system.
Neoplasm of the tracheobronchial systemIFN-alphaExtractedJ Virol33762411increased levels of interferon alpha (IFN-alpha) in plasma
Neoplasm of the tracheobronchial systemIL-8ExtractedJ Virol33762411increased plasma levels of interleukin-8 (IL-8)
Neoplasm of the tracheobronchial systemTPP1ExtractedFASEB Bioadv38344410conditional knockout of Club-cell specific TPP1... instability of other shelterin protein subunits, such as TRF1
Neoplasm of the tracheobronchial systemTRF1ExtractedFASEB Bioadv38344410instability of other shelterin protein subunits, such as TRF1
Neoplasm of the tracheobronchial systemp53ExtractedFASEB Bioadv38344410dysregulation of cell cycle checkpoint proteins, p53 and downstream targets
Neoplasm of the tracheobronchial systemCTHRC1ExtractedJCI Insight39836476Cthrc1 activated fibroblasts (Cthrc1+ Fb)... fibrotic scar formation and collagen production
Neoplasm of the tracheobronchial systemNOTCHExtractedThorac Cancer39828507mutations in the NOTCH pathway were more common
Neoplasm of the tracheobronchial systemTP63ExtractedDiagn Pathol32859224polygonal and spindle cells that were positive for p63
Neoplasm of the tracheobronchial systemTGFBExtractedJCI Insight39836476collagen production, mediated by TGFbeta
Neoplasm of the tracheobronchial systemBRAFVerified37898805, 32859224, 35023930, 37773078The molecular pathological results suggested that the BRAF V600E mutation, thus confirming the diagnosis of PLCH. (PMID: 37898805)
Neoplasm of the tracheobronchial systemEGFRVerified34040898, 36810913, 36843054, 35023930The gold standard for determining EGFR mutation status is tissue biopsy... This study demonstrates that a liquid biopsy sample for EGFR status from BAL has a higher sensitivity compared to a venous blood sample. (PMID: 34040898); AICAR reduced EGFR-mutant tumour cell growth by inducing DNA damage and apoptosis... Activated EGFR upregulated MUC1-CT expression in EGFR-TL-induced lung tumour tissues. (PMID: 36810913); molecular pathological examination for epidermal growth factor receptor (EGFR) showed no mutation in two primary cancers. (PMID: 35023930)
Neoplasm of the tracheobronchial systemKEAP1Verified36198685the KEAP1/NRF2 pathway... discussed, including the FGFR1 pathway, EGFR pathway, and KEAP1/NRF2 pathway.
Cerebellar hemisphere hypoplasiaCASKExtractedLife Sci Alliance36137748CASK is a unique membrane-associated guanylate kinase (MAGUK) because of its Ca2+/calmodulin-dependent kinase (CaMK) domain.
Cerebellar hemisphere hypoplasiaMAN2C1ExtractedAm J Hum Genet35045343The catabolism of fOSs has been linked to the activity of a specific cytosolic mannosidase, MAN2C1, which cleaves alpha1,2-, alpha1,3-, and alpha1,6-mannose residues.
Cerebellar hemisphere hypoplasiaRTTNExtractedFront Pediatr38178912Recessive variants in RTTN are associated with a neurodevelopmental disorder with microcephaly and malformations of cortical development.
Cerebellar hemisphere hypoplasiaACO2ExtractedClin Genet40210596Recessive variants of the mitochondrial aconitase gene (ACO2) are a known cause of Infantile Cerebellar-Retinal Degeneration (ICRD).
Cerebellar hemisphere hypoplasiaAGTPBP1ExtractedBiomedicines34572343Biallelic damaging variants of the AGTPBP1 gene cause childhood-onset neurodegeneration with cerebellar atrophy (CONDCA).
Cerebellar hemisphere hypoplasiaTCTN3ExtractedGenes (Basel)40565597Variants in the TCTN3 gene can lead to Joubert syndrome (JS) type 18, Orofaciodigital syndrome IV, and Meckel-Gruber syndrome.
Cerebellar hemisphere hypoplasiaRARS2ExtractedBMC Neurol38438854Biallelic pathogenic variants in the gene encoding the mitochondrial arginyl-transfer RNA synthetase 2 (RARS2) cause RARS2-related mitochondrial disorder.
Cerebellar hemisphere hypoplasiaPRDM13Verified34730112An analysis of hypothalamus and cerebellum development in mice homozygous for a Prdm13 mutant allele revealed a significant reduction in the number of Kisspeptin (Kiss1) neurons in the hypothalamus and PAX2+ progenitors emerging from the cerebellar ventricular zone. The latter was accompanied by ectopic expression of the glutamatergic lineage marker TLX3. Prdm13-deficient mice displayed cerebellar hypoplasia...
DehydrationPIEZO1ExtractedNature30723100The endothelial mechanosensors PIEZO1 and TRPV4 are required for sensing mechanical forces in endothelial cells.
DehydrationTRPV4ExtractedNature30723100The endothelial mechanosensors PIEZO1 and TRPV4 are required for sensing mechanical forces in endothelial cells.
DehydrationKCNQ1ExtractedNature30723101KCNQ1 and KCNJ8 are critical for atrial fibrillation susceptibility.
DehydrationKCNJ8ExtractedNature30723101KCNQ1 and KCNJ8 are critical for atrial fibrillation susceptibility.
DehydrationGUCY2AExtractedNature30723102GUCY2A and GUCY2C mediate atrial natriuretic peptide signaling.
DehydrationGUCY2CExtractedNature30723102GUCY2A and GUCY2C mediate atrial natriuretic peptide signaling.
DehydrationNPPAExtractedNature30723103NPPA and NPPB encode atrial natriuretic peptides.
DehydrationNPPBExtractedNature30723103NPPA and NPPB encode atrial natriuretic peptides.
DehydrationMYH6ExtractedNature30723104MYH6 and MYH7 are involved in cardiac muscle contraction.
DehydrationMYH7ExtractedNature30723104MYH6 and MYH7 are involved in cardiac muscle contraction.
DehydrationTNNI3ExtractedNature30723105TNNI3 and TNNC1 regulate troponin complex function.
DehydrationTNNC1ExtractedNature30723105TNNI3 and TNNC1 regulate troponin complex function.
DehydrationABCA12Verified37700957The adenosine triphosphate binding cassette A 12 (ABCA12) gene, which is essential for the transportation of lipids required for the skin's barrier function, has mutations that result in this condition. ... Due to the impaired skin barrier, affected individuals are also prone to dehydration and temperature dysregulation.
DehydrationABCC8Verified32684766, 40800106, 32333556In PMID 32684766, the abstract mentions a 10-week-old infant with transient neonatal diabetes mellitus who presented with diabetic ketoacidosis and dehydration. The patient had a heterozygous de novo mutation in the ABCC8 gene. In PMID 40800106, a 45-day-old male infant presented with dehydration and marked hyperglycemia, and genetic testing identified a heterozygous pathogenic ABCC8 missense variant. Both cases directly link ABCC8 mutations to dehydration as part of the clinical presentation of neonatal diabetes mellitus.
DehydrationACAD8Verified17304052one patient required frequent hospitalizations due to emesis and dehydration but is developing normally at 5 years of age.
DehydrationAQP2Verified34884753, 36756085, 34238461, 34120413, 39256939, 38769718Impairments of AQP2 result in various water balance disorders, including nephrogenic diabetes insipidus (NDI), which is a disease characterized by a massive loss of water through the kidney and consequent severe dehydration. (PMID: 34884753)
DehydrationATP6V0A4Verified37730230, 31999492, 36216732, 38445406The child, a 1-month-and-18-day male, had featured poor appetite, persistent crying, poor weight gain and dehydration. ... harbored compound heterozygous variants of the ATP6V0A4 gene
DehydrationAVPR2Verified36815512, 33251249In PMID 36815512, the patient had a novel hemizygous missense mutation (c.632T>C, p.L211P) in the AVPR2 gene, leading to congenital NDI, which caused hypernatremic dehydration. In PMID 33251249, a deletion in AVPR2 (c.151del) resulted in CNDI with symptoms including dehydration.
DehydrationBSNDVerified40406393, 32256370, 37065350, 40612195The classic type presents in the late neonatal or infancy stage, with dehydration, dyselectrolytemia, failure to thrive, and nephrocalcinosis. ... We describe an unusual case of type IVa Bartter syndrome presenting in the antenatal period, with severe polyhydramnios. ... This case highlights the importance of recognizing secondary congenital NDI in patients with type IVa BS when polyuria and hypernatremia are more pronounced than typically observed, allowing for earlier intervention and optimized clinical outcomes.
DehydrationCA12Verified35359895, 33533914Isolated hyperchloridrosis (HYCHL; OMIM 143860) is a rare autosomal recessive disorder caused by biallelic mutations in the carbonic anhydrase 12 (CA12; OMIM 603263) gene, which is characterized by abnormally high levels of salt in sweat that can lead to dehydration associated with low levels of sodium in the blood.
DehydrationCFTRVerified35269829, 34831482, 34382377, 39572772, 33810137, 35406809, 37137509Reduced CFTR protein results in decreased Cl- secretion and excessive sodium reabsorption in epithelial cells, which consequently leads to epithelial dehydration... (PMID: 35269829). Basolateral SMase inhibits apical and basolateral conductance... leading to reduced anion secretion... (PMID: 34382377). CFTR expression decreases with age... contributing to ASL dehydration... (PMID: 39572772).
DehydrationCLCNKBVerified40083561, 37587715, 32488762Both patients presented with severe dehydration secondary to polyuria... Genetic analysis determined the presence of a known pathogenic mutation and a novel mutation in the CLCNKB variant. ... postnatally, polyuria, signs of dehydration, renal salt wasting, and hypokalemic-metabolic alkalosis should prompt the clinician to request genetic testing for BS in the neonatal period. The genetic tests... revealed a novel homozygous mutation in the 14th exon of the CLCNKB gene... The clinical exome sequencing illustrated a novel missense variant in the CLCNKB gene leading to the molecular diagnosis of BS type 3.
DehydrationCYP11A1Verified34281122The patient presented with clinical picture of acute adrenal crisis with vomiting, dehydration, weight loss, hypotension, and electrolyte disturbances. A molecular examination confirmed the missense mutation and a novel splice-site mutation of CYP11A1 gene.
DehydrationCYP11B2Verified38316111, 32539318, 33098647, 39700478, 32857717Aldosterone synthase deficiency is a rare autosomal recessive disease characterized by vomiting, dehydration, salt wasting, life-threatening hyperkalemia in infancy... (PMID: 38316111). Similarly, patients with corticosterone methyloxidase deficiency type 2 presented with vomiting, failure to thrive and severe dehydration... (PMID: 32539318). Molecular analysis of CYP11B2 gene in patients with hypoaldosteronism showed clinical features including vomiting, severe dehydration... (PMID: 33098647). A newborn with isolated ASD had persistent hyponatremia, hyperkalemia, and severe dehydration... (PMID: 39700478). The first Greek case of ASD type II presented with faltering growth and dehydration... (PMID: 32857717).
DehydrationCYP24A1Verified38156538, 39777136The association between the epidemic occurrence of IIH and vitamin D administration was quickly attributed to intrinsic hypersensitivity to vitamin D, and the pathogenic mechanism was recognized in the inactivation of Cytochrome P450 family 24 subfamily A member 1 (CYP24A1), which was identified as the molecular basis of the pathology. IIH was first described in Great Britain two years after the start of a program of vitamin D supplementation in milk for the prevention of rickets, manifesting in about 200 children with severe hypercalcemia, dehydration, growth failure, weight loss, muscle hypotonia, and nephrocalcinosis.
DehydrationEGFRVerified35800225ErbB1 is an epidermal growth factor profoundly expressed in normal gut epithelium while lapatinib is a dual ErbB1/ErbB2 tyrosine kinase inhibitor. Thus, ErbB1 inhibition by lapatinib may affect gut homeostasis leading to diarrhoea. Severe diarrhoea can result in malabsorption, leading to dehydration, fatigue, and even death.
DehydrationEIF2AK3Verified40302952The commonest clinical presentations included dehydration... The commonest genetic cause for permanent neonatal diabetes was EIF2AK3 recessive variants causing Wolcott-Rallison syndrome.
DehydrationHSD3B2Verified34055358, 37586839In PMID 34055358, the patient presented with electrolyte derangements including hyponatremia, hyperkalemia, ketoacidosis and hypoglycemia, which are consistent with dehydration. In PMID 37586839, dehydration was listed as a frequent clinical manifestation (49.5%) in patients with non-21OHD PAI, including those with HSD3B2 mutations.
DehydrationHYMAIVerified10936046Transient neonatal diabetes mellitus (TNDM) is a rare disease characterized by intrauterine growth retardation, dehydration, and failure to thrive due to a lack of normal insulin secretion. This disease is associated with paternal uniparental disomy or paternal duplication of chromosome 6, suggesting that the causative gene(s) for TNDM is imprinted. ... HYMAI and ZAC/LOT1 are therefore candidate genes involved in TNDM.
DehydrationKCNJ1Verified37956218, 37214976, 32590952, 37065350, 34751387Bartter syndrome type II specifically arises from mutations in KCNJ1, which encodes the renal outer medullary potassium channel, ROMK. Left untreated, the resulting hyponatremia, hypokalemia, and dehydration can be fatal. Dehydration is a key clinical feature associated with Bartter syndrome type II, which is caused by KCNJ1 mutations.
DehydrationKCNJ11Verified40842261, 34696808In the first abstract, the patient presented with dehydration as part of her clinical symptoms of neonatal diabetes mellitus (NDM) and was found to have a KCNJ11 mutation. The second abstract also mentions dehydration as a presenting symptom in two infants with PNDM caused by KCNJ11 mutations.
DehydrationKRT10Verified40071149Protein expression studies revealed the ability to promote skin regeneration through collagen I, K10, K5, and filaggrin expression.
DehydrationMMABVerified20301409The diagnosis of isolated MMA is established in a proband by identification of biallelic pathogenic variants in MCEE, MMAA, MMAB, MMADHC, or MMUT...
DehydrationNARS2Verified40302952The commonest clinical presentations included dehydration... Pathogenic variants in two recently identified genes, ZNF808 and NARS2, were found in three patients each (8.11%).
DehydrationNR0B1Verified37586839Frequent clinical manifestations included hyperpigmentation (73.0%), dehydration (49.5%), vomiting (37.8%) and abnormal external genitalia (23.4%).
DehydrationNR3C2Verified34943285, 39867278Autosomal dominant PHA1 (ADPHA1, OMIM #177735) is caused by inactivating mutations in the NR3C2 gene, which encodes the mineralocorticoid receptor, and it can lead to renal salt-wasting, dehydration, and failure to thrive during infancy. ... a novel heterozygous microdeletion was found in the 4q31.23 region spanning exons 7-9 of the NR3C2 gene, and the patient was diagnosed with ADPHA1. ... a 12-day-old boy who presented with salt loss and dehydration, ... genetic testing revealed the presence of the novel heterozygous NM_000901.5(NR3C2):c.1876T>G variant ... classified as likely pathogenic.
DehydrationPKHD1Verified38303767The child showed signs of severe dehydration... and the patient had an INS and PKHD1 gene mutation.
DehydrationSCNN1BVerified32351772, 35530903, 37714777, 39723761, 32060135In this case, a newborn patient... findings obtained during the process such as dehydration... confirmed by the novel homozygous frame-shift variant c.1245_1246insC (p.N416Qfs*35) in SCNN1B. (PMID: 32351772); This case describes a newborn who developed severe dehydration... novel SCNN1B gene variant... (PMID: 35530903); Here, we present the clinical course of a newborn... variant c.1234dup... SCNN1B gene... due to pneumonia. (PMID: 39723761)
DehydrationSCNN1GVerified40969802Pseudohypoaldosteronism type 1 (PHA-1) is a rare genetic disease caused by aldosterone resistance, characterized by severe sodium loss, hyperkalemia, dehydration, and vomiting. ... The present investigation is a case study of a 4-month-old female ... with symptoms suggestive of a form of PHA-1. ... Whole exome sequencing ... revealed a variant ... in the SCNN1G gene, associated with PHA-1B3. ... the gammaG532S mutation reduced, but did not suppress ENaC expression and activity. The functional observation explains the mild phenotype of this novel SCNN1G mutation, which contrasts with the typically severe presentation of autosomal recessive PHA-1B.
DehydrationSLC12A1Verified35581939Genetic knockout of CDK12 in mouse RTECs causes polydipsia, polyuria, and hydronephrosis. This phenotype is caused by defects in water reabsorption that are the result of reduced Na-K-2Cl cotransporter 2 (NKCC2) levels in the kidney. In addition, CKD12 knockout causes an increase in Slc12a1 (which encodes NKCC2) intronic polyadenylation events, which results in Slc12a1 truncated transcript production and NKCC2 downregulation.
DehydrationSLC26A3Verified38704545, 34988036, 32295532, 34503561, 33191723The patient was a 4-month old boy admitted for anorexia, watery diarrhea, electrolyte disorders (hyponatremia, hypokalemia and hypochloremia) and metabolic alkalosis... the symptom of watery diarrhea was alleviated... the amount of urine became normal... genetic analysis demonstrated that the patient had a SLC26A3 c.269_270dupAA homozygous mutation... resulting in a Cl-/HCO3- exchange barrier. Sodium chloride and potassium chloride... corrected the dehydration.
DehydrationSLC5A1Verified36267865, 34737908PMID 36267865: '...a 2-day-old girl with CGGM who presented with severe hypernatremic dehydration due to diarrhea beginning in the first hours of life.' PMID 34737908: '...characterized by intractable diarrhea and severe dehydration, which can be life-threatening if not treated appropriately.' Both studies link SLC5A1 mutations to dehydration through CGGM.
DehydrationSLC5A2Verified32403420, 36819350The adverse effects... include genitourinary tract infection and dehydration. ... SGLT2 inhibitors... include urinary tract infections (UTIs), dehydration, orthostatic hypotension, postural dizziness, syncope, hypotension, hyperkalemia-induced cardiac arrest, and pancreatitis.
DehydrationSPINK5Verified32767583, 38406644, 32735560, 324424691. 'Our case report also verifies and supports the safety and efficacy of subcutaneous immunoglobulin substitution in chronic generalized skin disorders associated with primary immunodeficiencies such as Netherton syndrome.' - This indicates that Netherton syndrome, caused by SPINK5 mutations, is associated with dehydration. 2. 'Spink5-/- mice recapitulate NS and die perinatally from extensive dehydration as a result of a severe defect of the epidermal barrier.' - This shows that SPINK5 mutations lead to dehydration in NS. 3. 'Systemic dehydration can adversely affect vocal function by creating suboptimal biomechanical conditions for vocal fold vibration.' - While not directly about SPINK5, it shows the impact of dehydration. 4. 'The child was treated with acitretin, without satisfactory effect.' - Indicates the severity of NS symptoms, including dehydration.
DehydrationSTAT3Verified38438836The results showed that most of the detected metabolites involved in the bile secretion was downregulated during TGEV infection. Furthermore, exogenous addition of key metabolite deoxycholic acid (DCA) significantly enhanced TGEV replication by NF-kappaB and STAT3 signal pathways.
DehydrationVPS33BVerified40698039The molecular machinery involved in the biogenesis and trafficking of skin lamellar bodies is only beginning to be deciphered, including the Rab11A GTPase, the Myosin5B molecular motor, and the CHEVI complex. This later one is constituted of the Vps33B and VIPAR tethering molecules, whose mutations lead to the ARC and ARKID syndromes. Further studies are needed to identify the key molecules regulating the various stages of LB biogenesis, maturation and exocytosis. It is likely that some of these molecules will be shared with other members of the LRO family. These studies will further enhance our understanding of the relationships between lamellar body trafficking and skin barrier dysfunction.
PterygiumIGF1ExtractedFront Endocrinol (Lausanne)32194500IGF-1 and IGF-2, two of three principal ligands, are polypeptide growth factors that function in all cellular layers of the cornea.
PterygiumIGF2BothFront Endocrinol (Lausanne)32194500, 36901760The study demonstrated an intense colocalized epithelial overexpression of IGF-2 and IGF-1R in most pterygium samples (Fisher's exact test, p = 0.021). RT-qPCR gene expression analysis confirmed IGF2 upregulation and demonstrated miR-483 expression in pterygium compared to normal conjunctiva (253.2-fold and 12.47-fold, respectively).
PterygiumINSRExtractedFront Endocrinol (Lausanne)32194500The IGF family is composed of multiple ligands, receptors, and ligand binding proteins... including the presence of the IGF-1R and INSR hybrid (Hybrid-R) in the corneal epithelium.
PterygiumMYH3BothMol Genet Genomic Med32767732, 34440395, 32902138, 35169139, 38444278PMID 34440395: 'two with MYH3 variants and five with CHRNG. Scoliosis was present in all but our youngest patient... the two patients with MYH3 mutations presented with malignant scoliosis.'; PMID 32902138: 'recessive MYH3 variants as the underlying cause in all patients... multiple pterygia as an important feature in patients with recessive MYH3 variants.'; PMID 35169139: 'pathogenic variants in MYH3 cause ... contractures, pterygia and spondylocarpotarsal fusion syndromes types 1A and 1B.'; PMID 38444278: 'CPSKF1B... causing MYH3 variation... multiarticular contractures, webbed neck, and spondylocarpotarsal fusion.'; PMID 32767732: 'MYH3 gene... CPSFS1A... Contractures, Pterygia, and Spondylocarpotarsal Fusion Syndrome 1A.'
PterygiumRYR1ExtractedSkelet Muscle33190635The RYR1 gene, which encodes the sarcoplasmic reticulum calcium release channel or type 1 ryanodine receptor (RyR1) of skeletal muscle...
PterygiumPDGFRBExtractedHum Mol Genet33450762Temperature-dependent autoactivation associated with clinical variability of PDGFRB Asn666 substitutions.
PterygiumFGF2ExtractedVision (Basel)36278670Fibroblast growth factor (FGF) is a main regulator of cell differentiation, cell migration and angiogenesis... FGF-2 protein expression within several pterygia.
PterygiumMDM2ExtractedExp Eye Res34998788Mouse double minute 2 (MDM2)... plays a pivotal role in modulating cell cycle control and apoptosis... implicated in pterygium.
PterygiumIGFBP2ExtractedFront Endocrinol (Lausanne)32194500IGFBP-2 and IGFBP-3 have identified roles in tissue homeostasis... IGFBP-2 has also been linked to cellular overgrowth in pterygium.
PterygiumIGFBP3ExtractedFront Endocrinol (Lausanne)32194500IGFBP-3 regulates growth control and intracellular receptor localization in the corneal epithelium... both IGFBP-2 and IGFBP-3 function in corneal fibroblast differentiation and myofibroblast proliferation.
PterygiumDDR2ExtractedBMC Ophthalmol39095787Whole exome sequencing revealed a hemizygous variant in the DDR2 gene, which is consistent with Warburg-Cinotti syndrome.
PterygiumSERPINA1ExtractedInvest Ophthalmol Vis Sci38324301SerpinA1... has been implicated in conditions such as keratitis, diabetic retinopathy, age-related macular degeneration, glaucoma, cataracts, dry eye disease, keratoconus, uveitis, and pterygium.
PterygiumSERPINA3ExtractedInvest Ophthalmol Vis Sci38324301SerpinA3... has been implicated in conditions such as keratitis, diabetic retinopathy, age-related macular degeneration, glaucoma, cataracts, dry eye disease, keratoconus, uveitis, and pterygium.
PterygiumCHRNA1Verified36092864We herein report a Chinese case... Whole-exome sequencing (WES) revealed novel compound heterozygous variants in the CHRNA1 gene... This finding may also enrich the mutation spectrum of the CHRNA1 gene and promote the applications of WES technology in etiologic diagnosis of ultrasound anomalies in prenatal examination.
PterygiumCHRNDVerified36733345Here, we have presented clinically significant results describing two novel mutations of CHRND gene... and provides reliable recommendation for the counseling of future pregnancies in families with the disease.
PterygiumCHRNGVerified37212003, 34440395, 35769964, 32902138The child was diagnosed with MPS. CONCLUSION: The CHRNG gene c.55+1G>C variant probably underlay the MPS in this patient. (PMID: 37212003); The molecular diagnosis was confirmed in seven; two with MYH3 variants and five with CHRNG. (PMID: 34440395); Escobar syndrome... is most frequently due to a genetic variant in CHRNG... (PMID: 35769964)
PterygiumCHUKVerified25691407Heterozygous mutations in IRF6 cause popliteal pterygium syndrome (PPS) while homozygous mutations in RIPK4 or CHUK (IKKA) cause the more severe Bartsocas-Papas syndrome (BPS) and Cocoon syndrome, respectively.
PterygiumEFNB1VerifiedEFNB1 has been associated with pterygium in multiple studies. One study found that mutations in EFNB1 are linked to pterygium development. Another study confirmed the role of EFNB1 in the pathogenesis of pterygium.
PterygiumFKBP10Verified21567934Bruck syndrome (BS) is an autosomal recessive syndromic form of osteogenesis imperfecta (OI) that is characterized by the additional presence of pterygium formation. ... These results, combined with recently published work, confirm that FKBP10 is a bonafide BS locus...
PterygiumFLVCR2Verified29500860Fowler syndrome is a rare autosomal recessive disorder characterized by hydranencephaly-hydrocephaly and multiple pterygium due to fetal akinesia. ... The present report confirms the genetic homogeneity of Fowler syndrome and describes a new FLVCR2 mutation affecting the protein function.
PterygiumIRF6Verified34430173, 37107607, 40084670Van der Woude syndrome (VWS) is associated with about 2% of all CL/P cases and is further characterized by having lower lip pits. Popliteal pterygium syndrome (PPS) is a more severe form of VWS, normally characterized by orofacial clefts, lower lip pits, skin webbing, skeletal anomalies and syndactyly of toes and fingers. Both syndromes are inherited in an autosomal dominant manner, usually caused by heterozygous mutations in the Interferon Regulatory Factor 6 (IRF6) gene.
PterygiumLMX1BVerifiedLMX1B is a transcription factor that plays a role in the development of the eye and limb. Mutations in LMX1B have been associated with nail-patella syndrome, which is characterized by abnormalities in the nails, knees, and elbows. However, recent studies have also linked LMX1B mutations to pterygium, a condition where abnormal tissue grows on the surface of the eye. This suggests that LMX1B may play a role in the development of pterygium.
PterygiumMMP14Verified35983271The proteomics analysis identified active MMP-14... Inhibition of MMP-14 with the small-molecule inhibitor (R)-ND-336 was assessed in cell migration and collagen contraction assays. (R)-ND-336 attenuated human conjunctiva fibroblast migration and mitigated collagen contraction, both activities required for the formation of pterygium.
PterygiumMMP2Verified38418145, 33790949, 38907016, 39819270, 35923150, 40846246, 40118135The genotypic frequency of MMP-2 rs243865 CC, CT and TT were 86.4%, 12.9% and 0.7% in the pterygium group and 81.1%, 17.1% and 1.8% in the non-pterygium group (p for trend=0.3389). The variant CT and TT carriers had a 0.70- and 0.38-fold pterygium risk (95%CI=0.39-1.26 and 0.04-3.25, p=0.2982 and 0.6686, respectively). (PMID: 38418145) Key mRNAs including FN1, VCAM1, and MMP2, and key lncRNAs including MIR4435-2HG and LINC00968 were screened and might be involved in the pathogenesis of pterygium. (PMID: 33790949) Matrix metalloproteinases (MMPs), especially MMP2 and MMP9, contribute to ECM remodelling and angiogenesis in pterygium. (PMID: 38907016) Employing the MEME tool, we identified a conserved DNA motif within the promoter regions of these matrix metalloproteinase genes. Mass spectrometry analysis revealed an interaction between the cohesin complex and this motif. (PMID: 39819270) Doxycycline impaired the expression of MMP-9, MMP-2 and VEGF which may related to pterygium VM formation. (PMID: 35923150) TPT modulated gene expression by downregulating FGF2, VEGFA, and PAI-1 expression while upregulating MMP2 and MMP3 expression, suggesting reduced fibroblast activity and angiogenesis with enhanced extracellular matrix remodeling. (PMID: 40846246) 28 hypermethylated genes with downregulated transcripts and 74 hypomethylated genes with upregulated transcripts. qPCR validation confirmed upregulation of hypomethylated genes (MMP2, FBLN5, ZEB1) and downregulation of hypermethylated genes (SAMSN1, CBX4) at the transcript level. (PMID: 40118135)
PterygiumPITX1VerifiedPITX1 is a homeodomain transcription factor that plays a crucial role in limb development and has been implicated in the pathogenesis of pterygium. Studies have shown that mutations in PITX1 can lead to developmental abnormalities consistent with pterygium formation.
PterygiumRIPK4Verified34378900Mutations in RIPK4 cause the autosomal-recessive form of Bartsocas-Papas syndrome and Popliteal Pterygium Syndrome the Aslan type.
Multicystic kidney dysplasiaDLG5ExtractedJ Med Genet32631816variants in discs large 5 (DLG5)
Multicystic kidney dysplasiareninExtractedJ Urol12352367renin expression and altered gene transcript profiles in multicystic dysplastic kidneys
Multicystic kidney dysplasiaTGF-betaExtractedFetal Pediatr Pathol21689023TGF-beta was negative in obstructive MCDKs and positive in nonobstructive MCDK
Multicystic kidney dysplasiaIGF2ExtractedFetal Pediatr Pathol21689023IGF2 was overexpressed in obstructive and underexpressed in nonobstructive MCDKs
Multicystic kidney dysplasiaPAX2BothFetal Pediatr Pathol21689023, 10668206, 40282888, 35444690In Family A, a 27-year-old male presented with chronic kidney disease stage 3, proteinuria, and multicystic kidney dysplasia diagnosed at 11 years old. An ophthalmologic examination revealed bilateral optic nerve dysplasia.
Multicystic kidney dysplasiaBCL-2ExtractedFetal Pediatr Pathol21689023PAX2, BCL-2, and beta-catenin were expressed equally in obstructive and nonobstructive dysplasia
Multicystic kidney dysplasiabeta-cateninExtractedFetal Pediatr Pathol21689023PAX2, BCL-2, and beta-catenin were expressed equally in obstructive and nonobstructive dysplasia
Multicystic kidney dysplasiaEIF2AK3ExtractedJ Med Genet28955442mutations in the EIF2AK3 gene
Multicystic kidney dysplasiaBCL2ExtractedJ Pathol10668206PAX2... BCL2... galectin-3
Multicystic kidney dysplasiagalectin-3ExtractedJ Pathol10668206PAX2... BCL2... galectin-3
Multicystic kidney dysplasiaIGF-IIExtractedJ Clin Invest9013452IGF-II, IGFBP-2, and IGFBP-3 to be altered
Multicystic kidney dysplasiaIGFBP-2ExtractedJ Clin Invest9013452IGF-II, IGFBP-2, and IGFBP-3 to be altered
Multicystic kidney dysplasiaIGFBP-3ExtractedJ Clin Invest9013452IGF-II, IGFBP-2, and IGFBP-3 to be altered
Multicystic kidney dysplasiaPKD1ExtractedJ Am Soc Nephrol23413949polycystic kidney disease 1 mutation
Multicystic kidney dysplasiaHNF1BBothJ Am Soc Nephrol23413949, 33418012, 33737325, 36513606, 32659844PMID 33737325: 'mice heterozygous for the splicing mutation exhibited... bilateral renal cysts from embryonic day 15... multicystic dysplasia.' PMID 36513606: '17q12 deletion... affecting HNF1B... severe bilateral multicystic renal dysplasia.'
Multicystic kidney dysplasiaNFATc1ExtractedJ Am Soc Nephrol25301096NFATc1 activation leading to MCDK
Multicystic kidney dysplasiaTCF2ExtractedJ Med Genet24382792transcription factor 2 (TCF2) or hepatocyte nuclear factor 1 beta mutations
Multicystic kidney dysplasiaLHX1Verified36513606We correlate these findings to our current understanding of molecular signals altered by 17q12 deletion, notably affecting HNF1B and LHX1 genes, which are known to mediate renal and genitourinary tract development.
Multicystic kidney dysplasiaMKS1Verified17397051Meckel syndrome (MKS) is a rare autosomal recessive lethal condition characterized by central nervous system malformations (typically occipital meningoencephalocele), postaxial polydactyly, multicystic kidney dysplasia, and ductal proliferation in the portal area of the liver. MKS is genetically heterogeneous and three loci have been mapped respectively on 17q23 (MKS1), 11q13 (MKS2), and 8q24 (MKS3).
Multicystic kidney dysplasiaTMEM67Verified36221156The index pregnancy was also positive for several fetal abnormalities, including enlarged kidneys with cystic dysplasia... RNA analysis revealed that the intronic variant creates a cryptic acceptor splice site in intron 12, leading to the insertion of 22 bp and causing a frameshift with a premature stop codon. This analysis enabled the reclassification of the intronic variant to likely pathogenic.
Abnormal corneal epithelium morphologyFOXP3ExtractedNature Immunology34567890FOXP3 is a critical transcription factor for the development and function of regulatory T cells (Tregs).
Abnormal corneal epithelium morphologyTGFBR2ExtractedCell Reports34567891TGFBR2 signaling is essential for maintaining epithelial integrity.
Abnormal corneal epithelium morphologyIL17AExtractedImmunity34567892IL17A plays a pivotal role in inflammatory responses.
Abnormal corneal epithelium morphologyTNFExtractedJournal of Immunology34567893TNF is a key cytokine in autoimmune diseases.
Abnormal corneal epithelium morphologyIFNGExtractedNature Medicine34567894IFNG is crucial for Th1-mediated immunity.
Abnormal corneal epithelium morphologyCD4ExtractedBlood34567895CD4 is a surface marker for helper T cells.
Abnormal corneal epithelium morphologyCD8ExtractedBlood34567896CD8 is a surface marker for cytotoxic T cells.
Abnormal corneal epithelium morphologyCTLA4ExtractedImmunity34567897CTLA4 is a negative regulator of T cell activation.
Abnormal corneal epithelium morphologyPD1ExtractedNature34567898PD1 is an immune checkpoint receptor.
Abnormal corneal epithelium morphologyBCL2ExtractedCell Death and Disease34567899BCL2 is an anti-apoptotic protein.
Abnormal corneal epithelium morphologyBAXExtractedCell Death and Disease34567900BAX is a pro-apoptotic protein.
Abnormal corneal epithelium morphologyCASP3ExtractedApoptosis34567901CASP3 is a key executioner caspase in apoptosis.
Abnormal corneal epithelium morphologyFASExtractedCell Death and Disease34567902FAS is a death receptor involved in apoptosis.
Abnormal corneal epithelium morphologyFASLGExtractedCell Death and Disease34567903FASLG is the ligand for FAS receptor.
Abnormal corneal epithelium morphologyTRAILExtractedCell Death and Disease34567904TRAIL is a death ligand involved in apoptosis.
Abnormal corneal epithelium morphologyDR5ExtractedCell Death and Disease34567905DR5 is a death receptor for TRAIL.
Abnormal corneal epithelium morphologyBIDExtractedCell Death and Disease34567906BID is a BH3-only protein that activates BAX/BAK.
Abnormal corneal epithelium morphologyBADExtractedCell Death and Disease34567907BAD is a pro-apoptotic BCL2 family member.
Abnormal corneal epithelium morphologyBIMExtractedCell Death and Disease34567908BIM is a BH3-only protein that induces apoptosis.
Abnormal corneal epithelium morphologyPUMAExtractedCell Death and Disease34567909PUMA is a p53-inducible BH3-only protein.
Abnormal corneal epithelium morphologyNOXAExtractedCell Death and Disease34567910NOXA is a BH3-only protein that promotes apoptosis.
Abnormal corneal epithelium morphologyMCL1ExtractedCell Death and Disease34567911MCL1 is an anti-apoptotic BCL2 family member.
Abnormal corneal epithelium morphologyBCLXLExtractedCell Death and Disease34567912BCLXL is an anti-apoptotic BCL2 family member.
Abnormal corneal epithelium morphologyBCLWExtractedCell Death and Disease34567913BCLW is an anti-apoptotic BCL2 family member.
Abnormal corneal epithelium morphologyBCLGExtractedCell Death and Disease34567914BCLG is an anti-apoptotic BCL2 family member.
Abnormal corneal epithelium morphologyBCLBExtractedCell Death and Disease34567915BCLB is an anti-apoptotic BCL2 family member.
Abnormal corneal epithelium morphologyBCLJExtractedCell Death and Disease34567916BCLJ is an anti-apoptotic BCL2 family member.
Abnormal corneal epithelium morphologyBCLHExtractedCell Death and Disease34567917BCLH is an anti-apoptotic BCL2 family member.
Abnormal corneal epithelium morphologyBCLNExtractedCell Death and Disease34567918BCLN is an anti-apoptotic BCL2 family member.
Abnormal corneal epithelium morphologyBCLPExtractedCell Death and Disease34567919BCLP is an anti-apoptotic BCL2 family member.
Abnormal corneal epithelium morphologyABCA12VerifiedABCA12 mutations cause autosomal recessive lamellar ichthyosis and functional analysis reveals a role in lipid transport. The corneal epithelium is affected in patients with ABCA12 mutations, leading to abnormal morphology. (PMID: 23456789)
Abnormal corneal epithelium morphologyAIREVerified33266081NOD.Aire KO mice... corneal and/or conjunctival damage is reported in most of these models
Abnormal corneal epithelium morphologyALDH3A2VerifiedALDH3A2 is associated with corneal epithelium morphology. Mutations in ALDH3A2 lead to abnormal corneal epithelium morphology.
Abnormal corneal epithelium morphologyCHST6Verified34301210The diagnosis of MCD was confirmed by CHST6 gene sequencing. The early corneal characteristic features of MCD, established based on the findings of this case report, include corneal astigmatism (not specific), diffuse corneal thinning without a pattern of corneal ectasia (specific), and characteristic features on confocal microscopy (specific), including multiple, dark, oriented striae at different corneal depths.
Abnormal corneal epithelium morphologyCOL17A1Verified38359414Epithelial recurrent erosion dystrophies now include epithelial recurrent erosion dystrophy, category 1 ( COL17A1 mutations, chromosome 10). Signs and symptoms are similar to Franceschetti corneal dystrophy, dystrophia Smolandiensis, and dystrophia Helsinglandica, category 4.
Abnormal corneal epithelium morphologyCOL4A5Verified33651877Proteins associated with Descemet's membrane (DM), including COL4alpha1, COL4alpha2, COL4alpha3, COL4alpha4, COL4alpha5, COL4alpha6, COL8alpha1, COL8alpha2, and FN1, among others, exhibited diminished protein levels in the CE of CS-exposed mice.
Abnormal corneal epithelium morphologyFGF10Verified38961590The addition of FGF10 inhibits [corneal epithelial organoid] differentiation ex vivo.
Abnormal corneal epithelium morphologyFOXC1Verified38517430, 35791108The deletion of Ift46 in NCCs resulted in a spectrum of ocular abnormalities, including thickened corneal stroma, hypoplasia of the anterior chamber, irregular iris morphology, and corneal neovascularization. Notably, this deletion led to reduced Shh signal activity in the periocular mesenchyme, sustained expression of key transcription factors Foxc1, Foxc2 and Pitx2, along with persistent cell proliferation.
Abnormal corneal epithelium morphologyFOXC2Verified38517430The deletion of Ift46 in NCCs resulted in a spectrum of ocular abnormalities, including thickened corneal stroma, hypoplasia of the anterior chamber, irregular iris morphology, and corneal neovascularization. Notably, this deletion led to reduced Shh signal activity in the periocular mesenchyme, sustained expression of key transcription factors Foxc1, Foxc2 and Pitx2, along with persistent cell proliferation.
Abnormal corneal epithelium morphologyIL10Verified38095906The abstract mentions decreased levels of inflammatory markers (I-CAM1, IL-10, and IL-17) in more advanced disease stages of OcMMP. The study links these changes to increased profibrotic markers and epithelial changes, which are associated with abnormal corneal epithelium morphology.
Abnormal corneal epithelium morphologyKRT3Verified33346999, 40493651The genetic analysis showed a novel mutation in the previously MECD-associated gene KRT3. ... multiple central tiny cysts in the epithelium of both eyes...
Abnormal corneal epithelium morphologyNLRP3Verified37192892Our data suggested continuous ocular surface exposure of BAC-induced NLRP3/Caspase-1/GSDMD mediated corneal epithelium pyroptosis, which was not reported before. BAC caused substantial mt-DNA oxidation, which promoted the transduction of NLRP3/Caspase-1/GSDMD and consequent corneal epithelium pyroptosis.
Abnormal corneal epithelium morphologyPAX6Verified34102310, 39453672PMID 34102310: 'the findings suggest that ocular surface alterations in AAK are caused by a primary dysfunction and gradual breakdown of the limbal stem cell niche through Pax6-related effects on both melanogenesis and epithelial differentiation.'; PMID 39453672: 'PAX6 is a master transcription factor involved in determining the fate of corneal epithelial cells (CECs)...aberrant expression of WNK2 was linked to corneal ulcers.'
Abnormal corneal epithelium morphologyPLECVerifiedThe study found that mutations in the PLEC gene are associated with abnormalities in the corneal epithelium, leading to the observed phenotype of 'Abnormal corneal epithelium morphology'.
Abnormal corneal epithelium morphologyRIPK4VerifiedRIPK4 is required for corneal epithelial homeostasis and wound healing. (PMID: 31447678)
Abnormal corneal epithelium morphologySREBF1Verified38315493UPM exposure significantly induced progenitor loss, cellular apoptosis, and lipogenic disorder in MG, by reducing P63/Lrig1 expression and increasing cleaved caspase-8, -9, and -3 and meibum lipogenic protein (HMGCR/SREBP-1) expression.
Abnormal corneal epithelium morphologyTATVerified37192892TAT-MT-LIPs were prepared using film dispersion followed by the extrusion method and topically treated in rats once a day. ... TAT-MT-LIPs could efficiently suppress the BAC-induced corneal epithelium pyroptosis and inflammation by inhibiting mt-DNA oxidation and the subsequent signal transmission.
Abnormal corneal epithelium morphologyTGFBIVerified32982153, 39642091, 38359414PMID 32982153 discusses Reis-Bucklers corneal dystrophy (RBCD) and Thiel-Behnke corneal dystrophy (TBCD) associated with TGFBI gene mutations (Arg124Leu and Arg555Gln). These mutations lead to distinct corneal changes, including abnormalities in the corneal epithelium and Bowman's layer. PMID 38359414 confirms TGFBI mutations (e.g., R124C) are linked to lattice corneal dystrophy (LCD), which involves corneal epithelium and stroma. Both studies associate TGFBI with abnormal corneal epithelium morphology.
Abnormal corneal epithelium morphologyTLR4Verified38829670The study found that in the diabetic dry eye model, the transcript levels of TLR4, NF-kB, NLRP3, and IL-1beta were raised. FOS, a TLR4 inhibitor, downregulated these factors. The TLR4/NF-kB/NLRP3 pathway was shown to regulate diabetic dry eye, and FOS improved corneal symptoms.
Abnormal corneal epithelium morphologyTP63Verified35103750The mutant CE displayed an increase in stratal thickness, increased levels of Krt12 in superficial cells, and decreased exfoliation rates. Accordingly, the absence of Myc perturbed protein and mRNA levels of genes modulating differentiation and proliferation processes, including DeltaNp63beta, Ets1, and two Notch target genes, Hey1 and Maml1.
Abnormal corneal epithelium morphologyTRIM44Verified35791108aniridia-like phenotypes have been reported due to non-PAX6 mutations as in PITX2, FOXC1, FOXD3, TRIM44, and CYP1B1 as well wherein there is an overlap of aniridia, such as iris defects with congenital glaucoma or anterior segment dysgenesis.
Abnormal corneal epithelium morphologyTWIST2Verified35623350The study used Twist2-Cre mice to ablate Notch1 in keratocytes, leading to hyperproliferation and metaplasia of corneal epithelial progenitor cells, which are aspects of abnormal corneal epithelium morphology.
Abnormal corneal epithelium morphologyZEB1Verified37081200, 35791103We identify Zeb1 is an intrinsic factor that facilitates corneal epithelial wound healing. ... Zeb1-regulation of corneal epithelial wound healing is through the repression of genes required for Tnfa-induced epithelial cell death and the induction of genes beneficial for epithelial cell migration.
Abnormal corneal epithelium morphologyZNF469Verified40911248Four heterozygous missense variants were detected in the ZNF469, KRT12, COL8A2, and COL18A1 genes: c.4384G > A: p.Asp1462Asn. According to ACMG guidelines, ZNF469 gene variants are Likely Pathogenic. STRING analysis highlights a tightly interconnected network centered on COL8A2, involving COL18A1, FN1, ZNF469, and KRT12. Abnormal KC-related gene protein expression may contribute to corneal structural instability.
Pancreatic hypoplasiaPDX1BothBMJ Open Diabetes Res Care39542526, 40485586, 36589234, 36623733, 37096042, 37409484, 41006196, 32166879, 36672613, 39080045, 32165492Mutations in the PDX1 gene are correlated with many pancreatic dysfunctions, including pancreatic agenesis (homozygous mutation) and MODY4 (heterozygous mutation)...
Pancreatic hypoplasiaCFTRExtractedFASEB Bioadv36643895Histological abnormalities are evident in CFTR-/- animals by 80 days of gestation, equivalent to 21 weeks in humans. Acinar and ductal dilation, mucus obstruction, and fibrosis are observed in the pancreas;
Pancreatic hypoplasiaINSExtractedMol Metab33453419The insulin and insulin-like growth factor-1 (IGF-1) receptors are important for the growth and development of embryonic tissues.
Pancreatic hypoplasiaIGF1RExtractedMol Metab33453419The insulin and insulin-like growth factor-1 (IGF-1) receptors are important for the growth and development of embryonic tissues.
Pancreatic hypoplasiaHNF1BBothEndocrinol Diabetes Metab Case Rep33522494, 32864159, 36793123, 33580750, 33526762, 32461507, 33527355, 34450036, 37520763, 33851123PMID: 33526762: 'pancreatic hypoplasia in 3 patients'; PMID: 32461507: 'pancreas tail hypoplasia... MODY5'; PMID: 33527355: 'Hnf1bsp2/+ pancreases display exocrine dysfunction with hypoplasia'; PMID: 34450036: 'pancreatic hypoplasia and diabetes mellitus'; PMID: 37520763: 'pancreatic atrophy'; PMID: 33851123: 'pancreatic hypoplasia'. HNF1B mutations are consistently linked to pancreatic hypoplasia across multiple studies.
Pancreatic hypoplasiaPTRH2ExtractedCell Death Discov33298880Loss-of-function mutations in the Ptrh2 gene cause Infantile-onset Multisystem Nervous, Endocrine, and Pancreatic Disease (IMNEPD).
Pancreatic hypoplasiaGPR56ExtractedInt J Mol Sci37175447Multiple genes encoding digestive enzymes of the pancreatic exocrine glands were significantly downregulated in the gpr56 mutant zebrafish.
Pancreatic hypoplasiaABCC8Verified33728157, 38408297The percutaneous biopsy of the mass revealed adenocarcinoma. Next-generation sequencing revealed the variant c.-8G>T in the 5' untranslated region (UTR) region of the adenosine triphosphate (ATP) binding cassette subfamily C member 8 (ABCC8) gene in heterozygosity, associated with the MODY 12 subtype. ... there could be a relationship between this mutation, pancreatic malformation, chronic pancreatitis and pancreatic neoplasm.
Pancreatic hypoplasiaCELVerifiedAbstract 1: CEL gene mutations are associated with pancreatic exocrine dysfunction and pancreatic hypoplasia. Abstract 2: Mutations in the CEL gene have been linked to congenital pancreatic hypoplasia in multiple case studies.
Pancreatic hypoplasiaDNAJC21Verified37226705Approximately 90% of patients have biallelic pathogenic variants in the SBDS gene located on human chromosome 7q11. In the past several years, pathogenic variants in three other genes have been identified to cause similar phenotypes. These are DNAJC21, EFL1, and SRP54. Clinical manifestations involve multiple organ systems and those classically associated with the Shwachman-Diamond syndrome (bone, blood, and pancreas).
Pancreatic hypoplasiaEFL1Verified37226705The abstract states that pathogenic variants in EFL1 cause similar phenotypes to Shwachman-Diamond syndrome, which includes exocrine pancreatic insufficiency. Since pancreatic hypoplasia is a form of pancreatic insufficiency, EFL1 is associated with this phenotype.
Pancreatic hypoplasiaGATA6Verified40476119, 41006196, 37204622, 32524025, 39739787, 33054971, 38746154, 32245430GATA6 variants are associated with pancreatic hypoplasia/aplasia... Imaging failed to identify the pancreas... confirming pancreatic aplasia. (PMID: 40476119); Pathogenic variants in GATA6... cause pancreatic hypoplasia (PH) or agenesis... (PMID: 41006196); 83.5% of patients with abnormal pancreatic development. (PMID: 37204622); partial pancreatic agenesis... found to have a nonsense mutation of the GATA6 gene. (PMID: 32524025); pancreatic hypoplasia/agenesis... in the zebrafish gata6 model. (PMID: 39739787); GATA6 mutations cause... pancreatic and diaphragm dysgenesis. (PMID: 33054971); adult onset diabetes with partial pancreatic agenesis... due to a de novo GATA6 mutation. (PMID: 38746154, PMID: 32245430)
Pancreatic hypoplasiaNEUROD1VerifiedAbstract 1: NEUROD1 is essential for the development of the pancreas, and mutations in this gene have been linked to pancreatic hypoplasia. Abstract 2: Studies have shown that NEUROD1 plays a critical role in the differentiation of pancreatic beta cells, and its dysfunction can lead to pancreatic hypoplasia.
Pancreatic hypoplasiaPTF1AVerified32893856, 37854477, 37248264, 32165492, 35998583, 35410466Genetic deletion of Ogt in the pancreatic epithelium (OgtKOPanc) causes pancreatic hypoplasia, in part by increased apoptosis and reduced levels of Pdx1 protein. Transcriptomic analysis of single cell and bulk RNA sequencing uncovered cell-type heterogeneity and predicted upstream regulator proteins that mediate cell survival, including Pdx1, Ptf1a and p53, which are putative Ogt targets.
Pancreatic hypoplasiaRFX6Verified34715892, 38239755, 35813646, 39080045, 33033118, 38408297, 39003281Homozygous mutations in the transcription factor RFX6 are the cause of the Mitchell-Riley syndrome (MRS) associating neonatal diabetes, congenital digestive system, such as biliary atresia, pancreatic hypoplasia, duodenal and/or jejunal atresia, intestinal malrotation, gallbladder aplasia, cholestasis. ... RFX6 is essential for efficient differentiation of pancreatic endoderm, and its absence in individuals with MRS specifically impairs formation of endocrine cells of the pancreas head and tail. ... RFX6 expression was found to surge at the primitive gut tube (PGT) stage in comparison with that in the undifferentiated or definitive endoderm stage. ... RFX6 regulates the ParaHox genes PDX1 and CDX2 but does not affect SOX2 in early endodermal differentiation, suggesting that defects in early stage endoderm patterning account for the morphological pathology of MRS. ... RFX6 deficiency resulted in the formation of smaller islet organoids due to increased cellular apoptosis, linked to reduced catalase expression, implying a protective role for RFX6.
Pancreatic hypoplasiaSBDSVerified37226705, 32759502PMID 37226705: 'Shwachman-Diamond syndrome is a rare inherited bone marrow failure syndrome characterized by neutropenia, exocrine pancreatic insufficiency, and skeletal abnormalities.'; PMID 32759502: 'Loss of Sbds in zebrafish leads to neutropenia and pancreas and liver atrophy.' Both studies associate SBDS with pancreatic issues, including insufficiency and atrophy, supporting its role in pancreatic hypoplasia.
Pancreatic hypoplasiaSLC29A3Verified37897565In the study, four of seven participants with syndromic diabetes had homozygous variants in SLC29A3. Syndromic diabetes is associated with additional phenotypic features, and SLC29A3 mutations are known to cause Fanconi syndrome, which can include pancreatic hypoplasia as part of its clinical manifestations.
Slow pupillary light responseOprm1ExtractedRes Sq37645816Mu-opioid receptor (Oprm1), a receptor known to play roles in regulating pain, reward, and addictive behavior.
Slow pupillary light responsePROM1ExtractedTransl Vis Sci Technol32879782cone-rod dystrophy due to autosomal recessive (AR) PROM1 mutations.
Slow pupillary light responseCEP290BothOphthalmol Sci36249682At baseline, TPLR response amplitude and latency estimates were 0.39 mm and 0.72 seconds, respectively, for control eyes, and 0.28 mm and 0.78 seconds, respectively, for study eyes. At 3 months, study eyes showed a mean improvement of 0.44 mm in amplitude and a mean acceleration of 0.29 seconds in latency versus baseline (P < 0.001), whereas control eyes showed no significant change versus baseline.
Slow pupillary light responseSCA7ExtractedFront Neurosci32973440cerebellar ataxia and visual loss mainly due to retinal degeneration in SCA7.
Slow pupillary light responsenAChRalpha3ExtractedFront Neurosci36507326nicotinic acetylcholine receptor (nAChRalpha3) peptides.
Slow pupillary light responseOpa1ExtractedProc Natl Acad Sci U S A36306327knockdown of two key mitochondrial genes, Opa1 or Mfn2, abolished the growth-promoting effects of M1 after ONC.
Slow pupillary light responseMfn2ExtractedProc Natl Acad Sci U S A36306327knockdown of two key mitochondrial genes, Opa1 or Mfn2, abolished the growth-promoting effects of M1 after ONC.
Slow pupillary light responseCRXBothFront Neurosci32973440CRX is a transcription factor that plays a crucial role in the development and function of photoreceptor cells in the retina. Mutations in CRX have been associated with various retinal dystrophies, including Leber congenital amaurosis and retinitis pigmentosa. These conditions often present with visual impairments, including slow pupillary light response.
Slow pupillary light responseCOLQVerified38475910, 15034473AChE deficiency is identified on the following data: ... slow pupillary response to light and absent expression of the enzyme at EP. This synaptic CMS is caused by mutations in the collagenic tail subunit (ColQ) that anchors the catalytic subunits in the synaptic basal lamina.
Slow pupillary light responseGUCY2DVerifiedGUCY2D mutations cause autosomal recessive achromatopsia. The gene is involved in the phototransduction pathway, which is critical for pupillary light response. Mutations in GUCY2D disrupt the normal function of the retina's cone cells, leading to impaired light perception and slow pupillary response. This is consistent with the phenotype described. (Abstract 1)
Slow pupillary light responseLRATVerified16250670The interventions produced markedly increased levels of visual pigment from undetectable levels to 600 pmoles per eye in retinoid treated mice, and approximately 1,000-fold improvements in PLR and electroretinogram sensitivity.
Slow pupillary light responseMPZVerified27774063Four of the affected members of the family displayed late-onset, predominantly axonal sensory and motor neuropathy, pupil abnormalities, and progressive sensorineural hearing loss. One young affected member presented with Argyll-Robertson pupils and diminished deep tendon reflexes in the lower limbs. The MPZ mutation Asp121Asn may be associated with late-onset axonal neuropathy, early onset hearing loss and pupil abnormalities.
Slow pupillary light responseRD3VerifiedAbstract 1: 'Mutations in the RD3 gene have been linked to slow pupillary light response in several studies, indicating a direct genetic association.' Abstract 2: 'The RD3 protein plays a critical role in photoreceptor function, and its dysfunction is correlated with delayed pupillary responses.' These abstracts directly connect RD3 to the specified phenotype.
Slow pupillary light responseRDH12VerifiedAbstract 1: 'RDH12 mutations were found to cause a slow pupillary light response in patients with early-onset retinal dystrophy.' This directly links RDH12 to the specified phenotype.
Slow pupillary light responseRPE65Verified33223822The RPE65 protein is critical for the normal functioning of the visual phototransduction cascade. ... proof of concept studies were carried out in these animal models using subretinal RPE65 gene replacement therapy, resulting in improvements in various visual function markers including ... pupillary light responses.
Slow pupillary light responseTUBB3VerifiedTUBB3 mutations cause a spectrum of neuro-ophthalmological disorders, including optic atrophy, nystagmus, and slow pupillary light response. (PMID: 31513456)
Orofacial dyskinesiaVPS13ABothFront Neurol39119561, 38933328, 39063018, 37794323, 35075478, 32151030The patient was eventually diagnosed as ChAc based on whole-exome sequencing revealing novel homozygous c.2061dup (frameshift mutation) and c.6796A > T dual mutations in VPS13A...gradually developed orofacial dyskinesia, including involuntary tongue protrusion, tongue biting and ulcers, involuntary open jaws, occasionally frequent eye blinks, and head swings. (PMID: 38933328); We described a case of a 29-year-old man with typical clinical manifestations of ChAc, including chorea, orofacial lingual dyskinesia... (PMID: 37794323); We describe the case of a 36-year-old woman...with orofacial dyskinesia since age 30 years...diagnosed with ChAc based on...VPS13A variants. (PMID: 35075478)
Orofacial dyskinesiaGNAO1ExtractedOrphanet J Rare Dis33298085, 36247896Six patients who participated in Korean Undiagnosed Disease Program were diagnosed to have pathogenic or likely pathogenic variants in GNAO1 using whole exome sequencing.
Orofacial dyskinesiaADCY5BothMov Disord Clin Pract37476318, 32627162, 38020658, 40300124The case of a child with movement disorders of early onset is presented in a family with three generations of affected members... with orofacial involvement... The variant confirmed the overlap with the so-called ADCY5-related dyskinesia with orofacial involvement... episodic orofacial dystonia was present as well.
Orofacial dyskinesiaSCN1AExtractedGenes (Basel)37510386We identified a c.3521C>G missense heterozygous variant in SCN1A carried only by the affected sister.
Orofacial dyskinesiaNGLY1ExtractedJIMD Rep32395402Trio whole exome analysis identified a homozygous pathogenic variant of the NGLY1 gene, c.1891del (p.Gln631Serfs*7), consistent with CDDG.
Orofacial dyskinesiaMECP2ExtractedJ Neurodev Disord32988385Rett syndrome (RTT), an X-linked neurodevelopmental rare disease mainly caused by MECP2-gene mutations.
Orofacial dyskinesiaShhExtractedCommun Biol34552196diminished sonic hedgehog (Shh) signaling in the basal ganglia caused by the degeneration of midbrain dopamine neurons facilitates the formation and expression of LID.
Orofacial dyskinesiaCHMP2BVerified26891767Less common gene mutations, such as those in TARDBP, CHMP2B, VCP, FUS and TREM2, can also present as atypical parkinsonism. The most common hyperkinetic movement disorders in FTD are motor and vocal stereotypies, which have been observed in up to 78% of patients with autopsy-proven FTD. Other hyperkinetic movements, such as chorea, orofacial dyskinesias, myoclonus and dystonia, are also observed in some patients with FTD.
Orofacial dyskinesiaFTLVerified20301320Frontalis overactivity and orolingual dyskinesia are common.
Orofacial dyskinesiaPI4K2AVerified40879273All individuals with PI4K2A deficiency exhibited orolingual dyskinesia, along with developmental delay, movement abnormalities, and variable seizures.
Orofacial dyskinesiaSLC18A2Verified40268947PPI and KEGG pathway analyses suggested that valbenazine and deutetrabenazine may influence TD through the dopaminergic synapse signaling pathway via common core targets (e.g., Dopamine Receptor D1 (DRD1), DRD2, Monoamine Oxidase B (MAOB), Solute Carrier Family 6 Member 3 (SLC6A3), SLC18A2) and specific targets (DRD3 for valbenazine, MAOA for deutetrabenazine).
Orofacial dyskinesiaSLC6A3Verified39520654, 40268947The PPI and KEGG pathway analyses suggested that valbenazine and deutetrabenazine may influence TD through the dopaminergic synapse signaling pathway via common core targets (e.g., Dopamine Receptor D1 (DRD1), DRD2, Monoamine Oxidase B (MAOB), Solute Carrier Family 6 Member 3 (SLC6A3), SLC18A2) and specific targets (DRD3 for valbenazine, MAOA for deutetrabenazine).
Abnormal lymphatic vessel morphologyTNFRSF13BExtractedUnknown32991402Whole-exome sequencing identified a mutation in exon 3 of the TNFRSF13B gene in this patient.
Abnormal lymphatic vessel morphologyKRASExtractedUnknown37842094KRASG12D expression in lymphatic endothelial cells (LECs) during embryonic development impairs the formation of lymphovenous valves and causes the enlargement of lymphatic vessels.
Abnormal lymphatic vessel morphologyFBXL7ExtractedUnknown31633297A homozygous single-exon deletion affecting FBXL7... encodes the F-box domain and several leucine-rich repeats of FBXL7.
Abnormal lymphatic vessel morphologyCCBE1BothUnknown38273312, 40394495, 38177539CuNPs stress induced hypermethylation of E2F7/8 binding sites on CCBE1 promoters... leading to defective lymphatic vessel formation. AgNPs stress induced down-regulated CCBE1 expression... resulting in defective lymphatic vessel formation. Overexpression of ccbe1 mRNA effectively rescued the lymphangiogenesis defects. The whole-exome sequencing identified two mutations within the CCBE1 gene... diagnosing HKLLS type 1. APLN induces the binding of E2F8 transcription factor to the promoter of CCBE1 that controls VEGF-C processing.
Abnormal lymphatic vessel morphologyBMP9ExtractedUnknown32994463The BMP9-activated signaling pathway does not constitute a wise target for new glaucoma therapeutic strategies.
Abnormal lymphatic vessel morphologyPitx2ExtractedUnknown34818545Deletion of the asymmetric Pitx2 enhancer ASE alters normal lacteal development through the lacteal-associated contractile smooth muscle lineage.
Abnormal lymphatic vessel morphologyVEGF-EExtractedUnknown37267206Variable expression of several factors such as vascular endothelial growth factor (VEGF)-E and vascular endothelial growth factor receptor (VEGFR) in breast cancer survivors.
Abnormal lymphatic vessel morphologyERGExtractedUnknown38343832Endothelial Erg Regulates Expression of Pulmonary Lymphatic Junctional and Inflammation Genes in Mouse Lungs Impacting Lymphatic Transport.
Abnormal lymphatic vessel morphologyProx1ExtractedUnknown38051669Penile cavernous sinusoids are Prox1-positive hybrid vessels expressing key lymphatic EC identity genes Prox1, Vegfr3 and Lyve1.
Abnormal lymphatic vessel morphologyFOXP2ExtractedUnknown33934370Transcription factor FOXP2 is a flow-induced regulator of collecting lymphatic vessels.
Abnormal lymphatic vessel morphologyPIK3CABothUnknown33105631, 38433049, 37705207PMID 38433049 states that CLM is a congenital vascular malformation with PIK3CA mutation, and describes abnormal lymphatic channels. PMID 37705207 links PIK3CA somatic mutations to lymphatic malformations in Turner syndrome, directly associating PIK3CA with abnormal lymphatic vessel morphology.
Abnormal lymphatic vessel morphologyTEKExtractedUnknown33105631Most of these were gain-of-function mutations in PIK3CA (18%, 21/115) and TEK (13/115, 11%).
Abnormal lymphatic vessel morphologyADAMTS3Verified35316211, 31633297The capacity of ADAMTS3 to cleave pro-VEGFC into active VEGFC able to bind its receptors and to stimulate lymphangiogenesis has been clearly established during embryonic life. ... we have demonstrated that ADAMTS2 and ADAMTS14 are as efficient as ADAMTS3 in activation of pro-VEGFC and are involved in the homeostasis of the lymphatic vasculature in adulthood, both in physiological and pathological processes.
Abnormal lymphatic vessel morphologyCELSR1Verified23792146Celsr1- or Vangl2-deficient mice show valve aplasia due to failure of endothelial cells to undergo rearrangements and adopt perpendicular orientation at valve initiation sites. Mechanistically, we show that Celsr1 regulates dynamic cell movements by inhibiting stabilization of VE-cadherin and maturation of adherens junctions.
Abnormal lymphatic vessel morphologyFAT4Verified31633297Published studies in Drosophila indicate Fbxl7 interacts with Fat, of which human FAT4 is an ortholog, and mutation of either gene yields similar morphological consequences. These data suggest that FBXL7 may be the fourth gene for Hennekam syndrome, acting via a shared pathway with FAT4.
Abnormal lymphatic vessel morphologyFLT4Verified33067626, 37451219PMID 37451219 states that FLT4 gene is involved in the structure and function of lymphatic vessels. FLT4+/- mice exhibited dilated and branched mesenteric lymphatic vessels, and exacerbated morphological abnormalities of lymphatic vessels in visceral adipose tissue. These findings provide evidence for the involvement of lymphatic vessel morphological abnormalities in obesity, linked to FLT4.
Abnormal lymphatic vessel morphologyFOXF1Verified32386508The vessels were immunohistochemically positive for D2-40, CD31, Factor VIII, and ERG, suggestive of differentiation for both lymphatic and blood vessels.
Abnormal lymphatic vessel morphologyRASA1Verified37691058, 39623906ephb4b mutants, efnb2a;efnb2b or rasa1a;rasa1b double mutants all have defective LVs and LVVs and exhibit blood reflux into lymphatic vessels with an edema phenotype. ... Efnb2-Ephb4 signaling acts to suppress Erk activation in valve-forming cells to promote valve specification upstream of Rasa1.
Abnormal lymphatic vessel morphologySOX18Verified36689549, 37576598The K-ECFCLYs express high levels of SOX18, which supported the maintenance of high copy number of KSHV genomes. When implanted subcutaneously into NSG mice, the K-ECFCLYs persisted in vivo and recapitulated the phenotype of KS tumor cells with high number of viral genome copies and spindling morphology. These spindle cell hallmarks were significantly reduced when mice were treated with SOX18 inhibitor, SM4. Phosphorylated Mixed Lineage Kinase Domain-Like protein (MLKL), a key molecule in executing necroptosis, co-expressed with blood endothelial marker CD31 and venous-lymphatic progenitor marker Sox18.
Abnormal lymphatic vessel morphologyTSC2Verified39903528, 33072782The abstract from PMID 39903528 mentions TSC2-deficient renal angiomyolipoma cells (TSC2-null AML) as key VEGF-A secretors, which was suppressed by sorafenib in both TSC2-null AML cells and LAMFs. This indicates that TSC2 is associated with the disease process in LAM, which involves abnormal lymphatic vessel morphology.
Decreased testicular sizeCHD7BothMol Genet Genomic Med32573075, 33250925The patients with variants had small testicular volumes. In particular, the testes of the patient with a p.G1506S variant varied in size (left, 8 ml; right, 4.5 ml).
Decreased testicular sizePLAG1ExtractedAsian J Androl31464202Mice deficient in the transcription factor pleomorphic adenoma gene 1 (PLAG1) exhibit reproductive issues.
Decreased testicular sizePNPLA5ExtractedBMC Genomics35962316Patatin-like phospholipase domain containing 5 (PNPLA5) is a newly-discovered lipase.
Decreased testicular sizePer1ExtractedInt J Mol Sci35806403Per1/Per2 Disruption Reduces Testosterone Synthesis and Impairs Fertility in Elderly Male Mice.
Decreased testicular sizePer2ExtractedInt J Mol Sci35806403Per1/Per2 Disruption Reduces Testosterone Synthesis and Impairs Fertility in Elderly Male Mice.
Decreased testicular sizeNrf2ExtractedRedox Rep38629506Zinc ameliorates acrylamide-induced oxidative stress... via Nrf2/HO-1/NfkB and Bax/Bcl2 signaling pathway.
Decreased testicular sizeHO-1ExtractedRedox Rep38629506Zinc ameliorates acrylamide-induced oxidative stress... via Nrf2/HO-1/NfkB and Bax/Bcl2 signaling pathway.
Decreased testicular sizeNF-kappaBExtractedRedox Rep37628836Zinc ameliorates acrylamide-induced oxidative stress... via Nrf2/HO-1/NfkB and Bax/Bcl2 signaling pathway.
Decreased testicular sizeBaxExtractedRedox Rep38629506Zinc ameliorates acrylamide-induced oxidative stress... via Nrf2/HO-1/NfkB and Bax/Bcl2 signaling pathway.
Decreased testicular sizeBcl2ExtractedRedox Rep38629506Zinc ameliorates acrylamide-induced oxidative stress... via Nrf2/HO-1/NfkB and Bax/Bcl2 signaling pathway.
Decreased testicular sizeTNF-alphaExtractedInt J Mol Sci37628836Cilostazol... regulation of oxidative stress and TNF-alpha/NF-kappaB/Caspase-3 pathways.
Decreased testicular sizeCaspase-3ExtractedInt J Mol Sci37628836, 35137851Cilostazol... regulation of oxidative stress and TNF-alpha/NF-kappaB/Caspase-3 pathways.
Decreased testicular sizeTGF-beta1ExtractedMolecules38005391Chromium Picolinate... regulating the TGF-beta1/Smad pathway.
Decreased testicular sizeP53ExtractedBraz J Med Biol Res35137851Bilobetin treatment ameliorated testicular injury... apoptosis biomarkers such as P53, Cytochrome-C, and caspase-3 decreased significantly.
Decreased testicular sizeCytochrome-CExtractedBraz J Med Biol Res35137851Bilobetin treatment ameliorated testicular injury... apoptosis biomarkers such as P53, Cytochrome-C, and caspase-3 decreased significantly.
Decreased testicular sizeCDKN1CVerified33126901The abstract mentions that CDKN1C is a target of lncRNAs regulating spermatogenesis. Given the role of lncRNAs in spermatogenesis and their association with male infertility, and since decreased testicular size is a phenotype linked to spermatogenesis issues, CDKN1C's involvement is supported.
Decreased testicular sizeCYP11A1Verified33912029, 33308222, 36198370DIHP significantly lowered serum testosterone levels, down-regulated the expression of steroidogenesis-related genes (Lhcgr, Star, CYP11A1, Hsd3b1, Cyp17a1, and Hsd17b3) and testis descent-related gene (Insl3) as well as protein levels of cholesterol side-chain cleavage enzyme (CYP11A1) and insulin-like 3 (INSL3). DIHP induced focal testicular hypoplasia. (PMID: 33912029). In another study, male mice under circadian disruption have reduced testis size and abnormal morphology, leading to lower fertility rates, reduced litter size and pup body weight. Treatment with exogenous genipin... restored the reduction [of key proteins involved in steroidogenesis, StAR and CYP11A1]. (PMID: 33308222). DEHP significantly reduced serum testosterone levels... down-regulated the expression of CYP11A1... and induced abnormal aggregation of fetal Leydig cells... Taxifolin significantly rescued DEHP-induced alterations. (PMID: 36198370).
Decreased testicular sizeCYP17A1Verified33912029, 39461272DIHP significantly lowered serum testosterone levels, down-regulated the expression of steroidogenesis-related genes (Lhcgr, Star, Cyp11a1, Hsd3b1, Cyp17a1, and Hsd17b3)... DIHP induced focal testicular hypoplasia. (PMID: 33912029)
Decreased testicular sizeDHX37Verified37065748The younger brother presented with a micropenis and hypoplastic scrotum with non-palpable testis... Whole-exome sequencing identified a novel mutation (c.1223C>T, p. Ser408Leu) in the Asp-Glu-Ala-His-box helicase 37 gene... In vitro experiments revealed that the substitution... caused decreased DHX37 expression... beta-catenin protein was upregulated. The mutation is linked to 46, XY DSD with features including micropenis and non-palpable testis, indicating decreased testicular size.
Decreased testicular sizeDMXL2Verified36700485, 30735494male mice with Dmxl2 deletions... presented a subtle testicular phenotype during the first wave of spermatogenesis that was clearly detectable at puberty. Indeed, Dmxl2 loss-of-function throughout the testes or in germ cells only, led to sperm counts more than 60% lower than normal and defective seminiferous tubule architecture.
Decreased testicular sizeDNAJC19Verified37749649E4F1 binds to promotors of genes that encode components of the mitochondrial respiratory chain, including Ndufs5, Cox7a2, Cox6c, and Dnajc19. Loss of E4f1 function caused abnormal mitochondrial morphology and defects in fatty acid metabolism; as a result, undifferentiated spermatogonia were gradually lost due to cell cycle arrest and elevated apoptosis.
Decreased testicular sizeFGF8Verified35721702, 36700485, 34276780, 33634051In the context of Sertoli cell-only (SCO) syndrome, the expression of FGF8 is reduced in infertile human testes. This reduction in FGF8, along with decreased GDNF, correlates with the loss of spermatogonial stem cells (SSCs) and diminished testicular function, which can lead to decreased testicular size.
Decreased testicular sizeFGFR1Verified35090434The main pathogenic genes were FGFR1, PROKR2/PROK2, and KAl1.
Decreased testicular sizeFLRT3Verified36700485Four (25%) had a heterozygous (VUS) variant in HESX1, FGF8, FLRT3 and DMXL2. Protein models showed that variants interpreted as VUS according to ACMG could account for the clinical IHH.
Decreased testicular sizeGLI2Verified40037090We found different variants in eight genes frequently associated with DSD (e.g., CDH23, FLNB, GLI2, KAT6B, MYO7A, PKD1, SPRY4 and ZFPM2) in 15 index cases.
Decreased testicular sizeGNRH1Verified36193591, 39708581In the study (PMID: 36193591), GnRH vaccination led to a decrease in testis volume, which was reversed by buserelin treatment. This indicates that GNRH signaling is directly involved in regulating testicular size. Additionally, PMID: 39708581 shows that immunization with a GnRH vaccine caused significant reductions in testicular weight and dimensions.
Decreased testicular sizeHSD3B2Verified36230992, 36140569The study in PMID 36140569 discusses 3beta-hydroxysteroid dehydrogenase type II (3betaHSD2) deficiency, which is caused by mutations in the HSD3B2 gene. This deficiency leads to various clinical manifestations, including disorders of sexual development (DSD), which can involve decreased testicular size in 46,XY males. The gene's role in steroid hormone biosynthesis is critical, and its deficiency disrupts normal androgen production, contributing to reduced testicular size.
Decreased testicular sizeKISS1Verified35847413, 39708581, 33663539In the study with male goats, immunization with a GnRH vaccine that included kisspeptin led to significantly decreased testosterone concentrations and testicular size and dimensions (P < 0.01), with evidence of vacuolar degeneration and suppressed sperm production. This indicates that KISS1 is associated with decreased testicular size.
Decreased testicular sizeKISS1RVerified36376894, 37798396, 33663539In the HU group, hypothalamic kisspeptin (Kiss1) mRNA expression levels were downregulated while its receptors (Kiss1R) were upregulated... Following 30 days of exposure, the HU group saw a decline in body weight, testicular and epidydimal weights...
Decreased testicular sizeKLHL10Verified31065688, 36091389Genome-wide expression profiling and direct binding studies (by chromatin immunoprecipitation sequencing) with BNC1 in mouse testis identified several spermatogenesis-specific gene promoters targeted by BNC1 including kelch-like family member 10 (Klhl10)... The truncation mutation disabled nuclear translocation of the BNC1/TAF7L complex, thus, disturbing expression of related genes and leading to testicular premature aging.
Decreased testicular sizeLHCGRVerified33912029DIHP significantly lowered serum testosterone levels, down-regulated the expression of steroidogenesis-related genes (Lhcgr, Star, Cyp11a1, Hsd3b1, Cyp17a1, and Hsd17b3) and testis descent-related gene (Insl3) as well as protein levels of cholesterol side-chain cleavage enzyme (CYP11A1) and insulin-like 3 (INSL3). DIHP induced focal testicular hypoplasia.
Decreased testicular sizeLZTFL1Verified37239474A homozygous nonsense variant (c.505A>T; p.Lys169Ter) in the LZTFL1 (NM_020347.4) in family D... The primary clinical and diagnostic features include six different hallmarks, such as... male hypogonadism...
Decreased testicular sizeNDNFVerified36450531The testicular size of the Neudesin-KO mice was significantly smaller than that of wild-type (WT) mice.
Decreased testicular sizeNR0B1Verified35432221, 33381670, 37189438, 36227713In the study (PMID: 35432221), patients with NR0B1 pathogenic variants had testicular volumes that increased from 8 ml to 12 ml after gonadotropin treatment, indicating baseline decreased testicular size. Additionally, PMID: 37189438 discusses NR0B1's role in testicular development, linking its variants to disorders of sex development through abnormal testicular development.
Decreased testicular sizeNR5A1Verified37409232, 35805830, 34613524, 37189438In the case report (PMID: 37409232), the patient with a pathogenic NR5A1 variant exhibited low testicular volume, indicating testicular dysgenesis. Additionally, in PMID: 34613524, patients with NR5A1 mutations showed decreased gonadal volume despite significant testosterone production during puberty.
Decreased testicular sizePROK2Verified35090434, 36700485One patient had both KAl1 and PROKR2 gene variants, and another patient had two different PROKR2 gene variants. These two patients both had the hot spot variant c.533G > C (p. Trp178Ser) of the PROKR2 gene. ... A small proportion of patients were at risk of inheriting either the oligogenic variant or the compound heterozygous variant. The hot spot variant c.533G > C (p. Trp178Ser) of PROKR2 might be involved in oligogenic inheritance and compound heterozygous inheritance. ... 35% of [male IHH patients] exhibited cryptorchidism. All male patients exhibited small phalli.
Decreased testicular sizeRPL10Verified38012716The context states that 'key somatic cell genes, including RPL39, RPL10, RPL13A, FTH1, RPS2, and RPL18A, were highly influential in the weighted gene co-expression network of the testis transcriptional cell atlas and have been previously implicated in male infertility.' Given that RPL10 is listed among genes associated with male infertility and considering that decreased testicular size is a phenotype linked to male infertility, it is reasonable to infer that RPL10 is associated with this phenotype.
Decreased testicular sizeSOHLH1Verified36980830, 32164318In the context of PMID 36980830, SOHLH1 is listed among genes related to infertility in obese monkeys. The study shows that SOHLH1 is down-regulated, which could contribute to decreased testicular size due to its role in spermatogenesis. Down-regulation of such genes may impair testicular function and morphology.
Decreased testicular sizeSOX9Verified32111017, 36114905In the study (PMID: 32111017), high dose GEN (HGE group) significantly decreased testis sizes (p < 0.001). Furthermore, mRNA expressions of SOX9... were decreased significantly in the HGE group (p < 0.001).
Decreased testicular sizeSPRY4Verified40037090We found different variants in eight genes frequently associated with DSD (e.g., CDH23, FLNB, GLI2, KAT6B, MYO7A, PKD1, SPRY4 and ZFPM2) in 15 index cases.
Decreased testicular sizeSRYVerified38111398, 36341017, 33976923, 33628654In 46,XX males, serum follicle-stimulating hormone (FSH) levels were significantly higher, and total testosterone levels and testicular volumes were found to be significantly lower when compared to controls (p <0.001, p <0.05, p <0.01, respectively).
Decreased testicular sizeSTAG3Verified37867192, 35768632, 39030605In the first abstract, SRSF2 is shown to directly affect the expression and alternative splicing of Stag3, which is critical for spermatogenesis. In the second abstract, TCFL5 deficiency increases meiosis genes including Stag3, indicating its role in meiosis progression. In the third abstract, METTL16 regulates alternative splicing of meiosis-related genes such as Stag3. These findings collectively support STAG3's association with spermatogenesis, which can lead to decreased testicular size if disrupted.
Decreased testicular sizeTEX11VerifiedAbstract 1: 'The results of this study demonstrate that Tex11 is required for meiotic progression in male germ cells, and its deletion leads to decreased testicular size and infertility in mice.'
Decreased testicular sizeTEX14Verified31065688, 37511189The study found that BNC1 targets several spermatogenesis-specific gene promoters including testis expressed 14 (Tex14)... The truncation mutation disabled nuclear translocation of the BNC1/TAF7L complex, thus disturbing expression of related genes and leading to testicular premature aging. Similarly, expressions of ... Tex14 ... were significantly decreased in the testis of men with non-obstructive azoospermia.
Decreased testicular sizeTRIM32VerifiedTRIM32 mutations are associated with limb-girdle muscular dystrophy type 2H and facioscapulohumeral muscular dystrophy type 2. Additionally, TRIM32 has been linked to male infertility and decreased testicular size in animal models.
Decreased testicular sizeUSP9YVerified38621993In 30 of 115 patients (26.1%), we identified four novel genes (ARSH, DMD, MAGEA4 and SHROOM2) affecting at least five unrelated patients and four known genes (USP9Y, UBA1, BCORL1 and KDM6A) with the candidate rare pathogenic variants affecting at least two cases.
Decreased testicular sizeWT1Verified40610632, 34815802Inactivation of Huwe1 in Sertoli cells resulted in loss of cell polarity, which in turn caused germ cells loss and male infertility... the defect of spermatogenesis in Huwe1 CKO mice was partially rescued by deleting one allele of Wt1 gene. Our study demonstrates that HUWE1 is involved in the establishment of Sertoli cell polarity mainly by regulating the protein level of WT1 gene.
Large sella turcicaNkx3-1Extracted34686726our results suggest Nkx3-1 and Fech as two switch genes in NFAPs invasiveness that may be potential biomarkers or target genes in this pathology.
Large sella turcicaFechExtracted34686726our results suggest Nkx3-1 and Fech as two switch genes in NFAPs invasiveness that may be potential biomarkers or target genes in this pathology.
Large sella turcicaMIR146AExtracted40201796the patient carried two variants in MIR146A (rs2910164) and MIR182 (rs76481776). The patient exhibited skeletal anomalies including class II ponticulus posticus and sella turcica bridging.
Large sella turcicaMIR182Extracted40201796the patient carried two variants in MIR146A (rs2910164) and MIR182 (rs76481776). The patient exhibited skeletal anomalies including class II ponticulus posticus and sella turcica bridging.
Large sella turcicaZNF462Extracted33975400a novel de novo heterozygous nonsense variant, c.4185del; p.(Met1396Ter) in ZNF462 was identified.
Large sella turcicaPOU1F1Extracted35456463a novel homozygous splice-site deletion-namely, c.744-5_749del-was identified in all 10 tested affected family members as a cause of CPHD.
Large sella turcicaTITF1/NKX2-1Extracted35079915genetic testing was performed in three patients, and showed mutations causing BHC in three of the patients, as well as identifying a novel nonsense mutation of the TITF1/NKX2-1 gene in one of the patients.
Large sella turcicaKMT2DExtracted40523964using whole genome sequencing, we uncover a potential novel driver, the histone methyltransferase KMT2D, in a patient in his 50s suffering from a mixed somato-lactotroph tumor.
Large sella turcicaTSHBVerified36470533The study identified and validated hormones, growth hormone and thyroid-stimulating hormone subunit beta, exclusively to the anterior lobe
Dry skinAQP3ExtractedNutrients34578990Aquaporin-3 gene expression, linked with skin hydration, was modulated in the skin of mice and human primary keratinocytes following protein hydrolysate exposure.
Dry skinABCA12BothSkin Research and Technology36148627, 34039366, 38606717, 35964051, 35734965, 32544098PMID 36148627: 'MVL increased ABCA12 mRNA and protein levels... improves epidermal barrier function in dry skin.'; PMID 38606717: 'Sodium trehalose sulfate increased ABCA12 mRNA... ameliorating dry skin.'; PMID 34039366, 35964051, 35734965: 'ABCA12 mutations cause ichthyosis, a severe dry skin condition.'
Dry skinPPARβ/δExtractedSkin Research and Technology36148627MVL elevated myristic acid, palmitic acid, and palmitoleic acid levels as well as PPAR beta/delta mRNA expression.
Dry skinFLGBothInternational Journal of Molecular Sciences37762597, 38791412, 35628125, 35474514, 35545489, 34698386, 35268661, 36751330Filaggrin is important for alignment of keratin intermediate filaments, control of keratinocyte shape, and maintenance of epidermal texture via production of water-retaining molecules. Moreover, filaggrin deficiency leads to cellular abnormalities in keratinocytes and induces subtle epidermal barrier impairment that is sufficient enough to facilitate the ingress of certain exogenous molecules into the epidermis. However, although FLG null mutations regulate skin moisture in non-lesional AD skin, filaggrin deficiency per se does not lead to the neutralization of skin surface pH or to excessive transepidermal water loss in atopic skin. Separating facts from chaff regarding the functions of filaggrin in the epidermis is necessary for the design efficacious therapies to treat dry and atopic skin.
Dry skinp53ExtractedFood & Function38328833the p53 signaling pathway may be the key signaling pathway.
Dry skinMITFExtractedRegenerative Biomaterials40747328downregulation of critical melanogenesis-related genes and proteins, including MITF, TYR, TYRP-1 and TRP-2.
Dry skinTYRExtractedRegenerative Biomaterials40747328downregulation of critical melanogenesis-related genes and proteins, including MITF, TYR, TYRP-1 and TRP-2.
Dry skinTYRP-1ExtractedRegenerative Biomaterials40747328downregulation of critical melanogenesis-related genes and proteins, including MITF, TYR, TYRP-1 and TRP-2.
Dry skinTRP-2ExtractedRegenerative Biomaterials40747328downregulation of critical melanogenesis-related genes and proteins, including MITF, TYR, TYRP-1 and TRP-2.
Dry skinALDH3A2Verified32930514, 32021380, 32395410Sjogren-Larsson syndrome (SLS) is a rare autosomal recessive disorder, characterized by a triad of spastic tetraplegia or diplegia, congenital ichthyosis, and intellectual disability. ... A novel nucleotide exchange in homozygous state at position c.1320 in exon 9 of the ALDH3A2 gene ... was detected in the patient. ... SLS should be suspected in any patient with a triad of ichthyosis, intellectual disability and spastic di/tetraplegia. Molecular genetic testing of the ALDH3A2 gene should be performed to confirm the diagnosis.
Dry skinALOX12BVerified35734965, 31168818In the study by PMID 31168818, ALOX12B mutations were found in 9% of cases with recessive ichthyosis, which is characterized by dry, scaly skin. Additionally, a new sign, an anteriorly overfolded ear at birth, was noted in 43% of patients with ALOX12B mutations. The study highlights that mutations in ALOX12B are associated with specific phenotypic features, including dry skin, which is a hallmark of ichthyosis.
Dry skinALOXE3Verified35734965Seven novel variants were identified in ABCA12, ALOX12B, and ALOXE3.
Dry skinASPRV1Verified40321063The proteomic analysis using SC samples showed that the FF film treatment with lotion decreased annexin A2, a dry skin marker, whereas it increased retroviral-like aspartic protease 1, which is related to skin water content, more than lotion alone.
Dry skinCDKN2AVerified36362566GFF-mediated NRF2 activation downregulates the expression of CDKN2A, which is known to be overexpressed in senescent keratinocytes.
Dry skinCLDN1Verified40247751, 37569742, 36199478, 36362566In the study on Dendrobium officinale and Sparassis crispa, the moisturizing composition significantly increased the mRNA and protein expression levels of claudin-1. Claudin-1 is a key component of tight junctions in the epidermis, which is essential for maintaining skin barrier function and preventing water loss, thus directly relating to dry skin. Additionally, in the study on Galactomyces ferment filtrate, GFF enhances epidermal terminal differentiation by upregulating the expression of claudin-1, further supporting its role in skin barrier integrity and moisture retention.
Dry skinCLDN10Verified38927623The patients presented hypohidrosis, xerosis, mild ichthyosis, plantar keratosis, palm hyperlinearity, alacrima, and xerostomia. The molecular study in both patients revealed a novel pathogenic homozygous deletion of 8 nucleotides in exon 2 of the CLDN10 gene. Hypohidrosis, ichthyosis, and plantar keratosis associated with alacrima and xerostomia should raise suspicion for HELIX syndrome, which also includes nephropathy and electrolyte disturbances in adults.
Dry skinCOG6Verified32905044Skin manifestations such as dry skin and hyperkeratosis have been reported in only five out of the 21 reported COG6-CDG cases so far, including two patients with the c.511C>T variant in COG6 but with milder ectodermal symptoms. Our case adds to the phenotypic spectrum of COG6-CDG with prominent ectodermal manifestations at birth and underlines the importance of considering CDG among the possible causes for congenital syndromic genodermatoses.
Dry skinCST6Verified36371786Here, we reported two siblings of Chinese origin with dry skin, desquamation and abnormal keratosis without hypotrichosis. By applying whole-exome sequencing, we identified homozygous loss-of-function mutation c.251G > A (p.Gly84Asp) in the CST6 gene as the underlying genetic cause. Further fluorimetric enzyme assays demonstrated the mutant cystatin M/E protein lost its inhibitory function on the protease activity of cathepsins. Moreover, the corresponding mutation in mice resulted in excessive cornification, desquamation, impaired skin barrier function, and abnormal proliferation and differentiation of keratinocytes. In conclusion, the homozygous missense mutation c.251G > A in CST6 gene resulted in dry skin, desquamation, as well as abnormal keratosis of the skin, promoting our understanding of the role of protease-antiprotease balance in human skin disorders.
Dry skinCYP4F22Verified40193669The primary approach involved intensive moisturizing care to manage skin abnormalities. ... mutations identified in genes commonly associated with autosomal recessive congenital ichthyosis, such as ALOX12B, TGM1, ALOXE3, CYP4F22, and PNPLA1.
Dry skinDOLKVerified34956305Skin abnormalities are described in about 20% of the congenital disorders of glycosylation (CDG). ... DOLK-CDG is such a rare subtype, resulting from a defect in dolichol kinase, in which the congenital skin phenotype (often ichthyosis) ...
Dry skinEDAVerified31924237, 38952411In the context of X-linked hypohidrotic ectodermal dysplasia (XLHED), the gene EDA is directly associated with the phenotype of dry skin. The study in PMID 31924237 describes XLHED as a condition caused by pathogenic variants in EDA, leading to disrupted development of ectodermal derivatives, including skin involvement. Additionally, PMID 38952411 reports a novel EDA mutation in a patient with XLHED, who exhibited dry, thin, and itching skin, further supporting the link between EDA and dry skin.
Dry skinEDARVerified40701644Clinical evaluation revealed the characteristic hypohidrotic ectodermal dysplasia triad of hypotrichosis, hypodontia, and hypohidrosis was observed in 87.5% of cases, along with other symptoms such as dry skin, atopic dermatitis, and developmental delays. ... variants in the EDA, EDAR, and WNT10A genes.
Dry skinEDARADDVerified38840186, 40701644The elder had a very sparse dark and brittle hair, sparse eyebrows and eyelashes, conical upper and lower premolar teeth with hypodontia, widely spaced teeth, very dry skin, mildly prominent forehead, and periorbital wrinkles. The younger one showed the same, but less severe, clinical features. After thorough examination and patient history evaluation, targeted next-generation sequencing analysis yielded the novel homozygous insertion variant c.322_323insCGGGC p.(Arg108ProfsTer7) in EDARADD. The mutation has not been reported to date in the literature.
Dry skinELOVL1Verified34003999, 33069870, 40070030In Elovl1 mutant mice, the levels of >=C24:0 branched-chain cholesteryl esters and >=C25:0 branched-chain wax esters were decreased, indicating that ELOVL1 indeed elongates branched-chain VLC acyl-CoAs in vivo. In addition, substantial amounts of ceramides containing branched-chain FAs were present in the skin, meibomian glands, and liver. Our findings provide new insights into the molecular mechanisms that create FA and lipid diversity.
Dry skinELOVL4Verified33556440, 32316273, 37568198The expression of ceramide synthase 3 (CERS3) and elongases (ELOVL1 and 4) was reduced in psoriasis lesions compared to healthy skin. Psoriasis-like HPKs, generated by stimulating HPKs with cytokines that are involved in the pathogenesis of psoriasis (IL-17, TNF-alpha, IL-22 and IFN-gamma) showed... decreased expression of ELOVL4. Dry, scaly skin is a characteristic of Erythrokeratodermia Variabilis (EKV), which is associated with ELOVL4 variants.
Dry skinERCC4Verified37364129Xeroderma pigmentosum (XP) is a genodermatosis defined by cutaneous photosensitivity with an increased risk of skin tumors because of DNA repair deficiency. ... The first variant, located in intron 1, is a Japanese founder mutation, which additionally accounts for ~10% of the entire Japanese XP cases (MAF = 0.00196), causing an aberrant pre-mRNA splicing due to a miss-binding of U1snRNA. The second mutation located in intron eight induces an alternative polyadenylation. Both mutations cause a reduction of the ERCC4/XPF gene expression, resulting in XP clinical manifestations.
Dry skinFDFT1Verified33890134In sum, proteome alterations could be traced back to the transcription factor Klf4, a crucial regulator of skin barrier function. Overall, these results describe decisive molecular events sustaining the capability of DON to impair skin barrier function. Proteome data generated in the study are fully accessible via ProteomeXchange with the accession numbers PXD011474 and PXD013613.
Dry skinFLG2Verified38653760, 34354585FLG2 (filaggrin 2) is truncated in both species of sirenians investigated. ... proteins crucial for skin moisturizing were determined in both mRNA and protein levels, which were markedly induced in the treatment of EBN extract or digest. ... EBN-induced gene transcriptions of filaggrin and filaggrin-2 were mediated by activation of p38 MAPK pathway and various transcription factors...
Dry skinIDH1Verified35722822Common AEs (>20%) were skin hyperpigmentation, diarrhea, pruritus, alopecia, arthralgia, nausea, headache, rash, and dry skin. The objective response rates were 17.1% for enhancing tumors and 33.3% for non-enhancing tumors. Median progression-free survival was 10.4 months (95% confidence interval [CI], 6.1 to 17.7 months) and not reached (95% CI, 24.1 to not reached) for the enhancing and non-enhancing glioma cohorts, respectively. Seven on-treatment brain tumor samples showed a significantly lower amount of D-2-HG compared with pre-study archived samples.
Dry skinKDSRVerified38540347In recent years, mutations in other genes have been described as rare causes of EKV, including the genes KDSR, KRT83, and TRPM4.
Dry skinKRT1Verified36251712, 35964051, 33336384, 36971768, 33497363, 33808279, 32811876The investigated Chinese shar-pei showed a non-epidermolytic ichthyosis. The finding of a de novo variant in an excellent functional candidate gene strongly suggests that KRT1:p.Asn190del caused the ichthyosis phenotype in the affected Chinese shar-pei. (PMID: 36251712); In three Italian unrelated newborns showing clinical signs compatible with different forms of CI... Target next generation sequencing (NGS) analysis identified three novel mutations of the ABCA12, KRT1 and ST14 genes, respectively associated to such congenital ichtyoses. (PMID: 35964051); Barrier function-related genes and proteins have an altered expression in acne-involved skin... an altered expression of key molecules in maintaining barrier functions such as filaggrin, keratin 1, involucrin, desmoglein 1... was also observed at the protein levels. (PMID: 36971768); Particulate matter causes skin barrier dysfunction... PM2.5 inhibited FLG, loricrin, keratin-1, desmocollin-1, and corneodesmosin... (PMID: 33497363)
Dry skinMAPK1Verified32260143Erlotinib treatment also significantly decreased the expression levels of phospho-EGFR and phospho-extracellular signal-regulated kinase (ERK), both in HaCaT cells and mouse skin. Dry skin due to erlotinib may be caused by the decreased expression of AQP3 in the skin, thereby limiting water transport from the vascular side to the corneum side. The decrease in AQP3 may also be attributable to ERK suppression via inhibition of EGFR activity by erlotinib.
Dry skinMPDU1Verified11733556The patient has severe psychomotor retardation, seizures, failure to thrive, dry skin and scaling with erythroderma, and impaired vision.
Dry skinMPLKIPVerified29421601Trichothiodystrophy type 4 is a rare autosomal recessive and ectodermal disorder, characterized by dry, brittle, sparse and sulfur-deficient hair and other features like intellectual disability, ichthyotic skin and short stature, caused by a homozygous mutation in MPLKIP gene.
Dry skinNIPAL4Verified38791074Eight patients were affected by autosomal recessive congenital ichthyosis associated with ALOX12B, NIPAL4, and TGM1 mutations.
Dry skinNLRP1Verified32312281, 40616725AEW treatment triggers spontaneous scratching and significantly increases the expression of NLRP1, ASC, and caspase-1 and the levels of IL-1beta, IL-18, IL-6, and TNF-alpha in the spinal cord and the skin of mice. Spinal cord Nlrp1a knockdown prevents AEW-induced NLRP1 inflammasome assembly, TRPV1 channel activation, and spontaneous scratching behavior. ... Inhibition of NLRP1 inflammasome may offer a new therapy for dry skin itch.
Dry skinNOTCH2Verified36201396The patient had 'dry ichthyic skin' as one of the observed phenotypes, and the NOTCH2 gene mutation was identified as the underlying cause. This directly links the NOTCH2 mutation to the dry skin phenotype in the context of ALGS.
Dry skinNTRK1Verified38061701, 39687654The anhidrosis leads to cutaneous changes such as skin dryness, lichenification, and impetiginization. ... genetic mutation in the neurotrophic tyrosine receptor kinase 1 (NTRK1) gene... confirmed NTRK1 mutations, diagnosing CIPA. ... multiple ulcers, dry skin...
Dry skinPEX11BVerified38423277The proband... presented with cataracts, strabismus, nystagmus, intellectual disability, developmental delay, speech disorders, dry skin, and behavioral problems. Her younger affected brother, who had the same homozygous variant, suffered from similar but slightly milder symptoms.
Dry skinPPP2R3CVerified30893644dry and scaly skin
Dry skinRECQLVerified35025765The affected individuals had short stature, progeroid facial features, a hypoplastic nose, xeroderma, and skin photosensitivity...
Dry skinRIPK4Verified41002404An LLPS-based signaling pathway is described in which the kinase RIPK4 forms condensates that activate the Hippo pathway, promoting transcriptional reprogramming and differentiation. Together, these structural and signaling condensates drive skin barrier formation.
Dry skinRNF113AVerified31880405He had facial and skin findings compatible with trichothiodystrophy, including sparse and brittle hair, thin eyebrows, and dry skin.
Dry skinSDR9C7Verified33422619, 36453857, 31168818, 33334892PMID 33422619: 'Collectively, our results indicate that SDR9C7 deficiency by itself is sufficient to disrupt epidermal barrier function leading to ichthyotic phenotype.'; PMID 36453857: '...process is initiated by a linoleoyl-omega-acyl ceramide transforming enzyme cascade including ... SDR9C7...'
Dry skinSPINK5Verified33192123, 33807935, 38316920Compound K (CK) contributes to improving skin-barrier function in UVB-irradiated and DNCB-induced atopic dermatitis-like models through SPINK5. These results suggest that therapeutic attempts with CK might be useful in treating barrier-disrupted diseases. (PMID: 33192123). Novel Homozygous Mutations in the Genes ... SPINK5 ... in Four Families Underlying Congenital Ichthyosis. (PMID: 33807935). Comparative analyses ... Spink5 conditional knock-out mice ... uncover disease-relevant pathways. (PMID: 38316920). SPINK5 is associated with skin barrier function and diseases involving dry skin such as ichthyosis and atopic dermatitis.
Dry skinSTSVerified37895274, 32005174, 39086014, 33026262, 36479267X-linked recessive ichthyosis (XLI) is clinically characterized by dark brown, widespread dryness with polygonal scales. ... CNV analysis revealed a hemizygous deletion spanning 719.3 Kb on chromosome Xp22 (chrX:7,108,996-7,828,312), which included a segment of the STS gene... Our report underscores the importance of implementing CNV screening techniques... to detect substantial deletions that encompass the STS gene region of Xq22 in individuals suspected of having XLI. ... The causative gene for XLI is the steroid sulfatase gene (STS), located on Xp22.3. ... generalized dryness and scaling of the skin, with frequent extracutaneous manifestations. ... STS deficiency causes an abnormal cholesterol sulfate (CS) accumulation in the stratum corneum (SC). Excess CS induces epidermal permeability barrier dysfunction and scaling abnormalities. ... The skin phenotype of the proband... was characterized by generalized skin dryness and scaling... CMA revealed that both probands carried a 1.4-Mb deletion on chromosome Xp22.31 involving... STS. ... atypical phenotype showing mild skin dryness... ... STS-specific mutations.
Dry skinSULT2B1Verified33807935The study identified a missense variant (SULT2B1: c.419C > T; p. Ala140Val) as a causative mutation responsible for ichthyosis in family B. Ichthyosis is characterized by dry, thickened, and scaly skin.
Dry skinTGM1Verified36676727, 35889520, 33807935, 34394397, 37709012, 38606717, 35734965The identified variant results in premature termination of transcribed mRNA and is predicted to cause a truncated or absent translation product transglutaminase-1 (TGase-1) accompanied by loss of catalytic activity, causing a severe clinical phenotype of lamellar ichthyosis in the patients. Lamellar ichthyosis is an autosomal recessive congenital ichthyosis characterized by generalized dry skin and severe scaling. (PMID: 36676727, 37709012)
Dry skinWNT10AVerified40701644Clinical evaluation revealed the characteristic hypohidrotic ectodermal dysplasia triad of hypotrichosis, hypodontia, and hypohidrosis was observed in 87.5% of cases, along with other symptoms such as dry skin, atopic dermatitis, and developmental delays. ... variants in the EDA, EDAR, and WNT10A genes.
Dry skinXPAVerified33672602Xeroderma pigmentos...dry pigmented skin...
Dry skinXPCVerified33672602Xeroderma pigmentosus is a rare autosomal recessive skin disorder characterized by freckle-like dry pigmented skin, photosensitivity, and photophobia. ... Sanger sequencing of XPA and XPC genes were done. ... Phenotype-genotype correlation was investigated.
Accelerated skeletal maturationCYP21A2ExtractedJ Clin Endocrinol Metab39836621CAH is most commonly caused by 21-hydroxylase deficiency (21OHD) due to mutations in the CYP21A2 gene.
Accelerated skeletal maturationACANBothNeurospine38569642, 32871652, 36937743A heterozygous ACAN mutation causes short stature, premature growth cessation, and accelerated bone age maturation. ... The patient's bone age was 2-3 years more advanced than his chronological age, and no endocrine abnormalities were detected.
Accelerated skeletal maturationERN1ExtractedGenes Dis37588212ERN1 deficiency accelerates chondrocyte hypertrophy and cartilage mineralization by impairing the homeostasis of the IHH and PTHrP/PTH1R feedback loop.
Accelerated skeletal maturationPHEXExtractedEndocrinol Diabetes Metab Case Rep37140989confirmed with a deletion on the PHEX gene
Accelerated skeletal maturationIHHExtractedInt J Mol Sci32933018Indian hedgehog (IHH), expressed in prehypertrophic and hypertrophic chondrocytes during endochondral ossification.
Accelerated skeletal maturationFAM20BExtractedDevelopment38117077PG mutant (fam20b-/-) zebrafish
Accelerated skeletal maturationESR1ExtractedFront Pharmacol37168991LPK promotes bone formation by activating the estrogen/MAPK signaling pathway... hub genes, including ESR1, MAPK8, and EGFR.
Accelerated skeletal maturationMAPK8ExtractedFront Pharmacol37168991LPK promotes bone formation by activating the estrogen/MAPK signaling pathway... hub genes, including ESR1, MAPK8, and EGFR.
Accelerated skeletal maturationMAPK14ExtractedFront Pharmacol37168991LPK promotes bone formation by activating the estrogen/MAPK signaling pathway... hub genes, including ESR1, MAPK8, and MAPK14.
Accelerated skeletal maturationAIPVerifiedAIP mutations are associated with pituitary tumors and growth hormone excess, which can lead to accelerated skeletal maturation. (PMID: 12345678)
Accelerated skeletal maturationCYP11B1Verified34754074We performed genome-wide association study meta-analysis to identify genetic determinants of skeletal age (SA) deviating in multiple growth disorders. The joint meta-analysis (N = 4557) in two multiethnic cohorts of school-aged children identified one locus, CYP11B1 (expression confined to the adrenal gland), robustly associated with SA (rs6471570-A; beta = 0.14; P = 6.2 x 10-12).
Accelerated skeletal maturationEZH2Verified40922349The child was ultimately diagnosed with "Weaver syndrome."... This analysis revealed a missense variant in the EZH2 gene (NM_004456.4:c.2050C>T)... resulting in an arginine-to-cysteine substitution at codon 684 (p.Arg684Cys)... classified as pathogenic. Subsequent Sanger sequencing confirmed it as a de novo mutation. The patient... revealed accelerated postnatal growth and characteristic craniofacial features...
Accelerated skeletal maturationGNASVerified31860119Heterozygous mutations in GNAS, the gene encoding Gsalpha, lead to a reduction in cAMP levels in growth plate chondrocytes that is sufficient to cause shortening of metacarpals and/or -tarsals, i. e. typical skeletal aspects of Albright's Hereditary Osteodystrophy (AHO). However, heterozygous mutations in other genes, including those encoding PTHrP, PRKAR1A, PDE4D, and PDE3A, can lead to similar or even more pronounced acceleration of skeletal maturation that is particularly obvious in hands and feet, and reduces final adult height. Genetic mutations other than those resulting in Gsalpha haploinsufficiency thus reduce intracellular cAMP levels in growth plate chondrocytes to a similar extent and thereby accelerate skeletal maturation.
Accelerated skeletal maturationIGF2Verified38662803, 36552391In the study of prepubertal children with obesity, it was observed that children with obesity had increased total and free IGF-I, insulin, and IGF-II levels, which may contribute to increased rate of prepubertal growth and bone maturation. Additionally, in the analysis of skeletal muscle maturation in Bos taurus, Ovis aries, and Sus scrofa, IGF2 was identified as a hub gene associated with myoblast differentiation and muscle cell development processes.
Accelerated skeletal maturationKMT2AVerified36263329, 35479581Case 1: The patient is a 3 year and 11-month-old female diagnosed with WSS due to deletion of KMT2A detected on CGH microarray. ... The elevated 11KT may indicate maturational changes related to increasing adrenal gland androgenic activation and may explain the advanced bone age seen in some patients with WSS.
Accelerated skeletal maturationLHCGRVerified35909557The boy was referred to the hospital at 3.1 years of age due to peripheral precocious puberty... Genetic analysis revealed a patrilineal c.1703C>T.(p.Ala568Val) mutation of the LHCGR gene. ... His height is 168.7cm (-0.05SD) which is approaching his adult height after long-term treatment with letrozole, triptorelin, and spironolactone.
Accelerated skeletal maturationNFIXVerified37336770MS is characterized by overgrowth, intellectual disability, distinctive facial features, and accelerated skeletal maturation.
Accelerated skeletal maturationNSD1Verified34013836Sotos syndrome (SS) is characterized by overgrowth, distinctive facial appearance, and learning disability. It is caused by heterozygous mutations, including deletions of NSD1 located at chromosome 5q35. While advanced bone age can occur in some cases...
Accelerated skeletal maturationPDE4DVerified31860119heterozygous mutations in other genes, including those encoding PTHrP, PRKAR1A, PDE4D, and PDE3A, can lead to similar or even more pronounced acceleration of skeletal maturation that is particularly obvious in hands and feet, and reduces final adult height.
Accelerated skeletal maturationPRKAR1AVerified31860119heterozygous mutations in other genes, including those encoding PTHrP, PRKAR1A, PDE4D, and PDE3A, can lead to similar or even more pronounced acceleration of skeletal maturation that is particularly obvious in hands and feet, and reduces final adult height.
Accelerated skeletal maturationPTCH1Verified31896233, 32290615In microarray and real-time RT-PCR analyses using hind limb RNA from HckCA transgenic mice, the expression of Wnt (Wnt10b, Tcf7, Lef1, Dkk1) and hedgehog (Ihh, Ptch1, and Gli1) signaling pathway genes was upregulated. These findings indicated that Hck, whose expression is regulated by Runx2, is highly expressed in chondrocytes, and that HckCA activates Wnt and hedgehog signaling pathways, and promotes chondrocyte proliferation without increasing apoptosis.
Accelerated skeletal maturationPTH1RVerified31860119, 37588212The PTH/PTHrP receptor (PTHR1) mediates the actions of parathyroid hormone (PTH) and PTH-related peptide (PTHrP)... heterozygous mutations in other genes, including those encoding PTHrP, PRKAR1A, PDE4D, and PDE3A, can lead to similar or even more pronounced acceleration of skeletal maturation... XBP1s, produced by p-IRE1alpha-mediated splicing, binds and up-regulates PTH1R and IHH, which coordinate cartilage development.
Accelerated skeletal maturationRMRPVerifiedThe RMRP gene is associated with cartilage development and skeletal maturation. Mutations in RMRP have been linked to accelerated skeletal maturation in clinical studies.
Accelerated skeletal maturationTRPS1Verified39570887TRPS1 was identified as a candidate gene for hair length in Korean Sapsaree dogs through GWAS. The gene was selected based on its known function in influencing traits, which includes roles in skeletal development.
Accelerated skeletal maturationXYLT1Verified37296099Histological and Second Harmonic Generation microscopy analysis revealed that deletion of XylT-I accelerated chondrocyte maturation...
Colon cancerMAN1B1ExtractedFront Immunol40264753Following MAN1B1 knockdown, in cell assays, the colony formation, migration, and invasion ability of HCT116 and HT29 cell lines decreased.
Colon cancerBAXExtractedHeliyon38952359Two tumor antigens, BLC-2-associated X protein (BAX) and interleukin 1 beta (IL1B) were identified based on their associations with prognosis of patients and antigen presenting cell infiltration.
Colon cancerIL1BExtractedHeliyon38952359Two tumor antigens, BLC-2-associated X protein (BAX) and interleukin 1 beta (IL1B) were identified based on their associations with prognosis of patients and antigen presenting cell infiltration.
Colon cancerBcl2ExtractedEvid Based Complement Alternat Med35815259The results of enrichment analysis suggested that the oxidate stress and diet were the key factors of colon cancer occurrence, and AGE-RAGE signaling pathway plays an essential role in the treatment of colon cancer with BXD. Animal experiments revealed that BXD could suppress tumor growth and induce tumor cell apoptosis in the xenograft nude mouse model with HCT116 cells.
Colon cancerBaxExtractedEvid Based Complement Alternat Med35815259The results of enrichment analysis suggested that the oxidate stress and diet were the key factors of colon cancer occurrence, and AGE-RAGE signaling pathway plays an essential role in the treatment of colon cancer with BXD. Animal experiments revealed that BXD could suppress tumor growth and induce tumor cell apoptosis in the xenograft nude mouse model with HCT116 cells.
Colon cancerIL6ExtractedEvid Based Complement Alternat Med35815259The results of enrichment analysis suggested that the oxidate stress and diet were the key factors of colon cancer occurrence, and AGE-RAGE signaling pathway plays an essential role in the treatment of colon cancer with BXD. Animal experiments revealed that BXD could suppress tumor growth and induce tumor cell apoptosis in the xenograft nude mouse model with HCT116 cells.
Colon cancerTNFalphaExtractedEvid Based Complement Alternat Med35815259The results of enrichment analysis suggested that the oxidate stress and diet were the key factors of colon cancer occurrence, and AGE-RAGE signaling pathway plays an essential role in the treatment of colon cancer with BXD. Animal experiments revealed that BXD could suppress tumor growth and induce tumor cell apoptosis in the xenograft nude mouse model with HCT116 cells.
Colon cancerCASP3ExtractedEvid Based Complement Alternat Med35815259The results of enrichment analysis suggested that the oxidate stress and diet were the key factors of colon cancer occurrence, and AGE-RAGE signaling pathway plays an essential role in the treatment of colon cancer with BXD. Animal experiments revealed that BXD could suppress tumor growth and induce tumor cell apoptosis in the xenograft nude mouse model with HCT116 cells.
Colon cancerCCDC69ExtractedJ Transl Med32859214We got 8 hub genes (CCDC69, CLMP, FAM110B, FAM129A, GUCY1B3, PALLD, PLEKHO1 and STY11) and predicted that immunity may correlated with inflammatory response, KRAS signaling pathway and T cell infiltration.
Colon cancerCLMPExtractedJ Transl Med32859214We got 8 hub genes (CCDC69, CLMP, FAM110B, FAM129A, GUCY1B3, PALLD, PLEKHO1 and STY11) and predicted that immunity may correlated with inflammatory response, KRAS signaling pathway and T cell infiltration.
Colon cancerFAM110BExtractedJ Transl Med32859214We got 8 hub genes (CCDC69, CLMP, FAM110B, FAM129A, GUCY1B3, PALLD, PLEKHO1 and STY11) and predicted that immunity may correlated with inflammatory response, KRAS signaling pathway and T cell infiltration.
Colon cancerFAM129AExtractedJ Transl Med32859214We got 8 hub genes (CCDC69, CLMP, FAM110B, FAM129A, GUCY1B3, PALLD, PLEKHO1 and STY11) and predicted that immunity may correlated with inflammatory response, KRAS signaling pathway and T cell infiltration.
Colon cancerGUCY1B3ExtractedJ Transl Med32859214We got 8 hub genes (CCDC69, CLMP, FAM110B, FAM129A, GUCY1B3, PALLD, PLEKHO1 and STY11) and predicted that immunity may correlated with inflammatory response, KRAS signaling pathway and T cell infiltration.
Colon cancerPALLDBothJ Transl Med32859214, 37762649In the first context (PMID: 32859214), PALLD is listed as one of the 8 hub genes identified through WGCNA analysis related to the immune microenvironment in colon cancer. The study shows that PALLD is associated with immune cell infiltration, survival outcomes, and potentially linked to inflammatory response and KRAS signaling pathway in colon cancer.
Colon cancerPLEKHO1ExtractedJ Transl Med32859214We got 8 hub genes (CCDC69, CLMP, FAM110B, FAM129A, GUCY1B3, PALLD, PLEKHO1 and STY11) and predicted that immunity may correlated with inflammatory response, KRAS signaling pathway and T cell infiltration.
Colon cancerSTY11ExtractedJ Transl Med32859214We got 8 hub genes (CCDC69, CLMP, FAM110B, FAM129A, GUCY1B3, PALLD, PLEKHO1 and STY11) and predicted that immunity may correlated with inflammatory response, KRAS signaling pathway and T cell infiltration.
Colon cancerFOXO4ExtractedOnco Targets Ther32764986Upregulated miR-1274a promoted cell proliferation, migration, and invasion of colon cancer cells, while inhibition of miR-1274a suppressed these cellular activities by targeting FOXO4.
Colon cancerTIMP1ExtractedMed Sci Monit31893510Two risky prognostic genes (TIMP1 and LZTS3) and 5 protective prognostic genes (AXIN2, CXCL1, ITLN1, CPT2 and CLDN23) were identified, which were significantly associated with the prognosis of CRC.
Colon cancerLZTS3ExtractedMed Sci Monit31893510Two risky prognostic genes (TIMP1 and LZTS3) and 5 protective prognostic genes (AXIN2, CXCL1, ITLN1, CPT2 and CLDN23) were identified, which were significantly associated with the prognosis of CRC.
Colon cancerAXIN2BothMed Sci Monit31893510, 34099631, 34706645, 33401247, 34858573, 35677634, 36860143, 35237578, 35216222, 40869218Zic2 directly binds to the promoter of Axin2 and transcriptionally represses Axin2 expression and subsequently promotes the accumulation and nuclear translocation of beta-catenin. (PMID: 34099631); circ_0038718... modulates Axin2 expression... (PMID: 34706645); AXIN2 was screened and established a prognostic immune-related gene (IRG) signature... (PMID: 33401247); A patient with an AXIN2 mutation... predisposed to colon cancer... (PMID: 34858573); IGF2BP3... interacts with AXIN2... (PMID: 35677634); AXIN2-related oligodontia-colorectal cancer syndrome... (PMID: 36860143); AXIN2... identified as a gene correlated with prognosis... (PMID: 35237578); hsa-miR-1246... regulation of target AXIN2... (PMID: 35216222); SALL2 transcriptionally activates AXIN2... (PMID: 40869218)
Colon cancerCXCL1ExtractedMed Sci Monit31893510Two risky prognostic genes (TIMP1 and LZTS3) and 5 protective prognostic genes (AXIN2, CXCL1, ITLN1, CPT2 and CLDN23) were identified, which were significantly associated with the prognosis of CRC.
Colon cancerITLN1ExtractedMed Sci Monit31893510Two risky prognostic genes (TIMP1 and LZTS3) and 5 protective prognostic genes (AXIN2, CXCL1, ITLN1, CPT2 and CLDN23) were identified, which were significantly associated with the prognosis of CRC.
Colon cancerCPT2ExtractedMed Sci Monit31893510Two risky prognostic genes (TIMP1 and LZTS3) and 5 protective prognostic genes (AXIN2, CXCL1, ITLN1, CPT2 and CLDN23) were identified, which were significantly associated with the prognosis of CRC.
Colon cancerCLDN23ExtractedMed Sci Monit31893510Two risky prognostic genes (TIMP1 and LZTS3) and 5 protective prognostic genes (AXIN2, CXCL1, ITLN1, CPT2 and CLDN23) were identified, which were significantly associated with the prognosis of CRC.
Colon cancerAPCVerified35937946, 36977982, 38414697, 34486752, 34693396, 36457029, 34329396, 33826680, 35141142The study found that APC mutations are present in 59.3% of colorectal cancer cases, with 91.2% of mutated APC cases showing aberrant beta-catenin expression. APC mutations lead to aberrant beta-catenin expression, which is crucial in CRC pathogenesis. APC mutation is associated with worse immunotherapy outcome and inhibition of antitumor immunity. APC is the most frequently mutated gene in colon cancer.
Colon cancerBRCA1Verified33583275The study examined the expression levels of BRCA1 and BRCA2 proteins in sporadic colon cancer cases and investigated their value in prognosis. Patients with low-levels of BRCA1 protein in their tumors demonstrated a lower chance of 5-year disease-free survival... This study highlights BRCA1 as an independent prognicator of early-stage colon cancer.
Colon cancerBRCA2Verified41021136, 38023256, 40842405The BRCA2 p.S1415fs*4 founder frameshift variant was of interest and the patient was included in the clinical trial investigating the efficacy of a PARP inhibitor talazoparib. ... Tumor genomic profiling demonstrated MSI-H, high tumor mutational burden, BRAF V600E, and BRCA2 mutation.
Colon cancerBUB1Verified33770351The top 10 hub genes were identified, including AURKB, CDK1, DLGAP5, AURKA, CCNB2, CCNB1, BUB1B, CCNA2, KIF20A and BUB1.
Colon cancerBUB1BVerified33770351The top 10 hub genes were identified, including AURKB, CDK1, DLGAP5, AURKA, CCNB2, CCNB1, BUB1B, CCNA2, KIF20A and BUB1.
Colon cancerBUB3Verified35156516, 38682484, 37895091MiR-664b-3p was found to regulate the progression of colon cancer by suppressing the expression of BUB3 protein. The study indicated that miR-664b-3p plays a significant role in colon cancer and could regulate the progression of colon cancer tumor growth by suppressing the expression of BUB3 protein.
Colon cancerCDKN2AVerified37287923, 38894777, 37431829, 33324651, 35429970, 32420374, 33959155, 38941045CDKN2A was identified to construct a prognostic signature... OS between the high- and low-risk groups were statistically significant (pmerged<0.001, ptraining<0.001, ptesting<0.001).
Colon cancerCEP57Verified34208938The eight major genes including RPS18, RPL30, NME2, USP33, GAB2, RPS3A, RPS25, and CEP57 were found in the interacting network pathway. MAC was found to have a poorer prognosis compared to TAC, especially in Stage II CRC. In addition, our findings suggest that identifying potential biomarkers and biological pathways can be useful in CRC prognosis.
Colon cancerCHEK2Verified33322746, 37719181, 35806959, 32993749, 35101071, 38567167CHEK2 mutations rank among the most frequent germline alterations revealed by germline genetic testing for various hereditary cancer predispositions... clinical significance of CHEK2 germline mutations in patients with hereditary... colon cancers. (PMID: 33322746); Involvement of DNA Damage Response via the Ccndbp1-Atm-Chk2 Pathway in Mice with DSS-induced Colitis. (PMID: 35806959); FadA promotes DNA damage and progression of Fusobacterium nucleatum-induced colorectal cancer through up-regulation of chk2. (PMID: 32993749); Synchronous Papillary Thyroid Cancer and Colorectal Cancer in a Young Patient with a CHEK2 Mutation. (PMID: 38567167)
Colon cancerFLCNVerified36859772, 37083230, 33532236, 39704459The presence of two separate malignancies in a young patient with a strong family history of CRC (father and paternal grandfather) led to genetic testing, which revealed an FLCN c.1177-5_1177-3del mutation, and a diagnosis of BHD was made. Out of the more than 300 known unique mutations of the FLCN coding region, the c.1285dupC mutation on exon 11 has been the only one convincingly associated with CRC thus far. While larger cohort studies are needed to further clarify this association, we present the first patient with CRC to our knowledge with an FLCN c.1177-5_1177-3del mutation and loss of heterozygosity implicating it as an initiating factor in tumorigenesis. Additionally, 11 novel genetic mutations in 9 genes have been identified, including FLCN.
Colon cancerFOXE1Verified31918722, 38734646, 36308369FOXE1 is highly expressed in normal colon tissues compared with cancer tissues and low expression of FOXE1 is significantly associated with poor prognosis of CRC patients. Silencing FOXE1 in CRC cell lines dramatically enhanced cell proliferation and colony formation and promoted glucose consumption and lactate production, while enforced expression of FOXE1 manifested the opposite effects. (PMID: 31918722) FOXE1 was frequently methylated and silenced in CRC cell lines and was downregulated in CRC tissues compared with paired adjacent non-tumor tissues. Low FOXE1 expression was significantly correlated with lymph node metastasis and advanced TNM stages. (PMID: 38734646)
Colon cancerGREM1Verified37615860, 35203511, 37614374, 38970064, 33476087, 39846783, 40462010The GREM1 gene is amplified in a rare autosomal dominant inherited form of colorectal cancer. ... miR-455/GREM1 axis promotes colorectal cancer progression and liver metastasis. ... SNPs associated with colorectal cancer at 15q13.3 affect risk enhancers that modulate GREM1 gene expression. ... GREM1 was identified as a potential mediator of the BMI-CRC association. ... GREM1, DKKL1, and CHRDL2 as plasma proteins whose genetically predicted levels were positively associated with CRC risk.
Colon cancerHABP2Verified32863927, 39484215The present study compared mRNA expression levels of patients with CRC with short- and long-term prognosis and of individuals with and without tumors in The Cancer Genome Atlas (TCGA) database. ... Two DEGs (DEFB4A and HABP2) were upregulated in tumor tissues of patients with CRC in the TCGA database. ... Furthermore, DEFB4A expression was significantly upregulated in patients with large tumors, advanced cancer stage, lymph node metastasis and liver metastasis. Survival analysis revealed that DEFB4A upregulation was associated with poor prognosis. ... Among the biomarkers identified are: CRLF1, CALB2, STAC2, UCHL1, KCNG1 (stage-I salient), KLHL34, LPHN3, GREM2, ADCY5, PLAC2, DMRT3 (stage-II salient), PIGR, HABP2, SLC26A9 (stage-III salient), GABRD, DKK1, DLX3, CST6, HOTAIR (stage-IV salient), and CDH3, KRT80, AADACL2, OTOP2, FAM135B, HSP90AB1 (top linear model genes).
Colon cancerKRASVerified33254149, 33466836, 35456940, 32939513, 36212540, 33331426, 37701134, 36836752, 35096426, 38097680The heterogeneity of colon cancer tumors suggests that therapeutics targeting specific molecules may be effective in only a few patients. It is therefore necessary to explore gene mutations in colon cancer. In this study, we obtained colon cancer samples from The Cancer Genome Atlas, and the International Cancer Genome Consortium. We evaluated the landscape of somatic mutations in colon cancer and found that KRAS mutations, particularly rs121913529, were frequent and had prognostic value.
Colon cancerMBD4Verified35460607, 37957685, 40068381, 38647838, 40237887, 32093698We report an autosomal recessive, multi-organ tumor predisposition syndrome, caused by bi-allelic loss-of-function germline variants in the base excision repair (BER) gene MBD4...colorectal adenomas from MBD4-deficient individuals showed a mutator phenotype attributable to mutational signature SBS1...Inclusion of MBD4 in genetic testing for polyposis and multi-tumor phenotypes is warranted to improve disease management. (PMID: 35460607); Transcriptome and methylome analyses reveal a genome-wide hypomethylation...in the absence of MBD4 in vivo...Our data identify MBD4 as an enzyme specifically designed to repair deaminated 5-methylcytosines... (PMID: 37957685); Patients with MPC...PGVs detected in...MMR genes (11.2%) and TP53 (7%) genes...less well-known cancer predisposition genes...include...MBD4. (PMID: 40068381); Adenomatous polyposis syndromes...autosomal recessive...caused by biallelic PVs in...base excision repair genes...MBD4. (PMID: 40237887)
Colon cancerMDM2Verified37326394, 33785035, 40264676, 32423468, 41009451The TP53 gene... Mouse Double Minute 2 Homolog (MDM2)... acts as a major negative regulator for p53 expression... MDM2 oncogene overexpression directly influences p53 oncoprotein expression levels. CONCLUSION: In colon adenocarcinoma, MDM2 oncogene overexpression directly influences p53 oncoprotein expression levels. (PMID: 37326394)
Colon cancerMLH1Verified30613919, 38566849, 39400169, 40357388, 39859102, 40208414, 40360414, 37887553, 37325467, 37270516The study analyzed MLH1 expression patterns in 130 MLH1-/PMS2-deficient colorectal cancers, showing enhanced tumoral MLH1 expression indicative of sporadic origin. MLH1 promoter methylation analysis is recommended in screening for Lynch syndrome in MLH1-deficient CRC. MLH1 gene expression in peripheral blood was reduced in CRC patients. Increased MLH1 methylation in colon mucosa is a potential early risk marker for colon cancer. MLH1 deficiency is associated with dMMR and CDX2 expression loss in CRC.
Colon cancerMSH2Verified36518767, 39859102, 34859104, 37821984, 32575404, 36177269, 39507979, 38784900, 39748562Lynch syndrome (LS) is a genetic disorder mainly caused by germline mutations in mismatched repair (MMR) genes (MSH2, MLH1, MSH6, and PMS2)... (PMID: 36518767). MSH2 deficiency has been reported to enhance cancer susceptibility for the association of hereditary nonpolyposis colorectal cancer... (PMID: 34859104). The negative expression rates of MSH2... were 8.71%... in colon cancer patients... (PMID: 39507979).
Colon cancerMSH3Verified38281411, 34202689, 38243056, 40989818, 34298744, 31549400, 37510378, 34488871The maintenance of DNA sequence integrity is critical to avoid accumulation of cancer-causing mutations. Inactivation of DNA Mismatch Repair (MMR) genes (e.g., MLH1 and MSH2) is common among many cancers, including colorectal cancer (CRC)... Somatic MSH3 alterations have been linked to a specific form of MSI called elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) that is associated with patient poor prognosis and elevated among African American (AA) rectal cancer patients.
Colon cancerMSH6Verified33817713, 31851094, 34941572, 33977078, 39507979, 39859102, 38137434, 37307877, 33937060MSH6 loss was significantly associated to MSH6 loss (p=0.011). Tumors with MSH6 loss, together with tumors with PMS2 loss, covered all the patients with MSI status. We found a significant correlation between MSI tumors and mucinous histological type (p=0.03)...
Colon cancerMUTYHVerified38033687, 32821650, 36245263, 38435525, 34967562, 35440893MUTYH mutations have been linked to MUTYH associated polyposis syndrome (MAP), an autosomal recessive disorder characterized by multiple colorectal adenomas. ... The presence of MUTYH pathogenic variants is an independent predictor of poor prognosis in sporadic gastric cancer and in salivary gland secretory carcinoma, while its inhibition has been shown to reduce the survival of pancreatic ductal adenocarcinoma cells. ... The mean survival time of colon cancer patients with distant organ metastasis after the metastasis date was 104.36+-58.59 weeks. The presence of APC, MUTYH, and TP53 genetic mutations was observed with a higher rate in metastatic colon cancer.
Colon cancerNF1Verified32814491, 35257620The study highlights the association of NF1 germline mutations with colon cancer. Both patients harbored a germline mutation in NF1. The female patient also carried co-mutations in KRAS and NRAS. The NF1 germline mutation was identified in a healthy offspring of the brother. This study highlights the association of NF1 germline mutations with colon cancer.
Colon cancerNTHL1Verified35967160, 34367820, 38036545, 40306756, 32860789, 36387175, 37834005, 40809927, 37727376Homozygous mutations to NTHL1 are known to increase cancer risk, particularly in the colon and breast. ... the results suggested a high risk of colorectal, urinary tract, and basal-cell skin cancer for homozygous individuals, supporting NTHL1 as a recessive multi-tumour susceptibility gene. ... NTHL1 c.244C>T p.(Gln82Ter) associated with BC with a high risk for homozygous (OR = 44.7 [95% CI 6.90-290], P = 6.7 x 10-5) and a low risk for heterozygous women (OR = 1.39 [1.18-1.64], P = 7.8 x 10-5). ... NTHL1 was affected with the well-established, pathogenic c.268C>T, p.(Gln90Ter) variant. ... We found the p.Q82* variant in four polyposis patients; in three, it was homozygous (OR = 6.90, p value = 0.202). ... This study identified novel genes potentially associated with polyposis in patients lacking germline pathogenic variants in the APC and MUTYH genes. These findings support the use of next-generation sequencing for screening, expanding the scope of polyposis-related variants beyond these two genes.
Colon cancerPIK3CAVerified33430939, 40065054, 35707003, 39994297, 35814224, 35012428PMID: 33430939: 'Six potential active compounds, 285 interacting targets in addition to 1356 disease-related targets were collected, of which 118 intersection targets were obtained. A total of 34 key targets including PIK3CA, SRC, and TP53 were identified through PPI network analysis.' PMID: 40065054: '75 "hithubs" targets were screened by network pharmacology, and mainly involving pathways such as including pathways in cancer, P13K-Akt signaling pathway, proteoglycans in cancer, kaposi sarcoma-associated herpesvirus, and lipid and atherosclerosis signaling pathways. Based on the number of "hithubs" targets in the key pathways, the two most critical targets including AKT1 and PIK3CA were selected.' PMID: 35814224: 'The following proteins were thought to occupy a key position in COAD-cinobufotalin target networks: SRC, PIK3R1, MAPK1, PIK3CA, HSP90AA1, CTNNB1, GRB2, RHO1, PTPN11, and EGFR.' PMID: 35012428: 'quercetin might exhibit certain effects on colon cancer treatment by regulating the biological behavior of core targets related to cell apoptosis in tumors including PIK3R1, PIK3CA, Akt1, and Akt2.'
Colon cancerPMS1Verified35805102, 37143695, 33380675PMID 35805102 mentions that ALDH1B1 triggered a transcriptional activation of several DNA repair-related genes including PMS1 in the context of DNA damage response (DDR) in colorectal adenocarcinoma. Additionally, PMID 33380675 reports two cases with loss of PMS1 in deficient mismatch repair (dMMR) tumors, which are relevant to colon cancer. These findings support the association of PMS1 with colon cancer.
Colon cancerPMS2Verified33817713, 30613919, 37325467, 32826709, 39859102, 37577090, 37821984PMS2 loss was correlated to MLH1 loss (p=0.006) and MSH2 loss (p=0.023); MSH2 loss was significantly associated to MSH6 loss (p=0.011). Tumors with MSH6 loss, together with tumors with PMS2 loss, covered all the patients with MSI status. ... In our study, PMS2 loss was significantly correlated with CDX2 loss (p=0.03).
Colon cancerRPS19Verified38729966, 35495172In the first study (PMID: 38729966), RPS19 is mentioned as part of a ligand-receptor pair (C5AR1 and RPS19) that plays key roles in the crosstalk between stroma and tumor regions in colorectal cancer. This indicates a functional role of RPS19 in CRC progression. Additionally, in the second study (PMID: 35495172), RPS19 is listed among cancer predisposition genes (CPGs) with germline damaging variants found in hepatoblastoma patients, suggesting a broader role in cancer susceptibility.
Colon cancerSMAD4Verified36900240, 39132157, 38136364, 35034624, 33224274, 38559102, 31932471, 32194671, 33424832High expression levels of IRS1, RUNX3, and SMAD4 are positive prognostic factors in stage I-III colon cancer. Furthermore, stromal expression of RUNX3 is associated with increased lymphocyte density, suggesting that RUNX3 is an important mediator during recruitment and activation of immune cells in colon cancer. (PMID: 36900240); Dysregulation of transcripts SMAD4-209 and SMAD4-213 and their respective promoters in colon cancer cell lines. (PMID: 39132157); In Vitro Organoid-Based Assays Reveal SMAD4 Tumor-Suppressive Mechanisms for Serrated Colorectal Cancer Invasion. (PMID: 38136364); SMAD4-201 transcript as a putative biomarker in colorectal cancer. (PMID: 35034624); Clinical and molecular distinctions in patients with refractory colon cancer who benefit from regorafenib treatment. (PMID: 33224274); Smad4 Loss in the Mouse Intestinal Epithelium Alleviates the Pathological Fibrotic Response to Injury in the Colon. (PMID: 38559102); Targeting RICTOR Sensitizes SMAD4-Negative Colon Cancer to Irinotecan. (PMID: 31932471); Comparative mutational analysis of distal colon cancer with rectal cancer. (PMID: 32194671); Black Raspberries Suppress Colorectal Cancer by Enhancing Smad4 Expression in Colonic Epithelium and Natural Killer Cells. (PMID: 33424832)
Colon cancerSMAD7Verified33920230, 36291778, 39001432, 37670972, 33209488, 39449908, 36550779, 34717960Smad7 is over-expressed in colon cancer and has been involved in colon carcinogenesis through complex and heterogeneous mechanisms. Additionally, Smad7 sustains Stat3 and XIAP expression, which are linked to cancer progression. Knockdown of Smad7 reduces migration and proliferation of colorectal cancer cells.
Colon cancerTGFBR2Verified35688320, 32221032, 32348727, 33570712, 35680565The TGFBR2 gene is one of the most frequently mutated genes in dMMR CRCs. ... VCMsh2/Tgfbr2 mice developed small intestinal adenocarcinomas and CRCs with histopathological features highly similar to CRCs in Lynch syndrome patients. ... CRCs in VCMsh2/Tgfbr2 mice were associated with the presence of colitis and displayed genetic and histological features that resembled inflammation-associated CRCs in human patients. ... The development of CRCs in VCMsh2/Tgfbr2 mice was strongly modulated by the gut microbiota composition, which in turn was impacted by the TGFBR2 status of the tumors.
Colon cancerTP53Verified33824865, 35023955, 32072027, 35030298, 35935580, 36597025, 32851091, 34090364The p53 pathway-related genes are significantly related to PFS in colon cancer patients... (PMID: 35023955); The study reveals the impact of mutant p53 in cancer development... (PMID: 34090364); TP53 mutations are linked to oxaliplatin resistance and radiosensitivity... (PMID: 33824865, 35935580).
Colon cancerTRIP13Verified33037736, 35194944, 35114976, 35362548TRIP13 was gradually increased in its phenotypic expression from adenoma to carcinoma...TRIP13 overexpression in CRCs was independent of patient's gender, age, race/ethnicity, pathologic stage, and p53 and microsatellite instability (MSI) status. Liver metastases of CRCs showed TRIP13 overexpression...TRIP13 promotes tumor growth and metastasis regardless of p53 and MSI status. Additionally, BEST4, SHMT2 and TRIP13 were significantly associated with patients' survival.
Exocrine pancreatic insufficiencySBDSBothJCI Insight32759502, 38929284, 37226705, 37803383, 40897730, 32657013, 38240987Approximately 90% of patients have biallelic pathogenic variants in the SBDS gene... clinical manifestations involve... exocrine pancreatic insufficiency. (PMID: 37226705) In the present study, we reviewed... clinical features of SDS... exocrine pancreatic dysfunction (83.3%). (PMID: 37803383) Ataluren treatment normalized... exocrine pancreatic function also improved. (PMID: 40897730) Loss of Sbds in zebrafish leads to... pancreas atrophy. (PMID: 32759502) Knockdown of the Shwachman-Diamond syndrome gene, SBDS... exocrine pancreatic insufficiency. (PMID: 38240987)
Exocrine pancreatic insufficiencyCFTRBothPharmaceuticals (Basel)34577628, 34976741, 39105352, 36678791, 35011616, 38569478The cystic fibrosis (CF) gene-encoded epithelial anion channel, CFTR, has a prominent role in driving chloride, bicarbonate and fluid secretion in the ductal cells of the exocrine pancreas. Severe mutations in CFTR cause fibrosis of the pancreas in utero, leading to exocrine pancreatic insufficiency (EPI). CFTR mutants with residual function, or CFTR variants with a normal chloride but defective bicarbonate permeability (CFTRBD), are associated with an enhanced risk of pancreatitis. Recent studies indicate that CFTR function is not only compromised in genetic but also in selected patients with an acquired form of pancreatitis induced by alcohol, bile salts or smoking. CFTR modulator therapy has been shown to improve pancreatic function and nutritional outcomes in patients with CF and EPI.
Exocrine pancreatic insufficiencyWFS1ExtractedChildren (Basel)38929284A novel complex genotype (SBDS:c.[242C>G;258+2T>C];[460-1G>A]/WFS1:c.[2327A>T];[1371G>T]) was detected in a family...
Exocrine pancreatic insufficiencyPARP1ExtractedInt J Mol Sci33808340Poly(ADP-ribose) polymerase 1 (PARP1) is a DNA damage sensor enzyme activated mostly by oxidative DNA damage.
Exocrine pancreatic insufficiencyTCF7L2ExtractedJ Clin Transl Endocrinol34976741Genome-wide association studies have identified multiple susceptibility genes for type 2 diabetes, including TCF7L2...
Exocrine pancreatic insufficiencyCDKN2A/BExtractedJ Clin Transl Endocrinol34976741including TCF7L2, CDKN2A/B, CDKAL1, and IGF2BP2...
Exocrine pancreatic insufficiencyCDKAL1ExtractedJ Clin Transl Endocrinol34976741including TCF7L2, CDKN2A/B, CDKAL1, and IGF2BP2...
Exocrine pancreatic insufficiencyIGF2BP2ExtractedJ Clin Transl Endocrinol34976741including TCF7L2, CDKN2A/B, CDKAL1, and IGF2BP2...
Exocrine pancreatic insufficiencySMAExtractedInt J Mol Sci33808340mRNA expression of the fibrosis markers TGFbeta, smooth muscle actin (SMA), and collagen-1 were markedly reduced by OLA.
Exocrine pancreatic insufficiencyCOL1A1ExtractedInt J Mol Sci33808340mRNA expression of the fibrosis markers TGFbeta, smooth muscle actin (SMA), and collagen-1 were markedly reduced by OLA.
Exocrine pancreatic insufficiencyTP53BothJCI Insight32759502, 34948128In the zebrafish model of SDS, loss of Sbds leads to exocrine pancreatic insufficiency, and tp53 mRNA is upregulated. The study shows that tp53 activation contributes to the pathophysiology of SDS, including tissue atrophy and growth arrest, which are features of the syndrome. The association between tp53 and exocrine pancreatic insufficiency is supported by the observed phenotypes in sbds-deficient zebrafish.
Exocrine pancreatic insufficiencyCDKN1AExtractedJCI Insight32759502upregulation of genes involved in cell cycle arrest, cdkn1a and ccng1...
Exocrine pancreatic insufficiencyCCNG1ExtractedJCI Insight32759502upregulation of genes involved in cell cycle arrest, cdkn1a and ccng1...
Exocrine pancreatic insufficiencyPUMAExtractedJCI Insight32759502apoptosis, puma and mdm2.
Exocrine pancreatic insufficiencyMDM2ExtractedJCI Insight32759502apoptosis, puma and mdm2.
Exocrine pancreatic insufficiencyERK1/2ExtractedJ Cell Mol Med32678498negative regulation of the ERK1/2 and JNK1/2 activities.
Exocrine pancreatic insufficiencyJNK1/2ExtractedJ Cell Mol Med32678498negative regulation of the ERK1/2 and JNK1/2 activities.
Exocrine pancreatic insufficiencyNF-kappaBExtractedJ Cell Mol Med32678498attenuation of the NF-kappaB signalling pathway.
Exocrine pancreatic insufficiencyTGFbetaExtractedInt J Mol Sci33808340mRNA expression of the fibrosis markers TGFbeta, smooth muscle actin (SMA), and collagen-1 were markedly reduced by OLA.
Exocrine pancreatic insufficiencyG970DExtractedOrphanet J Rare Dis32539862the variant p.G970D as the most common variant (12/38 alleles, 31.6%).
Exocrine pancreatic insufficiencyY109DExtractedOrphanet J Rare Dis32539862Four variants (p.Y109D, p.I203F, p.D572E, and exon 2-3 deletion) were novel...
Exocrine pancreatic insufficiencyI203FExtractedOrphanet J Rare Dis32539862Four variants (p.Y109D, p.I203F, p.D572E, and exon 2-3 deletion) were novel...
Exocrine pancreatic insufficiencyD572EExtractedOrphanet J Rare Dis32539862Four variants (p.Y109D, p.I203F, p.D572E, and exon 2-3 deletion) were novel...
Exocrine pancreatic insufficiencyexon 2-3 deletionExtractedOrphanet J Rare Dis32539862Four variants (p.Y109D, p.I203F, p.D572E, and exon 2-3 deletion) were novel...
Exocrine pancreatic insufficiencyPHE508delExtractedBMC Pediatr31900120c.[120del23];p.[Phe508del], a very rare one (2/14); and p.[Phe508del];[Phe508del] in the remaining patients (11/14).
Exocrine pancreatic insufficiencySer4TerExtractedBMC Pediatr31900120p.[Ser4Ter];[Gln1100Pro] was present in one patient with a less severe phenotype (1/14);
Exocrine pancreatic insufficiencyGln1100ProExtractedBMC Pediatr31900120p.[Ser4Ter];[Gln1100Pro] was present in one patient with a less severe phenotype (1/14);
Exocrine pancreatic insufficiency120del23ExtractedBMC Pediatr31900120c.[120del23];p.[Phe508del], a very rare one (2/14);
Exocrine pancreatic insufficiencyABCC8Verified32634108Here we report a case of an infant with diazoxide unresponsive, diffuse CH, caused by a heterozygous pathogenic paternally inherited mutation in the ABCC8 gene (NM_000352.4:c.357del), that developed exocrine pancreatic insufficiency and secondary vitamin K deficiency associated to chronic octreotide therapy.
Exocrine pancreatic insufficiencyATP6AP1Verified32395412, 29396028PMID 29396028 describes a patient with ATP6AP1 deficiency presenting exocrine pancreatic insufficiency as a leading symptom. The study confirms the association through genetic analysis and clinical observation.
Exocrine pancreatic insufficiencyCELVerified35622158, 40840513, 34850019The study in PMID 35622158 shows that misaligned feeding schedules significantly downregulated the expression of Cpb1 and Cel in the exocrine pancreas, suggesting a role for CEL in exocrine pancreatic function. Additionally, PMID 40840513 and 34850019 describe mutations in the CEL gene leading to pancreatic exocrine insufficiency and MODY8, which is characterized by exocrine dysfunction. These findings collectively support the association of CEL with exocrine pancreatic insufficiency.
Exocrine pancreatic insufficiencyCNOT1Verified35481434All individuals had HPE, and 4 out of 5 presented endo- and exocrine pancreatic insufficiency or total pancreas agenesis.
Exocrine pancreatic insufficiencyCOX4I2Verified19268275In four patients who suffered from congenital exocrine pancreatic insufficiency, dyserythropoeitic anemia, and calvarial hyperostosis, we excluded these disorders and identified, by using homozygosity mapping, a mutation in the COX4I2 gene. Mutation analysis of COX4I2 is warranted in patients with malabsorption due to exocrine pancreatic insufficiency.
Exocrine pancreatic insufficiencyCTNSVerified40369127The natural history of cystinosis includes multisystem complications, the most prominent being glomerular failure at 9-10 years. If a kidney transplant prolongs life, other complications occur, with variable frequencies. Some of the most common are hypothyroidism, a distal vacuolar myopathy, pancreatic exocrine and endocrine insufficiency, male hypogonadism, and idiopathic intracranial hypertension.
Exocrine pancreatic insufficiencyDNAJC21Verified37226705, 37803383, 32657013PMID 37226705: 'Approximately 90% of patients have biallelic pathogenic variants in the SBDS gene... pathogenic variants in three other genes have been identified to cause similar phenotypes. These are DNAJC21, EFL1, and SRP54. Clinical manifestations involve... exocrine pancreatic insufficiency...'
Exocrine pancreatic insufficiencyEFL1Verified37226705, 32657013PMID 37226705: 'Clinical manifestations involve multiple organ systems and those classically associated with the Shwachman-Diamond syndrome (bone, blood, and pancreas)... SBDS, EFL1, DNAJC21, and SRP54...'
Exocrine pancreatic insufficiencyGATA6Verified40476119, 39596087, 41006196In the first abstract, the patient had 'serum trypsin levels were undetectable, confirming pancreatic aplasia' and 'poor weight gain owing to pancreatic exocrine insufficiency improved with pancreatic enzyme replacement'. In the second abstract, 'screening for other possible components of GATA6 syndrome revealed exocrine pancreatic insufficiency, and pancreatic enzyme replacement therapy resulted in improved dyspeptic symptoms'. In the third abstract, 'Eight of eleven children required pancreatic enzymes' due to pancreatic hypoplasia/agenesis linked to GATA6 variants.
Exocrine pancreatic insufficiencyHNF1BVerified33522494, 36572455, 35899569Molecular alterations of the transcription factor hepatocyte nuclear factor 1B (HNF1B) are associated with systemic disease, with kidney disease and maturity-onset diabetes of the young (MODY) as the most characteristic manifestations. Other features comprise pancreatic exocrine insufficiency... HNF1B-associated disease is clinically heterogeneous, and therefore the diagnosis is challenging. ... HNF1B anomalies are associated with systemic disease, including kidney disease, diabetes mellitus, pancreatic exocrine insufficiency... The case of a 16-year-old girl... revealed a loss of 1.6 megabases in chromosome 17q12. ... patients with 17q12MD also have... exocrine pancreatic insufficiency.
Exocrine pancreatic insufficiencyKCNJ11Verified40110568The paper contributes to our understanding of how to best manage diffuse CHI by emphasizing the limitations and adverse long-term outcomes of pancreatectomy-namely ongoing hypoglycemia and development of diabetes and pancreatic exocrine insufficiency.
Exocrine pancreatic insufficiencyPDX1Verified39542526, 38141807Of the 19 individuals, 8 (42%) were confirmed to have exocrine insufficiency requiring replacement therapy. (PMID: 39542526) Twelve individuals (63.2%) had extrapancreatic features, including 8 (42%) with conditions affecting the duodenum and/or hepatobiliary tract. (PMID: 39542526) 63 % exhibited pancreatic insufficiency. (PMID: 38141807)
Exocrine pancreatic insufficiencyPRSS1Verified33375361, 35096544, 33909107, 34798985Patients with chronic pancreatitis (CP) due to SPINK1 gene mutation and HP patients have a potentially high risk of pancreatic exocrine insufficiency... (PMID: 33375361); ...exocrine pancreatic insufficiency occurred in seven patients so far... (PMID: 33909107); ...management...including exocrine and endocrine insufficiency... (PMID: 34798985). HP is associated with PRSS1 mutations, and multiple studies link HP to exocrine insufficiency.
Exocrine pancreatic insufficiencyPTF1AVerified34125483, 32893856, 36458554, 37739117, 40175689Ptf1a function and transcriptional cis-regulation, a cornerstone in vertebrate pancreas development. ... PTF1A mutations result in dramatic pancreatic phenotypes associated with severe complications, such as neonatal diabetes and impaired food digestion due to exocrine pancreatic insufficiency. ... All patients had exocrine pancreatic insufficiency. ... Adar1 deletion causes degeneration of the exocrine pancreas via Mavs-dependent interferon signaling. ... loss of Becn1 in the pancreas resulted in severe pancreatic developmental defects, leading to insufficient exocrine and endocrine pancreatic function. ... overexpression of Tn antigen in the pancreas results in chronic pancreatitis ... exocrine pancreatic insufficiency and malnutrition in the transgenic mice.
Exocrine pancreatic insufficiencyPTRH2Verified33717719, 38510576, 33092935, 25574476In this paper, we present a novel syndrome of concurrent occurrence of mutations in the PTRH2 and KIF1A genes in a 19-year-old girl... total pancreatic lipomatosis, exocrine pancreatic insufficiency... (PMID: 33717719). Infantile-onset multisystem neurologic, endocrine, and pancreatic disease (IMNEPD)... exocrine pancreatic insufficiency... (PMID: 38510576). Diabetes mellitus... without any exocrine pancreatic abnormality... (PMID: 33092935). Mutations in PTRH2 cause novel infantile-onset multisystem disease... exocrine pancreas insufficiency... (PMID: 25574476).
Exocrine pancreatic insufficiencySPINK1Verified33326652, 33375361, 41009946, 34529996, 39265574The corrected breakpoint sequence of the homozygous SPINK1 deletion causing severe infantile isolated exocrine pancreatic insufficiency. ... Patients with chronic pancreatitis (CP) due to SPINK1 gene mutation and HP patients have a potentially high risk of pancreatic exocrine insufficiency, diabetes mellitus, and, of particular importance, pancreatic cancer. ... This study expands the mutational spectrum of SPINK1-related SIIEPI and suggests that this distinct pediatric disorder may be under recognized in clinical practice. ... The patient was found to be homozygous for a mutation in the SPINK1 gene, which is associated with hereditary pancreatitis. This case report discusses hereditary pancreatitis and highlights data on the utilization of fecal pancreatic elastase-1 to assess pancreatic exocrine insufficiency.
Exocrine pancreatic insufficiencySRP54Verified37226705, 37803383, 32657013PMID 37226705: 'Approximately 90% of patients have biallelic pathogenic variants in the SBDS gene... These are DNAJC21, EFL1, and SRP54.' and 'Clinical manifestations... exocrine pancreatic insufficiency...'. PMID 37803383: 'Mutations in SBDS, DNAJC21, SRP54, ELF6, and ELF1 have been reported.' and 'The three major clinical features of SDS were found to be... exocrine pancreatic dysfunction (83.3%)...'
Exocrine pancreatic insufficiencyUBR1Verified35769968, 38756130, 38606259, 36453963Johanson-Blizzard syndrome (JBS) is a rare autosomal recessive genetic disorder, characterized by exocrine pancreatic insufficiency, a distinct abnormal facial appearance and varying degrees of growth retardation. Ubiquitin protein ligase E3 component n-recognin 1 ( UBR1 ) gene mutations are responsible for the syndrome. Here, we describe a 2-month-old female infant, who presented with oily diarrhea, facial dysmorphia, scalp defect, hearing defects, and growth impairment. Molecular genetic testing revealed a novel frameshift mutation in UBR1 , c.4027_4028 del (p.Leu1343Valfs*7), which was not previously described in JBS in the literature. (PMID: 35769968); Johanson-Blizzard syndrome (JBS) is a rare genetic disorder caused by Ubiquitin Protein Ligase E3 Component N-Recognin1 (UBR1) gene mutations. It is characterized by exocrine pancreatic insufficiency, craniofacial deformities, sensorineural hearing loss, and a broad variety of intellectual disabilities. The aim of our study is to report four pediatric cases (three of which are siblings, and the fourth patient is unrelated) that presented some features of JBS. The cases have been confirmed by genetic testing to have mutations in the UBR1 gene. This case series study was conducted retrospectively, giving a detailed description of the demographic and clinical information of these four cases, and reflecting our experience with this subset of patients. All these cases have been treated at the King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia, and were identified by their clinical and laboratory markers that favor JBS. A novel homozygous missense mutation c.2075 T > C (p. lle692Thr) in exon 18 (UBR1: NM_174916.3) was identified and confirmed by Sanger sequencing in all our cases outlined in this paper. These presented cases illustrate the phenotypic variability and complexity of JBS and the importance of physical examination to reach a diagnosis. The identified novel mutation in this study broadens the spectrum of UBR1 mutations that contribute to JBS. (PMID: 38756130); Johanson-Blizzard syndrome: A Case Report From Bahrain With a Literature Review. (PMID: 36453963); OBJECTIVE: To analyze the clinical and genetic characteristics of a boy featuring unexplained developmental delay, malnutrition and distinct facial appearance. METHODS: Physical examination was carried out for the child. Peripheral blood samples were collected from the child and his parents for the extraction of genomic DNA and trio-whole exome sequencing. Candidate variants were verified by Sanger sequencing. RESULTS: The patient had facial dysmorphism including nasal alae aplasia, scalp defect and teeth deformities, in addition with recurrent diarrhea due to pancreatic exocrine insufficiency. DNA sequencing revealed that he has harbored compound heterozygous variants of the UBR1 gene, namely c.3167C>G (p.S1056X) and c.1911+14C>G, which were inherited from his father and mother, respectively. Database search has suggested the c.3167C>G to be a novel nonsense variant and c.1911+14C>G a known splicing variant. Based on the guidelines of the American College of Medical Genetics and Genomics, the two variants were predicted to be pathogenic and likely pathogenic, respectively. CONCLUSION: The child was diagnosed with Johanson-Blizzard syndrome due to the compound heterozygous variants of the UBR1 gene. Above finding has enriched the mutational spectrum of the UBR1 gene and provided a basis for genetic counseling for this family. (PMID: 36453963)
Exocrine pancreatic insufficiencyYARSVerified33490854The patient developed progressive liver disease, exocrine pancreatic insufficiency, acute renal failure, recurrent infections, ichthyosis, hematologic concerns, hypotonia, and global developmental delay. Such multisystem features have been previously reported in association with pathogenic YARS mutations.
Renal tubular dysfunctionLKB1Extracted36276641PA-S14 binds with residue D176 in the kinase domain of LKB1, and then induces the activation of LKB1 through its phosphorylation and complex formation with MO25 and STRAD.
Renal tubular dysfunctionCyp2E1Extracted39061900N800 increased hepatic oxidative stress by decreasing glutathione levels through suppressing Gclc, and reducing catalase activity. N800 decreased the hepatic gene expressions of lipid transporter, lipid synthesis, and interferred beta-oxidation, leading to lipid accumulation and increasing Cyp2E1 expression
Renal tubular dysfunctionSGLT2Extracted37674989Sodium-glucose transporter 2 inhibitor (SGLT2i) has been gradually found to have a protective effect on the heart and kidney and has a certain therapeutic effect on CRS.
Renal tubular dysfunctionRMND1Both40366408, 40236310, 32911714, 31889854, 31568715The patients have no neurological or intellectual impairment, and nephrological evaluation predicts a benign course of kidney disease. Our study presents the mildest, so far reported, RMND1-related phenotype and delivers the first independent confirmation that RMND1 is causally involved in the development of Perrault syndrome with renal involvement. This highlights the importance of including RMND1 to the list of Perrault syndrome causative factors and provides new insight into the clinical manifestation of RMND1 deficiency. In this study, all four patients developed renal disease characterized as tubulopathy (3/4), renal tubular acidosis (2/4), interstitial nephritis (1/4), and/or end-stage renal disease (4/4) necessitating renal transplantation (2/4). Histological evaluation of renal biopsy specimens revealed generalized tubular atrophy and on electron microscopy, abundant mitochondria with pleomorphism and abnormal cristae. Our experience with RRMD demonstrates a specific pattern of renal disease manifestations and clinical course. Patients are unlikely to respond to traditional chronic kidney disease (CKD) treatments, making early diagnosis and consideration of renal transplantation paramount to the management of RRMD.
Renal tubular dysfunctionHP1Extracted37589000heterochromatin protein 1 is an abnormally elevated gene related to DN and is further elevated by ferroptosis activators.
Renal tubular dysfunctionmiR21Extracted32266268meta-analyses of miRNAs downregulated by MSC-EVs, such as miR21, revealed the regulation of multiple pathways involved in kidney injury including fibrosis, inflammation, and apoptosis.
Renal tubular dysfunctionRNF20Extracted38068817Ring finger protein 20 (RNF20) is a ligase of nuclear receptor corepressor of peroxisome proliferator-activated receptors (PPARs). The transcriptome analysis revealed the involvement of RNF20-related transcriptome changes in PPAR signaling, lipid metabolism, and water transmembrane transporter under a high-fat diet and unilateral nephrectomy.
Renal tubular dysfunctionIGFBP3Extracted35370938the key hub genes IGFBP3 (adjusted P-value = 1.34x10-75 and log2(FC) = 2.64) interacted with 6 up-regulated and 12 down-regulated DE genes in the network that were enriched in the p53 signaling pathway.
Renal tubular dysfunctionAnxa2Extracted37955107Annexin A2 (Anxa2) is a calcium (Ca2+)-regulated phospholipid binding protein composed of a variable N-terminus and a conserved core domain.
Renal tubular dysfunctionNRF2Extracted37589000nuclear factor erythroid2-related factor2 (NRF2) was decreased in DN cell model, but increased under the action of ferroptosis activators. NRF2 silencing reversed the protective effects of HP1 inhibition on HK-2 cells.
Renal tubular dysfunctionALDOBVerified36052111, 31968011, 38534968, 38929922Renal involvement usually occurs in the form of proximal renal tubular acidosis and may lead to chronic renal insufficiency. ... fructose-bisphosphate aldolase B (aldolase B), and triosephosphate isomerase (TPI), decreased in the AA+P group.
Renal tubular dysfunctionATP6V0A4Verified40775604, 40299568, 34107482, 33033857, 32123165The ATP6V0A4 gene encodes the a4 subunit of Vacuolar H+-ATPase (V-ATPase), which mediates hydrogen ion transport across the membrane. ... mutations in ATP6V0A4 consistently result in a loss of function (LOF), impairing the hydrogen ion transport efficacy of V-ATPase and leading to distal renal tubular acidosis (dRTA) and sensorineural hearing loss. ... the V512L mutation was confirmed as a gain-of-function (GOF) mutation in the ATP6V0A4 gene. ... the p.S544L variant may be inherited in a dominant manner. ... ATP6V0A4 expression decreases during diabetes progression, contributing to tubular dysfunction and the development of diabetic kidney disease (DKD). These findings underscore the crucial role of ATP6V0A4 in maintaining renal acid-base balance, its influence on CKD progression, and the importance of genetic analysis for the early diagnosis and personalized management of dRTA.
Renal tubular dysfunctionATP6V1B1Verified34107482, 33033857, 40775604, 34609590Distal renal tubular acidosis (dRTA) is typically caused by defects in ATP6V0A4, ATP6V1B1, and SLC4A1, accounting for 60-80% of patients. ... Patients with WDR72 mutations show mild rate-dependent distal RTA with variable metabolic acidosis, and intact ability to acidify the urine on provocative testing. ... Hearing impairment (HI) is highly heterogeneous with over 123 associated genes reported to date, mostly from studies among Europeans and Asians. ... Variants in ATP6V1B1 only reported from North Africa.
Renal tubular dysfunctionATP7BVerified40306349, 38660122, 37681011, 37063668, 40629618, 33062584In vivo and in vitro data showed that lipid may induce mitochondrial dysfunction and promote cuproptosis in tubular epithelial cells, which was related to changes in copper transporter protein ATP7B. (PMID: 40306349); This review shed light on strong evidence for direct copper toxicity to renal tubular cells. Excessive tubular copper accumulation might present with various degrees of tubular dysfunction, ranging from mild hydroelectrolytic and acid-base disorders to complete Fanconi syndrome. (PMID: 38660122); We identified 25 potentially pathogenic ATP7B variants... Additionally, we described the thinning of the glomerular basement membrane as a rare pathologically damaging feature of Wilson's disease for the first time. (PMID: 37681011); The patient was diagnosed with WD... A genetic analysis identified a hemizygous variant (c.1718G > A, p. Gly573Asp) in COL4A5 and a homozygous variant (c.2975C > T, p. Pro992leu) in ATP7B. (PMID: 37063668); Patients with WD can present with hepatic dysfunction, neurological symptoms, rare hemolytic anemia, and renal tubular acidosis. (PMID: 40629618); Evaluation showed transaminitis, hypoalbuminemia, IgA hyperglobulinemia, and coagulation abnormalities... Homozygous pathogenic variant c.3207C>A (p.His1069Gln) of ATP7B was detected. (PMID: 33062584)
Renal tubular dysfunctionBCS1LVerified40332224, 37357212, 34662929The study describes a 27-month-old child with SNHL, proximal renal tubular acidosis, woolly hypopigmented hair, developmental delay, and metabolic alterations. (PMID: 40332224) Additionally, another study reports manifestations of mitochondrial respiratory chain complex III deficiency including renal tubular lesions in two affected children. (PMID: 37357212)
Renal tubular dysfunctionBSNDVerified32256370, 40612195, 35668994Type IVa BS, presents with severe salt wasting, sensorineural hearing loss, and impaired urinary concentrating ability. ... confirmed impaired urinary concentration of renal origin. ... due to a homozygous BSND variant
Renal tubular dysfunctionCA2Verified36637955Anti-carbonic anhydrase II (anti-CA II) antibody is correlated with renal tubular acidosis in pSS; ... anti-CA II antibody was most elevated in patients with defect in bicarbonate reabsorption, reflecting proximal renal tubular injury, rather than in patients with distal renal tubular acidosis as previously reported. In conclusion, anti-CA II antibody reflects renal (especially proximal renal tubular) and hematologic impairment...
Renal tubular dysfunctionCEP290Verified40570958xCEP290 morphants exhibited edema and dilated pronephric tubule, indicative of renal dysfunction. ... abnormal activation of IL-6/JAK/STAT3/FOSL1 signal axis is responsible for dilated pronephric tubule resembling cystic lesions observed in polycystic kidney disease of JSRD patients with CEP290 gene mutations.
Renal tubular dysfunctionCLCN5Verified36452359, 36578800, 38256038, 33015630, 35530822, 40555661, 38002082Dent disease is a group of inherited X-linked recessive renal tubular disorders... characterized by low molecular weight proteinuria (LMWP), nephrocalcinosis, hypercalciuria and renal failure. A novel deletion (c.1448delG) in the CLCN5 gene was identified... leads to Dent disease 1. Dent disease (DD) is a rare kidney disorder caused by mutations in the Cl-/H+ exchanger ClC-5... loss of ClC-5 function... impairs membrane traffic... causing low molecular weight proteinuria... Dent disease type 1 is an X-linked tubulopathy mainly caused by inactivating mutations in the chloride voltage-gated channel 5 (CLCN5) gene... structural dysfunction of renal tubules... hemizygous c.701dupA (p.Y234Ter) variant of the CLCN5 gene... underlay the pathogenesis of Dent disease... pre-mRNA Splicing Defects Caused by CLCN5... variants in the CLCN5 gene (Dent disease 1, DD1)...
Renal tubular dysfunctionCLCNKBVerified39405114, 33807568, 36671562, 39071140, 37063660, 32256370Mutations in the CLCNKB gene (1p36), encoding a basolateral chloride channel, ClC-Kb, cause type 3 Bartter's syndrome. ... The present data establish what we believe, are novel regulatory mechanisms of ClC-Kb activity and demonstrate nephron remodeling in man, caused by mutant ClC-Kb, with implications for renal electrolyte handling, blood pressure control, and kidney disease.
Renal tubular dysfunctionCLDN16Verified34151590, 38339056, 35354245, 40173198Patients with mutations in Cldn16 suffer from familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (FHHNC) which can lead to renal insufficiency. Mice lacking claudin-16 show hypomagnesemia and hypercalciuria, but no nephrocalcinosis. ... Claudin-16 and claudin-19 mediate paracellular transport of Na+, Ca2+, and Mg2+ in the TAL, where the expression of claudin-3/16/19 and claudin-10b are mutually exclusive. The claudin-16 or -19 mutation causes familial hypomagnesemia with hypercalciuria and nephrocalcinosis.
Renal tubular dysfunctionCNNM2Verified35806288Renal hypomagnesemia syndromes involving CNNM2 protein pathogenic variants are associated with variable degrees of neurocognitive dysfunction and hypomagnesemia. Here, we report a family with a novel CNNM2 p.Pro482Ala variant, presenting with overt hypomagnesemia and mild neurological involvement (autosomal dominant renal hypomagnesemia 6, HOMG6, MIM# 613882).
Renal tubular dysfunctionCPT1AVerified35408745, 35883847, 40522438, 40500698, 39038923, 32733282, 37377862, 40076489Transcriptomic and metabolomic analyses revealed that abnormal signaling pathways were involved in EMT and FAO disorders. RTE cell experiments showed that TGF-beta could inhibit the activity of Cpt1a, resulting in ATP depletion and lipid deposition. Cpt1a inhibitor induced EMT, while Cpt1 substrate or rhein inhibited EMT, indicating that Cpt1a-mediated FAO dysfunction is essential for RTE cells EMT. Further studies showed that Cpt1a activity were regulated by SirT1/STAT3/Twist1 pathway. Rhein inhibits RTE cell EMT by promoting Cpt1a-mediated FAO through the SirT1/STAT3/Twist1 pathway. Surprisingly and importantly, our experiments showed that FAO depression occurs before EMT, and EMT is one of the results of FAO depression. (PMID: 35408745); The study findings revealed that SIRT3 is downregulated in renal tubules during diabetes and interferes with the activity of CPT1a through deacetylation, disrupting fatty acid metabolism in the tubules and ultimately leading to tubular injury. (PMID: 40522438); This study is the first to confirm MFN2 as a target for renal protection by bavachin. Mechanistically, Bavachin alleviated cisplatin-induced lipid accumulation and apoptosis by upregulating MFN2 expression, which activated CPT1a to promote mitochondrial FAO. (PMID: 40500698); Astragaloside IV (ASIV) ameliorates oxidative stress-associated proximal tubular injury by upregulating CPT1A-mediated K99 succinylation of HSD17B10 to maintain RNase P activity. (PMID: 39038923); Renal proximal tubular cells are high energy-demanding cells mainly relying on fatty acid oxidation. In stress conditions, such as transient hypoxia, fatty acid oxidation (FAO) decreases and carbohydrate catabolism fails to compensate for the energy demand. In this scenario, the surviving tubular cells exhibit the peculiar phenotype associated with fibrosis that is the histological manifestation of a process culminating in chronic and end-stage kidney disease. Genome-wide transcriptome analysis revealed that, together with inflammation, FAO is the top dysregulated pathway in kidney diseases with a decreased expression of key FAO enzymes and regulators. Another evidence that links the derangement of FAO to fibrosis is the progressive decrease of the expression of peroxisome proliferator-activated receptor alpha (PPARalpha) in aged people, that triggers the age-associated renal fibrosis. To allow FAO completion, a coordinate network of enzymes and transport proteins is required. Indeed, the mitochondrial inner membrane is impermeable to fatty acyl-CoAs and a specialized system, well known as carnitine shuttle, is needed for translocating fatty acids moieties, conjugated with carnitine, into mitochondrial matrix for the beta-oxidation. The first component of this system is the carnitine palmitoyltransferase 1 (CPT1) responsible for transfer acyl moieties to carnitine. Several studies indicated that the stimulation of CPT1 activity and expression has a protective effect against renal fibrosis. (PMID: 32733282); Impact of renal tubular Cpt1a overexpression on the kidney metabolome in the folic acid-induced fibrosis mouse model. (PMID: 37377862); Integrin-Linked Kinase (ILK) Promotes Mitochondrial Dysfunction by Decreasing CPT1A Expression in a Folic Acid-Based Model of Kidney Disease. (PMID: 40076489)
Renal tubular dysfunctionCTNSVerified33625696, 34502306, 40111391, 38545650, 38127152, 32354056, 35011573, 38995697Cystinosis is a rare, incurable, autosomal recessive disease caused by mutations in the CTNS gene. This gene encodes the lysosomal cystine transporter cystinosin, leading to lysosomal cystine accumulation in all cells of the body, with kidneys being the first affected organs. The current treatment with cysteamine decreases cystine accumulation, but does not reverse the proximal tubular dysfunction, glomerular injury or loss of renal function.
Renal tubular dysfunctionEHHADHVerified34349672, 38879653, 38042745, 38310177, 40242153Mutation of EHHADH...results in decreased ATP synthesis and a consecutive transport defect. In contrast, mutations of GATM...leave ATP synthesis unaffected... (PMID: 34349672). EHHADH deficiency...accelerated renal injury...modulator of pexophagy (PMID: 38879653). ...mutations in six genes [...] GATM, EHHADH [...] (PMID: 38310177). ...the recurrent p.Glu3Lys variant in EHHADH is responsible for Fanconi syndrome [...] (PMID: 40242153).
Renal tubular dysfunctionFAHVerified33598652, 36369907, 34704422, 35800472The main biochemical abnormalities were elevated plasma tyrosine, serum transaminases and prothrombin time, and low serum phosphorous with elevated alkaline phosphatase compatible with hypophosphatemic rickets secondary to renal tubular dysfunction. ... Renal tubular dysfunction improved in all patients within the first week of starting nitisinone. ... The proband also showed apparent renal injury, including glomerular filtration barrier dysfunction and abnormal tubular protein reabsorption. These FAH mutations were inherited in an autosomal recessive manner and resulted in abnormal FAH protein expression and dysfunction, leading to fumarylacetoacetate (FAA) accumulation.
Renal tubular dysfunctionFAM20AVerified37675434, 37228816Enamel Renal Syndrome (ERS) (OMIM # 204690) is a rare genetic condition characterised by hypoplastic amelogenesis imperfecta, failed tooth eruption, intra-pulpal calcifications, gingival enlargement and occasionally nephrocalcinosis. In this case series, we report on four unrelated patients with a confirmed molecular diagnosis of ERS (FAM20A pathogenic variants) from Sub-Saharan Africa. ... One patient presented with nephrocalcinosis and abnormal kidney function, one had reduced kidney size with normal kidney function, and two had no renal abnormalities.
Renal tubular dysfunctionGATA3Verified37881737, 33163915Both abstracts mention the association of GATA3 mutations with Hypoparathyroidism, Deafness, and Renal dysplasia (HDR) syndrome. The first abstract describes a novel frameshift mutation in GATA3 in a patient with renal dysplasia and chronic kidney disease. The second abstract reports a patient with a GATA3 mutation diagnosed with HDR syndrome, including renal calcification and dysfunction, and improved renal function after kidney transplantation.
Renal tubular dysfunctionGATMVerified36148635, 34349672, 34071541, 38042745, 39544690, 38310177, 35784691Renal Fanconi syndrome (RFS) is a generalised disorder of the proximal convoluted tubule...We identified a novel variant in GATM; c.965G>C p.(Arg322Pro) segregating dominantly in the mother and daughter. (PMID: 36148635); 'Distinct Mitochondrial Pathologies Caused by Mutations of the Proximal Tubular Enzymes EHHADH and GATM...' (PMID: 34349672); 'Inherited non-FGF23-mediated phosphaturic disorders: A kidney-centric review.' (PMID: 38042745) discusses GATM as an underlying gene for Fanconi renotubular syndrome. 'Reduced guanidinoacetate in plasma of patients with autosomal dominant Fanconi syndrome due to heterozygous P341L GATM variant...' (PMID: 39544690) and 'Inherited Fanconi renotubular syndromes: unveiling the intricacies of hypophosphatemic rickets/osteomalacia.' (PMID: 38310177) further confirm GATM's role in Fanconi syndrome, a form of renal tubular dysfunction.
Renal tubular dysfunctionGNASVerified33758748, 37886236In the first case, the patient had renal tubular dysfunction and an activating point mutation (c.601C>T, p.Arg201Cys) in the GNAS gene. In the second study, extrahepatic manifestations such as renal tubular dysfunction could occur simultaneously with jaundice in MAS cases with GNAS mutations.
Renal tubular dysfunctionHBBVerified34872508, 36409722In the study with PMID 36409722, Sickle cell anemia (SCA) is caused by a single point variation in the beta-globin gene (HBB): c.20A> T (p.Glu7Val), in homozygous state. SCA is characterized by sickling of red blood cells in small blood vessels which leads to a range of multiorgan complications, including kidney dysfunction. The study shows a relatively high proportion of SCA nephropathy among patients living with SCA in Senegal. Microglucosuria, proteinuria, tubular proteinuria, microalbuminuria, hyposthenuria and glomerular hyperfiltration are the most prevalent biomarkers of nephropathy in this group of Senegalese patients with SCA.
Renal tubular dysfunctionHNF1BVerified36522156, 33434175, 32708349, 36672242Mutations in HNF1B are the most common monogenic causes of congenital renal malformations. ... HNF1B is essential for reprogramming mouse fibroblasts to induced renal tubular epithelial cells ... cross-species-conserved transcriptional targets were dysregulated in hnf1b CRISPR-depleted Xenopus embryos, confirming their dependence on hnf1b.
Renal tubular dysfunctionHNF4AVerified37308774, 35280445, 38042745, 37766831, 39019110The corresponding disorders are Renal Fanconi Syndrome... with the underlying genes encoding for GATM, EHHADH, HNF4A and NDUFAF6. (PMID: 38042745); ...present a clinical case... characterized by the association of renal Fanconi syndrome... Genetic investigations evidenced the recurrent heterozygous missense HNF4A (p.Arg76Trp) variant. (PMID: 35280445); ...features of Glycogen Storage Disease... renal Fanconi syndrome. (PMID: 37766831); ...HNF4alpha-mediated FGF21 sensitivity. (PMID: 39019110)
Renal tubular dysfunctionLRP2Verified32172431, 35528850Megalin is well known for its role in the reabsorption of proteins from the ultrafiltrate. Recent studies suggest that megalin also reabsorbs renin and angiotensinogen. ... megalin might also contribute to renal angiotensin production, as evidenced from studies in megalin knockout mice. ... urinary renin-angiotensin system components reflect diminished reabsorption rather than release from renal tissue sites. ... alterations in renal renin levels or megalin-dependent signaling need to be ruled out before concluding that angiotensin production at renal tissue sites is truly megalin dependent. ... megalin-mediated renin/angiotensinogen transcytosis (allowing interstitial angiotensin generation).
Renal tubular dysfunctionMMUTVerified37243446, 33453710Methylmalonic Acidemia (MMA) is a heterogenous group of inborn errors of metabolism caused by a defect in the methylmalonyl-CoA mutase (MMUT) enzyme... chronic kidney disease... Biomarker concentrations are higher in patients with the severe mut0 - and cblB-type MMA... show a significant response post-liver transplant.
Renal tubular dysfunctionNDUFA1Verified39306640, 39932912The IDH1-R132H mutation increases methylation of the Ndufa1 promoter, thereby suppressing NDUFA1 transcription and translation. This suppression disrupts NDUFA1's interaction with FSP1, reducing its resistance to cisplatin-induced tubular epithelial cell death. As a consequence, ROS accumulates, lipid peroxidation occurs, and ferroptosis is triggered, thereby promoting acute kidney injury.
Renal tubular dysfunctionNDUFAF6Verified38042745Several inherited forms of Fanconi renotubular syndrome (FRTS) have also been described with the underlying genes encoding for GATM, EHHADH, HNF4A and NDUFAF6.
Renal tubular dysfunctionNDUFS1Verified33663503, 40797341PMID 33663503: 'STZ-induced alpha-2u globulin nephropathy during diabetic kidney disease in association with deterioration of pedicels, renal tubular damage with adaptation and mitochondrial driven apoptosis.' and 'significantly upregulated ... NDUFS-1 proteins ...' in STZ-induced diabetic rats. PMID 40797341: 'qPCR confirmed FZ-induced downregulation of NDUFS1 ...' in amphotericin B-induced nephrotoxicity. NDUFS1 is part of mitochondrial complex I, linked to renal tubular dysfunction in both diabetic and drug-induced kidney disease models.
Renal tubular dysfunctionNDUFS2Verified35414767The context mentions that CLDN10 overexpression increases the levels of NDUFS2... thereby suppressing the growth and metastasis of ccRCC through increasing the levels of NDUFS2... and causing mitochondrial dysfunction. This suggests a link between NDUFS2 and mitochondrial dysfunction, which is a component of renal tubular dysfunction.
Renal tubular dysfunctionNDUFV1Verified37029501NDUFV1 was reduced in kidneys of renal ischemia/reperfusion (I/R) mice. ... All these detrimental outcomes were attenuated by increased expression of NDUFV1 in kidneys. ... NDUFV1 improved the integrity and function of mitochondria, leading to reduced oxidative stress and cell apoptosis.
Renal tubular dysfunctionPCVerified39836535Pyruvate carboxylase (PC) is a catalytic enzyme located within the mitochondria that is intricately linked with mitochondrial damage and metabolism. In the present study, the downregulation of PC in various fibrotic animal and human kidney samples is demonstrated. Renal proximal tubule-specific Pcx gene knockout mice (PcxcKO) has significant interstitial fibrosis compared to control mice, with heightened expression of extracellular matrix molecules. This is further demonstrated in a stable PC knock-out RTEC line.
Renal tubular dysfunctionNOTCH2Verified36294921The most substantial differences were observed in tubular epithelial cells in the period of 2 weeks after induction, with higher Snail and Wnt4 expression in PCT and increased Snail and Notch2 expression in DCT of diabetic animals (p < 0.0001; p < 0.001).
Renal tubular dysfunctionNPHP1Verified34246230, 40776899, 35482924, 33306870, 35264234Nephronophthisis (NPHP) is a chronic tubular interstitial disorder... genetic analysis of the NPHP1 gene showed complete deletion of this gene, leading to a definitive diagnosis of NPHP. ... NPHP is a recessive tubulointerstitial nephropathy... NPHP1 encodes a protein playing key functions at the primary cilium and cellular junctions. ... altered expression in EGFR signaling, extracellular components and adherens junctions, consistent with nephrocystin-1's known roles. ... Urinary renal epithelial cells for NPHP1 phenotyping... transcriptional profiling post-treatment showed AG556 reversed the disease signature more effectively that alprostadil. ... prostaglandin E2 receptor agonists can ameliorate several of the pleotropic phenotypes caused by the absence of NPHP1; this opens their potential as a first therapeutic option for juvenile NPH-associated ciliopathies. ... decreased expression of INPP5E specifically in the primary cilium, coupled with disorganized cilia morphology, suggests a novel role of NPHP1 that it is involved in regulating ciliary phosphoinositide composition in the ciliary membrane of renal tubular cells. ... urine-derived renal tubular epithelial cells (URECs) from patients with NPHP genes... distinct and reproducible epithelial properties of URECs. ... the cells from patients carrying PKHD1 variants were characterized by a high incidence of defective morphogenesis of monolayered spheroids-a property proposed to be suitable for corrective intervention.
Renal tubular dysfunctionOCRLVerified31811534, 31676724, 32427950, 35074682, 31707643, 33194915Lowe syndrome and Dent-2 disease are caused by mutations in the OCRL gene, which encodes for an inositol 5-phosphatase. The renal phenotype associated with OCRL mutations typically comprises a selective proximal tubulopathy, which can manifest as Fanconi syndrome in the most extreme cases. (PMID: 31811534) Mutations in OCRL causes Lowe syndrome (LS), a rare and complex disorder characterized by congenital cataracts, renal tubular dysfunction, and mental retardation. (PMID: 35074682) The oculocerebrorenal disorder of Lowe syndrome is an X-linked mutation in the gene oculocerebrorenal syndrome of Lowe 1 (OCRL), characterized by the triad of congenital cataracts, severe intellectual impairment, and renal tubular dysfunction. (PMID: 31707643) Dent disease is an X-linked recessive renal tubular disorder characterized by proximal tubule dysfunction. Typical features include low molecular weight proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis, rickets, and chronic renal failure. We present a case of a 6-year-old boy with nephrotic proteinuria without hypoalbuminemia or edema... The next generation sequencing identified pathogenic variant in OCRL gene causing Dent disease type 2. (PMID: 33194915)
Renal tubular dysfunctionPHEXVerified33107440, 36553684, 33660084, 38950880, 40295317, 40243526PHEX dysfunction results in increased production and secretion of the phosphaturic hormone fibroblast growth factor 23 (FGF23) from bone. The consequences of FGF23 excess are renal phosphate wasting and decreased calcitriol synthesis, leading to hypophosphatemia and subsequently rickets and osteomalacia. (PMID: 40295317)
Renal tubular dysfunctionPHKA2Verified34277355Here we describe the clinical presentation and course of a newborn boy with profound neonatal lactic and metabolic acidosis, renal tubulopathy, and sensorineural hearing loss (SNHL) diagnosed with GSD IXalpha2 through exome sequencing.
Renal tubular dysfunctionPIGAVerified32357555The origin of PNH is the somatic mutation in the X-linked phosphatidylinositol glycan class A (PIG-A) gene located on Xp22: this condition leads to the production of clonal blood cells with a deficiency in those surface proteins that protect against the lytic action of the activated complement system. ... Hemolysis and subsequent hemosiderin accumulation in tubular epithelium cells induce tubular atrophy and interstitial fibrosis.
Renal tubular dysfunctionPMM2Verified35154715, 35281664We report two patients with PMM2-CDG who developed end stage renal disease (ESRD). Renal abnormalities of clinical significance have only been reported in about 6% of patients with PMM2-CDG...
Renal tubular dysfunctionSEC61A1Verified39976632, 36531871, 34519781, 38027261Variants in UMOD, MUC1, REN, and SEC61A1 were identified in 52 patients from 40 families (18, 16, 5, and 1 family, respectively).
Renal tubular dysfunctionSLC12A3Verified35801212, 37197138, 33024786, 36945458, 32758178SLC12A3 gene variants are associated with diabetic nephropathy; however, their association with hypertensive nephropathy remains unknown. We aimed to investigate the association between SLC12A3 gene polymorphisms and renal function in patients with hypertension. ... Conclusion: SLC12A3 polymorphisms are associated with renal function in Chinese patients with hypertension. ... Mutations in the SLC12A3 gene have been reported to cause Gitelman syndrome (GS), characterized by hypokalemic metabolic alkalosis. ... Gitelman syndrome is a rare salt-losing renal tubular disorder associated with mutation of SLC12A3 gene, which encodes the Na-Cl co-transporter (NCCT). Gitelman syndrome is characterized by hypokalemia, metabolic alkalosis, hypomagnesemia, hypocalciuria, and renin-angiotensin-aldosterone system (RAAS) activation. ... These clinical manifestations and genotypes were consistent with the diagnostic criteria of GS. ... This study expands the mutation spectrum of SLC12A3 gene in GS.
Renal tubular dysfunctionSLC2A2Verified34828390, 33269285, 31816104Fanconi-Bickel syndrome (FBS) is a very rare but distinct clinical entity with the combined features of hepatic glycogen storage disease, generalized proximal renal tubular dysfunction with disproportionately severe glucosuria... Here, we report five cases... with pathogenic variants on both GLUT2 (SLC2A2) alleles. ... Our results provide further evidence for a genotype-phenotype correlation in patients with GLUT2 variants; non-functional variants result in the full picture of FBS while dysfunctional variants may result in milder presentations, even glucosuria only, without other typical signs of FBS.
Renal tubular dysfunctionSLC34A1Verified40225330, 38042745Molecular analysis identified a de novo monoallelic mutation (C.1006 + 1 G>A) in the solute carrier family 34 member 1 (SLC34A1) gene encoding a protein involved in actively transporting phosphate into cells via Na+ cotransport in the renal brush border membrane. ... inherited non-FGF23 mediated phosphaturic disorders are due to ... loss-of-function variants in SLC34A1 ... corresponding disorders are Renal Fanconi Syndrome ...
Renal tubular dysfunctionSLC34A3Verified38042745, 35842615, 37680384, 36692815Phosphate is freely filtered by the glomerulus and reabsorbed exclusively in the proximal tubule by two key transporters, NaPiIIA and NaPiIIC, encoded by SLC34A1 and SLC34A3, respectively. ... inherited non-FGF23 mediated phosphaturic disorders are due to ... loss-of-function variants in SLC34A1 or SLC34A3 ... The corresponding disorders are ... Hereditary Hypophosphataemic Rickets with Hypercalciuria ...
Renal tubular dysfunctionSLC4A1Verified36776909, 34107482, 32154456, 33033857The genetic and clinical characteristics of patients with distal renal tubular acidosis (dRTA) caused by SLC4A1 mutations have not been systematically recorded before. Here, we summarized the SLC4A1 mutations and clinical characteristics associated with dRTA... The patients with recessive dRTA are generally more severely affected than that with dominant SLC4A1 mutations. (PMID: 36776909). Additionally, mutations in SLC4A1 are linked to impaired urinary acidification leading to dRTA, as noted in PMID: 34107482 and PMID: 32154456.
Renal tubular dysfunctionSLC4A4Verified37123759, 39273556The child had a known case of proximal tubular dysfunction (homozygous mutation in the SLC4A4 gene).
Renal tubular dysfunctionSLC7A7Verified32504080, 37927490, 37486182, 31705628, 34095032Histopathological assessment revealed loss of brush border and lipid vacuolation in the renal cortex of Slc7a7Lbu/Lbu mice, which combined with aminoaciduria suggests proximal tubular dysfunction. ... Our case indicates that proximal and distal tubular damages are notable findings in patients with LPI.
Renal tubular dysfunctionSTAT3Verified32281218, 37525933, 35664078, 38411015, 33096924In the study with PMID 32281218, it was found that the SDF-1alpha/CXCR4 pathway was significantly suppressed in diabetic tubules, and after Sita treatment, this signaling pathway was restored, and the mitochondrial dynamics was improved. Furthermore, a direct interaction between STAT3 and OPA1 was found in the mitochondria of tubular cells, suggesting a possible link between DPP4-mediated SDF-1alpha/CXCR4/STAT3 signaling and mitochondrial dysfunction in diabetic tubular cells. In PMID 37525933, inhibition of PRMT1 in SI-AKI mice decreased the expression of TGF-beta1 and phosphorylation of Smad3 in the renal cortex, and downregulated the expression of sIL-6R and phosphorylation of STAT3 in the medulla. In PMID 35664078, Mecp2 bound to the promoter of proinflammatory cytokine Il-6 to negatively regulate its expression, thus inhibiting STAT3 activation. In PMID 38411015, the aberrant activation of the mechanistic target of rapamycin (mTOR) and the signal transducer and activator of transcription 3 (STAT3) signaling pathways were observed in septic AKI, and inhibition of STAT3 significantly improved renal function and reduced apoptosis and inflammation.
Renal tubular dysfunctionSURF1Verified38858654SURF1-rs183853102 was associated with diabetic nephropathies in UK-ROI.
Renal tubular dysfunctionTMEM126BVerified27374774the severe multisystem presentation (chronic renal failure and cardiomyopathy) in infancy
Renal tubular dysfunctionVIPAS39Verified35281816, 39736737, 37202112, 35151346, 37062417, 35761207Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome, a rare autosomal recessive disorder, exhibits genetic heterogeneity with the VIPAS39 gene pathological variants being a distinct contributor. ... The identified novel VIPAS39 pathological variants (c.762G > A; c.1064_1082delinsAGTG) emphasize the complex phenotypic expression of ARC syndrome. ... Our report aligns with others noting milder ARC courses and emphasizes the value of genetic testing, especially in atypical presentations.
Renal tubular dysfunctionVPS33BVerified33029437, 31463585, 35281816, 36568436, 35761207, 34999573, 35151346, 37062417, 39736737All abstracts discuss the association of VPS33B mutations with renal tubular dysfunction, a core feature of ARC syndrome. For example, PMID 33029437 reports renal tubular acidosis and Fanconi syndrome; PMID 31463585 describes distal renal tubular acidosis and nephrotic-range proteinuria; PMID 35281816 and others mention renal dysfunction as part of the ARCS phenotype.
HemianopiaBRAFVerified39664200The patient came in with bilateral homonymous hemianopsia... pathology showed a BRAF V600E mutated papillary craniopharyngioma. The use of targeted therapies... shows improvement after treatment with BRAF and MEK inhibitors.
HemianopiaPOLGVerified40062103The patient suffered from POLG-related neuropathy since the age of 14 and was admitted for her first SLE, which manifested clinically as hemianopia...
Arterial thrombosisSERPINC1Both37124980, 35720094The detection rates of the pathogenic variant in ischemic stroke or arterial thrombosis groups were both higher than those in the venous thrombosis-only group (54.5%).
Arterial thrombosisSIRT6Extracted38186648Platelets isolated from SIRT6-knockout mice (SIRT6-/-) exhibit a notable augmentation in thrombin-induced platelet activation, aggregation, and clot retraction.
Arterial thrombosisNF-kappaBExtracted32646046Auraptene attenuated NF-kappaB activation such as IkappaBalpha and p65 phosphorylation and reversed IkappaBalpha degradation in collagen-activated platelets.
Arterial thrombosisJAK2Extracted37350087The total and annual incidences of arterial thrombosis in JAK2-positive patients were 18.4% and 2.7%, respectively.
Arterial thrombosisPPARgammaExtracted34658891The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma) plays an important role in lipid metabolism, inflammation, and apoptosis.
Arterial thrombosisAKT1Verified37171028, 36469488, 31797367, 35526496, 32605190, 33086881, 33027814si-JCAD HAECs showed increased levels of phosphoinositide 3-kinases (PI3K)/ proteinkinase B (Akt) activation... The PI3K/Akt pathway inhibitor-wortmannin-prevented the effect of JCAD silencing on TF and PAI-1, indicating a causative role. Also, co-immunoprecipitation unveiled a direct interaction between JCAD and Akt. Confirming in vitro findings, PI3K/Akt and P-yes-associated protein levels were higher in Jcad-/- animals. Additionally, Apold1-/- mice displayed reduced phosphorylation of Akt... Moreover, memory-like response of platelets was also found to be related to PI3K/AKT signaling pathway... mSGF inhibited phosphorylation of PI3K/protein kinase B (Akt)... limiting PKM2 dimer formation downregulated phosphatidylinositol 3-kinase (PI3K)-mediated protein kinase B or serine/threonine-specific protein kinase (Akt)/GSK3 signaling... limiting PKM2 dimerization downregulated PI3K-mediated Akt/GSK3 signaling... Wild-type mice treated with ML265 were less susceptible to arterial thrombosis... These findings reveal a major role for PKM2 in coordinating multiple aspects of platelet function... and implicate PKM2 as a potential target for antithrombotic therapeutic intervention.
Arterial thrombosisCALRVerified36788855, 33280271, 40278216, 36611455, 33275803, 37457287The 5-year thrombosis-free survival (TFS) rate was 83.8%, 91.6% and 93.9% for the JAK2V617F, CALR-type 1 and CALR-type 2 groups, respectively (P = .002). Comparing CALR-type 1 and CALR-type 2 groups, TFS for venous thrombosis was lower in CALR-type 1 (P = .046), with no difference in TFS for arterial thrombosis observed. The cumulative incidence of thrombosis was significantly different comparing JAK2V617F vs CALR-type 2 groups but not JAK2V617F vs CALR-type 1 groups. Moreover, CALR-type 2 mutation was a statistically significant protective factor for thrombosis with respect to JAK2V617F in multivariate logistic regression (OR: 0.45, P = .04) adjusted by age. CONCLUSIONS: Our results suggest that CALR mutation type has prognostic value for the stratification of thrombotic risk in ET patients.
Arterial thrombosisCBSVerified32612202, 33868930, 33362545Cystathionine beta-synthase (CBS)-deficient patients are prone to vascular thrombosis. ... Proteins involved in blood coagulation and complement/coagulation cascades represented a greater fraction of the differentiating proteins in CBS-/- patients (51%) than in Cbs-/- mice (21%). The Coagulation System was affected stronger in CBS-/- humans than in Cbs-/- mice (- log[P-value] = 15 vs. 10, respectively).
Arterial thrombosisCCR1Verified39188323The objectives of our study were to identify potential biomarkers for PV-related AS and to explore the molecular biological association between PV and AS...CCR1 and MMP9 were selected as potential biomarkers...These biomarkers could regulate Toll-like signaling, NOD-like signaling, and chemokine signaling pathways associated with AS. Finally, we determined that these potential biomarkers had a strong correlation with macrophage M0 infiltration. Further, the potential biomarkers were highly expressed in macrophages from patients with AS.
Arterial thrombosisF2Verified33527057, 36999115, 33437541A prothrombin gene mutation (PTGM) is the second common cause of inherited thrombophilia after factor V Leiden. Hypercoagulable conditions have traditionally been reported to cause venous thrombosis, while arterial thrombosis is a rare occurrence. Studies have reported cases of preexisting hypercoagulable conditions associated with PTGM presenting as thromboembolism; however, none have been recorded with isolated PTGM. A 55-year-old patient was diagnosed to have unilateral popliteal artery thrombosis. ... The case is being reported for its uniqueness since this is the first documented case of popliteal artery thrombosis in a patient with isolated PTGM. Prothrombin gene mutation (prothrombin thrombophilia) is an inherited disorder that increases the risk of venous thrombosis. However, limited data exist on the risk of arterial stroke in an at-risk population. ... We report a 10-year-old Hispanic girl who presented to the emergency department with a seizure. ... Imaging revealed internal carotid artery (ICA) dissection with thrombus, ... Genetic testing showed a prothrombin gene mutation (G20210A). ... Prothrombin gene mutation was the most likely explanation for her stroke in the absence of a significant risk factor for arterial thrombosis or an underlying hypercoagulable disorder. ... In this single missense mutation, guanine is substituted by adenine base pair in the nucleotide position 20210 of the 3'-untranslated region of the prothrombin gene, resulting in abnormal thrombin production predisposing to both arterial or venous thrombosis.
Arterial thrombosisFASVerified36611455Some polymorphisms within XRCC1, FBG, F2, F5, F7, F12, MMP9, HPA5, MTHFR, SDF-1, FAS, FASL, TERT, ACE, and TLR4 genes may also play a role in MPN manifestation.
Arterial thrombosisIL10Verified36211709, 37112918In PMID 36211709, the baseline levels of interleukin-10... were found to differ statistically among the four groups (p < 0.05). Compared with that in the control group, the level of interleukin-6 in patients with arterial thrombosis increased by six-fold... In PMID 37112918, the levels of IL1b, IL-10, and IL2 were higher in the group that had thrombotic events.
Arterial thrombosisMPLVerified33280271, 36611455, 37457287Several lines of evidence indicate that mutations in JAK2, MPL, TET2 and ASXL1 gene and polymorphisms in several clotting factors (GPIa, GPIIa, and GPIIIa) are associated with the occurrence and prevalence of thrombosis in MPN patients. (PMID: 36611455)
Arterial thrombosisPIGAVerified32357555The origin of PNH is the somatic mutation in the X-linked phosphatidylinositol glycan class A (PIG-A) gene located on Xp22: this condition leads to the production of clonal blood cells with a deficiency in those surface proteins that protect against the lytic action of the activated complement system.
Arterial thrombosisPROS1Verified38398746, 40903772, 32266186, 40084314, 38292964, 35090264The study in PMID 38398746 reports a significant decrease of plasmatic PROS1 in coagulopathic SARS-CoV-2 positive patients, suggesting PROS1 cleavage by viral PLpro leads to loss of anticoagulant function, contributing to thrombotic events. Additionally, PMID 32266186 identifies a PROS1 gene variant (T630I) in a patient with catastrophic arterial thrombosis, indicating a genetic predisposition. PMID 40084314 and 38292964 further associate PROS1 deficiency with arterial thrombosis cases.
Arterial thrombosisPTPN22Verified35767715The study shows that PTPN22 deficiency significantly shortened tail-bleeding time and accelerated arterial thrombus formation. PTPN22-deficient platelets exhibited enhanced platelet aggregation... and clot retraction. ... inhibition of PTPN22 enhanced human platelet aggregation... and increased PDE5A phosphorylation (Ser92). In conclusion, our study shows a novel role of PTPN22 in platelet function and arterial thrombosis.
Arterial thrombosisSH2B3Verified34846914, 35877838, 38096361LNK/SH2B3 inhibits Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling... Lnk-deficient mice displayed accelerated carotid artery thrombosis... CONCLUSIONS: Hematopoietic Lnk deficiency promotes... arterial thrombosis... LNK(R262W) reduces LNK function... increases coronary artery disease risk... arterial thrombosis... essential role of eosinophil LNK in suppression of arterial thrombosis.
Arterial thrombosisTET2Verified32290079, 38190984, 38148396, 35733370, 36431092, 34130694Prior arterial thrombosis, age >60 years, cardiovascular risk factors and presence of TET2 or DNMT3A mutations were independently associated with arterial thrombosis in multivariable analysis. ARTS, an ARterial Thrombosis Score, based on these four factors, defined low- (0.37% patients-year) and high-risk (1.19% patients-year) patients.
Arterial thrombosisTLR4Verified36147190, 33322041, 36611455, 36636919PMID 36147190: 'Inflammatory mediator toll-like receptor (TLR)-4 plays a critical role in NIH, arterial thrombosis, and stenosis.'; PMID 33322041: 'MF significantly reduced the increased inflammatory signal of ... toll-like receptor 4 (TLR4)... and improved blood flow by inhibiting occlusion and thrombus formation.'; PMID 36636919: 'Study identifies TLR4-dependent pathways promoting platelet-dependent thrombus growth in SARS-CoV-2, suggesting TLR4 inhibition to counteract thrombosis.'
Arterial thrombosisTP53Verified37626784recent experimental evidence has demonstrated the involvement of somatically mutated TP53 genes with a high variant allele frequency (VAF) in PAD development and prognosis
Parietal foraminaTWIST1ExtractedEur J Hum Genet16251895Saethre-Chotzen syndrome (SCS) is an autosomal dominant craniosynostosis syndrome... caused by loss-of-function mutations of the TWIST 1 gene.
Parietal foraminaMSX2BothNat Genet10742104, 23593111, 23145080, 38447947FPP is an inherited disorder and arises due to mutations in either Msh homeobox 2 (MSX2) or aristaless-like homeobox 4 (ALX4) genes.
Parietal foraminaALX4BothClin Dysmorphol15057119, 15702131, 33269135, 38481039, 38447947, 33126574, 36555772PMID: 33269135: '...related to PFM due to mutations in the ALX4 homeobox gene.'; PMID: 38447947: '...arising due to mutations in either Msh homeobox 2 (MSX2) or aristaless-like homeobox 4 (ALX4) genes.'; PMID: 33126574: '...haploinsufficiency of three genes, ALX4 (parietal foramina)...'
Parietal foraminaEXT2ExtractedEur J Hum Genet15702131the deletion therefore includes EXT2, ALX4, WT1 and PAX6.
Parietal foraminaWT1ExtractedEur J Hum Genet15702131the deletion therefore includes EXT2, ALX4, WT1 and PAX6.
Parietal foraminaPAX6ExtractedEur J Hum Genet15702131the deletion therefore includes EXT2, ALX4, WT1 and PAX6.
Parietal foraminaBMPR1AExtractedDis Model Mech22773757Bone morphogenetic protein (BMP) receptor type 1A (BMPR1A) mutations are associated with facial dysmorphism...
Parietal foraminaFGFR2VerifiedThe mutation in FGFR2 is associated with the development of parietal foramina. This is supported by the study which found that mutations in the fibroblast growth factor receptor 2 gene lead to the formation of parietal foramina.
Parietal foraminaZIC1Verified32975022It can result from an isolated, enlarged parietal foramina or it can present as part of skeletal dysplasia syndromes associated with poor mineralization such as hypophosphatasia, osteogenesis imperfecta type II, and Saethre-Chotzen syndrome. ... Our observation adds to the clinical spectrum of ZIC1 related skull malformation.
Ocular painTRPV1ExtractedPain Rep39839966transient receptor potential cation channel subfamily V member 1 (TRPV1)
Ocular painTRPM8ExtractedPain Rep39839966transient receptor potential cation channel subfamily M (melastatin) member 8
Ocular painc-FosExtractedPain Rep39839966c-Fos
Ocular painATF3ExtractedPain Rep39839966activating transcription factor 3 (ATF3)
Ocular painNrf2ExtractedCells36552824Nrf2 activator through Keap1 protein inhibition
Ocular painKeap1ExtractedCells36552824Nrf2 activator through Keap1 protein inhibition
Ocular painMUC4ExtractedBMC Ophthalmol36522696decreased mucin (MUC) 4 expression
Ocular painZO-1ExtractedBMC Ophthalmol36522696decreased ZO-1 levels after the ES in vitro
Ocular painMUC5ACExtractedBMC Ophthalmol36522696decreased secretion of MUC5AC from the conjunctiva
Ocular painRictorExtractedSci Rep32165657Rictor, the rapamycin-insensitive complex-2 of mTOR (mTORC2)
Ocular painmTORC2ExtractedSci Rep32165657Rictor, the rapamycin-insensitive complex-2 of mTOR (mTORC2)
Ocular painNav1.8ExtractedInvest Ophthalmol Vis Sci34787642Nav1.8 expressing corneal afferents
Ocular painNGFExtractedChonnam Med J35169558nerve growth factor (NGF)
Ocular painCGRPExtractedChonnam Med J35169558calcitonin gene-related peptide (CGRP)
Ocular painSubstance PExtractedChonnam Med J35169558Substance P
Ocular painneuropeptide YExtractedChonnam Med J35169558neuropeptide Y
Ocular painvasoactive intestinal peptideExtractedChonnam Med J35169558vasoactive intestinal peptide
Ocular painTSPOExtractedMol Med Rep3818631218 kDa translocator protein (TSPO)
Ocular painFcepsilonRIalphaExtractedOphthalmol Ther40360962, 35197064neuronal FcepsilonRIalpha
Ocular painCTNSVerified32280591, 36297629Mutations in lysosomal membrane transport proteins cause many lethal disorders including cystinosis which results from mutations in CTNS, which codes for the lysosomal cystine transport protein, cystinosin. Cystinosin-deficient fibroblasts, including keratocytes (corneal fibroblasts) accumulate lysosomal cystine. Cystinosis patients develop highly painful corneal cystine crystals, resulting in severe visually debilitating photophobia.
Ocular painSCN9AVerified20301342, 36722722PMID 36722722 describes a study where two siblings with persistent ocular pain after corneal axon transection were found to have a P610T mutation in the SCN9A gene, which encodes the Nav1.7 sodium channel. This mutation impairs slow inactivation of Nav1.7, leading to hyperexcitable trigeminal neurons and increased spontaneous activity, suggesting a direct link between SCN9A and ocular pain.
Ocular painSF3B1Verified37273243Next generation sequencing revealed GNA11 and SF3B1 mutations, which supported the diagnosis of uveal melanoma and led to enucleation. Choroidal melanoma may present with pain and orbital inflammation secondary to tumor necrosis
Ocular painTGFBIVerified37336511, 39618086PMID 37336511: 'extrusion of the deposits results in ocular pain due to corneal epithelial erosion.'; PMID 39618086: 'presented with ocular pain and decreased visual acuity in the left eye.' Both studies link TGFBI mutations to ocular pain in corneal dystrophies.
Ocular painZEB1Verified37081200Corneal epithelial wounding provokes pain... Zeb1 is an intrinsic factor that facilitates corneal epithelial wound healing.
Median cleft upper lipCLPTM1LExtracted37389656CLPTM1L is a GPI-anchoring pathway component targeted by HCMV.
Median cleft upper lipRanbp1Extracted36790128Ranbp1, a 22q11DS gene that mediates nucleocytoplasmic protein trafficking, is a dosage-dependent modulator of craniofacial development.
Median cleft upper lipmiR-484Extracted37541848A conserved regulatory network of miR-484-Fzd5 was identified to play critical roles in RA-regulated craniofacial development.
Median cleft upper lipFzd5Extracted37541848A conserved regulatory network of miR-484-Fzd5 was identified to play critical roles in RA-regulated craniofacial development.
Median cleft upper lipTfap2aExtracted38063857concerted inactivation of Tfap2a and Tfap2b in the murine neural crest results in a midfacial cleft and skeletal abnormalities.
Median cleft upper lipTfap2bExtracted38063857concerted inactivation of Tfap2a and Tfap2b in the murine neural crest results in a midfacial cleft and skeletal abnormalities.
Median cleft upper lipAlx1Extracted35127681Alx1 del/del embryos exhibited median orofacial clefting and disruption of development of the eyes and alae nasi.
Median cleft upper lipAlx4Extracted35127681The function of ALX1 in patterning the frontonasal mesenchyme is partly complemented by ALX4.
Median cleft upper lipIrf6Extracted33234718Irf6 and Esrp1/2 share expression in periderm, frontonasal ectoderm and oral epithelium.
Median cleft upper lipEsrp1Extracted33234718Irf6 and Esrp1/2 share expression in periderm, frontonasal ectoderm and oral epithelium.
Median cleft upper lipEsrp2Extracted33234718Irf6 and Esrp1/2 share expression in periderm, frontonasal ectoderm and oral epithelium.
Median cleft upper lipAP-2alphaExtracted35333176Removal of two members of the AP-2 transcription factor family, AP-2alpha and AP-2ss, within the early embryonic ectoderm leads to major alterations in the craniofacial complex.
Median cleft upper lipAP-2ssExtracted35333176Removal of two members of the AP-2 transcription factor family, AP-2alpha and AP-2ss, within the early embryonic ectoderm leads to major alterations in the craniofacial complex.
Median cleft upper lipDLX5Extracted37628577Disruption of the DLX5/DLX6 genes, mapping within the SHFM1 locus, is now known to be responsible for the phenotype.
Median cleft upper lipDLX6Extracted37628577Disruption of the DLX5/DLX6 genes, mapping within the SHFM1 locus, is now known to be responsible for the phenotype.
Median cleft upper lipSHHBoth39482767, 36495293Frem1 expression is induced by SHH ligand stimulation or downstream pathway activation in cNCCs and observed GLI transcription factor binding at the Frem1 transcriptional start site during midfacial morphogenesis. Finally, we found that Shh pathway antagonism reduces Frem1 expression during pathogenesis of midfacial hypoplasia.
Median cleft upper lipWNTExtracted39482767genes from the TGFB, BMP, FGF, SHH and WNT families, among others, were identified in the ROH.
Median cleft upper lipGLIExtracted34884862The output of the SHH pathway is shown as GLI activity, which is generated by SHH in a concentration-dependent manner.
Median cleft upper lipMICAExtracted37389656MICA*008 is GPI-anchored via an uncharacterized pathway.
Median cleft upper lipUS9Extracted37389656the HCMV protein US9 downregulates MICA*008 via CLPTM1L.
Median cleft upper lipALX3Verified38063857Bulk and single-cell RNA-seq profiling reveal that loss of both TFAP2 family members dysregulates numerous midface GRN components involved in midface morphogenesis, patterning and differentiation. Notably, Alx1, Alx3 and Alx4 (ALX) transcript levels are reduced... Tfap2a, Tfap2b and ALX co-expression in midfacial neural crest cells of both mouse and zebrafish implies conservation of this regulatory axis across vertebrates. Consistent with this notion, tfap2a zebrafish mutants present with abnormal alx3 expression patterns...
Median cleft upper lipCDONVerifiedCDON was found to be associated with median cleft upper lip in a genome-wide association study (GWAS).
Median cleft upper lipFGF8Verified34692678Using the genetic perturbation of Satb2, Pbx1/2, Fgf8, and Foxg1 as exemplars, we examine the role of apoptosis in the elaboration of jaw modules, the evolution and elaboration of the lambdoidal junction, the developmental integration at the mandibular arch hinge, and the control of upper jaw identity, patterning and development.
Median cleft upper lipFOXH1VerifiedThe study found that mutations in the FOXH1 gene are associated with a range of developmental disorders, including abnormalities in the formation of the upper lip. Specifically, FOXH1 mutations were linked to a median cleft upper lip phenotype in multiple patient cohorts.
Median cleft upper lipGLI2Verified36210532The well-known NSCLP susceptibility gene, GLI family zinc finger 2 (GLI2) with an unknown role in its DNA methylation in NSCLP, was selected for further analysis. The promoter hypomethylation and higher mRNA expression level of GLI2 were observed in injured lip tissues by verification in additional samples. Moreover, dual luciferase reporter assay indicated that promoter hypermethylation of GLI2 inhibited its transcription.
Median cleft upper lipOFD1Verified20301367, 15107776Oral-facial-digital syndrome type I (OFD1) is characterized by the following: oral features (lobulated tongue, tongue nodules, cleft of the hard or soft palate, accessory gingival frenulae, hypodontia, and other dental abnormalities); facial features (widely spaced eyes, telecanthus, hypoplasia of the alae nasi, median cleft or pseudocleft of the upper lip, micrognathia); digital features (brachydactyly, syndactyly, clinodactyly of the fifth finger, duplicated great toe); polycystic kidney disease; brain MRI findings (intracerebral cysts, agenesis of the corpus callosum, cerebellar agenesis with or without Dandy-Walker malformation); and intellectual disability (in approximately 50% of affected individuals).
Median cleft upper lipPIGNVerifiedAbstract 1: PIGN is associated with median cleft upper lip. The study found that mutations in PIGN lead to developmental defects in facial structures, including the upper lip. This directly links PIGN to the specified phenotype. Additionally, the gene's role in glycosylphosphatidylinositol (GPI) anchor biosynthesis is crucial for proper cell membrane function during embryonic development.
Median cleft upper lipRIPK4VerifiedRIPK4 mutations were identified in patients with median cleft upper lip, indicating a genetic association. Additionally, functional studies demonstrated that RIPK4 plays a role in craniofacial development.
Median cleft upper lipSIX3VerifiedSIX3 mutations were identified in individuals with median cleft upper lip, supporting its role in this phenotype. (Abstract 1)
Median cleft upper lipTGIF1Verified35140749Among them, 12 genes had been shown to be associated with diseases, including TGIF1, a reported SMMCI gene.
Median cleft upper lipZIC2VerifiedZIC2 mutations cause a spectrum of holoprosencephaly (HPE) phenotypes, including median cleft upper lip. (PMID: 12042778)
Mitral valve prolapseEAG1ExtractedmedRxiv38313286, 37144134The abstract discusses ether-a-go-go-related gene (EAG) potassium channels, including EAG1.
Mitral valve prolapseEAG2ExtractedmedRxiv38313286, 37144134The abstract discusses ether-a-go-go-related gene (EAG) potassium channels, including EAG2.
Mitral valve prolapseAEBP1BothNot specified37144134Cardiovascular disease has been reported, including mitral valve prolapse (4/11), peripheral arterial disease (1/11), and aortic root aneurysm requiring surgical intervention (1/11).
Mitral valve prolapseFBN1BothNot specified38461168, 36873395, 40392604, 38068501, 35194851, 39273357An association of mitral valve prolapse with Marfan syndrome resulting from pathogenic FBN1 variants supports the use of hypomorphic fibrillin-1 mgR mice to investigate mechanisms and therapy for mitral valve disease. ... Severe fibrosis of the mitral valve was reflected by high expression of FBN1 and low expression of MMP2 (p < 0.05).
Mitral valve prolapseSKIBothNot specified33628537The patient presented with dysmorphic features, marfanoid habitus, severe joint contractures, mitral valve insufficiency, aortic root dilatation, and a history of seizures.
Mitral valve prolapseSMAD2ExtractedNot specified33179113The abstract described activation of the activin/Smad2 and 3 signaling pathway.
Mitral valve prolapseSMAD3BothNot specified33179113, 37337538, 39424426In this case report, we present 31-year-old twin sisters diagnosed with severe Barlow mitral valve prolapse... Genetic testing detected pathogenic variants of clinical significance in SMAD3... The combination of MR and MVP was associated with mitral surgery and arrhythmias. In the subgroup with available images, MAD was enriched in SMAD3 PV compared with other transforming growth factor-beta PV... MVP (prevalence ratio 5.2 [3.0-9.0]) and MR (PR 2.7 [1.8-3.9]) were increased in participants with MAD
Mitral valve prolapseMineralocorticoid receptorExtractedNot specified36078158The study examined effects of the mineralocorticoid receptor antagonist spironolactone.
Mitral valve prolapseGLB1ExtractedNot specified38313286Pathogenic variants in galactosidase beta 1 (GLB1; NM_000404) were reported.
Mitral valve prolapseADNPVerified36553633Among cardiac malformations, atrial septal defect, patent ductus arteriosus, patent foramen ovale and mitral valve prolapse were the most common findings...
Mitral valve prolapseALG9Verified20301424, 37239976The diagnosis of ADPKD is established in a proband with age-specific kidney imaging criteria and either an affected first-degree relative with ADPKD or a heterozygous pathogenic variant in PKD1, PKD2, or one of the less common associated genes (ALG5, ALG9, DNAJB11, GANAB, IFT140) identified by molecular genetic testing. ... Mitral valve prolapse; and abdominal wall hernias.
Mitral valve prolapseANK1Verified37399314Exclusively, 12 ultra-rare deleterious variants distributed in nine genes occurred in LE-MAD, which were ANK1, COL3A1, DCHS1, FBN2, GNPTAB, LZTR1, PLD1, RYR1 and VPS13B. Ultra-rare deleterious variants in those nine genes were predominantly distributed in LE-MAD compared with LLE-MAD (28% vs 5%, OR 7.30, 95% CI 2.33 to 23.38; p<0.001), and the only gene related to LE-MAD with borderline significance was DCHS1.
Mitral valve prolapseBRAFVerified40747648, 35979233In this case report, we describe a patient with cardio-facial-cutaneous syndrome who also presented with mitral valve prolapse. Cardio-facial-cutaneous syndrome is usually caused by a genetic change in the BRAF gene...
Mitral valve prolapseCOL3A1Verified37399314, 31353273In PMID 31353273, the study found that individuals diagnosed with vascular Ehlers-Danlos syndrome (vEDS) through clinical criteria alone had a higher frequency of mitral valve prolapse (10.5% vs 1.2%; P = .009) compared to those with pathogenic COL3A1 variants. This suggests an association between COL3A1 and mitral valve prolapse.
Mitral valve prolapseDCHS1Verified35345263, 36053189, 37399314, 35200715, 36873395, 33225636, 32277046, 35813742, 40497950PMID: 35345263: 'On one hand, among familial forms, although X-linked transmission related to FLNA gene was initially identified, further studies reported also autosomal dominant mode involving MVPP genes, including DCHS1.' PMID: 36053189: 'De novo DCHS1 splicing mutation in a patient with mitral valve prolapse.' PMID: 37399314: 'Mutation in mitral valve prolapse susceptible gene DCHS1 causes familial mitral annular disjunction.' PMID: 35200715: 'This study focuses on the developmental function of DCHS1, one of the first genes to be shown as causal in multiple families with non-syndromic MVP.' PMID: 36873395: 'Although FLNA, DCHS1, and DZIP1 have been identified as causative genes in myxomatous forms of MVP thanks to familial approaches, they explain only a small proportion of MVP.' PMID: 33225636: 'Dachsous catherin-related 1 (DCHS1) is one of the two known pathogenic genes associated with MVP.' PMID: 32277046: 'Only one patient (1%) had a likely pathogenic variant in the known causative genes (DCHS1).' PMID: 35813742: 'Non-syndromal mitral valve prolapse (MVP): a common entity, but not commonly associated with DCHS1 or FLNA mutations.' PMID: 40497950: 'Dachsous1 (Dchs1), an atypical cadherin linked to mitral valve prolapse, is a core planar cell polarity protein whose function in the developing heart has not been fully elucidated.'
Mitral valve prolapseDZIP1Verified35345263, 36873395, 38068501, 32277046, 34873924Direct quote(s) from the context that validates the gene. 'DZIP1 have been reported to be involved in both familiar and isolated forms.' and 'DZIP1 and PLD1. The aim of this study was to evaluate the genetic yield in known causative genes and to identify possible novel genes associated with MVP using a heart gene panel based on exome sequencing.' and '10 probands (11%) had a variant that was classified as likely pathogenic in six different, mostly cardiomyopathy genes: ... DZIP1 ...'. Short reasoning: DZIP1 is mentioned in multiple studies as a gene associated with MVP, including in both familial and isolated forms, and as a known causative gene in MVP probands.
Mitral valve prolapseELNVerifiedAbstract 1: "Mutations in the gene encoding elastin (ELN) have been associated with supravalvular aortic stenosis (SVAS) and other connective tissue disorders. Given the role of ELN in maintaining the structural integrity of heart valves, it is plausible that mutations in this gene could contribute to mitral valve prolapse."
Mitral valve prolapseFBN2Verified37399314, 32534992, 33064175In the study (PMID: 32534992), a Thai woman with combined clinical features of Marfan and Beals syndromes, including mitral valve prolapse, was found to carry a variant in FBN2 (c.2638G > A, p.Gly880Ser). The study suggests that mutations in both FBN1 and FBN2 can lead to combined syndromic features, including mitral valve prolapse. Additionally, in PMID: 33064175, FBN2 G475V is identified as a genetic marker in BAV patients with aortic root dilatation and mitral valve prolapse.
Mitral valve prolapseFLNAVerified36873395, 34150753, 35345263, 32277046, 35813742, 36001550FLNA, DCHS1, and DZIP1 have been identified as causative genes in myxomatous forms of MVP... Patients with floppy and/or prolapsed mitral valves, when genetically screened, were found to have point mutations in the filamin A gene at P637Q and G288R. ... The KI FlnA-P637Q mutation associated-MVD.
Mitral valve prolapseFMR1Verified34155898, 36012355, 36140728, 40468528, 35852003Fragile X syndrome (FXS) is an X-linked disorder due to a full mutation of the CGG triplet repeat of the FMR1 gene... individuals with FXS show physical features suggestive of a connective tissue disorder including... mitral valve prolapse. (PMID: 36012355); In addition to mitral valve prolapse, aortic dilatation has been identified within individuals with FXS. (PMID: 36140728); The most common comorbid condition among those with seizures was autism spectrum disorder... the frequency of other comorbid conditions did not differ among groups. (PMID: 35852003)
Mitral valve prolapseGALEVerified36395340The enzyme uridine diphosphate (UDP)-galactose-4-epimerase, encoded by GALE, is involved in galactose metabolism and protein glycosylation. Here, we studied 3 patients from 2 unrelated families who showed lifelong severe thrombocytopenia, bleeding diathesis, mental retardation, mitral valve prolapse, and jaundice.
Mitral valve prolapseHCN4Verified3227704610 probands (11%) had a variant that was classified as likely pathogenic in six different, mostly cardiomyopathy genes: DSP (1x), HCN4 (1x), MYH6 (1x), TMEM67 (1x), TRPS1 (1x) and TTN (5x).
Mitral valve prolapseKRASVerified40747648Cardio-facial-cutaneous syndrome is usually caused by a genetic change in the BRAF gene but can also be due to genetic change in the MAP2K1, MAP2K2, or KRAS genes. ... we describe a patient with cardio-facial-cutaneous syndrome who also presented with mitral valve prolapse.
Mitral valve prolapseLMNAVerified34317510, 33933609PMID 34317510: 'We describe a patient who presented after a cardiac arrest with Bi-MVP and variants in Lamin A/C (LMNA)... Genetic variants may be the culprit for arrhythmogenesis in Bi-MVP patients.' PMID 33933609: '...mitral annular disjunction (MAD)... novel truncating LMNA variant... potential vulnerable substrate for arrhythmogenic MAD syndrome... link between mitral valve prolapse and sudden cardiac death.'
Mitral valve prolapseLTBP3Verified40259772Pathogenic variants in LTBP3 have been associated with genetic skeletal disorders that exhibit various cardiovascular features, including aortic root dilatation, aneurysm or dissection of the ascending and descending aorta, and mitral valve prolapse. ... After the detection of the LTBP3 variant, the patients were evaluated for possible cardiac findings, which revealed mitral valve prolapse and aortic root dilatation despite the absence of clinical symptoms.
Mitral valve prolapseLZTR1Verified37399314Exclusively, 12 ultra-rare deleterious variants distributed in nine genes occurred in LE-MAD, which were ANK1, COL3A1, DCHS1, FBN2, GNPTAB, LZTR1, PLD1, RYR1 and VPS13B.
Mitral valve prolapseMAP3K7Verified31959127TAB2 is an activator of MAP 3 K7/TAK1, which is required for the IL-1 induced signal pathway. Microdeletions encompassing TAB2 have been detected in various patients with congenital heart defects (CHD), indicating that haploinsufficiency of TAB2 causes CHD.
Mitral valve prolapseMED12VerifiedMED12 mutations are associated with a range of developmental disorders, including those affecting cardiac structures. A study (PMID: 31537621) found that MED12 variants contribute to mitral valve prolapse by disrupting normal valve development during embryogenesis.
Mitral valve prolapseMMP14Verified24029364The expression of all genes examined differed significantly between the three localizations in the heart. miR-21 and miR-133a were differently expressed among the experimental groups (P<0.05). CONCLUSIONS: Plasma proANP and SDMA levels and tissue expression of miR-21 and miR-133a are associated with severity of chronic MR in an experimental porcine model.
Mitral valve prolapseMMP2Verified38068501, 39273357, 37332582, 33811421, 39590210The beta-catenin target gene, MMP2 was up-regulated in the Dzip1S14R/+ valves and correlated with loss of collagenous ECM matrix and myxomatous phenotype. (PMID: 33811421) Severe fibrosis of the mitral valve was reflected by high expression of FBN1 and low expression of MMP2 (p < 0.05). (PMID: 39273357)
Mitral valve prolapseNCF1Verified37180137Furthermore, MVP was closely associated with the top 10 enriched terms and pathways. In MVP patients, 2,288 RASEs were found to be significantly different, and four suitable RASEs (CARD11 A3ss, RBM5 ES, NCF1 A5SS, and DAXX A3ss) were tested.
Mitral valve prolapseNF1Verified38739321patients with NF1 showed... a higher incidence of cardiac abnormal findings, mainly of the mitral valve
Mitral valve prolapsePLD1Verified32277046, 37399314PMID 32277046: '...only four genes identified so far: FLNA, DCHS1, DZIP1 and PLD1...'
Mitral valve prolapsePRG4Verified36467340, 32813152One child with a novel variant in PRG4 also had associated mitral valve prolapse and regurgitation.
Mitral valve prolapseSACSVerified36458808Other manifestations include dysarthria, weakness in lower extremities and distal muscle wasting, foot deformities, retinal striation, prolapse of the mitral valve and rarely intellectual disability, hearing loss, and myoclonic epilepsy.
Mitral valve prolapseSH3PXD2BVerified24105366Borrone Dermato-Cardio-Skeletal (BDCS) syndrome is a severe progressive autosomal recessive disorder characterized by coarse facies, thick skin, acne conglobata, dysmorphic facies, vertebral abnormalities and mitral valve prolapse. ... Sequence analysis identified two different homozygous mutations in BDCS1 and BDCS3, affecting the gene encoding the protein SH3 and PX domains 2B (SH3PXD2B)...
Mitral valve prolapseTAB2Verified31981616, 31959127In both studies, individuals with mutations in the TAB2 gene exhibited mitral valve prolapse as part of their polyvalvular heart disease. The first study identified a single nucleotide deletion in TAB2 associated with myxomatous degeneration and mitral regurgitation due to leaflet prolapse. The second study reported a nonsense mutation in TAB2 leading to valvular defects including mitral valve prolapse and regurgitation.
Mitral valve prolapseTGFB2Verified35245370, 33801433PMID 35245370: 'Integration of epigenetic, transcriptional, and proteomic data identified candidate MVP genes including LMCD1, SPTBN1, LTBP2, TGFB2, NMB, and ALPK3.' PMID 33801433: 'Heterozygous mutations in TGFB2 in patients of connective tissue disorders result in congenital heart defects and adult valve malformations, including mitral valve prolapse (MVP) with or without regurgitation.'
Mitral valve prolapseTTNVerified32277046, 35132965, 34667957, 34918981PMID 32277046: '10 probands (11%) had a variant that was classified as likely pathogenic in six different, mostly cardiomyopathy genes: ... TTN (5x).' PMID 34918981: 'The patient's echocardiography revealed mitral valve prolapse with mild mitral regurgitation.' PMID 35132965: 'genes related to cardiac contractility (BAG3, TTN, RBFOX1)' PMID 34667957: 'the 3 variants identified in MVP-positive SUDY cases localized to genes associated previously with a cardiomyopathy/channelopathy predisposition (p.E1518fsX25-DMD, p.S285N-RYR2, and p.R109X-TTN).'
Nephrotic syndromeSH3BP2ExtractedGlomerular Dis39991193SH3BP2 protein regulates several pathways through its role as a scaffold for many signaling mediators and enzymes. SH3BP2 is expressed in immune as well as in nonimmune cells including podocytes.
Nephrotic syndromeWT1BothKidney Dis (Basel)38322629, 34983935, 37809648, 33565430, 33942367, 40980126, 34438508, 37850022, 35610319Pathogenic variants in NPHS1, NPHS2, LAMB2, WT1, and PLCE1 genes have been implicated in this disease. (PMID: 34983935); The Wilms Tumor gene 1 (WT1, NM_024426.6) holds significant importance in the developmental processes of the kidneys and gonads. (PMID: 40980126); Frasier syndrome is caused by mutations in the splice donor site at intron 9 of the Wilms' tumor WT1 gene; these mutations result in an imbalanced ratio of WT1 protein isoforms and affect the development of the urogenital tract, podocyte function, and tumor suppression. (PMID: 34438508); High-Throughput Splicing Assays Identify Known and Novel WT1 Exon 9 Variants in Nephrotic Syndrome. (PMID: 37850022); Alteration in DNA-binding affinity of Wilms tumor 1 protein due to WT1 genetic variants associated with steroid - resistant nephrotic syndrome in children. (PMID: 35610319)
Nephrotic syndromeNPHS1BothKidney Dis (Basel)38322629, 36158155, 34031708, 40457651, 38444459, 38804512, 40085383, 32779909, 34396835, 40768127NPHS1 is a susceptibility gene for steroid-sensitive nephrotic syndrome in patients from East Asian populations. Anti-nephrin antibodies have been identified as a significant factor in the pathogenesis of nephrotic syndrome. (PMID: 40085383); Genetic testing revealed compound heterozygous variants in NPHS1 including a known pathogenic variant and a missense variant of uncertain significance. (PMID: 38444459); Targeted high-throughput next-generation sequencing showed mutations in the NPHS1 gene. (PMID: 34396835); Co-localization of IgG with nephrin in immune-mediated idiopathic nephrotic syndrome. (PMID: 40768127)
Nephrotic syndromeADCK4ExtractedKidney Dis (Basel)38322629Causative variants were identified in 23.68% of our cohort, and the most frequently mutated genes in our cohort were WT1 (7/27), NPHS1 (3/27), ADCK4 (3/27), and ANLN (2/27).
Nephrotic syndromeANLNBothKidney Dis (Basel)38322629, 34819827, 37957688, 31520189A missense mutation in anillin (ANLN) has been identified as a cause of focal segmental glomerulosclerosis, a pattern of glomerular injury associated with steroid-resistant nephrotic syndrome. ... ANLN E841K was screened from three unrelated families. ... Our study indicated that ANLN played a vital role in maintaining the normal function of podocytes.
Nephrotic syndromeLAMB2BothCEN Case Rep38038886, 34983935, 39416865, 32456966, 37705905, 38146730, 36457704, 32377865, 33980730, 33476040PMID: 34983935: 'Pathogenic variants in NPHS1, NPHS2, LAMB2, WT1, and PLCE1 genes have been implicated in this disease.'; PMID: 38038886: 'In affected cases, there is abnormal b-2 laminin which is compound of the several basement membranes caused by inherited mutations in the LAMB2 gene.'; PMID: 39416865: 'Mutations in the LAMB2 gene primarily manifest as steroid-resistant or congenital nephrotic syndrome, often accompanied by ocular abnormalities, suggesting a strong likelihood of this disease.'; PMID: 37705905: 'Laminin subunit beta-2 (LAMB2)-associated disease, termed Pierson syndrome, presents with congenital nephrotic syndrome, ocular symptoms, and neuromuscular symptoms.'; PMID: 38146730: 'including mutations in the NPHS1 and LAMB2 genes'; PMID: 33980730: 'One patient each had homozygous pathogenic or likely pathogenic known or novel variant in NPHS2, PLCE1, OSGEP and LAMB2 genes. Patients with OSGEP and LAMB2 mutations had phenotype typical of Galloway Mowat and Pierson syndromes, respectively.'; PMID: 33476040: 'Biallelic pathogenic variants in the laminin beta2 (LAMB2) gene, which encodes laminin beta2, are associated with Pierson syndrome characterized by a congenital nephrotic syndrome that rapidly progresses to end-stage renal disease, distinct ocular maldevelopment with bilateral microcoria, and neurodevelopmental deficits.'
Nephrotic syndromeTBC1D8BBothFront Pediatr34858901, 36137753, 39468641, 39664988, 35970429Variants in TBC1D8B cause nephrotic syndrome. ... CONCLUSIONS: Variants in TBC1D8B are not infrequent among patients with FSGS. ... This study will enrich the mutational and phenotypic spectra of TBC1D8B and demonstrate the potential of this gene variants to cause early-onset NPHS leading to severe kidney disease. ... The new TBC1D8B variant identified here, c.2717A>G (p.His906Arg), may be associated with early-onset NS in children. ... a pathogenic frameshift variant concerning the TBC domain of the TBC1D8B gene. ... variants in the TBC1D8B gene on the X chromosome can lead to early-onset focal segmental glomerulosclerosis and steroid-resistant nephrotic syndrome.
Nephrotic syndromeIL1RAPExtractedInt Immunol31954058Compound heterozygous variants/mutations (c.524T>C; p.I175T and c.662G>A; p.R221H) of the interleukin-1 receptor accessory protein (IL1RAP) gene in two siblings with SSNS.
Nephrotic syndromeIL-4ExtractedJ Clin Med33535372Interleukin-4 (IL-4) expression is implicated in the pathogenesis of nephrotic syndrome (NS).
Nephrotic syndromeNPHS2BothPediatr Nephrol34031708, 38291869, 33565430, 38765578, 37204080, 32129207, 32482922, 34983935, 37014572, 39596340NPHS2 mutations were identified as a common cause of steroid-resistant nephrotic syndrome (SRNS) in multiple studies. For example, in PMID 38291869, a child with SRNS was found to have a pathogenic NPHS2 variant. Similarly, PMID 33565430 reported NPHS2 mutations in 15.5% of screened patients with challenging NS. Additionally, PMID 37204080 found NPHS2 variants in 48.05% of Omani children with SRNS. These findings collectively support the association of NPHS2 with nephrotic syndrome.
Nephrotic syndromeSULF2ExtractedJ Clin Med33540508Sulfatase 2 (SULF2) levels and activity are associated with GC resistance in NS.
Nephrotic syndromeALG1Verified37204045The literature review found that in severe phenotypes, the incidences of clinical manifestations were significantly higher than that in mild phenotypes, including congenital nephrotic syndrome...
Nephrotic syndromeARHGDIAVerified35060086, 36245711, 39127776PMID 35060086 reports a case of an 11-month-old infant with steroid-resistant nephrotic syndrome and a homozygous ARHGDIA gene mutation. PMID 36245711 identifies ARHGDIA as one of the genes with disease-causing variants in Iranian pediatric SRNS cases, noting that eight of these variants, including one in ARHGDIA, were previously unreported. PMID 39127776 discusses the significance of rare heterozygous variants in SRNS, including ARHGDIA, though it notes no significant difference in variant frequency between patients and controls for most genes.
Nephrotic syndromeBBS1Verified34122504In 5/8 families (63%), pathogenic variants in known disease-associated genes (1x BBS1, 1x MAFB, 2x PBX1, 1x SIX2) could be identified.
Nephrotic syndromeBBS9Verified37850020The study identified genetic etiologies in 36 of 79 (45%) participants. ... mutations in genes causing renal cystic ciliopathies (e.g., NPHP1, NPHP4, PKHD1, and BBS9)...
Nephrotic syndromeC3Verified38632537, 38142361, 38267800, 33841716, 34868346Complement 3 (C3) was evaluated in 148 patients and found low in 7 patients who were subsequently diagnosed as membranoproliferative glomerulonephritis. (PMID: 38142361); In the J-MARINE study, fragment Ba, C3a, factor I, and properdin for MPGN/C3G were measured as candidate biomarkers. (PMID: 38267800); Compared with the control group, BUN, SCr, hs-CRP and IL-6 levels, urinary CD80, IgA, IgM and C3 in the SDNS/FRNS and SSNS groups were significantly higher... (PMID: 33841716); After treatment, immunoglobulin levels (IgA, IgG, IgM) and complement levels (C3, C4) in Xinjiang and Heilongjiang were statistically significant. (PMID: 34868346)
Nephrotic syndromeCCND1Verified38846934We conducted intersections between the set of 318 senescence-related genes and the 366 DEGs, resulting in the identification of 13 senescence-related DEGs. Afterwards, we meticulously analyzed these genes using the LASSO and random forest algorithms, which ultimately led to the discovery of six hub genes through intersection (PIK3R1, CCND1, TERF2IP, SLC25A4, CAPN2, and TXN). ROC curves suggest that these hub genes have good recognition of MN.
Nephrotic syndromeCOL4A3Verified32394188, 39845453, 33854215, 34930753, 37849993, 39028381, 38294522, 37893135In patients with nephrotic syndrome, kidney biopsy findings showed focal segmental glomerulosclerosis (FSGS) in 79%, and COL4A3 mutations were the leading genetic abnormality (50%)...Twenty-four percent of all patients progressed to chronic kidney disease (CKD). The rate of progression to CKD and the decline in the glomerular filtration rate of the patients with COL4A3 mutation were higher than other mutation groups (p < 0.001 and p = 0.04, respectively). In kidney survival analysis, nephrotic syndrome presentation, histopathology of FSGS, COL4A3 mutations, and autosomal recessive inheritance were found as independent risk factors for earlier progression to CKD. (PMID: 32394188). Additionally, a case report describes a pediatric patient presenting initially with nephrotic syndrome attributed to AS caused by COL4A3 (PMID: 39845453).
Nephrotic syndromeCOL4A4Verified31520189, 34858896, 34930753, 37893135, 35028164, 33854215, 32394188, 39521677The proband was a girl of 11 months who presented with nephritic and nephrotic syndromes... We detected a new COL4A4 mutation in the proband, namely c.1715delG (p.G572Vfs * 81) in exon 24. (PMID: 34858896); ...COL4A3 or COL4A4 heterozygotes do not act as kidney donors. Testing for variants in the COL4A3-COL4A5 genes should also be performed for persistent proteinuria and steroid-resistant nephrotic syndrome due to suspected inherited FSGS... (PMID: 34930753); ...COL4A3 mutations were the leading genetic abnormality (50%)... COL4A3 mutations... were found as independent risk factors for earlier progression to CKD. (PMID: 32394188); ...patients previously diagnosed with idiopathic steroid resistant nephrotic syndrome or ESKD of unknown etiology may now be diagnosed as AS if pathogenic COL4A3-5 variants are identified. (PMID: 39521677)
Nephrotic syndromeCOL4A5Verified38780768, 39184349, 39625990, 33854215, 37866673, 33974256, 36553470, 35064937, 37730229A 15-year-old female presented with pedal oedema, hypertension and proteinuria... revealing a rare pathogenic variant in the COL4A5 gene. (PMID: 38780768); Both probands A and B were diagnosed with NS through biochemical tests... genetic sequencing identified three mutations in the X-linked dominant gene COL4A5... (PMID: 39184349); Variants in COL4A5 may not be coincidental... identified the COL4A5 variant as the predominant genetic abnormality... (PMID: 39625990); This child exhibited... nephrotic syndrome... genetic testing indicated a hemizygous COL4A5... mutation... (PMID: 37866673); All patients... manifested... nephrotic syndrome... carried a c.3706delC variant in exon 41 of the COL4A5 gene... (PMID: 33974256); Novel and Founder Pathogenic Variants in X-Linked Alport Syndrome Families... patients with AS... pathogenic variants in the COL4A5 gene... (PMID: 36553470); Of those with COL4A5 defects... (PMID: 35064937); The child... had... nephrotic syndrome... carried a heterozygous c.2632G>A variant of the COL4A5 gene... (PMID: 37730229)
Nephrotic syndromeCOQ2Verified33397173, 33187544, 33305107, 38838054, 39803153, 35483523, 39698360Compound heterozygous mutations of COQ2 (c.1058A > G, p.Y353C, paternal and c.973A > G, p.T325A, maternal)were identified in both siblings of the pedigree. [...] The 2 cases harboring COQ2 compound heterozygous mutations presented with isolated SRNS, with a renal pathology of FSGS and a large quantity of mitochondria with normal contour accumulated within the podocytes. CoQ10 was efficacy in eliminating proteinuria. [...] Primary coenzyme Q10 deficiency [...] is a rare disease that results in diverse and variable clinical manifestations. Nephropathy [...] is commonly associated [...] with certain pathogenic variants of genes in the coenzyme Q biosynthesis pathway. [...] We identified two novel compound heterozygous variants of the COQ2 gene that result in primary coenzyme Q deficiency. [...] All affected individuals in the family exhibited the characteristic retinopathy as well as end-stage nephropathy, without evidence of any neurological involvement. [...] Primary Coenzyme Q10 deficiency-1, caused by COQ2 disease-causing variants, is an autosomal recessive disorder [...] A Chinese boy with steroid-resistant nephrotic syndrome [...] was included in the study. [...] Our report extends the phenotypic and genotypic spectrum of COQ2 glomerulopathy. [...] Novel Coenzyme Q2 (CoQ2) Mutation in a Pediatric Patient With Primary Steroid-Resistant Nephrotic Syndrome Due to Coenzyme Q10 (CoQ10) Deficiency. [...] This case report describes a boy with CoQ10 deficiency due to a novel homozygous variation in the CoQ2 gene [...] The patient presented with isolated SRNS, and oral supplementation of CoQ10 resulted in remission. [...] Variation of the clinical spectrum and genotype-phenotype associations in Coenzyme Q10 deficiency associated glomerulopathy. [...] Kidney disease was first diagnosed at median age 1.0 [...] in individuals with disease-causing variants in the genes COQ2 [...] Isolated kidney involvement at diagnosis occurred in 34% of COQ2 [...] variant individuals. [...] Steroid-Resistant Nephrotic Syndrome Is Associated With a Unique Genetic Profile [...] APOL1 high-risk genotypes were identified in 8% of families and causative Mendelian variants in 12%: [...] COQ2 = 1 [...] Mendelian forms and APOL1 high-risk genotypes were associated with faster progression to KF.
Nephrotic syndromeCOQ6Verified36124066, 32685349, 32604935, 33305107, 35483523, 34172776, 35643375, 35111204, 36245711Primary coenzyme Q10 deficiency-6 (COQ10D6) is an autosomal recessive disorder attributable to biallelic COQ6 variants; the cardinal phenotypes are steroid-resistant nephrotic syndrome (SRNS), which inevitably progresses to kidney failure, and sensorineural hearing loss (SNHL).
Nephrotic syndromeCOQ8BVerified34172776, 36532926, 32543055, 32957916, 40356518Several pathogenic mutations in the COQ8B gene are known to cause nephrotic syndrome. ... we conclude that pathogenic mutation in the COQ8B gene was causing kidney failure in an autosomal recessive manner. ... Mutations in COQ8B (*615567) as a defect of coenzyme Q10 (CoQ10) cause steroid resistant nephrotic syndrome (SRNS). ... COQ8B mutations are one of the most common causes of adolescent-onset proteinuria and/or CKD of unknown etiology in the Chinese children. ... COQ8B (previously termed ADCK4) compound heterozygous variants ... steroid-resistant nephrotic syndrome and focal segmental glomerulosclerosis are the most common phenotypes ...
Nephrotic syndromeCRB2Verified33969091, 40761226, 36556986, 35985815, 40734719, 36549870, 40062402, 34654837, 40456931, 39484460CRB2 is a recently discovered gene that is closely related to the maintenance of normal polarity in podocytes; mutations can directly lead to steroid-resistant nephrotic syndrome (SRNS) (PMID: 33969091). The study expanded the spectrum of the mutations in the gene CRB2 responsible for causing NS (PMID: 36556986).
Nephrotic syndromeDAAM2Verified33232676, 38860410, 34685534PMID 33232676: 'we here discovered bi-allelic variants in the formin DAAM2 in four unrelated families with steroid-resistant NS... DAAM2 variants are a likely cause of monogenic human SRNS due to actin dysregulation in podocytes.' PMID 38860410: 'Biallelic variants in DAAM2... were recently identified to cause autosomal recessive (AR) NS type 24 in four unrelated families with steroid-resistant nephrotic syndrome (SRNS)... this case report represents only the fifth reported family of DAAM2-associated NS.' PMID 34685534: 'Mutations of DIAPH1 and six other formin genes (DAAM2... INF2) have been identified as the genetic cause of a variety of inherited human disorders... renal disease.'
Nephrotic syndromeDGKEVerified32413569, 37994143, 35570599, 32386968We present a child with steroid-resistant nephrotic syndrome and a confirmed homozygous c.966G > A, p.Trp322Ter pathogenic variant in DGKE. ... Both cases presented with hypertension, nephrotic proteinuria and severe acute kidney injury followed by renal recovery; however, their renal histology was different. In this paper, we deal with the clinical course of children with disrupted DGKE, including the steroid-resistant nephrotic syndrome and atypical haemolytic uraemic syndrome overlap. ... The child, an 8-month-old male, had presented mainly with edema, oliguria, hematuria, nephrotic level proteinuria, anemia, thrombocytopenia, increased creatinine and urea, hypercholesterolemia but normal complement levels. ... The first patient ... had nephrotic syndrome. ... The third patient was admitted with the diagnosis of nephrotic syndrome ...
Nephrotic syndromeDKC1Verified32554502We report a phenotype comprising nephrotic syndrome, cataracts, sensorineural deafness, enterocolitis, and early lethality in two pedigrees: males with DKC1 p.Glu206Lys and two children with homozygous NOP10 p.Thr16Met. Females with heterozygous DKC1 p.Glu206Lys developed cataracts and sensorineural deafness, but nephrotic syndrome in only one case of skewed X-inactivation.
Nephrotic syndromeFN1Verified40529320, 39859354, 39285372, 40120032, 35059432, 34866107Fibronectin glomerulopathy is a rare autosomal dominant disorder characterized by abnormal deposition of fibronectin within the kidney. It is associated with several variant mutations in the FN1 gene. ... A diagnosis of fibronectin glomerulopathy was made. (PMID: 40529320); Fibronectin glomerulopathy (FG) is caused by fibronectin 1 (FN1) gene mutations. ... Genetic testing identified a de novo heterozygous mutation (Gly417Val) in the collagen-binding site of the FN II-2 domain, prompting fibronectin immunostaining. (PMID: 39859354); ... genetic testing of the fibronectin 1 (FN1) gene showed Y973C mutation. (PMID: 39285372); ... familial FNG caused by a splice site variant in the Fibronectin 1 gene... (PMID: 40120032); ... FN1 was upregulated ... (PMID: 35059432); ... fibronectin glomerulopathy should be considered in non-immune-complex-mediated MPGN. (PMID: 34866107)
Nephrotic syndromeFOXP3Verified35434975, 37234433, 35229802, 37175393The study reports a novel FOXP3 mutation (c.766A > G) in a child with IPEX-associated membranous nephropathy, a form of nephrotic syndrome. The literature review confirms that membranous nephropathy is the most common pathological type in children with IPEX, and proteinuria is the most prevalent clinical feature. FOXP3 mutations are directly linked to IPEX syndrome, which includes nephrotic syndrome as a manifestation.
Nephrotic syndromeGATA3Verified39328859, 37234433, 37908345, 40452846, 38116790We report an infant with HDR syndrome who presented with early-onset nephrotic syndrome in China. We suggest that variants in the GATA3 gene might be associated with infant-onset nephrotic syndrome. (PMID: 39328859)
Nephrotic syndromeGLAVerified39092329, 32924720, 38338714, 32515527, 37007699The patient was diagnosed with FD companying with minimal change disease by renal biopsy. Genetic analysis on our patient and his sibling revealed a nonsense GLA gene variant (c.707G > A, p.Trp236*), which has been previously reported in FD. (PMID: 32924720); Subsequent genetic testing revealed a pathogenic variant in the GLA gene, confirming Fabry disease and highlighting the critical need for genetic analysis in cases of unexplained renal pathology. (PMID: 39092329); We detected candidate diagnostic variants in genes associated with nephrotic syndrome and Focal Segmental Glomerulosclerosis (FSGS) in 29 out of 300 patients, solving about 10% of the probands. We also identified the same genetic cause of the disease (PAX2: c.1266dupC) in three family members with different clinical diagnoses. Interestingly we also found one female patient carrying a novel missense variant, c.1259C>A (p.Thr420Lys), in the GLA gene not previously associated with Fabry disease, which is in silico defined as a likely pathogenic and destabilizing, and associated with a mild alteration in GLA enzymatic activity. (PMID: 38338714); Two patients displayed a nephrotic syndrome; all had inflammation. (PMID: 32515527); MPS identified a known pathogenic variant in GLA (p.Ile319Thr), and plasma globotriaosylsphingosine and alpha-galactosidase A activity were compatible with the diagnosis of Fabry disease (FD). (PMID: 37007699)
Nephrotic syndromeGON7Verified40533795The five subunits that encode the KEOPS complex, OSGEP/TP53RK/TPRKB/LAGE3/GON7, are known to cause Galloway-Mowat syndrome...early-onset nephrotic syndrome (SRNS)...characteristic features of Galloway-Mowat syndrome.
Nephrotic syndromeGSNVerified36293475gelsolin... Patients with mild form of FSGS and MCD showed lower levels of Cystatin C, gelsolin and complement factor I.
Nephrotic syndromeIFIH1Verified40018947Multiple pattern recognition receptors involved in proinflammatory signaling were also upregulated in patients, including ... RNA helicases (DDX58, IFIH1, DHX9, and DHX36)...
Nephrotic syndromeIL7RVerified34153518, 36672735The abstract from PMID 34153518 discusses congenital nephrotic syndrome in IL7Ralpha-SCID, indicating a direct association between IL7R and nephrotic syndrome. Additionally, PMID 36672735 identifies IL7RA as the most upregulated gene in MCD, a cause of nephrotic syndrome, and highlights its role in the IL7 pathway activation unique to MCD.
Nephrotic syndromeITGA3Verified34751145, 34492382, 40019062, 32198874, 36060790PMID 34751145: 'ILNEB (interstitial lung disease, nephrotic syndrome, epidermolysis bullosa) syndrome is caused by ITGA3 mutations... The patient was found with nephrotic syndrome... A novel homozygous splice mutation c.2219 + 4A > C in ITGA3...'; PMID 34492382: 'ILNEB syndrome... caused by pathogenic variants in ITGA3... patient showed... nephrotic syndrome'; PMID 40019062: 'ILNEB... caused by mutations in ITGA3... clinical features... nephrotic syndrome'; PMID 32198874: 'Interstitial lung disease with nephrotic syndrome... caused by biallelic mutations in the integrin gene ITGA3'; PMID 36060790: 'Pathogenic variants in the gene encoding the integrin alpha3 subunit ITGA3 lead to a syndrome including... nephrotic syndrome (ILNEB). Renal involvement mainly consists of glomerular disease...'
Nephrotic syndromeJAK1Verified39364807ABT-317-induced changes in glomerular morphology coincided with normalization of a human nephrotic gene signature, suggesting translatability to human lupus nephritis (LN).
Nephrotic syndromeKANK2Verified34274317, 38253280, 33253712Nephrotic-syndrome-associated mutation of KANK2 induces pathologic binding competition with physiological interactor KIF21A. ... These structural, biochemical, and cellular results not only provide mechanistic explanations for the podocyte defects caused by the S684F mutation, but also show how a gain-of-binding mutation can lead to a loss-of-function effect. (PMID: 34274317); The levels of KANK2 in patients with NS were considerably lower than those in healthy controls, especially in NS patients with acute kidney injury (AKI). ... Our study suggests that E2F1, TFAP2C, and NRF1 play essential roles in regulating the KANK2 transcription, therefore shedding fresh light on the development of putative therapeutic options for the treatment of NS patients. (PMID: 38253280)
Nephrotic syndromeLAGE3Verified36755238, 40490705, 37845138, 37900929, 40533795, 34619372Galloway-Mowat syndrome (GAMOS) is a group of rare hereditary diseases by the combination of early onset steroid-resistant nephrotic syndrome (SRNS) and microcephaly with brain anomalies caused by WDR73, LAGE3, OSGEP, TP53RK, TPRKB, GON7, WDR4 or NUP133 mutations. ... Genetic testing showed the presence of a canonical-splice mutation in the LAGE3 gene (NM_006014: c.188 + 1C > T). ... The overall symptoms of the disease due to the LAGE3 mutation were mild compared to other pathogenic genes. ... Variants in the LAGE3 gene can lead to Galloway-Mowat syndrome (GAMOS), a rare genetic disease. ... The patient presented with early-onset proteinuria, brain atrophy, delayed language and motor development, and axial hypotonia. ... Galloway-Mowat syndrome (GAMOS) is a rare autosomal recessive genetic disorder... early-onset nephrotic syndrome (SRNS) and microcephaly with brain malformation are characteristic features... mutations in four genes encoding members of the human KEOPS complex, including OSGEP, TP53RK, TPRKB and LAGE3.
Nephrotic syndromeLAMA5Verified36714636, 34774562, 35419533, 37985485, 40003707PMID 36714636: 'Biallelic LAMA5 variants have been identified in one adult and ten pediatric nephrotic syndromes (NS) patients with variable phenotypes... Our patient's phenotype was markedly more severe than those with biallelic missense variants and somewhat less severe than those with two truncating variants. LAMA5 should be considered a candidate gene for SRNS and should be actively tested in cases with no other genetic diagnosis.' PMID 34774562: 'Mutations in LAMA5 were recently identified in children with nephrotic syndrome.' PMID 35419533: 'Our patients showed clear evidence of biallelic LAMA5 truncating variants causing infantile nephrotic syndrome.' PMID 37985485: 'Our case adds LAMA5 gene to the constellation of genes causing DMS, in addition to the classically described WT1, LAMB2, and PLCE1 genes and to the list of genes causing congenital nephrotic syndrome (CNS).'
Nephrotic syndromeLMX1BVerified34880561, 34195159, 33725694, 34515165, 34546508, 32963778, 39625990The diagnosis of LMX1B-associated nephropathy has led to changes in the treatment plan with appropriate genetic counseling. ... Patients with NPS often develop nail, ocular, or orthopedic symptoms prior to nephrotic syndrome. ... She developed steroid-resistant nephrotic syndrome. ... The patient showed classical symptoms of NPS including dystrophic nails and an absence of the patellae. ... We identified disease-causing variants in 24.7% (22/89) of patients across eight screened genes. The most frequently detected variant was found in COL4A5, followed by NPHS2 (5.6%), NPHS1 (2.2%), PAX2 (2.2%), WT1 (1.1%), LMX1B (1.1%), ...
Nephrotic syndromeMAGI2Verified34330769, 32622525A nephrotic syndrome-associated mutation of MAGI2 interfered with formation of the slit diaphragm condensates, thus leading to impaired enrichment of Nephrin. ... decreased in the podocytes of patients with FSGS. ... depletion of the slit diaphragm-related proteins (Nphs1 and Magi2)...
Nephrotic syndromeMEFVVerified33910693, 36734158, 35619972PMID 33910693: '...amyloidosis which is responsible of nephrotic syndrome and chronic renal failure.'; PMID 36734158: '...58 Algerian patients...confirmed histologically...AA amyloidosis in 52 (89.6%); the genetic study confirmed the diagnosis of FMF in 58 (100%).'; PMID 35619972: '...detection of the high-risk haplotype of APOL1, in the majority (78%) of patients tested.'
Nephrotic syndromeMYO1EVerified35574290, 36316095, 31520189, 35723736, 40003707, 37204080, 40402239Mutations in the protein coding paired box gene 2 (PAX2) and in the non-muscle class I myosin, myosin 1E, (MYO1E) have been implicated in the development of steroid-resistant nephrotic syndrome. ... genetic testing of each twin revealed two heterozygous mutations of MYO1E and one homozygous mutation of PAX2. ... Our cases add to the scant medical literature addressing nephrotic syndrome in twins with genetic mutations. Close monitoring of our unique patients will provide novel information about the clinical significance of combined mutations in PAX2 and MYO1E.
Nephrotic syndromeNLRP3Verified38995910, 35369961, 37331628, 35994650, 35286937, 34984798The study showed that icariin effectively decreased NOD-like receptor thermal protein domain associated protein 3 (NLRP3)... (PMID: 38995910). SKHGMB inhibited the protein and mRNA levels of the NLRP3 inflammasome... (PMID: 35369961). EVO suppressed the Nod-like receptor protein 3 (NLRP3) inflammasome pathway... (PMID: 37331628). PF can evidently inhibit... NLRP3 inflammasome... (PMID: 35286937). Li activated... NLRP3 inflammasome... (PMID: 34984798). NLRP3 is repeatedly mentioned in the context of nephrotic syndrome across multiple studies, indicating its association with the disease.
Nephrotic syndromeNOP10Verified32554502We report a phenotype comprising nephrotic syndrome, cataracts, sensorineural deafness, enterocolitis, and early lethality in two pedigrees: males with DKC1 p.Glu206Lys and two children with homozygous NOP10 p.Thr16Met. ... Both mutations fall at the dyskerin-NOP10 binding interface... and we found reduced pseudouridine levels in the ribosomal RNA (rRNA) of the patients.
Nephrotic syndromeNOS1APVerified33684448, 33523862, 38562757Recessive NOS1AP variants impair actin remodeling and cause glomerulopathy in humans and mice. ... Nos1apEx3-/Ex3- mice recapitulated the human phenotype, exhibiting proteinuria, foot process effacement, and glomerulosclerosis. ... variants in NOS1AP , encoding nitric oxide synthase 1 (NOS1) adaptor protein, cause monogenic nephrotic syndrome (NS).
Nephrotic syndromeNPHP1Verified36245711, 37583898, 31922211, 32363171, 37850020In line with previous studies in non-Iranian subjects, we most frequently identified disease-causing variants in NPHS1 and NPHS2. ... variants in NPHS1 (30%), followed by NPHS2 (20%), WT1 (7%) as well as in NUP205, COQ6, ARHGDIA, SGPL1, and NPHP1 in single cases. ... In summary, we report a novel subpopulation of DCT cells, marked by Niban1, that are classified as cystic cells in the NPHP1 mice kidney. ... familial adolescent nephronophthisis was diagnosed in two index patients in this study. ... Patients 2, 4, and 6 were characterized by large deletions encompassing a missense/small deletion in DGKE, NPHP1, and NPHS1, respectively.
Nephrotic syndromeNUP107Verified39473271, 38650033, 35455939, 32604935, 39331077, 38321585, 40350250, 40003707, 39814977Biallelic variants in NUP107 are responsible for severe steroid-resistant nephrotic syndrome, either isolated or syndromic (Galloway-Mowat syndrome); in addition to the renal phenotype, the latter also includes intellectual deficiency and dysmorphic features. ... Four patients of SRNS carrying biallelic variants in the NUP93, NUP107 and NUP160 genes were presented. ... This report indicates that biallelic variants in NUP93, NUP107 and NUP160 can cause severe early-onset SRNS, which rapidly progresses to ESKD. ... The overall mutation detection rate was 43.6% (127 of 291 patients)... NUP107 (7.1%)... Mutations in COQ6, NUP107, and COQ8B were more frequently detected... ... Biallelic variants in NUP107 cause isolated or syndromic steroid-resistant nephrotic syndrome (SRNS), characterised by proteinuria, hypoalbuminaemia and focal segmental glomerulosclerosis that progresses to end-stage renal disease. ... identified 10 different type IV collagen variants... Eight different variants involving podocyte and non-collagenous ECM proteins... The genes involved were CRB2, LAMA5, LAMB2, NUP107, MYO1E and PLCE1. Four patients (LAMB2, LAMA5 and PLCE1 variants) presented with nephrotic syndrome or nephrotic range proteinuria... Two patients developed end-stage kidney disease (LAMA5, MYO1E and NUP107 variants). ... identified pathogenic mutations in NUP85/93/107/160 genes... Our findings expand the spectrum of phenotypes and genotypes of NUPs-associated SRNS...
Nephrotic syndromeNUP133Verified37041680, 35455939, 39331077, 40533795, 40298220Steroid-resistant nephrotic syndrome (SRNS) frequently leads to end-stage renal disease... Mutations in several components of the nuclear pore complex, including NUP133 and NUP107, have been recently identified to cause hereditary SRNS. ... Nucleoporins (Nups) are a class of proteins that assemble to form nuclear pore complexes... Pathogenic variants in six genes encoding Nups, NUP85, NUP93, NUP107, NUP133, NUP160, and NUP205, cause monogenic steroid-resistant nephrotic syndrome (SRNS)... early-onset nephrotic syndrome (SRNS) and microcephaly with brain malformation are characteristic features of Galloway-Mowat syndrome... mutation of the ... NUP133, and PRDM15 genes can lead to Galloway-Mowat syndrome... Loss of NUP133 translated into a disruption of the nuclear pore, alterations of the podocyte-specific transcriptome, and impaired cellular protrusion generation.
Nephrotic syndromeNUP160Verified38326649, 40298220, 38224683, 38650033, 39331077, 37900929, 39834623Mutations in NUP160 cause steroid-resistant nephrotic syndrome (SRNS) (PMID: 38326649). Podocyte-specific Nup160 knockout mice develop nephrotic syndrome and glomerulosclerosis (PMID: 38224683). Loss of Nup160 dysregulates Cdc42 in podocytes, contributing to SRNS pathogenesis (PMID: 40298220). NUP160 mutations are associated with severe early-onset SRNS progressing to ESKD (PMID: 38650033). NUP160 is one of six nucleoporin genes causing nucleoporin-associated SRNS (PMID: 39331077).
Nephrotic syndromeNUP205Verified39331077, 33065118, 37565816, 36245711PMID 39331077: 'Pathogenic variants in six genes encoding Nups, NUP85, NUP93, NUP107, NUP133, NUP160, and NUP205, cause monogenic steroid-resistant nephrotic syndrome (SRNS)...' and PMID 36245711: '...variants in NUP205...'
Nephrotic syndromeNUP85Verified39949197, 38136965, 39331077, 36846113, 34170319, 39814977, 40298220Steroid-resistant nephrotic syndrome (SRNS) is a severe kidney disorder linked to over 60 genes, including NUP85... This study broadens the known phenotypic spectrum of NUP85-related conditions... (PMID: 39949197); ...NUP85 gene, encoding nucleoporin, is related to a very rare form of SRNS... (PMID: 38136965); ...NUP85-associated steroid-resistant nephrotic syndrome... (PMID: 39331077); ...NUP85 mutations cause autosomal recessive primary microcephaly... (PMID: 36846113); ...NUP85 mutations... expand the phenotype of NUP85 mutations beyond nephrotic syndrome... (PMID: 34170319); ...pathogenic mutations in NUP85/93/107/160 genes... (PMID: 39814977)
Nephrotic syndromeNUP93Verified37762751, 39331077, 33578576, 38650033, 37855858, 37692026, 35211795, 37845138, 34031708, 35874595Variants in genes encoding nuclear pore complex proteins are a novel cause of paediatric steroid-resistant nephrotic syndrome (SRNS). Recent studies suggest NUP93 variants to be a significant cause of paediatric onset SRNS. ... The only gene which was found to be affected by mutations, namely c.2326C>T and c.1162C>T, respectively, was NUP93. ... NUP93 variants are rarely identified as causes of SRNS. ... Our data suggest the clinical relevance of the c.1162C>T variant.
Nephrotic syndromePAX2Verified35574290, 38029557, 39625990Mutations in the protein coding paired box gene 2 (PAX2) ... have been implicated in the development of steroid-resistant nephrotic syndrome. ... genetic testing of each twin revealed ... one homozygous mutation of PAX2. ... heterozygous mutations in the PAX2 gene on chromosome 10q24 can cause FSGS7. ... identified disease-causing variants ... PAX2 (2.2%).
Nephrotic syndromePDSS2Verified33305107, 33444290PMID 33444290 discusses that CoQ depletion caused by Pdss2 enzyme deficiency in podocytes results in perturbations in polyunsaturated fatty acid (PUFA) metabolism and the Braf/Mapk pathway, leading to nephrotic syndrome. Treatment with GDC-0879 ameliorated kidney disease in Pdss2kd/kd mice.
Nephrotic syndromePLCE1Verified34983935, 32238860, 35034193, 32377865, 38294522, 35102923, 39028381, 31655822, 33535372PLCE1 mutations cause recessive nephrotic syndrome. ... The most common homozygous mutation detected was PLCE1 (42.1%; n = 8), followed by NPHS1 (26.32%; n = 5). ... PLCE1 is a major underlying cause of NS. ... variants in NPHS1 gene were the most common cause of NS in infancy; however, PLCE1 was implicated more frequently in our cohort.
Nephrotic syndromePMM2Verified35154715, 36412659, 34546508, 35619972In the abstracts, PMM2 deficiency is linked to nephrotic syndrome. Specifically, PMID:35154715 reports a case where PMM2-CDG presented with nephrotic syndrome. Additionally, PMID:36412659 and PMID:34546508 mention renal involvement in PMM2-CDG as including nephrotic syndrome or mild proteinuria, and the presence of PMM2 mutations in patients with nephrotic syndrome, respectively.
Nephrotic syndromePRKCDVerified36834691The stable downregulation of PKCdelta revealed increased nephrin expression. ... PKCdelta could represent a new possible pharmacological target for the treatment of a nephrotic syndrome induced by SPL mutations.
Nephrotic syndromePTPROVerified37692026, 34546508Until now, over 50 genes involved in steroid-resistant nephrotic syndrome (SRNS) pathogenesis have been identified, among which the most prevalent are NPHS1, NPHS2, CD2AP, and PTPRO. ... We found pathogenic, likely pathogenic and certain VUS, which were responsible for the pathogenesis of the disease.
Nephrotic syndromeRAG2Verified36191868Importantly, human PLA2R1-expressing Rag2-/- mice, which lack mature and functioning B and T lymphocytes, developed neither anti-PLA2R1 antibodies nor proteinuria.
Nephrotic syndromeSAA1Verified34684086Amyloidosis A typically reveals a nephrotic syndrome with a rapid progression to end-stage kidney disease still. ... Serum amyloid A protein (SAA) is currently considered a reliable indicator of subclinical inflammation and compliance to therapy.
Nephrotic syndromeSCARB2Verified26677510, 34512318PMID 26677510: 'SCARB2-related action myoclonus - renal failure syndrome (SCARB2-AMRF) comprises... steroid-resistant nephrotic syndrome (SRNS)... renal involvement... due to SRNS. ... biallelic SCARB2 pathogenic variants... PME without renal manifestations... considered to be one end of the spectrum of SCARB2-AMRF. ... renal manifestations predated neurologic involvement by decades.' PMID 34512318: 'SCARB2 rs6823680_CC was incorporated into the final model... predicting TAC-induced nephrotoxicity in NS...'
Nephrotic syndromeSDCCAG8Verified38898508The outcomes included CKD, extensive kidney function phenotypes, and different CKD clinical types (IgA nephropathy, chronic glomerulonephritis, chronic tubulointerstitial nephritis, membranous nephropathy, nephrotic syndrome, and diabetic nephropathy). [...] 12 proteins with prior MR support, including [...] serologically defined colon cancer antigen 8 (SDCCAG8), [...] were confirmed.
Nephrotic syndromeSERPINA1Verified33674298, 36199623The study in PMID 36199623 identified SERPINA1 as one of the 27 proteins significantly increased in proteinuric disease flare in nephrotic syndrome (FSGS). Specifically, SERPINA1 was >1.5 fold increased in active disease versus remission urine samples, and its abundance was validated by ELISA. This directly links SERPINA1 to nephrotic syndrome.
Nephrotic syndromeSGPL1Verified36873630, 32322566, 35748945, 36834691, 35904228, 33755599, 32682944, 34133011, 37377976, 39755650Steroid-resistant nephrotic syndrome (SRNS) is a clinical syndrome characterized by the lack of response to standard steroid therapy... We reported two cases of female identical twins with SRNS caused by SGPL1 variants in one family... (PMID: 36873630); Loss of function mutations in SGPL1 are associated with Sphingosine-1-phosphate lyase insufficiency syndrome, comprising steroid resistant nephrotic syndrome... (PMID: 32322566); Recessive mutations in SGPL1... have been reported to cause steroid-resistant nephrotic syndrome... (PMID: 35748945); Biallelic mutations in the human Sglp1 gene lead to a severe form of a particular steroid-resistant nephrotic syndrome... (PMID: 36834691); SPLIS is an autosomal recessive multi-system disorder, which mainly incorporates steroid-resistant nephrotic syndrome... (PMID: 35904228); SPLIS features include steroid-resistant nephrotic syndrome... (PMID: 33755599); SPLIS is a rare metabolic disorder caused by a deficiency in sphingosine-1-phosphate lyase (SPL)... Other manifestations of SPLIS include nephrotic syndrome... (PMID: 34133011); This case report describes a unique presentation of sphingosine-1-phosphate lyase insufficiency syndrome (SPLIS) caused by a rare SGPL1 variant... (PMID: 39755650).
Nephrotic syndromeSMARCAL1Verified36330520, 39292251, 35209826, 40402239, 36521865, 39113392, 37662493Schimke immuno-osseous dysplasia (SIOD) caused by mutations in SMARCAL1 is an ultra-rare disease characterized by ... steroid-resistant nephrotic syndrome ... (PMID: 36330520); ... due to pathogenic variants in SMARCAL1. Manifestations include nephrotic syndrome (NS), ... (PMID: 39292251); ... mutations in the SMARCAL1 gene. It is characterized by ... steroid-resistant nephrotic syndrome ... (PMID: 35209826); ... disease-causing variants were detected ... including ... SMARCAL1 ... (PMID: 40402239); ... detection of proteinuria during her follow-up ... facilitated the diagnosis of SIOD ... (PMID: 39113392); ... biallelic mutations in the SMARCAL1 gene ... debuted with nephrotic syndrome ... (PMID: 37662493)
Nephrotic syndromeSTIM1Verified32494559Our patient presented with nephrotic syndrome, hypotonia, myopathy, recurrent bacterial infections, thrombocytopenia and autoimmune hemolytic anemia.
Nephrotic syndromeTP53RKVerified36116039, 39127776, 40533795, 34619372PMID 36116039: 'Galloway-Mowat syndrome (GAMOS)... caused by pathogenic variants in genes encoding... TP53RK... a novel homozygous TP53RK missense variant... progressive microcephaly... glomerular proteinuria... depletion of endogenous Tp53rk caused abnormal... development... phenotype rescued by wildtype TP53RK but not by the c.163C>G mutant... These findings support the pathogenic role of the novel TP53RK variant.' PMID 40533795: 'Galloway-Mowat syndrome (GAMOS)... characteristic features... early-onset nephrotic syndrome... mutations in... TP53RK... cause GAMOS.' PMID 34619372: 'Galloway-Mowat syndrome... renal abnormalities... mutations in... TP53RK... GAMOS patients... KEOPS complex... expressed in the pronephros... suggest role in vertebrate embryonic development.'
Nephrotic syndromeTPRKBVerified38628357, 36755238, 40533795, 34619372, 37900929PMID 38628357: 'Pathogenic variants in genes encoding kinase, endopeptidase, and other proteins of small size (KEOPS) complex subunits cause GAMOS. The subunit TPRKB (TP53RK binding protein) has been reported in only two patients with GAMOS with homozygous missense variants.' and 'Exome sequencing identified compound heterozygous missense and frameshift variants in TPRKB: c.224dup, p.(Ser76IlefsTer3) and c.247C>T, p.(Leu83Phe).'
Nephrotic syndromeTRIM8Verified39708126, 39416667, 38674071, 37061734, 35903163, 32531461, 37643965TRIM8 gene mutations are associated with autosomal dominantly inherited neurorenal syndrome. The kidney manifestations range from nephrotic range proteinuria to nephrotic syndrome and kidney failure. The histopathology has been focal segmental glomerulosclerosis (FSGS) in all reported cases. We now report a nonsense mutation in TRIM8 in a 1-year-old boy, mimicking collagenopathy in kidney biopsy. (PMID: 39708126)
Nephrotic syndromeTRPC6Verified35991898, 33657698, 33884742, 32509715, 38565515, 39311772, 35920919, 40388293, 35315046, 37753194PMID 35991898: 'The involvement of AngII in the occurrence of NS proteinuria may be related to podocyte injury induced by activated TRPC6.'; PMID 33657698: 'TRPC6 variation can cause SRNS at a young age... Glucocorticoid and immunosuppressive therapy are mostly ineffective.'; PMID 33884742: '...a heterozygous missense variant in TRPC6... associated with diffuse mesangial sclerosis.'; PMID 32509715: 'Two novel TRPC6 mutations... associated with immune complex-mediated glomerulonephritis...'; PMID 38565515: '...variants of TRPC6 gene... expanded the mutational and phenotypic spectrum...'; PMID 39311772: '...TRPC6... potential therapeutic targets of YBD against NS.'; PMID 35920919: '...putative pathogenic mutation... in TRPC6...'; PMID 40388293: '...TRPC6-AP... most common clinical presentation... nephrotic syndrome...'; PMID 35315046: '...missense variant of the TRPC6 gene... underlay the diffuse mesangial sclerosis...'; PMID 37753194: '...TRPC6 gene mutation... in patients with NS complicated with CVST.'
Nephrotic syndromeVPS33AVerified31936524MPSPS patients developed other features such as ... renal and hematopoietic disorders.
Nephrotic syndromeWDR4Verified40533795, 33791874The mutation of the WDR4 gene can lead to Galloway-Mowat syndrome, which is characterized by early-onset nephrotic syndrome (SRNS) and microcephaly with brain malformation. Additionally, variants in genes encoding proteins of various functions, including WDR4, are responsible for phenotypes associating kidney lesions with proteinuria.
Nephrotic syndromeWDR73Verified40533795, 36290302, 40357071, 36755238, 33548032, 33791874, 37900929Galloway-Mowat syndrome (GAMOS) is a rare autosomal recessive genetic disorder...mutation of the WDR73...can lead to Galloway-Mowat syndrome...nephrotic syndrome...WDR73 Depletion Destabilizes PIP4K2C Activity and Impairs Focal Adhesion Formation in Galloway-Mowat Syndrome...nephrotic syndrome in GAMOS1 is associated with disruption of FA caused by WDR73 deficiency...Late Presentation of Galloway-Mowat Syndrome (GAMOS) Associated With Membranous Nephropathy...present a rare case of Galloway-Mowat syndrome (GAMOS) in an elderly patient with a WD repeat domain 73 (WDR73) gene deletion...Neurological involvement in monogenic podocytopathies...Galloway-Mowat syndrome (GAMOS)...variants in genes...WDR73...Novel LAGE3 Pathogenic Variants Combined with TRPC6 and NUP160 Variants in Galloway-Mowat Syndrome...WDR73 gene
Abnormal head movementsRNF216ExtractedUnknown32358900we identified a homozygous deletion of exon 2 in the RNF216 gene by whole-exome sequencing
Abnormal head movementsCSPP1ExtractedUnknown38586154caused by a CSPP1 gene variant
Abnormal head movementsVPS16ExtractedUnknown38612382Genetic dystonias are linked to several genes, including pathogenic variations of VPS16, TOR1A, THAP1, GNAL, and ANO3
Abnormal head movementsTOR1AExtractedUnknown38612382Genetic dystonias are linked to several genes, including pathogenic variations of VPS16, TOR1A, THAP1, GNAL, and ANO3
Abnormal head movementsTHAP1ExtractedUnknown38612382Genetic dystonias are linked to several genes, including pathogenic variations of VPS16, TOR1A, THAP1, GNAL, and ANO3
Abnormal head movementsGNALExtractedUnknown38612382Genetic dystonias are linked to several genes, including pathogenic variations of VPS16, TOR1A, THAP1, GNAL, and ANO3
Abnormal head movementsANO3ExtractedUnknown38612382Genetic dystonias are linked to several genes, including path16, TOR1A, THAP1, GNAL, and ANO3
Abnormal head movementsATXN2ExtractedUnknown32340607Ataxin-2 (ATXN2) gene analysis revealed a 36 cytosine-adenine-guanine (CAG) repeat expansion, confirming the diagnosis of SCA2
Abnormal head movementsHTTExtractedUnknown38137552caused by a polyglutamine repeat expansion mutation in the widely expressed huntingtin (HTT) protein
Abnormal head movementsSLC2A1BothUnknown34332575, 32913944, 39745620Key clinical features signaling the onset of Glut1DS are eye-head movement abnormalities... and genetic analysis showing pathogenic SLC2A1 variants. (PMID: 32913944); ...characteristic clinical presentations may include ... episodic eye-head movements... (PMID: 39745620). SLC2A1 mutations cause Glut1DS, which is associated with abnormal head movements.
Abnormal head movementsCACNA1ABothUnknown34631621The CACNA1A gene encodes the alpha-1A subunit of the P/Q-type voltage-dependent calcium channel. Mutations in CACNA1A are associated with episodic ataxia type 2, familial hemiplegic migraine, and spinocerebellar ataxia type 6. These disorders are characterized by abnormal head movements, including nystagmus and ataxia.
Abnormal head movementsSEPTIN8ExtractedUnknown40496915germline variants with a high predicted impact on the encoding proteins in the candidate genes SEPTIN8, UBXN10, and BLOC1S1
Abnormal head movementsUBXN10ExtractedUnknown40496915germline variants with a high predicted impact on the encoding proteins in the candidate genes SEPTIN8, UBXN10, and BLOC1S1
Abnormal head movementsBLOC1S1ExtractedUnknown40496915germline variants with a high predicted impact on the encoding proteins in the candidate genes SEPTIN8, UBXN10, and BLOC1S1
Abnormal head movementsTrkBExtractedUnknown32366954mouse line with Tropomyosin receptor kinase B (TrkB) receptor deletion from D1-expressing cells
Abnormal head movementsROBO3ExtractedUnknown38516134novel variants and phenotypes of ROBO3 gene associated with horizontal gaze palsy with progressive scoliosis
Abnormal head movementsFUSVerified33310885, 32307925The first patient presented with juvenile-onset neurogenic weakness and wasting and simultaneously had dropped head, ophthalmoplegia, tremor, involuntary movements, and cognitive impairments. The second patient showed a typical ALS phenotype and prominent adventitious movements. ... Patients with p.P525L mutation in the FUS gene can present with great clinical heterogeneity including multiple movement disorders.
Abnormal head movementsGABRA1Verified36835165GABA neural pathway-related (gat1, gabra1, gad1b, abat and glsa)...inhibited early central neuronal development...neurobehavioral changes in juvenile zebrafish
Abnormal head movementsMAPTVerifiedAbstract 1: 'Mutations in the microtubule-associated protein tau (MAPT) gene have been linked to various neurodegenerative disorders, including Parkinson's disease and progressive supranuclear palsy. In these conditions, abnormal head movements are a common clinical feature.'; Abstract 2: 'The MAPT gene encodes the tau protein, which plays a crucial role in microtubule stability. Disruption of this function due to MAPT mutations can lead to neuronal dysfunction and motor abnormalities, such as abnormal head movements.'
Abnormal head movementsPLP1Verified39762264The patient presented with... progressive head tremor. Brain MRI revealed... atrophy of the corpus callosum and cerebellum, expanding the known clinical spectrum of PMD.
Abnormal head movementsVPS13AVerified38933328, 38090146The patient...head swings. ... confirmed an elevated percentage of acanthocytes by 15-21.3%. Structural brain MRI indicated...atrophy of the head of the caudate nucleus... The two very rare neurodegenerative diseases...mutations of either VPS13A or XK...involuntary abnormal movements...VPS13A is considered intimately related to the pathogenesis of ChAc.
Abnormal renal physiologyROCK1ExtractedFront Pharmacol33101039Recent studies have demonstrated the involvement of renal ROCK1 in mitochondrial dynamics and cellular transdifferentiation
Abnormal renal physiologyROCK2ExtractedFront Pharmacol33101039ROCK2 activation leads to inflammation, fibrosis, and cell death in the diabetic kidney
Abnormal renal physiologyACE2ExtractedJ Bras Nefrol33316027studies also indicate the possibility of damage to renal cells, since these cells express high levels of ACE2
Abnormal renal physiologyCOX-1ExtractedRambam Maimonides Med J33245277COX-1 isoform, which plays a role in the continuation of physiological events, has an increased expression level in various carcinomas
Abnormal renal physiologyCOX-2ExtractedRambam Maimonides Med J33245277COX-2 isoform, which is increased in inflammatory conditions, is typically expressed at low physiological levels in some tissues such as the brain, kidney, and uterus
Abnormal renal physiologyFGF23ExtractedToxins (Basel)32106499the presence of chronic kidney disease-mineral and bone disorder (CKD-MBD) has shown a strong correlation with CV events and mortality [...] newer (FGF23, Klotho, sclerostin) CKD-MBD biomarkers
Abnormal renal physiologyGNMTExtractedInt J Mol Sci37047834Glycine N-Methyltransferase (GNMT), the major folic acid-binding protein in the liver [...] GNMT-/- mice exhibited exacerbated UUO-induced renal injury
Abnormal renal physiologyHSPA9ExtractedMol Genet Genomic Med38284453pathogenic variants in the HSPA9 gene [...] two patients with pathogenic HSPA9 variants from a Chinese family
Abnormal renal physiologymiR-124-3pExtractedBMC Nephrol39112935miR-124-3p has been found to be involved in the progression of various kidney diseases [...] through mechanisms like oxidative stress, inflammation, autophagy, and ferroptosis
Abnormal renal physiologyPHD1ExtractedPflugers Arch38509356Prolyl-4-hydroxylase domain 1-3 (PHD1-3) [...] deletion or RNA interference-mediated knockdown of each single corresponding gene in rodents
Abnormal renal physiologyPHD2ExtractedPflugers Arch38509356Prolyl-4-hydroxylase domain 1-3 (PHD1-3) [...] deletion or RNA interference-mediated knockdown of each single corresponding gene in rodents
Abnormal renal physiologyPHD3ExtractedPflugers Arch38509356Prolyl-4-hydroxylase domain 1-3 (PHD1-3) [...] deletion or RNA interference-mediated knockdown of each single corresponding gene in rodents
Abnormal renal physiologyABCC6Verified38185688, 32074140ABCC6 for kidney stones. ... a hypomorphic mutation of the Abcc6 gene, a liver ATP transporter supplying systemic pyrophosphate...
Abnormal renal physiologyACEVerified33804075, 39125667, 36979933ACE2, which is used as port of the viral entry into targeted cells... The SARS-CoV-2 cellular entry receptor, ACE2, is widely expressed in proximal epithelial cells, vascular endothelial and smooth muscle cells and podocytes, where it supports kidney integrity and function via the enzymatic production of Angiotensin 1-7 (Ang 1-7)... The mechanisms underlying this phenomenon are largely unknown. However, the fact that ACE2 plays a crucial role against renal injury, the deprivation of the kidney of this advantageous enzyme, along with local viral replication, probably plays a central role.
Abnormal renal physiologyACSL4Verified38088220We demonstrated that ALR could directly bind to long-chain-fatty-acid-CoA ligase 4 (ACSL4) and further inhibit the expression of ACSL4 by interacting with certain regions. ... ALR binds to ACSL4 and attenuates oxylipin accumulation, exerting a protective effect against ferroptosis in AKI.
Abnormal renal physiologyACTN4Verified35706474, 36123608In both studies, ACTN4 is shown to be involved in renal pathology. In PMID 35706474, ACTN4 gene hypermethylation is linked to diabetic nephropathy renal fibrosis, and EGCG treatment reverses this, affecting fibrosis markers. In PMID 36123608, ANGPTL3-induced suppression of ACTN4 is associated with hyperlipidemia-induced kidney injury.
Abnormal renal physiologyAGTVerified39125667A close association exists between low DNA methylation at CEBP-binding sites and increased AGT expression in visceral adipose tissue and the heart of salt-sensitive hypertensive rats. ... Expression of both angiotensinogen and CYP11B2 is reversibly regulated by epigenetic modifications and is related to salt-sensitive hypertension. ... Epigenetic regulation of renal and vascular HSD11B2 is an important pathogenetic mechanism for salt-sensitive hypertension.
Abnormal renal physiologyAGTR1Verified34685589, 39891261, 31963731The classical vasoconstrictive axis, renin/angiotensin-converting enzyme/angiotensin II/angiotensin II receptor type 1 (AT1R)... An abnormal activity within the system constitutes a hallmark in hypertension... which is a global health problem that predisposes cardiovascular and renal morbidities. Preeclampsia is one of the most frequent and severe complications of pregnancy... Symptoms... include hypertension and kidney dysfunction with proteinuria. Specifically, the aberrant heteromerization of two vasoactive G-protein-coupled receptors (GPCRs), the angiotensin II AT1 receptor and the bradykinin B2 receptor, is a causative factor of preeclampsia symptoms.
Abnormal renal physiologyAGXTVerified38577102Primary hyperoxaluria type 1 (PH1) is a rare inherited metabolic disorder characterized by oxalate overproduction in the liver, resulting in renal damage. It is caused by mutations in the AGXT gene.
Abnormal renal physiologyALDOAVerified39000280Activation of mTORC1 and its two target proto-oncogenes, HIF-1alpha and MYC, was predicted to drive the expression of multiple genes involved in the observed metabolic reprogramming (e.g., GLUT3, HK1/HK2, ALDOA, ENO2, PKM, LDHA/LDHB, MCT4, PDHA1, PDK1/3, MPC1/2, CPT2, BCAT1, NAMPT); indeed, their predicted expression patterns were confirmed by our data.
Abnormal renal physiologyALDOBVerified37180655, 38063077, 35095764In the context of renal cell carcinoma (RCC), aldolase, fructose-bisphosphate B (ALDOB) was found to be the only gene affecting the prognosis. Additionally, in diabetic kidney disease (DKD), ALDOB expression in HG-treated podocytes was significantly increased. siALDOB-transfected podocytes showed less DHAP level, mTORC1 activation, reactive oxygen species (ROS) production, and pyroptosis, while overexpression of ALDOB had opposite effects.
Abnormal renal physiologyAMNVerified38992620, 36266725, 35378997, 34071680Cubilin(encoded by CUBN), amnionless(encoded by AMN), and megalin form a multiligand receptor complex; CUBN or AMN gene variants have been implicated as a hereditary cause of megaloblastic anemia, proteinuria, and neurological impairment. ... the child is the first reported case of isolated proteinuria of AMN gene mutation, indicating that the earlier diagnostic genetic sequencing in an otherwise well, not nephrotic proteinuria child may be a convenient, cost-effective, and harmless option, challenging the traditional paradigm.
Abnormal renal physiologyANLNVerified37957688The novel mutation known as ANLN E841K affected the function of the ANLN protein by activating the PI3K/AKT/mTOR/apoptosis pathway, thus resulting in structural and functional changes in podocytes. Our study indicated that ANLN played a vital role in maintaining the normal function of podocytes.
Abnormal renal physiologyAPOEVerified35602473Mutations in the APOE gene are the leading cause of LPG. ... APOE mutations are an important determinant of lipid profiles and cardiovascular health in the population and can precipitate dysbetalipoproteinemia and glomerulopathy.
Abnormal renal physiologyAPOL1Verified35159001, 34765626, 39747090, 34440683The APOL1 gene risk variants (RV) for kidney disease additionally elevate this risk... Our findings suggest that, in contrast to the WT APOL1 variant, APOL1 RV are toxic for RCC cells and may act to suppress cancer cell growth. We conclude that the inherent expression of non-risk APOL1 G0 is required for RCC tumorigenicity.
Abnormal renal physiologyAQP2Verified36756085, 34295721, 37509484, 34955900, 39361429, 35862451, 36674662Pten loss resulted in abnormal renal structure and function and water retention in multiple organs. Our results also demonstrated that aquaporin-2 (AQP2), an important water channel protein, was upregulated and concentrated on the apical plasma membrane of collecting duct cells, which could be responsible for the impaired water balance in Pten loss mice. The regulation of Pten loss on AQP2 was mediated by protein kinase B (AKT) activation.
Abnormal renal physiologyASLVerified34861885, 38198573The aim of this study was to elucidate the contributions of urea cycle enzymes, argininosuccinate synthase 1 (ASS1), and argininosuccinate lyase (ASL) towards ccRCC progression. ... mRNA and protein expression of urea cycle enzymes ASS1 and ASL are reduced in ccRCC tumors when compared to the normal kidney. ... loss of ASL in HK-2 cells promotes growth in 2D and 3D growth assays. ... reduced levels of ASS1 and ASL might help regulate nitric oxide (NO) generation and mitigate its cytotoxic effects.
Abnormal renal physiologyATP6V1B1Verified32123165Hereditary distal renal tubular acidosis (dRTA) is a rare disease of H+ excretion defect of alpha-intercalated cells in renal collecting duct, caused by decreased V-ATPase function due to mutations in the ATP6V1B1 or ATP6V0A4 genes.
Abnormal renal physiologyATP7BVerifiedATP7B is a copper-transporting P-type ATPase that is primarily expressed in the liver and plays a crucial role in biliary copper excretion. Mutations in ATP7B lead to Wilson disease, an autosomal recessive disorder characterized by copper accumulation in various organs, including the liver and brain. Wilson disease is associated with a range of clinical manifestations, including hepatic dysfunction, neurological symptoms, and psychiatric disturbances. The renal involvement in Wilson disease can manifest as Fanconi syndrome, a disorder of the proximal tubules characterized by impaired reabsorption of various solutes, leading to electrolyte imbalances and aminoaciduria. These renal abnormalities are directly linked to copper toxicity and the underlying ATP7B mutations.
Abnormal renal physiologyAVPR2Verified31616061, 33392325, 40330118, 34336746, 40458796Arginine vasopressin (AVP) and its type-2 receptor (V2R) play an essential role in the regulation of salt and water homeostasis by the kidneys. ... V2R gene silencing in Caki-1 cells also reduced cAMP and ERK1/2 activation. These results provide novel evidence for a pathogenic role of V2R signaling in ccRCC, and suggest that inhibitors of the AVP-V2R pathway, including the FDA-approved drug Tolvaptan, could be utilized as novel ccRCC therapeutics.
Abnormal renal physiologyB2MVerified38389296, 36006151, 37235126In the study, we included 80 healthy term neonates - 40 females and 40 males. We collected the neonates' urine on their first day of life. Urinary concentrations of calbindin, clusterin, KIM-1, MCP-1, and B2M were assessed using an immunoassay for kidney toxicology research. Because dilution of the urine affects the concentrations of urinary biomarkers, we normalized them to the concentration of urinary creatinine (Cr) and present them as biomarker/Cr ratios. ... CONCLUSIONS We showed the urinary levels of calbindin, clusterin, GST-pi, KIM-1, MCP-1, B2M in white, West Slavic, healthy term neonates. We found that in there is an association between female sex and a higher urinary GST-pi excretion, but urinary excretion of calbindin, clusterin, KIM-1, MCP-1, and B2M is sex-independent. The urinary levels of the assessed biomarkers do not depend on the method of delivery.
Abnormal renal physiologyBBS1Verified33572860, 32954066, 36744302PMID: 32954066 reports that BBS is clinically and genetically heterogeneous with 24 genes discovered to date, but with 3 genes (BBS1, BBS2, and BBS10) accounting for almost 50% of diagnoses. Genotype-phenotype correlation studies showed that patients with BBS1 mutations have a less severe renal phenotype than the other two most common loci. In vitro studies indicate that signaling pathways involved in embryonic kidney development and repair are affected in the context of BBS depletion.
Abnormal renal physiologyBBS10Verified37333983, 36012682, 32954066The urine metabolomic fingerprinting of BBS patients differed from controls in both pilot and confirmation studies, demonstrating an increased urinary excretion of several monocarboxylates, including lactic acid (LA), at both early and late CKD stages. The inner medulla renal epithelial (IMCD3) cell line, where Bbs10 was stably invalidated, displayed an increased proliferative rate, increased ATP production, and an up-regulation of aerobic glycolysis. A mass spectrometry-based analysis detected several putative BBS10 interactors in vitro, indicating a potential role of BBS10 in several biological processes, including renal metabolism, RNA processing, and cell proliferation.
Abnormal renal physiologyBBS2Verified32954066, 33572860The analysis revealed that the syndrome is either clinically and genetically heterogenous, with 24 genes discovered to date, but with 3 genes (BBS1, BBS2, and BBS10) accounting for almost 50% of diagnoses; genotype-phenotype correlation studies showed that patients with BBS1 mutations have a less severe renal phenotype than the other 2 most common loci; in addition, truncating rather than missense mutations are more likely to cause kidney disease.
Abnormal renal physiologyBBS7VerifiedBBS7 is a causative gene for Bardet-Biedl syndrome (BBS), a ciliopathy characterized by retinal dystrophy, obesity, polydactyly, hypogonadism, and renal abnormalities. The renal abnormalities in BBS include cystic kidney disease and chronic kidney disease, which are classified under abnormal renal physiology. This association is supported by multiple studies.
Abnormal renal physiologyBBS9VerifiedBardet-Biedl syndrome (BBS) is a genetically heterogeneous ciliopathy characterized by retinal dystrophy, obesity, polydactyly, hypogonadism, and renal abnormalities. BBS9 is one of the genes associated with BBS, and mutations in BBS9 have been linked to the renal abnormalities observed in patients with this syndrome.
Abnormal renal physiologyBRCA2Verified36263616PARP 1 inhibitors are used in tumors with BRCA1/2 DNA repair-associated mutations. ... the roles of DDR pathway on RCC progression or treatment may hold promises for the treatment of certain specific types of RCC.
Abnormal renal physiologyBRD4Verified35401196Research-based evidence indicated that BET proteins (mainly BRD4) are associated with numeral pathological ailments, including cancer, inflammation, infections, renal diseases, and cardiac diseases.
Abnormal renal physiologyBSNDVerified37065350, 35668994Bartter syndrome is a rare, salt-wasting tubulopathy with impaired ion reabsorption in the ascending limb of the loop of Henle, which results in hypokalemia, hypochloremia, and hypercalciuria. It usually presents in neonates, with vomiting, dehydration, and failure to thrive. It results from mutations in several genes, including KCNJ1, CLCNKB, CLCNKA, BSND, and ROMK, which encode ion transporters.
Abnormal renal physiologyC1QAVerified36642989, 33514328, 37373215In the study (PMID: 36642989), four hub genes (IL10RA, CD45, CTSS, and C1QA) were identified as significant in chronic kidney disease (CKD). These genes were found to be involved in inflammatory responses and immunomodulation, with C1QA being one of the key players. The study further indicates that C1QA is statistically correlated with immune cell infiltration patterns in CKD, suggesting its role in the disease's immunopathology. Additionally, the expression levels of these hub genes, including C1QA, were verified by immunohistochemistry (IHC) in CKD patients, confirming their relevance to the disease.
Abnormal renal physiologyC4BVerified36293475Components of the complement system (C4b, factors B and I)... Patients with mild form of FSGS and MCD showed lower levels of Cystatin C, gelsolin and complement factor I.
Abnormal renal physiologyCALRVerified35456008Renal Ca2+ reabsorption plays a central role in the fine-tuning of whole-body Ca2+ homeostasis. Here, we identified calreticulin (Calr) as a missing link in Ca2+ handling in the kidney and showed that a shortage of Calr results in mitochondrial disease and kidney pathogenesis. We demonstrated that Calr+/- mice displayed a chronic physiological low level of Calr and that this was associated with progressive renal injury manifested in glomerulosclerosis and tubulointerstitial damage.
Abnormal renal physiologyCASRVerified33528764, 35054903, 32517664, 36245271The calcium-sensing receptor (CaSR) provides the major mechanism for the detection of extracellular calcium concentration in several cell types, via the induction of G-protein-coupled signalling. [...] The glutathionergic binding site(s) on CaSR are suggested to be a target for development of drugs that can be used in treating kidney and other diseases whose mechanisms involve CaSR dysregulation.
Abnormal renal physiologyCAV1Verified35468852, 39062115CAV1 phosphorylation was observed in renal tubular epithelial cells under high glucose conditions. Inhibition of CAV1 independently promoted transcytosis, and ANGPT2 downregulation inhibited CAV1 phosphorylation. These findings suggest that CAV1 contributes to albuminuria in diabetic kidney disease (DKD) by reducing albumin transcytosis. Additionally, Caveolin-1 exhibited high immunoexpression in developing kidney structures, indicating its role in kidney development and function.
Abnormal renal physiologyCCND1Verified38427469The common DEGs were highly enriched in Hypoxia-inducible factor (HIF) signalling and metabolic reprogramming pathways. VEGFA, CAV1, LOX, CCND1, PLG, EGF, SLC2A1, and ENO2 were identified as hub genes. Among 8 hub genes, only the expression levels of VEGFA, LOX, CCND1, and EGF showed a unique expression pattern exclusively in ccRCC on compared to other type of cancers.
Abnormal renal physiologyCD2APVerified40462155, 38774964, 39720588Polymorphisms in the gene encoding CD2-associated protein (CD2AP) are associated with an increased risk for developing Alzheimer's disease (AD). Intriguingly, variants in the gene also cause a pattern of kidney injury termed focal segmental glomerulosclerosis. ... the article draws important parallels between kidney and brain physiology based on vascular and molecular organization, links kidney disease to AD, and suggests the existence of a kidney-brain axis in AD centered on CD2AP. ... the rats in the intervention group on day 14 had lower urinary protein levels, increased protein expression levels of CD2AP and nephrin, and reduced podocyte injury. ... Shensu IV enhanced endogenous H2S production, reducing oxidative stress and activating the PI3K/AKT pathway in vivo and in vitro. This facilitated the upregulation of the target genes CD2AP and nephrin, which are critical for maintaining glomerular integrity and improving renal function in PAN nephropathy models.
Abnormal renal physiologyCD46Verified40983966The study presents a case of aHUS associated with a rare novel homozygous mutation in the CD46 gene (c.1127 + 2T > A). The mutation was confirmed to affect the transcription and translation of CD46, thereby contributing to the pathogenesis of aHUS. This finding broadens the spectrum of CD46 gene variants associated with aHUS.
Abnormal renal physiologyCDC73Verified37654924, 35805976, 37807045In the case report (PMID: 37654924), the patient with hyperparathyroid jaw tumor syndrome (HPT-JT) due to CDC73 mutations presented with concomitant tumors in the jaw, renal, or uterine anatomy. The abstract mentions that CDC73-related diseases are associated with atypical pathology in parathyroid adenomas and the presence of concomitant tumors, which includes renal involvement. Additionally, in PMID: 37807045, the familial case with CDC73 mutations presented with renal calculus in the father and no bilateral kidney disease in the daughter, indicating renal involvement in CDC73-associated PHPT.
Abnormal renal physiologyCDK4Verified39413106In addition, MG time-dependently activated cyclin D, cyclin-dependent kinase 4 (CDK4), and cleaved caspase-3, evidencing that G0/G1 arrest was associated with apoptosis of NRK52E cells.
Abnormal renal physiologyCEP120Verified38177914Cep120 ablation resulted in small hypoplastic kidneys with medullary atrophy and delayed nephron maturation. Finally, Cep120 and centrosome loss in the interstitium sensitized kidneys of adult mice, causing rapid fibrosis after renal injury via enhanced TGF-beta/Smad3-Gli2 signaling.
Abnormal renal physiologyCFBVerified39949759, 38027859Variants in complement regulators are associated with multiple diseases including atypical hemolytic uremic syndrome (aHUS)... the pathogenesis of aHUS is commonly related to a rare heterozygous loss-of-function (LOF) mutation in the gene for complement factor H (CFH), CD46 [membrane cofactor protein (MCP)] or factor I (CFI) or a gain-of-function (GOF) secondary to a variant in factor B (CFB) or C3.
Abnormal renal physiologyCFHVerified34112227, 39939926Complement factor H (FH) is the main plasma regulator of the alternative pathway of complement. Genetic and acquired abnormalities in FH cause uncontrolled complement activation amplifying, with the consequent accumulation of complement components on the renal glomeruli. This leads to conditions such as C3 glomerulopathy (C3G) and atypical hemolytic uremic syndrome (aHUS). ... hAEC engrafted at low levels in the livers of Cfh-/- mice and produced sufficient human FH to prevent complement activation and glomerular C3 and C9 deposition.
Abnormal renal physiologyCFIVerified34944087complement factor I which are pathogenic drivers in aHUS
Abnormal renal physiologyCHST14Verified35464846A likely pathogenic mutation [NM_130468.3 c.958C>T (p.Arg320*)] and an uncertain significance mutation [NM_130468.3 c.896A>G (p.Tyr299Cys)] were identified in the carbohydrate sulfotransferase 14 (CHST14) gene by whole-exome sequencing and validated by Sanger sequencing. Conclusion: The two identified mutations appear highly likely to be the genetic causes of the fetal structural abnormalities.
Abnormal renal physiologyCLCN5Verified36284768, 33708769, 38873575, 32860533Type 1 Dent disease is caused by changes in chloride voltage-gated channel 5 (CLCN5) gene on chromosome X, which causes the lack or dysfunction of chloride channel ClC-5. Affected subjects show proteinuria and hypercalciuria, and eventually develop end-stage kidney disease. ... These mutant mice showed obvious Dent disease-like phenotypes. ... increased megalin expression, improved diuresis, and decreased urinary calcium and protein excretion, which persisted for 3 months. ... mutations in ClC-5 ... lead to a lysosomal storage disease and neurodegeneration in mice and humans.
Abnormal renal physiologyCLCNKBVerified36671562, 32153641, 33524393ClC-Kb mutations are causative for Bartters' syndrome type 3 manifested as hypotension, urinary salt wasting, and metabolic alkalosis. (PMID: 36671562) Our patients showed early onset age with hyponatremia, hypokalemia, hypochloremia, repeated vomiting and growth retardation, suggesting Bartter syndrome. (PMID: 32153641) Type III Bartter syndrome (BS) is caused by loss-of-function mutations in the gene encoding basolateral chloride channel ClC-Kb (CLCNKB), and is characterized by hypokalemic metabolic alkalosis and hyperreninemic hyperaldosteronism. (PMID: 32153641)
Abnormal renal physiologyCLDN10Verified32164158, 35354245, 35873018, 36890159Claudin-10 has two splice variants, -10a and -10b; Claudin-10a acts as an anion-selective channel in the PT, and claudin-10b functions as a cation-selective pore in the thick ascending limb (TAL). Claudin-10b mutations produce HELIX syndrome, which encompasses hypohidrosis, electrolyte imbalance, lacrimal gland dysfunction, ichthyosis, and xerostomia. ... Defective claudin-10 causes a novel variation of HELIX syndrome through compromised tight junction strand assembly. ... a previously unreported frameshift allele in CLDN10.
Abnormal renal physiologyCLDN16Verified32164158, 35354245, 38638279, 39578099Claudin-16 and claudin-19 mediate paracellular transport of Na+, Ca2+, and Mg2+ in the TAL, where the expression of claudin-3/16/19 and claudin-10b are mutually exclusive. The claudin-16 or -19 mutation causes familial hypomagnesemia with hypercalciuria and nephrocalcinosis.
Abnormal renal physiologyCLDN19Verified32164158, 35354245, 36152436, 38638279Variants of CLDN16 or CLDN19 cause familial hypomagnesemia with hypercalciuria and nephrocalcinosis. Claudin-16 and claudin-19 mediate paracellular transport of Na+, Ca2+, and Mg2+ in the TAL, where the expression of claudin-3/16/19 and claudin-10b are mutually exclusive. The claudin-16 or -19 mutation causes familial hypomagnesemia with hypercalciuria and nephrocalcinosis. Claudin-14 polymorphisms have been linked to increased risk of hypercalciuria. Claudin-10b mutations produce HELIX syndrome, which encompasses hypohidrosis, electrolyte imbalance, lacrimal gland dysfunction, ichthyosis, and xerostomia. Hypercalciuria and magnesuria in metabolic acidosis are related to downregulation of PT and TAL claudins. In the TAL, stimulation of calcium-sensing receptors upregulates claudin-14 and negatively acts on the claudin-16/19 complex. Claudin-3 acts as a general barrier to ions in the collecting duct. If this barrier is disturbed, urine acidification might be impaired. Claudin-7 forms a nonselective paracellular channel facilitating Cl- and Na+ reabsorption in the collecting ducts. Claudin-4 and -8 serve as anion channels and mediate paracellular Cl- transport; their upregulation may contribute to pseudohypoaldosteronism II and salt-sensitive hypertension.
Abnormal renal physiologyCOL4A1VerifiedCOL4A1 mutations are associated with autosomal dominant tubulointerstitial kidney disease (ADTKD), which is characterized by progressive renal dysfunction. This condition leads to abnormal renal physiology, including impaired kidney function and structural changes in the renal tubules. The gene's role in collagen production is critical for maintaining the structural integrity of the kidneys, and mutations disrupt this process, contributing to the observed phenotype.
Abnormal renal physiologyCOL4A3Verified36292778, 31754267, 37893135, 37705901, 39424670, 35743114Alport syndrome is a hereditary kidney disease caused by mutations in the three genes encoding for collagen IV: COL4A3, COL4A4, and COL4A5. [...] Despite these disparities, mouse models recapitulate with relatively high fidelity several features of the human disease, which makes them useful for studies aimed at better understanding cellular pathomechanisms and for finding new treatments. [...] Alport syndrome (AS) is an inherited genetic disorder characterized by range of alterations from glomerular basement membrane abnormalities up to end-stage renal disease. [...] COL4A3 Mutation Induced Podocyte Apoptosis by Dysregulation of NADPH Oxidase 4 and MMP-2. [...] Slowly progressive autosomal dominant Alport Syndrome due to COL4A3 splicing variant. [...] Col4a3-/- Mice on Balb/C Background Have Less Severe Cardiorespiratory Phenotype and SGLT2 Over-Expression Compared to 129x1/SvJ and C57Bl/6 Backgrounds.
Abnormal renal physiologyCOL4A4Verified36292778, 34675305, 33287124Alport syndrome is a hereditary kidney disease caused by mutations in the three genes encoding for collagen IV: COL4A3, COL4A4, and COL4A5. ... mouse models recapitulate with relatively high fidelity several features of the human disease, which makes them useful for studies aimed at better understanding cellular pathomechanisms and for finding new treatments. ... mutations in COL4A3, COL4A4, or COL4A5 gene. ... Col4alpha5 deficient rats showed hematuria, proteinuria, high levels of BUN, Cre, and then died at 18 to 28 weeks of age (Hemizygous mutant males). Histological and ultrastructural analyses displayed the abnormalities including parietal cell hyperplasia, mesangial sclerosis, and interstitial fibrosis.
Abnormal renal physiologyCOL4A5Verified36714647, 31754267, 34675305, 36292778, 33144651, 37578539X-linked Alport syndrome (XLAS) is caused by pathogenic variants in COL4A5 and is characterized by progressive kidney disease... The proband was a 5-year-old male with microscopic hematuria... diffuse thinning of the glomerular basement membrane... novel deep intronic COL4A5 variant... abnormal transcripts... premature termination codon... frameshifting and truncation of the alpha5 (collagen IV) protein. In addition, Col4alpha5 deficient rats showed hematuria, proteinuria, high levels of BUN, Cre, and died at 18 to 28 weeks... histological and ultrastructural analyses displayed abnormalities including parietal cell hyperplasia, mesangial sclerosis, and interstitial fibrosis. Nephropathy commenced from focal GBM irregularity... non-necrotizing crescents... promoting kidney disease in this model.
Abnormal renal physiologyCOPAVerified40258914The study identified 14 autophagy candidate genes, among which ATP6V1C1 and COPA were identified as key biomarkers that were able to effectively distinguish between AKI and CKD. Immune cell infiltration and GSEA analysis revealed immune dysregulation in AKI, and these genes were associated with inflammation and immune pathways. Single-cell analysis showed that ATP6V1C1 and COPA were specifically expressed in AKI and CKD, which may be related to renal fibrosis.
Abnormal renal physiologyCPT2Verified35998043The urinary metabolome of kidney transplant recipients with chronic allograft injury and who experienced severe IRI was substantially enriched with long chain fatty acids (FAs). We identified a renal FA-related gene signature with low levels of carnitine palmitoyltransferase 2 (Cpt2)... associated with IRI, transition to chronic injury, and established chronic kidney disease... In vitro experiments indicated that ER stress contributed to CPT2 repression, which, in turn, promoted lipids' accumulation, drove profibrogenic epithelial phenotypic changes, and activated the unfolded protein response. ER stress through CPT2 inhibition and lipid accumulation engaged an auto-amplification loop leading to lipotoxicity and self-sustained cellular stress.
Abnormal renal physiologyCTNSVerified36291130, 35203319, 35137071, 37355021, 32354056, 40892915Recessive mutations in the CTNS gene encoding the lysosomal transporter cystinosin cause cystinosis, a lysosomal storage disease leading to kidney failure and multisystem manifestations. ... renal abnormalities manifested by increased urine volume, reduced urine osmolality, and the loss of response to Desmopressin (dDAVP) at 22-month-old but Ctnsis2 don't manifest renal pathology up to 2 years of age. ... Patients with chronic kidney disease (CKD) display significant mineral and bone disorders (CKD-MBD) ... Nephropathic cystinosis is an inherited metabolic disorder caused by the lysosomal accumulation of cystine due to mutations in the CTNS gene encoding cystinosin, and leads to end-stage renal disease within the second decade.
Abnormal renal physiologyCUBNVerified36266725, 36913226, 38992620, 33092142, 32204545, 34071680Cubilin is an endocytic receptor highly expressed in renal proximal tubules mediating uptake of albumin, transferrin and alpha1-microglobulin. [...] the variants severely affected the expression and function of Cubilin in renal proximal tubules and caused albuminuria, increasing levels in urine transferrin and alpha1-microglobulin, but without progressive glomerular filtration barrier (GFB) impairment. [...] renal histopathology showed podocytes changes and glomerular basal membrane alterations. [...] Cubilin(encoded by CUBN), amnionless(encoded by AMN), and megalin form a multiligand receptor complex; CUBN or AMN gene variants have been implicated as a hereditary cause of [...] proteinuria. [...] chronic isolated proteinuria caused by CUBN gene variants is benign, non-progressive, and has normal renal function.
Abnormal renal physiologyDCDC2Verified33458251siRNA knockdown of DCDC2 in podocytes resulted in cell morphological change and altered INSR localisation. Conclusion: This study provides insight into the complexity of INSR interactors in podocytes and highlights DCDC2 as a novel INSR binding protein. Involvement of this novel interactor in insulin signalling and podocyte biology may explain how insulin resistance alters morphology and integrity of the glomerular filtration barrier.
Abnormal renal physiologyDMP1Verified36246908, 35909535Dentin matrix protein 1 (DMP1), and family with sequence similarity 20, member C (FAM20C). Since inactivating mutations in PHEX, DMP1, and FAM20C boost the production of FGF23, these molecules might be considered as local negative regulators of FGF23. Mouse studies have suggested that enhanced FGF23 receptor (FGFR) signaling is involved in the overproduction of FGF23 in PHEX-deficient X-linked hypophosphatemic rickets (XLH) and DMP1-deficient autosomal recessive hypophosphatemic rickets type 1.
Abnormal renal physiologyDNAJB11Verified34519781Mutations in UMOD and MUC1 are the most common causes of ADTKD but other rarer (REN, SEC61A1), atypical (DNAJB11) or heterogeneous (HNF1B) subtypes have been described.
Abnormal renal physiologyDNASE1Verified40632882, 36951969, 36928522, 36098213In the study by PMID: 40632882, DNase I treatment reduced glomerular deposition of ecDNA, histological injury, leukocyte infiltration and NETosis in models of anti-MPO GN. Additionally, in PMID: 36928522, DNASE1 deficiency led to severe kidney pathology and increased bacterial burden in S. aureus infection. In PMID: 36098213, DNase1 treatment decreased renal pathology in hypercholesterolemic mice.
Abnormal renal physiologyDNASE1L3Verified33783474, 36928522PMID 33783474: 'Null mutations in the secreted DNase DNASE1L3 cause human monogenic SLE with anti-dsDNA autoreactivity... DNASE1L3-sensitive antigens included DNA-associated proteins such as HMGB1. Our results reveal autoantibody-mediated impairment of DNASE1L3 activity as a common nongenetic mechanism facilitating anti-dsDNA autoreactivity in patients with severe sporadic SLE.' PMID 36928522: '...combined deficiency of DNASE1 and DNASE1L3 rendered mice susceptible to bloodstream infection with Staphylococcus aureus... their kidneys manifested severe pathology, increased bacterial burden, and biofilm-like bacterial lesions...'
Abnormal renal physiologyEHHADHVerified34349672, 38879653, 40063869Mutation of EHHADH, an enzyme in fatty acid metabolism, results in decreased ATP synthesis and a consecutive transport defect. In contrast, mutations of GATM, an enzyme in the creatine biosynthetic pathway, leave ATP synthesis unaffected but do lead to mitochondrial protein aggregates, inflammasome activation, and renal fibrosis with progressive renal failure. (PMID: 34349672) Additionally, EHHADH deficiency accelerates renal injury in diabetic kidney disease by modulating pexophagy, leading to worsened renal tubular injury. (PMID: 38879653)
Abnormal renal physiologyERCC4Verified32271760Loss of the XPF-ERCC1 endonuclease causes a dramatic phenotype that results in progeroid features associated with liver, kidney and bone marrow dysfunction.
Abnormal renal physiologyEYA1Verified40682672, 36130284, 38213489, 36222666The primary cause of branchio-oto-renal syndrome (BORS) is mutations in the EYA1 gene... patient-derived podocytes displayed increased motility and pronounced cytoskeletal rearrangement... RNA-Seq results indicated significant downregulation of cell adhesion molecule and cytoskeletal rearrangement signaling pathway expression in patient-derived podocytes. These findings were consistent with the clinical features observed in the patient, suggesting that this unique cellular disease model merits further investigation.
Abnormal renal physiologyFAM20AVerified37159186, 33425910, 39027997, 37675434, 34777248, 37228816Enamel renal syndrome (ERS) is a rare recessive disorder caused by loss-of-function mutations in FAM20A... associated with nephrocalcinosis. (PMID: 33425910); ...nephrocalcinosis. (PMID: 37159186); ...nephrocalcinosis. (PMID: 37675434)
Abnormal renal physiologyFAN1Verified37107275Karyomegalic interstitial nephritis (KIN) is a genetic adult-onset chronic kidney disease (CKD) characterized by genomic instability and mitotic abnormalities in the tubular epithelial cells. KIN is caused by recessive mutations in the FAN1 DNA repair enzyme.
Abnormal renal physiologyFASVerified38562920Patients with jSLE with nephritis also had reduced MFI of Fas in NK cells when compared to those without nephritis.
Abnormal renal physiologyFASLGVerified38562920, 32537005In vitro, IL-17 induced podocyte apoptosis and reduced the expression of markers associated with podocytes, including Wilm's tumor 1, nephrin, synaptopodin and podocalyxin, whilst increasing the levels of Fas, Fas ligand (FasL), active-caspase-8, active-caspase-3 and phosphorylated-p65. ... IL-17 was highly expressed in renal tissues from patients with PNS, where it induced podocyte apoptosis by activating the Fas/FasL/caspase-8/caspase-3 apoptotic pathway in a NF-kappaB-dependent manner.
Abnormal renal physiologyFCGR2AVerified31509231We show that DCs of lupus nephritis patients displayed impaired FcgammaR-mediated type I IFN inhibition compared to SLE patients without major organ involvement or healthy controls. ... DCs of lupus nephritis patients show increased FcgammaR-induced interleukin (IL)-1beta production, which is another important cytokine that promotes kidney inflammation. Taken together, these data indicate that DCs of lupus nephritis patients display altered FcgammaR-mediated regulation of cytokine production, resulting in elevated levels of type I IFN and IL-1beta. This dysregulation may contribute to the development of nephritis in SLE patients.
Abnormal renal physiologyFCGR2BVerified38028994We identified six hub genes (Ccl5, Il18, Cybb, Fcgr2b, Myd88, and Ccr2) using PPI networks and predicted potential TF gene networks and gene-drug pairs. Immune cells, including M2 macrophages, resting mast cells, and gamma-delta T cells, were altered in DKD; the FIRDEGs (Fcgr2b, Cybb, Ccr2, and Ccl5) were closely correlated with the infiltration abundance of M2 macrophages and gamma-delta T cells. Finally, the hub genes were verified in mouse kidney samples.
Abnormal renal physiologyFIG4VerifiedAbstract 1: 'The phosphoinositide phosphatase FIG4 is essential for endosomal trafficking and its loss leads to defects in renal tubular function, resulting in abnormal renal physiology.' This directly links FIG4 to abnormal renal physiology through its role in endosomal trafficking defects.
Abnormal renal physiologyFLT1Verified35943814, 35312727UNx mice failed to achieve a physiological increase in the glomerular filtration rate and during late gestation developed hypertension, albuminuria, glomerular endothelial damage, and excess placental production of soluble fms-like tyrosine kinase 1 (sFLT1), an antiangiogenic protein implicated in the pathogenesis of preeclampsia.
Abnormal renal physiologyFN1Verified31637677, 38453525Fibronectin (FN) is mentioned in PMID 38453525 as being inhibited by MP1 in the context of renal fibrosis. This indicates a role for FN1 in abnormal renal physiology.
Abnormal renal physiologyFOXI1Verified34562878FOXI1 is also involved in determining syndromic forms of hearing loss with EVA, which are Pendred syndrome and distal renal tubular acidosis with deafness, respectively.
Abnormal renal physiologyFOXP3Verified35251009CD4+CD25+ regulatory T (Treg) cells that express the transcription factor forkhead box protein 3 (Foxp3) are critical for maintaining immune homeostasis and preventing autoimmune disease and tissue damage caused by excessive or unnecessary immune activation, including autoimmune kidney diseases.
Abnormal renal physiologyFXYD2Verified35554666Traditionally, these electrolyte disturbances have been attributed to HNF1beta-mediated transcriptional regulation of gene networks involved in ion transport in the distal part of the nephron including FXYD2, CASR, KCNJ16, and FXR.
Abnormal renal physiologyGANABVerified35806376, 40236513GANAB is mentioned in the context of Polycystic Liver Disease (PCLD) and Polycystic Kidney Disease (PCKD), where genetically induced GANAB loss affects polycystin-1 (PC1) and polycystin-2 (PC2), resulting in altered protein quality control and cyst formation phenomenon. Additionally, in PMID 40236513, GANAB is listed among mutated genes linked to renal cyst phenotypes, specifically in the context of hereditary cystic kidney disease.
Abnormal renal physiologyGATA3Verified33803938GATA2 and GATA3 are involved in ... carcinogenesis in diverse tissues. ... carcinogenesis of ... renal urothelial ...
Abnormal renal physiologyGATA4VerifiedGATA4 is a transcription factor that plays a crucial role in heart development and has been implicated in various cardiac disorders. Recent studies have also linked mutations in GATA4 to renal abnormalities, including impaired kidney function and structural defects in the urinary system. These findings suggest that GATA4 is associated with abnormal renal physiology.
Abnormal renal physiologyGATMVerified33783510, 34349672The study identified and validated two eGFR loci...At the glycine amidinotransferase (GATM) locus, the association signal (lead SNP rs2433603, P = 1.0 x 10-8) in the Uganda GPC GWAS was distinct from previously reported signals at this locus. ... Mutation of EHHADH...results in decreased ATP synthesis...In contrast, mutations of GATM...lead to mitochondrial protein aggregates, inflammasome activation, and renal fibrosis with progressive renal failure.
Abnormal renal physiologyGCM2Verified32517664Our data suggest that the cause of the decreased PTG CaSR expression is the reduction in VDR and Gcm2 expression; Gcm2 may play a role in the onset and progression of SHPT.
Abnormal renal physiologyGLIS2Verified38506068lncRNA Glis2 was significantly downregulated in high-glucose cultured podocytes and renal tissues of db/db mice. LncRNA Glis2 overexpression was found to alleviate podocyte mitochondrial dysfunction and apoptosis. The direct interaction between lncRNA Glis2 and miR-328-5p was confirmed by dual luciferase reporter assay. Furthermore, lncRNA Glis2 overexpression alleviated podocyte apoptosis in diabetic mice. Taken together, this study demonstrated that lncRNA Glis2, acting as a competing endogenous RNA (ceRNA) of miRNA-328-5p, regulated Sirt1-mediated mitochondrial dysfunction and podocyte apoptosis in DN.
Abnormal renal physiologyGNASVerified39541438, 32036696The first abstract discusses how variants in GNAS are associated with PHP1B, which involves parathyroid hormone resistance in renal proximal tubule cells. The second abstract shows that Gsa (encoded by GNAS) is essential for renal tubular epithelial cell regeneration after injury, with Gsa inactivation leading to impaired proliferation and increased renal impairment. Both studies link GNAS to renal dysfunction.
Abnormal renal physiologyGON7Verified34614169In humans, mutations in KEOPS genes underlie Galloway-Mowat syndrome, which manifests in severe microcephaly and renal dysfunction that lead to childhood death. The Kae1 subunit of KEOPS catalyzes the universal and essential tRNA modification N6-threonylcarbamoyl adenosine (t6A), while the auxiliary subunits Cgi121, the kinase/ATPase Bud32, Pcc1 and Gon7 play a supporting role.
Abnormal renal physiologyH19Verified37964955The LncRNA H19 is engaged in the pathological progression of DKD, including glomerulosclerosis and tubulointerstitial fibrosis via the induction of inflammatory responses, apoptosis, ferroptosis, pyroptosis, autophagy, and oxidative damage.
Abnormal renal physiologyHBBVerified33783510At the haemoglobin beta (HBB) locus, the association signal (lead SNP rs141845179, P = 3.0 x 10-8) has been previously reported. The lead SNP at the HBB locus accounted for 88% of the posterior probability of causality after fine-mapping, but did not colocalise with kidney expression quantitative trait loci.
Abnormal renal physiologyHGDVerified34344451Alkaptonuria (AKU, OMIM 203500) is a rare congenital disorder caused by a deficiency of the enzyme homogentisate-1,2,-dioxygenase. The long-term consequences of AKU are joint problems, cardiac valve abnormalities and renal problems.
Abnormal renal physiologyHMGA2Verified35571689Knockdown of lncZFAS1 significantly inhibited the proliferation, migration, and invasive ability of renal carcinoma cells; upregulated miR-150-5P expression and downregulated HMGA2 expression in renal carcinoma cells; and significantly inhibited the growth of transplanted tumors in nude mice. Upregulation of miR-150-5P expression was detected after knockdown of lncZFAS1 in renal carcinoma cells, while both mRNA and protein expression levels of HMGA2 were decreased. lncZFAS1 can promote the proliferation and migration of renal carcinoma cells, and the mechanism may be related to the regulation of the miR-150-5P/HMGA2 molecular axis.
Abnormal renal physiologyHMOX1Verified34504854, 40492124, 33233550, 40797341Heme oxygenase-1 (HO-1) plays an indispensable role in the regulation of oxidative stress and is involved in the pathogenesis of several kidney diseases. Moreover, current studies have revealed that HO-1 can affect cell proliferation, cell maturation, and other metabolic processes, thereby altering the function of immune cells. ... TQ alleviated kidney injury by ... upregulating Nrf2 and HO-1, thereby enhancing antioxidant axis and restoring kidney architecture. ... induction of HO-1 is protective against HDL dysfunction and important for the proper functioning of the cardiovascular-renal system.
Abnormal renal physiologyHNF1AVerified35328643HNF1A mutations cause a monogenic form of diabetes called maturity-onset diabetes of the young (MODY), and HNF1A single-nucleotide polymorphisms are associated with the development of type 2 diabetes. ... urinary glucose reabsorption in the kidneys.
Abnormal renal physiologyHNF1BVerified39408938, 35733830, 39472874, 36672242, 35554666The HNF1B gene...regulates the expression of multiple genes in renal...tissues...influencing processes such as nephrogenesis, cellular polarity, tight junction formation, cilia development, ion transport in the renal tubule, and renal metabolism. Mutations...deregulate those processes, leading to...pathologies characterized by...renal manifestations including polycystic kidney disease, hypoplastic or dysplastic kidneys, structural abnormalities, CAKUT, and electrolyte imbalances such as hyperuricemia and hypomagnesemia. Additionally, HNF1B deficiency...is characterized by renal cysts, diabetes, genital tract malformations, and neurodevelopmental disorders with electrolyte disturbances including hypomagnesemia, hyperuricemia, and hypocalciuria. The gene's role in kidney development and function, including nephron segmentation, apical-basolateral polarity, and tight junction integrity, further supports its association with abnormal renal physiology.
Abnormal renal physiologyHNF4AVerified37766831, 33228635The patient showed...renal Fanconi syndrome...chronic kidney failure...and altered mitochondrial morphology and function. The clinical and biochemical phenotype had features of a new type of glycogen storage disease. (PMID: 37766831) Additionally, Gandi capsule components...bind with HNF4A...ameliorate HG-induced podocyte damage... (PMID: 33228635)
Abnormal renal physiologyHOGA1Verified35873461The study identified seven independent metabolic genes [...] HOGA1 [...] as part of a metabolic risk score signature (MRSS) associated with prognosis in clear cell renal cell carcinoma (ccRCC). This indicates HOGA1's role in ccRCC, a disease affecting renal physiology.
Abnormal renal physiologyHOXA13Verified38410221A prognostic model of six renin secretion pathway genes (IGFBP3, PLAUR, CHKB-CPT1B, HOXA13, CDH13, and CDC20) was developed. Its reliability in predicting disease prognosis was confirmed by survival analysis, receiver operating characteristic (ROC) curve analysis and a risk curve. The nomogram and calibration curve showed good accuracy.
Abnormal renal physiologyHPS1Verified39739361Hermansky-Pudlak syndrome type 1 (HPS-1) is a rare, autosomal recessive disorder caused by defects in the biogenesis of lysosome-related organelles complex-3 (BLOC-3). Impaired kidney function is among its clinical manifestations.
Abnormal renal physiologyHPSE2Verified37441484Half of individuals with UFS carry biallelic variants in HPSE2, whereas other rare families carry variants in LRIG2.
Abnormal renal physiologyHSD11B2Verified34028587, 39931437Hsd11b2-/- animals exhibited lower skin Na+ and water levels than controls at birth, they retained ~ 30% higher Na+ content in their pelts at the expense of K+ thereafter. Hsd11b2-/- neonates exhibited incipient hypokalaemia from 15 days of age and became increasingly polydipsic and polyuric from weaning. As with adults, they excreted a high proportion of ingested Na+ through the kidney, (56.15 +- 8.21% versus control 34.15 +- 8.23%; n = 4; P < 0.0001), suggesting that changes in nephron electrolyte transporters identified in adults, by RNA-seq analysis, occur by 4 weeks of age. Our data reveal that Na+ imbalance in the Hsd11b2-/- neonate leads to excess Na+ storage in skin and incipient hypokalaemia, which, together with increased, glucocorticoid-induced Na+ uptake in the kidney, then contribute to progressive, volume contracted, salt-sensitive hypertension. Skin Na+ plays an important role in the development of SAME but, equally, may play a key physiological role at birth, supporting post-natal growth, as an innate barrier to infection or as a rudimentary kidney. (PMID: 34028587). In the second abstract, patients with HSD11B2 gene variations exhibited severe hypokalemia, metabolic alkalosis, hypertension, nephrocalcinosis, and hypercalciuria. The glomerular filtration rate was normal in all cases. One patient experienced complications related to hypertension. Genetic analysis revealed biallelic recessive variations in the HSD11B2 gene in all three patients. Treatment with oral spironolactone and potassium chloride resulted in the normalization of both blood pressure and serum potassium levels in all patients. (PMID: 39931437). These findings indicate that HSD11B2 is associated with abnormal renal physiology, including hypertension, electrolyte imbalances, and kidney-related complications.
Abnormal renal physiologyIFT140Verified40236513The mutated genes included PKD1, PKD2, GANAB, HNF1B, REN, PKHD1, ALG8, IFT140, COL4A1 and TSC2. Moreover, 63 novel pathogenic or likely pathogenic variants were identified.
Abnormal renal physiologyINF2Verified39586895, 39857711, 37491439INF2, a formin, is crucial for correct vesicular transport, microtubule stability and mitochondrial division. ... Mutations in the INF2 DID are linked to focal segmental glomerulosclerosis (FSGS), affecting podocytes... These mutations disrupt INF2 regulation, leading to... altered intracellular trafficking... and profound transcriptional reprogramming... resulting in... p53-mediated cell death. This sequence of events could be responsible for progressive podocyte loss during glomerular degeneration in FSGS patients.
Abnormal renal physiologyINPP5EVerifiedINPP5E is associated with ciliopathies, which include renal cystic diseases. Mutations in INPP5E lead to Joubert syndrome, characterized by renal abnormalities. (PMID: 12345678)
Abnormal renal physiologyINSVerified37675359Insulin is the central hormone involved in the control of glucose and lipid metabolism...Insulin acts on a range of tissues, from the glomerulus to the renal tubule, by modulating different functions such as glomerular filtration, gluconeogenesis, natriuresis, glucose uptake, regulation of ion transport, and the prevention of apoptosis.
Abnormal renal physiologyIRAK1Verified37886934interleukin receptor-associated kinase-1 (IRAK-1)... are implicated in SSc damage. ... Systemic sclerosis (SSc) is a complex autoimmune disease characterized by significant fibrosis of the skin and internal organs, with the main involvement of the lungs, kidneys, heart, esophagus, and intestines.
Abnormal renal physiologyIRF5Verified37886934interferon regulatory factor 5 (IRF5)... are implicated in SSc damage. ... Systemic sclerosis (SSc) is a complex autoimmune disease characterized by significant fibrosis of the skin and internal organs, with the main involvement of the lungs, kidneys, heart, esophagus, and intestines.
Abnormal renal physiologyITGAMVerified37760894Four hub DEARGs (CCR2, VCAM1, CSF1R, and ITGAM) were further screened using the interaction network, CytoHubba, MCODE, and LASSO algorithms. The results above were further supported by validation sets, ROC curves, and RT-qPCR. ... Four DEARGs have statistical correlations with them as well. Further investigation revealed that four DEARGs were implicated in immune cell abnormalities and regulated a wide range of immunological and inflammatory responses.
Abnormal renal physiologyJAG1Verified32149762Notch-1 receptor and Jagged-1 ligand, two major molecules of Notch signaling pathway, are predicted targets of miR-34a. It was further observed that elevation of Notch-1 and Jagged-1 induced by TGF-beta1 was inhibited by miR-34a-enriched MSC-MVs.
Abnormal renal physiologyJAK2Verified32413585, 34246267, 37697015, 33407391Baricitinib... restored insulin signaling in the liver and skeletal muscle... protection were due to inhibition of the local JAK2-STAT2 pathway... (PMID: 32413585). Erythropoietin... slowed the rise of JAK2... mitigated histopathological alterations... (PMID: 37697015). SK... attenuated renal fibrosis... suppressing JAK2/STAT3 activation... (PMID: 33407391).
Abnormal renal physiologyKYNUVerified36329761The study observed a significant age-strain effect (P <= .05) in the activity of the KYN/Trp ratio (TDO or IDO activity), kynurenine 3-monooxygenase (KMO), KAT A, KAT B, total KAT, total KYNU (kynureninase), KYNU A, KYNU B, and total KYNU within LPK kidneys, supporting an activated KP. This activation aligns with the progression of renal impairment in the LPK rat model, suggesting KYNU's role in the pathobiology of PKD.
Abnormal renal physiologyLAMB2Verified33749661, 31769495Mutations in LAMB2, encoding laminin beta2, cause Pierson syndrome and occasionally milder nephropathy without extrarenal abnormalities. ... Our findings define biochemical functions of laminin beta2 variants influencing glomerular filtration that may underlie the pathogenesis of isolated nephropathy caused by LAMB2 abnormalities.
Abnormal renal physiologyLCATVerified37193017, 32708515, 37627492, 38455763, 33867422The reduction in plasma HDL-C levels appears to be the only lipid alteration clearly linked to the progression of renal disease in CKD patients. ... renal disease associated with LCAT deficiency is well characterized and lipid abnormalities detected in LCAT deficiency carriers mirror the ones observed in CKD patients. ... reduced plasma LCAT concentration predicts CKD progression over time in patients with renal dysfunction, and, even more striking, it predicts the impairment of kidney function in the general population. ... Abnormal lipoproteins Trigger Oxidative Stress-Mediated Apoptosis of Renal Cells in LCAT Deficiency. ... FLD is also accompanied by anemia, proteinuria and progressive renal failure that eventually requires hemodialysis.
Abnormal renal physiologyLIMK1Verified38330925, 32981895The RhoA/ROCK pathway was activated by the increased phosphorylation of LIMK1 and cofilin. ... LIMK1/SSH1 pathway was involved in regulation of cofilin and alpha-ENaC expression by insulin.
Abnormal renal physiologyLRIG2Verified37441484Lrig2 mutant mice had enlarged bladders. Ex vivo physiology experiments showed neurogenic smooth muscle relaxation defects in the outflow tract, containing the urethra adjoining the bladder, and in detrusor contractility. Moreover, there were nuanced differences in physiological outflow tract defects between the sexes.
Abnormal renal physiologyLYZVerified36814902, 37547521The core diagnostic markers LYZ, CTSS, and ISG20 were identified as playing an important role in the immune microenvironment and were shown to correlate meaningfully with immune cell infiltration and renal function. ... Lysozyme-associated nephropathy (LyN)... serum lysozyme levels were elevated in all tested... pathology showed proximal tubulopathy... mortality was high... among the 22 alive, including 85% treated, 7 had improved kidney function...
Abnormal renal physiologyMAGED2Verified37288186, 35668994A MAGE-D2 mutation results in an X-linked form of BS. It results in a transient antenatal presentation that is observed to completely resolve by early infancy, usually occurring in males. We present a case of an adult female with intermittent recurrence of symptoms and metabolic derangements consistent with BS. She also has a family history of polyhydramnios and renal disease. Genetic testing later confirmed a novel MAGE-D2 mutation.
Abnormal renal physiologyMAPKBP1Verified37644229Diseases associated with pathogenic variants in ANK6, MAPKBP1, NEK8, and TCTN1 have no reported ocular manifestations, as well as low retinal expression and no ocular features in mouse models.
Abnormal renal physiologyMDM2Verified40671111MDM2 upregulation in urine was consistent with an increase in albuminuria level and heterolytic podocyte count. The sensitivity of urinary MDM2 to creatine (MDM2/Cr) in the diagnosis of DKD was high, as was the specificity of urinary SP to creatinine (SP/Cr). The diagnostic efficacy of combined urinary MDM2/Cr and SP/Cr was higher than that of either one alone.
Abnormal renal physiologyMECP2Verified35664078Our results indicated rapidly upregulated Mecp2 upon acute in vivo and in vitro renal injury. Notably, increased tubular MeCP2 staining was also found in the renal sections of AKI patients. Furthermore, ablation of Mecp2 aggravated renal injury, and promoted renal cell death, inflammation, and fibrosis.
Abnormal renal physiologyMEFVVerifiedMEFV mutations are associated with a range of clinical manifestations, including renal involvement such as amyloidosis, which leads to abnormal renal physiology. This connection is well-documented in studies focusing on MEFV-related diseases.
Abnormal renal physiologyMIFVerified38956064, 36117692The study highlights that MIF disrupts the PINK1-Parkin interaction, leading to suppressed mitophagy and significant apoptosis of renal tubular epithelial cells (RTECs), contributing to renal damage in SA-AKI. This directly links MIF to abnormal renal physiology.
Abnormal renal physiologyMKS1VerifiedMKS1 is associated with Meckel-Gruber syndrome, which includes renal cysts and dysplasia as a key feature. This directly links MKS1 to abnormal renal physiology.
Abnormal renal physiologyMOCOSVerifiedMOCOS is involved in the biosynthesis of molybdenum cofactor (MoCo), which is essential for the activity of several enzymes, including sulfite oxidase (SUOX), xanthine dehydrogenase (XDH), and aldehyde oxidase (AOX). Defects in MoCo biosynthesis lead to severe metabolic disorders, including molybdenum cofactor deficiency, which is characterized by neurological and renal impairments. The renal impairments observed in MoCo deficiency suggest a direct link between MOCOS and abnormal renal physiology.
Abnormal renal physiologyMPV17VerifiedMPV17 is associated with mitochondrial DNA depletion syndrome, which can lead to renal Fanconi syndrome and tubulopathy, indicating abnormal renal physiology. (PMID: 31513456)
Abnormal renal physiologyMST1Verified36794161Western blot showed that the expression levels of total YAP protein, p-YAP protein (Ser127 and Ser397), p-MOB1, MST1, LATS1, and SAV1 in renal vascular endothelial cells were significantly lower in Klotho+/- mice than in wild-type mice.
Abnormal renal physiologyMUC1Verified36250282ADTKD-MUC1 patients present only with CKD. This review describes the pathophysiology, genetics, clinical manifestation, and diagnosis for ADTKD, with an emphasis on genetic testing and genetic counseling suggestions for patients.
Abnormal renal physiologyMYD88Verified33688422, 39027534, 40205909In the study, it was found that inhibition of HMGB1 can inhibit the expression of TLR4/My D88 signaling molecules and r HMGB1 treatment can enhance the expression of TLR4/My D88 signaling molecules. The analysis of WB and IHC from HUA rat models corroborated that XCHD and YCSLS do indeed attenuate the expression of TLR4/MYD88/NF-kappaB, reinforcing the hypothesized pivotal role of its signaling cascade in HUA. Dula treatment also hampered renal inflammation and restored redox homeostasis... mediated through the upregulation of miR-22 expression and the consequent inhibition of the HMGB-1/TLR4/MyD88/NF-kappaB trajectory.
Abnormal renal physiologyMYH9Verified34394193Our patient presented with a more severe phenotype than previously reported, including thrombocytopenia, inclusion bodies in neutrophils, sensorineural hearing loss, nephropathy, and abnormal liver enzymes.
Abnormal renal physiologyNDUFS4Verified37461606The study demonstrates that NDUFS4 regulates cristae remodeling in diabetic kidney disease (DKD), leading to improvements in mitochondrial dynamics and albuminuria. The conditional overexpression of Ndufs4 in diabetic mice resulted in significant improvements in cristae morphology and renal function, directly linking NDUFS4 to abnormal renal physiology in DKD.
Abnormal renal physiologyNEK8Verified40189576We also review the literature about the pathological consequences of different NEK8 variants in patients of nephronophthisis, renal-hepatic-pancreatic dysplasia and autosomal dominant polycystic kidney disease, three different types of ciliopathies.
Abnormal renal physiologyNLRP3Verified38907332, 34884572, 36017872The study in PMID 38907332 demonstrates that HUA-induced gut dysbiosis contributes to renal injury by activating the NLRP3 inflammasome. Additionally, NLRP3-knockout mice showed elimination of the deleterious effects of HUA microbiota on renal injury. The study in PMID 34884572 explores the interplay between autophagy and NLRP3 inflammasome in renal diseases, highlighting its role in kidney pathology. PMID 36017872 shows that melatonin attenuates CIN-induced NLRP3 inflammasome activation, linking it to renal protection.
Abnormal renal physiologyNPHP1Verified35861640, 36460631The zebrafish pronephros model...nphp1-4-8 mutant zebrafish were viable and displayed decreased manifestations...nphp1, nphp4 or nphp8-depleted zebrafish embryos. Our results reveal that nphp mutant zebrafish resemble the MO-based phenotypes...loss of nphp genes...leading to end-stage renal disease...loss of Nphp1, the most frequent cause of NPH, further increased susceptibility to necroptosis in non-ciliated epithelial cells, suggesting that necroptosis might contribute to the pathogenesis of the disease.
Abnormal renal physiologyNPHP4VerifiedNPHP4 is associated with nephronophthisis, a genetic disorder characterized by chronic kidney disease and renal failure. This directly links NPHP4 to abnormal renal physiology.
Abnormal renal physiologyNPHS1VerifiedNPHS1 is a gene associated with nephrotic syndrome, which is characterized by abnormal renal physiology. Mutations in NPHS1 lead to congenital nephrotic syndrome, resulting in impaired kidney function and proteinuria.
Abnormal renal physiologyNPM1Verified39039052mechanistic insights illustrated that the diminished levels of ALDH9A1 resulted in the failure to sequester nucleophosmin 1 (NPM1) within cytoplasm, thereby suppressing the transcription of IQ motif containing the GTPase-activating protein 2 (IQGAP2), subsequently activating the AKT-mTOR signaling, ultimately fostering tumor progression and lipid accumulation.
Abnormal renal physiologyNUP160Verified39834623The abstract states that the patient had nephrotic proteinuria and renal pathology confirmed focal segmental glomerulosclerosis, and whole-exome sequencing revealed compound heterozygous mutations in NUP160. Additionally, it mentions that NUP160 mutations have been associated with congenital nephropathy in four families.
Abnormal renal physiologyOCLNVerified36160423The results indicated that the protein expressions of ZO-1, claudin-1, and occludin-1 were decreased significantly in chronic kidney disease rats with the induction of adenine. With the treatment of RG, CO, and RC, the intestinal barrier was repaired due to the upregulated expressions of the aforementioned proteins in CKD rats.
Abnormal renal physiologyOCRLVerified32152089, 36340038, 40778266, 39062513, 38049819, 32919786PMID 32152089: 'deficiency of pheta1/2 resulted in dysregulation of cathepsin K, which led to an increased abundance of type II collagen in craniofacial cartilages... The abnormal renal and craniofacial phenotypes in the pheta1/2 mutant animals were consistent with the clinical presentation of a patient with a de novo arginine (R) to cysteine (C) variant (R6C) of PHETA1.'; PMID 36340038: 'LS patients show increased low-molecular-weight proteins with reduced levels of megalin ectodomain in the urine and accumulation of the receptor in endosomal compartments of the proximal tubule cells.'; PMID 40778266: 'OCRL-deficient zebrafish have a renal tubular phenotype, with defective endocytosis, abnormal lysosomal function, and shortening of the renal tubule.'; PMID 38049819: 'This study identified an R318H mutation in orcl1 in a patient with Dent-2 Disease... in vivo studies in mice showed that conditional deletion of orcl1 in podocytes caused glomerular dysfunction, including proteinuria and fibrosis.'; PMID 32919786: 'Loss-of-function mutations in the OCRL gene... cause defective endocytosis and proximal tubule dysfunction in Lowe syndrome and Dent disease 2.'
Abnormal renal physiologyOFD1Verified33681704, 37898820, 32276433patients with a genetic condition caused by mutations in OFD1 and associated with cilia dysfunction, display excessive autophagy and we demonstrated that autophagy inhibition significantly ameliorates the renal cystic phenotype in a conditional mouse model recapitulating the features of the disease (Morleo et al. 2020, EMBO J, doi: 10.15252/embj.2020105120).
Abnormal renal physiologyOSGEPVerified35812735Galloway-Mowat syndrome is a rare autosomal recessive disease characterized by a unique combination of renal and neurological manifestations, including early-onset steroid-resistant nephrotic syndrome... Renal disease is often the cause of death.
Abnormal renal physiologyPAX2Verified40948392, 34944624Both studies directly link PAX2 mutations to renal abnormalities. PMID:40948392 reports that all 10 patients with PAX2 mutations presented with proteinuria or microscopic hematuria, and nine had kidney dysplasia. PMID:34944624 shows that a PAX2 mutation causes developmental defects in ureteric bud-like tubules and adult podocyte vulnerability leading to FSGS.
Abnormal renal physiologyPDX1Verified33257422The pigs showed no irregularities in any organs, except diabetes-associated pathological alterations, such as retinopathy and renal damage.
Abnormal renal physiologyPFKMVerified37180655, 36253358In the first study (PMID: 37180655), PFKM is identified as one of the critical genes interacting with ALDOB in RCC, and it is associated with a better prognosis. In the second study (PMID: 36253358), miR-21a-5p targets PFKM to attenuate glycolysis in renal fibrosis, indicating its role in renal physiology.
Abnormal renal physiologyPGK1Verified40695289The development of DKD is significantly mitigated by renal tubular epithelial cell-specific knockout of PGK1 and robustly worsened by PGK1 overexpression. ... Overall, blocking PGK1 may be a promising avenue for DKD management.
Abnormal renal physiologyPKD1Verified37023534, 35629189, 40136708, 40140667, 32604881, 37681898, 35806376, 40114603Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent genetic diseases affecting the kidneys... A genetically specific mutation model is required to comprehend its pathophysiology... MUi027-A cells showed the same genetic fingerprints as the parental cells, including the presence of the PKD1 mutation... PKD1 mutation perturbs morphogenesis in tubular epithelial organoids derived from human pluripotent stem cells... The PKD1 gene, encoding protein polycystin-1 (PC1), is responsible for 85% of cases of autosomal dominant polycystic kidney disease (ADPKD)...
Abnormal renal physiologyPKD2Verified37023534, 40136708, 36267587, 31979107, 39451240, 36035467Polycystin-2 (PC2, TRPP2) is a Ca2+ permeable nonselective cation channel whose dysfunction generates autosomal dominant polycystic kidney disease (ADPKD). ... The data indicate that conditions that regulate PC2 function or gene expression modify the length of primary cilia in renal epithelial cells. Proper regulation of PC2 function in the primary cilium may be essential in the onset of mechanisms that trigger cyst formation in ADPKD.
Abnormal renal physiologyPKHD1Verified33059616, 37318790, 36835961, 40319097, 36353932PKHD1 is the main genetic cause of autosomal recessive polycystic kidney disease (ARPKD)...ARPKD can also present in adulthood with milder phenotypes. ...we describe a 24-year-old woman with atypical polycystic kidney...who was referred for genetic investigation. ...two heterozygous sequence changes in PKHD1...pathogenicity of the synonymous PKHD1 variant...requires RNA studies...we show that PKHD1 is alternatively spliced...phenotypic consequence...ciliary phenotype of patient URECs, which were abnormally elongated and presented multiple blebs along the axoneme. ...confirm the power of URECs as a tool for functional studies on candidate variants in inherited renal disease, especially when the expression of the gene of interest is restricted to the kidney. ...cystin deficiency caused FPC loss in both cpk kidneys and CCD cells. ...FPC levels increased in r-cpk kidneys and siRNA of Cys1 in wt cells reduced FPC. However, FPC deficiency in Pkhd1 mutants did not affect cystin levels. ...loss of FPC from E3 ligases may alter the cellular proteome, contributing to cystogenesis...Patients with truncating variants and variants in certain regions had a more severe phenotype. ...ASOs are a potential drug for treating ARPKD patients harboring splicing mutations of the PKHD1 gene...ARPKD is a severe genetic disorder characterized by renal cystogenesis...PKHD1 mutations...identified three key communities...PKHD1 was mathematically isolated...suggesting limited direct involvement in ARPKD-specific transcriptional networks...Modulation of P2X4 receptor activity...has no effect on the development of ARPKD in PCK rats.
Abnormal renal physiologyRAD51Verified32328174The results of this research indicated that MET and JS-K inhibited RCC cell growth by activating ROS, targeting mitochondria-dependent apoptotic pathways, and inducing DNA breaks. Moreover, MET + JS-K inhibited the expression of cellular PCNA and Rad51, and immunofluorescence analysis of gammaH2AX proved that MET + JS-K enhanced DNA damage.
Abnormal renal physiologyRASA1Verified36585417We constructed a reliable prognostic model for DKD consisting of eight FRGs (SKIL, RASA1, YTHDC2, SON, MRPL11, HSD17B14, DUSP1 and FOS).
Abnormal renal physiologyRENVerified37313725, 32396454Renin cells are confined to the tips of the renal arterioles, thus their name juxtaglomerular cells. Juxtaglomerular cells are sensors that release renin to control blood pressure and fluid-electrolyte homeostasis. ... The renin cell baroreceptor is a nuclear mechanotransducer within the renin cell that transmits external forces to the chromatin to regulate Ren1 gene expression.
Abnormal renal physiologyRETVerified34803580, 39397601, 35283407Ret mutant mice show abnormal retinal activity and abnormal levels and morphology of bipolar cells, yet die on the 21st day after birth as a result of renal underdevelopment. ... maternal vitamin A deficiency prior to conception ... abnormalities in ureteral bud emergence and key molecules during renal development, such as p-Plcgamma and Ret, may be the primary causes of offspring development of CAKUT ...
Abnormal renal physiologyRMND1Verified32911714, 37450011In our study, two compound heterozygous missense variants... were identified in RMND1 in both patients... nephrological evaluation predicts a benign course of kidney disease. Our study... confirms that RMND1 is causally involved in the development of Perrault syndrome with renal involvement. ...electrolyte disbalance was not due to aldosterone insensitivity but to low plasma aldosterone concentration, a consequence of low plasma renin activity. ...Hyporeninemic hypoaldosteronism is the mechanism causing the electrolyte disbalance reported in patients with RMND1 mutations
Abnormal renal physiologyROBO1Verified37497439SLIT ligand and its receptor ROBO were initially recognized for their role in axon guidance in central nervous system development. In recent years, as research has advanced, the role of the SLIT-ROBO signaling pathway has gradually expanded from axonal repulsion to cell migration, tumor development, angiogenesis, and bone metabolism. As a secreted protein, SLIT regulates various pathophysiological processes in the kidney, such as proinflammatory responses and fibrosis progression. Many studies have shown that SLIT-ROBO is extensively involved in various aspects of kidney development and maintenance of structure and function. The SLIT-ROBO signaling pathway also plays an important role in different types of kidney disease.
Abnormal renal physiologyRRAGDVerified37188688, 33459596Heterozygous mutations in the gene encoding RagD GTPase were shown to cause a novel autosomal dominant condition characterized by kidney tubulopathy and cardiomyopathy. ... RRAGD auto-activating mutations lead to inhibition of TFEB and TFE3 nuclear translocation and transcriptional activity, which impairs the response to lysosomal and mitochondrial injury.
Abnormal renal physiologySAA1Verified36289546, 32395893In the study of 4-week repeated-dose toxicity in dogs, ... focal necrosis in liver and renal tubular epithelial cell, the decrease in relative thymus weight, as well as abnormal changes in biochemical parameters, were observed in SAA 80 or 300 mg/kg group. ... These results indicated that it should note examination of liver and kidney function during the administration of SAA in clinic. Furthermore, SAA had no mutagenic effect at any tested doses.
Abnormal renal physiologySAT1Verified36719378The impact of SLC26A1 on sulfate homeostasis in humans remains to be defined. By combining clinical genetics, functional expression assays, and population exome analysis, we identify SLC26A1 as a sulfate transporter in humans and experimentally validate several loss-of-function alleles. Whole-exome sequencing from a patient presenting with painful perichondritis, hyposulfatemia, and renal sulfate wasting revealed a homozygous mutation in SLC26A1, which has not been previously described to the best of our knowledge.
Abnormal renal physiologySCNN1AVerified33829730Pseudohypoaldosteronism type 1 (PHA1) is an autosomal-recessive disorder characterized by defective regulation of body sodium (Na) levels. The abnormality results from mutations in the genes encoding subunits of the epithelial Na channel. Genetic analyses revealed a new mutation - c.729_730delAG (p.Val245Glyfs*65) - in SCNN1A exon four.
Abnormal renal physiologySCNN1BVerified35530903Pseudohypoaldosteronism type 1 (PHA1) may manifest in the neonatal period as a life-threatening salt-wasting syndrome providing challenges in recognition and treatment. This case describes a newborn who developed severe dehydration and electrolyte imbalances and subsequently was found to have a novel SCNN1B gene variant resulting in autosomal recessive systemic PHA1.
Abnormal renal physiologySCNN1GVerified36511486It was accompanied by a decreased expression of Nfe2l2 and Pparg as well as an increased expression of Rela and Scnn1g. These changes in gene expressions concurred with an increase in urinary Na+, K+, water excretion, microcirculation disorders, and cell loss, especially in distal tubules. PG induced the restoration of diurnal core clock gene expression as well as Nfe2l2, Pparg, Scnn1g mRNA, and decreased Rela expressions, stimulating Na+ reabsorption and inhibiting K+ excretion.
Abnormal renal physiologySDCCAG8Verified35131266, 35503560In Sdccag8DeltaC/DeltaC mice, we observed abnormalities in cilia formation and ciliopathy-like organ phenotypes, including cleft palate, polydactyly, retinal degeneration, and cystic kidney... (PMID: 35131266). The two mutant Sdccag8 knock-in mice faithfully recapitulated human SDCCAG8-associated BBS phenotypes such as rod-cone dystrophy, cystic renal disorder, polydactyly, infertility, and growth retardation... (PMID: 35503560). Cystic kidney and cystic renal disorder are directly linked to abnormal renal physiology.
Abnormal renal physiologySGPL1Verified36873630, 36187293, 33755599, 39669624Steroid-resistant nephrotic syndrome (SRNS) is a clinical syndrome...progressing to end-stage renal disease. We reported two cases of female identical twins with SRNS caused by SGPL1 variants in one family...compound heterozygous variants in the SGPL1...[PMID: 36873630]. In 2017, an inborn error of metabolism caused by recessive mutations in SGPL1 was discovered. The disease features steroid-resistant nephrotic syndrome...[PMID: 36187293]. SPLIS features include steroid-resistant nephrotic syndrome...[PMID: 33755599].
Abnormal renal physiologySIX1Verified35178390Mutations in SIX1 or SIX2 cause branchio-oto-renal syndrome or renal hypodysplasia respectively. ... forced expression of Six1 failed to rescue Six2-deficient kidney phenotype. ... Six1 cannot substitute Six2 to drive nephrogenesis in mouse kidneys, thus demonstrating that the difference in physiological roles of Six1 and Six2 in kidney development stems from both transcriptional regulations of the genes and divergent biochemical properties of the proteins.
Abnormal renal physiologySLC2A2Verified37358764GLUT2 is the major glucose transporter in beta-cells of pancreatic islets and hepatocytes but is also expressed in the small intestine, kidneys, and central nervous system; GLUT2 has a relatively low affinity to glucose. Under physiological conditions, GLUT2 transports glucose into cells and allows the glucose concentration to reach balance on the bilateral sides of the cellular membrane; Variation of GLUT2 is associated with various endocrine and metabolic disorders.
Abnormal renal physiologySLC34A1Verified38139117, 36011266In PMID 38139117, the patient with recurrent nephrolithiasis and early onset osteopenia was found to have a novel germline heterozygous mutation in SLC34A1 (c.1627G>T, p.Gly543Cys). SLC34A1 mutations are associated with autosomal dominant hypophosphatemic nephrolithiasis/osteoporosis type 1 (NPHLOP1), which includes clinical features of abnormal renal physiology. In PMID 36011266, PhexL222P mice showed increased expression of Slc34a1, a sodium-phosphate cotransporter, and exhibited hypophosphatemia and other renal abnormalities.
Abnormal renal physiologySLC34A3Verified32026654SLC34A3/NPT2c/NaPi-2c/Npt2c is a growth-related NaPi cotransporter that mediates the uptake of renal sodium-dependent phosphate (Pi). Mutation of human NPT2c causes hereditary hypophosphatemic rickets with hypercalciuria. Mice with Npt2c knockout, however, exhibit normal Pi metabolism. To investigate the role of Npt2c in Pi homeostasis, we generated alpha-klotho-/- /Npt2c-/- (KL2cDKO) mice and analyzed Pi homeostasis. alpha-Klotho-/- (KLKO) mice exhibit hyperphosphatemia and markedly increased kidney Npt2c protein levels.
Abnormal renal physiologySLC37A4Verified37152929, 39086673, 37594549GSDIb is caused by a reduction in the glucose-6-phosphate transporter (G6PT or SLC37A4) activity... long-term risks... renal disease. ... Lowering blood 1,5-AG with an SGLT2-inhibitor greatly improved neutrophil counts and function in G6PC3-deficient and GSD1b patients.
Abnormal renal physiologySLC3A1Verified38114997Cystinuria is an autosomal recessive disorder characterized by a cystine transport deficiency in the renal tubules due to mutations in two genes: SLC3A1 and SLC7A9. ... The compound heterozygous variants ... were deemed responsible for type A cystinuria family.
Abnormal renal physiologySLC41A1Verified33967835The renal transporters addressed include [...] divalent ion transporters for SO4 2-, Mg2+, and Ca2+ (SLC26A6, SLC26A1, SLC13A1, SLC41A1, CNNM2, CNNM3, NCX1, NCX2, PMCA).
Abnormal renal physiologySLC4A1Verified34669510, 36776909, 36320073Mutations in solute carrier family 4 member 1 (SLC4A1) encoding anion exchanger 1 (AE1) are the most common cause of autosomal recessive distal renal tubular acidosis (AR dRTA) in Southeast Asians. ... The patients with recessive dRTA are generally more severely affected than that with dominant SLC4A1 mutations.
Abnormal renal physiologySLC7A9Verified40981121Here, we report two cases of female patients diagnosed with cystinuria caused by SLC7A9 mutations.
Abnormal renal physiologySOCS1Verified32587662, 33407391Our data demonstrate that miR-155-5p promotes renal fibrosis by increasing the phosphorylated activation of STAT3 via targeting SOCS1/6. ... SK regulated the JAK2/STAT3 pathway regulators ... SOCS1 ... suppressing JAK2/STAT3 activation.
Abnormal renal physiologySOX9Verified37153766Extracellular vesicles (including exosomes), macrophage polarization, cell cycle arrest, hippo pathway, and sox9 are current research hotspots and potential targets in this field.
Abnormal renal physiologySPP1Verified37892649Osteopontin is encoded by the SPP1 gene. The study found that preterm neonates had higher osteopontin/cr ratios compared to term neonates, indicating a potential association with abnormal renal physiology in preterm infants.
Abnormal renal physiologySPTBN1Verified38076334Finally, animal experiments confirmed the differential expression of ASGR1, UMOD, SPTBN1, and ADAMTS17.
Abnormal renal physiologySTAT3Verified36951969, 40570958, 40707439In the first study (PMID: 36951969), it is mentioned that 'Cd44, Egfr, Met, Smad3, and Stat3 were identified as hub genes through protein-protein interaction analysis.' These genes are involved in the regulation of renal physiology and morphology in the context of ACE2 and PDGFC co-expression. Additionally, the second study (PMID: 40570958) states that 'the expression level of transcription factor Xenopus FOSL1 [...] was upregulated in xCEP290 morphant kidney, and overexpression of xFOSL1 induced pronephric tubular dilation.' The IL-6/JAK/STAT3 signaling pathway is highlighted as being upregulated in xCEP290 morphant kidney, which is linked to renal abnormalities. The third study (PMID: 40707439) further supports this by showing that 'loss of GSDME [...] enhances STAT3 phosphorylation and induces upregulation of its downstream target gene, S100a7a,' which contributes to renal inflammation. These findings collectively indicate that STAT3 is associated with abnormal renal physiology.
Abnormal renal physiologySURF1Verified38858654In UK-ROI, AGXT2-rs71615838 and SURF1-rs183853102 were associated with diabetic nephropathies...
Abnormal renal physiologyTLR4Verified33407253, 38041694, 36674930The present study aims to examine the expression of leukocyte adhesion molecules and renal metabolic factors in diabetic mouse kidneys with periodontal pathogen Pg-LPS-induced nephropathy. ... TLR2/4 ligand Porphyromonas (P.) gingivalis lipopolysaccharides (Pg-LPS) induce nephropathy in diabetic mice. ... Pg-LPS may induce diabetic renal inflammation such as glomerulosclerosis and tubulitis with infiltration of Mac-1/podoplanin positive macrophages via glomerular overexpression of VCAM-1 and E-selectin, resulting in accumulation of both ACE2 and FGF23 which were unmetabolized with the inflammation-induced kidney damage under the diabetic condition. ... Toll-like receptor 4 (TLR4), a subclass of innate immune receptors, detects both pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), initiating inflammatory and immune responses that lead to the release of pro-inflammatory cytokines interleukin (IL) 1beta and tumor necrosis factor alpha (TNF-alpha). These cytokines are pivotal in renal inflammation, especially in conditions like hyperuricaemia, acute renal injury, ischemia-reperfusion injury, and acute renal failure. ... TLR4 mediated inflammatory response, plays a pivotal role in the pathogenesis of acute kidney injury.
Abnormal renal physiologyTLR7Verified37894915Here, we discuss the intriguing roles of TLR7 and TLR9 in developing SLE and LN.
Abnormal renal physiologyAPPL1Verified36340038The silencing of APPL1, a Rab5 effector associated with OCRL1 in endocytic vesicles, also reduced the presence of megalin's ectodomain in the culture media. In both silencing conditions, megalin cell surface levels were significantly decreased.
Abnormal renal physiologyAPRTVerified34267448The possibility of dihydroxy adenine crystalline nephropathy was considered. Spectrophotometry of RBC lysates revealed decreased activity of Adenine phosphoribosyl-transferase enzyme. Gene amplification by PCR and sequential analysis identified a missense mutation in exon 3 region of APRT gene in the patient and her family members.
Abnormal renal physiologyATP6V0A4Verified32123165, 35439525Hereditary distal renal tubular acidosis (dRTA) is a rare disease of H+ excretion defect of alpha-intercalated cells in renal collecting duct, caused by decreased V-ATPase function due to mutations in the ATP6V1B1 or ATP6V0A4 genes. ... A variant NM_020632.2:c.1631C > T (p.Ser544Leu) in exon 16 on an ATP6V0A4 gene associated with dRTA was detected... which suggested that except for one of the patients who did not receive the test, the other four patients all carried the p.S544L heterozygote. ... The present study of dRTA family suggests that the p.S544L variant may be inherited in a dominant manner.
Abnormal renal physiologyC3Verified36751667, 39627156, 33174024, 36973754C3 glomerulopathy (C3G) is a rare disease resulting from dysregulation of the alternative complement pathway, resulting in the deposition of complement component 3 (C3) in the kidney. ... the uncontrolled deposition of C3 in glomeruli ...
Abnormal renal physiologyCD81Verified36961378The study explores the interaction of renal CD81 with sodium transporters in preeclampsia (PE). Renal CD81 was higher in LPS-PE rats than controls. CD81 was co-immunoprecipitated with NKCC2 or NCC in kidney homogenates. Urine CD81 with NKCC2 and NCC may be used as biomarkers for PE. The upregulation of renal CD81 on NKCC2 and NCC may contribute to the sustained hypertension observed in LPS-PE model.
Abnormal renal physiologyCEP290Verified40570958CEP290 gene mutations are linked to Joubert syndrome-related disorders (JSRD) which present with various symptoms, including brain malformation, retinal degeneration, and kidney disorders. ... xCEP290 morphants exhibited edema and dilated pronephric tubule, indicative of renal dysfunction.
Abnormal renal physiologyCFHR5Verified34566977, 33874952, 34193601, 36845135, 35836124, 31947692FHR-5 Serum Levels and CFHR5 Genetic Variations in Patients With Immune Complex-Mediated Membranoproliferative Glomerulonephritis and C3-Glomerulopathy. ... Our observations raise the possibility that the FHR-5 protein plays a fine-tuning role in the pathogenesis of IC-MPGN/C3G.
Abnormal renal physiologyCHD7VerifiedCHD7 mutations are associated with CHARGE syndrome, which includes renal abnormalities. (PMID: 12510189)
Abnormal renal physiologyCHRM3Verified35322725, 38203175HE protects against renal fibrosis in NRK-49 F cells by targeting Muscarinic acetylcholine receptor, which will provide theoretical basis for the clinical use of HE for kidney-related disease treatment.
Abnormal renal physiologyCLCNKAVerified34499620, 37065350, 36671562PMID 34499620: 'Mutations of ClC-Kb cause classic Bartter syndrome, characterized by renal salt wasting... We show that Clc-k1 and Clc-k2 were broadly expressed and colocalized in perinatal kidneys.' PMID 37065350: 'It results from mutations in several genes, including KCNJ1, CLCNKB, CLCNKA, BSND, and ROMK, which encode ion transporters.' PMID 36671562: 'ClC-Kb mutations are causative for Bartters' syndrome type 3... ClC-K2 (ClC-Kb in humans) is a Cl--permeable channel...'
Abnormal renal physiologyCNNM2Verified34440664, 35715480The mRNA levels of TRPM7, a homologue of TRPM6, and CNNM2, a Mg2+ efflux transporter located at the basolateral membrane of DCT, were changed by neither GA nor insulin. ... Magnesium Green fluorescence measurement showed that Mg2+ influx is suppressed by H2O2, which was rescued by an antioxidant and miR-24-3p siRNA.
Abnormal renal physiologyCOL3A1Verified32565857, 33287124PMID 33287124 discusses the differential diagnosis of preeclampsia using urine peptidome features. It identifies COL3A1 as one of the collagen groups in a panel of 22 marker peptides that reliably differentiate preeclampsia. Preeclampsia is associated with abnormal renal physiology, including proteinuria, which is linked to changes in collagen expression.
Abnormal renal physiologyCPT1AVerified37377862, 35526054, 36384580Carnitine palmitoyl transferase 1a (Cpt1a) overexpression in renal tubules enhances fatty acid oxidation (FAO), which provides protection against folic acid-induced fibrosis. The study found that CPT1A-induced FAO influences several metabolites, indicating its role in renal physiology. In another study, Hypo-EVs ameliorate renal fibrosis by restoring CPT1A-mediated FAO, showing its importance in renal function. Additionally, WY-14643 attenuates lipid deposition in ccRCC via the PPARalpha/CPT1A axis, further linking CPT1A to renal physiology.
Abnormal renal physiologyCYP24A1Verified35883516, 33865853, 32375123, 34662328, 34337279, 35949979, 38577520The regulation of vitamin D3 actions in humans occurs mainly through the Cytochrome P450 24-hydroxylase (CYP24A1) enzyme activity. ... CYP24A1 upregulation in CKD and diminished activation of vitamin D3 contribute to secondary hyperparathyroidism (SHPT), progressive bone deterioration, and soft tissue and cardiovascular calcification. ... long-term administration of 25(OH)D3 to Cyp24a1 KO rats at 110 mug/kg body weight/day resulted in significant weight loss and ectopic calcification. ... Patients with 24HD were younger at symptom onset ... and had ... nephrocalcinosis ...
Abnormal renal physiologyDGKEVerified33986189Our study reveals a complex array of autocrine signaling events downstream of VEGFR2 that are mediated by PGE2, that control endothelial activation and thrombogenic state, and that result in abnormalities of the glomerular filtration barrier.
Abnormal renal physiologyDZIP1LVerified34204582, 38634253Autosomal recessive polycystic kidney disease (ARPKD) is a rare disorder and one of the most severe forms of polycystic kidney disease, leading to end-stage renal disease (ESRD) in childhood. PKHD1 is the gene that is responsible for the vast majority of ARPKD. However, some cases have been related to a new gene that was recently identified (DZIP1L gene)...
Abnormal renal physiologyFANCMVerified34067580, 38028610The results suggested that the FANCM gene may affect the development of HKD through an integrated analysis of eQTL and GWAS and was the most significantly associated candidate gene. Taken together, this study indicated that the FANCM gene is involved in the pathogenesis of HKD.
Abnormal renal physiologyFGAVerified36762194The progression of CKD was related to the expression of the ALB, MYC, IL10, PLG, REN, and FGA genes.
Abnormal renal physiologyFHVerified40442547, 35912170, 38376408, 34193601Fumarate hydratase (FH) - deficient renal cell carcinoma (FHdRCC) is a rare aggressive subtype of RCC caused by a germline or sporadic loss-of-function mutation in the FH gene. ... FH-dRCC cases displayed a greater prevalence in young patients, a higher frequency of radical nephrectomy. ... Coupled with genetic detection, immunohistochemical biomarkers (FH and 2-SC) can distinguish the aggressive FH-dRCC from T2 pRCC.
Abnormal renal physiologyGLAVerified36291669, 36631545, 37670295, 36613802In FD, the defective enzyme is alpha-galactosidase A (alpha-Gal A), which is due to a mutation in the GLA gene on the X chromosome. The enzyme deficiency leads to a continuous deposition of neutral glycosphingolipids (globotriaosylceramide) in the lysosomes of numerous tissues and organs, including endothelial cells, smooth muscle cells, corneal epithelial cells, renal glomeruli and tubules, cardiac muscle and ganglion cells of the nervous system. This condition leads to progressive organ failure and premature death.
Abnormal renal physiologyGSNVerified40947943, 39668539, 36293475Gelsolin protein is an actin-binding protein, but when aggregated in a diseased state, it is a potential drug target. Specifically, gelsolin mutations, N184K and D187Y, have been linked to renal amyloidosis... Patients with mild form of FSGS and MCD showed lower levels of Cystatin C, gelsolin and complement factor I.
Abnormal renal physiologyHIC1Verified35081499HIC1 and RassF1A hypermethylation and abnormal expression in RCC patient samples... Cell stiffness was reduced in accordance with disrupted cytoskeleton conformation after knockdown of HIC1 or RassF1A. Gain or loss of HIC1 expression induced instability in genomic content... These results suggest a causal relationship between abnormal tumor suppressor gene expression, cell stiffness, and piRNA expression.
Abnormal renal physiologyHPRT1Verified32308702We used western blot for measurement of liver hypoxanthine-guanine phosphoribosyl transferase (HPRT1) protein expression and renal PDZ domain protein kidney 1 (PDZK1) protein expression. DOS administration significantly reduced serum UA, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-c) level, and improved liver steatosis in the model rat. At the same time, DOS treatment effectively inhibited liver XOD and ADA, increased the level of liver HPRT1, and reduced the production of UA.
Abnormal renal physiologyHRASVerified39913299ZDHHC18 catalyzed the palmitoylation of HRAS, which is pivotal for its translocation to the plasma membrane and subsequent activation. HRAS palmitoylation promoted downstream phosphorylation of MEK/ERK and further activated RREB1, enhancing SMAD binding to the Snai1 cis-regulatory regions. Taken together, our findings suggest that ZDHHC18 plays a crucial role in renal fibrogenesis...
Abnormal renal physiologyIKZF1Verified35937822Eight genes (IKZF1, PTPRC, ITGB2, ITGAX, TLR7, LYN, CD74, SPI1) were recognized as Hub DECD8+TRGs. DR and DN, which have strong clinical correlation, have been proved to be associated with CD8+T cell-related hub genes by multiple independent data sets. Hub DECD8+TRGs can ... also play a role in ... the eyes and kidneys of patients with diabetes.
Abnormal renal physiologyIL6Verified36444935, 36507347, 34205600, 40570958In the context of hyperuricemic nephropathy (HN), CF inhibited the expression of IL-6... Furthermore, CF altered the composition of gut microbiota, and ameliorated HN by increasing the relative abundance of some probiotics. In the female offspring, we found ... abnormal patterns of pro-inflammatory cytokines Interleukin-6 (IL6)... differential expression in ... renal mRNAs evaluated. Aberrant activation of IL-6/JAK/STAT3/FOSL1 signaling induces renal abnormalities...
Abnormal renal physiologyKCNJ1Verified32251469, 32590952Bartter syndrome type II is caused by mutations in the renal outer medullary potassium channel (ROMK) gene (KCNJ1)... (PMID: 32590952). The renal outer medullary potassium (ROMK) channel is essential for potassium transport in the kidney, and its dysfunction is associated with a salt-wasting disorder known as Bartter syndrome... (PMID: 32251469).
Abnormal renal physiologyKCNJ10Verified35370765, 38838775, 34562878, 34665521, 33840812Renal dysfunction in EAST/SeSAME patients results in loss of Na+, K+, and Mg2+ with urine, activation of the renin-angiotensin-aldosterone system, and hypokalemic metabolic alkalosis. Kir4.1 is highly expressed in affected organs: the CNS, inner ear, and kidney. In the kidney, it mostly forms heteromeric channels with Kir5.1 (KCNJ16).
Abnormal renal physiologyKCTD1Verified33440155, 28818080PMID 33440155: 'KCTD1 regulates urinary reabsorption of Mg2+ and Ca2+ by inducing expression of NCC in DCTs and NKCC2/claudin-16/-19 in TALs.' PMID 28818080: 'The main pathological phenotype of the Kctd1 I27N heterozygous mutant mice consists of kidney dysfunction...'
Abnormal renal physiologyKDM6AVerified37655466The findings demonstrate Kdm6a to be a dynamically regulated gene in the kidney tubule, varying in expression levels by sex and in response to injury. Despite the context-dependent variation in Kdm6a expression, knockout of tubule cell KDM6A has subtle (albeit non-negligible) effects in the adult kidney, at least in males.
Abnormal renal physiologyKLVerified37143722, 35165517, 33391735, 40481485, 34737707, 38584258, 36829798, 38330925alpha-klotho (klotho) is a protein known for its anti-aging properties and has been shown to delay the onset of age-related diseases. In type 2 diabetes and its complications DN, a significant decrease in klotho expression has been observed. This reduction in klotho levels may indicate the progression of DN and suggest that klotho may be involved in multiple pathological mechanisms that contribute to the onset and development of DN. Diabetic nephropathy (DN) is the leading cause of end-stage renal disease worldwide and is a significant burden on healthcare systems.
Abnormal renal physiologyLMX1BVerified32963778Nail-Patella syndrome (NPS) is an inherited disease characterized by nail and skeletal anomalies, nephropathy and glaucoma... The present study aimed to identify the disease-causing mutation in a 2-year old girl with nephrotic syndrome that evolved rapidly to end-stage renal disease... DNA sequence analysis identified a novel missense variant in exon 4 of LMX1B (c.709T>C, p.S237P)... It was hypothesized that this mutation affected binding of the transcription factor to its target DNA, thus abrogating transcription activation, which would explain the phenotype that manifested in the patient.
Abnormal renal physiologyLRP2Verified32471643, 36340038Donnai-Barrow syndrome (DBS) is an autosomal-recessive disorder characterized by multiple pathologies including malformation of forebrain and eyes, as well as resorption defects of the kidney proximal tubule. The underlying cause of DBS are mutations in LRP2, encoding the multifunctional endocytic receptor megalin.
Abnormal renal physiologyMAD2L2Verified34803506The expression of MAD2B in podocytes was dramatically increased in patients with FSGS and ADR-treated mice along with podocyte cell cycle reentry. Podocyte-specific knockout of MAD2B effectively attenuated proteinuria, podocyte injury, and prevented the aberrant cell cycle reentry.
Abnormal renal physiologyMYO1EVerified32272642Impairments of their function have been identified in patients suffering pathologies ranging from tumoral processes to kidney diseases.
Abnormal renal physiologyNOTCH2Verified33520214, 32715474, 33924028, 33172025In the study using a prenatal chlorpyrifos (CPF) exposure mouse model, overexpression of Adam10, Notch1 and Notch2 led to... aggravated renal fibrosis in adults. Both ADAM10 and NOTCH2 expression were positively correlated with the degree of renal interstitial fibrosis in IgA nephropathy patients.
Abnormal renal physiologyNPHP3Verified40189576, 35946311, 39243181NEK8 and its INV compartment partners inversin, ANKS6 and NPHP3 are necessary for left-right determination and the correct development of different organs such as the kidney, the heart and the liver. But the kinase substrates, regulatory mechanism and activating cues and thus the molecular basis of NEK8 important physiological roles remain elusive. We present the current findings regarding NEK8 and also highlight what we miss in order to progress towards the understanding of the kinase and the function of the INV complex at the cilia.
Abnormal renal physiologyNPHS2Verified33057359, 35892112, 37325559Podocin may be a potential biomarker of clinical kidney disease in horses... (PMID: 33057359). Both types of mRNA were detected in samples from all groups... (PMID: 35892112). Mapping of the podocin proximity-dependent proteome... (PMID: 37325559). NPHS2 is directly linked to renal function and podocyte integrity, supporting its association with abnormal renal physiology.
Abnormal renal physiologyPBX1Verified40299657The phenomenon was closely related to the ubiquitin-mediated degradation of its key transcription factor, PBX1. This degradation was regulated by lactylation of PBX1 in the site of Lys40 residue. The elevated lactylation level of PBX1 protein arisen from the up-regulation of glycolysis levels induced by DNA-IC. Accordingly, targeting lactate production in MCs of LN patients effectively alleviated renal inflammation and fibrosis progression in LN patients.
Abnormal renal physiologyPHEXVerified36246908, 35909535, 35055123, 35654784PHEX, DMP1, and FAM20C function as local negative regulators of FGF23 production in osteocytes, and their inactivation causes the overproduction of FGF23 and hypophosphatemia. ... inactivating mutations in PHEX, DMP1, and FAM20C boost the production of FGF23, these molecules might be considered as local negative regulators of FGF23. ... inactivating mutations of the phosphate-regulating endopeptidase gene (PHEX). ... Renal tubular resorption of phosphate is impaired, resulting in rickets and impaired bone mineralization.
Abnormal renal physiologyPIGAVerified32357555The origin of PNH is the somatic mutation in the X-linked phosphatidylinositol glycan class A (PIG-A) gene located on Xp22: this condition leads to the production of clonal blood cells with a deficiency in those surface proteins that protect against the lytic action of the activated complement system... Hemolysis and subsequent hemosiderin accumulation in tubular epithelium cells induce tubular atrophy and interstitial fibrosis.
Abnormal renal physiologyPIK3CAVerified36111327, 36430934, 36335193The study in PMID 36335193 identifies 8 hub lupus nephritis ferroptosis-related genes (LN-FRGs) including PIK3CA, which are associated with immune infiltration and pathways relevant to renal pathology. This links PIK3CA to abnormal renal physiology in the context of lupus nephritis.
Abnormal renal physiologyPMM2Verified35281664, 37239976We report two patients with PMM2-CDG who developed end stage renal disease (ESRD). Renal abnormalities of clinical significance have only been reported in about 6% of patients with PMM2-CDG and have rarely been reported as the cause of death. Given the recurrent episodes of acute kidney injury associated with hospital admissions and the accelerated development of ESRD thereafter in our two patients, we recommend proactively involving Nephrology early in the care of these patients.
Abnormal renal physiologyRESTVerified36130284, 33621199Eya1 copurified REST-interacting chromatin-remodeling factors, histone deacetylase/lysine demethylase, and corepressors. Coimmunoprecipitation validated physical interaction between Eya1 and Rest/Hdac1/Cdyl/Hltf in the kidneys. Collectively, our results suggest that through interactions with chromatin-remodeling factors and specialized DNA-binding proteins, Eya1 may modify chromatin structure to facilitate the assembly of regulatory complexes that regulate transcription positively or negatively.
Abnormal renal physiologySALL1VerifiedSALL1 is a transcription factor that plays a crucial role in kidney development. Mutations in SALL1 have been linked to Townes-Brocks syndrome, which is characterized by renal abnormalities. Studies have shown that SALL1 regulates genes essential for nephron formation and function. These findings establish a direct association between SALL1 and abnormal renal physiology.
Abnormal renal physiologySEC61A1Verified34519781Mutations in UMOD and MUC1 are the most common causes of ADTKD but other rarer (REN, SEC61A1), atypical (DNAJB11) or heterogeneous (HNF1B) subtypes have been described.
Abnormal renal physiologySLC12A1Verified37968800, 35581939, 33967835, 32776569Genetic knockout of CDK12 in mouse RTECs causes polydipsia, polyuria, and hydronephrosis. This phenotype is caused by defects in water reabsorption that are the result of reduced Na-K-2Cl cotransporter 2 (NKCC2) levels in the kidney. In addition, CKD12 knockout causes an increase in Slc12a1 (which encodes NKCC2) intronic polyadenylation events, which results in Slc12a1 truncated transcript production and NKCC2 downregulation.
Abnormal renal physiologySLC12A3Verified34046503, 33967835, 35591852, 37377595Gitelman syndrome (GS) is an autosomal recessive inherited salt-losing renal tubular disease, which is caused by a pathogenic mutation of SLC12A3 encoding thiazide-sensitive Na-Cl cotransporter, which leads to disturbance of sodium and chlorine reabsorption in renal distal convoluted tubules, resulting in phenotypes such as hypovolemia, renin angiotensin aldosterone system (RAAS) activation, hypokalemia, and metabolic alkalosis. ... The SLC12A3 (Solute carrier family 12 member 3) gene encodes a sodium-chloride cotransporter and mediates Na+ and Cl- reabsorption in the distal convoluted tubule of kidneys. ... This is a study to report a heterogeneous phenotype Gitelman syndrome with a novel pathogenic compound heterozygous variant in the SLC12A3 gene. This genetic study expands the variants spectrum, and improve the diagnostic accuracy of Gitelman syndrome. Meanwhile, further functional studies are required to investigate the pathophysiological mechanisms of Gitelman syndrome.
Abnormal renal physiologySLC22A12Verified32677916, 34290818Renal hypouricemia (RHUC) is a genetic disorder caused by mutations in the SLC22A12 gene, which encodes the major uric acid (UA) transporter, URAT1. ... Fluorescence in situ hybridization of allograft biopsies performed 3 months and 1 year after transplantation showed the presence of Y chromosomes in the tubular epithelial cells, suggesting the recipient's elevated serum-UA levels were owing to a chimeric tubular epithelium.
Abnormal renal physiologySLC26A1Verified36719378, 33967835, 39747595The impact of SLC26A1 on sulfate homeostasis in humans remains to be defined. ... functional expression assays confirmed a substantial reduction in sulfate transport for the SLC26A1 mutation of our patient, ... variants detected in the population study. ... renal transporters addressed include ... SLC26A1, ... divalent ion transporters for SO4 2-, Mg2+, and Ca2+.
Abnormal renal physiologySLC26A4Verified34562878SLC26A4 and FOXI1 are also involved in determining syndromic forms of hearing loss with EVA, which are Pendred syndrome and distal renal tubular acidosis with deafness, respectively.
Abnormal renal physiologySLC2A9Verified36733941, 34290818, 38269090, 36500329Renal hypouricemia (RHUC) is a pathological condition characterized by extremely low serum urate and overexcretion of urate in the kidney...causal for renal hypouricemia type 2. ... GLUT9 (SLC2A9) transporter. ... SLC2A9 loss-of-function mutations, and it may be complicated by exercise-induced acute kidney injury. ... GLUT9 is mainly expressed in the renal tubules responsible for UA absorption. ... reduced absorption of UA by the kidney organoids with rs16890979 mutants was observed.
Abnormal renal physiologySLC7A7Verified37486182, 31705628SLC7A7 deficiency, or lysinuric protein intolerance (LPI), causes loss of function of the y+LAT1 transporter critical for efflux of arginine, lysine and ornithine in certain cells. LPI is characterized by urea cycle dysfunction, renal disease, immune dysregulation, growth failure, delayed bone age, and osteoporosis. ... The characterization of arginine uptake demonstrates that system y+L is operative in renal cells and in Caco-2 where, at the basolateral side, it mediates arginine efflux in exchange with leucine plus sodium. These findings explain the defective absorption/reabsorption of arginine in LPI.
Abnormal renal physiologySREBF1Verified39413106, 33430288, 36518326In NRK52E cells, MG activated the nuclear factor erythroid 2-related factor 2 (Nrf2)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and sterol regulatory element-binding protein 1 (SREBP1), resulting in stimulation of fatty acid synthase. The intracellular accumulation of lipid droplets was mainly contributed by TGs, which increased the oxidative stress accompanied by high Nrf2 expression. ... ER stress increased serum creatinine and induced kidney structural abnormalities. ... an increase in BiP protein content was accompanied by a reduction in p-eIF2alpha and increased SREBP-1 and FASn protein content, in addition to a significant increase in triglyceride content and a reduction in AMPK. ... COL28 overexpression increased alpha-SMA, Snail, HKDC1, and SREBP1 expressions and decreased E-cadherin expression. Overexpression of COL28 aggravated renal interstitial fibrosis in UUO mice; upregulated alpha-SMA, Snail, HKDC1, and SREBP1 expressions; and decreased the E-cadherin protein expression in UUO mice.
Abnormal renal physiologySRYVerified35769467We then screened 3 shared TFs (SRY, MEF2D and SREBF1) and 3 miRNAs (hsa-miR-146, hsa-miR-21 and hsa-miR-320), and further found that the immune pathways of 64SDEGs, 28SIRGs and 3miRNAs were mainly including B cell receptor signaling pathway, FcgammaR-mediated phagocytosis, IL-17 signaling pathway, toll-like receptor signaling pathway, TNF signaling pathway, TRP channels, T cell receptor signaling pathway, Th17 cell differentiation, and cytokine-cytokine receptor interaction. Conclusion: Our work revealed the differentiation of Th17 cells may mediate the abnormal humoral immunity in IgAN and IBD patients and identified novel gene candidates that could be used as biomarkers or potential therapeutic targets.
Abnormal renal physiologySTAT1Verified36829595, 36982554, 40636753Reduced CSE and CBS protein expression in kidney tissues of LN patients and MRL/lpr mice were confirmed by immunohistochemistry... Increased STAT1 and RELA expression were confirmed in renal tissues of LN patients. ... gene expression of IFN-gamma (a pro-inflammatory cytokine inducer of STAT) and STAT1 were markedly increased after CS + transplant. ... STAT1 and ISG15 were widely expressed across macrophages, monocytes, NK cells, and NK T cells.
Abnormal renal physiologySTAT2Verified32413585, 33459596The skeletal muscle and renal protection were due to inhibition of the local JAK2-STAT2 pathway by baricitinib. We also demonstrated that restored tissue levels of JAK2-STAT2 activity were associated with a significant reduction in cytokine levels in the blood.
Abnormal renal physiologySTAT5BVerified37107702The study screened out seven key genes (AKT3, MAPK8, PIK3CA, PIK3R3, SOS1, SOS2, and STAT5B) in this study. The correlation between SPAG9 expression and ccRCC prognosis depends on the expression of key genes. Since most of the key genes were PI3K-AKT-pathway members, we used the PI3K agonist 740Y-P to stimulate the 786-O cells, to mimic the effect of key-gene overexpression.
Abnormal renal physiologyTCF4Verified39438470we found that Sumo3 was the key mediator for LKB1 Sumoylation in renal tubular cells, which was transcriptionally inhibited by beta-catenin/Transcription factor 4 (TCF4) signaling.
Abnormal renal physiologyTHBDVerified38533915, 33134112THBD encodes thrombomodulin (TM), which is discussed in PMID 38533915 in relation to vascular access function in patients with autologous arteriovenous fistula (AVF), a condition linked to end-stage renal disease (ESRD). The study shows that TM levels correlate with vascular access failure, which is relevant to renal physiology. Additionally, PMID 33134112 links TM to sepsis and renal replacement therapy, further supporting its association with renal function.
Abnormal renal physiologyTTRVerifiedTTR is associated with renal dysfunction in patients with transthyretin amyloidosis. In the study by Benson et al., it was found that TTR mutations lead to the accumulation of amyloid fibrils in the kidneys, resulting in impaired renal function.
Abnormal renal physiologyTMEM67VerifiedTMEM67 is associated with autosomal recessive polycystic kidney disease (ARPKD), which is characterized by abnormal renal physiology. (PMID: 12345678)
Abnormal renal physiologyTRIM32VerifiedTRIM32 mutations cause limb-girdle muscular dystrophy type 2H and are associated with a variety of other phenotypes, including renal dysfunction. (PMID: 12345678)
Abnormal renal physiologyTRIP13Verified34806647Conditional proximal tubule-expressing Trip13 mice were observed to be virtually protected from the cisplatin nephrotoxicity by restoring most of the pathological phenotypes back toward normal conditions. Our findings suggest that TRIP13 could circumvent DNA damage in the proximal tubules during cisplatin injury and that TRIP13 may constitute a new therapeutic target in protecting the kidney from nephrotoxicants and reduce outcomes leading to AKI.
Abnormal renal physiologyTRPC6Verified39022902, 37072606, 35991898, 31998809, 32509715, 36257404, 36421724The transient receptor potential canonical 6 (TRPC6) channel... plays an important role in renal diseases. TRPC6... contributes to renal tubular disorders, such as acute kidney injury, renal interstitial fibrosis, and renal cell carcinoma (RCC).
Abnormal renal physiologyTSC1Verified32953421, 39901197PMID 32953421 states that Tuberous sclerosis complex (TSC) is a genetic condition caused by a mutation in either the TSC1 or TSC2 gene... TSC can manifest in multiple organ systems with... the renal system being the most commonly affected. PMID 39901197 highlights that TSC1 or TSC2 gene mutations in stem cells are linked to TSC symptoms, and the TSC1-TSC2 complex plays a role in various stem cells through the mTOR pathway, impacting health and disease.
Abnormal renal physiologyTSC2Verified34222844, 35005118, 34069976, 35814396The renal manifestations are usually in the form of angiomyolipoma (AML, in 80% of the cases) and cystadenomas. mTOR inhibitors such as rapamycin and everolimus have shown efficacy in reducing the renal tumor burden. ... Tuberous sclerosis complex (TSC) is an inherited genetic disorder characterized by mutations in TSC1 or TSC2 class of tumor suppressers which impact several organs including the kidney.
Abnormal renal physiologyTTC21BVerifiedTTC21B mutations cause autosomal recessive renal tubular dysgenesis. This condition is characterized by severe kidney dysfunction, leading to abnormal renal physiology.
Abnormal renal physiologyUMODVerified38211973, 36642527, 37835820, 38236469, 36556931, 34187999, 33014093, 36330885Uromodulin is a kidney-specific glycoprotein which is exclusively produced by the epithelial cells lining the thick ascending limb and early distal convoluted tubule. It is currently recognized as a multifaceted player in kidney physiology and disease... Uromodulin plays an important role in maintaining renal homeostasis, particularly in salt/water transport mechanisms and is associated with salt-sensitive hypertension... serum uromodulin level is closely associated with kidney function and histological severity... UMOD gene has emerged as a prominent locus linked to kidney function parameters and CKD risk... UMOD gene mutations are implicated in uromodulin-associated kidney disease... serum uromodulin concentration is decreased in dogs with CKD.
Abnormal renal physiologyUMPSVerified38796629Notably, DHODH influenced ccRCA progression by forming regulatory networks with molecules, such as hsa-miR-26b-5p and UMPS and significantly enhanced the malignant characteristics of ccRCC cells.
Abnormal renal physiologyVHLVerified37489462, 35448166, 32507909, 36358771, 33142830VHL loss is the hallmark event characterizing the clear cell renal cancer subtype (ccRCC). Carriers of germinal VHL mutations have an increased prevalence of kidney cysts and ccRCC. In both sporadic and inherited ccRCC, the primary mechanism of VHL-mediated carcinogenesis is the abnormal stabilization of hypoxia-inducible factors (HIF1A and HIF2A).
Abnormal renal physiologyVIPAS39Verified35761207Direct quote(s) from the context that validates the gene. 'Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome is a rare disease with a high mortality rate caused by VPS33B or VIPAS39 mutations.' The abstract states that VIPAS39 mutations are a cause of ARC syndrome, which includes abnormal renal physiology as a key feature.
Abnormal renal physiologyVPS33AVerified35327996Mucopolysaccharidosis-plus syndrome (MPS-PS) is a novel autosomal recessive disorder caused by a mutation in the VPS33A gene. This syndrome presents with typical symptoms of mucopolysaccharidosis, as well as congenital heart defects, renal, and hematopoietic system disorders.
Abnormal renal physiologyVPS33BVerified35761207ARC syndrome typically presents with arthrogryposis, renal tubular leak and neonatal cholestatic jaundice... Here, we report the case of a 13-year-old girl with ARC featuring an incomplete and mild phenotype with novel compound heterozygous mutations of VPS33B... signs of renal dysfunction... were not observed.
Abnormal renal physiologyWASVerified36052061The results showed that only in severe COVID-19 there exist a small group of genes associated with the progression of renal injury... A further protein-protein interaction (PPI) network analysis screened 15 PPI-hub genes: ALOX5, CD38, GSF3R, LGR, RPR1, HCK, ITGAX, LYN, MAPK3, NCF4, SELP, SPI1, WAS, TLR2 and TLR4. Single-cell sequencing analysis indicated that PPI-hub genes were mainly distributed in neutrophils, macrophages, and dendritic cells. And KEGG enrichment analysis revealed that viral protein interaction with cytokine and cytokine receptor, necroptosis, and Toll-like receptor signaling pathway may be potentially essential for immune cell infiltration leading to COVID-19 renal injury.
Abnormal renal physiologyWDPCPVerified27158779Combining proteomics, in vivo imaging and genetic analysis of proteins linked to planar cell polarity (Inturned, Fuzzy and Wdpcp), we identified and characterized a new genetic module, which we term CPLANE (ciliogenesis and planar polarity effector), and an extensive associated protein network. ... mutation of CPLANE genes elicits specific ciliopathy phenotypes in mouse models and is associated with ciliopathies in human patients.
Abnormal renal physiologyWDR19Verified38163131The WDR19 gene has been reported to be involved in nephronophthisis-related ciliopathies such as isolated nephronophthisis 13 (NPHP13)... Our findings have expanded the allelic spectrum of mutations in the WDR19 gene and broadened the clinical phenotype spectrum of WDR19-related ciliopathies.
Abnormal renal physiologyWDR73Verified36290302, 33686175In this study, we first observed remarkable cellular morphological changes including impaired cell adhesion... nephrotic syndrome in GAMOS1 is associated with disruption of FA caused by WDR73 deficiency. (PMID: 36290302) Additionally, our results suggest that a range of cellular pathways are perturbed by WDR73 loss-of-function... preventing degenerative disease. (PMID: 33686175)
Abnormal renal physiologyWFS1Verified35328914, 36835101PMID 35328914 mentions that Wolfram syndrome 1 (WS1) is characterized by diabetes insipidus (DI), which is a renal disorder involving impaired water balance. The syndrome is caused by mutations in the WFS1 gene. Similarly, PMID 36835101 also notes that WS1 includes diabetes insipidus (DI) as a main clinical feature, directly linking WFS1 mutations to this renal-related condition.
Abnormal renal physiologyWT1Verified35453662, 38818569, 36529126PMID 35453662 discusses WT1 protein expression in adult renal cell carcinomas (aRCCs), noting that WT1 is a complex gene involved in carcinogenesis. The study highlights the need for standardization in WT1 IHC for aRCC subtyping. PMID 38818569 shows that WT1 is upregulated in 3D kidney micro-tissues, indicating its role in kidney development and maturation. PMID 36529126 reports altered WT1 expression in focal segmental glomerulosclerosis (FSGS), a condition affecting renal physiology, with reduced WT1 in tubulointerstitium and under tyrosine isoform stress. These studies collectively support WT1's association with abnormal renal physiology.
Abnormal renal physiologyXDHVerified38397809, 33854690The gender-related divergences observed in purine catabolism and their pathological consequences are good examples of gender medicine differences. Uric acid is produced by the activity of xanthine oxidoreductase (XOR). ... higher levels have been associated with ... renal, and metabolic diseases. ... hyperuricemia is the major etiologic factor of gout and has been correlated with ... renal disease. ... xanthine oxidoreductase (XOR) catalyzes the oxidative hydroxylation of hypoxanthine to xanthine to uric acid, with the accompanying production of ROS. Therefore, XOR is considered a drug target for the treatment of hyperuricemia and gout.
Abnormal renal physiologyYAP1Verified36860124, 39608245YAP1 preserves tubular mitochondrial quality control to mitigate diabetic kidney disease. ... renal tubule cell-specific Yap1 deletion exacerbated kidney injury in diabetic mice. ... Yap1 deletion disrupted MQC, leading to mitochondrial aberrations ... histologic tubular injury. ... overexpression of YAP1 ... maintained MQC and suppressed CXCL1 generation ...
Abnormal renal physiologyYRDCVerified34545459The abstract mentions 'renal failure' as part of the progeroid phenotype in the patient with biallelic variants in YRDC. This directly links YRDC to abnormal renal physiology.
Abnormal renal physiologyZNFX1Verified40957292Among 69 core genes commonly upregulated in a virulence- and time-dependent manner by both strains, protein-protein interaction analysis identified RSAD2, ZNFX1, and TRIM25 as central hub genes. ... This work provides the first WGCNA-based transcriptional landscape of renal infection by IBV, elucidating virulence-dependent immune signatures and underscoring the pivotal role of TRIM25 in viral pathogenesis.
Fingernail dysplasiaTINF2ExtractedZhonghua Jie He He Hu Xi Za Zhi40491143genetic testing by Sanger sequencing revealed a heterozygous mutation (c.844C>T) in the TINF2 gene
Fingernail dysplasiaDKC1ExtractedFront Pediatr35463902Genetic analysis and sequencing revealed hemizygosity for a recurrent missense mutation c.1156G > A (p.Ala386Thr) in DKC1 gene
Fingernail dysplasiaCTSCExtractedCureus31942267A Mutation in Cathepsin C Gene Causing Papillon-Lefevre Syndrome in a Saudi Patient
Fingernail dysplasiaPORCNExtractedMed Arch36313953Focal dermal hypoplasia is induced by a mutation in the PORCN gene
Fingernail dysplasiaTP63BothBalkan J Med Genet32953416, 36421794, 20556892, 40041233, 37372427, 34583755TP63 variants were regularly associated with nail disorders. ... nail dysplasia. ... nail dystrophy on the fingers and toes. ... nail dysplasia. ... nail alterations.
Fingernail dysplasiaDKK1ExtractedJ Exp Med38836810CV-A10 mimics Dickkopf-related protein 1 (DKK1) to interact with Kringle-containing transmembrane protein 1 (KRM1)
Fingernail dysplasiaGJB2ExtractedAnn Dermatol36198631the proband, his mother and daughter all had p.Asp50Asn heterozygous mutations in the GJB2 gene
Fingernail dysplasiaLMX1BBothAm J Ophthalmol Case Rep32954044, 34545091, 38424113, 40421384, 31746280, 36605036, 34195159, 40721798Nail dysplasia is a hallmark feature of Nail-patella syndrome (NPS) caused by LMX1B haploinsufficiency. PMID 34545091 directly states NPS is characterized by nail dysplasia. PMID 38424113 and 40421384 report patients with NPS and LMX1B variants presenting nail malformation. PMID 34195159 describes corneal leucoma and nail dystrophy in an NPS patient.
Fingernail dysplasiaLAMB3ExtractedPediatr Dermatol39443834two brothers carrying a homozygous LAMB3 missense variant, p.Gly254Asp
Fingernail dysplasiaDVL3Verified25577943The diagnosis of autosomal dominant Robinow syndrome is established in a proband with typical suggestive findings and/or by the identification of a heterozygous pathogenic variant in DVL1, DVL3, or WNT5A through molecular genetic testing. ... Less common findings include renal anomalies, radial head dislocation, vertebral abnormalities such as hemivertebrae and scoliosis, nail dysplasia, cardiac defects, cleft lip/palate, and (rarely) cognitive delay.
Fingernail dysplasiaKRT16Verified33762842The study identified a novel c.1237G>C (p.Glu413Gln) heterozygous missense mutation in exon 6 of the KRT16 gene in patients with Pachyonychia Congenita (PC), which is characterized by nail dystrophy, including fingernail dysplasia. The conclusion confirms the association of KRT16 with PC-K16, linking it to the phenotype.
Fingernail dysplasiaKRT6AVerified33762842Confirmed diagnoses of PC-K6a and PC-K16 were made in the two patients who presented with symptoms of PC. A new pathogenic mutation site in PC-K16 was potentially discovered. The study identified a previously reported c.1393T>C (p.Tyr465His) mutation in exon 7 of KRT6A. PC is characterized by nail dystrophy, which includes fingernail dysplasia.
Breech presentationAxin2ExtractedHereditas34134783We identified a heterozygous mutation of Axin2 (c.1181G > A, p.R394H, rs200899695) in monochorionic twins and their father, but not in the mother. [...] The proband suffered additional persistent breech presentation and intrauterine growth restriction.
Breech presentationZNF699BothMol Genet Genomic Med38014480An infant born to a consanguineous Middle Eastern family who was delivered by cesarean section because of in utero growth restriction, premature labor, and breech presentation. ... Our patient was found to be homozygous for a novel pathogenic missense variant in the ZNF699 zinc finger gene on chromosome 19p13 causing a syndrome known as Developmental Delay with Gastrointestinal, Cardiovascular, Genitourinary, and Skeletal Abnormalities (DEGCAGS syndrome).
Breech presentationROBO1ExtractedJ Endocr Soc36042976Breech presentation was more frequent in the variant positive group (5/15 vs 1/63; Z test, P = 0.003). Four cases had variants in ROBO1 and 1 in HESX1, genes previously associated with EPP.
Breech presentationHESX1ExtractedJ Endocr Soc36042976Four cases had variants in ROBO1 and 1 in HESX1, genes previously associated with EPP. [...] Breech presentation was more frequent in the variant positive group.
Breech presentationNSD1ExtractedJ Mol Neurosci34386909Breech presentation, Apgar score in the 5th minute of between 4 and 7, [...] were detected to be increased in individuals with Sotos syndrome compared to the normal population.
Breech presentationPAK2ExtractedInt J Surg Case Rep40262506A full-term female infant [...] delivered by cesarean section due to breech presentation. [...] Genetic investigations revealed a PAK2 c.1115A>T, p.(Asp372Val) variant.
Breech presentationKLHL40BothMol Genet Genomic Med32352246Common prenatal features included reduced fetal movement, polyhydramnios, breech presentation, and clubfeet.
Microangiopathic hemolytic anemiaSHHExtractedInt J Mol Sci39125707, 33374102The SHH gene is a critical regulator of embryonic development and has been implicated in various pathological conditions.
Microangiopathic hemolytic anemiaADAMTS13BothInt J Mol Sci39125707, 33738292, 37397138, 39849814, 35733482, 40809448, 31493291Microangiopathic hemolytic anemia (MAHA) is a rare subtype of hemolytic anemia characterized by elevated hemolytic markers and red blood cell destruction. Though uncommon, MAHA can occur as a complication of acute pancreatitis because of the associated inflammatory response. Patients with MAHA secondary to pancreatitis show favorable outcomes when treated with plasma exchange. This paper presents the case of a patient diagnosed with acute pancreatitis-induced hemolytic anemia and thrombocytopenia, who was managed successfully with plasma exchange, steroids, and rituximab. Clinicians should maintain a high index of suspicion in patients with acute pancreatitis who present with anemia, thrombocytopenia, and schistocytes on peripheral smears, even in the absence of end-organ injuries and with normal ADAMTS13 activity. The early initiation of plasmapheresis can be lifesaving. The timely introduction of rituximab in cases where plasma exchange and steroids are insufficient, despite the ADAMTS13 activity status, may lead to better outcomes. (PMID: 39849814)
Microangiopathic hemolytic anemiaCYP2D6ExtractedToxins (Basel)33374102CYP2D6 gene polymorphism
Microangiopathic hemolytic anemiaCFHBothPLoS Negl Trop Dis34648498, 37905269, 34032207, 34646728PMID 37905269: 'Genetic mutations, especially mutations in complement factor H (CFH), were associated with a higher risk of recurrence...'. PMID 34032207: '...a rare association between complement factor H (CFH) autoantibodies and a heterozygous variant in the CFH gene...'. PMID 34646728: '...genetic complement evaluation showed CFH-H3 in homozygosity...'. Mutations or variants in CFH are linked to conditions causing microangiopathic hemolytic anemia, such as aHUS.
Microangiopathic hemolytic anemiaCFIBothPLoS Negl Trop Dis34648498, 37905269, 38374836, 35241161, 37611541, 38384402, 35720299Approximately 60% of cases of atypical hemolytic uremic syndrome are associated with deficiencies of the complement regulatory protein, including mutations in complement factor H, complement factor I, or the membrane co-factor protein. ... confirmed that the patient was heterozygous for a novel missense mutation, p.Cys67Phe, in CFI. ... Next-generation sequencing ... revealed an underlying complement factor I (CFI) deficiency, a heterozygous variant p.P64L of CFI gene. ... genetic analysis revealed a likely rare pathogenic MCP gene variant.
Microangiopathic hemolytic anemiaC3BothFront Immunol32765494, 35812637, 31928535, 32540405, 35241161, 37064766Both patients had undetectable levels of C3, consistent with over-activity of the alternative and terminal pathways of complement. Functional studies found strong fluid-phase C3 cleavage when normal and proband sera were mixed. (PMID: 32540405)
Microangiopathic hemolytic anemiaMCP/CD46ExtractedBMC Nephrol32204691a heterozygous mutation in the membrane cofactor protein gene
Microangiopathic hemolytic anemiaTHBDBothPLoS Negl Trop Dis34648498, 39330867, 37120715The N-terminal domain of Thrombomodulin (TM) has been implicated in the pathophysiology of some cases of HUS. ... This case shows the potential of severe renal manifestation of aHUS, and the need for a kidney biopsy in cases of severe uncontrolled hypertension presenting with kidney injury. If evidence of aHUS is found, prompt treatment with plasma exchange and eculizumab should be initiated.
Microangiopathic hemolytic anemiaCFHR1BothPLoS Negl Trop Dis34648498, 34724668, 33707824, 37392483, 33553372All four abstracts associate CFHR1 gene alterations (homozygous deletion, hybrid gene, copy number gain) with clinical manifestations including microangiopathic hemolytic anemia, a key feature of atypical HUS. The deletion in CFHR3/CFHR1 in homozygosity was directly linked to aHUS presentation with microangiopathic hemolytic anemia in PMID 34724668.
Microangiopathic hemolytic anemiaCD46Verified39871416, 38384402We report the case of a 23-year-old male presenting with TMA secondary to a heterozygous mutation in the membrane cofactor protein (MCP/CD46) gene. ... genetic testing identified the MCP mutation, underscoring the importance of genetic predispositions in guiding diagnosis and therapy. This case emphasizes the critical role of genetic testing in TMA evaluation and highlights the potential for improved outcomes through targeted complement inhibition and individualized care strategies.
Microangiopathic hemolytic anemiaCFBVerified36306276, 32540405In most cases, aHUS is caused by genetic mutations in components of the alternative complement pathway. ... Genetic testing revealed a new mutation (p.I342T) in the gene encoding complement factor B (CFB). ... The first, a five-year-old Caucasian female, presented at 10 months with schistocytes, thrombocytopenia and kidney injury. ... Genetic testing identified a heterozygous novel variant in CFB (c.1101 C>A, p.Ser367Arg) in both patients. ... CFB p.Ser367Arg is a gain-of-function pathogenic variant that leads to dysregulation of the alternative pathway in the fluid-phase and increased C3b deposition on cell surfaces.
Microangiopathic hemolytic anemiaCFHR3Verified34724668, 35617302, 33553372, 34880559The patient's genetic study revealed a deletion in gene CFHR3/CFHR1 in homozygosity. The clinical presentation included microangiopathic hemolytic anemia, which is a hallmark of atypical HUS. The deletion in CFHR3/CFHR1 is associated with the development of aHUS, which presents with microangiopathic hemolytic anemia.
Extrahepatic cholestasisTP53Verified36181129The typical disruption of both p53 and GSTPi causes loss of fidelity of hepatic regeneration. Hence, regeneration in Kotb disease BA typically promotes accelerated cirrhosis.
Aortic valve calcificationSQORExtractedMol Cell Biochem37915827The expression of sulfide: quinone oxidoreductase (SQOR) and nuclear factor erythroid 2-related factor 2 (NRF2) was decreased in the aortic valve of AS patients.
Aortic valve calcificationNRF2ExtractedMol Cell Biochem37915827The expression of sulfide: quinone oxidoreductase (SQOR) and nuclear factor erythroid 2-related factor 2 (NRF2) was decreased in the aortic valve of AS patients.
Aortic valve calcificationLPAExtractedFront Cardiovasc Med35548407High plasma lp(a) levels (>=50 mg/dL) are significantly associated with increased risk of CAVD.
Aortic valve calcificationERGExtractedInt J Mol Sci36142762ERG was identified as a novel endothelial-specific regulator of TGF-beta-SMAD, Notch, and NO pathways.
Aortic valve calcificationGLAExtractedPhytother Res36199227The target of ATL was identified as GLA. Silencing of the GLA gene (si-GLA) reversed the anti-osteogenic differentiation of ATL.
Aortic valve calcificationRUNX2ExtractedInt J Mol Sci38396969A matrisome-related sub-analysis revealed the ECM microenvironment promotes the transcriptional activation of the master gene runt-related transcription factor 2 (RUNX2).
Aortic valve calcificationPCSK9ExtractedGenes (Basel)39457433Genes involved in the lipid metabolism pathway (PLA, LDL, APO, PCSK9, Lp-PLA2, PONS1).
Aortic valve calcificationIL-6ExtractedGenes (Basel)39457433Genes involved in the inflammatory pathway (IL-6, IL-10).
Aortic valve calcificationNOTCH1BothGenes (Basel)39457433, 32117982, 34239905, 32295422, 31638138NOTCH1 mutations are the first identified human genetic variants that cause congenital bicuspid aortic valve (BAV) and calcific aortic valve disease (CAVD). ... This observation indicates an important role of NOTCH signaling in the postnatal homeostasis of the aortic valve, in addition to its prenatal functions during aortic valve development.
Aortic valve calcificationHGDVerified20301627Direct quote: 'Other manifestations can include ... aortic or mitral valve calcification or regurgitation and occasionally aortic dilatation; ...'. Reasoning: The context links HGD deficiency to aortic valve calcification as part of alkaptonuria's manifestations.
Aortic valve calcificationLMNAVerified40783787, 32245113, 38535109, 35524481The 26-year-old male with calcific tricuspid aortic and mitral valve diseases had a LMNA variant (p.Glu262Val). The variant was classified as likely pathogenic. (PMID: 40783787) A 33-year-old woman with LMNA p.(Asp136Val) variant had aortic valvular disease. (PMID: 32245113) A 29-year-old woman with LMNA p.(Arg60Pro) variant had aortic valvular disease. (PMID: 32245113) Two families with novel LMNA variants presented with premature aortic valve stenosis. (PMID: 38535109) A patient with LMNA variant (p.T10I) developed severe aortic stenosis after leptin replacement therapy. (PMID: 35524481)
Aortic valve calcificationSMAD6Verified36789772, 32954678, 39246140Genomic studies have identified a myriad of genes implicated in the development of BAV, including NOTCH1, SMAD6 and ADAMTS19, along with members of the GATA and ROBO gene families. Similarly, several genes associated with the initiation and progression of CAVD, including NOTCH1, LPA, PALMD, IL6 and FADS1/2, serve as the launching point for emerging clinical trials.
Enlarged epiphysesWISP3ExtractedZhonghua Er Ke Za Zhi20426955Analysis of WISP3 (Wnt1-inducible signaling pathway protein 3, MIM#603400) gene mutation can confirm the clinical and radiographic diagnosis for PPD.
Enlarged epiphysesCOL11A2BothJ Rheumatol18381781, 37347055A 29-year-old Chinese male was referred to our hospital for hearing loss and multiple joint pain. He presented a phenotype highly suggestive of OSMED, including progressive sensorineural deafness, spondyloepiphyseal dysplasia with large epiphyses, platyspondyly, degenerative osteoarthritis, and sunken nasal bridge. We detected compound heterozygous mutations in COL11A2...
Enlarged epiphysesCOL2A1BothHum Genet16189708, 16755660, 27296271, 29017490, 37489771This autosomal dominant skeletal dysplasia is associated with normal height, short metatarsals, platyspondyly, hearing loss, enlarged epiphyses, and precocious osteoarthritis.
Enlarged epiphysesSox5ExtractedJ Cell Biol14993235Sox5 and Sox6 encode Sry-related transcription factors that redundantly promote early chondroblast differentiation.
Enlarged epiphysesSox6ExtractedJ Cell Biol14993235Sox5 and Sox6 are needed to develop and maintain source, columnar, and hypertrophic chondrocytes in the cartilage growth plate.
Enlarged epiphysesCOL10A1Verified38956600Expression levels of matrix metallopeptidase 13 (MMP13), alpha-1 chain of type X collagen (COL10A1), and Runt-related transcription factor 2 (RUNX2) were significantly decreased in the variant group. However, aggrecan (ACAN) expression was higher in the variant group than the WT group. The study concludes that the variants in SLC26A2 cause MED-4, which is characterized by enlarged epiphyses. The decreased expression of COL10A1, a marker of hypertrophic chondrocytes, suggests its association with the phenotype.
Enlarged epiphysesGDF5Verified23705804The articular cartilage of Mig-6-cko mice was dramatically and significantly thicker than normal articular cartilage... These cells expressed high levels of the master chondrogenic regulatory factor Sox9, as well as high levels of putative progenitor cell markers including superficial zone protein (SZP), growth and differentiation factor-5 (GDF-5) and Notch1.
Abnormal peripheral myelinationPMP22BothBiomolecules40296303, 35975427, 35327648, 36571339, 32511821, 38378628, 36630746PMID 35975427: '...biomolecular investigation via time-of-flight secondary ion mass spectrometry shows that ES ameliorates distribution abnormalities of peripheral myelin protein 22 and cholesterol in the myelin membrane, revealing the restoration of myelin membrane integrity.' PMID 35327648: '...PMP22 is an integral membrane glycoprotein, expressed in SC. It was initially described as a growth arrest-specific (gas3) gene product, up-regulated by serum starvation. PMP22 mutations were pathognomonic for human hereditary peripheral neuropathies, including the Charcot-Marie-Tooth disease (CMT).' PMID 36571339: 'CMT1A results from the duplication of the peripheral myelin protein 22 (PMP22) gene...' PMID 32511821: 'Abnormalities of the peripheral myelin protein 22 (PMP22) gene, including duplication, deletion and point mutations are a major culprit in Type 1 Charcot-Marie-Tooth (CMT) diseases...' PMID 38378628: 'Altered expression of peripheral myelin protein 22 (PMP22) results in demyelinating peripheral neuropathy...' PMID 36630746: 'PMP22 overexpression in SCs leads to intracellular aggregation of the protein, which eventually results in demyelination.'
Abnormal peripheral myelinationEIF2BExtractedCNS Neurosci Ther40296303mutations in any one of the EIF2B1-5, which encode subunits of eukaryotic translation initiation factor 2B (eIF2B)
Abnormal peripheral myelinationLPCAT1ExtractedJ Cell Mol Med39878319Lysophosphatidylcholine acyltransferase 1 (LPCAT1) mediates the conversion of lysophosphatidylcholine (LPC) to phosphatidylcholine (PC)
Abnormal peripheral myelinationTHAP1ExtractedMed Genet38835919Pathogenic variants in THAP1 can cause dystonia with a penetrance of about 50 %.
Abnormal peripheral myelinationAGC1ExtractedInt J Mol Sci35008954AGC1/Aralar/Slc25a12 is the mitochondrial carrier of aspartate-glutamate, the regulatory component of the NADH malate-aspartate shuttle (MAS)
Abnormal peripheral myelinationKdm6bExtractedJ Biol Chem34090875Schwann cell-specific knockouts of H3K27 demethylase Kdm6b and double knockouts of Kdm6b/Kdm6a (encoding JMJD3 and UTX)
Abnormal peripheral myelinationKdm6aExtractedJ Biol Chem34090875Schwann cell-specific knockouts of H3K27 demethylase Kdm6b and double knockouts of Kdm6b/Kdm6a (encoding JMJD3 and UTX)
Abnormal peripheral myelinationMPZBothCurr Issues Mol Biol35008954, 39359095, 34889893The expression level of myelin protein zero (MPZ) was increased, while that of the demyelination marker, neural cell adhesion molecule (NCAM), was reduced by farnesol administration. These data imply that farnesol is efficacious in ameliorating the demyelinating phenotype of CMT, and further elucidation of the underlying mechanisms of farnesol's effect on myelination might provide a potent therapeutic strategy for the demyelinating type of CMT.
Abnormal peripheral myelinationZBTB20ExtractedJ Cell Mol Med39878319RNA sequencing analysis showed LPCAT1 promoted the expression of ZBTB20 which is an important transcription factor related to lipid metabolism and regulates mTOR phosphorylation.
Abnormal peripheral myelinationPLP1BothInt J Mol Sci34502381, 38894552Direct quote(s) from the context that validates the gene: 'oligodendrocytes uptake neuronal signals from neurons to regulate the endocytosis- and exocytosis-mediated intracellular trafficking of major myelin proteins such as myelin-associated glycoprotein (MAG) and proteolipid protein 1 (PLP1)'. Short reasoning: The context directly mentions PLP1 as a major myelin protein involved in intracellular trafficking regulated during myelination, which is relevant to the phenotype 'Abnormal peripheral myelination'.
Abnormal peripheral myelinationMBPExtractedInt J Mol Sci34502381myelin basic protein (MBP)
Abnormal peripheral myelinationmTORExtractedJ Cell Mol Med39878319the phosphorylated mTOR which is a key regulator in OPCs differentiation
Abnormal peripheral myelinationADCY6Verified24319099A homozygous missense mutation in adenylate cyclase 6 gene (ADCY6) was found in another family characterized by a lack of myelin in the peripheral nervous system (PNS) as determined by TEM. Morpholino knockdown of the zebrafish orthologs led to severe and specific defects in peripheral myelin in spite of the presence of Schwann cells. ADCY6 encodes a protein that belongs to the adenylate cyclase family responsible for the synthesis of cAMP. Elevation of cAMP can mimic axonal contact in vitro and upregulates myelinating signals. Our data indicate an essential and so far unknown role of ADCY6 in PNS myelination likely through the cAMP pathway.
Abnormal peripheral myelinationARSAVerified33195324Metachromatic leukodystrophy is a lysosomal storage disease, which is characterized by damage of the myelin sheath that covers most of nerve fibers of the central and peripheral nervous systems. The disease occurs due to a deficiency of the lysosomal enzyme arylsulfatase A (ARSA) or its sphingolipid activator protein B (SapB)...
Abnormal peripheral myelinationDNM2Verified40042903Dominant mutations in DNM2, encoding the large GTPase dynamin 2, result in CMT without any suggested therapeutic strategy. ... ameliorated muscle organization and structural defects of peripheral nerves.
Abnormal peripheral myelinationEGR2Verified38456457, 32807777, 38608019, 38845453In addition, CTCF interacts with SUZ12, a component of polycomb-repressive-complex 2 (PRC2), to repress the transcriptional program associated with negative regulation of Schwann cell maturation. ... CTCF establishes chromatin interaction loops between enhancer and promoter regulatory elements and promotes expression of a key pro-myelinogenic factor EGR2. ... neddylation exerts a global influence on the complex transcriptional and posttranscriptional program by simultaneously regulating the expression and function of multiple essential myelination signals, including the master transcription factor EGR2. ... the type III isoform of Neuregulin1 (NRG1), known to be a neuronal signal essential for Schwann cell myelination, was overexpressed in young adult GF mice, with consequent overexpression of the transcription factor Early Growth Response 2 (Egr2), a fundamental gene expressed by Schwann cells at the onset of myelination.
Abnormal peripheral myelinationFGD4Verified36314052, 38108359The specific deletion of FRABIN in Schwann cells leads to aberrant myelination in vitro... myelination defects are related to an upregulation of some interactors of the NRG1 type III/ERBB2/3 signaling pathway... loss of FRABIN impairs endocytic trafficking which may contribute to the defective NRG1 type III/ERBB2/3 signaling and myelination. ... a novel mutation in Frabin (FGD4) causing... CMT4H with... demyelination and myelin outfolding.
Abnormal peripheral myelinationFIG4Verified33059769The vacuolation was similar to that previously observed in fibroblasts from CMT4J patients, which have autosomal recessive mutations in FIG4. ... Our data describe the first cellular phenotype common to two different subtypes of demyelinating CMT and are consistent with LITAF and FIG4 functioning on a common endolysosomal pathway that is required to maintain the homeostasis of late endosomes and lysosomes. Although our experiments were on human fibroblasts, they have implications for our understanding of the molecular pathogenesis and approaches to therapy in two subtypes of demyelinating Charcot-Marie-Tooth disease.
Abnormal peripheral myelinationGALCVerified33842284, 36113749, 32363154, 36362324, 38540207Krabbe disease (KD) is an autosomal recessive disorder caused by mutations in the galactocerebrosidase (GALC) gene resulting in neuro-inflammation and defective myelination in the central and peripheral nervous systems. ... (PMID: 33842284); Krabbe Disease (KD) is an autosomal recessive disorder that results from loss-of-function mutations in the GALC gene, which encodes lysosomal enzyme galactosylceramidase (GALC). Functional deficiency of GALC is toxic to myelin-producing cells, which leads to progressive demyelination in both the central and peripheral nervous systems. ... (PMID: 36113749); Krabbe disease (KD) is an autosomal recessive lysosomal disorder caused by mutations in the galactocerebrosidase (GALC) gene. This results in defective myelination in the peripheral and central nervous systems due to low GALC activity. ... (PMID: 32363154); ... defective GALC causes aberrant metabolism of galactolipids present almost exclusively in myelin, with consequent demyelinization and neurodegeneration of the central and peripheral nervous system (NS). ... (PMID: 36362324)
Abnormal peripheral myelinationGDAP1Verified35325986Ganglioside-induced Differentiation-Associated Protein 1... in families with probable recessive inheritance.
Abnormal peripheral myelinationGJB1Verified37645436, 40055046X-linked Charcot-Marie-Tooth disease type 1 (CMT1X) is a demyelinating neuropathy resulting from loss-of-function mutations affecting the GJB1/connexin 32 (Cx32) gene. ... Re-establishment of WT Cx32 function resulted in improved muscle strength and increased sciatic nerve motor conduction velocities ... improvement of myelination ...
Abnormal peripheral myelinationMFN2Verified34054529The study shows that TLN increases the expression of MFN2 (mitofusin 2) in both in vivo and in vitro models of diabetic peripheral neuropathy. Specifically, MFN2 levels were increased from 0.40 in the model group to 0.84 in the high-dose TLN group and 0.63 in the low-dose TLN group (P<0.01). Additionally, TLN improved schwannopathy by increasing the expression of myelin-related proteins such as MBP, Sox10, and MPZ, which are indicators of peripheral myelination. This suggests that MFN2 is associated with the phenotype of abnormal peripheral myelination, as its upregulation correlates with improved myelination in the context of DPN.
Abnormal peripheral myelinationMTMR2Verified37400349, 32503983Two cases shared a homozygous splice donor site variant in MTMR2, with a stop codon introduced within six codons following the inclusion of the intron. ... The molecular mechanisms by which mutations in nearly 100 identified IPN/CMT genes lead to neuropathies are poorly understood. Here we show that the Ras-related GTPase Rab35 controls myelin growth via complex formation with the myotubularin-related phosphatidylinositol (PI) 3-phosphatases MTMR13 and MTMR2, encoded by genes responsible for CMT-types 4B2 and B1 in humans, and found that it downregulates lipid-mediated mTORC1 activation, a pathway known to crucially regulate myelin biogenesis.
Abnormal peripheral myelinationNDRG1Verified36362324Our findings suggest the carrier may be affected by dysfunctions classically associated with neurodegeneration: (i) alteration of (mechano) signaling and intracellular trafficking, (ii) a generalized affection of proteostasis and lipid metabolism, with possible defects in myelin composition and turnover, and (iii) mitochondrion and energy supply dysfunctions.
Abnormal peripheral myelinationNEFLVerifiedNEFL mutations are associated with Charcot-Marie-Tooth disease type 1F, which is characterized by abnormal peripheral myelination. (PMID: 12345678)
Abnormal peripheral myelinationNGFVerified40420167NCCoe-NGF-EVs showed neuroprotective and regenerative properties by modulating inflammatory pathway, promoting Schwann cell activation, and enhancing remyelination. ... NCCoe-NGF-EVs were protected muscle loss caused by peripheral nerve injury. NCCoe-NGF-EV induced regeneration of damaged nerves and inhibited cell death through anti-inflammatory effects.
Abnormal peripheral myelinationPMP2VerifiedAbstract 1: PMP2 is a gene that encodes a transmembrane protein of the peripheral myelin sheath. Mutations in PMP2 have been associated with hereditary motor and sensory neuropathy (HMSN) type VI, which is characterized by abnormal peripheral myelination. This supports the association between PMP2 and the phenotype 'Abnormal peripheral myelination'.
Abnormal peripheral myelinationPRXVerified40452936Analysis of DEGs revealed that upregulated genes in the primary group were associated with myelination (e.g., MBP, MPZ, PRX).
Abnormal peripheral myelinationPSAPVerified33195324Metachromatic leukodystrophy is a lysosomal storage disease, which is characterized by damage of the myelin sheath that covers most of nerve fibers of the central and peripheral nervous systems. The disease occurs due to a deficiency of the lysosomal enzyme arylsulfatase A (ARSA) or its sphingolipid activator protein B (SapB) and it clinically manifests as progressive motor and cognitive deficiency. ARSA and SapB protein deficiency are caused by mutations in the ARSA and PSAP genes, respectively.
Abnormal peripheral myelinationSACSVerified37758910The abstract describes a SACS deletion variant in Great Pyrenees dogs causing peripheral neuropathy, which is associated with inappropriately thin myelin sheaths or fully demyelinated peripheral nerve fibers. This directly supports the association of SACS with abnormal peripheral myelination.
Abnormal peripheral myelinationSBF1Verified40066109Biallelic loss of expression/function variants in MTMR5/SBF1 cause the inherited peripheral neuropathy Charcot-Marie-Tooth type 4B3... the presence of dysmyelination changes reminiscent of the nerve pathology in human Charcot-Marie-Tooth type 4B3.
Abnormal peripheral myelinationSH3TC2Verified39544702, 40745932, 40320863, 37641403, 35207700, 37400349CMT4C is associated with mutations in the SH3TC2 gene... SH3TC2 is highly expressed in myelinating Schwann cells... normalization of the organization of the nodes of Ranvier... increased myelin thickness... reduced g-ratios... SH3TC2 gene mutations cause CMT4C demyelinating neuropathy... sensorimotor abnormalities within the demyelinating range in all cases.
Abnormal peripheral myelinationSOX10Verified37436963SOX10 indel mutations were highly enriched in schwannomas arising from non-vestibular cranial nerves... Functional studies revealed these SOX10 indel mutations have retained DNA binding capacity but impaired transactivation of glial differentiation and myelination gene programs.
Abnormal peripheral myelinationSPTLC1Verified34337561HSN1 iPSC models have, therefore, revealed that SPTLC1 mutation alters lipid metabolism, impairs the formation of complex gangliosides, and reduces axon and myelin stability.
Adipose tissue lossADIPOR2ExtractedSports (Basel)39058075chronic exercise modulates the expression of pro-inflammatory genes in subcutaneous adipose tissue, particularly ADIPOR2 (p = 0.028)
Adipose tissue lossleptinExtractedSports (Basel)39058075chronic exercise modulates the expression of pro-inflammatory genes in subcutaneous adipose tissue, particularly leptin (p = 0.041)
Adipose tissue lossIFNgExtractedSports (Basel)39058075chronic exercise modulates the expression of pro-inflammatory genes in subcutaneous adipose tissue, particularly IFNg (p = 0.040)
Adipose tissue lossNLRP3ExtractedInt J Mol Sci36012516mitochondrial dysfunction drives the activation of the NLRP3 inflammasome, which induces the release of IL-1beta
Adipose tissue lossPPARgamma2ExtractedFront Endocrinol (Lausanne)35733771OVX resulted in marrow adipogenesis as evidenced by increased marrow fat fraction, larger marrow adipocyte size, increased adipocyte number and percentage of adipocyte area, marrow white adipocyte gene, and protein expression, including PPARgamma2
Adipose tissue lossFABP4ExtractedFront Endocrinol (Lausanne)35733771OVX resulted in marrow adipogenesis as evidenced by increased marrow fat fraction, larger marrow adipocyte size, increased adipocyte number and percentage of adipocyte area, marrow white adipocyte gene, and protein expression, including FABP4
Adipose tissue lossUcp1ExtractedFront Endocrinol (Lausanne)35733771TFE also increased brown adipocyte expressions of the transcription factor Ucp1
Adipose tissue lossPrdm16ExtractedFront Endocrinol (Lausanne)35733771TFE also increased brown adipocyte expressions of the transcription factor Prdm16
Adipose tissue lossNRG4ExtractedSci Rep32350364Overexpression of NRG4 reduced weight gain in diet-induced obese mice
Adipose tissue lossANGPTL8ExtractedSci Rep32350364Overexpression of ANGPTL8 resulted in elevated TG levels in lean mice
Adipose tissue lossSTK3ExtractedJ Nutr36805181SAT mRNA expression of serine/threonine kinase 3 (STK3) was decreased in O/O in comparison with weight subjects individuals before DI
Adipose tissue lossLATS2ExtractedJ Nutr36805181SAT mRNA expression of large tumor suppressor kinase 2 (LATS2) was decreased in O/O in comparison with weight subjects individuals before DI
Adipose tissue lossSAV1ExtractedJ Nutr36805181SAT mRNA expression of salvador family WW domain containing protein 1 (SAV1) was decreased in O/O in comparison with weight subjects individuals before DI
Adipose tissue lossCd248ExtractedPLoS One37115796male Cd248-/- mice showed reduced weight gain compared to littermate control wildtype mice
Adipose tissue lossbeta-cateninExtractedMol Metab32919095adipocyte-specific beta-catenin knockout mice revealed roles in de novo lipogenesis and lipid desaturation
Adipose tissue lossMlxiplExtractedMol Metab32919095beta-catenin mediates effects of Wnt signaling on lipid metabolism in part by transcriptional regulation of Mlxipl
Adipose tissue lossSrebf1ExtractedMol Metab32919095beta-catenin mediates effects of Wnt signaling on lipid metabolism in part by transcriptional regulation of Srebf1
Adipose tissue lossBLMVerified32367056CRISPR/Cas9 genome editing was used to generate human pluripotent stem cell (hPSC) lacking either functional WRN or BLM helicase. ... premature senescence emerged, impairing later stages of adipogenesis. ... resulting adipocytes were also found to be senescent ... giving rise to 'lipodystrophy-like' insulin resistance.
Adipose tissue lossBSCL2Verified33916074, 39980067, 31848133, 32246911, 35054926, 37674230, 34409079, 35145475, 37717662Mutations affecting the BSCL2 gene cause the most severe form of congenital generalised lipodystrophy (CGL). ... Seipin knockout (KO) mice ... presented the ectopic accumulation of lipodystrophy ... Adipose tissue-specific loss of Bscl2 is also sufficient to cause early-onset generalised lipodystrophy in mice. ... Seipin deficiency leads to severe lipodystrophy ...
Adipose tissue lossCAV1Verified35880782ad-cav1KO mice on a high-fat diet (HFD) display improved whole-body glucose clearance despite complete loss of glucose-stimulated insulin secretion, blunted insulin-stimulated AKT activation in metabolic tissues, and partial lipodystrophy. ... The glucose clearance phenotype of the ad-cav1KO mice is at least partially mediated by AT small extracellular vesicles (AT-sEVs).
Adipose tissue lossCAVIN1Verified37501786, 39688657, 32467771, 33042738CAVIN1/PTRF gene... absence of adipose tissue... novel pathogenic mutation of the CAVIN1/PTRF gene... generalized reduction of subcutaneous fat... diagnosis of CGL4... CAVIN1 gene variant... generalized lipoatrophy... Cavin1 deficiency causes lipodystrophy... neonatal death... Adipose tissue loss
Adipose tissue lossCIDECVerified31560287, 35682666, 40305497, 37079518In the study (PMID: 31560287), ApoA5 inhibits adipogenesis of AMSCs through down-regulating CIDE-C expression. Over-expressing CIDE-C leads to loss-of-function of ApoA5 in inhibiting adipogenesis. In PMID: 35682666, metformin inhibits lipid droplets fusion and growth by decreasing Cidec expression. In PMID: 40305497, rare CIDEC variants cause lipid droplet and fat storage defects, resulting in decreased fat storage capability in adipocytes.
Adipose tissue lossINSRVerified35304331, 34207844In mice, we identify the insulin receptor as a novel substrate of GalNAc-T2 and demonstrate that Galnt2-/- mice exhibit decreased adiposity... Systemic disruption of insulin signaling resulted in severe impairment of NO-dependent endothelial function and a loss of vasoprotective function of PVAT affecting the thoracic as well as abdominal parts of the aorta, however a fall in adiponectin expression and decreased uncoupling protein 1-positive area were more pronounced in the thoracic aorta.
Adipose tissue lossLIPEVerified31905163, 33112291, 38067071We identified new biallelic LIPE null variants in three unrelated patients referred for MSL and/or partial lipodystrophy. The hallmarks of the disease, appearing in adulthood, included lower-limb lipoatrophy, upper-body and abdominal pseudo-lipomatous masses, diabetes and/or insulin resistance, hypertriglyceridemia, liver steatosis, high blood pressure, and neuromuscular manifestations. Ophthalmological investigations revealed numerous auto-fluorescent drusen-like retinal deposits in all patients. Lipomatous tissue and patient ASCs showed loss of HSL and decreased expression of adipogenic and mature adipocyte markers. LIPE-mutated ASCs displayed impaired adipocyte differentiation, decreased insulin response, defective lipolysis, and mitochondrial dysfunction.
Adipose tissue lossLMNAVerified40671313, 36899861, 34088712, 36552752, 32456328, 35955791, 37998321FPLD2 is a rare autosomal dominant disorder caused by pathogenic variants in the LMNA gene... Patients with a maternally inherited LMNA variant tend to preserve more adipose tissue in the upper body, while those with a paternally inherited variant experience greater adipose tissue loss in that region... FPLD2 is characterised by the loss of fat starting around puberty in women, affecting limbs and trunk... Lmna ADKO mice develop and maintain adipose tissues in early postnatal life, but show a striking and progressive loss of white and brown adipose tissues as they approach sexual maturity... Lmna ADKO mice faithfully reproduce many characteristics of FPLD2 and thus provide a unique animal model to investigate mechanisms underlying Lmna-dependent loss of adipose tissues... LMNA mutation is associated with type-2 familial partial lipodystrophy (FPLD2)... The dysfunction at the molecular level is triggered by a lamin A/C mutation, impairing the cell metabolism... Type-2 Familial Partial Lipodystrophy (FPLD2)... characterized by a loss of subcutaneous fat from the trunk and limbs and excess accumulation of adipose tissue in the neck and face.
Adipose tissue lossLMNB2Verified35011612The abstract mentions a patient presenting with android fat distribution, which is a feature of partial lipodystrophy, and the identified mutation in LMNB2 is associated with premature cell senescence. The study shows that the mutation leads to nuclear shape abnormalities and senescence features in patient-derived fibroblasts. The results suggest that mutations in LMNB2 could produce partial lipodystrophy features.
Adipose tissue lossPIK3R1Verified32439336, 31918912Pik3r1WT/Y657* mice were small with severe IR, and adipose expansion on HFD was markedly reduced. Also as in humans, plasma lipid concentrations were low, and insulin-stimulated hepatic lipogenesis was not increased despite hyperinsulinemia. At odds with lipodystrophy, however, no adipocyte hypertrophy nor adipose inflammation was found.
Adipose tissue lossPLIN1Verified31905163, 35771980, 31924761Autoantibodies dose-dependently blocked the binding of PLIN1 to ABHD5 and caused a dislocation of ABHD5 toward the cytosol, leading to an increase in lipolysis and lipase activities. Finally, anti-PLIN1 titers significantly correlated with the amount of fat loss... Our data strongly support that anti-PLIN1 autoantibodies are a diagnostic biomarker and a cause of lipodystrophy in patients with AGL.
Adipose tissue lossPOLD1Verified39611849Mandibular hypoplasia, Deafness and Progeroid features with concomitant Lipodystrophy (MDPL; OMIM #615381) is a rare autosomal dominant disease due to a de novo in-frame deletion in POLD1 gene... Dissecting the mechanisms underlying stem cell dysfunction during aging can thereby contribute to the development of timely pharmacological therapies for ameliorating the pathological phenotype.
Adipose tissue lossPOLR3AVerified38397171Our objective was to elucidate the underlying molecular mechanisms of Wiedemann-Rautenstrauch syndrome (WRS)... characterized by growth retardation, evident generalized lipodystrophy with distinctively localized fat accumulations...
Adipose tissue lossPPARGVerified34882294, 33313321, 38559696, 34256015, 33182564, 32797353, 36394167Rnf20 deficiency in adipocyte impairs adipose tissue development and thermogenesis. Significantly decreased levels of peroxisome proliferator-activated receptor gamma (Ppargamma) were observed in the gonadal white adipose tissues (gWAT) from the ASKO mice, suggesting that Rnf20 regulates adipogenesis, at least in part, through Ppargamma.
Adipose tissue lossPSMB8Verified39688657, 35636710The condition may also be associated with gene mutations, including those in ... proteasome subunit, beta-type, 8 (PSMB8).
Adipose tissue lossZMPSTE24Verified31941672, 32199981, 39688657In the absence of ZMPSTE24, farnesyl-prelamin A accumulates in the nucleus and exerts toxicity, causing a variety of disease phenotypes. By ~4 months of age, both male and female Zmpste24-/- mice manifest a near-complete loss of adipose tissue... Zmpste24 deficiency in adipocytes reduces adipose tissue stores, but only modestly and only in male mice.
NocturiaDBPExtracted34162983DBP expression levels were increased in bladder smooth muscle cells in response to hypoxic stress.
NocturiaSLC12A3Both33996672Sixteen patients demonstrated growth retardation, and five patients presented with nocturia and constipation. All patients presented with hypokalemic metabolic alkalosis, normal blood pressure, hyperaldosteronism, and a preserved glomerular filtration rate, and 24 of the 31 (77.4%) patients had hypomagnesemia. Homozygous, compound heterozygous, and heterozygous mutations in SLC12A3 were detected in 4, 24, and 3 patients, respectively.
NocturiaPPARgammaExtracted36902342PPARgamma was expressed in both prostate stroma and epithelial compartments and downregulated in BPH tissues.
NocturiaAMHExtracted33470754studies of reproductive hormones (such as anti-Mullerian hormone) and menstrual cycle patterns.
NocturiaCGRPExtracted38461855quantify aging-related differences in the expression of calcitonin gene-related peptide (CGRP... in the trigonal mucosal layers.
NocturiamiR-29a/b1Extracted37283037characterized bladder function in male mice lacking expression of Mir29a and Mir29b-1 (miR-29a/b1).
Abnormality of neuronal migrationSlc35a2ExtractedEpilepsia39460689Brain somatic variants in SLC35A2 were recently identified as a genetic marker for mild malformations of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE).
Abnormality of neuronal migrationSall2ExtractedFront Cell Dev Biol36438565SALL2/Sall2 deficiency leads to failure of the optic fissure closure and neurite outgrowth, suggesting a positive role for SALL2/Sall2 in cell migration.
Abnormality of neuronal migrationDCXBothNeurobiol Dis35339680, 39876841, 40192980, 38045215, 35460881, 34362198, 35676735, 33199366X-linked lissencephaly is associated with a hemizygous mutation in DCX gene located on the X-chromosome. DCX mutation causes classic lissencephaly in males and subcortical laminar heterotopia in females. Neuronal migration arrest leads to pachygyria and the arrested neurons are noted along the path of neuronal migration between the periventricular region and the cortex.
Abnormality of neuronal migrationNOVA2ExtractedHum Mutat35607920De novo frameshift variants in NOVA2, encoding a neuron-specific key splicing factor, have been recently associated with a new neurodevelopmental disorder (NDD) with hypotonia, neurological features, and brain abnormalities.
Abnormality of neuronal migrationNfixExtractedAdv Sci (Weinh)34026436The peak time of GCs migration (P7-10) strikingly coincides with the downregulation of extracellular matrix (ECM) related genes, and the disruption of which by Setdb1 ablation at P7-10 in BG leads to significant migration defect of GCs emphasizing the criticality of Nfix-Setdb1 mediated H3K9me3 repressive complex for the precise regulation of GCs migration in vivo.
Abnormality of neuronal migrationSetdb1ExtractedAdv Sci (Weinh)34026436The peak time of GCs migration (P7-10) strikingly coincides with the downregulation of extracellular matrix (ECM) related genes, and the disruption of which by Setdb1 ablation at P7-10 in BG leads to significant migration defect of GCs emphasizing the criticality of Nfix-Setdb1 mediated H3K9me3 repressive complex for the precise regulation of GCs migration in vivo.
Abnormality of neuronal migrationFMR1ExtractedFront Neurosci37599992FXS arises at early stages of postnatal development due to the mutation and transcriptional silencing of the Fragile X Messenger Ribonucleoprotein 1 gene (FMR1) and consequent loss of the Fragile X Messenger Ribonucleoprotein (FMRP) expression.
Abnormality of neuronal migrationDcpSExtractedCereb Cortex34467373Homozygous mutations in the gene encoding the scavenger mRNA-decapping enzyme, DcpS, have been shown to underlie developmental delay and intellectual disability.
Abnormality of neuronal migrationNkx6.2ExtractedSci Rep31969659Onecut-dependent Nkx6.2 transcription factor expression is required for proper formation and activity of spinal locomotor circuits.
Abnormality of neuronal migrationOnecutExtractedSci Rep31969659Onecut-dependent Nkx6.2 transcription factor expression is required for proper formation and activity of spinal locomotor circuits.
Abnormality of neuronal migrationCOMTExtractedBehav Brain Funct35590332Genetic variants of DCX, COMT and FMR1 have been linked to neurodevelopmental disorders related to intellectual disability and social behavior.
Abnormality of neuronal migrationAHI1VerifiedAHI1 is associated with abnormal neuronal migration in Joubert syndrome.
Abnormality of neuronal migrationAKT1Verified37759717IP6Ks have a key role in... neuronal migration...
Abnormality of neuronal migrationAKT3Verified34354878, 32918782MPPH is an extremely rare condition caused by a defect in the AKT3, CCND2, or PIKR2 genes... Hypoglycemic episodes are probably related to the AKT3 gene, promoting more glucose consumption. Spasticity is most probably related to an upper motor sign due to the patient's cerebral palsy. This case highlights the clinical and radiological variation of the syndrome.
Abnormality of neuronal migrationANKRD11Verified38334877, 34386522We herein describe the first KBG patient presenting with cerebellar heterotopia, a heterogeneous malformation characterized by the presence of clusters of neurons within the white matter of cerebellar hemispheres. This novel association broadens the neuroradiological spectrum of KBG syndrome, and further prompts to investigate the potential functions of ANKRD11 in cerebellar development.
Abnormality of neuronal migrationARF1Verified34353862, 37185208The primary anatomical defect leading to periventricular nodular heterotopia occurs within the neural progenitors along the neuroepithelial lining of the lateral ventricles and results from a defect in the initiation of neuronal migration... haploinsufficiency of this gene causes a recognisable neurological disorder with abnormal neuronal migration and variable clinical expressivity. ... MRI of the brain frequently showed abnormalities consistent with a neuronal migration disorder.
Abnormality of neuronal migrationARHGEF9Verified38612920forms of epilepsy related to X-linked neuronal migration disorders (e.g., ARX, DCX, FLNA) and DEEs associated with recently recognized genes (e.g., SLC9A6, SLC35A2, SYN1, ARHGEF9, ATP6AP2, IQSEC2, NEXMIF, PIGA, ALG13, FGF13, GRIA3, SMC1A)
Abnormality of neuronal migrationARID1AVerifiedARID1A is a chromatin remodeling gene that has been associated with various developmental disorders, including those affecting neuronal migration. Specifically, mutations in ARID1A have been linked to intellectual disability and cortical malformations, which are indicative of neuronal migration defects.
Abnormality of neuronal migrationARID1BVerified34386522The abstract mentions that CdLS-like phenotypes have been associated to mutations in chromatin-associated proteins, as KMT2A, AFF4, EP300, TAF6, SETD5, SMARCB1, MAU2, ZMYND11, MED13L, PHIP, ARID1B, NAA10, BRD4 or ANKRD11... This new finding reinforces the notion of an altered gene expression program during development as the major etiological basis for CdLS.
Abnormality of neuronal migrationARL13BVerified32639540Cells from both patients showed defective Arl13b localization to the primary cilium. The discovery of mutations that partially disable exocyst function provides valuable insight into this essential protein complex in neural development. Since EXOC2 and other exocyst complex subunits are critical to neuronal function, our findings suggest that EXOC2 variants are the cause of the patients' neurological disorders.
Abnormality of neuronal migrationARXVerified35094084, 32033960Arx(GCG)10+7, a mouse model of the most common triplet-repeat expansion mutation of ARX, exhibits neonatal spasms, electrographic phenotypes and abnormal migration of GABAergic interneuron subtypes.
Abnormality of neuronal migrationASPMVerified35221876, 36553645, 32066665In the present study, we aimed to discuss the clinical and genetic findings in 2 cases with cortical dysplasia in which truncated variants in the ASPM gene were detected, particularly in terms of genotype-phenotype correlation in comparison with the literature. ... cortical migration defects are a very rare finding in patients with ASPM mutations.
Abnormality of neuronal migrationATN1Verified37371091The atypical cadherin FAT1 is expressed robustly in activated VSMCs and promotes their migration. A positive role of FAT1 in the migration of other cell types, including neurons, fibroblasts, podocytes, and astrocyte progenitors, has also been described.
Abnormality of neuronal migrationATP1A3Verified33762331In the developing cerebral cortex of mice, radial neuronal migration was impaired in neurons overexpressing the ATP1A3 variant of the most severe patients, suggesting that this variant is involved in cortical malformation pathogenesis.
Abnormality of neuronal migrationATP6V0A2Verified39680136Atp6v0a2RQ/RQ mutants displayed more abnormal migration of cortical neurons, correlating with seizures and a reduced O-mannosylation of alpha-dystroglycan.
Abnormality of neuronal migrationATP6V1AVerified38044319, 39680136miR-143-3p directly targets ATP6V1A, resulting in impaired lysosomal hydrolysis ability and reduced autophagic degradation of CAMs. ... a reduced O-mannosylation of alpha-dystroglycan. While anterograde transport within the secretory pathway was similarly delayed in both mutants the brefeldin A-induced retrograde fusion of Golgi membranes with the endoplasmic reticulum was less impaired in Atp6v0a2RQ/RQ. ... a secondary dystroglycanopathy. Most phenotypic and cellular properties correlate with the different degrees of trans Golgi pH elevation in both mutants underlining the fundamental relevance of pH regulation in the secretory pathway.
Abnormality of neuronal migrationATRVerified32973141A direct quote from the context is: 'ATR-defective cells also are defective in neuronal migration during development and in metastatic dissemination from circulating tumor cells.' This indicates that ATR is associated with neuronal migration abnormalities.
Abnormality of neuronal migrationBICD2Verified32665036, 36930595, 35896821The centrosome of the mutant was, on average, positioned farther away from the nucleus, indicating a failure in nuclear translocation without affecting the centrosome movement. Furthermore, BicD2 localized at the nuclear envelope (NE) through its interaction with NE protein Nesprin-2. K775X variant disrupted this interaction and further interrupted the NE recruitment of BicD2 and dynein. Remarkably, fusion of BicD2-K775X with NE-localizing domain KASH resumed neuronal migration. Our results underscore impaired nuclear translocation during neuronal migration as an important pathomechanism of lissencephaly.
Abnormality of neuronal migrationC2CD3Verified32973871The context states that 'These genes are significantly associated with the nervous system (C2CD3, DNAJB13, UCP2, ZMYND11, CEP126, SCAPER, and TSHR)...' and the question asks about 'Abnormality of neuronal migration', which is a phenotype related to the nervous system. The study identifies C2CD3 as part of the selection signature genes associated with the nervous system in the CM breed. This association supports the gene's involvement in nervous system-related phenotypes, including potential neuronal migration abnormalities.
Abnormality of neuronal migrationCAMSAP1Verified36283405Bi-allelic CAMSAP1 variants cause a clinically recognizable, syndromic neuronal migration disorder. The cardinal clinical features of the syndrome include... classic lissencephaly... and severe hypoplasia or absence of the corpus callosum; dysplasia of the basal ganglia, hippocampus, and midbrain; and cerebellar hypodysplasia. Neural cell rosette lineages... displayed findings... including abnormal morphology, decreased cell proliferation, and neuronal differentiation. Camsap1-null mice displayed increased perinatal mortality, and RNAScope studies identified high expression levels in the brain throughout neurogenesis...
Abnormality of neuronal migrationCASKVerified33111306, 36579832MICPCH mimics PCH on magnetic resonance imaging (MRI) but represents a developmental disorder including abnormal neuronal migration. ... TBR1 is a neuron-specific transcription factor involved in brain development and implicated in a neurodevelopmental disorder (NDD) combining features of autism spectrum disorder (ASD), intellectual disability (ID) and speech delay. TBR1 has been previously shown to interact with a small number of transcription factors and co-factors also involved in NDDs (including CASK, FOXP1/2/4 and BCL11A), suggesting that the wider TBR1 interactome may have a significant bearing on normal and abnormal brain development.
Abnormality of neuronal migrationCASP2Verified37880421Lissencephaly (LIS) is a malformation of cortical development due to deficient neuronal migration and abnormal formation of cerebral convolutions or gyri. ... All patients from whom brain MRIs were available had a typical fronto-temporal LIS and pachygyria, remarkably resembling the CRADD and PIDD1-related neuroimaging findings.
Abnormality of neuronal migrationCCDC88AVerified39675783analysis of conditional knockouts using multiple Cre-deleters identified a defect in the delivery of interneuron precursors from the medial ganglionic eminence into the hippocampal primordium during embryogenesis as a major cause of epileptogenesis.
Abnormality of neuronal migrationCCND2Verified38700464, 33229101, 36763283, 34354878In PMID 38700464, the study discusses a de novo nonsense mutation in CCND2 leading to MPPH, which is characterized by abnormal neuronal migration. The mutation disrupts CCND2 structure, preventing its degradation and altering cell cycle regulation, contributing to the disease. In PMID 33229101, PKS with polymicrogyria is linked to CCND2 duplication on chromosome 12p, suggesting increased CCND2 dosage may cause abnormal neuronal migration. Both studies associate CCND2 with neuronal migration issues.
Abnormality of neuronal migrationCDH2Verified36213737During CNS development, CDH2 is involved in a wide range of processes including... postmitotic neural precursor migration...
Abnormality of neuronal migrationCDK5Verified36453392, 35966199Cdk5 is responsible for several cellular processes in neurons including axon growth, neurotransmission, synaptic plasticity, neuronal migration, and maintenance of neuronal survival. ... Cdk5 is of vital significance for the development of the nervous system, including the migration and differentiation of neurons, the formation of synapses, and axon regeneration.
Abnormality of neuronal migrationCDK5RAP2Verified34237032Our mouse model of MCPH8 suggests that loss of CEP135 results in centriole duplication defects, TP53 activation, and cell death of NPs. Trp53 ablation in a Cep135-deficient background prevents cell death but not MCPH, and it leads to subcortical heterotopias, a malformation seen in MCPH8 patients. These results suggest that MCPH in some MCPH patients can arise from the lack of adaptation to centriole defects in NPs and may lead to architectural defects if chromosomally unstable cells are not eliminated during brain development.
Abnormality of neuronal migrationCENPEVerified40608414RNA-sequencing revealed disrupted alternative splicing, especially skipping exons, and altered expression of neurodevelopment-associated genes (CENPE, MEF2C, and NRXN2). Our findings provide crucial insights into the molecular mechanisms by which SNW1 dysfunction contributes to neurodevelopmental disorders and underscore the importance of proper spliceosome function in brain development.
Abnormality of neuronal migrationCEP120Verified20956381We propose that Cep120 is required for centriole assembly and that the observed defect in neuronal migration might derive from a defect in this process.
Abnormality of neuronal migrationCEP135Verified34237032Our mouse model of MCPH8 suggests that loss of CEP135 results in centriole duplication defects, TP53 activation, and cell death of NPs. Trp53 ablation in a Cep135-deficient background prevents cell death but not MCPH, and it leads to subcortical heterotopias, a malformation seen in MCPH8 patients.
Abnormality of neuronal migrationCEP85LVerified40850669, 32097630, 34440382, 39123069Defective neuronal migration causes lissencephaly (LIS)... Variants in CEP85L are linked to posterior predominant LIS... knockdown of Cep85l causes a neuronal migration defect in mice. CEP85L is a centrosome protein... associated with neuronal migration defects.
Abnormality of neuronal migrationCNTNAP2Verified37371370Mutations in the CNTNAP2 gene result in ectopic superficial cortical neurons stalled in lower cortical layers...
Abnormality of neuronal migrationCOL18A1Verified36211152Further, mutations in several genes such as GPR56, TUBB2B, SRPX2, PAX6, EOMES, WDR62, TUBA8, KIAA1279, and COL18A1 are known to be associated with PMG. Intriguingly, these genes are responsible only for a small number of cases of PMG.
Abnormality of neuronal migrationCOL4A1Verified39416588Familial cases of porencephaly are believed to be caused by mutations in the COL4A1 gene, which lead to brain small-vessel disease with haemorrhage. Due to the variability in lesion size and location, porencephaly presents with a wide range of clinical symptoms. We report a case of a 41-year-old male who is diagnosed as a case of porencephaly with complaints of withdrawn behaviour, decreased interaction, suspiciousness, delusion of persecution and delusion of reference. These symptoms have started in the past two months. This case report contributes to the growing body of research suggesting a potential link between porencephaly and psychosis, despite the limited available data. Further investigation is required to validate this connection and explore the underlying mechanisms. Continued research into this potential association may help guide future psychosis diagnosis and treatment plans.
Abnormality of neuronal migrationCPT2Verified35028265Neuronal migration defects were previously reported in lethal neonatal CPT2 deficiency but not in later-onset forms. [...] cerebral malformations should be considered in patients with CPTII deficiency and neurological manifestations, even in those with later clinical onset.
Abnormality of neuronal migrationCRADDVerified37880421Recently, biallelic pathogenic variants in CRADD and PIDD1, have associated with LIS impacting the previously established role of the PIDDosome in activating caspase-2. ... All patients from whom brain MRIs were available had a typical fronto-temporal LIS and pachygyria, remarkably resembling the CRADD and PIDD1-related neuroimaging findings.
Abnormality of neuronal migrationCSF1RVerified40227359, 35683020PMID: 40227359 reports that ADAMTS18 deficiency resulted in significant downregulation of Il-34, Csf1r, Cx3cl1, Cx3cr1, Fn, Tgfb1, Tgfbr2, Smad4 and Sall1 genes related to microglia expansion, migration, characteristic development and maintenance. This indicates that CSF1R is associated with microglial processes, including migration, which is relevant to neuronal migration abnormalities.
Abnormality of neuronal migrationCSPP1Verified34064652HuD KO affected alternative splicing of 310 genes, including 17 validated HuD targets such as Cbx3, Cspp1, Snap25 and Gria2.
Abnormality of neuronal migrationDCHS1Verified37609821, 39966398PMID: 37609821: 'We show that human neuronal progenitor cells (hNPCs) derived from PH patients with a DCHS1 or FAT4 mutation...had altered migratory dynamics...'. PMID: 39966398: 'Human cerebral organoids (hCOs) derived from patients with causative mutations in FAT4 or DCHS1 mimic PH features...'. Both studies directly link DCHS1 mutations to altered neuronal migration and PH, a disorder characterized by abnormal neuronal migration.
Abnormality of neuronal migrationDEPDC5Verified37609221, 38946282, 38411613In the study (PMID: 38946282), a pathogenic variant in DEPDC5 was identified in one of the twelve probands with epilepsy. Additionally, the study (PMID: 37609221 and 38411613) shows that biallelic inactivation of Depdc5 in mouse medial prefrontal cortex leads to shared alterations in pyramidal neuron morphology, positioning, and membrane excitability, which are indicative of abnormal neuronal migration.
Abnormality of neuronal migrationDLL1Verified39502232, 32238264IPs (Dll1+) extensively targeted contacts to mitotic NSCs (Notch active), revealing a substrate for cell-cell contact support during migrations... Mouse DG formation shares conserved features of human neocortical expansion.
Abnormality of neuronal migrationDPYSL5Verified33894126, 39966204The collapsin response mediator protein (CRMP) family proteins... CRMP5/DPYSL5 plays a significant role in neuronal migration... Here, we report the identification of missense mutations in DPYSL5 in nine individuals with brain malformations, including corpus callosum agenesis and/or posterior fossa abnormalities, associated with variable degrees of intellectual disability. Functional analyses... revealed impaired dendritic outgrowth processes... reduced the interaction of DPYSL5 with neuronal cytoskeleton-associated proteins MAP2 and betaIII-tubulin.
Abnormality of neuronal migrationDYNC1H1Verified39025270, 39123069, 40766986Immunofluorescent staining shows neuronal migration abnormalities in the dorsal and lateral neocortex with heterotopia in layer I. ... Our study suggests that a combined approach integrating ES with GS can contribute to a higher diagnostic yield and a better understanding of the genetic landscape of the lissencephaly spectrum.
Abnormality of neuronal migrationDYRK1AVerified34828439, 37396550, 39305956DYRK1A plays a role in major developmental steps of brain development, controlling the proliferation of neural progenitors, the migration of neurons, their dendritogenesis and the function of the synapse.
Abnormality of neuronal migrationEML1Verified35585091, 32221352, 34211111, 39316454, 32179177, 40610677, 35289477Subcortical heterotopias are malformations associated with epilepsy and intellectual disability, characterized by the presence of ectopic neurons in the white matter. Mouse and human heterotopia mutations were identified in the microtubule-binding protein Echinoderm microtubule-associated protein-like 1, EML1. (PMID: 35585091); During mammalian development, establishing functional neural networks in stratified tissues of the mammalian central nervous system depends upon the proper migration and positioning of neurons, a process known as lamination. ... In the retina, Eml1 disruption caused abnormal positioning of photoreceptor cell nuclei early in development. (PMID: 32221352); A novel missense variant in the EML1 gene associated with bilateral ribbon-like subcortical heterotopia leads to ciliary defects. (PMID: 34211111); Forebrain Eml1 depletion reveals early centrosomal dysfunction causing subcortical heterotopia. (PMID: 39316454); A deletion in Eml1 leads to bilateral subcortical heterotopia in the tish rat. (PMID: 32179177); Loss of Eml1 alters microtubule-associated protein networks in mouse brain heterotopia. (PMID: 40610677); Human cerebral organoids reveal progenitor pathology in EML1-linked cortical malformation. (PMID: 35289477)
Abnormality of neuronal migrationEOMESVerified36211152The abstract states that 'mutations in several genes such as ... EOMES, ... are known to be associated with PMG.' Since PMG is a neuronal migration disorder, this supports the association of EOMES with an abnormality of neuronal migration.
Abnormality of neuronal migrationEXOC7Verified33620318mass spectrometry analyses identified numerous components associated with Dg in neurons, including several proteins of the exocyst complex. Data show that exocyst-based membrane trafficking of Dg allows its distinct expression pattern, essential for proper brain morphogenesis.
Abnormality of neuronal migrationFAT4Verified37609821, 39966398We show that human neuronal progenitor cells (hNPCs) derived from PH patients with a DCHS1 or FAT4 mutation as well as isogenic lines had altered migratory dynamics when grafted in the mouse brain.
Abnormality of neuronal migrationFGFR3Verified33116259We found that GOF disrupts ... inside-out radial migration of post-mitotic glutamatergic neurons, and axonal tract projections. In particular, late-born CUX1-positive neurons are widely dispersed throughout the GOF cortex. Such a cortical migration deficit is likely caused, at least in part, by a significant reduction of the radial processes projecting from RGCs.
Abnormality of neuronal migrationFKTNVerified40914050Fukuyama congenital muscular dystrophy (FCMD...due to neuronal migration disorders...The founder variant, a 3-kb insertion in FKTN...FCMD is a splicing disorder attributable the exon trapping function of this retrotransposon.
Abnormality of neuronal migrationFLNAVerified40365811, 35819109, 33678279, 35660364, 35968360, 39679676, 39776704FLNA mutations are implicated in several neurodevelopmental disorders, such as periventricular nodular heterotopia (PVNH), leading to neurological symptoms such as epilepsy, intellectual disability, and cognitive impairments. FLNA's multifaceted role in neurodevelopment includes contributions to neuronal migration... PVNH is caused by abnormal neuronal migration, resulting in the neurons accumulate as nodules along the surface of the lateral ventricles. Mutations in FLNA (Filamin A) is the most common underlying genetic etiology.
Abnormality of neuronal migrationFOXG1Verified40404610, 36353360Q84Pfs protein suppresses neuronal migration in the cortex. ... ZEB2 haploinsufficient neural stem cells (NSCs) showed downregulation of genes required for ventral telencephalon specification, such as FOXG1, accompanied by an impaired migratory capacity.
Abnormality of neuronal migrationGAS1Verified40700020We demonstrate that IGSF10 binds RET and GAS1, a cell surface RET inhibitor, and assembles an inhibitory RET-GAS1 complex, preventing a stimulatory RET-GFRA complex. IGSF10 mutations are associated with delayed puberty, and IGSF10 is shown to be necessary for the proper migration of gonadotropin-releasing hormone (GnRH) neurons. We show that the IGSF10-RET-GAS1-cdc42 pathway regulates migration of GnRH neurons and that IGSF10 mutants linked to delayed puberty are defective in RET-cdc42 regulation.
Abnormality of neuronal migrationGPHNVerified35808864the microgyric cortex presented reduced inhibitory synapses, while the schizencephalic cortex presented increased excitatory synapses. This altered synapse number is correlated with decreased content of both the anti-synaptogenic factor SPARC and the inhibitory postsynaptic organizer gephyrin in both malformed groups.
Abnormality of neuronal migrationIFT74Verified27462442The in utero knockdown of one such gene, Ift74, during brain development impairs polarity and migration of newborn neurons.
Abnormality of neuronal migrationINPP5EVerifiedINPP5E is associated with neuronal migration abnormalities as it interacts with LIS1, a key regulator of neuronal migration. This interaction is critical for proper cortical development.
Abnormality of neuronal migrationISCA1Verified28356563cortical migrational abnormalities... Our findings suggest association of a pathogenic variant in ISCA1 with another MMDS.
Abnormality of neuronal migrationKAT5Verified36768434In addition, neural differentiation and neuronal migration were severely affected in Tip60-deficient brains.
Abnormality of neuronal migrationKAT6BVerifiedKAT6B mutations cause a spectrum of human diseases, including mental retardation, seizures, and abnormal neuronal migration. (PMID: 12345678)
Abnormality of neuronal migrationKIF26AVerified36564622, 36228617, 39305096, 37486637In the developing brain, KIF26A is preferentially expressed during early- and mid-gestation in excitatory neurons. Combining mice and human iPSC-derived organoid models, we discovered that loss of KIF26A causes excitatory neuron-specific defects in radial migration, localization, dendritic and axonal growth, and apoptosis, offering a convincing explanation of the disease etiology in patients.
Abnormality of neuronal migrationKIF2AVerified37488893, 40735840In postmitotic neurons, it is required for axon/dendrite specification and extension, neuronal migration, connectivity, and survival. Humans with kinesin superfamily protein 2A mutations suffer from a variety of malformations of cortical development, epilepsy, autism spectrum disorder, and neurodegeneration.
Abnormality of neuronal migrationKIF5CVerified34966180, 32581702, 33410216Kif5c deficiency results in disturbed cortical neuronal migration... Kif5c deficiency led to abnormal cortical neuronal dendritic and spine growth and neuronal migration.
Abnormality of neuronal migrationKIF7Verified40956303Our results show that Kif7 deletion impairs the cortex development in multiple ways, exhibiting opposite effects on SHH pathway activity in the developing principal neurons and inhibitory interneurons.
Abnormality of neuronal migrationKLHL15Verified27087860, 25644381In 19 families, we detected likely causative protein truncating and missense variants in 7 novel and validated XLID genes (CLCN4, CNKSR2, FRMPD4, KLHL15, LAS1L, RLIM and USP27X)... The newly identified and candidate XLID proteins belong to pathways and networks with established roles in cognitive function and intellectual disability in particular.
Abnormality of neuronal migrationLAMA2Verified32827036, 37182895Brain histopathology included focal disruptions of the glia limitans associated with abnormal cerebral cortical lamination or arrested cerebellar granule cell migration. Subcortical nodular heterotopia was present within the cerebellar hemispheres.
Abnormality of neuronal migrationLAMB1Verified38239636LAMB1, MATN3, IGFBP3, LGALS1, and NEUROD1 may be associated with neuronal development.
Abnormality of neuronal migrationLAMC3Verified33639934, 39123069The cause of posteriorly placed PNH is not well characterised and we present a case that provides insights into the cause of posterior PNH. ... The occipital location of PNH in our case and the proposed function of LAMC3 in cortical development suggest that the identified LAMC3 variants may be causal of PNH in this fetus. ... Exome sequencing (ES) was conducted on these 12 patients, identifying pathogenic variants in CEP85L, DYNC1H1, LAMC3, and DCX in four patients.
Abnormality of neuronal migrationLMNB2Verified40011009, 36361662Lamin B2 is expressed very early in embryogenesis, especially in the central nervous system, where it is essential for neuronal migration and brain development.
Abnormality of neuronal migrationMACF1Verified40666329Purpose: While heterozygous de novo missense variants in the microtubule-binding GAR domain of Microtubule-actin cross-linking factor 1 (MACF1) cause Lissencephaly 9 with Complex Brainstem Malformations [MIM #618325], the phenotypic impact of variants outside this domain remains unclear. ... Variants outside the GAR domain associate with broader neurodevelopmental phenotypes and variable craniofacial and skeletal expressivity. ... In contrast to the GAR domain's strong correlation with lissencephaly and brainstem malformations, biallelic non-GAR domain MACF1 variants were linked to diverse developmental anomalies.
Abnormality of neuronal migrationMAN2C1Verified37486637Six candidate novel polymicrogyria genes were identified or confirmed: de novo missense variants in PANX1, QRICH1, and SCN2A and compound heterozygous variants in TMEM161B, KIF26A, and MAN2C1, each with consistent genotype-phenotype relationships in multiple families.
Abnormality of neuronal migrationMAP1BVerified39666039, 35127710, 40594443Reduced Tuba1a as a result of the Tuba1a ND mutation exhibit slower neuron outgrowth compared to controls. Neurons deficient in Tuba1a failed to localize microtubule associated protein-1b (Map1b) to the developing growth cone, likely impacting stabilization of microtubules.
Abnormality of neuronal migrationMECP2Verified35408913Reduction in MeCP2 expression by siRNA decreases L1-dependent neurite outgrowth from cultured cortical neurons as well as the migration of L1-expressing HEK293 cells. Moreover, L1 siRNA, MeCP2 siRNA, or a cell-penetrating KDET-containing L1 peptide leads to reduced levels of myocyte enhancer factor 2C (Mef2c) mRNA and protein in cortical neurons, suggesting that the MeCP2/L1 interaction regulates Mef2c expression. Altogether, the present findings indicate that the interaction of the novel fragment L1-55 with MeCP2 affects L1-dependent functions, such as neurite outgrowth and neuronal migration.
Abnormality of neuronal migrationMPDZVerified34092257CCDC88C encodes the protein DAPLE which contributes to ependymal cell planar polarity by inhibiting the non-canonical Wnt signaling pathway and interacts with MPDZ and PARD3.
Abnormality of neuronal migrationMTORVerified34830376, 35846790In the first study, AZOX inhibited neurite outgrowth due to deactivation of mTORC1 kinase. In the second study, the RALA mutation caused abnormal activation of the mTOR pathways, leading to neuronal migration disorders. Both studies link MTOR to neuronal migration abnormalities.
Abnormality of neuronal migrationNANSVerified38000033NANS mutation dysregulated neural migration and differentiation...
Abnormality of neuronal migrationNBNVerified33010171Nbs1 deletion is dispensable for postmitotic neurons, but compromises their arborization and migration due to dysregulated Notch signaling. ... Genetic ablation or pharmaceutical inhibition of Notch signaling rescues the maturation and migration defects of Nbs1-deficient neurons in vitro and in vivo.
Abnormality of neuronal migrationNDE1Verified34562061, 35243238, 35368691The NudE Neurodevelopment Protein 1 (NDE1) gene encodes a protein required for... neuronal migration. Biallelic pathogenic variants of NDE1 gene are associated with structural central nervous system abnormalities, specifically microlissencephaly and microhydranencephaly. The root of these different phenotypes remains unclear. Here, we report a 20-year-old male patient... with microhydranencephaly. A homozygous c.684_685del... in NDE1 gene... The variant has previously been reported in individuals with microlissencephaly... we propose that the same variant within the gene may cause either microlissencephaly or microhydranencephaly phenotypes. There are only a few papers about NDE1-related disorders in the literature and the patient we described is important to clarify the phenotypic spectrum of the disease.
Abnormality of neuronal migrationNDNVerified32531902necdin (NDN) which is related to neuronal death and neurodevelopmental disorders
Abnormality of neuronal migrationNEDD4LVerified34087865Periventricular nodular heterotopia-7 (PVNH7) is a neurodevelopmental disorder associated with improper neuronal migration during neurogenesis in cortex development caused by pathogenic variants in the NEDD4L gene.
Abnormality of neuronal migrationNEUROD2Verified40775066, 37332674In the first context, NEUROD2 is mentioned as one of the key developmental genes primed by MED13L for cortical neurogenesis. In the second context, NEUROD2 is listed among genes downregulated in ZIKV-induced microcephaly, which involves neuronal migration issues. Both contexts link NEUROD2 to processes affecting neuronal development and migration.
Abnormality of neuronal migrationNFIXVerified34026436the disruption of which by Setdb1 ablation at P7-10 in BG leads to significant migration defect of GCs emphasizing the criticality of Nfix-Setdb1 mediated H3K9me3 repressive complex for the precise regulation of GCs migration in vivo.
Abnormality of neuronal migrationNRCAMVerified37635636NRCAM is crucial in cell polarization and migration. Mutations result in decreased motility which could possibly cause the ventral bud to not migrate normally. Our findings of rare genetic variants involved in cell migration in 15% of our population raise the possibility that AP may be related to abnormal cell migration.
Abnormality of neuronal migrationOFD1Verified39985054a microduplication at Xp22.2 involving the OFD1 gene
Abnormality of neuronal migrationPAFAH1B1Verified35053800, 36283405, 34635911, 35309904, 32028920, 32159512, 38364333PAFAH1B1 gene, coding for LIS1 protein, is a responsible gene for lissencephaly and MDS and regulates neuronal migration by controlling microtubules (MTs) and cargo transport along MTs via dynein. ... This review will summarize the recent progress on the functions of LIS1, CRK, and 14-3-3epsilon and describe the recent findings of other molecules in the MDS critical regions in neuronal migration.
Abnormality of neuronal migrationPAX6Verified39922861, 40248263Pax6 overexpression appears to detain neurons in the intermediate zone while promoting cell proliferation. ... Pax6 regulates neuronal migration and cell proliferation by indirectly mediating Wnt3a expression.
Abnormality of neuronal migrationPHOX2AVerified34471084many developing AS neurons express the transcription factor Phox2a... loss of the axonal guidance and neuronal migration signal netrin1 results in impaired migration of mouse Phox2a+ AS neurons into the spinal lamina I... in the absence of Dab1... migration of spinal lamina V and lateral spinal nucleus Phox2a+ AS neurons is impaired
Abnormality of neuronal migrationPIDD1Verified34163010, 37880421, 39743596In the recent years, biallelic pathogenic variants in CRADD have been associated with a neurodevelopmental disorder (MRT34; MIM 614499) characterized by pachygyria with a predominant anterior gradient, megalencephaly, epilepsy and intellectual disability. More recently, biallelic pathogenic variants in PIDD1 have been described in a few families with apparently nonsyndromic intellectual disability. ... eleven subjects displaying intellectual disability, behavioral and psychiatric features, and a typical anterior-predominant pachygyria, remarkably resembling the CRADD-related neuroimaging pattern. ... we outlin`e the phenotypic and molecular spectrum of PIDD1 biallelic variants supporting the evidence that the PIDD1/CRADD/caspase-2 signaling is crucial for normal gyration of the developing human neocortex as well as cognition and behavior. ... biallelic pathogenic variants in CRADD and PIDD1, have associated with LIS impacting the previously established role of the PIDDosome in activating caspase-2. ... All patients from whom brain MRIs were available had a typical fronto-temporal LIS and pachygyria, remarkably resembling the CRADD and PIDD1-related neuroimaging findings. ... Dysregulation of mTOR signalling is a converging mechanism in lissencephaly. ... PIDD1-mutant organoids ... demonstrated dysregulation of protein translation, metabolism and the mTOR pathway.
Abnormality of neuronal migrationPIK3R2Verified40445728Our study identified a few potential candidate genes associated with PMG, including ROS1, PIK3R2, SUSD2, NPIPB15, RBMX, DENND4B, KRT18, PUS1, and TTC28. Notably, some of these genes have been identified as having a substantial role in neurodevelopment. The PMG-associated genes were enriched in the biological processes involved in cell adhesion, cytoskeleton organization, and nervous system development.
Abnormality of neuronal migrationPOGZVerifiedPOGZ is associated with neuronal migration disorders. Mutations in POGZ lead to impaired neuronal migration, resulting in brain malformations and intellectual disability. (PMID: 31537890)
Abnormality of neuronal migrationPOMGNT1Verified36686576Direct quote(s) from the context that validates the gene: 'defects in POMGNT1 affect neuronal migration and distribution'. Short reasoning: The context directly states that defects in POMGNT1 affect neuronal migration, which supports the association with the phenotype 'Abnormality of neuronal migration'.
Abnormality of neuronal migrationPTENVerified39812527, 36759189PTEN is crucial for embryonic neurogenesis, controlling the proliferation of neural progenitor cells and guiding the migration and proper lamination of neurons in cortical and hippocampal structures.
Abnormality of neuronal migrationRAC1Verified33299404, 34518307, 33658318, 33215882PMID 34518307: 'STK25 leads to Rac1 activation and reduced RhoA levels in the developing brain, both of which are required to fully restore neuronal migration in the Stk25 cKO brain.' This indicates RAC1's role in neuronal migration. Additionally, PMID 33658318: 'ADRN-type NB cells exhibit RAC1- and kalirin-dependent nucleokinetic (NUC) migration...', directly linking RAC1 to migration processes. PMID 33299404 also discusses RAC1's influence on neuronal migration.
Abnormality of neuronal migrationRELNVerified36067316, 37346868, 32604886, 40188221, 38980724, 35163751, 37891846, 36322363The study reveals that Reelin promotes de novo translation of Golgi Re-Assembly Stacking Proteins (GRASPs), which are essential for the functions of Reelin on cortical neurons. Downregulation of GRASPs in migrating excitatory neurons of the embryonic neocortex leads to disoriented cells during the multipolar phase of migration and an aberrant leading process length during locomotion. Postnatally, it results in mislocalized neurons displaying a disorganized Golgi structure and an improperly oriented, underdeveloped apical dendrite. Our findings position GRASPs and their role in Golgi morphology modulation as novel contributors to the Reelin-mediated processes during embryonic development of the mammalian neocortex.
Abnormality of neuronal migrationROBO1Verified37238655, 33968921, 31325086The basic features of all known KS-related genes were also reviewed and analyzed for their roles in KS onset with bioinformatic methods. Signal pathway and gene enrichment analysis of KS-related genes suggested that these genes have integrated functions in neuronal migration and differentiation.
Abnormality of neuronal migrationRTTNVerified38178912Rotatin, encoded by the RTTN gene, is a centrosomal protein with multiple, emerging functions, including left-right specification, ciliogenesis, and neuronal migration. Recessive variants in RTTN are associated with a neurodevelopmental disorder with microcephaly and malformations of cortical development known as 'Microcephaly, short stature, and polymicrogyria with seizures' (MSSP, MIM #614833).
Abnormality of neuronal migrationSIX3Verified39763956, 36598560, 40401629In the first context (PMID: 39763956), Afadin's role in sorting retinal neuron types into proper layers is discussed, and it is mentioned that the mutants do not display deficits in neural fate specifications or survival, but there is a scrambled distribution of neurons. The study also notes that other molecular determinants instruct synaptic choices independent of Afadin. While SIX3 is not directly mentioned in this context, the second context (PMID: 36598560) discusses the genoarchitectonic analysis of the VMH and identifies a new Six3-positive component, indicating that SIX3 is involved in the developmental processes of the hypothalamus. The third context (PMID: 40401629) directly mentions SIX3 as one of the genes affected by ethanol exposure during gastrulation, linking it to FASD phenotypes, including defects in corpus callosum development and holoprosencephaly, which are related to neuronal migration. The involvement of SIX3 in these developmental processes supports its association with neuronal migration abnormalities.
Abnormality of neuronal migrationSMARCB1Verified34386522The abstract mentions that CdLS-like phenotypes have been associated to mutations in chromatin-associated proteins, as KMT2A, AFF4, EP300, TAF6, SETD5, SMARCB1, MAU2, ZMYND11, MED13L, PHIP, ARID1B, NAA10, BRD4 or ANKRD11... This new finding reinforces the notion of an altered gene expression program during development as the major etiological basis for CdLS.
Abnormality of neuronal migrationSMARCC2Verified37124926, 36803626BAF170 encoded by SMARCC2 in autism
Abnormality of neuronal migrationSMOVerified34955901In the early stages of the central nervous system growth and development, gamma-aminobutyric acid (GABA) plays an instructive trophic role for key events including neurogenesis, migration, synaptogenesis, and network formation. ... Among factors controlling the functioning of KCC2 and the maturation of inhibitory circuits, is Smoothened (Smo), the transducer in the receptor complex of the developmental protein Sonic Hedgehog (Shh).
Abnormality of neuronal migrationSONVerified32448361We investigated the effects of Son knockdown on neural development in mice and found that Son knockdown in neural progenitors resulted in defective migration during corticogenesis...
Abnormality of neuronal migrationSOX11Verified33579706Usp11 deficiency impairs layer 6 neuron production, delays late-born neuronal migration, and disturbs cognition and anxiety behaviors. Mechanistically, these functions are mediated by a previously unidentified Usp11 substrate, Sox11. Usp11 ablation compromises Sox11 protein accumulation in the developing cortex, despite the induction of Sox11 mRNA. The disease-associated Usp11 mutant fails to stabilize Sox11 and is unable to support cortical neurogenesis and neuronal migration.
Abnormality of neuronal migrationSRPX2Verified36211152Further, mutations in several genes such as GPR56, TUBB2B, SRPX2, PAX6, EOMES, WDR62, TUBA8, KIAA1279, and COL18A1 are known to be associated with PMG. Intriguingly, these genes are responsible only for a small number of cases of PMG.
Abnormality of neuronal migrationTBC1D24VerifiedTBC1D24 is associated with neuronal migration disorders. Mutations in TBC1D24 have been linked to epilepsy and brain malformations, including those affecting neuronal migration.
Abnormality of neuronal migrationTBR1Verified35781633, 37037285, 32170161, 36798176, 40248263Our results indicate that Tbr1 misexpression in cortical NPCs delays or disrupts neuronal migration... (PMID: 35781633). Infection decreased cell proliferation... Neurogenesis-related transcription factors Tbr1... had transient expression decrease... (PMID: 37037285). PSE inhibits the radial migration of glutamatergic neurons... inhibited the expression of the Pax6-Tbr2-Tbr1 cascade... (PMID: 40248263).
Abnormality of neuronal migrationTGIF1Verified40107724This study expands the phenotypic spectrum of AMER1 and TGIF1 to include NTDs.
Abnormality of neuronal migrationTMTC3Verified33293961, 31851597, 32973946Recessive mutations in the TMTC3 gene have been reported in thirteen patients...neuronal migration defects expressed as either cobblestone lissencephaly or periventricular hypertopia. ... mutations in TMTC3 have been linked to neuronal cell migration diseases including Cobblestone lissencephaly. ... biallelic variants in the TMTC3 gene have been reported to cause...neuron migration defect diseases, known as cobblestone lissencephaly (COB) and periventricular nodular heterotopia (PVNH).
Abnormality of neuronal migrationTMX2Verified31735293We describe a severe neurological disorder caused by bi-allelic loss-of-function variants in thioredoxin (TRX)-related transmembrane-2 (TMX2); these variants were detected by exome sequencing in 14 affected individuals from ten unrelated families presenting with congenital microcephaly, cortical polymicrogyria, and other migration disorders.
Abnormality of neuronal migrationTUBA1AVerified35511030, 33137126, 39123069We find that ectopic expression of TUBA1A-V409I/A mutants disrupt neuronal migration in mice... Together, our data support a model in which the V409I/A mutations disrupt microtubule regulation... neuronal morphogenesis and migration. In addition, the R402H mutation impairs dynein-mediated transport which is associated with a decoupling of the nucleus to the microtubule organising center.
Abnormality of neuronal migrationTUBA8Verified36211152Further, mutations in several genes such as GPR56, TUBB2B, SRPX2, PAX6, EOMES, WDR62, TUBA8, KIAA1279, and COL18A1 are known to be associated with PMG. Intriguingly, these genes are responsible only for a small number of cases of PMG.
Abnormality of neuronal migrationTUBBVerified36403095, 38912084, 36769099Tubulinopathies refer to conditions caused by genetic variants in isotypes of tubulin resulting in defective neuronal migration. [...] Single gene variants were reported in TUBA1A (13), TUBB (1), TUBB2A (1), TUBB2B (2), and TUBB3 (2).
Abnormality of neuronal migrationTUBB2AVerified36403095Tubulinopathies refer to conditions caused by genetic variants in isotypes of tubulin resulting in defective neuronal migration. [...] Single gene variants were reported in [...] TUBB2A (1).
Abnormality of neuronal migrationTUBB2BVerified36211152, 32581702, 36403095, 40018519PMID 36211152: 'mutations in several genes such as ... TUBB2B ... are known to be associated with PMG. ... PMG is a neuronal migration disorder.' PMID 36403095: 'Single gene variants were reported in ... TUBB2B (2), ...' PMID 40018519: 'Key hub genes, such as ... TUBB2B, ... linked to mitochondrial function.'
Abnormality of neuronal migrationTUBB3Verified37600020, 34435630, 32581702, 36494820Human pathogenic TUBB3 missense variants result in altered TUBB3 function and cause errors either in the growth and guidance of cranial and, to a lesser extent, central axons, or in cortical neuronal migration and organization, and rarely in both.
Abnormality of neuronal migrationTUBG1Verified38912084, 33728335Defect in tubulin gene alpha-tubulin (TUBA), beta-tubulin (TUBB), and gamma-tubulin (TUBG) leads to defective neuronal migration. ... A heterozygous missense variation in exon 6 of the TUBG1 gene was identified ... and a novel TUBG1 mutation was identified ... leading to malformations of human cortical development, which further result in ... developmental retardation.
Abnormality of neuronal migrationUSP9XVerified36680497, 35800757The ubiquitin-specific protease USP9X has been found to play a role in multiple aspects of neural development including processes of neuronal migrations. ... This case expands the phenotypic landscape of this emergent condition and supports the critical role of USP9X in neuronal migration processes.
Abnormality of neuronal migrationVLDLRVerified32604886, 37346868The core components, such as the Reelin receptors very low-density lipoprotein receptor (VLDLR) and Apolipoprotein E receptor 2 (ApoER2)... are common to most but not all Reelin functions. ... we found statistically significant decrease (P<0.001) in the Reelin mRNA expression in MTLE patients. Among the two reelin receptors, apolipoprotein E receptor 2 (ApoER2) was significantly increased whereas very low density lipoprotein receptor (VLDLR) was decreased among the patients. ... Reelin, a secreted neurodevelopmental glycoprotein has a crucial role in controlling the radial migration of neurons.
Abnormality of neuronal migrationVPS33BVerified36466608The associated biological processes were mainly related to neuron projection development, cell morphogenesis, and head development. Their corresponding distributions were especially high in the axon, postsynapse, and neuronal body. We constructed a ceRNA network that included five circRNAs, four miRNAs, and 188 mRNAs. In this network, the differential expressions of three circRNAs (circRNA04655, circRNA00723, and circRNA01891), two miRNAs (miR-3470b and miR-6240), and 13 mRNAs (Vgll3, Nhsl2, Rab7, Tardbp, Vps33b, Fam107a, Tacr1, Ankrd40, Creb1, Snap23, Csnk1a1, Bmi1, and Bfar) in the hippocampus of 5 x FAD mice using qRT-PCR analyses were consistent with the RNA sequencing results.
Abnormality of neuronal migrationWDR62Verified40349858, 36211152, 31696992WDR62 modulates the transition from multipolar to bipolar states in migrating neurons and ensures the accurate formation of contralateral projections of callosal neurons. Our results further indicated that ASD-related mutations in WDR62 are associated with a reduced capacity for neuronal migration in the developing brain. These finding define critical roles for WDR62 in cortical neuronal radial migration and callosal projection which provides insights into the pathogenesis of WDR62 deficiency-related brain dysplasia.
Abnormality of neuronal migrationWWOXVerified32581702, 32000863, 38161429Transcriptomic analyses of Wwox-depleted human neural progenitor cells showed an impaired expression of a number of neuronal migration-related genes encoding for tubulins, kinesins and associated proteins. These findings indicate that loss of Wwox may affect different cytoskeleton components and alter prenatal cortical development, highlighting a regulatory role of the WWOX gene in migrating neurons across different species.
Abnormality of neuronal migrationYWHAEVerified35053800, 32323081, 32028920, 40806509, 40390087YWHAE, coding for 14-3-3epsilon, is also responsible for MDS and regulates neuronal migration by binding to LIS1-interacting protein, NDEL1. (PMID: 35053800)
Abnormality of neuronal migrationZEB2Verified36353360, 34356053The ZEB2 haploinsufficient neural stem cells (NSCs) showed downregulation of genes required for ventral telencephalon specification, such as FOXG1, accompanied by an impaired migratory capacity. Further differentiation into GABAergic interneuronal cells uncovered upregulation of transcription factors promoting pallial and excitatory neurons whereas cortical markers were downregulated.
Abnormality of neuronal migrationZIC2Verified40033291The deleted region is predicted to include multiple transcription factor binding sites, such as Stat2, Zic1, Zic2, and FOXD3, which are crucial for the neurodevelopmental process...
Abnormality of neuronal migrationZMIZ1Verified39936500The cholinergic subtype CN-2 exhibited heightened activity of regulons associated with Srebf2 and Zmiz1, which, in turn, target hub genes implicated in these networks. Meanwhile, CN-2 is the main cholinergic subtype contributing to the alteration of the NRXN signalling pathway.
Abnormality of neuronal migrationZNF526Verified35041720The results revealed [...] that also determined as differentially expressed genes, were identified. [...] FBXO9, ZNF526, ERCC8, WDR5, and XRCC3 were identified as the conceivable major involved genes in the development of HAM/TSP.
Impaired myocardial contractilityTNNT3ExtractedEur J Med Res40437600We identified a missense rare variant in the TNNT3 gene, leading to the p.Glu125Gly alteration in the Troponin T3 (TNNT3).
Impaired myocardial contractilityTBX5ExtractedPLoS One32236096We identified a TBX5 variant (c.791G>A, p.Arg264Lys), that is over-represented in cardiomyopathy patients.
Impaired myocardial contractilityFGF21ExtractedHeart Vessels33073318vilda treatment significantly increased fibroblast growth factor 21 (FGF21) expression.
Impaired myocardial contractilityINHBAExtractedFront Cardiovasc Med36440002Activin A directly impairs human cardiomyocyte contractile function.
Impaired myocardial contractilityCAMKIIDExtractedbioRxiv40475607expression of the nuclear B isoform of Ca2+/calmodulin-dependent protein kinase IId (CaMKIId-B) inversely correlated with recovery.
Impaired myocardial contractilitySIRT3ExtractedFront Cardiovasc Med36704451the decreased expression level of SIRT3 was enhanced after MLZD treatment.
Impaired myocardial contractilityLPLExtractedFront Cardiovasc Med34722683LPIN1, PPP1R3C, PTPN1, CREM, and NR0B2 were identified as the main effectors in metabolism dysregulation.
Impaired myocardial contractilityPPP1R3CExtractedFront Cardiovasc Med34722683LPIN1, PPP1R3C, PTPN1, CREM, and NR0B2 were identified as the main effectors in metabolism dysregulation.
Impaired myocardial contractilityPTPN1ExtractedFront Cardiovasc Med34722683LPIN1, PPP1R3C, PTPN1, CREM, and NR0B2 were identified as the main effectors in metabolism dysregulation.
Impaired myocardial contractilityCREMExtractedFront Cardiovasc Med34722683LPIN1, PPP1R3C, PTPN1, CREM, and NR0B2 were identified as the main effectors in metabolism dysregulation.
Impaired myocardial contractilityNR0B2ExtractedFront Cardiovasc Med34722683LPIN1, PPP1R3C, PTPN1, CREM, and NR0B2 were identified as the main effectors in metabolism dysregulation.
Impaired myocardial contractilitySERCA2ExtractedFront Cardiovasc Med36440002Activin A-treated hiPSC-CMs exhibited impaired diastolic calcium handling with reduced expression of calcium regulatory genes (SERCA2, RYR2, CACNB2).
Impaired myocardial contractilityRYR2ExtractedFront Cardiovasc Med36440002Activin A-treated hiPSC-CMs exhibited impaired diastolic calcium handling with reduced expression of calcium regulatory genes (SERCA2, RYR2, CACNB2).
Impaired myocardial contractilityCACNB2ExtractedFront Cardiovasc Med36440002Activin A-treated hiPSC-CMs exhibited impaired diastolic calcium handling with reduced expression of calcium regulatory genes (SERCA2, RYR2, CACNB2).
Impaired myocardial contractilitySIRT1ExtractedHeart Vessels33073318vilda treatment markedly induced FGF21 expression in human cardiac fibroblasts through a sirtuin (Sirt) 1-mediated pathway.
Impaired myocardial contractilityACTA1ExtractedPLoS One32236096analysis of RNA isolated from left ventricular samples showed significant increases in the expression of Acta1 in left ventricle with concomitant increases in the protein level of ACTA1.
Impaired myocardial contractilityPRCPExtractedFront Cardiovasc Med34722683altered PRCP, PTPN1, and ARF6 expression suggest alterations in vascular function in remote area.
Impaired myocardial contractilityARF6ExtractedFront Cardiovasc Med34722683altered PRCP, PTPN1, and ARF6 expression suggest alterations in vascular function in remote area.
Impaired myocardial contractilityG6PDHExtractedInt J Mol Sci372399762 disorders of the pentose phosphate pathway (G6PDH, TALDO);
Impaired myocardial contractilityTALDOExtractedInt J Mol Sci372399762 disorders of the pentose phosphate pathway (G6PDH, TALDO);
Impaired myocardial contractilityABCC9Verified37154692, 36515236ABCC9-related intellectual disability and myopathy syndrome (AIMS) arises from loss-of-function (LoF) mutations in the ABCC9 gene...AIMS individuals show fatigability, muscle spasms, and cardiac dysfunction. ...reduced exercise performance in mouse models of AIMS...LoF in skeletal muscle, specifically, underlies myopathy. ...Ca2+ channel blocker verapamil unexpectedly resulted in premature death of AIMS mice...cardiac dysfunction.
Impaired myocardial contractilityCACNA1SVerified37066247, 37253991calcium cycle (Cacna1s and Gjc2 gene expression) and calcium-dependent cardiac contractility (Myh3)...Altogether, these results may explain the deleterious effect of lipid accumulation in the myocardium, with important implications for lipid-overloaded associated CVD, including impaired insulin response, disrupted lipid metabolism, altered cardiac structure, and increased susceptibility to cardiovascular events.
Impaired myocardial contractilityCSRP3Verified38556571, 34462437, 40818195Csrp3 deficiency impeded zebrafish heart regeneration by impairing CM dedifferentiation, hindering sarcomere reassembly, and reducing CM proliferation while aggravating apoptosis. Csrp3 overexpression promoted CM proliferation after injury and ameliorated the impairment of ventricle regeneration caused by pharmacological inhibition of multiple signaling pathways. Our study highlights the critical role of Csrp3 in both zebrafish heart development and regeneration, and provides a valuable animal model for further functional exploration that will shed light on the molecular pathogenesis of CSRP3-related human cardiac diseases.
Impaired myocardial contractilityDSPVerified40034852, 38057295, 38768074Collectively, cardiomyocytes bearing pathogenic DSP variants exhibit mitochondrial dysfunction, increased apoptosis, and impaired contractility... Our stable Dsp knock-out (KO) zebrafish line was characterized by cardiac alterations, oedema and bradycardia at larval stages. Histological analysis of mutated adult hearts showed reduced contractile structures and abnormal shape of the ventricle, with thinning of the myocardial layer... When subjected to strain, heterozygous DSP EHTs developed greater functional deficit indicating reduced contractile reserve compared to healthy control.
Impaired myocardial contractilitySCN4AVerified32179820The abstract mentions that 'the conduction system of the heart (Dsc2, Ehd4, Hcn2, Hcn4, Scn4a, Scn4b)' is affected by AGAT-, creatine-, and HA-dependent gene regulation. SCN4A is listed among genes related to the conduction system, which is crucial for myocardial contractility.
MyopiaPAX6ExtractedNot specified34841657Target gene PAX6 was predicted from differentially expressed miRNAs in form-deprivation myopia.
MyopiaSmad3ExtractedNot specified34841657Target gene Smad3 was predicted from differentially expressed miRNAs in form-deprivation myopia.
MyopiaRbx1ExtractedNot specified34841657Hub genes identified included Rbx1, Fbxl3, Fbxo27, Fbxl7, Fbxo4, Cul3, Cul2, Klhl5, Fbxl16, and Klhl42.
MyopiaFbxl3ExtractedNot specified34841657Hub genes identified included Rbx1, Fbxl3, Fbxo27, Fbxl7, Fbxo4, Cul3, Cul2, Klhl5, Fbxl16, and Klhl42.
MyopiaFbxo27ExtractedNot specified34841657Hub genes identified included Rbx1, Fbxl3, Fbxo27, Fbxl7, Fbxo4, Cul3, Cul2, Klhl5, Fbxl16, and Klhl42.
MyopiaFbxl7ExtractedNot specified34841657Hub genes identified included Rbx1, Fbxl3, Fbxo27, Fbxl7, Fbxo4, Cul3, Cul2, Klhl5, Fbxl16, and Klhl42.
MyopiaFbxo4ExtractedNot specified34841657Hub genes identified included Rbx1, Fbxl3, Fbxo27, Fbxl7, Fbxo4, Cul3, Cul2, Klhl5, Fbxl16, and Klhl42.
MyopiaCul3ExtractedNot specified34841657Hub genes identified included Rbx1, Fbxl3, Fbxo27, Fbxl7, Fbxo4, Cul3, Cul2, Klhl5, Fbxl16, and Klhl42.
MyopiaCul2ExtractedNot specified34841657Hub genes identified included Rbx1, Fbxl3, Fbxo27, Fbxl7, Fbxo4, Cul3, Cul2, Klhl5, Fbxl16, and Klhl42.
MyopiaKlhl5ExtractedNot specified34841657Hub genes identified included Rbx1, Fbxl3, Fbxo27, Fbxl7, Fbxo4, Cul3, Cul2, Klhl5, Fbxl16, and Klhl42.
MyopiaFbxl16ExtractedNot specified34841657Hub genes identified included Rbx1, Fbxl3, Fbxo27, Fbxl7, Fbxo4, Cul3, Cul2, Klhl5, Fbxl16, and Klhl42.
MyopiaKlhl42ExtractedNot specified34841657Hub genes identified included Rbx1, Fbxl3, Fbxo27, Fbxl7, Fbxo4, Cul3, Cul2, Klhl5, Fbxl16, and Klhl42.
MyopiaPDE1CExtractedNot specified34241624Candidate gene PDE1C was suggested from linkage peak on chromosome 7p15.2-14.2.
MyopiaVIPR2ExtractedNot specified37795829, 32166996SNPs in VIPR2 were associated with high myopia.
MyopiaZMAT4ExtractedNot specified37795829, 32166996SNPs in ZMAT4 were associated with high myopia.
MyopiaCCDC66ExtractedNot specified39585677Mutations in CCDC66 were reported to cause high myopia.
MyopiaCOL1A1ExtractedNot specified39585677COL1A1 involvement was noted along with glycine-associated connective tissue changes.
MyopiaHIF1AExtractedNot specified35783515HIF-1alpha was involved in hypoxia-related changes in form-deprivation myopia.
MyopiaMMP2ExtractedNot specified35783515MMP-2 was part of the extracellular matrix remodeling response in myopia.
MyopiaTIMP2ExtractedNot specified35783515TIMP-2 expression changes were observed in scleral remodeling.
MyopiaSERPINC1ExtractedNot specified36674802Antithrombin-III was differentially expressed in the retina.
MyopiaFGGExtractedNot specified36674802Fibrinogen gamma chain was differentially expressed in the retina.
MyopiaFGBExtractedNot specified36674802Fibrinogen beta chain was differentially expressed in the retina.
MyopiaDLGAP1ExtractedNot specified33824778Candidate gene DLGAP1 was identified on the MYP2 locus.
MyopiaEMILIN2ExtractedNot specified33824778Candidate gene EMILIN2 was identified on the MYP2 locus.
MyopiaMYOM1ExtractedNot specified33824778Candidate gene MYOM1 was identified on the MYP2 locus.
MyopiaACSL4Verified39986367, 40520556In the first context, miR-224-3p was found to target ACSL4, which was associated with ferroptosis and inflammation in high myopia cataract (HMC) patients. The second context shows that quercetin-loaded exosomes prevent myopia by targeting ferroptosis through GRP78-ACSL4 interactions in scleral fibroblasts. Both studies link ACSL4 to myopia-related processes.
MyopiaADAMTS10Verified34605977, 34057920PMID 34605977: [New variant in ADAMTS10 gene in 30-year-old patient with myopia and narrow-angle glaucoma]. PMID 34057920: A 9-year-old boy had bilateral narrow-angle glaucoma with lens subluxation, elevated intraocular pressure, and severe myopia since early childhood... confirmed a homozygous familial variant of the ADAMTS10 gene identified by carrier gene testing.
MyopiaADAMTS17Verified37206179, 35496767, 36698805, 40144770, 34057920The three affected siblings presented with ... high myopia ... Genetic analysis verified a homozygous missense mutation ... in ADAMTS17 ... (PMID: 37206179). The patient ... had high myopia ... with compound heterozygous variants in ADAMTS17 ... (PMID: 35496767). Case presentation: ... high myopia ... with compound heterozygous variants ... in ADAMTS17 ... (PMID: 36698805).
MyopiaADAMTS18Verified39902400, 40946907, 38249507In PMID: 39902400, the patient had mild myopia. In PMID: 40946907, patients presented with myopia, and variants in ADAMTS18 were identified. In PMID: 38249507, myopic chorioretinal atrophy is mentioned in the context of ADAMTS18-related ASD.
MyopiaADAMTSL1Verified34222226, 34500691In the first study (PMID: 34222226), the abstract mentions that a mutation in ADAMTSL1 (c.G848A (p.G283D)) was detected in a family with high myopia (HM). The second study (PMID: 34500691) states that a C-mannosylation-defective gene mutation was identified in humans as the disease-associated variant affecting a C-mannosylation motif of W-x-x-W of ADAMTSL1, which suggests the involvement of defects in protein C-mannosylation in human diseases such as myopia.
MyopiaADAMTSL4Verified36089008, 38190127The primary phenotypes caused by ADAMTSL4 variants include EL, EP, poor pupillary dilation, and axial elongation. Highly varying phenotypes including glaucoma, high myopia retinapathy, and poor vision and so on may be the secondary impairments. All these secondary impairments may be improved if proper clinical interventions are implemented in time. Variants in ADAMTSL4 (1.3%)... cause EL. The axial length (AL) and refractive error increased more rapidly with age in preschool EL children than normal children, and the increased rate of AL was slower in patients with surgery than those without surgery;... worse vision and earlier onset age were observed in patients with non-FBN1 variants (all P < 0.05).
MyopiaAGKVerified29346494Gene-based analyses implicated 21 novel candidate myopia genes (ADAMTS18, ADAMTS2, ADAMTSL4, AGK, ALDH18A1, ASXL1, COL4A1, COL9A2, ERBB3, FBN1, GJA1, GNPTG, IFIH1, KIF11, LTBP2, OCA2, POLR3B, POMT1, PTPN11, TFAP2A, ZNF469).
MyopiaAKT1Verified34001063, 40216914, 36242032, 34285659, 36113118, 40864167The PI3K/AKT/mTOR signaling pathway is involved in insulin-mediated regulation of pathological myopia-related factors in retinal pigment epithelial cells. Insulin activates the phosphorylation of AKT and mTOR, which is suppressed by the PI3K inhibitor LY294002. The effect of insulin on PM-related proteins is restored with LY294002. The PI3K/Akt signaling pathway is also involved in scleral remodeling in experimental myopia, with changes in AKT2 levels and pathway activation. Inhibitors of the AKT pathway, such as Miransertib, are used in the treatment of Proteus Syndrome, which includes myopia as a symptom. FJ and PV extracts inhibit myopia progression by suppressing AKT-mediated inflammatory reactions. Diacerein inhibits myopia progression by attenuating the phosphorylation of AKT and NF-kappaB pathways. ZC3H11A mutations cause high myopia by triggering PI3K-AKT and NF-kappaB-mediated signaling pathways.
MyopiaANKRD11Verified37964495Out of the 40 participants with pathogenic or likely pathogenic variants, ... myopia was reported in 6 (15.0%) participants, respectively. ... variants in ANKRD11 play a role in abnormal development of the visual system.
MyopiaARID1BVerified37355654, 38790056The patient had excessive eoHM... The genetic assessment revealed that the patient carries a de novo heterozygous frameshift insertion variant in the ARID1B c.3981dup (p.Glu1328ArgfsTer5)... RT-qPCR showed that mRNA expression of the ARID1B gene in the proband was approximately 30% lower... variant was pathogenic... association of eoHM with variant in ARID1B gene.
MyopiaARR3Verified36769483, 40134578, 33482870, 38958970, 39420435, 37795829, 34966409, 37268727, 38517428, 40013354The ARR3 gene (cone arrestin, OMIM: 301770) has gained significant attention as a pivotal factor in the etiology of myopia, particularly early-onset high myopia (eoHM).
MyopiaASPHVerified35567543, 37133842, 30600741In 20% of our high myopic study population, WES using an eye gene panel enabled us to diagnose the genetic cause for this disorder...Pathogenic variants were identified in...other genes (ASPH and CNNM4). Eye genes known to cause retinal dystrophy, developmental or syndromic disorders can cause high myopia without apparent clinical features of other pathology. Additionally, a novel splicing homozygous pathogenic variant (PV) (c.1765-1G>A) of the ASPH gene...detected in a Brazilian patient with clinical features including high myopia. Loss of ciliary zonule protein hydroxylation...as a predicted consequence of biallelic ASPH variation, leading to lens instability and high myopia.
MyopiaASXL1Verified38790056, 36751885, 29346494PMID 36751885: 'Bohring-Opitz syndrome (BOS) is a rare genetic condition caused by pathogenic variants in ASXL1, which is a gene involved in chromatin regulation. BOS is characterized by ... severe myopia, ...' and PMID 29346494: '... gene-based analyses implicated 21 novel candidate myopia genes ... including ASXL1 ...'. These extracts directly associate ASXL1 with myopia in both syndromic contexts.
MyopiaATF6Verified36216837, 37746069, 40520556Pharmacological inhibition of both PERK and ATF6 suppressed myopia progression, which was confirmed by knocking down above two genes via CRISPR/Cas9 system. ... BPA administration activated scleral PERK and ATF6 pathways, and 4-PBA eye drops attenuated ER stress response and suppressed myopia progression. ... Exo-Que inhibited the activation of the IRE1-XBP1, PERK-eIF2, and ATF6 pathways, alleviating endoplasmic reticulum stress.
MyopiaATP6V0A2Verified30474613Our patients do not have gross structural brain defects besides microcephaly, strabismus, myopia, and growth or developmental delay.
MyopiaATP6V1B2Verified40330779The proteomic analysis revealed a low abundance of ATP6V1B2 in the myopic samples.
MyopiaBBS2Verified36672825Patient 3 had Bardet-Biedl syndrome and carried a homozygous mutation in BBS2 (c.209G>A; p.Ser70Asn). Her clinical findings included global developmental delay, disproportionate short stature, myopia, retinitis pigmentosa, obesity, pyometra with vaginal atresia, bilateral hydronephrosis with ureteropelvic junction obstruction, bilateral genu valgus, post-axial polydactyly feet, and small and thin fingernails and toenails, tooth agenesis, microdontia, taurodontism, and impaired dentin formation.
MyopiaBMP4Verified34926457, 39774722, 35022715, 32452548PMID 34926457 reports that BMP4 truncation mutations contribute to a novel phenotype of pathologic myopia in eight patients from four Chinese families. The study found that heterozygous BMP4 truncations resulted in pathologic myopia rather than microphthalmia. Additionally, PMID 35022715 identifies BMP4 as a novel candidate gene associated with refractive error, including myopia. These findings support the association of BMP4 with myopia.
MyopiaBRD4Verified20301283Other frequent findings include cardiac septal defects, gastrointestinal dysfunction, hearing loss, myopia, and cryptorchidism or hypoplastic genitalia. DIAGNOSIS/TESTING: The diagnosis of CdLS is established in a proband with suggestive clinical features and/or by identification of a heterozygous pathogenic variant in NIPBL, RAD21, SMC3, or BRD4, or a hemizygous pathogenic variant in HDAC8 or SMC1A by molecular genetic testing.
MyopiaCABP4Verified33369259, 39322243In Saudi Arabia, a total of 24 patients with CSNB were identified... CABP4 accounted for the majority of cases (13) and were associated with high myopia in the former and hyperopia in the latter.
MyopiaCACNA1FVerified38474172, 33668843, 39079892Myopia was common in the CACNA1F-retinopathy study (n = 15; mean: -6.32 diopters). Additionally, in a multicentre study on CSNB, patients with CACNA1F variants showed significant myopic predicted SER at birth (-3.076D) and progression of myopia per year (-0.254D). These findings establish a clear association between CACNA1F and myopia.
MyopiaCAMK2GVerified37644183Furthermore, SFRP-1 elevates the intracellular Ca2+ concentration and activates Ca2+/calmodulin-dependent protein kinase II (CaMKII) signaling in a simian choroidal vascular endothelial cell line, and elicits vascular endothelial cell dysfunction.
MyopiaCBSVerified35658358, 40299504, 32245022, 34342182The major clinical manifestations were marfanoid features, lens dislocation and (or) myopia, developmental delay, osteoporosis, and cardiovascular diseases. ... The study was carried out to investigate a Pakistani family presenting bilateral congenital cataract with symptoms of classical homocystinuria ... A missense allelic variant (NM_000071.3: c.253G>A) of the CBS gene was revealed ... This variant was reported first time in association with congenital cataract instead of ectopia lentis. Congenital cataract was developed secondarily in these patients and provided a clue for the early diagnosis of metabolic disorders like homocystinuria to prevent further complications and morbidity.
MyopiaCLDN19Verified39206762The patient exhibited high myopia... We identified a homozygous missense variant, c.59G>A p.Gly20Asp, in the CLDN19 gene as the cause of renal and ocular manifestations.
MyopiaCNGA3Verified40013354, 33168939, 35456423Day-blind sheep are significantly more myopic than both Afec-Assaf and WT Awassi controls. ... Day-blind sheep were found to exhibit myopia and increased vitreous chamber depth, providing a naturally occurring large animal model of myopia. ... Fundus examination and optical coherence tomography (OCT) imaging revealed myopia, thin retina, retinal pigment epithelial cells loss at fovea/perifovea, and macular atrophy.
MyopiaCNGB3Verified40013354, 33560291, 36980963, 40935931The prevalence of refractive errors was high and broadly distributed. Astigmatic refractive errors were frequent but did not seem to increase with age. Results presented here support the theory that chromatic cues and cone photoreceptors may play a role in emmetropization in humans but that it is not essential. (PMID: 33560291); In the Danish study, progressive deterioration of BCVA only attributable to achromatopsia was found in three of 58 patients. Progressive phenotype was seen with variants in CNGB3 and PDE6C. The results indicate that myopia could be more frequently occurring with variants in GNAT2, PDE6C and PDE6H and support the evidence that achromatopsia is a predominantly stationary condition with respect to BCVA. (PMID: 36980963); In the natural course study, CNGA3, CNGB3, and CRB1 were associated with high hypermetropia, remaining high with time in CRB1. In contrast, Congenital Stationary Night Blindness (CSNB) and Blue Cone Monochromacy (BCM) demonstrated high myopia, worsening over time in CSNB, with an increasing rate in high myopia from 51.5% to 69.7% from first to last visit. (PMID: 40935931)
MyopiaCOL11A2Verified36140739, 33356723, 34405586Stickler syndrome is a connective tissue disorder characterized by ocular, skeletal, orofacial and auditory manifestations. Its main symptoms are high myopia, retinal detachment, joint hypermobility, early osteoarthritis, cleft palate, midfacial hypoplasia, micrognathia and hearing loss. Large phenotypical variability is apparent and partly explained by the underlying genetic heterogeneity, including collagen genes (COL2A1, COL11A1, COL11A2, COL9A1, COL9A2, COL9A3) and non-collagen genes (BMP4, LRP2, LOXL3).
MyopiaCOL18A1Verified34680907, 35693012, 33238767, 34249907, 32700429, 37269665, 35567543, 40725504, 36994995, 38450462Knobloch syndrome is an inherited disorder characterized by high myopia, retinal detachment, and occipital defects. Disease-causing mutations have been identified in the COL18A1 gene. (PMID: 34680907); Knobloch syndrome is a rare collagenopathy characterized by severe early onset myopia, retinal detachment, and occipital encephalocele with various additional manifestations due to biallelic changes in the COL18A1 gene. (PMID: 35693012); High myopia with alopecia areata in the cranial midline could be treated as an early diagnostic clue for ophthalmologists to consider the two kinds of rare diseases. (PMID: 34249907); Knobloch syndrome is an autosomal recessive disorder characterized by high myopia, retinal detachment, and occipital skull defects. Mutations in the COL18A1 gene have been identified to cause KNO1. (PMID: 37269665); The causative genes linked to the Knobloch... are COL18A1... (PMID: 40725504); Knobloch syndrome - a rare collagenopathy, revealing peripheral avascular retina. (PMID: 36994995); The results of the conducted molecular genetic testing expand our understanding of the mutation spectrum in the genes of children with both isolated cases of ophthalmic pathology, as well as syndromic pathology. (PMID: 38450462)
MyopiaCOL2A1Verified32756486, 38073514, 33295219, 38788144, 32196734, 32427345, 37107605, 32071555The probands presented with high myopia and retinal detachment, and pathogenic mutations were detected in 35 (83%) probands, with 27 (64%) having COL2A1 mutations. (PMID: 32756486) Additionally, mutations in COL2A1 were identified in families with high myopia, including novel and reported mutations, with myopia being a common phenotype. (PMID: 38073514, 33295219, 38788144, 32196734, 32427345, 37107605, 32071555)
MyopiaCOL4A1Verified34302427, 34424299RNA-seq and qRT-PCR revealed the transcription decrease in COL1A1, COL2A1, COL4A1, FN1 and LAMA1 in the KO cells. ... Overall, the SLC39A5 depletion-induced zinc deficiency destabilized Smad proteins, which inhibited the TGF-beta signalling and downstream ECM synthesis, thus contributing to the pathogenesis of high myopia.
MyopiaCOL4A3Verified36579937, 37578539In the eye, KCTD1 and its downstream targets, TFAP2, and the collagen IV alpha3 and alpha4 chains localised to the cornea and near the retinal amacrine cells. ... COL4A3 and COL4A4 knockout mice had myopia.
MyopiaCOL4A4Verified36579937, 35022715, 32328353, 37578539PMID 36579937: 'In the eye, KCTD1 and its downstream targets, TFAP2, and the collagen IV alpha3 and alpha4 chains localised to the cornea and near the retinal amacrine cells... COL4A3 and COL4A4 knockout mice had myopia.' PMID 35022715: 'COL4A4... as a novel candidate gene associated with refractive error.'
MyopiaCOL4A5Verified37191617Hemizygous mutations in COL4A5, NYX, and CACNA1F were detected in this study.
MyopiaCOL5A1Verified37884635, 40175531, 38450462, 36516480In patients with isolated cases of ophthalmic pathology (peripheral retinal degenerations and high myopia) with a confirmed genetic diagnosis, mutations in the COL2A1 gene were detected in 77.4% of cases, and in the COL11A1 gene - in 22.6% of cases. ... mutations in the genes COL5A1, COL18A1, VPS13B, FBN1, VCAN were detected in 55.6% of cases. ... The results of the conducted molecular genetic testing expand our understanding of the mutation spectrum in the genes of children with both isolated cases of ophthalmic pathology, as well as syndromic pathology. ... Four pathogenic gene mutations were identified according to ACMG guidelines: ... c.G1291A in COL5A1, and c.G10242T in ZNF469. ... 7 patients (25.0%, 7/28) carried pathogenic variants in seven candidate genes for ocular disease (POLA1, TMEM231, HK1, GSN, COL5A1, CRYBB3, and WDR), which were identified as potentially pathogenic in Chinese eoHM patients for the first time. ... UVA downregulated Smad3 protein and reduced TGF-beta-induced collagen I protein production following UVA exposure in HSF.
MyopiaCOL9A1Verified35885918, 33951325, 33356723, 36140739High myopia is near-universal, and sensorineural hearing loss is very common in patients with variants in genes for type IX or XI collagen, although hearing appears spared in the LRP2 and LOXL3 patients and is variable in GZF1. ... COL9A1 (homozygous) in two. ... Both subjects were homozygous for the mutation c.1332del in COL9A2. Their parents were heterozygous for the same mutation. The boys demonstrated reduced visual acuity, vitreous changes and myopia.
MyopiaCOL9A2Verified33356723, 35885918, 34405586, 33570243The boys demonstrated reduced visual acuity, vitreous changes and myopia. ... High myopia is near-universal, and sensorineural hearing loss is very common in patients with variants in genes for type IX or XI collagen, although hearing appears spared in the LRP2 and LOXL3 patients and is variable in GZF1.
MyopiaCOL9A3Verified33570243, 33633367, 35885918, 33356723, 34405586, 36140739The clinical features included severe sensorineural hearing loss, high myopia, vitreoretinal degeneration, and early-onset arthropathy of the lower limbs. (PMID: 33570243); Variants in COL9A3 have not previously been reported to cause vitreoretinal degeneration and/or retinal detachments. (PMID: 33633367); High myopia is near-universal, and sensorineural hearing loss is very common in patients with variants in genes for type IX or XI collagen, although hearing appears spared in the LRP2 and LOXL3 patients and is variable in GZF1. (PMID: 35885918)
MyopiaCPSF1Verified40920702, 37191617, 35002215, 36964802In PMID: 40920702, the study found a likely pathogenic variant (NM_013291: c.799C > G) in CPSF1 in 4 out of 83 probands with early-onset high myopia (eo-HM). The variant was confirmed by Sanger sequencing and showed low allele frequency in population databases. In PMID: 37191617, CPSF1 was identified as one of the genes associated with eoHM, with mutations detected in 24 families. In PMID: 35002215, a variant (c.415C>T, p.P139S) in CPSF1 was found in a patient with nonsyndromic high myopia. In PMID: 36964802, CPSF1 was found to have potentially pathogenic variants, including c.1270G > T/p.V424L and c.3980C > T/p.S1327L, in families with nonsyndromic early-onset high myopia.
MyopiaCRIPTVerified27250922Direct quote: 'Additional clinical features included high myopia...'
MyopiaCRYAAVerified32010934, 32439395This is the case of a congenital lamellar cataract phenotype with myopia associated with the mutation of Arg12Cys (p.R12C) in CRYAA. Our finding confirms the high rate of mutations at this dinucleotide. In addition, these results demonstrate a myopia susceptibility locus in this region, which might also be associated with the mutation in CRYAA.
MyopiaCRYABVerified40175531Thirteen hub genes, including RPGR, COL5A1, CRYAB, and FBN1, were crucial for the pathogenesis of myopia.
MyopiaCRYBB2Verified40330779The top three downregulated proteins were RPS5 (FC = -2.41, p=0.004), ACOT7 (FC=-2.15, p = 0.04) and CRYBB2 (FC = -2.14, p = 0.05).
MyopiaCRYGDVerified40449652, 35410372GJA3 variants were often associated with high myopia, and CRYGC variants were often linked to microcornea or microphthalmia; 4) A predominance of CRYAA, LIM2 and MIP variants involve arginine to cysteine changes, and CRYGD variants involve proline to threonine changes
MyopiaCTNNB1Verified35586671, 33983548, 40810225, 38430983, 40933557, 36685896In the study (PMID: 35586671), CTNNB1 was identified as a transcription factor involved in myopia-related functions and pathways. Additionally, in PMID: 38430983, CTNNB1 was found to be one of the hub genes in the Rap1 signaling pathway in the ciliary body associated with myopia. Furthermore, in PMID: 36685896, CTNNB1 was listed as a target of differentially methylated miRNAs associated with high myopia.
MyopiaDNAJC21Verified35464845, 38408162, 38682429In the first abstract, the patient presented with 'high myopia' and the variants in DNAJC21 were identified through whole-genome sequencing. In the second abstract, the girl had 'myopia' as part of her clinical features. Both cases link DNAJC21 variants to myopia.
MyopiaDSEVerified31655143, 32130795A 32 year old man with ... myopia ... [and] a homozygous pathogenic DSE variant ... The second patient has a phenotype consistent with previously reported cases of DSE associated musculocontractural EDS. ... supports previous suggestions that patients with DSE associated mcEDS present with a milder phenotype compared to those with CHST14 mutations.
MyopiaDYRK1AVerified32838606Reported ocular features include deep-set eyes, myopia, and strabismus. We present a case of DYRK1A-related intellectual disability syndrome with ocular findings of albinism...
MyopiaEFEMP1Verified36891459, 38101653, 39607017, 40640104, 40111354, 31792352, 39367272, 35946471, 32006683, 39067805PMID 36891459: 'EFEMP1 may be involved in the regulation of choroidal thickness in myopia patients.'; PMID 38101653: 'adjusting EFEMP1 concentrations could potentially serve as a viable approach to prevent and treat myopia'; PMID 39607017: 'efemp1 modification changed the expression of efemp1... and altered retinal function'; PMID 40640104: 'EFEMP1 is associated with myopia'; PMID 40111354: 'Targeting EFEMP1 may offer a novel therapeutic strategy for the prevention and treatment of myopia'; PMID 31792352: 'EFEMP1 causes Doyne honeycomb degeneration of the retina'; PMID 39367272: 'EFEMP1 variants can cause a severe and distinct subtype of heritable connective tissue disorder with myopia'; PMID 35946471: 'association of EFEMP1 with juvenile-onset open angle glaucoma in a patient with concomitant COL11A1-related Stickler syndrome'; PMID 32006683: 'homozygous missense variant in the EFEMP1 gene... associated with myopia'; PMID 39067805: 'efemp1 modification changed the expression... and altered retinal function in dark-reared zebrafish model for myopia studies.
MyopiaERBB3Verified38790056, 37964886, 29346494In the first abstract (PMID: 38790056), the STRING protein-protein interactions (PPIs) network analysis revealed that the ARID1A protein interacts with the high myopia gene-related proteins FGFR3, ASXL1, ERBB3, and SOX4. In the third abstract (PMID: 29346494), ERBB3 is listed as one of the 21 novel candidate myopia genes identified through pathway analysis and GWAS comparisons, which are associated with syndromic and nonsyndromic myopia.
MyopiaEXOSC2Verified26843489Three individuals from two unrelated German families presented with a novel Mendelian disorder encompassing childhood myopia...
MyopiaFBN1Verified39421111, 37245000, 32679894In the study by PMID: 32679894, it is stated that patients with cys-missense variants in FBN1 showed earlier onset of myopia (p = 0.02) compared to those with other missense variants. Additionally, missense variants in FBN1 correlated with a higher prevalence of ectopia lentis (p = 0.002) and earlier onset of pulmonary artery dilatation (p = 0.03) than nonsense/frameshift variants.
MyopiaFBN2Verified37962692, 32534992In the first abstract, the father had 'high myopia' and a heterozygous variant in FBN2 was identified. In the second abstract, the patient had 'myopia' and carried a variant in FBN2. Both studies associate FBN2 variants with myopia.
MyopiaFGFR2Verified36124135, 38012225, 38909058The Fibroblast growth factor-2 (FGF-2) was reported involved in scleral remodeling in myopia models. ... the mRNA expression of scleral Fgf-2, Fgfr1, Fgfr2, Fgfr3, and Fgfr4 was increased in mature SFs. Notably, exogenous FGF-2 showed increased cell proliferation and led to decreased expression of alpha-SMA, MMP2, and collagen 1 in mature SFs.
MyopiaFGFR3Verified38059098, 38790056, 38012225, 36124135Achondroplasia is an autosomal dominant congenital disorder of endochondral ossification, induced by abnormal activity of fibroblast growth factor receptor 3. ... high myopia ... FGFR3, ASXL1, ERBB3, and SOX4
MyopiaFN1Verified32260532, 40122360, 34302427The study in PMID 32260532 shows that atropine and 7-methyl-xanthine inhibited fibronectin production in choroidal fibroblasts, linking FN1 to myopia development. Additionally, PMID 40122360 discusses fibronectin's role in improving biocompatibility in myopia treatments, further supporting its association with myopia.
MyopiaFZD4Verified38706142, 38243264, 38315492Most (N = 33/35, 94%) were classified as not visually impaired. Despite unilateral visual loss present in some, they did not meet the criteria of visual impairment according to the WHO classification. Two study patients (N = 2/35, 6%) had severe visual impairment. The most common FEVR stage in study patient's eyes (N = 28/70 eyes, 40%) was FEVR stage 1, that is, avascular periphery or abnormal vascularisation. Most of FZD4-variant-positive study patient's eyes (N = 31/50 eyes, 62%) were myopic. (PMID: 38706142) Additionally, exome sequencing identified 21 potential pathogenic variants of 13 genes in 20 of 75 (26.7%) probands, including genes for FEVR (FZD4, LRP5, and TSPAN12; 5/20). (PMID: 38243264)
MyopiaFZD5Verified33633439, 38154732, 34926457Conclusions: The data presented in this study confirmed that variants in FZD5, not only frameshift variants but also missense variants, are a common cause of uveal coloboma. In addition, ICH, ODH, and high myopia may be variant phenotypes that are frequently associated with FZD5 variants. (PMID: 33633439) and 'Mutations in FRIZZLED5 (FZD5) have been associated with microphthalmia, coloboma, and, more recently, high myopia.' (PMID: 38154732)
MyopiaGJA8Verified38315492, 34283211In the genotype-phenotype association analysis, 60% (201/335) of suspected msHM cases were recalled and 25 patients (12.4%) received a definitive genetic diagnosis. Pathogenic variants were distributed in 18 msHM-related diseases, mainly involving retinal dystrophy genes (e.g. TRPM1, CACNA1F, and FZD4), connective tissue disease genes (e.g. FBN1 and COL2A1), corne2al or lens development genes (HSF4, GJA8, and MIP), and other genes (TEK).
MyopiaGLRA2Verified35396272, 40227176PMID 35396272: 'GLRA2 was identified as a novel HM-causing gene.' and 'Variants c.458G>A and c.539C>T altered the localisation of GlyRalpha2 on the cell membrane and decreased agonist sensitivity.' PMID 40227176: 'Variants in the GLRA2 gene have been linked to early-onset and nonsyndromic high myopia with a X-linked inheritance.' and 'The GLRA2-eoHM relationship was classified as 'strong'.'
MyopiaGNAT1Verified40013354, 34064005PMID 40013354 states that pathogenic variants in genes encoding phototransduction proteins, including GNAT1, can give rise to significant vision impairment, accounting for a substantial portion of inherited retinal disease. Additionally, PMID 34064005 notes that GNAT1 mutations are associated with Riggs type CSNB, which presents mild myopia.
MyopiaGNAT2Verified40013354, 32049342, 36980963, 38278208In Danish Achromatopsia Patients, progressive deterioration of BCVA only attributable to achromatopsia was found in three of 58 patients. Progressive phenotype was seen with variants in CNGB3 and PDE6C. The results indicate that myopia could be more frequently occurring with variants in GNAT2, PDE6C and PDE6H.
MyopiaGNB3Verified40013354, 33369259PMID 40013354 mentions that some conditions also entail myopia. PMID 33369259 states that GNB3 is associated with CSNB with dysfunction of the phototransduction (Riggs type) and that cCSNB is associated with high myopia.
MyopiaGNPTGVerified29346494Gene-based analyses implicated 21 novel candidate myopia genes (..., GNPTG, ...).
MyopiaGPR143Verified37749571, 38243264In the first study (PMID: 37749571), a missense variant c.98G > T (p.Cys33Phe) of GPR143 gene was identified in a pedigree with X-linked recessive hereditary eye disease and early-onset high myopia. The variant was classified as pathogenic or likely pathogenic according to ACMG guidelines. In the second study (PMID: 38243264), GPR143 was listed among 13 genes with potential pathogenic variants identified in 20 of 75 probands with unilateral high myopia.
MyopiaGPR179Verified36613663, 36669906, 38243264, 33691579, 40766553Mutations in GPR179 are one of the most common causes of autosomal recessive complete congenital stationary night blindness (cCSNB)... associated with high myopia. ... the lack of Gpr179 and the subsequent impaired ON-pathway could lead to myopic features in a mouse model of cCSNB. ... identified 21 potential pathogenic variants of 13 genes in 20 of 75 (26.7%) probands, including ... GPR179 ...
MyopiaGRK1Verified40013354, 38430983In the ciliary body, two crucial genes, Grk1 and Pde6a, which are mainly expressed in retinal photoreceptors, were enriched in visual perception in the ciliary body in functional analysis and were verified to be expressed in the ciliary body. These findings indicate the molecular pathogenetic role of the ciliary body in myopia and provide new insights into the underlying mechanism of myopia development.
MyopiaGRM6Verified36669906, 37191617, 33691579, 40766553Complete congenital stationary night blindness (cCSNB) in humans and animal models represents an ON-bipolar cell signal transmission defect and is also associated with high myopia. ... Mutations in NYX, GRM6, TRPM1, GPR179 , and LRIT3 lead to this condition. ... gene augmentation by expressing LRIT3 in the rods of mature Lrit3 -/- retinas restores function and scotopic visual acuity, and when expressed on cones, improves both photopic and scotopic visual acuity.
MyopiaGZF1Verified33009817, 35885918, 28475863Two patients presenting hip dislocation, scoliosis and severe myopia... (PMID: 33009817); High myopia is near-universal... (PMID: 35885918); ... severe myopia... (PMID: 28475863). All three studies associate GZF1 variants with myopia.
MyopiaHADHAVerified33107778LCHADD causes retinopathy associated with low vision, visual field defects, nyctalopia and myopia. We report a retrospective long-term single-center study of 6 LCHADD patients... All carried HADHA variants...
MyopiaHDAC8Verified20301283, 38348454The abstract from PMID: 20301283 mentions Cornelia de Lange syndrome (CdLS) and states that individuals with CdLS may exhibit myopia. It also specifies that HDAC8-CdLS is inherited in an X-linked manner. This indicates that HDAC8 is associated with CdLS, which includes myopia as one of its manifestations.
MyopiaHS6ST2Verified30471091The c.916G>C variant affects the HS6ST2 substrate binding site, and its effect was considered "deleterious" by in-silico tools. An in-vitro enzymatic assay showed that the HS6ST2 mutant isoform had significantly reduced sulphotransferase activity. Taken together, the results suggest that mutant HS6ST2 is possibly involved in the development of myopia and cognitive impairment, characteristics of the probands reported here.
MyopiaHSPG2Verified33344623, 36123715, 38724173PMID 33344623 mentions 'severe ophthalmological problems such as high myopia... and mutations in HSPG2... contributing factors to her unique findings.' Additionally, PMID 36123715 links HSPG2 mutations to developmental dysplasia of the hip and suggests HSPG2 mutations may contribute to myopia-related phenotypes.
MyopiaIFT43Verified26892345, 29896747The deleted region contains 65 protein-coding genes, including the ciliary gene IFT43. ... demonstrating defective retrograde ciliary transport. This could suggest a ciliary defect in the pathogenesis of this disorder. (PMID: 26892345) and ... the patient has carried a homozygous c.1A>G (p.M1V) mutation of the IFT43 gene ... high-degree myopia ... (PMID: 29896747)
MyopiaIGF1Verified32025377, 35862416, 35647299, 34713181, 34001063, 32495406The SNP rs2162679 in IGF1 was associated with myopia in a young Chinese population. The G allele in the SNP rs2162679 may protect against myopia. (PMID: 32025377); Meta-analysis of updated data reveals that the G allele of the IGF1 rs2162679 SNP is a potential protective factor for any myopia. (PMID: 35862416)
MyopiaKDM5CVerified40716584, 36672956A potentially pathogenic KDM5C variant in X-linked high myopia. We propose that this report represents a potential correlation of a KDM5C variant with high myopia, which provides a new understanding of X-linked high myopia and expands the KDM5C variant spectrum.
MyopiaKIF11Verified39596324, 39004865In the preschool group, 32.4% of the isolated IRDs were related to forms of Leber's congenital amaurosis (most frequent were RPE65 (11%) and CEP290 (8.2%)), 31.5% were related to stationary IRDs, 15.1% were related to macular dystrophies (ABCA4, BEST1, PRPH2, PROM1), and 8.2% to rod-cone dystrophies (RPGR, RPB3, RP2, PDE6A). All rod-cone dystrophies (RCDs) were subjectively asymptomatic at the time of genetic diagnosis. At schoolage, 41% were attributed to cone-dominated disease (34% ABCA4), 10.3% to BEST1, and 10.3% to RCDs (RP2, PRPF3, RPGR; IMPG2, PDE6B, CNGA1, MFRP, RP1). Ciliopathies were the most common syndromic IRDs (preschool 37%; schoolchildren 45.1%), with variants in USH2A, CEP290 (5.6% each), CDH23, BBS1, and BBS10 (3.7% each) being the most frequent in preschoolers, and USH2A (11.7%), BBS10 (7.8%), CEP290, CDHR23, CLRN1, and ICQB1 (3.9% each) being the most frequent in syndromic schoolkids. Vitreoretinal syndromic IRDs accounted for 29.6% (preschool: COL2A1, COL11A1, NDP (5.6% each)) and 23.5% (schoolage: COL2A1, KIF11 (9.8% each)), metabolic IRDs for 9.4% (OAT, HADHA, MMACHD, PMM2) and 3.9% (OAT, HADHA), mitochondriopathies for 3.7% and 7.8%, and syndromic albinism accounted for 5.6% and 3.9%, respectively.
MyopiaLAMA1Verified35616092, 35535551, 34249907, 34302427, 35671446All four had myopia. ... detailed retinal manifestations in two unrelated families. ... High myopia with alopecia areata in the cranial midline could be treated as an early diagnostic clue for ophthalmologists to consider the two kinds of rare diseases. ... early onset high myopia with midline alopecia areata could be caused not only by mutations of the COL18A1 gene but also by mutations in the LAMA1 gene.
MyopiaLAMB2Verified37678612, 40725504, 36829142, 37578539PMID 37678612 describes patients with a novel homozygous LAMB2 variant presenting with early-onset myopia. The mean refraction was -7.9 diopters, indicating significant myopia. PMID 40725504 links LAMB2 to non-syndromic high myopia with retinal detachment risk. PMID 36829142 reports a LAMB2 mutation case with high myopia as an ocular feature. PMID 37578539 associates LAMB2 with myopia in genetic FSGS contexts.
MyopiaLCA5Verified40091069, 39766915In PMID 40091069, LCA5 (OR = 9.27, P = 0.0089) was found to harbor an excess number of nonsynonymous variants in patients with slow progression of high myopia. In PMID 39766915, a novel homozygous variant (c.720+1G>T) and a reported variant (c.1495+1G>A) in LCA5 were identified in families with severe IRD phenotype, indicating its role in retinal dystrophy and myopia.
MyopiaLOXVerified34698138The mRNA expressions of ECM modulators and ER stress-related genes were also altered with increasing AL length (down-regulation of LOX...). The findings presented herein suggest that ... in myopic eyes.
MyopiaLOXL3Verified38957076, 36917121, 36610533, 35885918PMID 38957076 reports a case of a young boy with early onset high myopia (eoHM) due to a homozygous LOXL3 pathogenic variant. PMID 36917121 identifies biallelic LOXL3 variants in nine families with early-onset high myopia (MYP28), providing evidence for LOXL3's role in this condition. PMID 36610533 describes a mouse model with LOXL3 mutation leading to severe myopia as part of Stickler syndrome. These studies collectively support LOXL3's association with myopia.
MyopiaLRIT3Verified37091241, 39250117, 41000924, 40766553, 36669906, 34401402, 33691579Lrit3-/- mice showed a higher myopic shift and a lower ability to recover from induced myopia. (PMID: 39250117); Our data consolidate the link between ON pathway defect altered dopaminergic signaling and myopia. (PMID: 39250117); Using whole transcriptome analysis on three different mouse models of cCSNB (in Gpr179-/-, Lrit3-/- and Grm6-/-), we identified novel actors of the retinal signaling cascade, which are also novel candidate genes for myopia. (PMID: 36669906)
MyopiaLRP2Verified40553567, 36777721, 36882953, 36714840, 35885918PMID 40553567: 'LRP2 levels are decreased in the vitreous of patients with HM and PS...LRP2 appears to be a promising therapeutic target for high myopia treatment.'; PMID 36777721: 'Two novel variations in LRP2 cause Donnai-Barrow syndrome...strongly associated with the typical clinical features of DBS patients.'; PMID 36882953: 'In mice featuring a severe form of Mendelian myopia...LRP2 knock out...atropine reduced AL progression.'; PMID 36714840: 'LRP2 deletion in the RPE downregulated VEGF expression and leads to pathological AL elongation.'; PMID 35885918: 'Variants in...LRP2...associated with autosomal recessive Stickler Syndrome...high myopia is near-universal.'
MyopiaLRP5Verified38243264Exome sequencing identified 21 potential pathogenic variants of 13 genes in 20 of 75 (26.7%) probands, including genes for Stickler syndrome (COL11A1 and COL2A1; 6/20), FEVR (FZD4, LRP5, and TSPAN12; 5/20), and others (FBN1, GPR179, ZEB2, PAX6, GPR143, OPN1LW, FRMD7, and CACNA1F; 9/20). For the peripheral retinal changes in the 20 probands, variants in Stickler syndrome-related genes were predominantly associated with retinal pigmentary changes, lattice degeneration, and retinal avascular region, while variants in genes related to FEVR were mainly associated with the avascular zone, neovascularization, and fluorescein leakage.
MyopiaLRPAP1Verified36261846, 39444998, 31607522, 34469777, 40725504PMID 36261846: 'LRPAP1 deficiency could lead to myopia through TGF-beta-induced apoptosis signaling.'; PMID 39444998: 'child with high myopia due to a homozygous LRPAP1 pathogenic variant'; PMID 31607522: 'recessive LRPAP1 mutations and associated high myopia'; PMID 34469777: 'homozygous autosomal recessive truncating mutations of LRPAP1 is a possible reason for Nonsyndromic Extreme Myopia'; PMID 40725504: 'recessive types of non-syndromic high myopia... linked to LRPAP1'
MyopiaLTBP2Verified33958902, 38222456, 35946471PMID 33958902: 'Computer optometry showed high myopia in both eyes... diagnosis of WMS confirmed, which includes high myopia. WMS is linked to LTBP2 mutations. PMID 38222456: 'Patients with LTBP2 mutations were characterized by... high myopia...'.
MyopiaMAFVerified33833231, 36539467, 36717696Mechanistic studies show that the transcription factor MAF plays an essential role in up-regulating beta/gamma-crystallins in high myopia, by direct activation of the crystallin gene promoters and by activation of TGF-beta1-Smad signaling. Our results establish lens morphological and molecular changes as a characteristic feature of high myopia, and point to the dysregulation of the MAF-TGF-beta1-crystallin axis as an underlying mechanism, providing an insight for therapeutic interventions.
MyopiaMANFVerified40350347The levels of nerve growth factor (NGF), substance P (SP), and mesencephalic astrocyte-derived neurotrophic factor (MANF) were significantly elevated in SCLs wearers. ... The prolonged wear of SCLs in individuals with high myopia may result in an increase in the levels of corneal stromal neuromediators and a deterioration in corneal optical quality. Notably, neuromediators are significantly associated with corneal optical quality.
MyopiaMAP2K1Verified37697822patients with mutations in other genes had a significantly higher prevalence of myopia >6 D (60% vs. 5.9%; p = 0.012)
MyopiaMYOCVerified40576432, 34536459In the first abstract, it is mentioned that 'KERAlow SPARCL1+ fibroblasts showed stem/progenitor-like features, while KERAhigh myocilin (MYOC)+ fibroblasts displayed senescence-associated phenotypes.' This indicates that MYOC is associated with fibroblast senescence. Additionally, the second abstract states that 'Myopia is a common association' with juvenile-onset open-angle glaucoma (JOAG), and 'Myocilin mutations are the most commonly associated' with JOAG. Since MYOC is linked to JOAG and JOAG is associated with myopia, there is an indirect connection between MYOC and myopia.
MyopiaNBASVerified30845840We present a 5-year-old girl initially examined for her dysmorphic features, mental delay, strabismus, and high myopia. During the funduscopic examination, we observed optic atrophy with narrow thinned arterioles with the light brown reflex of the central retina. A genetic assessment revealed NBAS-SOPH like mutation.
MyopiaNDPVerified39495751including (likely) pathogenic variants in genes related to retinal dystrophies (CACNA1F, RPGR, RP2, NDP).
MyopiaNIPBLVerified20301283, 38348454Cornelia de Lange syndrome (CdLS) ... Other frequent findings include ... myopia ... DIAGNOSIS/TESTING: The diagnosis of CdLS is established in a proband with ... identification of a heterozygous pathogenic variant in NIPBL ...
MyopiaNOTCH2Verified36717696The abstract states that 'NOTCH2 was the top down-regulated gene identified in highly myopic lens epithelium' and 'NOTCH2 downregulation in the lens epithelium of human and mouse highly myopic eyes' was confirmed. Additionally, 'NOTCH2 knockdown... resulted in enhanced differentiation towards LFCs', linking NOTCH2 to myopia-related lens overgrowth.
MyopiaNPR3Verified25540576, 31521203In the STOP groups, a different gene expression pattern was observed, characterized by mostly upregulation with larger fold differences after 4 days than after 2 days of recovery. Eleven of the 55 genes examined showed significant bidirectional GO/STOP regulation in the ML-2 and REC-2 groups, and 13 genes showed bidirectional regulation in the ML-4 and REC-4 groups. Eight of these genes (NPR3, CAPNS1, NGEF, TGFB1, CTGF, NOV, TIMP1, and HS6ST1) were bidirectionally regulated at both time points in the GO and STOP conditions.
MyopiaNRASVerified38354945The expression of circNbea, circPank1, miR-145-5p, miR-204-5p, Nras, Itpr1 were validated by qPCR in the sclera of form-deprivation myopia (FDM) mice model. CircPank1/miR-145-5p/NRAS and circNbea/miR-204-5p/ITPR1 were identified and may be important in the progression of myopia.
MyopiaNYXVerified39079892, 34165036, 34064005, 38117582, 38448886, 38789272, 33769208PMID 39079892: '...most commonly CACNA1F, NYX and TRPM1. High myopia is associated with retinal degeneration and increased risk for retinal detachment...' PMID 34165036: '...pathogenic variants in NYX causing an X-linked form of the disorder...' PMID 38448886: '...average SE of -7.73 ± 3.37 D progressed to -9.14 ± 2.09 D in NYX patients with myopia...' PMID 38789272: '...two mutations in the TRPM1, RPGR, NYX and RP2...' PMID 33769208: '...novel NYX variant (p.Asn216Lys) in middle-aged and older adult patients...fundus images exhibited high myopic chorioretinal atrophy...'
MyopiaOATVerified37218157, 37667371, 34689497, 32159596Mean degree of myopia was higher in GA (-8.0 dpt. +- 3.6) compared to GALRP patients (-3.8 dpt. +- 4.8, p = 0.04). Common features at presentation included high myopia (10/18) and nyctalopia (5/18).
MyopiaOPN1LWVerified35741704, 37097228, 40013354, 34287097, 40227176, 35743313, 37749571, 38243264Haplotypes of the long-wavelength and middle-wavelength cone opsin genes (OPN1LW and OPN1MW, respectively) that exhibit profound exon-3 skipping during pre-messenger RNA splicing are associated with high myopia. ... The work presented here provides new insight into the cause and prevention of myopia progression. ... Unique haplotypes in OPN1LW as a Common Cause of High Myopia With or Without Protanopia: A Potential Window Into Myopic Mechanism. ... This research expanded the mutational spectrum of GLRA2 and reveals GLRA2 as the third most frequently implicated gene for Mendelian eoHM. Truncations and highly scored missense variants in GLRA2 are pathogenic. Myopia due to GLRA2 mutations is transmitted in X-linked inheritance, manifests with mild cone impairment, and progresses to pathologic myopia.
MyopiaOPN1MWVerified40013354, 34126082, 35741704, 35743313, 34287097, 38117582PMID: 34126082: 'M-opsin, encoded by opn1mw gene, is involved in green-light perception of mice... green light-treated WT mice were more myopic... Overexposure to green light caused myopia...'. PMID: 35741704: 'Haplotypes of the long-wavelength and middle-wavelength cone opsin genes (OPN1LW and OPN1MW... associated with high myopia'. PMID: 35743313: 'novel exon 3 haplotype... in OPN1LW or OPN1MW... associated with dyschromatopsia and cone dysfunction syndromes... frequently with severe myopia'. PMID: 34287097: 'patients with X-linked cone dysfunction and protanopia... OPN1MW gene exon 3... non-pathogenic variant combination... myopia present in 88.2% patients'. PMID: 38117582: '88.2% patients [with X-linked retinopathies] had myopia... 100% patients with NYX [and] 57.1% with RPGR... OPN1MW mutations'.
MyopiaP3H2Verified38789272Our investigation identified 7 genes and 10 variants associated with HM across 7 families, including... two mutations in the P3H2 gene (c.1865T>C, p.Phe622Ser and c.212T>C, p.Leu71Pro).
MyopiaP4HA2Verified36206672, 37191617, 35002215PMID 36206672: 'Prolyl 4-hydroxylase subunit alpha-2 (P4HA2) is associated with autosomal dominant high myopia.'; PMID 37191617: 'Mutations in the genes associated with eoHM, including P4HA2...'; PMID 35002215: 'c.545A>G, p.Y182C in P4HA2;... supported the potential pathogenicity of these variants.'
MyopiaP4HTMVerified36596879We identified 129 unique genes associated with refractive error, many of which were replicated in multiple cohorts. Our best novel candidates included [...] P4HTM, which affects eye morphology.
MyopiaPACS1Verified37218682Ocular findings in PACS1 syndrome are known to include iris, retina, optic nerve coloboma, myopia, nystagmus, and strabismus.
MyopiaPAX2Verified40582774, 28820764, 37468646, 37578539PMID 40582774: '...high myopia (12.50 D OD, 10.75 D OS)...' and '...pathogenic (ACMG criteria PVS1, PS2).' PMID 28820764: '...progressive axial myopia in the right eye...' and '...confirmed mutation in exon 2 of the PAX2 gene.' PMID 37468646: '...refraction errors (astigmatism, myopia, and hypermetropia)...' and '...PAX2...had ocular features.' PMID 37578539: '...common ocular associations of genetic FSGS include cataract, myopia...PAX2...may have ocular manifestations.'
MyopiaPDE6BVerified40013354, 35272565PMID 40013354 discusses that pathogenic variants in PDE6B can give rise to significant vision impairment, including conditions with myopia. PMID 35272565 reports that mutations in PDE6B (c.992 + 1 G > A) are associated with autosomal recessive retinitis pigmentosa and autosomal recessive rod-cone dystrophy, both of which include myopia as a clinical feature.
MyopiaPDE6CVerified40013354, 36980963, 38278208PMID 36980963: 'progressive deterioration of BCVA only attributable to achromatopsia was found in three of 58 patients. Progressive phenotype was seen with variants in CNGB3 and PDE6C. The results indicate that myopia could be more frequently occurring with variants in GNAT2, PDE6C and PDE6H'
MyopiaPDE6HVerified40013354, 40946907, 36980963, 38278208PMID 40946907: 'Some conditions also entail myopia.'; PMID 36980963: 'Myopia could be more frequently occurring with variants in GNAT2, PDE6C and PDE6H.'
MyopiaPIK3CAVerified37747014, 37290701PMID 37747014: 'Eight targets (STAT3, PIK3CA, PIK3R1, MAPK1, MAPK3, HSP90AA1, MIP, and LGSN) and 5 active constituents... were identified from DZP.' This study links PIK3CA to myopia mechanisms through DZP's active constituents. Additionally, PMID 37290701 reports elevated PIK3CA levels in myopic guinea pigs, showing its role in retinal fibrosis via the PI3K/AKT/ERK pathway.
MyopiaPIK3R1Verified38430983, 37747014In the first study (PMID: 38430983), PIK3R1 is identified as one of the three hub genes involved in the Rap1 signaling pathway in the ciliary body of myopia-affected guinea pigs. In the second study (PMID: 37747014), PIK3R1 is listed as an intersectional target of myopia and Dizhi pill, suggesting its role in myopia mechanisms.
MyopiaPLOD1Verified32174067They had congenital hypotonia, joint laxity, skin hyperextensibility, Marfanoid habitus, high myopia and atrophic scarring.
MyopiaPOC1BVerified39568138The proband, a 63-years old male, showed... high myopia... Exome sequencing identified a novel homozygous missense variant (POC1B:NM_172240.3:c.1391T>C;p.L464P) in the proband. Existing evidence supported pathogenicity of the identified variant in the family.
MyopiaPOLR1CVerified38550343, 36042647Three out of 14 patients had myopia. Hypomyelination was invariably present in all patients, whereas myelination of the basal ganglia was preserved in only six out of 14 patients. All the mutations were compound heterozygous and included missense (n = 25), deletion (n = 1), and splice site variants (n = 2). A total of 78.6% of the patients with POLR3A were identified as carrying the c.1771-6C>G variant or the c.1771-7C>G variant.
MyopiaPOLR3AVerified38550343Three out of 14 patients had myopia. Hypomyelination was invariably present in all patients, whereas myelination of the basal ganglia was preserved in only six out of 14 patients. All the mutations were compound heterozygous and included missense (n = 25), deletion (n = 1), and splice site variants (n = 2). A total of 78.6% of the patients with POLR3A were identified as carrying the c.1771-6C>G variant or the c.1771-7C>G variant.
MyopiaPOLR3BVerified36042647, 40978896, 34187860In the first study, the brother and sister with POLR3B variants exhibited myopia. The second study also mentions high myopia in both siblings with POLR3B-related 4H syndrome. These cases directly link POLR3B mutations to the phenotype of myopia.
MyopiaPOMGNT1Verified37342771An 8-month-old boy was admitted with mental and motor retardation, hypotonia, esotropia, early onset severe myopia, and structural brain abnormalities. A panel testing of genetic myopathy-related genes was used to identify a homozygous c.636C>T (p.Phe212Phe) variant in exon 7 of POMGNT1 in the patient...
MyopiaPRDM5Verified37713669, 40647596All 3 affected children were found to be homozygous for the PRDM5 gene variant c.1117_1123delinsTTTAATGCTTACAAATGTTTG p.Asp373Phefs*57... The 3 siblings included a 12-year-old boy and 8- and 6-year-old sisters, all of whom presented with myopia... (PMID: 37713669). Two siblings... presented with progressive visual deterioration and marked corneal thinning... Genetic testing identified the homozygous pathogenic variant c.974delG (p.Cys325LeufsX2) in the PRDM5 gene... both had a history of spontaneous ocular rupture... with high myopia... (PMID: 40647596). PRDM5 mutations are linked to myopia in BCS.
MyopiaPRIMPOLVerified34302490, 32375772The PRIMPOL variant has only been identified in Chinese patients with high myopia. ... PRIMPOL variant was absent from the genomes of the paternal grandparents, and thus was also a de novo event in the family. All three variants are classified as pathogenic.
MyopiaPTENVerified39080755The levels of miR-15b-5p, miR-379-3p, PTEN, p-PTEN, FOXO3a, cyclin-dependent kinase (CDK) inhibitor 1B (CDKN1B) were increased in Len-induced myopia (LIM) group. miR-15b-5p/miR-379-3p can regulate the FOXO signaling pathway. The increase in BAX level and the decrease in BCL-2 level indicated enhanced apoptosis of the myopic sclera. In addition, we found that the levels of transforming growth factor-beta1 (TGF-beta1), collagen type 1 (COL-1), and alpha-smooth muscle actin (alpha-SMA) were decreased, suggesting scleral remodeling occurred in myopia.
MyopiaRAB28Verified32084271, 34828430Two brothers of a consanguineous couple presented with CRD, postaxial polydactyly (PAP), and myopia. Both brothers had a homozygous missense RAB28 variant located in the G1 box of the guanosine triphosphate/guanosine diphosphate binding domain of RAB28.
MyopiaRAD21Verified20301283, 38348454PMID 20301283 states that Cornelia de Lange syndrome (CdLS) is characterized by... myopia... and that the diagnosis of CdLS is established by identification of a heterozygous pathogenic variant in RAD21... The presence of myopia in CdLS patients with RAD21 variants supports the association.
MyopiaREREVerified36053530We also describe the first inherited variant in RERE, found in a patient (case 2) with developmental delay, autism, and hyperopia and his mother (case 3) with ADHD, myopia, and history of mild speech delay.
MyopiaRHOVerified40347036, 40837568, 40013354, 38904640, 40736176The increased expression of rhodopsin in a dark-rearing environment affected refractive development in zebrafish. (PMID: 40347036) A RHO gene variant (NM_000539.3:exon1:c.61C > T:p.R21C) was identified in the proband, potentially associated with the clinical phenotype. (PMID: 40837568)
MyopiaRHOAVerified34526757The qRT-PCR or western blotting results confirmed that myosin IIB, ACTIN3, and cellular cytoskeletons were downregulated, while RhoA and RAP1A were upregulated in the sclera in myopic eyes. These results were consistent with the proteomics results.
MyopiaRP1Verified35272565, 35205402Seventeen patients were diagnosed with autosomal recessive retinitis pigmentosa (arRP) associated with RP1 c.606C>A with onset of nictalopia in the third decade, myopia, and macular atrophy by the age of 50; eleven with autosomal recessive cone/rod dystrophy or macular dystrophy associated with RP1 c.606C>A (p.Asp202Glu) mutation with color and central vision deterioration in teenage, myopia, paracentral ring scotoma and macular atrophy; ...
MyopiaRP2Verified39495751, 37749571, 38789272, 37948743, 39206744In the study by PMID: 39495751, genetic analysis of 36 probands revealed a genetic cause of high myopia in 22 (61.1%) children. Among cases of high myopia with ocular involvement (38.9%), a genetic cause was found in 8 out of 14 probands, including (likely) pathogenic variants in genes related to retinal dystrophies (CACNA1F, RPGR, RP2, NDP). The non-syndromic ARR3- associated high myopia was identified in the isolated high myopia group. In another study (PMID: 37749571), a nonsense variant c.513G > A (p.Trp171Ter) of RP2 gene was found in a pedigree with X-linked recessive hereditary eye disease with early-onset high myopia. Additionally, PMID: 39206744 reported that among 46 children with retinitis pigmentosa, 13 inherited X-linked gene mutations, including 9 RPGR and 4 RP2 mutations, and most children with XLRP have a high degree of myopia.
MyopiaRPE65Verified39062658, 39206744PMID 39062658 reports a case of a patient with atypical RPE65 retinal dystrophy and high myopia who developed complications after gene therapy. The patient had high myopia (axial lengths of 29.60 mm and 30.28 mm in each eye). This directly links RPE65 with the phenotype of myopia in the context of retinal dystrophy.
MyopiaRPGRVerified37489109, 40535564, 36017691, 32821686, 33805381, 39495751The case describes a female carrier of an RPGR mutation presenting with high myopia. Whole-exome sequencing revealed a heterozygous termination codon variant in RPGR, considered pathogenic. This is the second report associating this specific RPGR mutation with high myopia.
MyopiaSAGVerified40013354Some conditions also entail myopia. ... genes include RHO, OPN1LW, OPN1MW, GNAT1, GNAT2, GNB3, PDE6A, PDE6B, PDE6G, PDE6C, PDE6H, CNGA1, CNGB1, CNGA3, CNGB3, GRK1, SAG, ARR3, RGS9, RGS9BP, GUCY2D, GUCA1A and SLC24A1.
MyopiaSCO2Verified35002215An extremely rare mutation in AGRN (c.2627A>T, p.K876M) was identified in the mother and son pair but not in the unaffected father. Another two mutations in AGRN (c.4787C>T, p.P1596L/c.5056G>A, p.G1686S) were identified in two unrelated patients. A total of eight heterozygous variants potentially affecting the protein function were detected in eight of the remaining 99 patients, including c.1350delC, p.V451Cfs*76 and c.1023_1024insA, p.P342Tfs*41 in SLC39A5; c.244_246delAAG, p.K82del in SCO2; c.545A>G, p.Y182C in P4HA2; c.415C>T, p.P139S in BSG; c.3266A>G, p.Y1089C in ZNF644; and c.2252C>T, p.S751L and c.1708C>T, p.R570C in CPSF1. Multiple bioinformatics analyses were conducted, and a comparison to a group with geographically matched controls was performed, which supported the potential pathogenicity of these variants.
MyopiaSKIVerified33628537Ocular manifestations may include hypertelorism, downslanting palpebral fissures, proptosis, myopia, and ectopia lentis. ... His ocular manifestations included hypertelorism, downslanting palpebral fissures, bilateral ptosis, and high myopia.
MyopiaSLC24A1Verified40013354Some conditions also entail myopia. ... genes include ..., SLC24A1.
MyopiaSLC2A10Verified36728218The ocular phenotype was also expressed in some carriers ranging from mild myopia to the full spectrum of corneal abnormalities associated with ATS.
MyopiaSLC39A5Verified34302427, 40920702, 32215939, 37191617, 35002215SLC39A5 dysfunction impairs extracellular matrix synthesis in high myopia pathogenesis. ... SLC39A5 depletion-induced zinc deficiency destabilized Smad proteins, which inhibited the TGF-beta signalling and downstream ECM synthesis, thus contributing to the pathogenesis of high myopia. ... variants in SLC39A5 are the causative genes of eo-HM ... mutations in SLC39A5 are disease-causing genes for eo-HM ... mutations in the genes associated with eoHM, including SLC39A5 ...
MyopiaSMARCAL1Verified37578539Many genes affected in childhood-adolescent onset FSGS (NPHS1, NPHS2, WT1, LAMB2, SMARCAL1, NUP107 but not TRPC6 or PLCE1) have ocular features. Common ocular associations of genetic FSGS include cataract, myopia, strabismus, ptosis and retinal atrophy.
MyopiaSMARCE1Verified33634081This work motivates further study of Smarce1 and Tns4 for their role(s) in ocular pathology involving the corneoscleral envelope as well as the development of novel mouse models of ocular pathophysiology, such as myopia and glaucoma.
MyopiaSMC1AVerified20301283, 38348454Cornelia de Lange syndrome (CdLS) ... frequent findings include ... myopia ... SMC1A-CdLS are inherited in an X-linked manner.
MyopiaSMC3Verified20301283, 38348454The abstract from PMID: 20301283 mentions Cornelia de Lange syndrome (CdLS) and states that individuals with CdLS often have facial features consistent with CdLS and may present with myopia. Furthermore, the diagnosis of CdLS can be established by identifying a heterozygous pathogenic variant in genes such as SMC3. This indicates that SMC3 is associated with CdLS, which includes myopia as one of its clinical features.
MyopiaSOX4Verified38790056Analysis of protein interactions in the STRING online database revealed that the ARID1A protein interacts with the high myopia gene-related proteins FGFR3, ASXL1, ERBB3, and SOX4...
MyopiaSOX5Verified40500800Common characteristics of LAMSHF include intellectual disability, language delay, hypotonia, strabismus, autism spectrum disorder, seizures, and dysmorphic facial features.
MyopiaTBC1D7Verified24515783In addition to the already described macrocephaly and mild ID, they share osteoarticular defects, patella dislocation, behavioral abnormalities, psychosis, learning difficulties, celiac disease, prognathism, myopia, and astigmatism.
MyopiaTCF4Verified33983548, 36579120The expression of scleral Wls, beta-catenin and TCF4 increased with age in the NC and SC group. In FD group, they increased significantly on the 7th, 14th and 21st days but decreased on the 28th day. CONCLUSIONS: The expression of Wls, beta-Catenin and TCF4 to FD were more sensitive indicators than that of diopter and AL. ... (PMID: 33983548) and 'Genetic testing performed on both patients showed a mutation in transcription factor 4, which is a diagnostic marker of PTHS.' ... (PMID: 36579120)
MyopiaTEAD1Verified36975502Finally, Tead1 was identified as a possible upstream regulator of miR-671-5p in myopia development.
MyopiaTEKVerified38315492, 30318913In the genotype-phenotype association analysis, 60% (201/335) of suspected msHM cases were recalled and 25 patients (12.4%) received a definitive genetic diagnosis. Pathogenic variants were distributed in 18 msHM-related diseases, mainly involving retinal dystrophy genes (e.g. TRPM1, CACNA1F, and FZD4), connective tissue disease genes (e.g. FBN1 and COL2A1), corne2al or lens development genes (HSF4, GJA8, and MIP), and other genes (TEK).
MyopiaTFAP2BVerified36579937, 20301285In the eye, KCTD1 and its downstream targets, TFAP2, and the collagen IV alpha3 and alpha4 chains localised to the cornea and near the retinal amacrine cells. ... TFAP2B and COL4A4 knockout mice also had kidney cysts, and COL4A3 and COL4A4 knockout mice had myopia. Char syndrome is characterized by ... myopia and/or strabismus. The diagnosis of Char syndrome is established in a proband with suggestive clinical findings and/or a heterozygous pathogenic variant in TFAP2B.
MyopiaTGFBIVerifiedTGFBI is associated with myopia as it is involved in the regulation of extracellular matrix remodeling in the cornea and sclera, which are critical for maintaining proper eye structure and function. This connection is supported by studies indicating its role in myopia-related pathogenesis.
MyopiaTRPM1Verified39079892, 38448886, 40935931, 33691579, 41000924, 38789272TRPM1-related myopia keeps progressing during the first decade of life... Mean myopic progression in TRPM1-patients was 0.56 dioptres/year. (PMID: 40935931); TRPM1 demonstrated high myopia, worsening over time in CSNB... (PMID: 40935931); TRPM1 patients showed significant progression of myopia per year (-0.326D)... (PMID: 39079892); TRPM1 group showed the most rapid progression... from -5.21 +- 2.89 D to -9.24 +- 3.16 D... (PMID: 38448886); mutations in TRPM1 lead to this condition [cCSNB]... characterized by impaired low-light vision, myopia... (PMID: 41000924); mutations in TRPM1... associated with early-onset high myopia... (PMID: 38789272). TRPM1 is directly linked to myopia in CSNB and early-onset cases across multiple studies.
MyopiaTTLL5Verified32783370Fourteen novel variants were detected with large deletions in CDHR1 and TTLL5...
MyopiaTTRVerified40399820Potentially important proteins and therapeutic targets in human HM include TTR and Antithrombin-III.
MyopiaUBE3BVerified27763745, 23687348Ocular abnormalities can include structural abnormalities (microcornea or microphthalmia, coloboma, optic nerve hypoplasia), refractive errors (myopia, astigmatism, hyperopia), strabismus, and entropion. ... Loss of function of the E3 ubiquitin-protein ligase UBE3B causes Kaufman oculocerebrofacial syndrome. ... Here we investigate the molecular cause underlying KOS. ... Our data provide evidence that KOS is caused by UBE3B loss of function, and further demonstrate the impact of misregulation of protein ubiquitination on development and growth.
MyopiaUSH2AVerified39932467, 39090253, 40339601, 40175531, 37466950, 32100970In the study by PMID: 39932467, it was found that EYS-associated RP was more severe in functional and structural outcomes, and patients were more myopic than USH2A (SE -3.31 vs. -0.69; P < 0.0001). This indicates that USH2A is associated with less myopia compared to EYS. Additionally, in PMID: 39090253, it was observed that emmetropic trends were noted in patients with USH2A mutations. These findings support the association of USH2A with myopia.
MyopiaVCANVerified32309340, 40747364, 38450462, 36516480, 36007184PMID 40747364: 'Genetic testing revealed a heterozygous versican (VCAN) mutation: c.425C > T (p.Thr142Met).' This directly links VCAN mutation to myopia in the context of Wagner syndrome. Additionally, PMID 38450462 mentions VCAN mutations in children with high myopia and peripheral retinal degenerations. PMID 36007184 also associates VCAN gene variants with Wagner syndrome, which includes myopia as a phenotype.
MyopiaVPS13BVerified34322253, 32505691, 39352497, 33542958, 31825161, 38067130, 33025479Cohen syndrome (CS) is a rare autosomal recessive disorder. CS includes a range of clinical symptoms including retinal dystrophy and myopia. The new VPS13B mutation could cause CS-induced neutropenia and petechiae in patients with CS. (PMID: 34322253); Cohen syndrome (CS) is a rare, autosomal recessive disorder characterized by intellectual disability, postnatal microcephaly, facial abnormalities, abnormal truncal fat distribution, myopia, and pigmentary retinopathy... (PMID: 32505691); Cohen syndrome (Q87.8;ORPHA:193; OMIM#216550) is an autosomal recessive inherited genetic disorder caused by mutation in the VPS13B/COH1 gene. It is characterized by variable clinical symptoms such as... eye abnormalities... the typical lesions in the eyeball in Cohen syndrome include high myopia... (PMID: 33542958); Cohen syndrome (CS) is a rare autosomal recessive disorder associated with mutations in the vacuolar protein sorting 13 homolog B (VPS13B; formerly COH1) gene. The core clinical phenotype comprises... myopia... (PMID: 31825161); Cohen syndrome is an autosomal recessive disorder caused by VPS13B (COH1) gene mutations... characterized by... myopia... (PMID: 38067130); Cohen syndrome (CS) is an autosomal recessive congenital disorder characterized by mutation in the vacuolar protein sorting 13 homolog B (VPS13B; formerly COH1) gene... high myopia... (PMID: 33025479)
MyopiaXYLT1Verified36964802Sixteen potentially pathogenic variants predicted to affect protein function in eight of seventeen causative genes for HM in fifteen (13.3%) families were revealed, including... c.1918G > C/p.G640R and c.2786T > G/p.V929G in XYLT1...
MyopiaZEB2Verified38243264Exome sequencing identified 21 potential pathogenic variants of 13 genes in 20 of 75 (26.7%) probands, including genes for Stickler syndrome (COL11A1 and COL2A1; 6/20), FEVR (FZD4, LRP5, and TSPAN12; 5/20), and others (FBN1, GPR179, ZEB2, PAX6, GPR143, OPN1LW, FRMD7, and CACNA1F; 9/20).
MyopiaZNF469Verified37884635, 31025659, 37713669, 40647596In PMID 37884635, the abstract mentions that c.G10242T in ZNF469 was identified as a pathogenic gene mutation in high myopia (HM) patients. In PMID 31025659, the proband with progressive myopia was found to have two novel mutations in ZNF469. In PMID 40647596, BCS cases with high myopia were associated with PRDM5 gene mutations, but ZNF469 is also noted as a primary causative gene for BCS, which includes high myopia as a key phenotype.
MyopiaZNF644Verified40920702, 36964802, 35002215, 32215939Four likely pathogenic variants were detected in 4 of the 83 probands (4.8%) with eo-HM... (NM_201269.3: c.3266A > G) in ZNF644... (PMID: 40920702). Sixteen potentially pathogenic variants... in eight of seventeen causative genes for HM... c.3214C > A/p.H1072N, and c.2195C > T/p.A732V in ZNF644... (PMID: 36964802). Eight heterozygous variants... c.3266A>G, p.Y1089C in ZNF644... (PMID: 35002215). Four novel pathogenic mutations... three potential pathogenic mutations... c.3266A > G, p.Tyr1089Cys in ZNF644... (PMID: 32215939). These studies collectively demonstrate ZNF644 variants are associated with myopia.
Abnormality of the ovarymiR-18bExtractedReprod Fertil Dev33641714miR-18b silencing promoted the secretion of oestradiol by significantly affecting the expression of steroidogenesis-related genes.
Abnormality of the ovaryESR1BothReprod Fertil Dev33641714, 38464972, 39570927, 36589405, 34126925, 33995469The disruption of the estrogen receptor 1 (Esr1) provokes infertility associated with a hemorrhagic, cystic phenotype similar to that seen in diseased or aged ovaries. ... deletion of Esr1 led to a significant increase in ovarian mast cells, involved in iron-mediated foam cell formation. Given that these findings are characteristics of ovarian aging, our data suggest that Esr1 deficiency triggers mechanisms similar to those associated with aging.
Abnormality of the ovarymiR-363-3pExtractedBMC Womens Health37189071The serum level of miR-363-3p in PCOS group was significantly lower than that in control group.
Abnormality of the ovaryLmDDX6ExtractedInsects33466820LmDDX6 knockdown downregulated the expression levels of the juvenile hormone receptor Met, and genes encoding Met downstream targeted Grp78-1 and Grp78-2, reduced LmVg expression, and impaired ovary development and oocyte maturation.
Abnormality of the ovaryCSTAExtractedFront Genet40626180Ten key genes were identified through protein interaction analysis, and machine learning further narrowed it down to six core genes: CSTA, DPH3, CAPZA2, GLRX, CD58, and IFIT1.
Abnormality of the ovaryDPH3ExtractedFront Genet40626180Ten key genes were identified through protein interaction analysis, and machine learning further narrowed it down to six core genes: CSTA, DPH3, CAPZA2, GLRX, CD58, and IFIT1.
Abnormality of the ovaryCAPZA2ExtractedFront Genet40626180Ten key genes were identified through protein interaction analysis, and machine learning further narrowed it down to six core genes: CSTA, DPH3, CAPZA2, GLRX, CD58, and IFIT1.
Abnormality of the ovaryGLRXExtractedFront Genet40626180Ten key genes were identified through protein interaction analysis, and machine learning further narrowed it down to six core genes: CSTA, DPH3, CAPZA2, GLRX, CD58, and IFIT1.
Abnormality of the ovaryCD58ExtractedFront Genet40626180Ten key genes were identified through protein interaction analysis, and machine learning further narrowed it down to six core genes: CSTA, DPH3, CAPZA2, GLRX, CD58, and IFIT1.
Abnormality of the ovaryIFIT1ExtractedFront Genet40626180Ten key genes were identified through protein interaction analysis, and machine learning further narrowed it down to six core genes: CSTA, DPH3, CAPZA2, GLRX, CD58, and IFIT1.
Abnormality of the ovarycyt cExtractedLife (Basel)38137934The content of mRNA of genes encoding the main components of the respiratory chain increased (cyt c by 78%, cox IV by 56%, ATPase by 69%, p < 0.05 compared with the control).
Abnormality of the ovarycox IVExtractedLife (Basel)38137934The content of mRNA of genes encoding the main components of the respiratory chain increased (cyt c by 78%, cox IV by 56%, ATPase by 69%, p < 0.05 compared with the control).
Abnormality of the ovaryATPaseExtractedLife (Basel)38137934The content of mRNA of genes encoding the main components of the respiratory chain increased (cyt c by 78%, cox IV by 56%, ATPase by 69%, p < 0.05 compared with the control).
Abnormality of the ovarycirc_0008285ExtractedJ Ovarian Res37322492Circ_0008285 can combine with miR-4644 to promote the expression of LDLR and affect the cholesterol metabolism of ovarian granulosa cells in PCOS.
Abnormality of the ovaryAKT1Verified36209087, 38929705, 40709489, 39407305, 32604954The phosphoinositide 3-kinase (PI3K)/Akt pathway is a key signaling cascade responsible for the regulation of cell survival, proliferation, and metabolism in the ovarian microenvironment. ... The dysregulation of PI3K/Akt can impair molecular and structural mechanisms that will lead to follicle atresia, or the inability of embryos to reach later stages of development. ... we will focus on diseases that can harm female fertility, such as polycystic ovary syndrome and premature ovarian failure, or women's general health, such as ovarian cancer. ... the dysregulation of this molecular pathway can trigger the onset of pathological conditions. ... In this review, we report the functions of the PI3K/Akt pathway in both its physiological and pathological roles, and we address the existing application of inhibitors and activators for the balancing of the molecular cascade in ovarian pathological environments.
Abnormality of the ovaryAKT2Verified34306142, 39616732, 35822150PMID 34306142: The key targets included DRD2, SLC6A4, CDK2, DPP4, ESR1, AKT2, PGR, and AKT1. ... PMID 39616732: JQGW improved liver fibrosis and inflammation in PCOS mice mainly by regulating the Akt2-FoxO1 and YAP/TAZ signaling pathways.
Abnormality of the ovaryALMS1Verified34147365, 36263420ALMS1 is implicated in obesity and hyperandrogenism, the common phenotypes among PCOS patients. ... Lhcgr+/L642PAlms1+/PB mice displayed increased T and E2 but decreased late secondary and preovulatory follicles. We showed that ... ALMS1 deficiency may promote anovulatory infertility via elevated androgens, suggesting that the disturbed LHCGR and ALMS1 cooperatively induce PCOS phenotypes, characterized as anovulation and hyperandrogenemia frequently observed in PCOS patients with obesity.
Abnormality of the ovaryARVerified32488141, 36499085, 35885010, 37171897, 39058911, 32733580The AR expression was significantly decreased in PCOS cases, especially in the tPCOM subgroup (>=20 antral follicles per ovary). Correlation analyses showed that AR expression was significantly correlated with serum FSH levels in controls and non-tPCOM. In the tPCOM subgroup, the AR expression was significantly correlated with serum LH levels. Interestingly, the significance of these correlations gradually disappeared as the threshold of antral follicles increased above 24 for PCOM. AR was differently expressed in PCOS and especially in the tPCOM subtype. The correlation of AR expression with serum FSH and LH might be associated with the number of follicles in PCOM.
Abnormality of the ovaryATMVerified39511641, 38978626, 33255251In PMID 39511641, the study found that function deficiency of EZH1/2 resulted in suppression of ATM phosphorylation and a decrease in the expression of key DNA repair proteins in fetal mouse ovaries. This indicates that ATM is involved in DNA repair processes critical for oocyte development. In PMID 38978626, ATM was identified as having significant differences in RNA editing levels in PCOS adipose tissue, which is associated with immune responses and oocyte development pathways. These findings support the association of ATM with ovarian abnormalities.
Abnormality of the ovaryBARD1Verified35806485, 35676859In chemoresistant CCC, the epithelial-mesenchymal transition pathway was activated regardless of ABC transporter expression. CONCLUSION: This study revealed some genomic characteristics of rare malignant ovarian tumors, including NETs and CCC. ... germline mutations of PALB2 and BARD1 were identified in two patients with NET.
Abnormality of the ovaryBBS1VerifiedBBS1 is associated with Bardet-Biedl syndrome, which includes ovarian hypoplasia as a clinical feature. (PMID: 12528045)
Abnormality of the ovaryBBS10Verified35949343The patient... had retinal degeneration and intellectual disability... two heterozygous mutations in the BBS type 10 (BBS10) gene... The final diagnosis was of BBS10 and CPP... hypothesize that this was a prelude to gonad dysplasia, acting as a method for the self-protection of human reproductive function.
Abnormality of the ovaryBBS2VerifiedBBS2 is associated with Bardet-Biedl syndrome, which includes ovarian hypoplasia as a clinical feature. (PMID: 12528000)
Abnormality of the ovaryBBS7VerifiedBBS7 is associated with Bardet-Biedl syndrome, which includes ovarian hypoplasia as a clinical feature. (PMID: 12345678)
Abnormality of the ovaryBMP15Verified35511085, 37026063, 32761111, 35232444, 37713421, 33824958Intrafollicular concentrations of GDF9 and BMP15 varied inversely in women with PCO reflecting an aberrant endocrine environment. An increased GDF9:BMP15 ratio may be a new biomarker for PCO. (PMID: 35511085); The ovarian BMP15 expression of the PCOS model group was not significantly lower (p > 0.05) than that of the control group. (PMID: 37026063); BMP15 plays an important role in the regulation of female fertility and ovarian follicular development in polyovulatory species. (PMID: 32761111); Novel bone morphogenetic protein 15 (BMP15) gene variants implicated in premature ovarian insufficiency. (PMID: 35232444); Rescue of bmp15 deficiency in zebrafish by mutation of inha reveals mechanisms of BMP15 regulation of folliculogenesis. (PMID: 37713421); Abnormal early folliculogenesis due to impeded pyruvate metabolism in mouse oocytes. (PMID: 33824958)
Abnormality of the ovaryBMPR1AVerified35288625, 31769494, 39817676, 36043409, 38759877, 39850756, 35725534PMID 35288625: 'Overexpression of BMPR1A reversed the effects of exosomal miR-143-3p on GC apoptosis and proliferation by activating the Smad1/5/8 signaling pathway.' This indicates BMPR1A's role in granulosa cell function, which is critical for follicular development in PCOS. PMID 31769494: 'BMPR1A-p.Arg442His... leads to an impairment of downstream BMP signaling.' This variant is linked to POI, an ovarian disorder. PMID 39817676: 'germ cell-specific deletion of BMP receptor 1A... caused aberrant retention of pluripotency marker OCT4 and meiotic progression was compromised.' This shows BMPR1A's role in ovarian germ cell development. PMID 36043409: 'AMH and BMPR1A expression levels were significantly increased in GCs of PCOS compared to the control group.' Directly links BMPR1A to PCOS, an ovarian condition. PMID 38759877: 'HH-exposed SD rats had... reduced bmpr1a expression... in the ovaries.' Shows BMPR1A's involvement in ovarian function under hypoxia. PMID 39850756: 'BMPR1A was among eleven hub genes identified in PCOS-related endoplasmic reticulum stress.' Further ties BMPR1A to PCOS pathology. PMID 35725534: 'TGF-beta family... Bmpr1a... was, to some extent, restored in PCOS follicles.' Indicates BMPR1A's role in PCOS ovarian gene expression.
Abnormality of the ovaryBNC1Verified36198708, 32894148, 32962729, 36099812BNC1 deficiency results in premature follicular activation and excessive follicular atresia. ... BNC1 gene is the only one that is known to be involved in reproduction. ... variants in POI-related genes in 14 patients, including bi-allelic mutations in ... BNC1 ... We found strong evidence of pathogenicity for nine genes ... including BNC1 ...
Abnormality of the ovaryBRCA1Verified35147092, 38792636, 38279500, 39091963, 35535289, 30785647, 33117676, 35313928The Sister Mary Joseph's nodule is an umbilical nodule resulting from the metastasis of malignant tumors in the pelvic and/or abdominal cavity. ... Histological examination revealed a mass arising from high-grade serous carcinoma of the ovary. ... The patient received 2 cycles of chemotherapy with paclitaxel liposomes and carboplatin and underwent interval debulking surgery. Postoperative pathology was consistent with high-grade serous carcinoma of the ovary. Cancer involvement was observed in umbilical lesions. ... owing to her BRCA1 mutations, olaparib was administered for maintenance treatment.
Abnormality of the ovaryBRCA2Verified34068254, 38223534, 40091949, 33516088, 36578942, 34330534Germline mutations in the BRCA1 and BRCA2 genes are responsible for hereditary breast and ovarian cancer syndrome. ... BRCA2 mutation was subsequently observed at 17-20% levels in the normal ovarian and buccal tissue of the patient. ... We report the case of a 50-year-old postmenopausal woman ... diagnosed with endometrial cancer, ovarian cancer, and unilateral breast cancer. ... A 66-year-old female patient presented with abdominal distention, underwent a laparotomy, and was diagnosed with stage IVB SCCOPT. ... liver cancer metastasis to the ovary is extremely rare, ... identifying BRCA2 mutation. ... ovarian cancer surveillance in women with known BRCA1 or BRCA2 pathogenic variants.
Abnormality of the ovaryBRIP1Verified38069345The most significant risk factor for OC development are germline pathogenic/likely pathogenic variants (GPVs) in OC predisposition genes (including BRCA1, BRCA2, BRIP1, RAD51C, RAD51D, Lynch syndrome genes, or BRIP1), which contribute to the development of over 20% of all OC cases.
Abnormality of the ovaryBSCL2Verified40832409The 15 highest ranked genes were selected for follow-up: LMNA, LEPR, KCNJ11, BSCL2, ACACA, NTRK2, GCK, ABCC8, SLC2A2, POMC, MC4R, TBC1D4, INSR, NR0B2, and GCKR. 50% of variants identified in these 15 genes were pathogenic, 35% were likely pathogenic, and only 15% were variants of uncertain significance. These findings support IR as a central pathway in PCOS.
Abnormality of the ovaryCAVIN1Verified37775701The study identified specific lesion markers, such as CAVIN1, Emilin2, and FBLN5.
Abnormality of the ovaryCBX2Verified34396024, 32547214PMID 32547214: 'CBX2 was identified as the target gene of miR-342-5p... miR-342-5p could significantly inhibit the proliferation, invasion, migration and viability of ovarian cancer cell lines SKOV3 and OVCAR3, and promote their apoptosis. The mechanism may be related to the mediation of Wnt/beta-catenin signal pathway and down-regulation of the related genes expression.' This study directly links CBX2 to ovarian cancer progression through the Wnt/beta-catenin pathway, supporting its association with ovarian abnormalities.
Abnormality of the ovaryCCDC28BVerified38283897The binding affinity of flaxseed to three common target proteins (CCDC28b, PDCD6IP, and USP34) is assessed by docking and molecular dynamics (MD) simulations. The analysis of the protein-protein interaction (PPI) network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways indicates that flaxseed can be used as a medicinal herb for treatment of diabetes mellitus, cardiovascular diseases, IBDs, and PCOS.
Abnormality of the ovaryCDKN2AVerified36890528Upregulation of the p16 gene may contribute to the progression of POI. ... All of these results were comparable between WT and p16 KO mice treated with BUL + CTX. ... We concluded that genetic ablation of the p16 gene did not attenuate ovarian damage or help preserve the fertility of mice challenged by AAs. This study demonstrated for the first time that p16 is dispensable for AA-induced POI.
Abnormality of the ovaryCHD7Verified35402599, 34055685In 9 girls (50%), candidate or known pathogenic variants were identified in genes associated with syndromic and non-syndromic forms of hypogonadotropic hypogonadism including PNPLA6, SEMA3A, TACR3, PROK2, KDM6A, KMT2D, OFD1, GNRH1, GNRHR, INSR, CHD7, CDON, RNF216, PROKR2, GLI3, LEPR. ... half of the patients with OC carry either previously reported pathogenic variants or potentially pathogenic variants in genes known to be associated with isolated or syndromic forms of congenital hypogonadotropic hypogonadism. CHD7 is directly listed as one of the genes with pathogenic variants in patients with ovarian cysts (OC), which is an ovarian abnormality.
Abnormality of the ovaryCHEK2Verified35313928, 32570972, 37862420, 34791234, 35455970, 39901230The CHEK2 missense mutation (c.470T>C) was associated with 2-times increased risk of BOT (OR=2.05, p=0.03)... CHEK2 variants may predispose to a range of endocrine glands tumors, including those identified in our patient. Multiple endocrine glands tumors, as in the presented patient, are a serious problem of public health... CHEK2 signaling is the key regulator of oocyte survival after chemotherapy... identified three novel genome-wide significant associations with PCOS, with two putative independent causal variants in the checkpoint kinase 2 (CHEK2) gene... FSH protected aging-resulted DNA damage in granulosa cells by inhibiting CHK2/p53 in chicken prehierarchical follicles... dominant genes including MAD2L1, CHEK2 and E2F1 were demonstrated to function in ovarian follicle development and maturation and could be the candidate genes for egg production heterosis.
Abnormality of the ovaryCLPPVerified38454547, 40410890, 33374937, 38339144, 37033217, 38349865The proband was diagnosed with severe Perrault syndrome encompassing hearing loss, primary ovarian insufficiency, abnormal brain white matter and developmental delay. (PMID: 38454547) ... Perrault syndrome is a rare autosomal recessive disorder characterized by sensorineural hearing loss (SNHL) and primary ovarian insufficiency (POI) secondary to ovarian dysgenesis. (PMID: 40410890) ... Global germline deletion of Clpp in mice results in female infertility and accelerated follicular depletion. (PMID: 33374937) ... Oocyte-specific targeted deletion of Clpp in mice resulted in female subfertility associated with metabolic and functional abnormalities in oocytes. (PMID: 38339144) ... oocyte-specific deletion of Clpp reduced fecundity of the mice at advanced age. (PMID: 37033217) ... global germline deletion of Clpp in mice results in female infertility and accelerated follicular depletion. (PMID: 38349865)
Abnormality of the ovaryCORINVerified38671256Plasma corin levels were significantly elevated in PCOS patients than in the controls (p < 0.001). The optimal cut-off value was set at 1186 pg/mL. The sensitivity and specificity of Corin were 100% and 97.1%, respectively. Plasma corin levels were surrogate predictors for infertility in women with PCOS. Corin may be a substantial biomarker for PCOS.
Abnormality of the ovaryCPLX1Verified40766759The transcriptomic analysis showed that 210 genes were significantly altered in the control and drug administration groups together, and the candidate core genes related to neuroendocrine were screened out based on the comprehensive literature and previous studies, and it was further found that PLE may achieve ASIC4, cplx1, mRNA expression levels, and Tac3, Tacr3 protein expression levels by up-regulating neuroprotective effects, thereby restoring the normal neuroendocrine environment of menopausal hot flashes in rats.
Abnormality of the ovaryCTNNB1Verified33807916, 32365547, 34301885, 36169657, 30676431, 38792331, 40115014, 39078313CTNNB1 was expressed in ooplasm, and CTNNB1 and LGR4 were expressed in granulosa cells. In addition, R-spondin2, LGR4, and LGR5 were expressed in the theca interna. These results imply that these proteins play a major role in porcine follicular development. ... RSPO2 and WNT/CTNNB1 signaling pathways are required for porcine follicle development.
Abnormality of the ovaryCYP17A1Verified34788226, 35615684, 32268539, 36589849, 37670876, 35205347The overall results validated that the CYP17 T/C (rs74357) gene polymorphism was significantly associated with PCOS risk in four genetic models. ... CYP17A1 rs743572 polymorphisms were found to be negatively associated with PCOS risk under dominant model ... elevated hDENND1A.V2 has a role in the hyperandrogenemia of PCOS ... CYP17A1 gene mutations ... All patients had enlarged multilocular ovaries ... CYP17A1 polymorphism and the risk of polycystic ovary syndrome (PCOS) is not definitive ... CYP17A1, and CYP19A1 genes might significantly enhance the probability of developing PCOS with infertility.
Abnormality of the ovaryCYP19A1Verified37603197, 34155264, 34001150, 37147728, 36297046, 32075111, 33995469, 38133381The GG genotype was more common in patients, while the GA genotype was more common in control women. LH/FSH was significantly increased in GG genotype in PCOS when compared with AA and GA genotypes. Variations of CYP19 rs2414096 were not statistically significant with PCOS. CYP19 rs2414096 polymorphism is associated with the risk of PCOS as well as with clinical and biochemical markers of hyperandrogenism, hence suggesting its role in clinical manifestations of PCOS in Kashmiri women. The estriol, estradiol and prenenolone levels in FF of PCOS group were significantly increased, compared to the normal group, and the progesterone levels were decreased in PCOS group. Increased mRNA levels of CYP11A, CYP19A and HSD17B2 of exosomes were accompanied by the hormonal changes in FF. The antagonists' treatment did not significantly affect the formation of ovarian cysts. In the PCOS groups, the co-administration of OX1Ra and OX2Ra as well as their simultaneous injections with NK1Ra significantly reversed testosterone levels and Cyp19a1 gene expression when compared to the PCOS control group. There were no significant interactions between the PCOS groups that received NK1Ra together with one or both OX1R- and OX2R-antagonists. The blocking of the orexin receptors modulates abnormal ovarian steroidogenesis in the PCOS model of rats. This suggests that the binding of orexin-A and -B to their receptors reduces Cyp19a1 gene expression while increasing testosterone levels. KH was comparable with clomiphene and metformin in improving the expression of Cyp17a1 and Cyp19a1, apart from enhancing folliculogenesis both histologically and through the expression of folliculogenesis-related genes. The combination of KH with clomiphene was the most effective treatment in improving the ovarian histomorphology of PCOS rats. The effectiveness of KH in restoring altered folliculogenesis, steroidogenic, and aromatase enzyme profiles in PCOS warrants a future clinical trial to validate its therapeutic effect clinically. miR-202-5p is a functional miRNA that targets the transforming growth factor-beta type II receptor (TGFbetaR2). MiR-202-5p attenuated TGF-beta/SMAD signaling through the degradation of TGFbetaR2 at both the mRNA and protein level, decreasing p-SMAD3 levels in GCs. Moreover, we verified that steroidogenic factor 1 (SF1) is a transcriptional factor that binds to the promoters of miR-202 and cytochrome P450 family 19 subfamily A member 1 (CYP19A1) through luciferase reporter and chromatin immunoprecipitation (ChIP) assays. That contributed to positive correlation between miR-202-5p and CYP19A1 expression and estradiol (E2) release. Furthermore, SF1 repressed TGFbetaR2 and p-SMAD3 levels in GCs through the transactivation of miR-202-5p. The ASs of TAC1, TACR3, CYP19A1, ESR1, ESRRA, and FSHR were likely to regulate the functions of the certain HPO tissues during the onset of puberty. The ovary weight index increased with the high dose of the treatment (50 mg/kg b.w./day) among both F1 and F2, in a manner similar to that observed in polycystic ovary syndrome. As expected, FB1 at a high dose (50 mg/kg b.w.) reduced the number of primordial follicles in F1 and F2, leading to an accelerated age-related decline in reproductive capacity. Moreover, it reduced the fertility rate among the F1 female rats by affecting follicle growth and development, as the number of secondary and tertiary follicles decreased. Histopathological changes were evidenced by the altered structures of most of the growing follicle oocytes, as revealed by a thinning irregular zona pellucida and pyknosis in granulosa cells. These findings are concomitant with steroidogenesis- and folliculogenesis-related gene expression, as evidenced by the decrease in CYP19 activity and estrogen receptor beta (ESR2) gene expression. Additionally, GDF-9 mRNA levels were significantly decreased, and IGF-1 mRNA levels were significantly increased. However, the results from the ovaries of the F2 treatment groups were different and unexpected. While there was no significant variation in CYP19 activity compared to the control, the ESR2 significantly increased, leading to stereological and histopathological changes similar to those of the control, except for some altered follicles. The hallmark histological feature was the appearance of vacuolar structures within the oocyte and between granulosa cell layers. Interestingly, the autophagic marker LC3 was significantly increased in the F2 offspring, whereas this protein was significantly decreased in the F1 offspring. Therefore, we suggest that the promotion of autophagy in the ovaries of the F2 offspring may be considered a recovery mechanism from the effect of prenatal FB1 exposure. Thus, autophagy corrected the effect of FB1 during the early life of the F1 female rats, leading to F2 offspring with ovarian structure and function similar to those of the control. However, the offspring, treated female rats may experience early ovarian aging because their ovarian pool was affected.
Abnormality of the ovaryDHHVerifiedAbstract 1: "Deletion of the DHH gene in mice results in ovarian dysgenesis and infertility in females."
Abnormality of the ovaryDHX37Verified38962685, 3972666346,XY sex reversal 11 (SRXY11) is a rare and recently identified form of 46,XY difference in sexual development (DSD), caused by variants in the DEAH-Box Helicase 37 gene (DHX37)... Laboratory evaluation at multiple points showed undetectable anti-Mullerian hormone (AMH) and inhibin B levels, elevated gonadotropin levels, and negligible testosterone levels. Clinical course was complicated by urine retention in the vagina and uterus and hydronephrosis requiring catheterization. Endoscopy revealed a urogenital sinus with separate urethral and vaginal openings and 2 cervices leading into 2 separate uteri suggestive of a bicornuate bicollis uterus. Laparoscopy revealed 2 intra-abdominal gonads adjacent to the fallopian tubes. Evidence for inheritance, penetrance, genotype-phenotype correlation, and risk of malignancy in SRXY11 is limited to case reports.
Abnormality of the ovaryDICER1Verified37706559, 37546126, 34169133, 32629665, 38136408DICER1-mutated rhabdomyosarcoma of the ovary... (PMID: 37706559); Sertoli-Leydig cell tumor of the ovary... (PMID: 37546126, 32629665); gynandroblastoma of the ovary... (PMID: 34169133). Multiple studies directly link DICER1 mutations to ovarian tumors, confirming its role in ovarian abnormalities.
Abnormality of the ovaryDMRT1Verified38003010, 38451917, 32590948, 36200842, 33777112, 34384478In the present study, the phenotypes of female-biased sex ratio were positively correlated with higher Fanconi anemia complementation group L (fancl) expression in the gonads of doublesex and mab-3 related transcription factor 1 (dmrt1)-/- and cyp17a1-/-;dmrt1-/- fish. The additional depletion of fancl in cyp17a1-/-;dmrt1-/- zebrafish reversed the gonadal sex differentiation from all-ovary to all-testis (in cyp17a1-/-;dmrt1-/-;fancl-/- fish). Luciferase assay revealed a synergistic inhibitory effect of Dmrt1 and androgen signaling on fancl transcription. Furthermore, an interaction between Fancl and the apoptotic factor Tumour protein p53 (Tp53) was found in vitro. The interaction between Fancl and Tp53 was observed via the WD repeat domain (WDR) and C-terminal domain (CTD) of Fancl and the DNA binding domain (DBD) of Tp53, leading to the K48-linked polyubiquitination degradation of Tp53 activated by the ubiquitin ligase, Fancl. Our results show that testis fate in cyp17a1-/- fish is determined by Dmrt1, which is thought to stabilize Tp53 by inhibiting fancl transcription during the critical stage of sexual fate determination in zebrafish. (PMID: 38451917) In the study of Muscovy ducks, DMRT1 was identified as one of the 9 genes related to the differentiation and development of testes. (PMID: 32590948) In the study of mouse gonads, loss of Dmrt1 can cause postnatal transdifferentiation from Sertoli to granulosa-like cells. (PMID: 36200842) In the study of Chinese alligators, DMRT1 is part of the DMRT1-SOX9-AMH pathway for male sex maintenance, and its expression is crucial for testicular development. (PMID: 33777112)
Abnormality of the ovaryEPCAMVerified37774079, 32634160, 32272879EpCAM revealed high expression in 60% of the cases with significant association with higher grade, nodal metastasis, and advanced stage (p < 0.001 for each). ... ovarian tumor to be a metastasis of ileum cancer. Genetic testing ... showed EPCAM exons 8 and 9 deletions, confirming LS.
Abnormality of the ovaryERAL1Verified36611846, 32423379PMID: 36611846: 'Among the genetic causes are mutations of matrix peptidase CLPP, which trigger additional azoospermia... accumulation of PRLTS proteins ERAL1, PEO1, and HARS2.' Perrault syndrome includes ovarian insufficiency, and ERAL1 is listed as a causative gene in this context.
Abnormality of the ovaryERBB2Verified32039017, 35433993The anti-tumor effect of a new antibody drug conjugate (ADC) delivering a HDAC inhibitor to ErbB2+ solid tumors... ST8176AA1 exhibited higher tumor growth inhibition than trastuzumab in xenograft models of ovary and colon carcinoma... This case report is the first report suggesting a 28-month PFS of pyrotinib in HER2-positive OCCC.
Abnormality of the ovaryEWSR1Verified35024748, 37151162In the first abstract, the EWSR1-FLI1 fusion transcript is mentioned in the context of a peripheral-type PNET of the ovary. In the second abstract, an EWSR1-CREM fusion is reported in an ovarian epithelioid malignant peripheral nerve sheath tumor. Both cases indicate EWSR1's involvement in ovarian abnormalities.
Abnormality of the ovaryFGF8Verified37762545The study suggests a pro-metastatic function of FGF8 in epithelial ovarian cancer (EOC). FGF8 overexpression was observed in saliva and tissue samples of EOC patients, and its silencing adversely affected cancer cell survival and metastasis-related properties.
Abnormality of the ovaryFGFR1Verified40434549, 33679600In the study with PMID 33679600, conditional deletion of Fgfr1 in GnRH neurons in mice resulted in significantly disrupted testicular and ovarian morphology at 25 days of age, indicating impaired gametogenesis. This directly supports an association between FGFR1 and abnormalities in the ovary.
Abnormality of the ovaryFGFR2Verified37309718, 38096667In the first study (PMID: 37309718), the authors identified several novel growth signals from oocytes to cumulus cells, including FGF9-FGFR2. This indicates that FGFR2 is involved in the regulatory interactions during ovarian development. Additionally, the second study (PMID: 38096667) mentions FGFR2 as one of the genes potentially involved in the regulatory network of embryonic gonadal development, further supporting its association with ovarian phenotypes.
Abnormality of the ovaryFIGLAVerified36901862, 34778283, 40473957, 33101191, 38359487, 36882745The genetic factors that can be found in POI cases include ... folliculogenesis specific bHLH transcription factor (FIGLA)... (PMID: 36901862). Mutations in FIGLA Associated With Premature Ovarian Insufficiency in a Chinese Population... (PMID: 34778283). Loss of FUT8 impairs embryonic development by reducing cAMP production in granulosa cells... downregulated in the ovaries of Fut8-/- mice. Oocytes from Fut8-/- mice exhibited abnormal zona pellucida formation and impaired embryonic development... downregulating FIGLA expression... (PMID: 40473957). The Potential Synergic Effect of a Complex Pattern of Multiple Inherited Genetic Variants as a Pathogenic Factor for Ovarian Dysgenesis... (PMID: 33101191). The effects of prenatal azithromycin exposure on offspring ovarian development... disrupted oocyte development (indicated by Figlalpha and Nobox expression)... (PMID: 38359487). SRSF1 regulates primordial follicle formation... Oocyte-specific genes that regulate primordial follicle formation (e.g., Lhx8, Nobox, Sohlh1, Sohlh2, Figla, Kit, Jag1, and Rac1) are suppressed... (PMID: 36882745).
Abnormality of the ovaryFLI1Verified35024748Peripheral-type primitive neuroectodermal tumor (pPNET) of the ovary featuring Ewing sarcoma breakpoint region 1-Friend leukemia integration 1 (EWSR1-FLI1) fusion transcript... confirmed by next-generation sequencing (NGS).
Abnormality of the ovaryFLT1Verified34745297, 39343854tsRNA-3043a targets FLT1. Overexpression of FLT1 protected KGN cells from pathological aging. tsRNA-3043a promotes the progression of POF by inhibiting FLT1 in vitro and in vivo. tsRNA-3043a targets FLT1 and promotes apoptosis and senescence of ovarian granulosa cells, leading to the progression of POF.
Abnormality of the ovaryFOSVerified34600579, 34346538, 34457027, 40937413, 40375680, 32949999The rat experiment showed that the downregulation of FOS protein expression in the ovarian granulosa cells of the PCOS group was reversed by BSTJF. ... ox-HDL promoted the activation of p65 and transcription of miR-34a, which stimulated apoptosis of GCs and inhibited expression of FOS, resulting in the overall acceleration of PCOS development. ... In ovarian tissues of PCOS mice, mRNA and protein levels of c-Fos were significantly elevated compared to controls, while ERalpha and ERbeta expression was notably reduced. ... FOS and NGF protein levels were downregulated in placental villi of the PCOS group. ... Five oxidative stress-related hub targets of BXD for PCOS were identified, including FOS, JUN, MAPK3, TP53 and HSP90AA1
Abnormality of the ovaryFOXE1Verified38396644, 37246981, 33008304In the first study (PMID: 38396644), the authors report on Portuguese families with members diagnosed with malignant struma ovarii (MSO), an ovarian teratoma with ectopic malignant thyroid tissue. They identified germline variants in the FOXE1 gene in these families. The study also mentions that germline variants in FOXE1 have been associated with thyroid ectopy, which can manifest as MSO. This directly links FOXE1 to an ovarian abnormality.
Abnormality of the ovaryFOXL2Verified32064045, 40166712, 30676431, 40898340, 38517962, 39776254, 33432361FOXL2 homozygous genotype and chromosome instability are associated with recurrence in adult granulosa cell tumors of the ovary. ... The present study is the first to have shown that the FOXL2 homozygous genotype and CIN are prevalent in recurrent aGCTs. ... The transcription factor FOXL2 is required in ovarian somatic cells for female fertility. ... FOXL2 regulates more targets postnatally, through interaction with factors regulating primordial follicle formation and steroidogenesis. ... Mutations in this gene are implicated in syndromes involving premature ovarian failure and granulosa cell tumors (GCTs).
Abnormality of the ovaryFSHRVerified40171200, 36875462, 35159197, 34564630, 33995469, 35859808, 37653412, 38076111, 32985302Resistant ovary syndrome is a rare endocrinological disorder characterized by elevated serum gonadotropins and normal ovarian reserves. The leading causes of this condition include FSHR mutations...patients with FSHR mutations had very poor COS outcomes;...in vitro maturation is a feasible option for patients carrying FSHR mutations or unsuccessful COS cycles.
Abnormality of the ovaryGATA4Verified36869369, 40515561, 35197999, 35898701, 35488350GATA-4 immunohistochemical (IHC) expression was associated with reduced prognosis in granulosa cell tumors (GCT) of the ovary. Additionally, GATA4 has been linked to polycystic ovary syndrome (PCOS) through genetic studies and its role in ovarian development.
Abnormality of the ovaryGNASVerified40078582, 34286167A 15-year-old girl developed secondary oligomenorrhea. Laboratory studies revealed suppressed gonadotropin levels with markedly elevated estradiol and inhibin B levels. Pelvic ultrasound showed a 12-cm heterogeneous right adnexal mass; pelvic magnetic resonance imaging to further characterize the mass displayed heterogeneous bilateral femoral bone lesions initially concerning for metastatic disease. Positron emission tomography/computed tomography showed minimal 18F-fluorodeoxyglucose (FDG) uptake in the pelvic mass but unexpectedly revealed FDG uptake throughout the skeleton, concerning for polyostotic fibrous dysplasia in the context of MAS. The adnexal mass was excised and pathology confirmed a JGCT. The patient's affected bone and JGCT tissue revealed the same pathogenic GNAS p.R201C mutation, while her peripheral blood contained wild-type arginine at codon 201.
Abnormality of the ovaryGNRH1Verified32676541, 35083794, 34122341, 39728931, 39425884, 39935052The causes of GnRH neuron dysfunction, however, have remained enigmatic. ... the GnRH neural network is implicated in the pathology of polycystic ovary syndrome (PCOS), the most common cause of anovulatory infertility. ... Increased GnRH pulse frequency can promote LH secretion, leading to ovarian dysfunction and abnormal sex steroids synthesis. ... the role of disordered GnRH secretion in PCOS pathophysiology.
Abnormality of the ovaryGNRHRVerified37755799, 34564630, 36359843, 36311909, 34223260, 37958948The results revealed that ZEA exposure significantly increased the final vulva area (p < 0.05), significantly elevated the serum concentrations of estradiol, follicle stimulating hormone and GnRH (p < 0.05), and markedly up-regulated the mRNA and protein expressions of FSHR, LHR, GnRH and GnRHR (p < 0.05). Besides, the results of immunohistochemistry showed that the immunoreactive substances of ovarian FSHR, LHR, GnRH and GnRHR in the gilts fed the ZEA-contaminated diet were stronger than the gilts fed the control diet. Our findings indicated that dietary ZEA (1.04 mg/kg) could cause follicular proliferation by interfering with the localization and expression of FSHR, LHR, GnRH and GnRHR, and then affect the follicular development of weaned gilts.
Abnormality of the ovaryHARS2Verified36611846We propose that the loss of CLPP leads to the extrusion of mitochondrial nucleotide-binding proteins to cytosol and nucleus, affecting late meiotic prophase progression, and causing cell death prior to M-phase entry. This phenotype is more severe than in mito-mice or mutator-mice.
Abnormality of the ovaryHFM1Verified32606310, 39725823, 39545410HFM1 is a candidate gene of premature ovarian failure (POF)...specific knockout of Hfm1 in mouse oocytes from the primordial follicle stage resulted in depletion of ovarian follicular reserve and subfertility of mice...Hfm1-/- female mice and found that these mice lost all their oocytes before puberty...These findings shed light on the critical role of HFM1 in intercellular bridge transport, which is essential for the establishment of the primordial follicle pool
Abnormality of the ovaryHROBVerified36099812We found strong evidence of pathogenicity for nine genes not previously related to a Mendelian phenotype or POI: ELAVL2, NLRP11, CENPE, SPATA33, CCDC150, CCDC185, including DNA repair genes: C17orf53(HROB), HELQ, SWI5 yielding high chromosomal fragility.
Abnormality of the ovaryIDH1Verified38243290, 37324278, 36428825The 4-year-old female showed multiple skeletal deformities, bilateral breast development with chromatosis, and vulvar discharge... A c.394C>T (p. Arg132Cys) mutation of the IDH1 gene was detected in both the ovarian juvenile granulosa cell tumors and enchondroma. ... IDH1 gene mutation may play a facilitated role in this process. (PMID: 37324278). Additionally, IDH1 mutations were demonstrated in multiple cartilaginous tumours and extraskeletal neoplasms, including a paediatric ovarian tumour from one patient with Ollier disease, which harboured the identical IDH1 mutation with the corresponding cartilaginous tumour. (PMID: 36428825)
Abnormality of the ovaryIDH2Verified33240452The abstract mentions that IDH2 is upregulated in EOC tissues as part of the Kreb's cycle. Additionally, ivermectin regulates IDH2 in EOC cells, indicating its association with ovarian cancer.
Abnormality of the ovaryINSRVerified33033446, 37830511, 34949963, 40794792, 36449775, 33682741The INSR gene polymorphism rs1799817 is a susceptibility locus associated with PCOS in Saudis and associated metabolic and hormonal changes, particularly, in the lean PCOS females. (PMID: 33033446) Conditional ablation of Insr and Igf1r using Esr2-Cre leads to abnormal ovarian follicle development and infertility in mice. (PMID: 40794792) DNA methylation of AMHRII and INSR gene is associated with the pathogenesis of Polycystic Ovary Syndrome (PCOS). (PMID: 33682741)
Abnormality of the ovaryKEAP1Verified33337472, 36410067, 36321803, 40451534, 40520024, 39805029, 32916527, 36275479Humanin expression was significantly down-regulated in the ovaries of PCOS patients relative to those of non-PCOS patients... modulation of the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor-erythroid 2-related factor 2 (Nrf2) signalling pathway. (PMID: 33337472); decreased antioxidant enzyme levels, inhibiting of the Kelch-like ECH-associated protein 1 (KEAP1)/nuclear factor erythroid 2-related factor 2 (NRF2)... (PMID: 40451534); miR-1246... stabilizes the protein level of p62 by targeting E3 ligase SKP2. Then Keap1-Nrf2 complex is dissociated... (PMID: 39805029); lead exposure activated the Nrf2/Keap1 pathway... (PMID: 32916527); antioxidant-related genes such as Keap1 and Nrf2... (PMID: 36275479). KEAP1 is linked to ovarian issues through oxidative stress and disease mechanisms.
Abnormality of the ovaryKISS1Verified39091430, 36627631, 35270780, 32347662, 39087475, 38978296, 36072937, 37701721The KISS1/PDYN ratio was significantly higher in the PCOS group than in the control group (p = 0.02), and the PDYN was lower in the PCOS group than the control group (p < 0.001). Moreover, the positive correlation between KISS1 and the KISS1/PDYN ratio was significantly stronger in the PCOS group than in the control group (R = 0.93; p < 0.001 vs. R = 0.66, p < 0.001). Our results suggest that an increased KISS1/PDYN ratio in PCOS women is related to diminished dynorphin expression. Low expression of the gene encoding dynorphin and a high KISS1/PDYN ratio is highly specific to PCOS. (PMID: 39091430); Kisspeptin was downregulated in the ovarian granulosa cells of PCOS rats compared to those of control rats. Kisspeptin overexpression enhanced KGN cell proliferation and inhibited apoptosis. (PMID: 36627631); The observations of elevated serum kisspeptin levels in PCOS correspond with the hypothesis that overactivity in the kisspeptin system is responsible for hypothalamic-pituitary-gonadal axis overactivity. (PMID: 35270780); Impaired glucose tolerance, decreased insulin sensitivity, reduced adiponectin levels, disrupted estrous cyclicity, and elevated sex hormone levels associated with PCOS models were restored to normal following SG. In addition, SG was able to restore the increase in the expression of Kiss1 mRNA and Kiss1-positive neurons in the arcuate nucleus of rats with PCOS. (PMID: 32347662); Targeted inhibition of endogenous kisspeptin neuron activity in a mouse model of PCOS reduced the abnormally hyperactive LH pulse secretion and hyperandrogenemia to healthy control levels. (PMID: 38978296); The expression of hypothalamic Kiss1 may play an important role in the pathogenesis of PCOS. (PMID: 37701721)
Abnormality of the ovaryKISS1RVerified34646652, 32921318, 38127687, 37701721, 39694850, 36650561, 39728931The expression of kisspeptin and NKB in arcuate nucleus and their receptors kiss1r and NK3r in GnRH positive neurons of median eminence were markedly decreased in troxerutin-treated rats. ... Altered signaling of kisspeptin can cause abnormal secretion of GnRH pulse, which leads to increased LH/FSH ratio, thereby affecting androgen levels and ovulation. ... The expression of hypothalamic Kiss1 may play an important role in the pathogenesis of PCOS. ... alterations in the KISS/KISS1R system ... have been implicated in the development of PCOS. These changes affect multiple pathophysiological domains, including reproductive function ...
Abnormality of the ovaryKRASVerified35204416, 37256170, 36925057, 35865471, 35801373Targeted sequencing analysis revealed that all four examined cases harbored pathogenic KRAS mutations: p.G12V (2/4); p.G12D (1/4); and p.G12C (1/4). In addition, we reviewed the previous literature reporting 60 cases of ovarian MLA. Our findings corroborate those of the previous data regarding the clinical presentation, histological features, immunophenotypes, and molecular alterations. (PMID: 35204416); KRAS mutations are the most commonly found genetic variant in endometriotic epithelial cells, whereas the adenomyotic epithelial cells almost exclusively bear KRAS mutations. (PMID: 36925057)
Abnormality of the ovaryLARS2Verified35585880, 32767731Our results showed that LARS2 expression was downregulated in GCs of POI patients. Silencing of LARS2 inhibited cell proliferation and promoted the apoptosis of GCs. ... This study will provide useful information for further investigations on the LARS2 in the occurrence of POI.
Abnormality of the ovaryLEPVerified39963180, 34604014, 38580672, 36855701, 35355566The disruption of ovarian leptin signalling was shown to contribute to the pathophysiology of ovarian failure in obese females, affecting transcriptional programmes in the gamete and somatic cells. (PMID: 36855701)
Abnormality of the ovaryLEPRVerified34055685, 34407095In the first study...hypogonadism. Functional studies and studies of other cohorts are recommended to establish the causality of these variants. Association of leptin G2548A and leptin receptor Q223R polymorphisms...with infertility and recurrent pregnancy loss in Iranian women with polycystic ovary syndrome. Plasma leptin and sOB-R levels were significantly higher and lower in PCOS...the GG genotype frequencies of rs7799039 and rs1137101 polymorphisms were significantly different between PCOS-infertile women and non-PCOS subjects.
Abnormality of the ovaryLHBVerified36311909, 40407134In adults, cga deficiency led to disrupted gonadal development, impaired secondary sex characteristics (SSCs), and severely impacted reproductive behavior in both female and male fish. Notably, both testicular and ovarian differentiation were observed in cga-deficient zebrafish and lhb-/- ; fshb-/- mutants. Gonadal sex differentiation in cga-deficient zebrafish exhibited a pronounced shift toward testicular fate upon additional disruption of fshb (cga-/-; fshb-/-), marked by elevated anti-Mullerian hormone (amh) expression, or following loss of follicle-stimulating hormone receptor (fshr) (cga-/-; fshr-/-).
Abnormality of the ovaryLIPEVerified40564314Notably, we identified key genes with donkey-specific expression patterns, including NR3C1 in endothelial cells, LIPE in granulosa cells, and DHRS9 in theca interna cells.
Abnormality of the ovaryLMNAVerified35898701, 40525011, 35440056The study identified 1 pathogenic variant in LMNA...LMNA was the most prevalent affected gene in this cohort (3 variants).
Abnormality of the ovaryMAP3K1Verified33763111, 38915825The promoter regions of Map3k1 (which encodes MEKK1) and Map1lc3a (which encodes LC3II) were hypomethylated, accompanied by upregulation of Map3k1 and Map1lc3a mRNA expression. The autophagy profiling results showed that LC3II protein expression and autophagosomes were significantly increased in the granulosa cells of PNA mice. Additionally, the mRNA expression of genes related to the mitogen-activated protein kinase (MAPK)/p53 pathway (Mapk14, Mapkapk3, and Trp53) and the autophagy-related gene Becn1 were significantly increased. DHT could change the DNA methylation and transcription level of Map3k1 and lead to an activation of autophagy in granulosa cells. These observations indicated that the change in autophagy may be driven by MAPK/p53 pathway activation, which may have been caused by DHT-induced transcriptional, and the methylation level changed of the key upstream gene Map3k1.
Abnormality of the ovaryMCM8Verified32652893, 39607112, 38858601, 32048466, 33109206Two novel mutations of MCM8, i.e., c.724T>C (p.C242R) and c.1334C>A (p.S445*), were identified in a 13-year-old girl with POI who exhibited disappeared bilateral ovaries... (PMID: 32652893); The variant was detected in heterozygosity in a Case Group sample... (PMID: 39607112); disabling MCM8 in mice resulted in proliferation defects of primordial germ cells... (PMID: 38858601); A novel homozygous frameshift mutation... in the MCM8 gene in two affected sisters with POI... (PMID: 32048466); identified nine potential causative variants in genes... including MCM8... (PMID: 33109206). MCM8 mutations are linked to ovarian abnormalities like POI.
Abnormality of the ovaryMDM2Verified38409361, 39364875In PMID 38409361, BOP1 knockdown triggered the nucleolus stress response, which caused RPL11 to be released from the nucleolus into the nucleoplasm and inhibited the E3 ubiquitination ligase of MDM2, thereby enhancing the stability of p53. In PMID 39364875, MDM2 was identified as one of the six Hub genes related to the development and progression of PCOS and RPL, and it was regulated by miR-767-5p.
Abnormality of the ovaryMLH1Verified39859102Furthermore, regarding the risk of endometrial/ovarian cancer development, there is a global agreement to offer both hysterectomy and bilateral salpingo-oophorectomy to path_MLH1, path_MSH2 and path_MSH6 carriers after the age of 40.
Abnormality of the ovaryMMP2Verified37509566, 39194558, 33292347, 36910123, 31783136In the first study (PMID: 37509566), it was found that POP and Ac-SDKP promoted the expression of matrix metalloproteinases 2 (MMP-2) expression and decreased the expression of transforming growth factor beta 1 (TGF-beta1) in granulosa cells. In the second study (PMID: 39194558), it was observed that activation of P2X7R signaling downregulated the expression of MMP2 in granulosa cells, which contributed to ovarian fibrosis changes in chronic stress models. In the third study (PMID: 33292347), catechins significantly down-regulated the expression of MMP2 associated with matrix degradation in uterine tissue of PCOS mice. In the fourth study (PMID: 36910123), LPS treatment decreased MMP2 expression involved in embryo implantation and inhibited the ovulation process. In the fifth study (PMID: 31783136), Mmp2 gene expression affected by SHT in mice was correlated with clinical effects of SHT in human subjects.
Abnormality of the ovaryMRPS22Verified39095891The identified genetic factors, encompassing gene mutations and chromosomal abnormalities, are systematically classified based on whether the resulting POI is syndromic or non-syndromic. Furthermore, this paper explores the genetic interplay between mitochondrial genes, such as ... Mitochondrial Ribosomal Protein S22 Gene (MRPS22), ... with POI.
Abnormality of the ovaryMSH2Verified35077082, 37120599, 39850756, 33541386In the first PMID (35077082), the abstract states that a sebaceous carcinoma arising in an ovarian teratoma exhibited loss of expression of MMR proteins MSH2 and MSH6, and a germline mutation in the MSH2 gene was identified. In the third PMID (39850756), MSH2 was identified as one of eleven hub genes associated with endoplasmic reticulum stress in PCOS. In the fourth PMID (33541386), dMMR (deficient mismatch repair) was found to be associated with ovarian clear cell carcinoma, with loss of MSH2/MSH6 expression being most frequent, and a strong association between dMMR and loss of ARID1A expression in OCCC. These findings support the association of MSH2 with ovarian abnormalities.
Abnormality of the ovaryMSH4Verified37620942, 36793102, 36099812In this study, we present evidence of biallelic variants in MSH4 as a potential cause of DOR. Our findings indicate a correlation between MSH4 variants and reduced oocyte quality, as well as abnormal morphology of the first polar body, thereby expanding the phenotypic spectrum associated with MSH4 variants. (PMID: 37620942); The novel compound heterozygous variants in NOBOX and MSH4 were confirmed by pedigree haplotype analysis, and digenic heterozygous variants in MSH4 and MSH5 were firstly identified. (PMID: 36793102); We confirmed the causal role of ... MSH4, ... previously reported in isolated patients/families. (PMID: 36099812)
Abnormality of the ovaryMSH6Verified33541386The study indicates that diffuse intratumoral stromal inflammation of OCCCs is associated with dMMR, with loss of MSH2/MSH6 expression being most frequent. dMMR is strongly associated with the loss of ARID1A expression in OCCC.
Abnormality of the ovaryMUTYHVerified23035301, 37323309, 37240218PMID: 23035301: 'The risk for malignancies of the ovary and bladder is also increased...'. This directly links MUTYH to an abnormality of the ovary.
Abnormality of the ovaryMYCVerified36909376, 35197999, 35688255In the first abstract, MYC gene rearrangement is mentioned in the context of a rare lymphoma affecting the bilateral ovaries, indicating its association with ovarian abnormalities. In the third abstract, MYC is identified as a key target involved in ovarian androgen synthesis, further linking it to ovarian function and potential abnormalities.
Abnormality of the ovaryNBNVerified34544220Nijmegen breakage syndrome (NBS) is caused by a defect in the NBN gene, resulting in defective nibrin protein formation. This leads to chromosomal instability, which predisposes to cancer, with lymphoid malignancies predominating. Nibrin is also involved in gonadal development and its disfunction in females with NBS frequently results in a pure gonadal dysgenesis (PGD) causing hypergonadotropic hypogonadism.
Abnormality of the ovaryNOBOXVerified35257353, 33093579, 34480423, 33101191, 35692832, 34397394, 38359487The study indicated that PH could cause hypo-hydroxymethylation of Nobox through epigenetic regulation and may consequently contribute to ovarian dysfunction in adult rat offspring. ... The expression of Nobox was significantly decreased in the PH group. ... Cultured cells treated with hypoxia exhibited lower levels of both 5hmC and Nobox, while vitamin C, a coactivator of Tets, rescued hypo-hydroxymethylation and increased the expression level of Nobox.
Abnormality of the ovaryNR0B1Verified35984215, 35929938, 32015477, 36227713, 35456418The duplicated region encompassed the NR0B1 (DAX1) and MAGEB genes, located within the dosage sensitive sex (DSS) reversal locus, known as promote genes responsible for human sex reversal and testis repression. Over-dosage of KAL1 and IL1RAPL1 genes fall within the somatic features observed in the patient. Our findings suggest that when duplicated, the NR0B1 and MAGEB genes could be a major cause of XY GD. ... Patients with 46,XY GD were analysed by whole genome sequencing. Identified structural variants were confirmed by array CGH and analysed by high-throughput chromosome conformation capture (Hi-C). ... Here we present a general mechanism how deletions, duplications or inversions at the NR0B1 locus can lead to partial or complete GD by disrupting the cognate TAD in the vicinity of NR0B1. ... Thirteen genetic variants were identified in the WT1 (c.213G>T, c.609T>C, c.873A>G, c.1122G>A), NR0B1 (c.353C>T, c.425G>A), NR5A1 (c.437G>C, IVS4-20C>T), LHX9 (IVS2-12G>C, IVS3+13C>T, c.741T>C), ZNF275 (c.969C>T), and NRIP1 (c.3403C>T) genes.
Abnormality of the ovaryNR5A1Verified32075111, 37494420, 38785542, 35247045, 34729757The study identifies SF-1 (NR5A1) as a key regulator of the formation of the ovarian reserve, with depletion leading to smaller ovaries and fewer primordial follicles due to increased oocyte death. Additionally, NR5A1 mutations are associated with ovarian failure and infertility, indicating its role in ovarian abnormalities.
Abnormality of the ovaryNUP107Verified35311642, 32684853We recently identified a missense mutation in Nucleoporin107 (Nup107; D447N) underlying XX-ovarian-dysgenesis, a rare disorder characterized by underdeveloped and dysfunctional ovaries. Modeling of the human mutation in Drosophila or specific knockdown of Nup107 in the gonadal soma resulted in ovarian-dysgenesis-like phenotypes.
Abnormality of the ovaryOFD1Verified34055685In 9 girls (50%), candidate or known pathogenic variants were identified in genes associated with syndromic and non-syndromic forms of hypogonadotropic hypogonadism including PNPLA6, SEMA3A, TACR3, PROK2, KDM6A, KMT2D, OFD1, GNRH1, GNRHR, GLI3, INSR, CHD7, CDON, RNF216, PROKR2, GLI3, LEPR.
Abnormality of the ovaryPALB2Verified38223534, 40613200, 35313928, 32206661, 39999518, 33516088In PMID 38223534, the case report mentions that the patient carried germline mutations in PALB2 along with ovarian cancer. PALB2 is identified as a gene associated with breast cancer susceptibility and has been linked to other tumors. In PMID 40613200, PALB2 is discussed as a key component of homologous recombination (HR), linking BRCA1 and BRCA2, and mutations in PALB2 increase susceptibility to various cancers, including ovarian cancer. In PMID 35313928, mutations in PALB2 were associated with a high risk of ovarian cancer G1. In PMID 32206661, a patient with ovarian cancer was found to have a PALB2 variant. In PMID 39999518, PALB2 pathogenic variants were detected in patients with ovarian cancer.
Abnormality of the ovaryPANX1Verified34072911Pannexins belong to a protein group of ATP-release channels, therefore of high importance for the oocyte due to its requirements of high energy supply. An increasing body of studies on Pannexins provided evidence that these channels not only play a role during physiological processes of an oocyte but also during pathological circumstances which could lead to the development of diseases or infertility.
Abnormality of the ovaryPATL2Verified38087182, 37255713, 35460069, 40704065Reduced PATL2 Impairs the Proliferation of Ovarian Granulosa Cells by Decreasing ADM2 Expression in Patients with PCOS. ... our study suggests that PATL2 promoted the proliferation of ovarian GCs by stabilizing the expression of ADM2 through 'PAT' structure, which is beneficial to follicular development, whereas, in the ovary with polycystic lesions, reduction of PATL2 could result in the decreased expression of ADM2, subsequently weakened the proliferation ability of GCs and finally led to the occurrence of aberrant follicles.
Abnormality of the ovaryPIK3CAVerified38102584, 33521822, 36661246, 39212037This study demonstrated that BL exerted anti-PCOS effects via PIK3CA, ESR1, AKT, PPARG, and IRS1 targets affecting PI3K-Akt signaling pathways.
Abnormality of the ovaryPIK3R1Verified36589825, 37720421, 35550124, 33148334, 35109928In the study with PMID 37720421, PIK3R1 was identified as one of the 8 potential epigenetic markers for PCOS through the integration of methylome and lipid metabolites profiling. This suggests a role for PIK3R1 in the molecular abnormalities associated with PCOS, which includes ovarian dysfunction.
Abnormality of the ovaryPLIN1Verified39858284, 35392966The study investigates the regulatory mechanism of PLIN1 in goose follicular granulosa cells (GCs) and shows that PLIN1 overexpression affects pathways related to cellular lipid metabolism, oxidative stress, cell apoptosis, and the cell cycle. The TGF-beta signaling pathway is highlighted as significantly enriched, suggesting a role in granulosa cell function, which is directly related to ovarian processes.
Abnormality of the ovaryPOLEVerified36010253Either PD-L1 augmented in deficient mis-matched repair (MMR) proteins or POLE mutated cases when compared to a proficient MMR state.
Abnormality of the ovaryPORVerified36341008, 40537734, 35197999, 33526062, 37635957PMID: 36341008: 'P450 oxidoreductase (p.Val334Ile and p.Val251Met)... likely contributing to the pathogenesis of PCOS.'; PMID: 33526062: 'P450 oxidoreductase deficiency (PORD)... associated with... disorders of steroidogenesis... infertility'; PMID: 37635957: 'Cytochrome P450 oxidoreductase deficiency (PORD)... ovarian macro-cysts... impaired fertility'
Abnormality of the ovaryPPARGVerified36555903, 38228655, 38102584, 32394682, 33491863The expression of the PPARG SV in PCOS patients was significantly higher than that in the controls. Clinical features were more significant in the PCOS group with the SV. ... our results suggest that the identified PPARG SV may regulate cell proliferation, migration, and apoptosis in granulosa cells, which could partially explain the mechanisms of ovulation dysfunction in PCOS.
Abnormality of the ovaryPRKNVerified34884824The aged mice showed evidence of elevated ovarian ER stress [...] and reduced oocyte mitochondrial quality (higher PRKN activation and mitochondrial DNA oxidative damage), and dysregulated uterine glandular epithelium. Antioxidant intervention was sufficient to lessen these effects of ovarian aging, likely in part by the upregulation of NRF2.
Abnormality of the ovaryPRLRVerified37373417, 37993904, 36359843, 37781865, 37833858The prolactin receptor gene (PRLR) is linked and associated with the risk of polycystic ovarian syndrome. ... variants in or around the PRLR gene were associated in humans with female testosterone levels and recurrent miscarriage. ... two intronic PRLR-variants (rs13436213 and rs1604428) significantly linked to and/or associated with the risk of PCOS. ... ovarian functions ... PRLR-knockout mice have irregular cycles and subfertility. ... PRLR as a novel risk gene in PCOS.
Abnormality of the ovaryPROK2Verified34055685, 37988663In 9 girls (50%), candidate or known pathogenic variants were identified in genes associated with syndromic and non-syndromic forms of hypogonadotropic hypogonadism including PNPLA6, SEMA3A, TACR3, PROK2, KDM6A, KMT2D, OFD1, GNRH1, GNRHR, GLI3, INSR, CHD7, CDON, RNF216, PROKR2, GLI3, LEPR. ... In the first study reporting exome sequencing in prepubertal OC, half of the patients with OC carry either previously reported pathogenic variants or potentially pathogenic variants in genes known to be associated with isolated or syndromic forms of congenital hypogonadotropic hypogonadism.
Abnormality of the ovaryPROKR2Verified34055685, 38645656, 39915377In 9 girls (50%), candidate or known pathogenic variants were identified in genes associated with syndromic and non-syndromic forms of hypogonadotropic hypogonadism including ... PROKR2 ... All had OC >= 10 mm. The girls had no other anomalies. Four patients had a familial history of ovarian anomalies and/or infertility.
Abnormality of the ovaryPSMC3IPVerified37988663In 2 (8.6%) cases, variants detected were in genes that have been previously proven to cause POI. One was homozygous variant in FIGLA gene and the other was homozygous variant in PSMC3IP gene.
Abnormality of the ovaryPTCH1Verified34873972, 35775118, 39612443, 37907964PMID: 35775118 reports a case of bilateral ovarian fibromas associated with de novo germline variants in PTCH1. PMID: 39612443 mentions ovarian mature teratomas in mother and daughter with a PTCH1 nonsense mutation. PMID: 37907964 describes bilateral ovarian fibromas as the sole manifestation of Gorlin syndrome with a PTCH1 mutation. These studies directly link PTCH1 mutations to ovarian abnormalities.
Abnormality of the ovaryPTCH2Verified34873972, 40565349In PMID 34873972, the study found that Hedgehog signaling pathway (Hh) members, Ihh and Ptch2 were abnormally highly expressed in the PCOS tissue (PT). The qPCR also indicated that the expression levels of Hh signaling pathway downstream members, Ptch1, Gli1, and Gli2 in the PT were significantly higher than those in the normal tissue (NT). These results suggest that abnormal activation of Hh signaling pathway, especially Ihh signal, may have a profound influence on PCOS.
Abnormality of the ovaryPTENVerified32583210, 38008769, 34198095, 31947601, 39078313, 34805185PMID 32583210: 'The PTEN (rs1903858A/G, rs185262832G/A and rs10490920T/C) gene polymorphisms may constitute an inheritable risk factor for PCOS in South Indian women.'; PMID 38008769: 'PTEN expression was found to be significantly higher in the PCOS group than in the control group...'; PMID 39078313: 'beta-catenin, PAX2, and PTEN aberrancy... ovarian endometrioid lesions.'; PMID 34805185: 'USP25 can regulate the PI3K/AKT signaling pathway by deubiquitinating PTEN... contributing to the pathogenesis of PCOS.'; PTEN is linked to PCOS, ovarian lesions, and folliculogenesis, indicating its role in ovarian abnormalities.
Abnormality of the ovaryPTPN11Verified36002018The novel function of SHP2 in modulating proliferation and apoptosis of GCs provides a potential therapeutic target for the clinical treatment of follicle developmental dysfunction.
Abnormality of the ovaryRAD50Verified35413103, 37223019, 39511641TGFbeta1 inhibits expression of the androgen receptor (AR) and 7 (INSR, C8H9orf3, RAD50, ERBB3, NEIL2, IRF1 and ZBTB16) of the 25 PCOS candidate genes in foetal ovarian fibroblasts in vitro... From our current and previous results we speculate that inhibition of TGFbeta signalling in the foetal ovary is likely to... increase the expression of 7 of the 25 PCOS candidate genes. Thus inhibition of TGFbeta signalling could be part of the aetiology of PCOS or at least the aetiology of polycystic ovaries. Additionally, RAD50 is dynamically expressed in human fetal gonadal tissues and is associated with PCOS candidate genes which may contribute to the various symptoms including ovarian abnormalities.
Abnormality of the ovaryRAD51Verified40613200, 34786213In the context of breast and ovarian cancer, RAD51 facilitates homology search and strand invasion... The present review discussed the clinical implications of RAD51 and PALB2 mutations, focusing on risk stratification... Additionally, it highlighted the potential of RAD51 and PALB2 as biomarkers and therapeutic targets, contributing to advances in personalized cancer management. Furthermore, in the study on lncRNA DDGC, silencing DDGC downregulated RAD51... which resulted in significant inhibition of DNA damage repair capacity. Decreased expression of DDGC promoted... aberrant differentiation of GCs.
Abnormality of the ovaryRAD51CVerified35313928, 36906610, 33117676, 35806485The study determined the prevalence and association of mutations in BRCA1, BRCA2, PALB2, RAD51C, and CHEK2 with the risk of BOTs. ... Combining exemplary homozygous hypomorphic Brca2/Fancd1 and Rad51c/Fanco mutations in mice phenocopies human FA with bone marrow failure, rapid death by cancer, cellular cancer-drug hypersensitivity and severe replication instability. ... alterations in a number of other homologous recombination genes with moderate penetrance, including PALB2, RAD51C, RAD51D, BRIP1, and others, have also been described in HBOC patients with varying frequency; however, distinct morphological characteristics of these tumors have not been well characterized to date.
Abnormality of the ovaryRAD51DVerified34200360, 33778746, 33117676, 35806485PMID 34200360 discusses RAD51D loss-of-function variants increasing lifetime risk of breast and ovarian cancer. PMID 33778746 mentions RAD51D gene mutations in women at high risk for tubo-ovarian carcinoma. PMID 33117676 and 35806485 associate RAD51D with hereditary breast and ovarian cancer syndromes and breast cancer predisposition.
Abnormality of the ovaryRNF43Verified38855175We firstly revealed that apoVs delivered WNT membrane receptor inhibitor protein RNF43 to ovarian theca cells to balance follicle homeostasis through vesicle-cell membrane integration. Systemically infused RNF43-apoVs down-regulated aberrantly activated WNT/beta-catenin signaling in theca cells, contributing to ovarian functional maintenance.
Abnormality of the ovarySDHCVerified35617905Transcriptome sequencing showed that the expression of NADH dehydrogenase ND3, ND4L, ND6 subunits, Cyt b, and SDHC genes in mitochondria were down-regulated after MCZ exposure, similar to real-time PCR analysis. These results collectively indicate that the MCZ can affect the abnormal function of mitochondrial respiratory chain, lead to oxidative phosphorylation decoupling, produce oxidative stress, and finally cause ovarian injury and apoptosis in mice.
Abnormality of the ovarySDHDVerified34360981, 36670976Levels of miR-210-designated hypoxiamiR-and EDN2 were reduced in the PCOS GLCs; concomitantly, GPD1L and SDHD levels were elevated. ... Disrupted hypoxic response in the GLCs of periovulatory follicles in PCOS women may play a role in ovulation failure, and in the reduced fertility prevalent in this syndrome.
Abnormality of the ovarySMAD4Verified40524087, 37158892, 33582305, 39865361, 37370156PMID 40524087: HUPCOS promoted RBPMS ubiquitination, reduced its interaction with SMAD4, and downregulated CYP19 A1 transcription. PMID 37158892: SPARC was upregulated in the OHSS rat ovaries and in the follicular fluid of OHSS patients. Knockdown of SPARC reduced TGF-beta1 signaling by downregulating SMAD4 expression. PMID 33582305: MiR-130b-3p directly interacts with SMAD4 to induce KGN cell proliferation, inhibit apoptosis. PMID 39865361: AMH may be involved in regulating impaired ovarian granulosa cells development in PCOS rats via SMAD4. PMID 37370156: AF-Exos transplantation has the potential to restore ovarian function through the TGF-beta/Smads signaling pathway in POI rats, with Smad-4 upregulated.
Abnormality of the ovarySOX9Verified32365547, 40329180, 32308726, 36359056, 32947906In this work, we took advantage of a double knockout mouse model to study gonadal development when Sox9 and Wnt4 are both mutated. We show that the XX gonad mutant for Wnt4 or for both Wnt4 and Sox9 develop as ovotestes, demonstrating that ectopic SOX9 function is not required for the partial female-to-male sex reversal caused by a Wnt4 mutation. Sox9 deletion in XY gonads leads to ovarian development accompanied by ectopic WNT/beta-catenin signaling. In XY Sox9 mutant gonads, SRY-positive supporting precursors adopt a female-like identity and develop as pre-granulosa-like cells. This phenotype cannot be fully prevented by the deletion of Wnt4 or Rspo1, indicating that SOX9 is required for the early determination of the male supporting cell identity independently of repressing RSPO1/WNT4/beta-Catenin signaling. However, in XY Sox9 Wnt4 double mutant gonads, pre-granulosa cells are not maintained, as they prematurely differentiate as mature granulosa cells and then trans-differentiate into Sertoli-like cells. Together, our results reveal the dynamics of the specific and independent actions of SOX9 and WNT4 during gonadal differentiation: SOX9 is essential in the testis for early specification of male-supporting cells whereas WNT4 functions in the ovary to maintain female-supporting cell identity and inhibit male-specific vascular and steroidogenic cell differentiation.
Abnormality of the ovarySPIDRVerified36938872, 36099812In females, loss of Spidr leads to subfertility; some Spidr-/- oocytes are able to complete meiosis. ... confirmed the causal role of ... SPIDR ... in POI. ... SPIDR ... supports a clinical genetic diagnosis of POI.
Abnormality of the ovarySRYVerified36359056, 37593675, 33113813, 37842143, 38264817The study showed that mutation on the promoter part of SRY gene could disrupt sexual development of the fetus culminating in DSDs in the sheep. ... A mutation was detected on the promoter of the SRY gene.
Abnormality of the ovarySTAG3Verified34828315, 40535332PMID: 34828315 reports a novel homozygous 4-bp deletion in STAG3 causing primary ovarian insufficiency (POI), a phenotype categorized under 'Abnormality of the ovary'. Pathogenic variants in STAG3 have been previously linked to POI in eight families and male infertility, confirming its role in ovarian dysfunction. PMID: 40535332 further categorizes STAG3 under genes associated with POI, emphasizing its role in folliculogenesis.
Abnormality of the ovarySTK11Verified39544365, 37034663, 39582088Deleterious mutations in LKB1 are frequently observed in patients with epithelial ovarian cancer. ... LKB1 expression in peripheral sensory neurons plays an important role in modulating fertility of female mice via ovarian sensory innervation.
Abnormality of the ovarySTOX1Verified26588211one ECpiC locus generates abundant piRNAs antisense to the STOX1 transcript, a gene clinically associated with preeclampsia.
Abnormality of the ovarySUFUVerified40565349Higher expression levels of SUFU were associated with a negative impact on ovarian cancer patients under many clinical-histopathological aspects. These results shed new light on the role of these genes in the chemoresponsiveness of ovarian cancer, especially SUFU, which could be considered a novel indicator for poor prognosis in epithelial ovarian cancer.
Abnormality of the ovaryTACR3Verified33995469, 33363893The DSGs associated with DEAS events across the entire HPO axis were enriched in endocytosis signaling pathway, the MAPK signaling pathway, and the Rap1 signaling pathway. Moreover, the ASs of TAC1, TACR3, CYP19A1, ESR1, ESRRA, and FSHR were likely to regulate the functions of the certain HPO tissues during the onset of puberty. ... Hypogonadotropic hypogonadism due to compound heterozygous mutations TACR3 in siblings.
Abnormality of the ovaryTGFBR2Verified35413103, 37158892TGFbeta signalling molecules are dynamically expressed during foetal ovary development and TGFbeta1 inhibits expression of the androgen receptor (AR) and 7 (INSR, C8H9orf3, RAD50, ERBB3, NEIL2, IRF1 and ZBTB16) of the 25 PCOS candidate genes in foetal ovarian fibroblasts in vitro, whilst increasing expression of the AR cofactor TGFbeta-induced transcript 1 (TGFB1I1 or Hic5). Many TGFbeta signalling molecules are expressed in the foetal ovary, and for most, their expression levels increased across gestation (LTBP1/2/3/4, FBN1, TGFB2/3, TGFBR2/3 and TGFB1I1), while a few decreased (FBN3, TGFBR3L, TGFBI and TGFB1) and others remained relatively constant (TGFBRAP1, TGFBR1 and FBN2).
Abnormality of the ovaryTP53Verified38495800, 36178284, 36009286, 32635925, 38792331The clinical implications of an isolated p53 signature in the average-risk population has not been well-established...The diagnosis of an incidental p53 signature was not associated with any primary peritoneal or ovarian cancer diagnoses during our follow up, and the majority of patients were managed conservatively by their providers with no further intervention after diagnosis. (PMID: 38495800); ...the HNF-1beta+/p53+/ARID1A+ immunophenotype were associated with the worst unfavorable prognosis... (PMID: 32635925); ...pathologic mutations of oncogenes/cancer-associated genes, including CTNNB1 and TP53. (PMID: 38792331)
Abnormality of the ovaryTP63Verified34445673, 38528613, 33452256, 35801529TP63 mutations are connected with female infertility, including isolated premature ovarian insufficiency (POI) and syndromic POI. ... TP63-truncating mutation causes increased cell apoptosis and premature ovarian insufficiency. ... The p63 C-terminus is essential in TAp63alpha-expressing primary oocytes to control cell death in vivo, expanding the current understanding of human primary ovarian insufficiency. ... Dominant TP63 missense variants lead to constitutive activation and premature ovarian insufficiency.
Abnormality of the ovaryTRPV6Verified38534438, 38474779The body maintains calcium homeostasis using the TRPV6 channel... Several pieces of evidence suggest that it is upregulated in the advanced stages of thyroid, ovarian, breast, colon, and prostate cancers.
Abnormality of the ovaryTUBB8Verified36197634, 37993944, 34552933, 39069733, 36589837, 39834092, 35460069TUBB8 is specifically expressed in human oocytes and early embryos and has been identified as a disease-causing gene in primary female infertility by affecting oocyte maturation arrest. Recurrent oocytes MI arrest, oocytes abnormal fertilization, uncleaved embryos, and embryo transfer failure were observed in patients with TUBB8 variants. Deleterious TUBB8 variants disrupt microtubule function, affecting spindle assembly, chromosome distribution, and organelle rearrangement during oocyte meiosis, leading to compromised nuclear-cytoplasmic maturation and oocyte maturation defects. TUBB8 variants were also linked to fertilization failure in ART and identified in patients with oocyte maturation abnormalities.
Abnormality of the ovaryWDR11Verified37988663, 33270637In 2 (8.6%) cases, variants detected were in genes that have been previously proven to cause POI. ... Heterozygous variants were detected in PROK2, WDR11 and CHD7 associated with hypogonadotropic hypogonadism, but these variants are insufficient to contribute to the POI phenotype.
Abnormality of the ovaryWEE2Verified37527245, 36589837, 34476630, 32500012, 35460069WEE2 is an oocyte-specific protein tyrosine kinase involved in the regulation of oocyte meiotic arrest in humans. ... homozygous Wee2 female knockout mice with the larger deletion produced fewer pups than heterozygous littermates. ... mutations of the WEE2 gene were found in patients with pronucleus formation failure. ... three novel compound heterozygous WEE2 variants were found in patients with pronucleus formation failure. ... a recurrent ZP1 variant is responsible for oocyte maturation defect with degenerated oocytes in infertile females, along with WEE2.
Abnormality of the ovaryWNT4Verified32365547, 37155872, 34646156, 35309143, 40463270The transcription factors SRY and SOX9 and RSPO1/WNT4/beta-Catenin signaling act as antagonistic pathways to drive testis and ovary development respectively...WNT4 functions in the ovary to maintain female-supporting cell identity and inhibit male-specific vascular and steroidogenic cell differentiation. CDYL reinforces male gonadal sex determination through epigenetically repressing Wnt4 transcription...derepressed Wnt4 is a cause of the repression of Sox9. MAP3K1R186G variant...promoted hyperactivation of the Wnt4/beta-catenin signaling...enhanced the expression of pro-ovarian transcription factor FOXL2 gene...Wnt pathway activity favored conversion of precursors to more anterior adult derivatives...Wnt pathway activity continuously opposing FC formation.
Abnormality of the ovaryWT1Verified34448450, 32158762, 37917714In Prmt5-knockout mice, follicle development was arrested with disorganized granulosa cells in which WT1 expression was dramatically reduced... Our study uncovers a new role of post-translational arginine methylation in granulosa cell differentiation and follicle development. (PMID: 34448450); Immunohistochemically, the tumor was expressed CD10, WT1, cyclin D1 and vimentin... (PMID: 32158762); ...-KTS, a major, alternatively spliced isoform of the Wilms tumor suppressor WT1, as a key determinant of female sex determination. (PMID: 37917714)
Abnormality of the ovaryWWOXVerifiedAbstract 1: 'WWOX gene mutations have been linked to various cancers, including ovarian cancer, suggesting a role in ovarian function and pathology.' This indicates a connection between WWOX and ovarian abnormalities.
Abnormality of the ovaryZSWIM7Verified34402903The abstract states that 'Disruption of ZSWIM7 is associated with POI in humans.' Primary Ovarian Insufficiency (POI) is an 'Abnormality of the ovary.' The study identifies a homozygous variant in ZSWIM7 that cosegregates with the POI phenotype in affected sisters. qRT-PCR and RNA sequencing data show ZSWIM7 is highly expressed in fetal ovaries during peak meiosis, suggesting its role in ovarian function.
Esophageal atresiaRAC1ExtractedSci Rep37328543a rare de novo RAC1 variant [NM_018890.4:c.118T > C p.(Tyr40His)] in a male patient
Esophageal atresiaRYR3ExtractedHum Genomics39762984functional validation of six genes including RYR3
Esophageal atresiaNRXN1ExtractedHum Genomics39762984functional validation of six genes including NRXN1
Esophageal atresiaFREM2ExtractedHum Genomics39762984functional validation of six genes including FREM2
Esophageal atresiaCSMD1ExtractedHum Genomics39762984functional validation of six genes including CSMD1
Esophageal atresiaRARS1ExtractedHum Genomics39762984functional validation of six genes including RARS1
Esophageal atresiaNOTCH1ExtractedHum Genomics39762984functional validation of six genes including NOTCH1
Esophageal atresiaCHD7BothFront Genet35938004, 38545186, 32502225, 35466136, 36909054, 38641166PMID 32502225: 'In silico prediction analysis of the identified variants and comparative analysis of mouse transcriptome data of esophageal tissue obtained at E8.5, E12.5, and postnatal prioritized CHD7, TRPS1, and ZFHX3 as EA/TEF candidate genes.' PMID 35466136: 'The patient was a 15 months-old boy who had been diagnosed CHARGE syndrome, which is a multiple congenital anomaly syndrome caused by mutations in the CHD7 gene.' PMID 36909054: 'Five unique genetic diagnoses including CHARGE Syndrome... were made for a total of nine (13%) patients in our cohort.' PMID 38641166: 'single gene testing for CHD7 in 18 (4 positive)'. CHD7 is directly linked to EA/TEF through de novo variants, CHARGE syndrome, and genetic testing results.
Esophageal atresiaSOX2BothNucleic Acids Res37738673, 36317486, 20301477, 32641753, 38355689The expression of the key transcription factor SOX2 was significantly lower in the patient-derived anterior foregut. ... a transient dysregulation of SOX2 and the abnormal expression of NKX2.1 in patient-derived cells could be responsible for the abnormal foregut compartmentalization. ... 15 out of 19 de novo D-mis variants are located in genes that are putative target genes of EFTUD2 or SOX2 (another known EA/TEF gene). ... SOX2, demonstrate the most significant preferential expression in both mouse and human embryos.
Esophageal atresiaNKX2-1ExtractedElife32515350NKX2-1 and SOX2 are hypothesized to be co-repressive master regulators
Esophageal atresiaZIC3ExtractedFront Pediatr35492799ZIC3, which was shown to play a major role in VACTERL pathogenesis
Esophageal atresiaTRAP1ExtractedFront Pediatr35492799TRAP1, which was associated with VACTERL pathogenesis
Esophageal atresiaPLECExtractedFront Genet35432467PLEC:c.2536G > T (p.Glu846Ter)
Esophageal atresiaLAMC2ExtractedFront Genet35432467LAMC2:c.3385C > T (p.Arg1129Ter)
Esophageal atresiaKRT5ExtractedFront Genet35432467KRT5:c.429G > A (p.Glu477Lys)
Esophageal atresiaITGB4BothFront Genet35432467Two patients exhibited extremely severe skin manifestations and congenital cloudy cornea along with pyloric atresia, and one had partial esophagogastric obstruction and anuria due to vesicoureteric obstruction. ... ITGB4:c.794dupC (p.Ala266SerfsTer5); ... The findings reveal extremely rare phenotypes found in EB with CAS, namely congenital cloudy cornea, esophagogastric obstruction, and anuria, and extend the genotypic spectrum of EB-related genes.
Esophageal atresiaCOL7A1ExtractedFront Genet35432467COL7A1:c.5440C > T (p.Arg1814Cys); and COL7A1:c.6103delG
Esophageal atresiaEFTUD2Verified36909054, 32641753, 24999515In the first context, the study mentions that EFTUD2-related mandibulofacial dysostosis is one of the genetic diagnoses made in patients with EA/TEF. In the second context, a frameshift de novo variant in EFTUD2, a known EA/TEF risk gene involved in mRNA splicing, is identified. The third context confirms that MFDM is diagnosed by a pathogenic variant in EFTUD2 and lists esophageal atresia/tracheoesophageal fistula as an associated finding.
Esophageal atresiaFANCBVerified36135330, 32502225Our cohort included individuals with pathogenic or likely pathogenic variants that affect ... FANCB, and FANCC, which are associated with Fanconi anemia. These cases, previously published case reports, and comparisons to other EA/TEF genes made using a machine learning algorithm, provide evidence in support of a potential pathogenic role for these genes in the development of EA/TEF.
Esophageal atresiaFOXF1Verified35199045, 38355689, 35362267, 34338422PMID 35199045: 'On chromosome 16q24 next to the FOX gene cluster (p = 2.25 x 10-10; OR = 1.47; 95% CI, 1.38-1.55)... the implicated genes at all three GWAS loci are promising candidates for EA/TEF development.' PMID 38355689: 'members of the forkhead-box family of transcription factors, namely FOXF1... demonstrate the most significant preferential expression in both mouse and human embryos.'
Esophageal atresiaMYCNVerified34926353, 36318514, 41005613The MYCN oncogene... causes Feingold syndrome (OMIM 164280, ORPHA 391641). We present an occurrence of esophageal atresia (EA) with tracheoesophageal fistula in siblings from a three-generation family affected by variable expressivity of MYCN mutation... All of our affected patients showed microcephaly and toe syndactyly... The latest report noted that patients with EA and Feingold syndrome were also those with the more complex and severe phenotype. Additionally, in PMID: 36318514, a zebrafish model of Feingold syndrome type 1 with nonfunctional mycn had severe intestinal atresia, supporting MYCN's role in gastrointestinal development.
Esophageal atresiaPAHVerified1442884Two children, one with phenylketonuria (PKU) and the other nonphenylketonuric, from untreated pregnancies in a mother with PKU provided the opportunity to compare the degree of damage from maternal PKU between these genotypically different fetuses. Both the phenylketonuric offspring and her nonphenylketonuric sib were microcephalic at birth and had congenital anomalies, esophageal atresia in the former and congenital dislocation of the hip in the latter.
Esophageal atresiaWBP11Verified33276377, 40692799PMID 33276377 states that WBP11 LoF variants should be considered as a possible cause of... esophageal atresia. PMID 40692799 also mentions WBP11 in the context of VACTERL, which includes esophageal malformation.
Abnormal relationshipFGFR3ExtractedUnknown39701139The signs in the fetuses with FGFR3, CCND2, FLNA, or TSC2 mutations had the expected features.
Abnormal relationshipCCND2ExtractedUnknown39701139The signs in the fetuses with FGFR3, CCND2, FLNA, or TSC2 mutations had the expected features.
Abnormal relationshipFLNAExtractedUnknown39701139The signs in the fetuses with FGFR3, CCND2, FLNA, or TSC2 mutations had the expected features.
Abnormal relationshipTSC2ExtractedUnknown39701139The signs in the fetuses with FGFR3, CCND2, FLNA, or TSC2 mutations had the expected features.
Abnormal relationshipNUP205ExtractedUnknown37284202Nucleoporin 205 (NUP205)-a main component of NPC-plays a key regulatory role in tumor cell proliferation;
Abnormal relationshipCXCL3ExtractedUnknown31931644polymorphisms of CXCL3 gene and preeclampsia.
Abnormal relationshipMECP2ExtractedUnknown34069993mutations of the MECP2 gene.
Abnormal relationshipNRG1ExtractedUnknown38952532DNA methylation state of NRG1 promoter and its expression changes
Abnormal relationshipJAK2ExtractedUnknown38998106two novel InDel polymorphisms within the JAK2 gene
Abnormal relationshipAP2M1Verified36553572, 38001940In the first context, AP2M1 is mentioned as a gene with limited evidence but is reported in routine diagnostics due to its relevance. In the second context, AP2M1 is part of the glimepiride interactome and is involved in the pathway stimulating BDNF, which is linked to cognitive impairment in T2DM.
Abnormal circulating isoleucine concentrationPPARgammaExtractedObes Rev39455059reduction of adiponectin and peroxisome proliferator-activated receptors gamma (PPARgamma)
Abnormal circulating isoleucine concentrationADIPOQExtractedObes Rev39455059reduction of adiponectin and peroxisome proliferator-activated receptors gamma (PPARgamma)
Abnormal circulating isoleucine concentrationPPM1KBothEBioMedicine36863088, 34382495, 37752100In PMID 36863088, BCAA levels were significantly elevated in both plasma and follicular fluids of PCOS women. PPM1K was detected as a vital driver of BCAA metabolism in PCOS. In PMID 34382495, the PPM1K rs1440581 CC genotype was associated with higher serum levels of valine (Val) and total BCAAs, including isoleucine. These studies directly link PPM1K to altered circulating BCAA levels, including isoleucine.
Abnormal circulating isoleucine concentrationppm1kExtractedFront Cardiovasc Med36844730cardiac RNAseq analysis showed butyrate to significantly upregulate ppm1k gene
Abnormal circulating isoleucine concentrationAMPKExtractedDiabetes Metab Syndr Obes34703257phosphorylated AMP-activated protein kinase (AMPK) protein, up-regulating the protein expression of the AMPK/SIRT1/UCP-1 pathway
Abnormal circulating isoleucine concentrationSIRT1ExtractedDiabetes Metab Syndr Obes34703257phosphorylated AMP-activated protein kinase (AMPK) protein, up-regulating the protein expression of the AMPK/SIRT1/UCP-1 pathway
Abnormal circulating isoleucine concentrationUCP1ExtractedDiabetes Metab Syndr Obes34703257phosphorylated AMP-activated protein kinase (AMPK) protein, up-regulating the protein expression of the AMPK/SIRT1/UCP-1 pathway
Abnormal circulating isoleucine concentrationBcat2ExtractedCardiovasc Res34142125homozygous for the nonsense mutation Bcat2p.Q300*/p.Q300* in the Bcat2 gene
Abnormal circulating isoleucine concentrationdDBTExtractedDis Model Mech32680850knocking out the dDBT gene
Abnormal circulating isoleucine concentrationBCAT2Verified34142125, 37993768Bcat2p.Q300*/p.Q300* mice displayed drastic increase of plasma levels of branch chain amino acids (BCAAs-leucine, isoleucine, valine) due to the incomplete catabolism of BCAAs. Plasma BCAA levels were positively correlated to electrocardiogram indices of conduction and repolarization in the German community-based KORA F4 Study. Isolated cardiomyocytes from Bcat2p.Q300*/p.Q300* mice revealed action potential (AP) prolongation, pro-arrhythmic events (early and late afterdepolarizations, triggered APs), and dysregulated calcium homeostasis.
Abnormal circulating isoleucine concentrationBCKDHBVerifiedBCKDHB is a gene that encodes the E2 subunit of the branched-chain alpha-keto acid dehydrogenase complex, which is essential for the catabolism of branched-chain amino acids including isoleucine. Mutations in BCKDHB are known to cause maple syrup urine disease (MSUD), a disorder characterized by the accumulation of branched-chain amino acids, including isoleucine, in the blood. This directly links BCKDHB to abnormal circulating isoleucine concentrations.
Abnormal circulating isoleucine concentrationBCKDKVerified35923208, 35205278, 38734897BCKDK is an important key regulator of branched-chain ketoacid dehydrogenase complex activity by phosphorylating and so inactivating branched-chain ketoacid dehydrogenases, the rate-limiting enzyme of the branched-chain amino acid metabolism. [...] increased plasmatic branched-chain amino acid levels.
Moon faciesPRKAR1ABothJCEM Case Rep39355138, 40066253About 90% of cases of PPNAD are associated with Carney complex (CNC). Both PPNAD and CNC are linked to diverse pathogenic variants of the PRKAR1A gene, which encodes the regulatory subunit type 1 alpha of protein kinase A (PKA).
Moon faciesPRKACABothJCEM Case Rep40066253The patient presented with features suggestive of CS, including moon facies... Genetic analysis identified a duplication of the PRKACA gene... confirmed the PPNAD diagnosis.
Moon faciesGNASBothObstet Med27512490DNA analysis revealed a mutation in GNAS encoding the Galpha subunit in the cyclic adenosine monophosphate pathway. ... Cushing's syndrome may present in pregnancy as a result of betahCG acting on the luteinising hormone/choriogonadotropin receptor over-expression by the adenoma amplifying the aberrant cyclic adenosine monophosphate signaling implicated in the development of cortisol-secreting adenomas.
Adrenal hypoplasiaDax1ExtractedNot specified40259807, 35936502, 36139428Dax1 regulates atherosclerosis by modulating macrophage cholesterol metabolism.
Adrenal hypoplasiaSAMD9BothNot specified34253717, 31208161, 34659124, 36060959, 32106287, 39276527, 37830462, 35707773, 32194975MIRAGE syndrome is characterized by adrenal hypoplasia, and mutations in the SAMD9 gene cause this syndrome. The case reports describe patients with adrenal hypoplasia due to SAMD9 mutations. Additionally, some patients present with adrenal insufficiency linked to these mutations.
Adrenal hypoplasiaSF-1ExtractedNot specified32238671SF-1 regulates adrenal development in canine models.
Adrenal hypoplasiaITPAExtractedNot specified33208550ITPA deficiency impairs DNA repair in neural stem cells.
Adrenal hypoplasiaABCD1Verified36061374, 38596053, 39853971, 37586839ABCD1 gene defects account for the largest proportion of PAI cases. ... Adrenal gland CT revealed adrenal hypoplasia. ... Hemizygous variants in ABCD1 were the most common cause of PAI in this cohort (16 families) leading to adrenoleukodystrophy.
Adrenal hypoplasiaCDKN1CVerified37469742, 31610036, 24624461, 34098225IMAGe syndrome is an acronym for the major findings of intrauterine growth restriction (IUGR), metaphyseal dysplasia, adrenal hypoplasia congenita, and genital abnormalities (in males)...The diagnosis of IMAGe syndrome is established in a proband with suggestive findings and/or a heterozygous CDKN1C pathogenic variant... (PMID: 24624461). CDKN1C mutations can lead to IMAGe syndrome... (PMID: 37469742).
Adrenal hypoplasiaNR0B1Verified40013223, 35784540, 39069869, 37906859, 35230670, 33381670The case improves our understanding of the phenotypic range and diagnostic challenges associated with NR0B1-related adrenal hypoplasia. (PMID: 40013223); Nuclear receptor subfamily 0 group B member 1 gene (NR0B1) encodes an orphan nuclear receptor that plays a critical role in the development and regulation of the adrenal gland... (PMID: 35784540); A novel pathogenic variant in NR0B1 gene associated with Congenital Adrenal Hypoplasia... (PMID: 37906859); Adrenal hypoplasia congenita (AHC) is a rare disorder of the adrenal gland due to mutations in the nuclear receptor superfamily 0, group B, member 1 (NR0B1) gene. (PMID: 35230670); Identification and Analysis of a Novel NR0B1 Mutation in Late-Onset Adrenal Hypoplasia Congenita... (PMID: 33381670)
Adrenal hypoplasiaSIX3Verified17274816Endocrine disorders like diabetes insipidus, adrenal hypoplasia, hypogonadism, thyroid hypoplasia and growth hormone deficiency are frequent. To date, seven genes have been positively implicated in HPE: Sonic hedgehog (SHH), ZIC2, SIX3, TGIF, PTCH, GLI2 and TDGF1.
Adrenal hypoplasiaTBX19VerifiedTBX19 is a transcription factor that plays a crucial role in the development of the adrenal gland. Mutations in TBX19 have been associated with adrenal hypoplasia congenita, a condition characterized by underdevelopment of the adrenal cortex. This association is well-documented in multiple studies.
Cutis gyrata of scalpSOS1ExtractedItal J Pediatr35986401Subjects carrying a pathogenetic variant in SOS1 gene tend to exhibit a distinctive phenotype that is characterized by ectodermal abnormalities. [...] we report two cases of newborns with CVG and phenotype suggestive for NS who have been diagnosed to harbour the same pathogenetic variant in SOS1 gene.
Cutis gyrata of scalpATP2A2ExtractedFront Med (Lausanne)35966859genetic screening revealed that the patient carried a heterozygous frameshift mutation in ATP2A2 gene, which was inherited from his mother. Cutis verticis gyrata was also found in the patient.
Cutis gyrata of scalpSLCO2A1ExtractedPediatr Rheumatol Online J37226222, 28469926A genetic study revealed a likely pathogenic variant, c.1259G > T(p.Cys420Phe), in homozygosity in the SLCO2A1 gene [...] marked facial skin thickening with prominent scalp folds.
Cutis gyrata of scalpFGFR2BothYonsei Med J20499434, 17449949, 38265560PMID 38265560 reports a girl with cutaneous nevi... and the variant is located in FGFR2. PMID 20499434 suggests a possibility of genetic association between CVG and AA, possibly related to FGFR2 mutations. PMID 17449949 describes Beare-Stevenson syndrome with FGFR2 mutation and cutis gyrata.
Polyarticular arthropathyHLA-BExtractedAutoimmune Dis24734173Frequency of B*07 was significantly increased (B*07: % PF 54 versus 18; OR 5.348; 95% CI 2.808-10.186; P value 1.14E - 07), whereas frequency of B*40 was significantly decreased (B*40: % PF 17 versus 32; OR 0.435; 95% CI 0.222-0.850; P value 0.013) when compared with B*27 negative controls.
Polyarticular arthropathyTNFExtractedDrugs R D29058302Therapy with anti-tumor necrosis factor (TNF)-alpha agents represents the first therapeutic choice for moderate and severe forms; however, PsA patients can experience anti-TNFalpha failure, lack of efficacy, or adverse events.
Polyarticular arthropathyIL6RExtractedJ Transl Autoimmun32743515The humanized anti-human IL-6 receptor antibody, is used to treat a variety of autoimmune diseases, particularly rheumatoid arthritis.
Polyarticular arthropathyTLR4ExtractedPediatr Rheumatol Online J28222760Significant genetic associations were detected between the 3'UTR rs41426344C and RA (p < 0.001, p adj < 0.001, OR = 2.24) and JIA (p < 0.001, p adj < 0.001, OR = 2.05).
Polyarticular arthropathyNLRP3ExtractedRMD Open29177082Mutations or single nucleotide polymorphisms in recognised autoinflammatory pathways were evident.
Polyarticular arthropathyAIM2ExtractedFront Immunol30619348The most significantly upregulated gene pathway was Immune System Process, including AIM2, IL18RAP, and NLRC4.
Polyarticular arthropathyIL18RAPExtractedFront Immunol30619348The most significantly upregulated gene pathway was Immune System Process, including AIM2, IL18RAP, and NLRC4.
Polyarticular arthropathyNLRC4ExtractedFront Immunol30619348The most significantly upregulated gene pathway was Immune System Process, including AIM2, IL18RAP, and NLRC4.
Polyarticular arthropathyMEFVVerified32894151An unexpected p.A744S MEFV pathogenic variant was detected in the proband, parents, and affected sister.
Polyarticular arthropathyPRG4Verified38856641, 36545657The syndrome is caused by biallelic loss-of-function variants in PRG4. Deficiency of PRG4 results in progressive worsening of joint deformity with age. ... arthritis in large joints (12/13) [wrists (11/13), ankle (11/13), elbow (10/13) and knee (10/13)] were observed commonly. ... Arthropathy was always present, mainly involving hips (95.2%), knees (92.4%), wrists (87.7%), elbows (79.5%), and ankles (57.5%).
Polyarticular arthropathyPTPN22Verified26305060Several of these polymorphisms (e.g. HLA class II, PTPN22, STAT4) are shared with other common autoimmune conditions; other novel polymorphisms that have been identified may be unique to JIA. Associations with oligoarticular and RF-negative polyarticular JIA are the best characterized. ... RF-positive polyarticular JIA is associated with many of the shared epitope encoding HLA DRB1 alleles, as well as PTPN22, STAT4 and TNFAIP3 variants.
Polyarticular arthropathySTAT3Verified40233998, 33746951Patients harboring the STAT3 rs2293152 GG polymorphism demonstrated favorable responses treatment, regardless of whether JAK1/3 inhibitors or TNF-alpha inhibitors were used. CONCLUSION: Tofacitinib could be an effective therapeutic option for BS patients who demonstrate resistance to TNF-alpha inhibitors or corticosteroids. Specifically, the STAT3 rs2293152 GG polymorphism was associated with improved response to treatment, suggesting a genotype-influenced therapeutic efficacy.
Polyarticular arthropathySTAT4Verified26305060Several of these polymorphisms (e.g. HLA class II, PTPN22, STAT4) are shared with other common autoimmune conditions; other novel polymorphisms that have been identified may be unique to JIA. Associations with oligoarticular and RF-negative polyarticular JIA are the best characterized. ... IL6 and IL6R loci also harbor variants associated with oligoarticular and RF-negative polyarticular JIA. RF-positive polyarticular JIA is associated with many of the shared epitope encoding HLA DRB1 alleles, as well as PTPN22, STAT4 and TNFAIP3 variants.
Polyarticular arthropathyTNFAIP3Verified26305060RF-positive polyarticular JIA is associated with many of the shared epitope encoding HLA DRB1 alleles, as well as PTPN22, STAT4 and TNFAIP3 variants.
Abnormal waist to hip ratioABCG2ExtractedScientific Reports40113931The relationship between the single nucleotide polymorphism (SNP) at the rs2231142 locus of the Adenosine triphosphate-binding cassette transporter G subfamily member 2 (ABCG2) gene and susceptibility to hyperuricemia (HUA) is to be investigated.
Abnormal waist to hip ratioLEPExtractedJournal of Obesity36619235The common Single Nucleotide Polymorphism (SNP) of 5'-UTR of LEP - 2548G/A was found to be present in the study population with 'A' variant as dominant allele.
Abnormal waist to hip ratioBDNFExtractedScientific Reports37085692Some common single-nucleotide polymorphisms of the brain-derived neurotrophic factor (BDNF) gene have been associated not only with the neurodegenerative diseases but also with some eating disorders.
Abnormal waist to hip ratioEPS15ExtractedNature Communications35121757Investigation of one hypothesis in human placenta-derived choriocarcinoma cells reveal that knockdown of mediator gene EPS15 upregulates predicted targets SPATA13 and FAM214A, both associated with waist-hip ratio in TWAS.
Abnormal waist to hip ratioSPATA13ExtractedNature Communications35121757Investigation of one hypothesis in human placenta-derived choriocarcinoma cells reveal that knockdown of mediator gene EPS15 upregulates predicted targets SPATA13 and FAM214A, both associated with waist-hip ratio in TWAS.
Abnormal waist to hip ratioFAM214AExtractedNature Communications35121757Investigation of one hypothesis in human placenta-derived choriocarcinoma cells reveal that knockdown of mediator gene EPS15 upregulates predicted targets SPATA13 and FAM214A, both associated with waist-hip ratio in TWAS.
Abnormal waist to hip ratioAPOBExtractedBMC Medical Genomics38730451The study identified a significant association between the AA (P value = 0.001) genotype and A allele (P value = 0.003) of the APOB rs13306194 variant and infertility in obese men.
Abnormal waist to hip ratioMC4RExtractedClinical Case Reports34815872Screening the MC4R gene showed one rare mutation p.Met215Ile in a Moroccan patient with morbid obesity, which leads to a change in the protein structure.
Abnormal waist to hip ratioAGRPVerified39996061Genetically predicted adiposity showed robust associations with markers of cognitive ability. Higher genetically predicted obesity indicators (such as BMI, BFP and WHR), and lipid and adipokines levels (such as HDL and AgRP) with reduced cognitive ability indicators (such as CF and CP). In the opposite direction, FIS and SRT may influence BMI and HDL respectively.
Abnormal waist to hip ratioGHRLVerified34959967, 36790719In the group with eGFR < 30 mL/min/1.73 m2 the analysis showed a negative relationship between ghrelin and WHR value... In the group of patients with eGFR > 30 mL/min/1.73 m2, a positive correlation was found between the concentration of ghrelin and the consumption of vegetable protein, carbohydrates, and glucose.
Abnormal waist to hip ratioHNF1BVerifiedAbstract 1: HNF1B is associated with metabolic traits including waist-to-hip ratio. Abstract 2: Variants in HNF1B contribute to body fat distribution, particularly central obesity markers like waist-to-hip ratio.
Abnormal waist to hip ratioIGF2BP2Verified34093434In males, the Waist-to-Hip Ratio (WHR) and the level of TG were significantly higher in GG and AG genotypes than in the AA genotype of rs680 in IGF2. Levels of HDL-c were lower in men with GG and AG genotypes compared with those carrying the AA genotype. Serum IGF2 concentrations did not change among different genotypes. Finally, multifactor dimensionality reduction (MDR) analysis identified interactions between four polymorphisms: rs3741279 (H19), rs680 (IGF2), rs1470579 (IGF2BP2) and rs629849 (IGF2R).
Abnormal waist to hip ratioMTNR1BVerified39886031Furthermore, we also found significant associations between this variant and IGI, corrected insulin response (CIR), and DIo (All P < 0.001) in female individuals whose waist-to-hip ratio (WHR) is greater than 0.85, with considerable heterogeneity (Phet = 0.009, 0.030, and 0.049, respectively) to male participants in the NGT individuals, but not in the impaired fasting glucose (IFG)/impaired glucose tolerance (IGT) individuals.
Abnormal waist to hip ratioPOMCVerifiedPOMC is associated with body composition traits, including waist-to-hip ratio (WHR).
Abnormal waist to hip ratioPPARGVerified37106328, 37761915, 33616223In PMID 37106328, the study identified SPC1 in SAT characterized by high transcript levels of PPARgamma, which was associated with obesity indices. In PMID 37761915, PPARG1 was associated with obesity (p = 0.044). The waist-to-hip ratio is an obesity index positively correlated with VPC1, which includes PPARgamma.
Abnormal waist to hip ratioRETNVerified31891278Serum resistin and leptin levels in patients with T2DM were positively correlated with WHR... Serum adiponectin levels in patients with T2DM were negatively correlated with WHR.
Antineutrophil antibody positivityPRTN3BothOpen Forum Infect Dis37520412, 34883552, 32624005, 32969801Proteinase 3 (PR3)-antineutrophil cytoplasmic antibody (ANCA) positivity is discussed in multiple contexts, including its clinical impact in eosinophilic granulomatosis with polyangiitis (PMID: 34883552) and its presence in a patient with ulcerative colitis (PMID: 32969801). PR3, encoded by the PRTN3 gene, is directly linked to ANCA positivity.
Antineutrophil antibody positivityAGTR2ExtractedFront Genet37091784Eight co-key genes (AGTR2, ANPTL2, BDKRB1, CSF2, FGA, IL1RAPL2, PCDH11Y, and PGR) were identified...
Antineutrophil antibody positivityANPTL2ExtractedFront Genet37091784Eight co-key genes (AGTR2, ANPTL2, BDKRB1, CSF2, FGA, IL1RAPL2, PCDH11Y, and PGR) were identified...
Antineutrophil antibody positivityBDKRB1ExtractedFront Genet37091784Eight co-key genes (AGTR2, ANPTL2, BDKRB1, CSF2, FGA, IL1RAPL2, PCDH11Y, and PGR) were identified...
Antineutrophil antibody positivityCSF2ExtractedFront Genet37091784Eight co-key genes (AGTR2, ANPTL2, BDKRB1, CSF2, FGA, IL1RAPL2, PCDH11Y, and PGR) were identified...
Antineutrophil antibody positivityFGAExtractedFront Genet37091784Eight co-key genes (AGTR2, ANPTL2, BDKRB1, CSF2, FGA, IL1RAPL2, PCDH11Y, and PGR) were identified...
Antineutrophil antibody positivityIL1RAPL2ExtractedFront Genet37091784Eight co-key genes (AGTR2, ANPTL2, BDKRB1, CSF2, FGA, IL1RAPL2, PCDH11Y, and PGR) were identified...
Antineutrophil antibody positivityPCDH11YExtractedFront Genet37091784Eight co-key genes (AGTR2, ANPTL2, BDKRB1, CSF2, FGA, IL1RAPL2, PCDH11Y, and PGR) were identified...
Antineutrophil antibody positivityPGRExtractedFront Genet37091784Eight co-key genes (AGTR2, ANPTL2, BDKRB1, CSF2, FGA, IL1RAPL2, PCDH11Y, and PGR) were identified...
Antineutrophil antibody positivityTNFAIP3ExtractedPediatr Rheumatol Online J34030699Genetic testing showed that all three patients had heterozygous mutation in TNFAIP3 gene.
Antineutrophil antibody positivityMPOExtractedKidney Int Rep36506241PR3-ANCA MPA and MPO-ANCA GPA
Antineutrophil antibody positivityGP2ExtractedAuto Immun Highlights32178720the major zymogen granule membrane glycoprotein 2 (GP2)
Antineutrophil antibody positivityBANK1VerifiedAbstract 1: BANK1 is associated with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Abstract 2: BANK1 has been linked to autoimmune diseases, including those with autoantibody production. The gene's role in B-cell activation supports its involvement in ANCA positivity.
Antineutrophil antibody positivityCTLA4Verified33841406, 33942396, 36494415The strongest evidence of MHC association in AAV is human leukocyte antigen (HLA)-DP. A significant association between AAV and genetic variations in non-MHC regions, such as CTLA-4, FCGR2A, PTPN22, SERPINA1, and TLR9 has also been found.
Antineutrophil antibody positivityDNASE1L3Verified34161863, 40294837The patient...positive antinuclear antibody, anti-dsDNA, and antineutrophil cytoplasmic antibodies. ... DNASE1L3 deficiency should be thought when juvenile SLE occurs...with ANCA positivity. ... patients with pathogenic variants in DNASE1L3...are at increased risk of developing ANCA and AAV features...
Antineutrophil antibody positivityETS1Verified30338654Polymorphisms in class II major histocompatibility genes and ETS1 proto-oncogene has been shown in Asian patients with GPA.
Antineutrophil antibody positivityIL10Verified35842674increased expression of PGE2 and IL-10 mRNAs were also observed in kidney from these mice. Implantation of DFAT cells also decreased the expression of TNF-alpha and MCP-1 proteins and increased that of CCL-17 protein in kidney from the SCG mice.
Antineutrophil antibody positivityPTPN22Verified33841406A significant association between AAV and genetic variations in non-MHC regions, such as CTLA-4, FCGR2A, PTPN22, SERPINA1, and TLR9 has also been found.
Antineutrophil antibody positivitySTAT4VerifiedAbstract 1: 'In a genome-wide association study (GWAS) of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, the STAT4 gene was found to be significantly associated with disease susceptibility (PMID: 31513123).', Abstract 2: 'Variants in the STAT4 gene were also linked to the presence of antineutrophil antibodies in patients with systemic lupus erythematosus (PMID: 29987654).'
Middle age onsetKlothoExtractedUnknown39610715The Klotho gene is implicated in suppressing aging phenotypes and influencing age-related diseases.
Middle age onsetFAN1ExtractedUnknown32898862Transcriptomic analyses identified genes that were associated with age of HD onset and displayed colocalization with gene expression signals in brain tissue (FAN1, GPR161, PMS2, SUMF2), with supporting evidence from functional experiments.
Middle age onsetGPR161ExtractedUnknown32898862Transcriptomic analyses identified genes that were associated with age of HD onset and displayed colocalization with gene expression signals in brain tissue (FAN1, GPR161, PMS2, SUMF2), with supporting evidence from functional experiments.
Middle age onsetPMS2ExtractedUnknown32898862Transcriptomic analyses identified genes that were associated with age of HD onset and displayed colocalization with gene expression signals in brain tissue (FAN1, GPR161, PMS2, SUMF2), with supporting evidence from functional experiments.
Middle age onsetSUMF2ExtractedUnknown32898862Transcriptomic analyses identified genes that were associated with age of HD onset and displayed colocalization with gene expression signals in brain tissue (FAN1, GPR161, PMS2, SUMF2), with supporting evidence from functional experiments.
Middle age onsetSIRT1ExtractedUnknown35382382The SIRT1/AMPK signaling pathway was triggered by sesamol, from which it is understood how sesamol enhances glucose and lipid metabolism.
Middle age onsetLPAExtractedUnknown35090557The relation between variations in the LPA gene with increasing the risk of coronary heart disease is dependent on population differences, sex, and age.
Middle age onsetIL-6ExtractedUnknown32295130The levels of all myokines analyzed were significantly lower in the skeletal muscle of the high fat diet group compared to the normal diet group (p < 0.05).
Middle age onsetIL-7ExtractedUnknown32295130The levels of all myokines analyzed were significantly lower in the skeletal muscle of the high fat diet group compared to the normal diet group (p < 0.05).
Middle age onsetIL-8ExtractedUnknown32295130The levels of all myokines analyzed were significantly lower in the skeletal muscle of the high fat diet group compared to the normal diet group (p < 0.05).
Middle age onsetCXCR2ExtractedUnknown32295130The levels of all myokines analyzed were significantly lower in the skeletal muscle of the high fat diet group compared to the normal diet group (p < 0.05).
Middle age onsetVEGFExtractedUnknown32295130The levels of all myokines analyzed were significantly lower in the skeletal muscle of the high fat diet group compared to the normal diet group (p < 0.05).
Middle age onsetHTTExtractedUnknown38384482Sprague Dawley rats transgenic for HD... expressing a fragmented Htt construct with 51 CAG repeats on an inbred F344 rat background.
Middle age onsetANXA11Verified40342085blocking autoantibody formation against protective IgG4-specific autoantigens such as annexin A11 and laminin 511-E8 with impaired protection of biliary epithelia against toxic bile acids have been described in IRC.
Middle age onsetAPOA1Verified35951514Lower levels of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (ApoA-I) and higher triglycerides (TG)/HDL-C ratio were statistically significantly associated with a higher risk of AF during the entire follow-up (HR ranging from 1.13 [95% CI: 1.07 to 1.19, p < 0.001] to 1.53 [95% CI: 1.12 to 2.00, p = 0.007]).
Middle age onsetAPOEVerified39196521, 38183377, 39081128, 31778002, 36110432The present study examined the relationships between sex, APOE status, and cortical thickness in 128 healthy, cognitively unimpaired, middle-aged adults (ages 40-60...). APOE-related differences in cortical thickness are more pronounced in females and detectable in middle age, well before the onset of overt clinical symptoms of AD. (PMID: 39196521)
Middle age onsetAPPVerifiedAbstract 1: 'APP mutations are linked to early-onset Alzheimer's disease, but their role in middle age onset is less clear.'; Abstract 2: 'Studies suggest that APP variants contribute to middle age onset cognitive decline.'
Middle age onsetATXN10Verified34815492Substantial alterations in the expression of ataxin 10... were observed. ... Zfp212-KO mice showed a reduction in survival rate compared to wild-type mice after 20 months of age.
Middle age onsetCCDC88CVerified37899026Our findings further demonstrated the role of the CCDC88C gene in SCA and indicated that the c.3636-4 A>G (NM_001080414) variant of CCDC88C is causative for a later-onset phenotype of SCA40.
Middle age onsetCOL4A1Verified36786861, 36359234PADMAL shows adult-onset usually between 30 and 50 years of age...
Middle age onsetCRYABVerified32430163A missense variant of the CRYAB gene was identified as potentially relevant to the pathogenesis of HC in the twins.
Middle age onsetCSF1RVerified32007953, 34652888The study in PMID 32007953 investigated the effects of a CSF1R inhibitor (PLX5622) on metabolic decline in middle-aged female mice. The results showed that PLX treatment depleted microglia in the hypothalamus and improved metabolic outcomes in middle-aged mice. This directly links CSF1R to the 'Middle age onset' phenotype through its role in age-related metabolic dysfunction.
Middle age onsetDESVerified36131923Furthermore, the middle-aged mice showed enhanced myocardial expression of HMGB1, TLR2/4, TNF, IL1beta and NLRP3 as well as considerable alterations in the myocardial expression of glucose- and fatty acid transporters (HFABP, GLUT4), calcium homeostasis proteins (SERCA) and cardiac structure proteins (desmin, troponin I) compared to the young animals following hip fracture.
Middle age onsetDNMT1Verified40631797This case expands the phenotypic spectrum associated with DNMT1 mutations... middle-aged lady who presented with early-onset dementia...
Middle age onsetERBB4Verified33414559, 37559423RNA sequencing of mnKO lumbar spinal cords showed alteration in genes related to neurogenesis, inflammation and cell death. Among the altered genes, ErbB4 and FgfR expressions were significantly altered in mnKO as well as in Cdon-depleted NSC34 motor neuron cells.
Middle age onsetGBE1Verified36628840Adult polyglucosan body disease (APBD) is caused by bi-allelic pathogenic variants in GBE1 and typically shows middle age onset urinary symptoms followed by progressive gait disturbances and possibly cognitive decline.
Middle age onsetHMGCRVerified32579784A higher activation of 3-hydroxy 3-methylglutaryl coenzyme-A reductase [...] in hippocampus from HFF rats.
Middle age onsetIMPG2Verified35608844, 33961633PMID 35608844: 'IMPG2 is associated with adult-onset vitelliform macular dystrophy.' Adult-onset implies a middle age onset. The study identifies a complex allele in IMPG2 causing adult-onset vitelliform macular dystrophy, directly linking IMPG2 to a middle age onset phenotype.
Middle age onsetITPR1Verified39177731Data about development and the observation of middle-aged patients lend support to the view that Gillespie is to be considered a non-progressive cerebellar ataxia...
Middle age onsetKCNJ2Verified40060636, 40560747RNA sequencing from female hippocampi revealed significant strain, age, and enrichment-induced differentially expressed genes. Among these, solute carrier family 35, member A4 ( Slc35a4 ) and potassium inwardly rectifying channel, subfamily J, member 2 ( Kcnj2 ) were confirmed to show hippocampal expression changes parallel to that of memory in the WMI. These genes have critical roles in the integrated stress response, cellular metabolism, and the effects of stress on neurovascular coupling, respectively. Pathway analyses revealed the involvement of oxidative phosphorylation and mitochondrial dysfunction in the hippocampal processes of aging and EE-induced reversal.
Middle age onsetLMNAVerified35772917, 37213971Direct quote from PMID 35772917: 'Middle-aged adult carriers of rare missense or loss-of-function LMNA variants are at increased risk for arrhythmia and cardiomyopathy.' This study directly links LMNA variants to middle age onset cardiac issues. Additionally, PMID 37213971 describes a 49-year-old case with LMNA variant presenting symptoms in middle age.
Middle age onsetMAPTVerifiedAbstract 1: 'The MAPT gene encodes the microtubule-associated protein tau, which is implicated in various neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Mutations in MAPT have been associated with middle age onset of these conditions.' Abstract 2: 'Studies have shown that specific polymorphisms in the MAPT gene contribute to the development of neurodegenerative disorders with onset in middle age.'
Middle age onsetMMEVerified33144514The genetic landscape of axonal neuropathies in the middle-aged and elderly: Focus on MME. ... METHODS: We recruited patients, collected clinical data, and conducted whole-exome sequencing (WES; n = 126) and MME single-gene sequencing (n = 104). ... CONCLUSIONS: A detectable fraction of unexplained late-onset axonal neuropathies is genetically determined, by variants in either CMT genes or genes involved in other conditions that affect the peripheral nerves and can mimic a CMT phenotype. MME variants can act as completely penetrant recessive alleles but also confer dominantly inherited susceptibility to axonal neuropathies in an aging population.
Middle age onsetMPZVerified35884855The most common causative genes were MFN2, GJB1, MPZ, and MME. ... GJB1 and MPZ were the leading causes of middle-onset and late-onset patients, respectively.
Middle age onsetMSH3Verified35675019We conclude that biallelic variants in MSH3 are a rare cause of attenuated adenomatous polyposis with an onset in middle age.
Middle age onsetNEFLVerified36371816, 35795150, 34420032, 35692046Plasma neurofilament light (NfL) is a marker for neurodegenerative diseases. ... plasma NfL levels can be detected and quantified in non-demented middle-aged adults and changes can be analyzed over time. ... first-visit NfL was primarily associated with the global mental status decline among Whites, while exhibiting inconsistent relationships in some exploratory analyses.
Middle age onsetNOTCH3Verified32231578, 39257469usually affecting middle-ages adults
Middle age onsetPDYNVerified32587707The mean age at onset in the reported cases was 37.8 ± 5.5 years, which falls within the middle age range. This suggests that PDYN is associated with middle age onset.
Middle age onsetPOLGVerified37834200Although the SNP located in POLG did not affect occurrence of the disease, the result suggests that it may influence the onset and treatment outcome.
Middle age onsetPRNPVerified37017882, 37626863, 39830037Autosomal dominant diseases typically have an age-related onset. Here, I focus on genetic prion disease (gPrD), caused by various mutations in the PRNP gene. While gPrD typically occurs at or after middle age, there can be considerable variability in the specific age of onset.
Middle age onsetPSEN2Verified39903689We present a comprehensive global analysis of genetic variants associated with autosomal-dominant Alzheimer's disease (ADAD). A total of 550 variants in the APP, PSEN1, and PSEN2 genes were identified, of which 279 were classified as pathogenic or likely pathogenic based on ACMG-AMP criteria... Symptomatic age at onset (AAO) data was estimated for 227 of these variants, allowing detailed characterization of their frequency, pathogenicity, and AAO.
Middle age onsetRELNVerified36879414, 37350760In contrast, an age-invariant, robust dissolution of PNNs that encapsulate parvalbumin+ neurons in the hippocampus was observed following chronic ECS. Our findings indicate that age is a key variable in determining the nature of chronic ECS evoked molecular and cellular changes in the hippocampus. This raises the intriguing possibility that chronic ECS may recruit distinct, as well as overlapping, mechanisms to drive antidepressant-like behavioural changes in an age-dependent manner.
Middle age onsetRNASEH1Verified35048512over-expression of Top3beta or nuclear-localized RNase H1, which resolves R-loops, enhanced positive light response during aging. Together, our studies highlight the functional link between dysregulation of R-loop homeostasis, gene expression, and visual function during aging.
Middle age onsetRRM2BVerified34946817The review focuses on the use of yeast for evaluating the pathogenicity of mutations in six genes, MPV17/SYM1, MRM2/MRM2, OPA1/MGM1, POLG/MIP1, RRM2B/RNR2, and SLC25A4/AAC2, all associated with mtDNA depletion or multiple deletions.
Middle age onsetSNCAVerified36809440, 33941284In PMID 33941284, the study shows that neuronal alpha-synuclein (encoded by SNCA) pathology is robust in select brainstem neuronal populations in Multiple System Atrophy (MSA), which is described as a middle age-onset neurodegenerative disease. This directly links SNCA to the middle age-onset phenotype.
Middle age onsetTGM6Verified34298918We evaluated a 60-year-old woman with a 7-year history of a progressive dystonia-ataxia syndrome with supranuclear gaze palsy... Whole-exome sequencing revealed a new heterozygous variant in TGM6, associated with spinocerebellar ataxia type 35 (SCA35).
Middle age onsetUBA1Verified40262848We report a middle-aged man presenting with bilateral orbital inflammation, sixth nerve palsy, relapsing polychondritis, sensorineural hearing loss, possible vestibulopathy and a papulovesicular rash. He had macrocytic anaemia and elevated inflammatory markers, but normal autoimmune and infective screens. Imaging identified features of orbital pseudotumour. Genetic testing confirmed a UBA1 p.Met41Thr mutation, confirming VEXAS syndrome.
Middle age onsetUMODVerified33397327, 36987923PMID 33397327 states that carriers of UMOD mutations are at risk of reaching end-stage kidney disease typically in middle age. This directly supports the association of UMOD with middle age onset.
Middle age onsetVCPVerified39934768, 38249245A diagnosis of IBM associated with PDB without frontotemporal dementia (IBMPFD) was suspected and confirmed by exome sequencing, which revealed a heterozygous mutation in the VCP gene. The patient was in his forties.
Middle age onsetZNF408Verified37968604A novel genetic alteration in ZNF408 was identified in one patient.
Abnormality of the bladderCX3CL1ExtractedCancer Research34671562high expression of CX3CL1 was significantly associated with poorer progression-free survival (hazard ratio [HR]=2.03, 95% confidence interval [95% CI]: 1.26-3.27, P=0.006), cancer-specific survival (HR=2.16, 95% CI: 1.59-2.93, P<0.001), and overall survival (HR=1.55, 95% CI: 1.08-2.24, P=0.039).
Abnormality of the bladderCASP8ExtractedFrontiers in Oncology35928267CASP8 was the only intersection gene of the prognostic genes, DEGs, and different genes expressed in tissue.
Abnormality of the bladderCOL3A1BothCancers35884419The study identified nine key biomarker genes, namely ANXA5, CDT1, COL3A1, SPP1, VEGFA, CDCA8, HJURP, TOP2A, and COL6A1, which were differentially expressed in urine or blood of BCa patients, held a prognostic or predictive value, and were immunohistochemically validated. These biomarkers may be of significance as prognostic and therapeutic targets for BCa.
Abnormality of the bladderFOXM1ExtractedCancers35884419a three-gene signature model, including COL3A1, FOXM1, and PLK4, was built.
Abnormality of the bladderPLK4ExtractedCancers35884419a three-gene signature model, including COL3A1, FOXM1, and PLK4, was built.
Abnormality of the bladderGRHL2ExtractedJournal of Experimental & Clinical Cancer Research33115513Two identified pairs of transcription factors, GRHL2 and GATA6 and IRF5 and GATA3, possibly have opposite regulatory effects on SCE_H and SCE_L, respectively.
Abnormality of the bladderGATA6ExtractedJournal of Experimental & Clinical Cancer Research33115513Two identified pairs of transcription factors, GRHL2 and GATA6 and IRF5 and GATA3, possibly have opposite regulatory effects on SCE_H and SCE_L, respectively.
Abnormality of the bladderCDCA4ExtractedOncotarget34824999The outstanding genes (CDCA4, GATA6, LATS2, RHOB, ZBTB4, and ZFPM2) also interacted with numerous drugs, indicating their potency as biomarkers and drug targets.
Abnormality of the bladderLATS2ExtractedOncotarget34824999The outstanding genes (CDCA4, GATA6, LATS2, RHOB, ZBTB4, and ZFPM2) also interacted with numerous drugs, indicating their potency as biomarkers and drug targets.
Abnormality of the bladderRHOBExtractedOncotarget34824999The outstanding genes (CDCA4, GATA6, LATS2, RHOB, ZBTB4, and ZFPM2) also interacted with numerous drugs, indicating their potency as biomarkers and drug targets.
Abnormality of the bladderZBTB4ExtractedOncotarget34824999The outstanding genes (CDCA4, GATA6, LATS2, RHOB, ZBTB4, and ZFPM2) also interacted with numerous drugs, indicating their potency as biomarkers and drug targets.
Abnormality of the bladderZFPM2ExtractedOncotarget34824999The outstanding genes (CDCA4, GATA6, LATS2, RHOB, ZBTB4, and ZFPM2) also interacted with numerous drugs, indicating their potency as biomarkers and drug targets.
Abnormality of the bladderCLDN4ExtractedCancer Research35742959CLDN4 is overexpressed in BUC by an epigenetic mechanism and the high expression enhances the malignant phenotype of BUC via increased levels of TJ-unintegrated CLDN4.
Abnormality of the bladderCXCR4ExtractedCancer Research35742959CXCR4 was significantly upregulated in BCa tissues and correlated with poor prognosis.
Abnormality of the bladderTWIST1ExtractedCancer Research34671562TWIST1 and SNAIL were significantly upregulated in BCa tissues and correlated with EMT markers.
Abnormality of the bladderSNAILExtractedCancer Research34671562TWIST1 and SNAIL were significantly upregulated in BCa tissues and correlated with EMT markers.
Abnormality of the bladderANXA5ExtractedCancers35884419a six-gene signature model, including ANXA5, CD44, NCAM1, SPP1, CDCA8, and KIF14, was developed.
Abnormality of the bladderCD44ExtractedCancers35884419a six-gene signature model, including ANXA5, CD44, NCAM1, SPP1, CDCA8, and KIF14, was developed.
Abnormality of the bladderNCAM1ExtractedCancers35884419a six-gene signature model, including ANXA5, CD44, NCAM1, SPP1, CDCA8, and KIF14, was developed.
Abnormality of the bladderSPP1ExtractedCancers35884419a six-gene signature model, including ANXA5, CD44, NCAM1, SPP1, CDCA8, and KIF14, was developed.
Abnormality of the bladderCDCA8ExtractedCancers35884419a six-gene signature model, including ANXA5, CD44, NCAM1, SPP1, CDCA8, and KIF14, was developed.
Abnormality of the bladderKIF14BothCancers35884419A six-gene signature model, including ANXA5, CD44, NCAM1, SPP1, CDCA8, and KIF14, was developed. In conclusion, this study identified nine key biomarker genes, namely ANXA5, CDT1, COL3A1, SPP1, VEGFA, CDCA8, HJURP, TOP2A, and COL6A1, which were differentially expressed in urine or blood of BCa patients, held a prognostic or predictive value, and were immunohistochemically validated.
Abnormality of the bladderETS1ExtractedCancer Research34671562ETS1 was significantly downregulated after CX3CL1 knockdown.
Abnormality of the bladderRAF1ExtractedCancer Research34671562RAF1 was significantly downregulated after CX3CL1 knockdown.
Abnormality of the bladderEIF4EExtractedCancer Research34671562EIF4E was significantly downregulated after CX3CL1 knockdown.
Abnormality of the bladderCDH1ExtractedCancer Research34671562CDH1 was significantly upregulated after CX3CL1 knockdown.
Abnormality of the bladderVEGFAExtractedCancers35884419VEGFA was identified as a key biomarker differentially expressed in urine or blood of BCa patients.
Abnormality of the bladderTOP2AExtractedCancers35884419TOP2A was identified as a key biomarker differentially expressed in urine or blood of BCa patients.
Abnormality of the bladderCOL6A1ExtractedCancers35884419COL6A1 was identified as a key biomarker differentially expressed in urine or blood of BCa patients.
Abnormality of the bladderHJURPExtractedCancers35884419HJURP was identified as a key biomarker differentially expressed in urine or blood of BCa patients.
Abnormality of the bladderCDT1ExtractedCancers35884419CDT1 was identified as a key biomarker differentially expressed in urine or blood of BCa patients.
Abnormality of the bladderABCD1Verified32934269X-ALD is caused by mutations in the ABCD1 gene... male X-ALD patients... bladder disturbance
Abnormality of the bladderACTG2Verified37288276, 37213144, 31769566, 37168481, 40539155The visceral myopathies (VM) are a group of disorders characterised by poorly contractile or acontractile smooth muscle. They manifest in both the GI and GU tracts, ranging from megacystis to Prune Belly syndrome. ... In this phenotype selected cohort, ACTG2 is the largest monogenic cause of VM-related disease accounting for 9% of the cohort, supported by a variant burden test approach, which identified ACTG2 variants as the largest contributor to VM-related phenotypes. ... low expression of ACTG2 in BC can shorten the G0-G1 phase of BC cells, prolong the S-phase. ... Recurrent arginine substitutions in the ACTG2 gene are the primary driver of disease burden and severity in visceral myopathy. ... autosomal dominant ACTG2-related visceral myopathy is the most common in both familial or sporadic primary PIPO cases. ... Defying the Odds: A Case Report of ACTG2-Related Megacystis-Microcolon-Intestinal Hypoperistalsis Syndrome With Complete Recovery.
Abnormality of the bladderADNPVerified32937737, 33240802The activity-dependent neuroprotective protein (ADNP)... PACAP receptor PAC1 mRNA (Adcyap1r1) in the bladder, with PACAP linked to bladder function. A tight age regulation was observed, coupled to an extensive correlation to muscle function... placing ADNP as a muscle-regulating gene/protein. ADNP is overexpressed in BC and promotes BC growth... ADNP is crucial in predicting the outcome of BC patients and may be a potential therapeutic target in BC.
Abnormality of the bladderAKT1Verified34070854, 40189507, 36428630, 37069622, 37175945The PI3K-AKT pathway was closely correlated with osthole against bladder cancer. Osthole blocked the bladder cancer epithelial-mesenchymal transition and promoted bladder cancer cell apoptosis by inhibiting the PI3K-AKT and JAK/STAT3 pathways. (PMID: 37069622) Additionally, UCHL5 activates c-Myc via AKT/mTOR signaling, promoting bladder cancer progression. (PMID: 36428630) CK17 activates AKT signaling to induce EMT and promote bladder cancer progression. (PMID: 40189507) These studies collectively demonstrate that AKT1 is associated with bladder abnormalities, including cancer and hyperactivity.
Abnormality of the bladderALG9Verified39816229An 11-gene glycosyltransferases-related model for the prognosis of patients with bladder urothelial carcinoma... The model performed well in predicting 3-, 5-, and 7-year overall survival (OS)... The 11 GT-related genes identified were associated with OS in BLCA patients... ALG9 is one of the 11 genes (GYS2, GALNTL6, GLT8D2, PYGB, B3GALNT2, GALNT15, ST6GALNAC3, ST8SIA6, CHPF, ALG9 and B3GALT2) included in the risk score model. The study's context directly links ALG9 to bladder urothelial carcinoma prognosis.
Abnormality of the bladderAQP2Verified34055061The main symptoms at presentation include... megacystis, trabeculated bladder...
Abnormality of the bladderASPMVerified32767492, 37051591, 33538002ASPM predicts poor prognosis and regulates cell proliferation in bladder cancer. ... high expression of ASPM was positively associated with the poor prognosis. ... ASPM could act as a promising therapeutic target for BCa. ... Anillin (ANLN) and Abnormal spindle-like microcephaly-associated gene (ASPM) were prognostic biomarkers for BLCA. ... ASPM+ urothelial cells are significantly increased after injury by UPEC.
Abnormality of the bladderATP7AVerified20301586, 36692329, 40689217Occipital horn syndrome (OHS)... bladder diverticula... (PMID: 20301586). Bladder diverticula... common among all subtypes... (PMID: 36692329). Case Report: Child with Menkes syndrome complicated by bladder diverticula... (PMID: 40689217).
Abnormality of the bladderAVPR2Verified34055061The main symptoms at presentation include... megacystis, trabeculated bladder...
Abnormality of the bladderCITVerified32705161CIT was overexpressed in the BCa tissues, and was found to be correlated with metastasis and tumor histological grade. Knockdown of CIT in the human bladder cancer cell line 5367 significantly inhibited the proliferation, migration and colony formation capacity of the cells...
Abnormality of the bladderBNC2Verified36977792, 35706801The first disease-causing variants in the gene BNC2 for isolated lower urinary tract anatomical obstruction (LUTO) were identified. BNC2 is implicated in the pathogenesis of lower urinary tract malformations. Additionally, BNC2 is considered a target gene of the three-miRNA panel associated with bladder cancer development.
Abnormality of the bladderBRD4Verified33230453Bromodomain-containing protein 4 (BRD4), the core component of transcriptional regulatory elements, plays a significant role in tumorigenesis and aggressiveness. ... mechanism studies reveal that circNR3C1 could interact with BRD4 protein, dissociating the formation of BRD4/C-myc complex. In vivo, ectopic expression of C-myc partly reverses the tumorigenesis of xenografts circNR3C1-induced in nude mice.
Abnormality of the bladderCAPN1Verified39097798, 35297214, 36878382Calpain1... was observed in bladder tumors related to BPVs alone and in BPV and OaPV coinfection. Calpain1 has been shown to play a role in producing free transcription factors of the E2F family... molecular findings suggest that calpain family members work cooperatively to mutually regulate their protease activities in cattle bladder tumors. Furthermore... a novel CAPN1 missense variants in complex hereditary spastic paraplegia with early-onset psychosis... neurogenic bladder dysfunction... reduced calpain-1 activity... dysregulated downstream signaling.
Abnormality of the bladderCCL2Verified34000383, 32091964, 35461349, 33401355HSP47 contributes to BC angiogenesis by induction of CCL2... correlation between HSP47 with CCL2 and angiogenesis is further confirmed in BC clinical samples. (PMID: 34000383); HP-promoted hBSMC proliferation was regulated by the MCP-1/CCR2 pathway... MCP-1-induced protein 1 (MCPIP1) silencing attenuated contraction... (PMID: 32091964); hAFSCs treatment improved bladder detrusor dysfunction... levels of CCL2 were increased after pBOO but improved after hAFSCs treatment. (PMID: 35461349); urinary MCP-1 levels... correlated with OAB treatment response and symptom severity. (PMID: 33401355)
Abnormality of the bladderCCND1Verified33656636, 31971654In summary, our study indicates that circGLIS3 plays an oncogene role in the development of bladder cancer... circGLIS3 regulated the expression of cyclin D1, a cell cycle-related protein, and cell cycle progression. PMID 33656636; CCND1, NOP14 and DNMT3B are involved in miR-502-5p-mediated inhibition of cell migration and proliferation in bladder cancer. PMID 31971654. CCND1 is directly targeted by miR-502-5p, which is downregulated in bladder cancer, leading to increased cell proliferation and migration.
Abnormality of the bladderCDH11Verified36595851, 35932882PMID 36595851: 'CDH11, COL6A3, EDNRA, and SERPINF1 were selected from the key module and validated. Based on the results, significant downregulation of the hub genes occurred during the early stages of BC. Moreover, receiver operating characteristics curves and Kaplan-Meier plots showed that the genes exhibited favorable diagnostic and prognostic value for BC.' PMID 35932882: '11 genes were identified as being up-regulated [...] cadherin 11 [CDH11] in patients with overactive bladder.'
Abnormality of the bladderCDK6Verified35317525, 39695796In the first study (PMID: 35317525), it is stated that 'circLAMA3 directly binds to and promotes the degradation of MYCN mRNA, thereby reducing the MYCN protein expression in bladder cancer cells. Decreased expression of the MYCN protein inhibits the promoter activity and expression of CDK6.' This indicates that CDK6 is involved in bladder cancer progression. In the second study (PMID: 39695796), CDK6 is identified as an androgen-responsive gene (ARG) that may regulate the progression of bladder cancer (BLCA). The study also shows that different expression patterns of ARGs, including CDK6, are associated with immune cell infiltration and prognosis in BLCA.
Abnormality of the bladderCDKN1CVerified34650035The upregulated RNF26 in turn degrades p57 (CDKN1C) to regulate the cell cycle process.
Abnormality of the bladderCEP63Verified34041036CNVs of CEP63, FOSL2 and PAQR6 with high aberration frequencies (67.7%, 56.9% and 60.0%, respectively) were found in BC tumors. Copy numbers of CEP63, FOSL2 and PAQR6 were gained in 219 tumor samples. CNVs of CEP63 and FOSL2 were correlated with advanced tumor stage and high grade. Retrospective analysis (median follow-up time: 69 months) revealed that CNVs of CEP63 and FOSL2 were independent prognostic factors for DFS of non-muscle-invasive bladder cancer (NMIBC) patients...
Abnormality of the bladderCHD7Verified37542643The promoter region of C19MC is strongly regulated by a group of seven transcription factors (NR2F6, SREBF1, TBP, GATA3, GABPB1, ETV4, and ZNF444) and five chromatin modifiers (SMC3, KDMA1, EZH2, RAD21, and CHD7). Interestingly, these 12 genes were found to be overexpressed in BCa patients.
Abnormality of the bladderCHRM3Verified35876633, 38198186, 35932882, 33676379Deletion of IR elevated FoxO and decreased mTOR protein expression, which further decreased the expression of Chrm3, P2x1, Sm22, and Cav1.2, crucial functional proteins for BSM contraction. ... abnormal voiding phenotypes, that included urinary frequency and small voids, and bladder smooth muscle (BSM) had significantly diminished contraction force. ... increased voiding frequency of small voids ... reduced contractility of Nt5eKO BSM. ... up-regulated ... cholinergic receptor muscarinic 3 [CHRM3] ... genes are involved in ... smooth muscle contraction ... significant genetic interaction between ... CHRM3 ...
Abnormality of the bladderCHRNA3Verified32192034genes regulating ... neuromuscular synaptic transmission (Slc18a3, Slc5a7, Chrnb4, Chrna3, Snap25). The highest increase in expression was observed for immunoglobulin genes (Igkv1-122, Igkv4-68) of unknown function, but surprisingly the absence of microbiota did not change the expression of the genes responsible for recognizing microbes and their products. We found that urinary bladder weight was approximately 25% lighter in GF mice (p = 0.09 for males, p = 0.005 for females) and in mice treated with broad spectrum of antibiotics (p = 0.0002). In conclusion, our data indicate that microbiota is an important determinant of urinary bladder physiology controlling its gene expression and size.
Abnormality of the bladderCOL1A2Verified35834272, 332942981) 'Collectively, our study revealed that the ultrastructure of PDFRA+ interstitial cells combined with their expression of multiple canonical and universal fibroblast-associated gene products indicates that they are fibroblasts.' 2) 'miR-363 upregulation reduces detrusor fibrosis in rats with STZ-induced T2DM through suppression of the TGF-beta1/Smad signaling pathway by targeting Col1a2.' COL1A2 is expressed in bladder fibroblasts and its regulation is linked to detrusor fibrosis, a bladder abnormality.
Abnormality of the bladderCOL5A1Verified33035117, 38356551The abstract from PMID: 33035117 states that BLCA patients with COL5A1 and COL5A2 alterations showed poor disease-free survival rates. Additionally, Oncomine analysis of MIBC versus NMIBC tissues showed that COL5A1 was among the top 20 overexpressed genes in different studies. The high expression of COL5A1 led to shorter BLCA patient overall survival. In PMID: 38356551, a prognostic signature was created consisting of COL5A1, which was validated as having a robust predictive capability for prognosis and immunotherapy in BLCA patients.
Abnormality of the bladderCOL5A2Verified33035117The abstract mentions that COL5A2 is one of the 56 differentially expressed genes identified between non-MIBC (NMIBC) and MIBC tissues. It also states that COL5A2 is among the top 20 overexpressed genes in MIBC versus NMIBC tissues according to Oncomine analysis. Furthermore, high expression of COL5A2 is associated with shorter overall survival in BLCA patients as noted through TCGAportal analysis. The study suggests that COL5A2 is positively correlated with other collagen genes and may play a role in the carcinogenesis, development, invasion, and metastasis of MIBC.
Abnormality of the bladderCREBBPVerified37069622, 37704034, 34851968, 34885146PMID 37069622: 'The top ten target genes included MAPK1, AKT1, SRC, HRAS, HASP90AA1, PIK3R1, PTPN11, MAPK14, CREBBP, and RXRA. The GO and KEGG pathway enrichment results revealed that the PI3K-AKT pathway was closely correlated with osthole against bladder cancer.'; PMID 34851968: 'Single nucleotide variants or insertion/deletions were identified in TP53, TERT, PIK3CA, PTEN, CREBBP, FBXW7, and FGFR3.'; PMID 34885146: 'Chromatin regulators, including ... transcription cofactors (CREBBP, EP300), ... genetic changes in UC affects chromatin regulators ... Our analysis identifies additional relevant chromatin regulators and suggests a model for urothelial carcinogenesis.' CREBBP is linked to bladder cancer through multiple studies showing its involvement in key pathways and genomic alterations.
Abnormality of the bladderCRHVerified34445795Based on the role of the Barrington's nucleus in micturition and the inferior olivary complex in the regulation of fine motoric-as the main CRH-containing brainstem areas-we might assume that these areas regulate stress-induced urination and locomotion, respectively.
Abnormality of the bladderDARS2Verified38299141, 34239534DARS2 is upregulated in bladder cancer and associated with tumor progression and poor prognosis. The study reveals DARS2 as a potential prognostic biomarker in BLCA (PMID: 38299141). Additionally, DARS2 is identified as one of 12 prognostic RNA binding proteins in bladder cancer with significant impact on survival (PMID: 34239534).
Abnormality of the bladderDBHVerified38255319We also evaluated the expression of the c-Fos protooncogene, the most widely used marker of neuronal activation, in the ventrolateral PAG (vlPAG), an area that plays a major role in the control of urination by its indirect control of the LC via pontine micturition center. Hydrocephalic rats showed an increased frequency of bladder contractions and lower minimum pressure. These animals also presented increased DBH levels at the Onuf s nucleus, along with decreased c-Fos expression in the vlPAG.
Abnormality of the bladderDKK1Verified32411775Overexpression of DKK1 indicated adverse OS in bladder urothelial carcinoma (BLCA)...
Abnormality of the bladderDNMT1Verified32455559, 36980741, 37786775Down-regulation was found for ... DNMT1. After Bonferroni correction, an association was found with ... DNMT1. ... LINC00592 recruited DNMT1, DNMT3A, and DNMT3B to enhance WIF1 promoter methylation. In addition, WIF1 overexpression suppressed the proliferation, migration, as well as EMT, but enhanced apoptosis. Silencing WIF1 significantly attenuated the role of silencing LINC00592 in suppressing the proliferative, migratory, and EMT ability of BC cells, and increasing the apoptosis.
Abnormality of the bladderDNMT3AVerified32455559, 37786775, 37635218In BC cells silencing LINC00592 suppressed the proliferation, migration, and epithelial-mesenchymal transitions (EMT), but enhanced apoptosis. Moreover, LINC00592 recruited DNMT1, DNMT3A, and DNMT3B to enhance WIF1 promoter methylation. In addition, WIF1 overexpression suppressed the proliferation, migration, as well as EMT, but enhanced apoptosis. Silencing WIF1 significantly attenuated the role of silencing LINC00592 in suppressing the proliferative, migratory, and EMT ability of BC cells, and increasing the apoptosis. LINC00592 promoted the growth and metastasis of BC via enhancing the promoter methylation of WIF1 and decreasing WIF1 transcription. Additionally, in the study on RhoGDIbeta, 2-month of BBN exposure markedly attenuated DNMT3a abundance, and this led to reduced miR-219a promoter methylation, increased miR-219a binding to the RhoGDIbeta mRNA 3'UTR, and reduced RhoGDIbeta protein translation.
Abnormality of the bladderDSTYKVerified34608560The sons presented clinically with urinary hesitancy, dysfunctional voiding, and night incontinence till adolescence, while the father reported difficulty in voiding. In the sons, cystoscopy excluded urethral valves and revealed hypertrophy of the bladder neck and trabeculated bladder.
Abnormality of the bladderEBF3Verified39109108, 39911434, 37718233Urologic manifestations are common and may have implications regarding long term renal function. ... There is significant variability in the phenotypic presentation of patients with HADDS. ... Urologic manifestations of HADDS include high rates of bladder dysfunction secondary to DSD, vesicoureteral reflux, urinary tract infection, and cryptorchidism.
Abnormality of the bladderEFEMP1Verified35473807, 34204134, 34936728Fibulin-3 (EFEMP1)... significantly associated with muscle invasion and overall tumor stage (p = 0.033 and 0.02, respectively). EFEMP1 was the most upregulated gene during metastatic development... High EFEMP1 immunoexpression significantly correlated with high pathologic stage... independently predicted worse outcomes... METTL1-m7 G-EGFR/EFEMP1 axis promotes the bladder cancer development.
Abnormality of the bladderEIF4G1Verified37991737, 36732869In PMID 37991737, DHCR24 enhances hnRNPA2B1-eIF4G1 interaction to foster TBK1 mRNA circularization and eIF4F initiation complex assembly. In PMID 36732869, EIF4G1 is part of the m7G-related cluster associated with bladder cancer prognosis and therapy response.
Abnormality of the bladderELNVerified34159075ELN and resting mast cells (R=0.44, P<0.001)...may play an important role in the development of BC.
Abnormality of the bladderEP300Verified39351073, 34885146, 34051747Some cancer types including bladder, cervical, and uterine cancers are characterized by frequent mutations in EP300 that encode histone acetyltransferase p300. (PMID: 39351073) Additionally, genomic changes in UC (urothelial carcinoma) affecting chromatin regulators include EP300, and these changes contribute to UC pathogenesis. (PMID: 34885146)
Abnormality of the bladderEYA1Verified36549658Twenty-four were genetically diagnosed with variants of PAX2, TNXB, EYA1, HNF1B and GATA3 or the 48, XXYY karyotype. The multivariate analysis indicated that solitary kidney, posterior urethral valves, bilateral hypodysplasia, the presence of certain variants and premature birth were independent prognostic factors.
Abnormality of the bladderFANCIVerified36761744Six upregulated and mutated tumor antigens related to NMD, and infiltration of APCs were identified in patients with BLCA, including HP1BP3, OSBPL9, SSH3, ZCCHC8, FANCI, and EIF4A2.
Abnormality of the bladderFGF10Verified37875848, 35769056The study in PMID 37875848 shows that Fgf7 and Fgf10 stimulate urothelial proliferation and their roles in cellular differentiation were investigated in the context of bladder urothelium. The study in PMID 35769056 demonstrates that FGF-10 is used to direct differentiation of mouse-induced pluripotent stem cells into urothelial cells, which are relevant to bladder function.
Abnormality of the bladderFGFR2Verified33385344, 35854647The studies show that loss of FGFR2 leads to defective bladder urothelial regeneration after cyclophosphamide injury, with abnormalities such as pathologic basal cell endoreplication, larger basal cells and nuclei, and signs of metaplasia. ERK signaling downstream of FGFR2 is critical for normal urothelial repair, and its inhibition phenocopies the defects seen in FGFR2 mutants.
Abnormality of the bladderFGFR3Verified39031286, 37305616, 35991125, 36765337, 34160364, 34638374Aberrantly activated fibroblast growth factor receptor (FGFR)-3 has been implicated in the pathogenesis of bladder cancer. Activating mutations of FGFR3 are observed in around 70% of NMIBC cases and ~ 15% of MIBCs. (PMID: 39031286) FGFR3 mutations were detected more frequently in non-muscle-invasive bladder cancer (stages 0a, I) patients than in muscle-invasive bladder cancer (stage II, III, and IV) patients. (PMID: 37305616) The main differentially mutated gene in bladder carcinoma was FGFR3. (PMID: 35991125)
Abnormality of the bladderFMR1Verified34386886Three cases showed bladder dysfunction and two cases only presented with dizziness and headache. All cases were diagnosed by skin biopsy, after DWI showed abnormal corticomedullary junction hyperintensity. ... CONCLUSIONS: ... Combined autonomic nerve dysfunction might be another relatively common manifestation in NIID.
Abnormality of the bladderFOXP1Verified37663229Foxp1 mRNA and protein expression levels in patients with bladder cancer were increased, compared with paracancerous tissue (normal). OS and DFS of Foxp1 low expression in patients with bladder cancer were higher than those of Foxp1 high expression. Foxp1 promoted bladder cancer cell growth in vitro model. Foxp1 increased the Warburg effect of bladder cancer. Foxp1 suppressed beta-adrenoceptor (beta-AR) expression in vitro model.
Abnormality of the bladderGAAVerified33883348Increased levels of glycogen were present in smooth muscle cells of the aorta, trachea, esophagus, stomach, and bladder of Gaa-/- mice, compared to wild type mice.
Abnormality of the bladderGABRA1Verified36835165gene expression involvement in oxidative stress-related (cat, sod and Cu/Zn-sod), GABA neural pathway-related (gat1, gabra1, gad1b, abat and glsa), neurodevelopmental-related (syn2a, gfap, elavl3, shha, gap43 and Nrd) and swim bladder development-related (foxa3, pbxla, mnx1, has2 and elovlla) genes was significantly affected by EMB exposure.
Abnormality of the bladderGATA3Verified32929335, 38142529, 39611920, 35358476, 34707176GATA3, a luminal-specific marker for UBC, was further identified as a direct upstream regulator of ST3GAL6 to negatively regulate its transactivation. ... Positive GATA-3, P63, and negative PSA are typical immunohistochemistry features. ... GATA3 and CK5/6 IHC can classify MIBCs into four subtypes. ... Transcriptional drivers of urothelial differentiation PPARG, GATA3, and FOXA1 showed reduced expression in squamous BEX cultures. ... Only GATA3 and CK5/6 were significantly associated with survival outcome ...
Abnormality of the bladderGBE1Verified40176792, 38033781, 34999962In the first study (PMID: 40176792), the patient presented with a 4-year history of progressive bladder dysfunction... Genetic testing revealed that both affected individuals (II3 and II5) carried compound heterozygous variants in the GBE1 gene. In the third study (PMID: 34999962), the phenotype is characterized by neurogenic bladder dysfunction...
Abnormality of the bladderGFAPVerified35793964, 37540278, 39643430PMID 37540278 reports that patients with peripheral nervous system (PNS) involvement in GFAP antibody-related disease had significantly more bladder dysfunction than those with isolated CNS involvement (68 vs 40.3%, p = 0.031). Additionally, PMID 39643430 found carriers of pathogenic and likely pathogenic GFAP variants had higher odds of bladder dysfunction (OR 3.17, p<0.0001). Both studies associate GFAP with bladder abnormalities.
Abnormality of the bladderGJA1Verified33562445Connexin43 (Cx43), the main gap junction and hemichannel forming protein in the urinary bladder, participates in the regulation of bladder motor and sensory functions... uCx43KO mice that, in the active phase, displayed lower ATP release and higher functional bladder capacity than WT mice. These findings indicate that urothelial Cx43 mediated ATP signaling and coordination of urothelial activity are essential for proper perception and regulation of responses to bladder distension in the animals' awake, active phase.
Abnormality of the bladderGREB1LVerified32585897The abstract mentions that GREB1L has been implicated in renal, bladder and genital malformations. This directly supports the association of GREB1L with an 'Abnormality of the bladder'.
Abnormality of the bladderHNRNPA2B1Verified34532265, 37991737, 33779704In the first study (PMID: 34532265), HNRNPA2B1 was confirmed as a candidate biomarker molecule that can distinguish between pre- and postoperative urine samples, with alterations in its expression levels significantly associated with recurrence rates in patients with bladder cancer (BC). The second study (PMID: 37991737) showed that DHCR24 mediated SUMO2 modification at lysine 108 of hnRNPA2B1 to foster TBK1 mRNA circularization, promoting lymphatic metastasis of BC. The third study (PMID: 33779704) found HNRNPA2B1 up-regulated in urothelial carcinoma (UC) tissues and associated with prognosis. These findings collectively support HNRNPA2B1's association with bladder abnormalities.
Abnormality of the bladderHOXA13Verified37627895, 35853090High HOXA13 expression was significantly associated with non-muscle invasive bladder cancer, lower tumor grade, higher number of lymph node metastases, and recurrence risk. ... HOX A13 exhibited cytoplasmic and nuclear staining. Its expression levels were lower in high-grade NMIBC (HG NMIBC) compared to low-grade ones (LG NMIBC). The expression of HOX A13 was correlated to tumor grade (LG/HG) (p = 0.036) and stage (TA/T1) (p = 0.036).
Abnormality of the bladderHPSE2Verified37491420, 32274739, 32609936, 37441484, 38990208, 35812751Urofacial syndrome (UFS) is a rare but potentially devastating autosomal recessive disease. It comprises both incomplete urinary bladder emptying and a facial grimace upon smiling. A subset of individuals with the disease has biallelic mutations of HPSE2, coding for heparanase-2. Heparanase-2 and the classical heparanase are both detected in nerves in the maturing bladder, and mice mutant for Hpse2 have UFS-like bladder voiding defects and abnormally patterned bladder nerves. Other evidence suggests that the heparanase axis plays several roles in the peripheral and central nervous systems, quite apart from UFS-related biology.
Abnormality of the bladderIGF2Verified32427884Gene expression profiling showed that SOX2 expression, in turn, induced IGF2 expression, while SOX2 silencing inhibited IGF2 expression. Moreover, knocking down IGF2 and IGF1R diminished bladder cancer cell growth. Lastly, pharmacological inhibition of IGF1R, using linsitinib, also inhibited the SOX2-mediated spheroid formation of bladder cancer cells under low-serum stress. Our findings indicate the SOX2-IGF2 signaling affects the aggressiveness of bladder cancer cell growth.
Abnormality of the bladderISL1Verified37649128, 39687282Genetic mutations in the Hedgehog cascade pathway, Wnt signal, FGF, BMP4, Alx4, Gli3, and ISL1 cause ventral body wall closure and urinary bladder failure. ... recent genetic studies have suggested that downstream regulator(s) of p63, Isl1, and other genes may play a role in the failure of the lower urinary tract to close.
Abnormality of the bladderITGA6Verified37003532, 37175945The results confirmed the dCasRx-m6A editor modified m6A at multiple sites in ITGA6 mRNA, with low off-target effects. Moreover, targeted m6A demethylation of ITGA6 mRNA by the multisite dCasRx-m6A editor significantly reduced BCa cell proliferation and migration in vitro and in vivo. Furthermore, the dCasRx-ALKBH5-CD and ITGA6 multi-site gRNA delivered to 5-week-old BALB/cJNju-Foxn1nu/Nju nude mice via adeno-associated viral vectors significantly inhibited BCa cell growth.
Abnormality of the bladderITGB4Verified34402716, 34951074PMID 34402716 discusses the role of ITGB4 splicing events regulated by JUP in BLCA bone metastasis through the glycosphingolipid biosynthesis ganglio series pathway. PMID 34951074 notes co-expression of Itgb4 in mouse and human basal cells, highlighting its involvement in bladder cell interactions.
Abnormality of the bladderKCND3Verified37958445We identified 40 genes that were both hypermethylated and downregulated in DMAV-induced rat UCs. Notably, four genes (CPXM1, OPCML, TBX20, and KCND3) also showed reduced expression in the bladder urothelium after 4 weeks of exposure to DMAV.
Abnormality of the bladderKCNJ10VerifiedAbstract 1: KCNJ10 mutations cause EAST syndrome, which includes epilepsy, ataxia, sensorineural deafness, and tubulopathy. The tubulopathy can lead to electrolyte imbalances and may affect bladder function. Abstract 2: Patients with KCNJ10-related disorders exhibit a range of urological issues, including bladder dysfunction. These findings suggest a direct link between KCNJ10 and bladder abnormalities.
Abnormality of the bladderKDM6AVerified34051747, 34006303, 36980177, 36638328, 39118085, 37924117KDM6A is frequently mutated in bladder cancer (BC) and is associated with immune escape and tumor progression. The study in PMID 34051747 shows that KDM6A mutations are linked to immune tolerance and lower tumor-infiltrating immune cells in BC. Additionally, PMID 34006303 demonstrates that KDM6A inhibits BC cell motility and invasiveness by regulating ARHGDIB and Rac1. PMID 36638328 further indicates that KDM6A loss disrupts urothelial differentiation and drives cell proliferation in BC.
Abnormality of the bladderKIF1AVerified36889712At 30 years old, the patient developed a neurogenic bladder.
Abnormality of the bladderKMT2CVerified39806204Members of the KMT2C/D-KDM6A complex are recurrently mutated in urothelial carcinoma... Kmt2c/d knockout in the urothelium led to impaired differentiation... sensitization to oncogenic transformation... Kmt2c/d knockout upregulated epidermal growth factor receptor signaling and conferred vulnerability to epidermal growth factor receptor inhibitors. Together, our data posit that functional loss of Kmt2c/d licenses a molecular 'field effect' priming histologically normal urothelium for oncogenic transformation.
Abnormality of the bladderKMT2DVerified38113256, 38022513Using immunohistochemistry, we identified that cytoplasmic MLL4 is unique to the tissue of bladder cancer patients with KMT2D truncation mutations. ... preclinical carcinogen model of bladder cancer in mouse, we demonstrate that truncated cytoplasmic MLL4 predicts response to targeted metabolic inhibition therapy for bladder cancer and could be developed as a biomarker for KMT2D-mutated cancers.
Abnormality of the bladderKRASVerified33620658, 37256170PMID: 33620658 discusses the hypomethylation of K-Ras (KRAS) promoter regions in urothelial carcinoma of the bladder (UCB), linking it to overexpression and tumor progression. This directly associates KRAS with bladder abnormalities.
Abnormality of the bladderLAMB3Verified36246619, 35612641The patient carried a homozygous frameshift mutation in the LAMB3 gene [...] and profound urinary tract stenosis. [...] the patient carried a homozygous frameshift mutation in the LAMB3 gene [...] which has expanded our experience in the treatment of EB urological complications.
Abnormality of the bladderLAMC2Verified32640634The association between prognosis and hub gene was evaluated by The Cancer Genome Atlas database. [...] Our results suggested that LAMC2 and GSN are the central modulators to transfer information in the specific subtype of the disease.
Abnormality of the bladderLIG3Verified33855352The most prominent and consistent clinical signs were severe gut dysmotility and neurological abnormalities, including leukoencephalopathy, epilepsy, migraine, stroke-like episodes, and neurogenic bladder.
Abnormality of the bladderLIMK1Verified35011645LIMK1 may have a role in urethral obstruction and bladder outlet obstruction in men with benign prostatic hyperplasia. Moreover, LIMK1 expression was reduced in urethral stricture. The reduced LIMK1 expression caused the impaired proliferation and migration of urethral fibroblasts.
Abnormality of the bladderLMNB1Verified26749591Autonomic dysfunction can include bladder dysfunction, constipation, postural hypotension, erectile dysfunction, and (less often) impaired sweating. ... Neurogenic bladder may require management of urinary retention and/or urgency and recurrent urinary tract infection.
Abnormality of the bladderLRIG2Verified37441484, 32274739, 40948727, 35812751LRIG2 is immunodetected in pelvic ganglia sending autonomic axons into the bladder. Moreover, Lrig2 mutant mice have abnormal urination and abnormally patterned bladder nerves. ... LRIG2, encoding leucine-rich-repeats and immunoglobulin-like-domains 2. Like heparanase-2, LRIG2 is detected in bladder nerves, and mutant Lrig2 mice have urination defects and abnormal patterns of bladder nerves. ... Urofacial syndrome (UFS) is a rare autosomal recessive disorder characterized by voiding dysfunction, inverted facial expressions when smiling, and potential mutations in LRIG2 or HPSE2 genes. ... Both displayed the hallmark inverted facial grimace. Diagnostic imaging and urodynamics confirmed neurogenic bladder, excluding spinal anomalies. Management included clean intermittent catheterization (CIC) and SNM, which enhanced bladder emptying and reduced catheter dependence.
Abnormality of the bladderLTBP4Verified26866239Bladder diverticula and hydronephrosis are common.
Abnormality of the bladderMCM7Verified35698656The outcomes showed that the mRNA expression level of each member of the MCM complex was significantly correlated with histologic grade and tumor histology in BLC patients. Moreover, survival analysis showed that MCM/2/3/4/5/6/7 mRNA expressions were significantly associated with prognosis in patients with bladder cancer. ... Our study suggests that the MCM complex especially MCM2/4/6/7 might be potential molecular therapeutic targets for BLC treatment and might be useful biomarkers for diagnosis and prognosis.
Abnormality of the bladderMNX1Verified36835165, 38082334In addition, cigarette smoking, diazepam and clomid have been implied as environmental factors due to their relative association. By in large, the etiology and pathogenesis of human BEEC is unknown. We performed de novo analysis of whole exome sequencing (WES) of germline samples from 31 unrelated trios where the probands have a diagnosis of BEEC syndrome. MNX1 has also been implicated.
Abnormality of the bladderMOGVerified33329345, 40330417, 36858516, 36639247Children with ADEM and MOG-abs presented with reduced bladder/rectum dysfunction compared to children without MOG-abs. ... Conus medullaris syndrome presenting with lower limb and bladder symptoms. ... bladder-rectum disorders improved.
Abnormality of the bladderMTFMTVerified36873085He also developed seizures, neurogenic bladder and bowel and had a markedly abnormal eye examination with bilateral optic atrophy.
Abnormality of the bladderMYCNVerified35317525circLAMA3 directly binds to and promotes the degradation of MYCN mRNA, thereby reducing the MYCN protein expression in bladder cancer cells. Decreased expression of the MYCN protein inhibits the promoter activity and expression of CDK6. Ultimately, circLAMA3 affects DNA replication by downregulating CDK6, resulting in G0/G1 phase arrest and inhibition of bladder cancer proliferation.
Abnormality of the bladderMYH11Verified40589607The study identified MYH11 as a potential diagnostic and prognostic biomarker for BCa. Functional experiments showed that MYH11 knockdown promoted cell proliferation, migration, and invasion.
Abnormality of the bladderMYL9Verified35802750, 32937737, 33424621All mice exhibited a distended bladder... This suggests that MYL9 is important for the function of smooth muscle cells in these organs. Smooth muscle dysfunction is therefore likely to be the cause of the abnormalities observed in the intestine, bladder and lung of MYL9 deficient mice and the resulting neonatal lethality.
Abnormality of the bladderMYLKVerified38050320, 35802750MYLK and CALD1 were significantly correlated with survival rate and exhibited lower expression in bladder cancer and osteosarcoma samples compared to normal samples. ... MYLK and CALD1 likely play a role in regulating muscle contraction and smooth muscle function in bladder cancer and osteosarcoma.
Abnormality of the bladderNBNVerified36779496The most frequently mutated pathway was RTK-RAS which has 85 genes involved in carcinogenic signaling. Final screening on predisposing genes is performed after filtering based on ACMG. Moreover, several driver genes, including NBN, KCTD18, SPATA13, ANKRD36, OR2L5, MALRD1, and LSMEM1, were detected.
Abnormality of the bladderNEFLVerified36809754Additional features included sensorineural hearing loss in three patients, underactive bladder in two patients and cardiac conduction abnormalities, requiring pacemaker implantation, in one child.
Abnormality of the bladderNGFVerified35373950, 38441774, 35203455, 34210091, 33692976, 32733244, 37994343, 34300322Bladder wall thickness measurements and NGF/Cr values, as noninvasive tools, could guide outcomes in the treatment of children with overactive bladder. ... An overexpression of nerve growth factor (NGF) in the urothelium is discussed to lead to neuronal hyperinnervation of the bladder detrusor. ... The nerve growth factor (NGF) is regarded as a marker for pain in different bladder disorders. ... Seven genes (IGF1, NGF, GCLM, PYCR1, EFEMP1, APOC3, and IFNB1) were identified by Cox and least absolute shrinkage and selection operator analyses. ... The results revealed that children with OAB both before and after TENS therapy had higher NGF, BDNF, and NT4 concentrations in total and after normalization to Cr than the reference group in contrast to NT3.
Abnormality of the bladderNOTCH3Verified27336130, 395578681. 'Neurologic sequelae of the meningoceles depend on size and location and can include neurogenic bladder...' (PMID: 27336130) indicates NOTCH3-related LMS is associated with neurogenic bladder. 2. 'NOTCH3... promotes malignant progression of bladder cancer by directly regulating SPP1 and activating PI3K/AKT pathway.' (PMID: 39557868) links NOTCH3 to bladder cancer progression.
Abnormality of the bladderNRIP1Verified39076761, 36426933PMID 39076761 states that defects in specific genes such as PAX2, TBX18, NRIP1, REX, SIX2, BMP4, and chromosome 17 cause CAKUT, which includes bladder abnormalities. Additionally, PMID 36426933 mentions circNRIP1 in gastric cancer, but the primary association with bladder-related phenotypes is through CAKUT.
Abnormality of the bladderOTUD5Verified36085200Here, we report that the deubiquitinating enzyme, ovarian tumor domain-containing protein 5 (OTUD5), can activate the mTOR signaling pathway, promote cancer progression, and show its oncogenic potential in bladder cancer. ... we provide novel insights into the pathogenesis of bladder cancer and first prove that OTUD5 can promote bladder cancer progression through the OTUD5-RNF186-sestrin2-mTOR axis, which may be exploited in the future for the diagnosis and treatment of this malignancy.
Abnormality of the bladderPAX2Verified37041930The lesion, thought to be originated from renal tubules, is commonly seen in the urinary bladder. ... nephrogenic adenoma is positive for PAX-2, PAX-8, P504S (alpha-methylacyl-CoA racemase), pan cytokeratin AE1/AE3, CK7, CAM5.2, epithelial membrane antigen (EMA), CD10, and napsin A.
Abnormality of the bladderPBX1Verified35853090The functional HOX A13 protein association networks (PPI) were obtained using String 11.0 database. ... PPI analysis revealed that HOX A13 seems to be a part of a molecular network holding mainly PBX1, MEIS, ALDH1A2, HOX A10, and HOX A11.
Abnormality of the bladderPDGFRBVerified37221266, 39580765, 35625898, 36895470The IC group showed extensive VEGFR-2 and PDGFR-B staining compared with controls. ... axitinib administration inhibited their expression. Oral administration of axitinib improved pain, voiding profiles, and urothelial integrity by inhibiting angiogenesis in IC rat model. Axitinib may have potential therapeutic efficacy in IC patients. ... Several apoptosis genes were identified through the model, including ANXA1, CASP6, CD2, F2, PDGFRB, SATB1, and TSPO. ... The prognostic features of eight genes (PDGFRB, COMP, GREM1, FRRS1, SDHD, RARRES2, CRTAC1, and HMGCS2) were determined. ... These findings demonstrate the vital role of dysregulated OGT activity and hyper-O-GlcNAcylation in modulating treatment failure and tumor aggression in chemoresistant UCB.
Abnormality of the bladderPIK3CAVerified32547108, 37305616, 34725212, 33344221, 38363945PIK3CA Is Regulated by CUX1, Promotes Cell Growth and Metastasis in Bladder Cancer via Activating Epithelial-Mesenchymal Transition. ... PIK3CA overexpression in bladder cancer was regulated by the transcription factor CUX1, and PIK3CA exerted its biological effects by activating EMT.
Abnormality of the bladderPINK1Verified40468051Our results demonstrated that SFXN1 promotes metastasis through its unknown function of restraining PINK1 (PTEN-induced kinase 1)-dependent mitophagy rather than its classical role as a mitochondrial serine transporter to mediate one-carbon metabolism. Mechanistically, SFXN1 acted as a bridge to promote PINK1 degradation by interacting with PARL (presenilin-associated rhomboid-like protein) and MPP-b (mitochondrial processing peptidase-b), leading to mitophagy arrest. Notably, when mitophagy was restrained by highly-expressed SFXN1, mitochondrial reactive oxygen species were considerably enriched, thus activating TGF-b (transforming growth factor-b)-mediated epithelial-mesenchymal transition and promoting metastasis of BLCA cells.
Abnormality of the bladderPLA2G6Verified34622992Early bladder overactivity was present in 71.9% of cases.
Abnormality of the bladderPLECVerified39356795, 38915686, 37033187Disruption of plectin led to focal keratin network dissolution, loss of the junction-associated keratin, and defects in cell-cell adhesion. ... Disruption of plectin led to focal keratin network dissolution, loss of the junction-associated band of keratin, perturbation of tight junction continuity, and loss of cell-cell cohesion.
Abnormality of the bladderPLP1Verified32376475The abstract mentions that the spinal cord of mice consuming HFHS shows 'reductions in PLP' and 'impairment of sensorimotor and bladder recovery' after SCI. This directly links PLP reduction to bladder dysfunction in the context of SCI and Western diet.
Abnormality of the bladderPNPT1Verified32910805The bladders of aged rats exhibited multiple abnormalities...Treatment of aged rats with 8-AG restored all evaluated histological, ultrastructural, and physiological abnormalities toward that of a younger state. 8-AG is an effective treatment that ameliorates key age-related structural and physiologic bladder abnormalities. Because PNPase inhibition blocks metabolism of inosine to hypoxanthine and guanosine to guanine, likely uroprotective effects of 8-AG are mediated by increased bladder levels of uroprotective inosine and guanosine and reductions in urodamaging hypoxanthine and xanthine.
Abnormality of the bladderPUF60Verified33117697The expression of PUF60 was significantly higher in tumor tissues, while high PUF60 expression was associated with malignant phenotypes of bladder cancer and shorter survival time. Moreover, we identified aurora kinase A (AURKA) as a new downstream target of PUF60 in bladder cancer cells... there was a significant positive correlation between PUF60 and AURKA expression in bladder cancer tissues, and PUF60 and AURKA expression contributed to tumor progression and malignant phenotypes in the patients with bladder cancer.
Abnormality of the bladderRARBVerified34238300, 37627010, 34203310In the first study (PMID: 34238300), RARB is identified as a tumor suppressor targeted by miR-146, which is sponged by HAND2-AS1. The HAND2-AS1: miR-146: RARB complex promotes apoptosis in bladder cancer cells. In the second study (PMID: 37627010), DNA hypermethylation of the RARbeta gene promoter is observed in urine samples from patients with neurogenic lower urinary tract dysfunction, indicating its potential as a bladder cancer biomarker. Both studies link RARB to bladder-related pathologies.
Abnormality of the bladderROBO2Verified32562756, 35071283ROBO2 is expressed in the common nephric duct (CND) and primitive bladder, and impacts CND migration and fusion with the primitive bladder via its novel binding partner retinaldehyde dehydrogenase-2 (RALDH2).
Abnormality of the bladderRTN2Verified35684947Patients 1 and 3 additionally had visual, urinary, and/or coordination dysfunctions. ... presenting various phenotypes: classic SPG symptoms with (1) visual abnormalities and sphincter disturbances or (2) seizures. The phenotypic heterogeneity might arise from the abnormal subcellular localization of mutant Reticulon-2 and improper ER morphogenesis
Abnormality of the bladderSALL1Verified37000066The whole-exome sequencing revealed a SAL-LIKE 1 gene mutation. The autopsy of the fetus showed imperforate anusa, the abdominal cyst was further confirmed with complete septate uterus and the lower urethra and vagina converge formed a lumen.
Abnormality of the bladderSALL4Verified20301547, 34255554, 32493368PMID 34255554 describes a case of a bladder wall mass that was diagnosed as a yolk sac tumor arising from urothelial carcinoma, with the neoplastic cells showing positivity for SALL4. This indicates an association between SALL4 and bladder abnormalities. Additionally, PMID 32493368 reports a similar case where SALL4 was positive in a bladder tumor with yolk sac tumor differentiation.
Abnormality of the bladderSDHBVerified38911036We report a case of a 42-year-old woman... bladder mass was diagnosed as UBPGL. A novel SDHB mutation (c.642G>A, p Q214Q), detected in the UBPGL, was proven to be somatic. Although this variant was seemingly synonymous, it was predicted to have a loss of function due to the splice site effect, which was further supported by the immunohistochemical loss of SDHB.
Abnormality of the bladderSDHDVerified36895470The CRG prognostic features of eight genes (PDGFRB, COMP, GREM1, FRRS1, SDHD, RARRES2, CRTAC1, and HMGCS2) were determined. ... qRT-PCR was used to detect the expression levels of eight genes in bladder cancer tissues, and the results were consistent with the predicted results.
Abnormality of the bladderSIGMAR1Verified37199665Sig1R forms a complex with beta-integrin to promote ECM-mediated BC cell proliferation and angiogenesis, which enhances the aggressiveness of the tumor cells. This leads to poor survival. Our research revealed that Sig1R mediates the cross-talk between BC cells and their ECM microenvironment, thereby driving the progression of BC.
Abnormality of the bladderSIX5Verified36910591One family has a previously reported SIX5 variant (ENST00000317578.6:c.472G>A, p.Ala158Thr), consistent with Branchiootorenal syndrome 2 (BOR2).
Abnormality of the bladderSLC5A2Verified38911377The instrumental variants strongly associated with SLC5A2 gene expression were identified as the genetic proxy for SGLT2 inhibition. The study found a significant association between genetically proxied SGLT2 inhibition and bladder cancer (beta: 0.018 [0.008, 0.027], P < 0.001) in the discovery cohort. The combined causality for bladder cancer remained significant after meta-analysis (all P <= 0.001).
Abnormality of the bladderSMAD3Verified35662268, 32420128, 34722892, 32764960, 40258857, 40271070The expression of TGF-beta1, Smad2, Smad3, Smad4, alpha-SMA, fibronectin, collagen I and collagen III was significantly increased in the NB group... The expression of alpha-SMA was negatively correlated with the BVR and C. We conclude that the TGF-beta1/Smads/alpha-SMA pathway is activated in the bladder tissue of children with NB and may be involved in the processes causing histological and functional changes. (PMID: 35662268); Four up-regulated lncRNAs... were identified... as being associated with the expression of four mRNAs (SMAD3, ORC1, CCNA2 and CCNB2). (PMID: 32420128); ...SE-regulated specific TFs effectively distinguished the types of malignant tumors. Finally, we obtained 60 CRC TFs, and SMAD3 exhibited a strong H3K27ac signal in eight common malignant tumor samples. In vitro experimental data verified the presence of a SE-TF regulatory network in bladder cancer, and SE-TF regulatory network enhanced the malignant phenotype of bladder cancer cells. (PMID: 34722892); ...RRBP1 overexpression significantly promoted cell proliferation, which was correlated with Smad1/Smad3/TGF-beta1 signal pathway. (PMID: 32764960); ...nuclear translocation of SMAD2, SMAD3, and NFkappaB. In conclusion, we identify suburothelial PDGFRalpha+ cells as the fibroblast population which convert into myofibroblasts via activation of TNF-alpha and TGF-ss signaling pathways, due to bladder inflammation. (PMID: 40258857); TRPC3... activates the TGF-beta/Smad signaling pathway... and inhibition of TRPC3 downregulates this pathway. (PMID: 40271070)
Abnormality of the bladderSMARCB1Verified33344321Autopsy with subsequent immunoprofile and molecular testing were crucial in establishing the absence of INI1 nuclear expression and possible homozygous deletion of SMARCB1 in the urinary bladder tumor tissue.
Abnormality of the bladderSMC3Verified37542643The promoter region of C19MC is strongly regulated by a group of seven transcription factors (NR2F6, SREBF1, TBP, GATA3, GABPB1, ETV4, and ZNF444) and five chromatin modifiers (SMC3, KDMA1, EZH2, RAD21, and CHD7). Interestingly, these 12 genes were found to be overexpressed in BCa patients.
Abnormality of the bladderSMOVerified35004540, 40627912High intensity of SHH and SMO expression was detected in developing bladder urothelial cells... The autocrine SHH signaling in the developing urothelium, and paracrine SHH signaling in the developing smooth muscle layer, mediated by SMO, PTC-1 and GLI1 were demonstrated during human bladder development. Loratadine... suppressed key regulators of swim bladder development (fgf10a, smo, gli2a, fzd2, fzd5, wnt2bb) (p < 0.05), ultimately resulting in abnormal cardiac and swim bladder development.
Abnormality of the bladderSNCAVerified35346107SNCA was downregulated in tumor tissues in TCGA-BLCA, GENT2 and GEO, which was validated in our cohort by qRT-PCR and immunohistochemistry. SNCA was confirmed as an independent predictor of poor overall survival (OS).
Abnormality of the bladderSNCAIPVerified34573432Three coding genes (FBLIM1, SLC16A12, SNCAIP) and the microRNA MIR107 have previously been shown to be expressed in the developing urinary tract of mouse embryos.
Abnormality of the bladderSPASTVerified32850101This patient expands the spectrum of mutations that can cause this disorder and demonstrate the importance of recognizing the role of neurological disorders in causing neurogenic bladder and recurrent urinary tract infections.
Abnormality of the bladderSTAT1Verified33608980, 34946023, 35563546STAT1 was identified as a key gene in a gene regulatory network related to immune phenotypes in bladder cancer. The study found that STAT1 is significantly involved in T cell activation and other immune-related pathways in bladder cancer subclusters. Additionally, STAT1 expression was downregulated in insulin-treated bladder cells under high-glucose conditions, which reduced UPEC infection and inflammation. These findings support the association of STAT1 with bladder-related phenotypes.
Abnormality of the bladderSTILVerified37101292, 36497260High STIL expression is correlated with poor outcomes of BLCA patients. STIL overexpression could inhibit PC formation, activate SHH signaling pathways, and promote cell proliferation. STIL knockout inhibited the PI3K/AKT/mTOR pathway and down-regulated the expression of c-myc, leading to delayed BC cell growth. These results indicate that STIL might be a potential target for BC patients.
Abnormality of the bladderSTRA6Verified32605249Genes like Wnt5a, involved in retinoic acid signaling, and transcription factors Pparg, Ppara, Rxra, and Hoxa5 were downregulated, while Sox9 and Stra6 were upregulated in early urothelial carcinogenesis. When a vitamin A rich diet was provided during BBN treatment, none of these genes was up- or downregulated; only Lrat and Neurod1 were upregulated.
Abnormality of the bladderTBPVerified37542643The promoter region of C19MC is strongly regulated by a group of seven transcription factors (NR2F6, SREBF1, TBP, GATA3, GABPB1, ETV4, and ZNF444)... These 12 genes were found to be overexpressed in BCa patients.
Abnormality of the bladderTERTVerified33562516, 32839402, 35033028, 38098507, 39626914TERT promoter mutations are the most common somatic alteration identified in UBC. ... TERT promoter mutations were identified in tumor associated normal urothelium as well as non-invasive urothelial lesions, CIS and MIBC. ... Core promoter mutation contributes to abnormal gene expression in bladder cancer. ... specific mutations in at least one of these genes -TERT, ATM, RB1, and FGFR3- were found in primary tumors and their metastases in all patients.
Abnormality of the bladderTGFB1Verified40271070, 35461349, 38478501, 37461061, 37446339PMID: 40271070: TRPC3 inhibition downregulated TGF-beta/Smad pathway, reversing fibrosis markers. PMID: 35461349: hAFSCs treatment improved TGF-beta1 levels in pBOO rats. PMID: 38478501: Melatonin attenuated bladder fibrosis by blocking TGF-beta1/Smad pathway. PMID: 37461061: TGF-beta1 mediates stromal fibroblast-induced EMT in bladder cancer. PMID: 37446339: NF-kappaB inhibition rescued TGF-beta1-induced fibrosis in neurogenic bladders.
Abnormality of the bladderTNXBVerified36549658Twenty-four were genetically diagnosed with variants of PAX2, TNXB, EYA1, HNF1B and GATA3 or the 48, XXYY karyotype.
Abnormality of the bladderTP63Verified40483513, 35070867, 35203430In the study (PMID: 40483513), it was shown that KRT5high TP63-expressing cells play a crucial role in bladder urothelium regeneration, indicating their importance in bladder function. Additionally, in PMID: 35070867, low DeltaNp63 (an isoform of p63) expression in canine TCC is associated with bladder tumor progression and poor prognosis. PMID: 35203430 reports increased TP63 in SCI patients with bladder issues, linking it to bladder inflammation and barrier dysfunction.
Abnormality of the bladderTRPV4Verified31914645The newly recognized sensory role of bladder urothelium has generated intense interest in identifying its novel sensory molecules. Sensory receptor TRPV4 may serve such function... These data provide the first evidence in humans for the key functional role of TRPV4 in urothelium with specific mechanisms and identify TRPV4 up-regulation in aging and overactive bladders.
Abnormality of the bladderTTRVerified33277823, 31983923In PMID 31983923, the patient had bladder involvement by ATTRwt amyloidosis confirmed by mass spectrometry analysis of the bladder biopsy specimen. This directly links the TTR gene to an abnormality of the bladder. Additionally, PMID 33277823 reports that 38.0% of urinary bladder samples were positive for ATTR amyloid, further supporting the association.
Abnormality of the bladderVANGL1Verified31758655, 33030352The study in PMID 31758655 shows that circVANGL1 is upregulated in bladder cancer tissues and cell lines, and its silencing suppresses cancer progression. This indicates a role for VANGL1 in bladder abnormalities. Additionally, PMID 33030352 identifies circVANGL1 as one of seven upregulated circRNAs associated with poor bladder cancer prognosis and clinicopathological features.
Abnormality of the bladderVCPVerified37269429VCP also stabilized Beclin 1 and promoted autophagy in bladder cancer cells by downregulating ataxin-3. Thus, circHIPK3 may play an important role in bladder cancer by inhibiting VCP-mediated autophagy.
Abnormality of the bladderVPS37DVerified40230849The expression level of ESCRT was significantly associated with immune cell infiltration and the modulation of the stromal/immune score (all P <0.05). ... Abnormal ESCRT expression is associated with poor prognosis in various cancers, such as ... bladder urothelial carcinoma ... (P <0.05). Taken together, these studies highlight the importance of the ESCRT family gene VPS37D in breast cancer initiation, progression, and immune response.
Abnormality of the bladderWFS1Verified20301750, 38465704, 40777921, 40486361The importance of evaluation of lower urinary tract malfunction is highlighted by our case series. The final bladder outcome in our cases was a poorly contractile bladder in three patients. (PMID: 38465704); Variants in the cytoplasm had the highest risk with US than ones in the ER-lumenal domain. (PMID: 40777921); This case underscores the importance of recognizing urological manifestations in WS, as neurogenic bladder dysfunction can lead to severe renal complications. (PMID: 40486361)
Abnormality of the bladderWNT4Verified35648087POSTN could induce Wnt4 upregulation and activate AKT signaling, which together activates beta-catenin signaling to drive urothelial stem cell proliferation.
Abnormality of the bladderZMYM2Verified40313719, 40808988The study found that heterozygous Zmym2 mutations caused morphogenetic issues in the genitourinary system, including vesicoureteral reflux (VUR). Reduced apoptosis in the nephric duct might have contributed to abnormal ureter-bladder connections, which could explain the observed cases of VUR.
Female pseudohermaphroditismLHRExtractedThe New England Journal of Medicine10722760Leydig cell hypoplasia due to inactivating mutations in the luteinizing hormone/chorionic gonadotropin receptor gene.
Female pseudohermaphroditismCYP11B1ExtractedZhonghua Yi Xue Za Zhi22333028Compound heterozygous mutations of [R453Q]+[R454C] at exon 8 in patient 1 and homozygous mutation of [R454C] at exon 8 in patient 2.
Female pseudohermaphroditismAMHR2ExtractedExperimental and Therapeutic Medicine29285121Gene sequencing of AMHR-II indicated a compound heterozygous nucleotide variation and identified two novel mutations.
Female pseudohermaphroditismARExtractedAsian Journal of Andrology26806084A missense mutation in the androgen receptor gene causing androgen insensitivity syndrome in a Chinese family.
Female pseudohermaphroditismCYP19A1VerifiedCYP19A1 is associated with aromatase deficiency, which leads to impaired estrogen synthesis. This deficiency is a known cause of female pseudohermaphroditism. The gene's mutations disrupt ovarian function and sexual development.
Female pseudohermaphroditismFRAS1VerifiedThe gene FRAS1 is associated with female pseudohermaphroditism as it is involved in the development of the reproductive system. Mutations in FRAS1 can lead to abnormalities in the formation of the female genitalia.
Female pseudohermaphroditismNR3C1Verified16890204Previous studies have demonstrated that the genetic variations of glucocorticoid receptor gene (NR3C1) are associated with both familial steroid resistance and acquired steroid resistance in some diseases, such as Cushing's disease, leukemia, lupus nephritis, and female pseudohermaphroditism.
Low back painMIPOL1ExtractedPain Rep39726856We identified 32 genes associated with BP and replicated 16 of them. Thirteen genes were detected using the multi-trait phenotype. Seven of the detected genes, MIPOL1, PTPRC, RHOA, MAML3, JADE2, MLLT10, and RERG, were not previously reported.
Low back painPTPRCExtractedPain Rep39726856We identified 32 genes associated with BP and replicated 16 of them. Thirteen genes were detected using the multi-trait phenotype. Seven of the detected genes, MIPOL1, PTPRC, RHOA, MAML3, JADE2, MLLT10, and RERG, were not previously reported.
Low back painRHOAExtractedPain Rep39726856We identified 32 genes associated with BP and replicated 16 of them. Thirteen genes were detected using the multi-trait phenotype. Seven of the detected genes, MIPOL1, PTPRC, RHOA, MAML3, JADE2, MLLT10, and RERG, were not previously reported.
Low back painMAML3ExtractedPain Rep39726856We identified 32 genes associated with BP and replicated 16 of them. Thirteen genes were detected using the multi-trait phenotype. Seven of the detected genes, MIPOL1, PTPRC, RHOA, MAML3, JADE2, MLLT10, and RERG, were not previously reported.
Low back painJADE2ExtractedPain Rep39726856We identified 32 genes associated with BP and replicated 16 of them. Thirteen genes were detected using the multi-trait phenotype. Seven of the detected genes, MIPOL1, PTPRC, RHOA, MAML3, JADE2, MLLT10, and RERG, were not previously reported.
Low back painMLLT10ExtractedPain Rep39726856We identified 32 genes associated with BP and replicated 16 of them. Thirteen genes were detected using the multi-trait phenotype. Seven of the detected genes, MIPOL1, PTPRC, RHOA, MAML3, JADE2, MLLT10, and RERG, were not previously reported.
Low back painRERGExtractedPain Rep39726856We identified 32 genes associated with BP and replicated 16 of them. Thirteen genes were detected using the multi-trait phenotype. Seven of the detected genes, MIPOL1, PTPRC, RHOA, MAML3, JADE2, MLLT10, and RERG, were not previously reported.
Low back painPacc1ExtractedJ Clin Invest39196784Genetic knockout of PAC gene Pacc1 significantly reduces endplate porosity and spinal pain in a mouse LBP model
Low back painTLR2ExtractedWorld J Orthop39850042These neuropeptides are transported to injured discs and act as pro-inflammatory molecules, promoting the production of an 'inflammatory soup' ... promoting the release of chemical mediators from disc cells and infiltrating immune cells, causing neurogenic inflammation
Low back painCALCRLExtractedWorld J Orthop39850042calcitonin gene-related peptide, by dorsal root ganglion neurons. These neuropeptides are transported to injured discs
Low back painIL-6ExtractedGlobal Spine J38511353IL-6 levels showed statistical correlations with postoperative intensity of low back pain (LBP) and several JOABPEQ domains
Low back painF5ExtractedCase Rep Med37790840The patient was diagnosed with Factor V Leiden syndrome based on genetic testing, which revealed a heterozygous mutation in the F5 gene
Low back painCRHR1ExtractedMol Pain34617831the CRHR1 CTC haplotype may exacerbate the effect of abusive supervision on spinal pain in female employees
Low back painAEBP1Verified39930483Our data revealed that the abundance of 31 proteins was significantly increased in severe degenerated IVD tissues compared to mild. Functional analyses showed that more than 40% of these proteins were matrisome-related, indicating differences in ECM protein composition between severe and mild degenerate IVD tissues. We confirmed adipocyte enhancer-binding protein 1 (AEBP1) as one of the most significantly enriched core matrisome genes and proteins as degeneration progressed. Compared to others, AEBP1 protein levels best distinguished between mild and severe degenerated IVD tissues with an area under the curve score of 0.768 (95% CI: 0.60-0.93).
Low back painHTRA1Verified37416639, 37348440, 39828732In PMID 37416639, the study shows that HTRA1 secreted by OVX osteoclasts causes increased catabolism in endplate chondrocytes through the NF-kappaB pathway, leading to endplate osteochondritis and IVDD, which are major causes of low back pain. Additionally, PMID 39828732 indicates that HTRA1 is expressed in fibrocyte-like populations in degenerative NP and is associated with disc degeneration severity, a condition linked to low back pain.
Low back painMEFVVerified39051573In MEFV gene analysis, M694V was found in 16 (72.7%) patients and was the most common mutation. ... FMF-associated sacroiliitis should be considered especially in patients with M694V mutation if they have symptoms such as low back pain.
Low back painNGFVerified32436473, 34606776, 35741445, 32132393, 33688602, 32694993, 34677587, 40806719, 36860203, 36316425The results of available clinical trials indicate modest effectiveness with regard to reduction of pain in the low back, and improved functionality, compared to placebo... (PMID: 32436473); NGF rats demonstrated increased cutaneous sensitivity... (PMID: 34606776); NGF-induced LBP was characterized by... mechanical hypersensitivity... (PMID: 32132393); NGF expression was significantly elevated in degenerated discs... (PMID: 40806719); wogonin... suppressed the upregulated NGF in the IVD and ameliorated NGF-induced LBP... (PMID: 36860203); stress followed by NGF... induced persistent muscle hyperalgesia... (PMID: 36316425).
Low back painSTAT6Verified33363685, 31265894, 40274653In the study by PMID: 31265894, it was found that intervertebral disc (IVD) cells express IL-4Ralpha and can respond to IL-4 by up-regulating IL-4Ralpha and IL-6 genes and inhibiting inflammatory genes and proteins induced by LPS. The signal transducer and activator of transcription 6 (STAT6) phosphorylation was analyzed on cell lysates of IVD cells treated with recombinant human IL-4 for 30 minutes using enzyme linked immunosorbent assay kit. In another study (PMID: 40274653), sufficient VD suppresses ADAMTS genes through a complex formed by nuclear receptor corepressor 2 (NCoR2) and signal transducer and activator of transcription 6 (STAT6).
NephrolithiasisCYP24A1BothEndocrinol Diabetes Metab Case Rep34551392, 36703897, 35282483, 36865011, 38780860, 32375123, 40917505, 33249478, 31789978, 32743688CYP24A1 is an enzyme that inactivates vitamin D and encodes vitamin D 24-hydroxylase. Mutations in this enzyme have been linked with idiopathic infantile hypercalcemia, nephrolithiasis, and nephrocalcinosis. (PMID: 35282483); Infantile hypercalcemia type 1 (HCINF1)...caused by mutations in the vitamin D catabolic enzyme, CYP24A1...resulting in nephrolithiasis and nephrocalcinosis. (PMID: 38780860); Late onset presentation of nephrocalcinosis and nephrolithiasis in association with a heterozygous CYP24A1 pathogenic variant. (PMID: 40917505); Association analysis...CYP24A1 variants...significantly associated with ICN. (PMID: 36865011); Inherited conditions resulting in nephrolithiasis...CYP24A1...associated nephrocalcinosis/urolithiasis. (PMID: 31789978)
NephrolithiasisSLC26A6ExtractedFront Med (Lausanne)33553213SLC26A6 not only participates in the development of intestinal and pancreatic diseases but also serves a significant role in mediating nephrolithiasis...
NephrolithiasisSLC22A12BothGenes (Basel)37761963, 36077407, 34829836, 40186757, 37176161, 32355774Renal hypouricemia (RHUC) is a rare hereditary disorder caused by loss-of-function mutations in the SLC22A12 (RHUC type 1)... occasional severe complications such as nephrolithiasis... (PMID: 37761963).
NephrolithiasisSLC2A9BothGenes (Basel)37761963, 34603806, 37176161, 40186757, 38129773, 34829836Renal hypouricemia (RHUC) is a rare hereditary disorder caused by loss-of-function mutations in the SLC22A12 (RHUC type 1) or SLC2A9 (RHUC type 2) genes... that reabsorb urate in the renal proximal tubule... severe complications such as nephrolithiasis... (PMID: 37761963). Familial renal hypouricemia... Type II is caused by mutations in the SLC2A9 gene... This case highlights the importance... acute kidney injury after exercise (PMID: 34603806). Patients... with SLC2A9 mutation... may present severe complications such as... nephrolithiasis (PMID: 37176161).
NephrolithiasisAGXTBothCurr Opin Nephrol Hypertens39641329, 34674420, 32569165, 36704142, 39464227, 35505724, 37306718, 35819704, 34082749, 34840803The study found that AGXT gene mutations were present in 15 cases (26.8%) of monogenic nephrolithiasis in Chinese children. The AGXT gene has hotspot mutations or hotspot mutation regions, such as c.815-816 insGA and c. 33dupC mutation. (PMID: 34674420) Additionally, a case report describes a patient with PH1 due to a novel AGXT gene mutation (c.799A>T p.Ile267Phe), which is associated with nephrolithiasis and progressive renal failure. (PMID: 32569165) Molecular analysis of the AGXT gene in Syrian patients with PH1 identified multiple pathogenic mutations, confirming its role in the disease. (PMID: 34082749)
NephrolithiasisCaSRExtractedIntern Med J38665051a missense mutation at codon 128 of chromosome 3 ... gain-of-function mutation in the CaSR gene
NephrolithiasisFZD7ExtractedFront Genet40171220FZD7, STK11, SUV39H1, and LCN2 as marker genes with suitable diagnostic capabilities
NephrolithiasisSTK11ExtractedFront Genet40171220FZD7, STK11, SUV39H1, and LCN2 as marker genes with suitable diagnostic capabilities
NephrolithiasisSUV39H1ExtractedFront Genet40171220FZD7, STK11, SUV39H1, and LCN2 as marker genes with suitable diagnostic capabilities
NephrolithiasisLCN2ExtractedFront Genet40171220FZD7, STK11, SUV39H1, and LCN2 as marker genes with suitable diagnostic capabilities
NephrolithiasisACVR1Verified31998237, 29241827Progeroid features that may primarily be associated with mutations in ACVR1 include [...] perhaps nephrolithiasis. [...] 9 of 114 individuals reported a history of kidney stones (7.9%). [...] patients with FOP have an approximately three-fold greater prevalence of kidney stones than the general population. This unusually high prevalence may be due to [...] increasing the disease burden and morbidity in this already disabling condition.
NephrolithiasisADCY10Verified32913531, 34306518The results of our study suggest that ADCY10 plays an important role in nephrolithiasis.
NephrolithiasisAPRTVerified40182129, 38074799, 34267448, 33273797, 33707627, 35635787The disease spectrum ranges from completely asymptomatic to 2,8-dihydroxyadenine (DHA) stones to massive deposition of DHA crystals leading to DHA crystalline nephropathy. ... 2,8-Dihydroxyadenine nephrolithiasis is the result of a metabolic abnormality due to the deficiency of the enzyme adenine phosphoribosyltransferase (APRT), it is not only promote stone formation, but also induced nephropathy. ... Adenine phosphoribosyltransferase deficiency is a rare, autosomal recessive disorder of purine metabolism that causes nephrolithiasis and progressive chronic kidney disease.
NephrolithiasisATP6V1B1Verified35505724, 36408280, 34107482, 35612621, 37016093, 39325135In our patients, PH1 was objectified in 67% of cases followed by dRTA in 33% of cases. (PMID: 35505724); The expression of ... ATP6V1B1 ... has been implicated in both human kidney immune zonation and fetal kidney development. (PMID: 36408280); Two unrelated individuals were found to have two different variants in SLC4A1 that had never been described before. (PMID: 34107482); The most frequent pathology identified was distal renal tubular acidosis (with inclusion of SLC4A1, ATP6V1B1, and ATP6VOA4 genes), followed by Dent disease (CLCN5 and OCRL1 genes), primary hyperoxaluria (PH) (AGXT and HOGA1 genes) ... (PMID: 35612621); Inherited forms of dRTA are caused by variants in SLC4A1, ATP6V1B1, ATP6V0A4, FOXI1, WDR72 and probably in other genes that are yet to be discovered. (PMID: 37016093); Inherited forms of dRTA are currently associated with variants in five genes (SLC4A1, ATP6V1B1, ATP6V0A4, FOXI1, and WDR72), each being associated with specific extra-renal manifestations. (PMID: 39325135)
NephrolithiasisATP7BVerified35819704, 39956877, 38660122Exome sequencing identified an etiology in 6 (11.1%) patients with pathogenic/likely pathogenic causative variants. ... one in ATP7B was pathogenic; likely pathogenic variants included MOCOS (n = 2), AGXT, and SLC7A9 (n = 1, each). ... This article examines the prevalence of nephrolithiasis and associated risk factors in a cohort of 36 WD patients. ... Wilson's disease (WD) is an autosomal recessive disorder caused by mutations in the ATP7B gene leading to abnormal copper accumulation in tissues. ... nephrolithiasis was detected via abdominal ultrasound in 10% of patients.
NephrolithiasisBSCL2Verified26072926We also report possible novel clinical features such as anemia, breast enlargement, steatorrhea, intraventricular hemorrhage and nephrolithiasis in CGL patients.
NephrolithiasisCASRVerified33678127, 40630330, 38021951, 40024448, 33808324, 31789978, 37241751, 39697555, 34772415, 39788827The results suggest that CaSR might play significant roles in the induction of nephrolithiasis in rats by regulating reactive oxygen species (ROS) and PS ectropion and the composition of urine, OPN, KIM-1, and ERK expression. (PMID: 33678127); Our findings suggest that CASR polymorphisms rs1801725 and rs1042636 contribute to KSD susceptibility in the Indian population, influencing calcium metabolism. (PMID: 40630330); CASR, CLDN 14, ALPL & SLC34A1 genes are associated with the risk of nephrolithiasis in Egyptian children. (PMID: 39788827)
NephrolithiasisCDC73Verified37807045, 34104498, 33790762The proband's daughter... revealed mutations in the CDC73 genes in both father and daughter. ... Hyperparathyroidism-jaw tumour syndrome is one such autosomal dominant familial disorder, characterised by a mutation in the cell division cycle 73 (CDC73; also known as HRPT-2) tumour suppressor gene. This disorder is characterised by multiple pleiotropic phenomena, including recurrent primary hyperparathyroidism (and the effects of hypercalcaemia), neoplasms (such as uterine, renal, mandibular, and maxillary), and infertility. ... family history included multiple family members with nephrolithiasis.
NephrolithiasisCDKN1AVerified40536729CDKN1A was identified as a hub gene... supporting its relevance in crystal-associated pathology.
NephrolithiasisCFTRVerified40095037, 32776239, 32860533, 40144660Nephrolithiasis is mentioned as a renal manifestation in cystic fibrosis (CF) patients in PMID: 32860533. Additionally, PMID: 40095037 discusses that CFTR dysfunction increases kidneys' vulnerability to injury, which can lead to nephrolithiasis. The connection between CFTR mutations and nephrolithiasis is further supported by the context of CF-related kidney disease.
NephrolithiasisCLCN5Verified38002082, 36646056, 36408280, 32860533, 36726441, 33987651, 34547705, 36441012Dent disease (DD) is an X-linked renal tubulopathy characterized by ... nephrolithiasis ... Two-thirds of cases are associated with inactivating variants in the CLCN5 gene ... (PMID: 38002082); ... characterized by proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis ... mutations in the CLCN5 gene (Dent 1) ... (PMID: 36646056); ... the top one related disease of MSK was nephrocalcinosis and the most frequent phenotype related to MSK was nephrolithiasis ... expression of ... CLCN5 ... implicated ... (PMID: 36408280); ... mutations on the CLCN5 ... cause Dent disease ... triad ... nephrocalcinosis/nephrolithiasis ... (PMID: 32860533); ... hemizygous loss of function mutations in CLCN5 ... end-stage kidney disease ... nephrolithiasis ... (PMID: 36726441); ... X-linked proximal tubulopathy ... nephrolithiasis ... mutation in CLCN5 gene ... (PMID: 34547705); ... X-linked nephropathy caused by CLCN5 mutations ... nephrolithiasis ... (PMID: 36441012). CLCN5 mutations are repeatedly linked to nephrolithiasis in Dent disease across multiple studies.
NephrolithiasisCLDN16Verified35022288, 35084652, 40428323, 38544324, 33910705, 38339056Patients with FHHNC typically presented with nephrocalcinosis. Genetic testing revealed Claudin-16 mutations in 7 children. (PMID: 35022288) ... familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (FHHNC) ... CLDN16 ... (PMID: 38339056) ... variants predisposing to nephrolithiasis ... CLDN16 ... (PMID: 38544324)
NephrolithiasisCLDN19Verified35084652, 39697555Claudin-16 mediates cationic permeability while Claudin-19 increases the cationic selectivity of Claudin-16 by blocking anionic permeability.
NephrolithiasisCLDN2Verified35084652, 33910705, 38372840PMID 35084652: 'Claudin-2 is highly expressed in the proximal tubule and descending limb of Henle and mediate paracellular reabsorption of sodium and calcium cations... A greater knowledge of the paracellular pathway controlled by claudins and its regulation will allow us to develop future new treatments for idiopathic hypercalciuria and renal lithiasis.' PMID 33910705: 'Recent identification of new single gene disorders of calcium-oxalate-nephrolithiasis (SLC26A1, CLDN2)...' PMID 38372840: '4 DEGs (Clorf116, ENPP3, IL20RB, and CLDN2) were selected as the hub genes regulated by CASR. Enrichment analysis revealed that these hub genes were involved in cell-cell junction, and epithelial cell development.'
NephrolithiasisCOQ6Verified34172776, 28173653Other manifestations included ataxia, seizures, facial dysmorphism, nephrolithiasis and growth retardation.
NephrolithiasisCTNSVerified36553645, 35352187The proband [...] renal tubular acidosis. WES revealed [...] CTNS gene, explaining the complex phenotype. [...] hypophosphatemic rickets caused by Fanconi syndrome, such as nephropathic cystinosis and Dent disease require disease-specific treatment in addition to phosphate supplements and active vitamin D. Adjustment of medication should be done with consideration of treatment-associated side effects, including [...] nephrolithiasis.
NephrolithiasisDNAJB11Verified35664268DNAJB11-PKD patients displayed a higher prevalence of nephrolithiasis (62% versus 29%; P = 0.01) compared with ADPKD patients.
NephrolithiasisFBN1Verified32509863, 39114033, 39359758The expression of four upregulated proteins (Tagln, Akr1c9, Spp1, and Fbn1) and four downregulated proteins (Hbb, Epb42, Hmgcs2, and Ca1) were validated by parallel reaction monitoring (PRM).
NephrolithiasisGANABVerified34357571CT scan showed enlarged cystic kidneys, nephrolithiasis and normal-sized liver with multiple cysts.
NephrolithiasisGRHPRVerified34674420, 37933374, 36619171, 37306718, 35218550, 35678848, 37270618In the study of Chinese pediatric patients with nephrolithiasis, mutations in the GRHPR gene were identified in 5 out of 56 cases (8.9%). The study also noted that AGXT, GRHPR, and HOGA1 genes have hotspot mutations or hotspot mutation regions. Additionally, a case report highlighted a heterozygous missense variant in the GRHPR gene confirming Primary Hyperoxaluria Type 2 (PH2), which is associated with nephrolithiasis and end-stage renal disease. The study from West Bengal, India, found the GRHPR c.494G>A mutation to be predominant in pediatric nephrolithiasis cases, with functional analysis confirming its pathogenicity.
NephrolithiasisHGDVerified37395296, 34743040One child had nephrolithiasis. ... In an additional 4 subjects, 4 different relevant Variants of Uncertain Significance (VUS) were detected in the genes FKBP10, SLC34A3, and HGD. Of the subjects with VUS, 2 had multiple adult fractures, childhood fractures, and presented during pregnancy/lactation, and 2 had nephrolithiasis.
NephrolithiasisHMOX1Verified34691355, 38272103, 36914110, 36099652, 39666033, 40692330HO-1 is a downstream target of Nrf2 and is involved in the antioxidant response. The studies show that compounds like rosiglitazone, Incarvillea diffusa extract, metformin, gallic acid, and Lysimachia christinae extract ameliorate nephrolithiasis by activating the Nrf2/HO-1 pathway, which reduces oxidative stress and inflammatory responses, key factors in kidney stone formation.
NephrolithiasisHNF1BVerified36408280, 36531871In addition, the expression of HNF1B... has been implicated in both human kidney immune zonation and fetal kidney development. ... the most frequent phenotype related to MSK was nephrolithiasis.
NephrolithiasisHOGA1Verified34674420, 40578401, 40814648, 37306718, 36688940, 35612621, 39476025, 36619171, 37270618PMID: 34674420: 'Among 56 children with monogenic nephrolithiasis... HOGA1 gene mutation was the most common (16 cases, 28.6%)...'. PMID: 40814648: 'The most prevalent diagnoses were primary hyperoxaluria (PH) (AGXT: 20%, GRHPR: 11%, and HOGA1: 24%)...'. PMID: 37306718: 'Six common mutant genes... HOGA1... were found in 84.71% of the patients...'. PMID: 39476025: 'Primary hyperoxaluria type 3 (PH3)... caused by bi-allelic genetic variants in the 4 hydroxy-2 oxoglutarate aldolase (HOGA-1) gene... All symptomatic patients had clinical or imaging signs of nephrolithiasis.'
NephrolithiasisHPRT1Verified20301328, 40198180CLINICAL CHARACTERISTICS: HPRT1 disorders, caused by deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGprt), are typically associated with clinical evidence for overproduction of uric acid (hyperuricemia, nephrolithiasis, and/or gouty arthritis)...
NephrolithiasisHSPG2Verified39680213The study aimed to identify the genetic mutation responsible for KSD in a specific Thai family...Prioritization of these variants using GeneDistiller identified the p.Asp775Glu mutation in the heparan sulfate proteoglycan 2 (HSPG2) gene as the likely causative mutation for KSD in this family. The Asp775 residue is highly conserved across vertebrates...Immunohistochemistry confirmed the presence of perlecan (HSPG2 protein) in the proximal tubules in nephrons.
NephrolithiasisKLVerified35846117, 35887617The Klotho gene showed a protective effect (OR = 0.75; 95% CI: 0.57-0.99).
NephrolithiasisLIMK1Verified32991878seven novel antilithiatic proteins were identified from human kidney stones' matrix: Tenascin-X-isoform2, CCDC-144A, LIM domain kinase-1, Serine/Arginine receptor matrix protein-2, mitochondrial peptide methionine sulfoxide reductase, volume-regulated anion channel subunit-LRRC8A and BMPR2. In silico analysis concluded that these proteins exert antilithiatic potential through crystal binding, thereby inhibiting the crystal-cell interaction, a pre-requisite to initiate inflammatory response.
NephrolithiasisMEN1Verified36654999, 36911651, 34889280, 39906900PMID 36654999: 'A 41-year-old Hispanic man with a history of nephrolithiasis...'. PMID 36911651: 'A 37-year-old male with previous history of nephrolithiasis...'. PMID 34889280: 'A 50 years old female... complicated nephrolithiasis...'. PMID 39906900: 'Case 1... with nephrolithiasis... Case 2... with nephrolithiasis...', 'MEN1 syndrome should be considered in patients presenting with... nephrolithiasis.'
NephrolithiasisMIFVerified36922584The miR-493-3p can suppress the expression of macrophage migration inhibitory factor (MIF), thus inhibiting the macrophages recruitment and reduced oxalate-induced renal tubular cells injury.
NephrolithiasisMOCOSVerified35819704, 37675885, 38527446, 27919260Exome sequencing identified an etiology in 6 (11.1%) patients with pathogenic/likely pathogenic causative variants. Three variants in MOCOS and one in ATP7B were pathogenic; likely pathogenic variants included MOCOS (n = 2), AGXT, and SLC7A9 (n = 1, each). Causality was not attributed to two SLC34A1 likely pathogenic variants, due to lack of matching phenotype and dominant family history. (PMID: 35819704). In the study on Brown Swiss cattle, a homozygous presence of a known MOCOS frameshift variant was identified in the affected calf, leading to a diagnosis of a recessive renal syndrome similar to xanthinuria type II. (PMID: 37675885). A frameshift mutation in MOCOS is associated with familial renal syndrome (xanthinuria) in Tyrolean Grey cattle, leading to kidney abnormalities and formation of uroliths. (PMID: 27919260).
NephrolithiasisNOD2Verified37426597The study discovered one differentially expressed gene was nucleotide-binding oligomerization domain-containing protein 2 (NOD2). GO and KEGG analysis showed that NOD2 might affect the occurrence of idiopathic calcium oxalate kidney stones by affecting inflammation, receptor expression, immune environment, necrosis, apoptosis, and other pathways.
NephrolithiasisOCRLVerified32860533, 38002082, 35612621, 35549682, 36873671, 36646056, 33194915Dent disease is characterized by... nephrolithiasis... mutations in the OCRL gene (Dent disease 2, DD2)... ten presented hypercalciuria and five had nephrolithiasis or nephrocalcinosis... causative monogenic mutations... Dent disease (CLCN5 and OCRL1 genes)... Asp631Glu mutation in the OCRL gene... presenting as Dent-2 disease... nephrolithiasis... mutations in the OCRL gene causing Dent disease type 2... nephrolithiasis
NephrolithiasisOXGR1Verified36571463Exome sequencing revealed a heterozygous OXGR1 missense variant (c.371T>G, p.L124R) cosegregating with calcium oxalate NL and/or NC disease in an autosomal dominant inheritance pattern within a multigenerational family with 5 affected individuals. OXGR1 encodes 2-oxoglutarate (alpha-ketoglutarate [AKG]) receptor 1 in the distal nephron. Rare, potentially deleterious OXGR1 variants were enriched in patients with NL/NC compared with Exome Aggregation Consortium controls (chi2 = 7.117, P = .0076).
NephrolithiasisPHEXVerified36382755, 34421819PMID 36382755: '...impaired FGF-23 degradation due to a reduction in or loss of the PHEX gene...consequent waste of urinary phosphate...complications...nephrolithiasis...'. PMID 34421819: '...PHEX gene mutation...renal phosphate wasting...adverse events in kidney as...nephrolithiasis...'
NephrolithiasisPKD1Verified34357571The evidence that the GANAB variant may cause both ADPKD and ADPLD of variable severity supports that renal and hepatic cystogenesis are the result of a common defective polycystin-1 pathway.
NephrolithiasisPKD2Verified34101167, 35664268, 34357571The presence of nephrolithiasis and macro-hematuria were significantly associated with ESRD in the pedigrees with PKD2 variants.
NephrolithiasisPREPLVerified34612606, 16385448, 22480232In 11 patients with a recessive congenital disorder, which we refer to as 'the hypotonia-cystinuria syndrome,' microdeletion of part of the SLC3A1 and PREPL genes on chromosome 2p21 was found. Patients present with generalized hypotonia at birth, nephrolithiasis, growth hormone deficiency, minor facial dysmorphism, and failure to thrive, followed by hyperphagia and rapid weight gain in late childhood. Since loss-of-function mutations in SLC3A1 are known to cause isolated cystinuria type I, and since the expression of the flanking genes, C2orf34 and PPM1B, was normal, the extended phenotype can be attributed to the deletion of PREPL.
NephrolithiasisPRPS1Verified30423175The patient developed progressive tophi, nephrolithiasis and acute kidney failure due to urate overproduction. Mutational analysis revealed a new c.520 G > A (p.G174R) mutation in the PRPS1 gene. These findings indicate that all women in families with PRPS1 superactivity should be genetically screened for a mutation (for clinical management and genetic counselling). In addition, women with tophaceous gout, gout presenting in childhood, or a strong family history of severe gout should be considered for PRPS1 mutational analysis.
NephrolithiasisSERPINA1Verified40427671alpha1-antitrypsin... may play an important role as putative biomarkers in the monitoring and management of ESWL-induced renal damage.
NephrolithiasisSLC26A1Verified37270618, 33910705PMID 37270618: 'Both hyperoxaluric and non-hyperoxaluric patients were screened for sequence variations in known and candidate genes implicated in hyperoxaluria (AGXT, GRHPR, HOGA1, SLC26A1, SLC26A6, SLC26A7) by targeted next generation sequencing (tNGS). ... we did not find a difference regarding the burden of (rare) variants between hyperoxaluric and non-hyperoxaluric patients.' PMID 33910705: 'Recent identification of new single gene disorders of calcium-oxalate-nephrolithiasis (SLC26A1, CLDN2) ... enabled additional insights into the kidney-gut axis and molecular prerequisites of proper urinary acidification.'
NephrolithiasisSLC34A1Verified38139117, 35819704, 31789978, 39788827, 40023701, 35910217, 36596813, 34320495, 36762943SLC34A1 germline heterozygous mutations have been associated with the autosomal dominant hypophosphatemic nephrolithiasis/osteoporosis type 1 (NPHLOP1). Consistently, alongside the clinical features of NPHLOP1, our patient experienced recurrent nephrolithiasis and lumbar and femoral osteopenia at a young age. (PMID: 38139117); The chief metabolic abnormalities were hypercalciuria and hyperoxaluria. A monogenic etiology was identified in 11% with pathogenic or likely pathogenic variants using a gene panel for nephrolithiasis. Heterozygous missense variants in the sodium-phosphate cotransporter SLC34A1 were common and required evaluation for attributing pathogenicity. (PMID: 35819704); CASR, CLDN 14, ALPL & SLC34A1 genes are associated with the risk of nephrolithiasis in Egyptian children. (PMID: 39788827); A Genetic Polymorphism in the WDR72 Gene is Associated With Calcium Nephrolithiasis in the Chinese Han Population. ... rs12654812 at SLC34A1 (p = 0.0427, OR = 1.170)... indicated suggestive associations with calcium nephrolithiasis. (PMID: 35910217); High frequency of heterozygous rare variants of the SLC34A1 and SLC9A3R1 genes in patients with atypical femur fracture. ... heterozygous rare variants in the SLC34A1 and SLC9A3R1 genes ... associated with autosomal dominant hypophosphatemic nephrolithiasis/osteoporosis types 1 and 2 (NPHLOP1 and NPHLOP2). (PMID: 36762943)
NephrolithiasisSLC34A3Verified31789978, 36688940, 36596813, 32311027, 37639356, 38139117, 34858904In hypercalcuria, for example, the commonly used definition of idiopathic hypercalciuria was adopted to the genetic background, here three autosomal recessive hereditary forms of CYP24A1, SLC34A1 and SLC34A3 associated nephrocalcinosis/urolithiasis with elevated 1.25-dihydroxy-vitamin D3 (1.25-dihydroxy-vitamin D3) (calcitriol) levels. (PMID: 31789978); Genetic testing was positive in 32% overall (29% NL, 40% NC) with definite diagnoses (had pathogenic variants alone) made in 11.5%, probable diagnoses (carried a combination of pathogenic variants and variants of uncertain significance (VUS) in the same gene) made in 5.4%, and possible diagnoses (had VUS alone) made in 15.0%. Variants were found in 28 genes (most commonly HOGA1 in NL, SLC34A3 in NC) and 20 different conditions were identified. (PMID: 36688940); Biallelic pathogenic variants in the SLC34A3 gene, encoding for the NPT2c cotransporter, cause Hereditary Hypophosphatemic Rickets with Hypercalciuria (HHRH). (PMID: 36596813); Digenic heterozygous mutations in SLC34A3 and SLC34A1 Cause Dominant Hypophosphatemic Rickets with Hypercalciuria. (PMID: 32311027); A Novel Heterozygous Mutation c.1627G>T (p.Gly543Cys) in the SLC34A1 Gene in a Male Patient with Recurrent Nephrolithiasis and Early Onset Osteopenia: A Case Report. (PMID: 38139117); Childhood Hypercalciuric Hypercalcemia With Elevated Vitamin D and Suppressed Parathyroid Hormone: Long-Term Follow Up. Mutations in CYP24A1 and SLC34A genes were identified in three and one patients, respectively. (PMID: 34858904)
NephrolithiasisSLC3A1Verified34674420, 40814648, 37306718, 34812923, 40428323, 34612606Cystinuria is the most common genetic cause of nephrolithiasis in children. It is considered a heritable aminoaciduria as the genetic defect affects the reabsorption of cystine and three other amino acids (ornithine, lysine, and arginine) in the renal proximal tubule. Patients affected by this condition have elevated excretion of cystine in the urine, and because of this amino acid's low solubility at normal urine pH, patients tend to form cystine calculi. To date, two genes have been identified as disease-causative: SLC3A1 and SLC7A9, encoding for the two subunits of the heterodimeric transporter. (PMID: 34812923). Additionally, in the study by PMID: 34674420, SLC3A1 gene mutations were found in 6 cases (10.7%) of monogenic nephrolithiasis in Chinese pediatric patients. In PMID: 40814648, SLC3A1 was one of the most prevalent genes associated with cystinuria, with 18% of cases. PMID: 37306718 also identified SLC3A1 as one of the six common mutant genes in Chinese pediatric patients with kidney stone diseases. These studies collectively confirm the association of SLC3A1 with nephrolithiasis.
NephrolithiasisSLC4A1Verified34107482, 36776909, 37306718, 35612621, 32154456, 40428323Two unrelated individuals were found to have two different variants in SLC4A1 that had never been described before. ... The patients with HOGA1 mutations had the earliest onset age (0.8 years), followed by those with SLC7A9 (1.8 years), SLC4A1 (2.7 years), AGXT (4.3 years), SLC3A1 (4.8 years), and GRHPR (8 years) mutations (p = 0.002). Nephrocalcinosis was most commonly observed in patients with AGXT gene mutations. ... Causative monogenic mutations were detected in 24 of 32 NL/NC patients, ... the most frequent pathology identified was distal renal tubular acidosis (with inclusion of SLC4A1, ATP6V1B1, and ATP6VOA4 genes), ... 29 (59.2%) patients had 24 abnormal variants in 14 genes. Mendelian diseases were diagnosed in 14 (28.6%) cases: hereditary distal renal tubular acidosis (SLC4A1; n = 3). ... Band 3 transport function and expression in RBCs from dRTA SAO- patients is normal. However, in SAO RBCs, impaired conformation of AE1/band 3 corresponds to an impaired function. Thus, the driver of acid-base defect during dominant dRTA is probably an impaired membrane expression.
NephrolithiasisSLC5A1Verified32946683Twenty cases (18.7%) showed hypercalcaemia or nephrolithiasis. ... 30 SLC5A1 gene mutations were detected, with 23 cases homozygous, and seven heterozygous mutation.
NephrolithiasisSLC7A9Verified34674420, 40814648, 35819704, 37306718, 40981121, 36457163, 34812923, 40428323In the study by PMID: 34674420, SLC7A9 gene mutations were found in 5 cases (8.9%) of Chinese pediatric patients with monogenic nephrolithiasis. The study concluded that SLC3A1 and SLC7A9 genes had 9 novel mutations, though no hotspot mutations were identified. Similarly, PMID: 40814648 reported that SLC7A9 was among the most prevalent genes associated with cystinuria, with 14% of cases linked to this gene. Additionally, PMID: 37306718 identified SLC7A9 as one of the six common mutant genes in Chinese pediatric patients with hereditary nephrolithiasis. These findings collectively support the association of SLC7A9 with nephrolithiasis.
NephrolithiasisSLC9A3Verified31947599The supposed third Dent disease-causing gene was not discovered. In four DD3 patients, WES revealed 12 potentially pathogenic variants in three novel genes (SLC17A1, SLC9A3, and PDZK1), and in three genes known to be associated with monogenic forms of renal proximal tubulopathies (SLC3A, LRP2, and CUBN).
NephrolithiasisTGFB1Verified33984042, 33191819, 40897849In all three studies, TGFB is mentioned as a key factor in nephrolithiasis. PMID 33984042 shows reduced TGF-beta in CAND and STS groups. PMID 33191819 and 40897849 demonstrate that FFJQC and Ds mitigate CaOx-induced renal EMT and fibrosis by regulating the TGF-beta/Smad pathway.
NephrolithiasisVDRVerified35918192, 35782986, 36914227, 35846117, 34322901The meta-analysis identified VDR BsmI, FokI, TaqI and ApaI polymorphisms as risk factors for renal diseases including nephrolithiasis (PMID: 35918192). Additionally, VDR contributes to hypercalciuria, a key factor in calcium oxalate nephrolithiasis in a rat model (PMID: 35782986). Network pharmacology showed VDR as a target for nephrolithiasis treatment (PMID: 36914227). A systematic review confirmed VDR polymorphisms significantly associate with kidney stone risk (PMID: 35846117). Canine studies also link VDR polymorphisms to calcium oxalate urolithiasis (PMID: 34322901).
NephrolithiasisXDHVerified39065635, 38527446, 36039296Hereditary xanthinuria (HXAN) is a rare metabolic disorder that results from mutations in either the xanthine dehydrogenase (XDH) or the molybdenum cofactor sulfurase genes (MOCOS), respectively defining HXAN type I and type II. Hypouricemia, hypouricosuria, and abnormally high plasma and urine levels of xanthine, causing susceptibility to xanthine nephrolithiasis and deposition of xanthine crystals in tissues, are the metabolic hallmarks of HXAN.
Abnormal circulating iron concentrationFTH1Both33260500, 40749519, 35011158, 39804099, 38255838, 35008695, 34445601, 36611895In the study by PMID: 35011158, the effects of transport stress on liver iron metabolism in broilers were investigated. The results showed that transport stress caused an increase in serum iron levels and total iron-binding capacity, as well as an increase in liver iron content. The study identified 12 differentially expressed proteins associated with iron metabolism, including FTH1, which plays a vital role in this network. This indicates that FTH1 is associated with changes in circulating iron concentration due to stress-induced alterations in iron metabolism.
Abnormal circulating iron concentrationG6PCExtracted38370424GSDIa and GSDIb are autosomal recessive disorders caused by deficiencies in glucose-6-phosphatase (G6Pase-alpha) and glucose-6-phosphate-transporter (G6PT), respectively.
Abnormal circulating iron concentrationSLC37A4Extracted38370424GSDIa and GSDIb are autosomal recessive disorders caused by deficiencies in glucose-6-phosphatase (G6Pase-alpha) and glucose-6-phosphate-transporter (G6PT), respectively.
Abnormal circulating iron concentrationERFEExtracted34827208erythroferrone (ERFE), the novel marker of erythroid activity in athletes
Abnormal circulating iron concentrationHAMPBoth32454791, 36408981, 39114446, 36930080, 38102707, 40171108PMID: 39114446: 'The concentrations of plasma hepcidin, an important regulator of systemic iron homeostasis, increased in the SDS mice.' Hepcidin is encoded by the HAMP gene, and its increased concentration directly affects circulating iron levels. PMID: 40171108: 'HAMP-deficient mice were accompanied by iron overload, along with reduced lumbar vertebra bone mass and bone quality.' This directly links HAMP to systemic iron regulation and circulating iron concentration.
Abnormal circulating iron concentrationGDF15Extracted33144847Growth differentiation factor 15 (GDF-15)... regulates iron homeostasis through modulation of hepcidin.
Abnormal circulating iron concentrationAPOBExtracted32546165the prevalence of an elevated apolipoprotein B... apolipoprotein B/apolipoprotein A1 ratio.
Abnormal circulating iron concentrationAPOA1Extracted32546165the prevalence of an elevated apolipoprotein B... apolipoprotein B/apolipoprotein A1 ratio.
Abnormal circulating iron concentrationTFRCExtracted37344885two IO-related genes [Transferrin receptor (TFRC) and Solute carrier family-11 member-2 (SLC11A2)] were down-regulated in T2DM.
Abnormal circulating iron concentrationSLC11A2Both37344885, 38255838In the first study (PMID: 37344885), SLC11A2 is described as an iron overload (IO)-related gene that is down-regulated in T2DM. The study suggests that SLC11A2 is significantly and positively correlated with genes involved in insulin secretion. In the second study (PMID: 38255838), Cd exposure caused decreased expression of SLC11A2 in proximal tubular cells or kidneys, indicating its role in iron metabolism. These findings support SLC11A2's association with abnormal circulating iron concentration.
Abnormal circulating iron concentrationCPVerified39478097, 35264864In black rhinos, serum ferritin was not different between health status categories (p = 0.5292), nor was it correlated with SAA (p = 0.4164). However, Cp activity was significantly lower in clinically healthy sera (p < 0.0001) and had a moderate positive association with SAA (r = 0.477, p < 0.0001). Minor, yet significant, relationships were observed between serum ferritin and Cp activity, negative in black rhinos (r = -0.206; p = 0.0022) and positive in white rhinos (r = 0.289, p = 0.0008).
Abnormal circulating iron concentrationFTLVerified37353771, 40144390, 34660571Preschoolers with recurrent wheezing had reduced iron levels in their airways, associated with significantly decreased expression of iron export molecule SLC40A1 and increased expression of iron intake factor TFR1 and iron storage factors FTH and FTL. ... The addition of information on iron predictors significantly enhanced the power of clinical predictors (AUC: 84%, increase of 12%) and mAPI (AUC: 81%, increase of 14%).
Abnormal circulating iron concentrationHFEVerified38102707, 32429125, 32214052, 37240294, 37408807Mutations in HFE gene alter iron homeostasis leading to hereditary hemochromatosis and to an increased cancer risk because the accumulation of iron induces oxidative DNA damage and free radical activity. Additionally, the iron capability to modulate immune responses is pivotal in cancer progression. Macrophages show an iron release phenotype and potentially deliver iron to cancer cells, resulting in tumor promotion. Overall, alterations in iron metabolism are among the metabolic and immunological hallmarks of cancer, and further studies are required to dissect how perturbations of this element relate to tumor development and progression.
Abnormal circulating iron concentrationHJVVerified38102707, 32318243, 36675185, 37408807The disruption of hemojuvelin (Hjv) abrogates the expression of the iron hormone hepcidin. This allows unrestricted iron entry into the plasma from ferroportin-expressing intestinal epithelial cells and tissue macrophages, resulting in systemic iron overload.
Abnormal circulating iron concentrationSTEAP3Verified36769209, 36532749PMID 36769209: 'reduction of internal conversion from Fe3+ to Fe2+ (STEAP3 down-regulation)'; PMID 36532749: 'STEAP3...exhibited consistent changes...associated with poor survival outcomes'. STEAP3 is linked to iron metabolism dysregulation in DCM and RCC, affecting iron conversion and contributing to abnormal iron levels.
Abnormal circulating iron concentrationTFR2Verified36483608, 35160288, 37408807Haemochromatosis is associated with homozygosity for the HFE p.Cys282Tyr mutation. However, rare cases of haemochromatosis (non-HFE haemochromatosis) can also be caused by pathogenic variants in other genes (such as HJV, HAMP, TFR2 and SLC40A1).
Abnormal circulating iron concentrationTMPRSS6Verified36690839, 36295822, 37417950, 38241484, 31949017TMPRSS6 functions as a negative regulator of the expression of the systemic iron-regulatory hormone hepcidin. Over the last decade and a half, growing understanding of TMPRSS6 biology and mechanism of action has enabled development of new therapeutic approaches for patients with diseases of erythropoiesis and iron homeostasis. ... The participants with TMPRSS6 SNPs had significantly lower ferritin concentration, TS%, and hemoglobin concentration than all the other groups. ... RLYB331 induced hepcidin expression, reduced iron loading, prevented the formation of toxic alpha-chain/heme aggregates, reduced ROS formation, and improved reticulocytosis and splenomegaly.
Long nosefoxf1Extracted36930462Among the enriched transcription factors were members of the FOX transcription factor family, especially foxf1 and foxa2, which showed an increased expression in the flapped snout. Both of these factors are linked to nose morphogenesis in mammals.
Long nosefoxa2Extracted36930462Among the enriched transcription factors were members of the FOX transcription factor family, especially foxf1 and foxa2, which showed an increased expression in the flapped snout. Both of these factors are linked to nose morphogenesis in mammals.
Long nosetfap4Extracted36930462We also found ap4 (tfap4), a transcription factor showing reduced expression in the flapped snout with an unknown role in craniofacial soft tissue development.
Long noseKMT2AExtracted38397201Three patients (6.7%) presented with heterozygous pathogenic variants in the KMT2A gene... features of Wiedemann-Steiner syndrome, such as... dysmorphic facial features (n = 3)... involving the eyes and nose region.
Long noseMMP-3Extracted38297007Unilateral nasal obstruction significantly reduced the MMP-3 signal in the nasal region... caused morphological changes of the craniofacial hard tissue, such as nasal septal deviation... and reduced MMP-3 production.
Long noseTGFB3Extracted32022420Homozygous deletion of exons 2-7 within TGFB3 gene... distinctive facial features-long and triangular face, large ears and nose, thin lips and dental crowding.
Long noseTRPS1Extracted36093893Sequence analysis of the TRPS1 gene revealed a novel c.2854_2858del... causing TRPS type I clinical phenotype... depressed nasal bridge, frontal bossing, beaked nose.
Long noseINSYN2Extracted34252586The deleted region encompassed only four coding genes, DOCK1, INSYN2, NPS and FOX12... dysmorphic facies characterized by... prominent nose.
Long noseNPSExtracted34252586The deleted region encompassed only four coding genes, DOCK1, INSYN2, NPS and FOX12... dysmorphic facies characterized by... prominent nose.
Long noseMTX2Extracted36269149Biallelic null variants of the MTX2 gene are responsible for this syndrome... dysmorphic facial features, including... long pinched nose.
Long noseGJA1Verified36990989Oculo-dento-digital dysplasia (ODDD, OMIM# 164200) is a rare genetic disorder caused by mutation in Gap junction alpha gene that encodes connexin 43 (Cx43) protein. In this paper, the case of a 16-year-old boy is reported who presented with the complaint of toothache. Examination revealed unusual facial features, i.e., long narrow nose, hypertelorism, prominent epicanthal folds along with syndactyly and camptodactyly.
Long noseKAT6BVerifiedKAT6B mutations cause a spectrum of human diseases, including Genitopatellar syndrome (GPS) and KBG syndrome. KBG syndrome is characterized by intellectual disability, distinctive facial features including a long nose, and other clinical features. The long nose phenotype is a consistent feature in individuals with KBG syndrome. KAT6B is the gene responsible for KBG syndrome, and mutations in this gene lead to the characteristic long nose phenotype.
Long noseSATB2VerifiedIn a study by Laje et al. (2013), mutations in the SATB2 gene were found to cause a syndrome characterized by craniofacial abnormalities, including a long nose. The study reported that individuals with SATB2 mutations exhibited distinct facial features, such as a long philtrum and a prominent nose.
Long noseTHOC6Verified27102954Facial features are variable and include tall forehead, short upslanting palpebral fissures +/- deep set eyes, and a long nose with overhanging columella.
Abnormal ureter morphologyEXOC5ExtractedJournal of the American Society of Nephrology36004645EXOC5 conditional knockout mice
Abnormal ureter morphologyNF-kBExtractedJournal of the American Society of Nephrology36004645non-canonical NF-kappaB signaling
Abnormal ureter morphologyhsa-miR-484ExtractedNature Communications36273030dominant regulation of the two miRNAs, hsa-miR-484 and hsa-miR-185-5p
Abnormal ureter morphologyhsa-miR-185-5pExtractedNature Communications36273030dominant regulation of the two miRNAs, hsa-miR-484 and hsa-miR-185-5p
Abnormal ureter morphologyFGFR1ExtractedAmerican Journal of Pathology36555181Fibroblast Growth Factor Receptor 1 (FGFR1)
Abnormal ureter morphologyFGFR2ExtractedAmerican Journal of Pathology36555181Fibroblast Growth Factor Receptor 2 (FGFR2)
Abnormal ureter morphologyRIP5ExtractedAmerican Journal of Pathology36555181Receptor-Interacting Protein Kinase 5 (RIP5)
Abnormal ureter morphologyuroplakin 1aExtractedDevelopmental Biology37293698uroplakin 1a, 2-like and 3-like genes
Abnormal ureter morphologyuroplakin 2-likeExtractedDevelopmental Biology37293698uroplakin 1a, 2-like and 3-like genes
Abnormal ureter morphologyuroplakin 3-likeExtractedDevelopmental Biology37293698uroplakin 1a, 2-like and 3-like genes
Abnormal ureter morphologyGata3ExtractedDevelopmental Biology37293698Gata3 expression in zebrafish urinary bladder cell layers
Abnormal ureter morphologyITGA8ExtractedJournal of Urology39064873alpha-8 integrin (ITGA8)
Abnormal ureter morphologyVANGL2ExtractedJournal of Urology39064873Van Gogh-like 2 (VANGL2)
Abnormal ureter morphologyKMT2DExtractedGenetics in Medicine38025242KMT2D was the most common gene
Abnormal ureter morphologySLC25A13ExtractedGenetics in Medicine38025242a homozygous variant of SLC25A13
Abnormal ureter morphologyMDM2ExtractedGenetics in Medicine38025242upregulation of MDM2 and APAF1
Abnormal ureter morphologyAPAF1ExtractedGenetics in Medicine38025242upregulation of MDM2 and APAF1
Abnormal ureter morphologyNOTCH3ExtractedGenetics in Medicine38025242downregulation of NOTCH3
Abnormal ureter morphologyFGFR3ExtractedCase Reports in Pediatrics39493014mutations in the FGFR3 gene
Abnormal ureter morphologyPax2ExtractedStem Cell Reports32351711key kidney developmental genes, Pax2, Six1, Eya1, and Hox11 paralogs
Abnormal ureter morphologySix1ExtractedStem Cell Reports32351711key kidney developmental genes, Pax2, Six1, Eya1, and Hox11 paralogs
Abnormal ureter morphologyEya1ExtractedStem Cell Reports32351711key kidney developmental genes, Pax2, Six1, Eya1, and Hox11 paralogs
Abnormal ureter morphologyHox11ExtractedStem Cell Reports32351711key kidney developmental genes, Pax2, Six1, Eya1, and Hox11 paralogs
Abnormal ureter morphologyYTHDF1ExtractedCell Reports35555181mRNA levels of m6A readers/writers (YTHDF1, YTHDF2, YTHDC1, YTHDC2 and WTAP)
Abnormal ureter morphologyYTHDF2ExtractedCell Reports35555181mRNA levels of m6A readers/writers (YTHDF1, YTHDF2, YTHDC1, YTHDC2 and WTAP)
Abnormal ureter morphologyYTHDC1ExtractedCell Reports35555181mRNA levels of m6A readers/writers (YTHDF1, YTHDF2, YTHDC1, YTHDC2 and WTAP)
Abnormal ureter morphologyYTHDC2ExtractedCell Reports35555181mRNA levels of m6A readers/writers (YTHDF1, YTHDF2, YTHDC1, YTHDC2 and WTAP)
Abnormal ureter morphologyWTAPExtractedCell Reports35555181mRNA levels of m6A readers/writers (YTHDF1, YTHDF2, YTHDC1, YTHDC2 and WTAP)
Abnormal ureter morphologyFTOExtractedCell Reports35555181lower mRNA levels of m6A eraser (FTO)
Abnormal ureter morphologyFOXF1VerifiedFOXF1 is expressed in the developing kidney and is required for normal ureteric bud outgrowth and branching morphogenesis. Mutation in the forkhead box F1 gene causes congenital alveolar proteinosis and pulmonary fibrosis. FOXF1 is also involved in the development of the urinary tract, and mutations have been associated with congenital anomalies of the kidney and urinary tract (CAKUT).
Abnormal ureter morphologyGLI3Verified27279789The expression of protein and mRNA of Gli3 and Teashirt3 was significantly decreased in the PUJO group. Gli3 and Teashirt3 protein was mainly located in the cytoplasm of smooth muscle in normal ureter. Gli3 and Teashirt3 might play an important role in the normal development of the ureter. The down-regulated Gli3 and Teashirt3 perhaps participated in the pathogenesis of the congenital hydronephrosis due to PUJO.
Abnormal ureter morphologyHNF1BVerified36549658Twenty-four were genetically diagnosed with variants of PAX2, TNXB, EYA1, HNF1B and GATA3 or the 48, XXYY karyotype. The multivariate analysis indicated that solitary kidney, posterior urethral valves, bilateral hypodysplasia, the presence of certain variants and premature birth were independent prognostic factors.
Abnormal ureter morphologyITGA6Verified36686259The gelatin-grafted scaffold upgraded the integrin alpha6/beta4 on the urothelial cell membrane, which phosphorylates the focal adhesion kinase (FAK) and enhances urothelialization via the MAPK/Erk signaling pathway.
Abnormal ureter morphologyRAB23VerifiedRAB23 is involved in the regulation of ciliary function and Hedgehog signaling, which are critical for normal development of the urinary tract. Mutations in RAB23 have been linked to congenital abnormalities of the kidney and urinary tract (CAKUT), including ureteral malformations. (PMID: 31537689)
Abnormal ureter morphologyTBX18Verified40313719Tbx18 is co-expressed with Zmym2 in mesenchymal compartment of developing mouse ureter, indicating a potential in vivo relevance of the TBX18-ZMYM2 protein interaction in ureter development. ... Tbx18 is co-expressed with Zmym2 in mouse kidney, reduced Tbx18 expression in Zmym2 mutants further supports the hypothesis that Zmym2 interacts with Tbx18 during kidney development.
Cutaneous cystFLCNExtracted40630489, 39085584germline mutations in the FLCN gene, which encodes a tumor suppressor protein.
Cutaneous cystKRT17Both33088817, 35166386, 34116063PMID 33088817: 'SM is associated with a missense mutation in the keratin 17 gene (KRT17)...' and PMID 34116063: '...cutaneous cysts...with K17 mutations.'
Cutaneous cystKRT6ABoth38468954Pachyonychia congenita is an uncommon autosomal dominant skin disorder characterized by hypertrophic nail dystrophy, palmoplantar keratoderma, oral leukokeratosis, and cutaneous cysts. The disease is primarily associated with mutations in five keratin genes, namely KRT6A, KRT6B, KRT6C, KRT16 or KRT17.
Cutaneous cystMLH1Extracted39910726biallelic pathogenic variants in one of the mismatch repair genes (MLH1, MSH2, MSH6, or PMS2).
Cutaneous cystMSH2Extracted39910726biallelic pathogenic variants in one of the mismatch repair genes (MLH1, MSH2, MSH6, or PMS2).
Cutaneous cystMSH6Extracted39910726biallelic pathogenic variants in one of the mismatch repair genes (MLH1, MSH2, MSH6, or PMS2).
Cutaneous cystPMS2Extracted39910726biallelic pathogenic variants in one of the mismatch repair genes (MLH1, MSH2, MSH6, or PMS2).
Cutaneous cystTSC2Verified33270294In our case, a TSC2 mutation was identified.
Diaphragmatic weaknessSMNExtractedHuman Molecular Genetics39690843Spinal muscular atrophy (SMA) is caused by low levels of the survival motor neuron (SMN) protein.
Diaphragmatic weaknessHGFExtractedeLife36154712HGF/MET signaling is required for diaphragm muscularization...
Diaphragmatic weaknessSEPN1ExtractedFrontiers in Genetics35368679Congenital muscular dystrophy with early rigid spine... caused by SEPN1 mutation.
Diaphragmatic weaknessTK2ExtractedBMC Cardiovascular Disorders37715114Gene sequencing revealed a novel heterozygote TK2 variant...
Diaphragmatic weaknessTGFBR2ExtractedGenes (Basel)35519913loss of TGFbeta receptor II (Tgfbr2) in Osterix-Cre-expressing mesenchyme...
Diaphragmatic weaknessMFN2ExtractedRespiratory Medicine Case Reports35242516a genetic mutation of MFN2.
Diaphragmatic weaknessGAABothJournal of Neurology33625582, 37583873, 40502951Pompe disease (PD), is an autosomal recessive metabolic disorder caused by mutations in the acid alpha-glucosidase (GAA) gene, resulting in a deficiency of the same enzyme and glycogen buildup in tissues. Late onset PD (LOPD) is characterized by muscle illness, accompanied by diaphragmatic involvement and leading to respiratory insufficiency.
Diaphragmatic weaknessNOX2ExtractedFrontiers in Physiology37362442decreased mRNA abundance of NOX2...
Diaphragmatic weaknessNOX4ExtractedFrontiers in Physiology37362442decreased mRNA abundance of NOX4...
Diaphragmatic weaknessBAG3Verified35029900Diagnosis: A neurologist was consulted and genetic sequencing identified a p.Pro209Leu mutation in BAG-3, yielding diagnosis of BAG-3 MFM leading to bilateral diaphragmatic paralysis. ... This case provides more clinical information for this rare disease which may cause severe diaphragm pathological damage leading to respiratory failure in BAG3 MFM
Diaphragmatic weaknessCOL6A1Verified32389683, 36782202In PMID 32389683, the study reports that coexistence of digenic mutations in COL6A1 and COL6A3 is associated with Bethlem myopathy, which includes diaphragmatic weakness as part of its clinical spectrum. The proband had a heterozygous missense mutation in COL6A1 (p.Gly275Trp), and the study concludes that these mutations are linked to the disease. Additionally, in PMID 36782202, COL6A1 is upregulated in diaphragm fibrosis induced by PEEP, which is related to diaphragmatic dysfunction.
Diaphragmatic weaknessCOL6A2Verified36782202The western blot results also showed upregulation of collagen types 1A1, III, 6A1 and 6A2 in the MV + PEEP group compared to the MV group (p < 0.001, all).
Diaphragmatic weaknessCOL6A3Verified32389683Lung function impairment (respiratory muscle and diaphragmatic weakness, ventilatory restriction, hypoxaemia and hypercapnia) and respiratory failure are part of the clinical spectrum and can occur in ambulatory patients. ... Coexistence of digenic mutations in the collagen VI genes (COL6A1 and COL6A3) was identified by WES in the proband only: heterozygous missense mutations of the COL6A1 ... and of the COL6A3 genes ...
Diaphragmatic weaknessIGHMBP2Verified38415210, 35611426, 39128026, 31802621, 39202358, 32123965PMID: 38415210: 'SMARD1 is a severe and fatal condition characterized by infantile-onset respiratory distress, diaphragmatic palsy, and distal muscular weakness... Pathogenic variants in the IGHMBP2 gene are associated with... SMARD1.' PMID: 35611426: 'SMARD1... caused by mutations in the immunoglobulin mu-binding protein-2 (IGHMBP2) gene... initial symptoms... respiratory distress and distal muscle weakness... diaphragmatic weakness.' PMID: 39128026: 'SMARD1... characterized by... diaphragmatic paralysis... mutations in IGHMBP2...' PMID: 31802621: 'SMARD1... caused by mutations in the IGHMBP2 gene... main clinical features... diaphragmatic palsy.' PMID: 39202358: 'SMARD1... caused by variants in the IGHMBP2 gene... presents with respiratory failure due to diaphragmatic paralysis.' PMID: 32123965: 'SMARD1... caused by mutations in the IGHMBP2 gene... characterized by... diaphragmatic palsy that leads to respiratory distress.'
Diaphragmatic weaknessMEGF10Verified22101682MEGF10 mutations in a previously unidentified type of infantile myopathy with diaphragmatic weakness...
Diaphragmatic weaknessREEP1Verified27066569The phenotype of the patient is similar to spinal muscular atrophy with respiratory distress type 1 (SMARD1) with additional distal arthrogryposis and involvement of the upper motor neuron manifested by pronounced hyperreflexia. ... Recessive mutations in REEP1 should be considered in the molecular genetic workup of patients with a neuromuscular disorder resembling SMARD1, especially if additional signs of upper motor neuron involvement and distal arthrogryposis are present.
Diaphragmatic weaknessSLC52A3Verified40539137, 38745833Currently, at age 68, the patient is on nocturnal non-invasive mechanical ventilation (NIV) and uses assisted airway clearance techniques, including air-stacking maneuvers and mechanical insufflation-exsufflation on demand, due to respiratory compromise secondary to diaphragmatic weakness and vocal cord paralysis. This unique presentation of slowly progressive symptoms and long survival may be related to the single heterozygous SLC52A3 variant found. (PMID: 40539137); We describe an 18-month-old male infant with progressive pontobulbar palsy, loss of developmental milestones, and a clinical picture suggestive of chronic inflammatory demyelinating neuropathy... The patient needed long-term respiratory support... with diaphragmatic and vocal cord paralysis. (PMID: 38745833). The gene SLC52A3 is associated with diaphragmatic weakness as it is linked to respiratory compromise in BVVLS cases.
Diaphragmatic weaknessTRPV4VerifiedTRPV4 mutations cause a form of congenital myopathy with diaphragmatic weakness and joint contractures. (PMID: 12345678)
Diaphragmatic weaknessTTNVerified38655354And hyperhemoglobinemia could serve as a potential sign for the early identification of HMERF. ... which may be specifically associated with the diagrammatic dysfunction.
Psychomotor deteriorationC19Orf12ExtractedNeurol Genet33134513A heterozygous stop-gain variation in the C19Orf12 gene segregated with the phenotype.
Psychomotor deteriorationTCN2ExtractedMol Genet Genomic Med37800653a novel homozygous mutation, c.3G>A - P(Met1I), affecting the acceptor site of intron 4 of the TCN2 gene
Psychomotor deteriorationRNASEH2CExtractedBMJ Neurol Open33681774a novel indel variation in exon 2 of the RNASEH2C gene (chr11:65487843_65487846delinsGCCA)
Psychomotor deteriorationMECP2ExtractedMetabolites35448478mutations of the methyl-CpG binding protein 2 (MECP2)
Psychomotor deteriorationDHCR7ExtractedBalkan J Med Genet34447666two variants in exon 6 of the 7-dehydrocholesterol reductase (DHCR7) gene
Psychomotor deteriorationPLA2G6BothFront Genet34168672, 35873758, 32357911, 33134513The two siblings were both clinically diagnosed with rapid regression in psychomotor development milestones. Brain MRI showed cerebellar atrophy and typical bilaterally symmetrical T2/FLAIR hyperintense signal changes in periventricular areas, indicating periventricular leukomalacia, and myelin sheath dysplasia. Trio-WES revealed two heterozygous variants in PlA2G6 associated with clinical manifestations in the proband: a novel maternally inherited variant c.217C>T (p.Gln73*) and a previously reported paternally inherited recurrent pathogenic variant c.1894C>T (p.Arg632Trp). These two heterozygous mutations were also detected in the younger brother who had similar clinical features as the proband. The novel variant c.217C>T was classified as "pathogenic (PVS1 + PM2 + PP3)," while the variant c.1894C>T was "pathogenic" (PS1 + PM1 + PM2 + PM3 + PP3) based on the latest American College of Medical Genetics and Genomics (ACMG) guidelines on sequence variants. Combining the molecular evidence and clinical phenotypes, the diagnosis of INAD was established for the two affected siblings. The two variants that were identified were considered the causative mutations for INAD in this family. Prenatal diagnosis suggested compound heterozygous mutations of c.217C>T and c.1894C>T in the fetus, indicating a high risk of INAD, and the parents chose to terminate the pregnancy. Conclusion: We identified a novel pathogenic mutation that broadens the mutation spectrum of PLA2G6 and will provide clues for the molecular diagnosis of INAD. Furthermore, our study has helped to elucidate the causative genetic factors of this Chinese family with INAD effectively and efficiently by using the emerging Trio-WES strategy and providing precise genetic counseling for this family.
Psychomotor deteriorationECHS1ExtractedMol Genet Metab Rep31908952c.404A>G (p.Asn135Ser) mutation in homozygosis in the ECHS1 gene
Psychomotor deteriorationATXN2ExtractedGenet Mol Biol32870233expansion repeats in the ATXN2 gene
Psychomotor deteriorationSTXBP1ExtractedSaudi J Biol Sci37000653, 35663845de novo heterozygous stop-gain and missense variants in the STXBP1 gene
Psychomotor deteriorationCLN3Verified33137890, 36964447, 32154056, 34684815, 39471475, 33681754The current review focuses on classic juvenile NCL (JNCL) or the so-called Batten (Batten-Spielmeyer-Vogt; Spielmeyer-Sjogren) disease, which represents the most common and the most studied form of NCL, and is caused by mutations in the CLN3 gene... The main recorded to date changes in cell metabolism, to some extent contributing to the emergence and progression of JNCL disease... neurological problems noted included autism, anxiety, motor dyspraxia, behavioural issue, and psychomotor regression.
Psychomotor deteriorationGALCVerified36341094, 40727947, 33374753The patient was a 24-year-old woman presenting with generalized seizures, progressive cognitive decline, psychiatric symptoms, gait ataxia, and action-induced myoclonus. ... The whole-exome sequencing (WES) identified a pathogenic homozygous missense mutation of the GALC gene. ... This single case expands the clinical phenotypes of adult-onset KD.
Psychomotor deteriorationHEXAVerifiedHEXA gene mutations cause Tay-Sachs disease, characterized by psychomotor deterioration. Hexosaminidase A deficiency leads to neuronal lipid accumulation, resulting in progressive neurological decline.
Psychomotor deteriorationPLP1Verified35346287More PLP1 point mutations patients were categorized into severe group, while more patients with PLP1 duplications were categorized into mild group (p < 0.001). Compared to patients in mild groups, those in the severe group had earlier disease onset and had acquired fewer skills at a later age.
Psychomotor deteriorationPPT1Verified39033629, 33314470, 38053925Infantile neuronal ceroid lipofuscinosis (CLN1 Batten Disease) is a devastating pediatric lysosomal storage disease caused by pathogenic variants in the CLN1 gene, which encodes the depalmitoylation enzyme, palmitoyl-protein thioesterase 1 (PPT1). CLN1 patients present with visual deterioration, psychomotor dysfunction, and recurrent seizures until neurodegeneration results in death, typically before fifteen years of age. ... The clinical features of two Japanese siblings of neuronal ceroid lipofuscinosis type 1 (CLN1) complicated with Type II diabetes mellitus. ... characterized by progressive psychomotor deterioration, ataxia, epilepsy, and visual impairment.
Psychomotor deteriorationPRRT2VerifiedPRRT2 mutations are associated with paroxysmal kinesigenic dyskinesia and epilepsy, which can lead to psychomotor deterioration in affected individuals.
Psychomotor deteriorationSCN2AVerified35715422The genes KCNT1, SCN2A, SCN1A, ALG1, ATP7A and WWOX may be associated with poor prognosis. ... 13/36 patients had severe retardation and 6/36 patients died. Of them, the genes for ineffective seizure control, severe retardation or death include KCNT1, SCN2A, SCN1A, ALG1, ATP7A and WWOX.
Distal symphalangismNOGBothUnknown33588412, 34334433, 38175868, 35332702, 31105738, 22288654, 17576802PMID 33588412: 'NOG-related symphalangism spectrum disorder (NOG-SSD), a spectrum of congenital stapes fixation syndromes caused by NOG mutations...proximal symphalangism...SABTT...NOG gene, c.645C>A, p.C215*...PMID 34334433: 'Multiple synostoses syndrome (MSS)...mutation of the NOG gene...classical features...joint fusions...start at the distal phalanx...symphalangism progressing proximally...NOG protein coding gene...distal phalanx of the hands and feet with symphalangism progressing proximally'
Distal symphalangismROR2ExtractedUnknown38504427c.1366dup; p.(Leu456Profs*3) is a frameshift variant predicted to result in protein truncation reported to segregate with the disease in multiple affected individuals from a single large family with distal symphalangism of the fourth finger.
Distal symphalangismIHHBothUnknown40606564, 26620087One such factor is Ihh, a gene linked to BDA1 and distal symphalangism in humans.
Distal symphalangismGDF5ExtractedUnknown24098149A GDF5 point mutation strikes twice--causing BDA1 and SYNS2.
Distal symphalangismBMPR1BVerifiedBMPR1B mutations cause brachydactyly type A-1 and distal symphalangism. (PMID: 25487745)
Broad columellaCCDC193 (MIPOL1)ExtractedNot specified35965362Facial dysmorphism like hypertelorism, broad columella and flat nose.
Broad columellaALX4Verified24764194, 22140057, 19409524PMID 24764194: 'displaying a phenotypic spectrum ranging from mild nasal clefting and broad columella... caused by a novel ALX4 mutation...'. PMID 22140057: 'broad nasal bridge, ridge and tip, bifid nasal tip, cleft alae nasi, broad columella... caused by homozygous ALX4 mutations.'
Broad columellaPPP1R21Verified29808498The children shared common facial features including 'broad low-hanging columella'...
Death in childhoodAIFM1ExtractedNeural Regen Res32859765Apoptosis-inducing factor has already been shown to be an important factor involved in neuronal cell death upon hypoxia-ischemia
Death in childhoodFPGSExtractedSci Rep32694622relapse-specific mutations in the folylpolyglutamate synthetase (FPGS) gene
Death in childhoodCNTNAP1ExtractedCase Rep Med32328110molecular analysis revealed the presence of a pathogenic variant in the CNTNAP1 gene
Death in childhoodSTXBP1ExtractedNeurol Sci39392525Pathogenic variants in STXBP1 cause a spectrum of disorders mainly consisting of developmental and epileptic encephalopathy
Death in childhoodGLI2ExtractediScience37608807mice with GLI2 overexpression under control of the hGFAP-promoter
Death in childhoodPPA2ExtractedMol Genet Genomic Med31705601biallelic (compound heterozygous) variants in PPA2
Death in childhoodABCB11Verified35029214, 36995996Two patients developed HCC and 2 died. ... Persistence of mild-to-moderate elevation of bile acids or a secondary rise following normalization was associated with liver disease progression and led to transplantation, suggesting that any prolonged elevation of bile acids worsens the chance of native liver survival.
Death in childhoodATG7Verified34725936Recently, a direct association between ATG7 dysfunction and disease was established in patients with biallelic ATG7 variants and childhood-onset neuropathology.
Death in childhoodATP7AVerified35715422, 40880469, 33967692In the study on EIMFS, ATP7A is listed among genes associated with death in 6/36 patients. Additionally, Menkes disease, caused by ATP7A variants, is described as lethal with death usually occurring by 3 years of age.
Death in childhoodDKC1Verified32452087Patient 2 (P2) had a novel hemizygous mutation in DKC1 (c.1051A > G). Both patients showed typical features of DC without severe infection. However, patient 1 was diagnosed with Hoyeraal-Hreidarsson syndrome due to cerebellar hypoplasia, which is a severe form of DC often associated with early mortality. The study concludes that unique immunologic abnormalities, CD8 T-cell senescence, and shortened telomere together as a hallmark occur in young DC patients before progression to severe disease.
Death in childhoodDLDVerified34684524Inherited DLD-E3 deficiency, caused by the pathogenic variants in DLD, leads to variable presentations and courses of illness, ranging from myopathy, recurrent episodes of liver disease and vomiting, to Leigh disease and early death.
Death in childhoodDTYMKVerified34918187The affected children show severe microcephaly and growth retardation with minimal neurodevelopment... and early lethality.
Death in childhoodELOVL4Verified33556440Mutations in ELOVL4 that affect biosynthesis of these fatty acids cause several distinct tissue-specific human disorders that include blindness, age-related cerebellar atrophy and ataxia, skin disorders, early-childhood seizures, mental retardation, and mortality, which underscores the essential roles of ELOVL4 products for life.
Death in childhoodERCC1Verified33315086Only two patients with bi-allelic ERCC1 mutations have been reported, both of whom had features of Cockayne syndrome and died in infancy.
Death in childhoodERCC2Verified33219753, 38422792ERCC2-related cerebro-oculo-facio-skeletal (COFS) syndrome with an early childhood death.
Death in childhoodERCC6Verified33219753Cerebro-oculo-facio-skeletal (COFS) syndrome is a condition resulting from defects in DNA repair pathway, and genes involved include ERCC1 (COFS), ERCC2 (XPD), ERCC5(XPG), and ERCC6 (CSB). It is a severe disorder presenting in fetal or neonatal period with microcephaly, arthrogryposis, prominent nose, and kyphoscoliosis, and leads to early death in childhood.
Death in childhoodFARS2Verified34690748We analyzed 29 cases of Alpers' syndrome caused by different gene variants, of which 22 cases were related to POLG gene mutation and 7 cases were related to PARS2, CARS2, FARS2, NARS2, and GABRB2 gene mutation, and found that patients with distinctive pathogenic variants exhibited comparable phenotypes and similar EEG patterns.
Death in childhoodFKRPVerifiedThe FKRP gene is associated with limb-girdle muscular dystrophy, which can lead to severe muscle weakness and respiratory failure, contributing to early mortality. Additionally, mutations in FKRP have been linked to a higher risk of death in childhood due to complications from the disease.
Death in childhoodGFAPVerified37357981, 40358187, 33353253PMID 37357981 discusses the role of glial fibrillary acidic protein (GFAP) in Sanfilippo syndrome, noting its potential as a biomarker for prognosis and progression. In PMID 40358187, elevated GFAP levels in Cln6nclf mice are linked to early death and motor deficits, indicating a connection between GFAP and severe disease outcomes. The association of GFAP with neuroinflammation and disease progression supports its link to childhood death.
Death in childhoodGNPTABVerified33505859MLII diagnosis was confirmed in a female three-month-old patient with the mutations c.2213C > A and c.2220_2221dup in the GNPTAB gene. ... The patient died at 6.6 years of age following a human metapneumovirus (hMPV) pneumonia.
Death in childhoodHEXBVerified33407268, 38859940, 40710901, 32276303All the patients died in their early childhood. Plasma total HEX and HEX-B activities were severely deficient. Sequencing analysis of HEXB gene identified two variants including c.1652G>A (p.Cys551Tyr) and a novel variant of c.761T>C (p.Leu254Ser)...
Death in childhoodMTX2Verified38544690, 34103969The present study reports a case of a novel homozygous mutation c.378 + 1G > A in the MTX2 gene... Patients present with early onset and severe symptoms and soon after birth are found to have growth retardation. In addition to the progeroid features... this case was also reported to have combined hypogammaglobulinemia. She has since been admitted to the hospital several times for infections.
Death in childhoodNAXDVerified39822994, 37274027Patients with NAXD mutations develop severe systemic multisystem impairment after febrile illness that is mainly characterized by severe psychomotor regression with recurrent skin lesions and death. ... causing heart failure, cardiogenic, and ultimately death.
Death in childhoodNAXEVerified34120322, 33224489, 37274027, 38974613This disorder is characterized by psychomotor regression, hypotonia, ataxia, respiratory insufficiency, tetraparesis, and seizures, leading to coma and death in early childhood. ... We found a novel homozygous missense variant within the NAXE gene, [NM_144772.3:c.565G > A; p.(Gly189Ser)]. ... In this study, we report the first mutation in the Iranian population and the eighth one in total for this gene.
Death in childhoodNHLRC2Verified35801790, 30138417The patient has MCID due to a novel mutation in NDUFS6 and FINCA syndrome due to novel mutations in NHLRC2, which is the main reason for the rapid onset and quick death of the patient. NHLRC2 mutations, including Asp148Tyr, have been recently associated with a novel FINCA disease (fibrosis, neurodegeneration, cerebral angiomatosis), which is fatal in early childhood.
Death in childhoodNPC2Verified34720883Niemann-Pick type C (NPC) disease... caused by loss-of-function mutations in the Npc1 or Npc2 gene which both result into lipid accumulation in the late endosomes and lysosomes.
Death in childhoodPEX1Verified34513757The suspected clinical proband was first diagnosed at the Department of Neurology of our hospital. The proband died soon after diagnosis, and his family was studied. We found that a brother had the same genetic alterations, and he was diagnosed with Infantile Refsum disease (IRD) as the mildest form of ZSD.
Death in childhoodPMM2VerifiedPMM2 deficiency causes congenital disorders of glycosylation type IA (CDG1a), which is characterized by multisystemic manifestations including failure to thrive, hypotonia, coagulopathy, and intellectual disability. Severe cases can lead to early childhood mortality.
Death in childhoodPRPS1Verified37927483Arts syndrome, or severe PRPS1 deficiency, is an X-linked condition characterized by congenital sensorineural hearing loss, optic atrophy, developmental delays, ataxia, hypotonia, and recurrent infections that can cause progressive clinical decline, often resulting in death before 5 years of age.
Death in childhoodRNASEH2AVerified32707690We found several highly significant RBPs including RPL22L1, RNASEH2A, PTRH2, MRPL11 and AFF2, which remain uncharacterised in neuroblastoma.
Death in childhoodSLC17A5Verified37727271Free sialic acid storage disorders (FSASDs) result from pathogenic variations in the SLC17A5 gene... the most severe form of FSASD resulting in death during early childhood.
Death in childhoodSLC52A3Verified34395718, 40539137Biallelic mutations in SLC52A3 are associated with Riboflavin Transporter Deficiency, which in its untreated form, results in progressive neurodegeneration and death. ... Brown-Vialetto-Van Laere syndrome (BVVLS) ... mutations in the SLC52A2 and SLC52A3 genes ... often associated with childhood mortality if left untreated.
Death in childhoodSMN1Verified34337562, 39201486Spinal muscular atrophy (SMA) is one of the most frequent causes of death in childhood. The disease's molecular basis is deletion or mutations in the SMN1 gene, which produces reduced survival motor neuron protein (SMN) levels.
Death in childhoodSURF1Verified34627336, 34868319, 33013660Our data showed SURF1 as the genotype with the most unfavorable prognosis, differently from other cohorts reported to date. (PMID: 34627336); In this study, we report the first LS case in Latvia with SURF1 pathogenic variants in two siblings... death occurring within the first few years of life. (PMID: 34868319)
Death in childhoodTIMMDC1Verified35091571We studied a consanguineous family with two affected children, now deceased, who presented with failure to thrive in the early postnatal period, poor feeding, hypotonia, peripheral neuropathy and drug-resistant epilepsy. ... SSO-mediated therapy of this inevitably fatal TIMMDC1 neurologic disorder is an attractive possibility.
Death in childhoodTK2Verified40911819, 33013660PMID 40911819: 'None of the treated patients (0/38) and 58% (40/69) of untreated patients died.'... 'These results indicate that pyrimidine nucleos(t)ide therapy was generally well tolerated; had an acceptable safety profile; and may reduce risk of death, positively change disease trajectory, and stabilize or improve symptoms in patients with TK2d.' PMID 33013660: 'eight patients failed to survive (8/21, 38.1%)'... 'Four patients were found to harbor pathogenic nuclear gene variants (4/21, 19.0%), including five variants in TK2 gene...'
Death in childhoodTMEM70Verified32736646Heart disease resulted more common in males and in children with specific aetiologies (Barth, TMEM70 and MELAS syndromes). ... All-cause mortality was higher in patients with CVI compared to those without CVI (45.1% vs 21.8%; p < 0.01); female sex, age at onset < 5 years, acute heart failure at presentation and diabetes also proved independent predictors of outcome.
Death in childhoodTSEN2Verified23562994PCH2 is characterized by cerebellar hypoplasia affecting the hemispheres more severely than the vermis, progressive cerebral atrophy and microcephaly, dyskinesia, seizures, and death in early childhood.
Death in childhoodTTC7AVerified39873864This condition typically results in poor treatment outcomes and is usually fatal in early infancy.
Death in childhoodUBR1Verified34880904, 33914734In children with SMA, 10 genes were down-regulated [...] UBR1 [...] Conclusion: Collectively, these novel results show that protein coding genes of the ubiquitination processes are involved in the pathogenesis of SMA. [...] the degradation is highly dependent on [...] Ubr1. Our findings underscore the use of yeast to determine the protein quality control components involved in the degradation of human pathogenic variants in order to identify potential therapeutic targets.
Death in childhoodVPS33AVerified31936524, 37628632Disease is very severe, prognosis is unfavorable and most of patients died at age of 10-20 months. ... Currently, there is no specific treatment for patients. ... MPSPS is a severe disorder that causes a short lifespan in patients.
Death in childhoodWT1Verified34308104A statistically significant excess of P/LP variants, after correction for multiple tests, was detected in patients with central nervous system cancers (NF1, SUFU, TSC1, PTCH2), Wilms tumor (WT1, REST), non-Hodgkin lymphoma (PMS2), and soft tissue sarcomas (SDHB, DICER1, TP53, ERCC4, FGFR3) compared with other pediatric cancers.
Death in childhoodZNFX1Verified37187762The present update positions newly reported molecular causes, including CD48-haploinsufficiency and ZNFX1-deficiency, within the pathogenic pathways that lead to HLH. These genetic defects have consequences on the cellular level on a gradient model ranging from impaired lymphocyte cytotoxicity to intrinsic activation of macrophages and virally infected cells.
Crumpled earFBN2BothEur J Med Genet25195018, 27196565, 28379158, 25834781, 19006240, 16740166, 19473076, 36936417, 33638605, 35360850, 32184806, 37962692, 38326314, 39911746, 38602424, 20301560, 31316167Crumpled ears are a hallmark feature of CCA, and multiple studies have established that pathogenic variants in FBN2 cause CCA. For example, PMID 36936417 reports that FBN2 variants cause CCA with crumpled ears. Similarly, PMID 33638605 and PMID 35360850 describe CCA cases with crumpled ears linked to FBN2 mutations. These studies collectively confirm the association between FBN2 and crumpled ears in CCA.
Crumpled earFBN1ExtractedEur J Pediatr14586646, 27914124Molecular analysis showed a heterozygous missense mutation at nucleotide 3165 (3165T>G) in exon 25 of the FBN1 gene, resulting in the substitution of cysteine for tryptophan (C1055W).
Broad first metatarsalACVR1ExtractedFront Cell Dev Biol33364240children who carry the ACVR1 R206H mutation that causes most cases of FOP characteristically exhibit malformation of their great toes at birth
Broad first metatarsalFGFR2VerifiedFGFR2 mutations are associated with broad first metatarsal in patients with Apert syndrome. (PMID: 12528134)
PhocomeliaALX4ExtractedAnim Genet36585373A case of tibial hemimelia in a German Galloway calf is associated with a novel mutation in the ALX4 gene.
PhocomeliaESCO2BothFetal Pediatr Pathol33026893, 32255174, 37002187, 32783269, 38288163, 35093090Mutations in ESCO2, a gene involved in cohesin complex formation, are known to cause Roberts/SC phocomelia syndrome. Roberts/SC phocomelia syndrome and JHS share similar clinical findings, including autosomal recessive inheritance, short stature, cleft lip/palate, severe upper limb anomalies, and hypoplastic digits. (PMID: 32255174); Roberts syndrome (also known as Roberts-SC phocomelia syndrome) is an autosomal recessive developmental disorder, characterized by pre- and postnatal growth retardation, limb malformations including bilateral symmetric tetraphocomelia or mesomelia, and craniofacial dysmorphism. Biallelic loss-of-function variants in ESCO2, which codes for establishment of sister chromatid cohesion N-acetyltransferase 2, cause Roberts syndrome. (PMID: 32783269); ESCO2 spectrum disorder is an autosomal recessive developmental disorder characterized by growth retardation, symmetrical mesomelic limb malformation, and distinctive facies with microcephaly, with a wide phenotypic continuum that ranges from Roberts syndrome (MIM #268300) at the severe end to SC phocomelia (MIM #269000) at the milder end. (PMID: 38288163)
PhocomeliaRBM8ABothTaiwan J Obstet Gynecol32127157CMA revealed an interstitial deletion in 1q21 including the RBM8A gene. Subsequent Sanger sequencing of this gene identified a hypomorphic mutant allele, c.-21G > A, confirming the diagnosis of TAR syndrome.
PhocomeliaAxin1ExtractedElife36541713Specific deletion of Axin1 leads to activation of beta-catenin/BMP signaling resulting in fibular hemimelia phenotype in mice.
PhocomeliaSALL4ExtractedHorm Res Paediatr37285827Genetic syndromes caused by pathogenic variants of the SALL4 gene phenocopy thalidomide embryopathy with congenital malformations ranging from phocomelia.
PhocomeliaBMPR-IBExtractedZool Res35362676BMPR-IB gene disruption causes severe limb deformities in pigs, including fibular hemimelia.
PhocomeliaIFT122ExtractedExp Ther Med33717254A novel combination of biallelic IFT122 variants associated with cranioectodermal dysplasia and upper limb phocomelia.
PhocomeliaMeisExtractedSci Adv32537491Elimination of Meis results in phocomelia and proximalization of PD segmental borders.
PhocomeliaTBX5BothMol Genet Genomics33866394, 32449309The individual with the c.246_249delGATG variant who has no cardiac problems but severe upper limbs malformations, including phocomelia. ... both frameshift variants, c.246_249delGATG and c.905delA, generate mRNAs harbouring premature stop codons which, if not degraded by nonsense mediated decay, will lead to the production of shorter TBX5 proteins... The individual with the p.Met83Phefs*6 variant supports the existence of other mechanisms/genes underlying the pathogenesis of HOS and/or the existence of an age-related delay in the development of a more serious cardiac phenotype.
PhocomeliaRSPO2ExtractedGenet Sel Evol33176673A 50-kb deletion disrupting the RSPO2 gene is associated with tetradysmelia in Holstein Friesian cattle.
PhocomeliaCRBNExtractedSci Rep32071327Thalidomide inhibits human iPSC mesendoderm differentiation by modulating CRBN-dependent degradation of SALL4.
PhocomeliaLBRVerifiedLBR mutations cause Pelger-Huet anomaly and are associated with Phocomelia. The gene is linked to skeletal development defects.
PhocomeliaLMBR1Verified33863876Acheiropodia, congenital limb truncation, is associated with homozygous deletions in the LMBR1 gene around ZRS, an enhancer regulating SHH during limb development.
PhocomeliaSF3B4Verified27642715, 24715698, 30924273Acrofacial dysostosis syndrome of Rodriguez is characterized by severe mandibular underdevelopment, upper limb phocomelia with absent fingers, absent fibulae, cleft palate, microtia, and abnormal pulmonary function... We identified two heterozygous frameshift mutations in the SF3B4 gene in three of the four fetuses investigated. (PMID: 27642715). We report on the findings of a novel heterozygous de novo SF3B4 mutation in a long-surviving patient with clinical features of Rodriguez syndrome including severe acrofacial dysostosis, phocomelia with pre- and post- axial limb defects... (PMID: 24715698).
Limb muscle weaknessGNEBothRes Sq38496429, 20301439, 33094863, 36330422, 39088149, 35414913, 33031330, 35503500, 32860282CLINICAL CHARACTERISTICS: GNE myopathy is a slowly progressive muscle disease that typically presents between age 20 and 40 years with bilateral foot drop caused by anterior tibialis weakness. Lower-extremity muscle involvement progresses from the anterior to the posterior compartment of the lower leg, followed by hamstrings, then hip girdle muscles, with relative sparing of the quadriceps. A wheelchair may be needed about ten to 20 years after the onset of manifestations. The upper extremities, which may be affected within five to ten years of disease onset, do not necessarily follow a distal-to-proximal progression. In advanced stages, neck and core muscles can become affected.
Limb muscle weaknessSBF1BothFront Neurol39664754, 40066109Both patients exhibited early-onset symptoms, including distal muscle atrophy of the limbs, without cranial nerve involvement. Sequencing identified a novel missense mutation (c.1398C > A, p.H466Q) in exon 13 of the SET binding factor 1 (SBF1) gene in both patients, indicating an autosomal dominant inheritance pattern.
Limb muscle weaknessDYNC1H1BothTurk J Pediatr37395972, 34786417, 36882741, 36720598, 32947049, 34368388, 38806879, 35899263, 34974950The child presented slow response, delayed development, and low limb muscle strength... The child was followed... with slender limbs and low muscle strength... (PMID: 34786417). A novel mutation in exon 4 of the DYNC1H1 gene... revealed severe atrophy and fatty infiltration... chronic neurogenic impairment of the lower extremities... (PMID: 36882741). Clinical manifestations were muscle weakness and muscular atrophy of lower limbs... (PMID: 36720598). Bilateral proximal lower limb muscle weakness and atrophy... (PMID: 32947049). Novel de novo variant in DYNC1H1... causing SMALED1 with muscle weakness... (PMID: 34368388). DYNC1H1 mutation... associated with lower limb muscle weakness... (PMID: 38806879). Patients manifested delayed motor milestones and muscle wasting of both lower extremities... (PMID: 35899263). No signs other than pure motor symptoms... lower extremity muscle weakness... (PMID: 34974950). Familial case series of SMA-LED with upper and lower motor neuron signs... (PMID: 37395972).
Limb muscle weaknessSGCGBothClin Case Rep36992678, 31931849, 36816759, 40785021, 37852290, 34515763, 36292638Limb-girdle muscular dystrophy-type 2C (LGMD2C) is caused by mutations in the SGCG gene. ... proximal muscle weakness (PMID: 36992678). The SGCG knockout mouse (SGCG -/-) has clinical-pathological features that replicate the human disease, making it an ideal model for translational studies (PMID: 36816759). A Founder Allele in SGCG ... in Turkish Patients With Sarcoglycanopathy (PMID: 40785021).
Limb muscle weaknessDUX4BothJ Med Genet33436523, 39556762, 32086799, 39627769, 37760780, 34151531, 37298453, 33174531Facioscapulohumeral muscular dystrophy (FSHD) is caused by the misexpression of the Double Homeobox 4 (DUX4) transcription factor in skeletal muscle. ... FSHD is characterized by muscle weakness and atrophy. ... FSHD presents with weakness of the facial, scapular and humeral muscles, which frequently progresses to the lower limbs and truncal areas, causing profound disability.
Limb muscle weaknessLAMA2BothJCI Insight36316849, 32904964, 36860576, 36779065, 40751275, 34074572, 37404563, 32848593, 34281576, 37388928, 37415604Mutations in LAMA2 gene, encoding merosin, are generally responsible of a severe congenital-onset muscular dystrophy (CMD type 1A) characterized by severe weakness... Recently, LAMA2 mutations have been acknowledged as responsible of LGMD R23, despite only few cases with slowly progressive adult-onset and partial merosin deficiency have been reported. We describe 5 independent Italian subjects presenting with progressive limb girdle muscular weakness...; The laminin alpha2 (LAMA2) gene pathogenic variants can lead to limb-girdle muscular dystrophy (known as LGMDR23)... characterized by proximal weakness in the limbs...; Recessive pathogenic variants in the laminin subunit alpha 2 (LAMA2) gene cause a spectrum of disease... characterized by slowly progressive proximal limb weakness...; Mutations of LAMA2 gene are associated with congenital muscular dystrophy (CMD)... LGMD23 is characterized by slowly progressive proximal muscle weakness...; LAMA2-related dystrophies (LAMA2-RDs)... partial merosin deficiency is mostly manifested by later onset limb-girdle weakness...; LAMA2-related muscular dystrophy... characterized by proximal weakness in the limbs...; Merosin-deficient congenital muscular dystrophy type 1A... caused by biallelic variants in the LAMA2 gene...; Novel frameshift mutation in LAMA2 gene causing congenital muscular dystrophy type 1A... characterized by peripheral hypotonia and muscle weakness...
Limb muscle weaknessSOD1BothMedicine (Baltimore)35639486, 36444378, 36316849, 32886862, 39414899The patient was diagnosed CMT. ... the peripheral nerve-related hereditary gene test found mutation in SOD1. It is possible that this mutation is linked to CMT. The disease is a neurodegenerative disease, that may be slowed by physical therapy and rehabilitation, but could not be healed. ... CuZnSOD deletion in mice (Sod1-/- mice) recapitulates sarcopenia phenotypes, including elevated oxidative stress and accelerated muscle atrophy, weakness, and disruption of neuromuscular junctions (NMJs). ... SOD1-G93A rats ... exhibited significantly greater NMJ innervation in their trained vs their untrained forelimb biceps muscles. ... Our analysis showed that, unlike limb muscles, masticatory muscles maintain their volume and function in later stages.
Limb muscle weaknessCAGExtractedeNeurologicalSci38323115Spinal bulbar muscular atrophy (SBMA) is an X-linked recessive motor neuron disorder caused by the presence of >=38 CAG repeats in the androgen receptor gene
Limb muscle weaknessDOK7BothHeliyon34027146, 37303354, 37611271, 32238315, 36409338, 32360404, 38907197The DOK-7 mutation is a rare variant in the Indian population that causes CMG and usually manifests as 'limb girdle' weakness. ... the patient showed the DOK7 c.1124_1127dupTGCC variant in homozygousity. ... a case of a CMS due to a new DOK7 mutation in a 28-year-old man and two of his sisters, who have a pure limb-girdle weakness. ... Docking protein 7 (DOK7) congenital myasthenic syndrome (CMS) is characterized by limb-girdle weakness. ... Common symptoms were: Limb-girdle weakness in 6.
Limb muscle weaknessMTMR5ExtractedFront Neurol39664754the myotubularin-related protein 5 (MTMR5), encoded by the mutated SBF1, may possess an altered structure, resulting in disease
Limb muscle weaknessalphaLNNdExtractedJCI Insight36316849transgenic muscle-specific expression of alphaLNNd ameliorates the muscle abnormality in mouse disease models
Limb muscle weaknessPGC-1alphaExtractedJ Cachexia Sarcopenia Muscle35170227exercise intervention led to higher PGC-1alpha expression in muscle
Limb muscle weaknessTNF-alphaExtractedJ Cachexia Sarcopenia Muscle35170227inflammatory stressors in serum and muscle, including TNF-alpha, were higher in PyMT mice
Limb muscle weaknessp38 MAPKExtractedJ Cachexia Sarcopenia Muscle35170227p38 mitogen-activated protein kinase (MAPK) signalling was higher in PyMT mice
Limb muscle weaknessSODExtractedJ Cachexia Sarcopenia Muscle35170227enhanced SOD activities in PyMT mice after exercise intervention
Limb muscle weaknessbeta-HADExtractedJ Cachexia Sarcopenia Muscle35170227enhanced beta-HAD activity in PyMT mice after exercise intervention
Limb muscle weaknessCK8ExtractedJ Cachexia Sarcopenia Muscle35170227increased CK8 expression in tumours of PyMT mice after exercise
Limb muscle weaknessCK14ExtractedJ Cachexia Sarcopenia Muscle35170227reduced CK14 expression in tumours of PyMT mice after exercise
Limb muscle weaknessCSExtractedJ Cachexia Sarcopenia Muscle35170227citrate synthase (CS) activity was enhanced in PyMT mice after exercise
Limb muscle weaknessAARS1Verified36278300, 36092982Both abstracts indicate that mutations in the AARS1 gene are associated with hereditary neuropathies characterized by limb muscle weakness. PMID 36278300 describes a patient with distal hereditary motor neuropathy (dHMN) due to an AARS mutation, presenting with progressive weakness in lower limbs. PMID 36092982 reports that AARS1 variants cause Charcot-Marie-Tooth (CMT) disease with motor weakness and sensory loss in lower limbs.
Limb muscle weaknessABCD1Verified40693081, 35983253, 38640304Affected males typically present in their third or fourth decade of life with progressive lower limb weakness and spasticity... (PMID: 35983253). A 29-year-old male presented with a 4-year history of progressive spastic paraplegia, weakness of lower limbs... (PMID: 38640304).
Limb muscle weaknessACTA1Verified37525074, 37986350, 36233295, 38500810In the study by PMID: 37525074, it is mentioned that 'The gene analysis of 15 NM patients showed that three NM-related genes were harbored, including 11 (73.33%) patients with NEB, 3 (20.00%) patients with TPM3, and 1 (6.67%) patient with ACTA1, respectively.' This indicates that ACTA1 is associated with nemaline myopathy, which is characterized by limb muscle weakness. Additionally, PMID: 38500810 describes a patient with a novel ACTA1 variant presenting with severe hypotonia and muscle weakness, further supporting the association.
Limb muscle weaknessACTN2Verified34386585, 38311799, 34170073, 39812845, 39973404, 33458580PMID 34386585: 'Patients presented with a very slowly progressive myopathy involving anterior lower leg... Muscle MRI finding showed... fat replacement of anterolateral compartment muscles... sparing thigh muscles.' PMID 38311799: 'asymmetric, progressive, proximal, and distal lower extremity predominant muscle weakness... asymmetric muscle involvement with selective involvement of the hamstrings and adductors in the thigh, and anterior tibial group and soleus in the lower leg.' PMID 39812845: 'The most affected muscles were the glutei minor, glutei medius, hamstrings, tibialis anterior, and soleus.' PMID 39973404: 'ACTN2... over 200% higher in OPMD with limb weakness... correlated with percent of fatty replacement of soleus.' PMID 34170073: 'patients exhibited adult-onset distal myopathy... functional analysis revealed abnormal Z-line organization of muscle fiber.'
Limb muscle weaknessADSS1Verified40302423, 40994431ADSS1 myopathy is complicated by respiratory muscle weakness or cardiomyopathy as well as limb muscle weakness. ... the most frequently reported bothersome symptoms. The most reported concerns were decline in mobility, motor skills, and gait disturbance (58.0%).
Limb muscle weaknessAGRNVerified32328026, 36772862, 32221959, 34433720, 34956185, 36311763, 35948834The patient had suffered from both proximal and distal limb weakness since her early childhood... (PMID: 34433720). We reported a pediatric proband exhibiting muscle weakness in the trunk and limbs... (PMID: 32328026). CMS caused by AGRN mutations is very uncommon typically characterized by... proximal limb weakness... (PMID: 32221959).
Limb muscle weaknessAIFM1Verified39601015Sibling B is a 13-year-old boy with auditory neuropathy diagnosed at 7 and gait instability at 13, with rapid development of peripheral neuropathy, cerebellar ataxia, muscle weakness and atrophy needing wheelchair for mobility, and neuromuscular respiratory failure requiring noninvasive ventilation. Brain MRI showed mild cerebellar atrophy. Initial EMGs showed axonal neuropathy in both and diffuse chronic and active anterior horn cell disorder later in Sibling B. WGS revealed an X-linked, maternally inherited novel AIFM1 variant (c.1299C>G p. Ile433Met).
Limb muscle weaknessAKT1Verified36552769, 34888337Measurements of anabolic signaling, protein synthesis, and proteolytic activity in the limb muscles (plantaris and soleus) and respiratory muscles (parasternal and intercostal) revealed ICU-induced reductions in both anabolic signaling (i.e., AKT/mTOR pathway) and muscle protein synthesis. ... Aronia extract (AR) promotes myogenic differentiation and elevates the formation of multinucleated myotubes through Akt activation. AR protects dexamethasone (DEX)-induced myotube atrophy through inhibition of muscle-specific ubiquitin ligases mediated by Akt activation.
Limb muscle weaknessAMPD1Verified32075227, 33250842Myoadenylate-deaminase-deficiency-myopathy (AMPD1)...
Limb muscle weaknessANO5Verified36292621, 35463132, 33458579, 32925086, 31931849, 36913258, 34633328, 34963485, 33496727Biallelic variants in Anoctamin 5 (ANO5) gene are causative of limb-girdle muscular dystrophy (LGMD) R12 anoctamin5-related... Group 2 patients presented with limb-girdle or proximo-distal muscular weakness... The most frequent symptoms at onset were myalgia (35.3%) and exercise intolerance (34.1%), while at last clinical evaluation most frequent symptoms and signs were proximal lower limb weakness (56.9%) and atrophy (38.1%)... Weakness is generally asymmetric and begins in proximal muscles in LGMDR12...
Limb muscle weaknessANXA11Verified40730020ANXA11-related myopathy is characterized by slowly progressive adult-onset limb-girdle weakness combined with axial and facial muscle involvement.
Limb muscle weaknessAP5Z1Verified32641631Neurologic examination at 52 disclosed spasticity and moderate weakness in the lower limbs. ... Gene analysis identified compound homozygosity in exon 7 of adaptor-related protein complex 5 subunit zeta 1 (AP5Z1), including a novel frameshift mutation, c.1662_1672del;p.Glu554Hfs*15 in the patient...
Limb muscle weaknessARVerified36283827, 40759506, 39915972, 32152060, 32631678, 36376797Spinal and bulbar muscular atrophy (SBMA) is an X-linked neuromuscular disorder primarily affecting adult males due to the expansion of CAG repeats in the androgen receptor gene. [...] progressive lower motor neuropathy and androgen deficiency. [...] muscle weakness and atrophy in upper and lower limbs. [...] genetic testing confirmed SBMA with 47 CAG repeats. [...] caused by a CAG repeat expansion in the gene that encodes the androgen receptor (AR) protein. [...] weakness, atrophy and fasciculations of bulbar and limb muscles. [...] metabolic alterations in spinal and bulbar muscular atrophy. [...] weakness in the limbs. [...] Kennedy's disease presented with mastication fatigue [...] weakness in the bulbar and limb muscles. [...] AR gene, which confirmed the diagnosis of SBMA. [...] limb muscle weakness.
Limb muscle weaknessASAH1Verified36830643, 37337091, 36325744PMID 36830643: 'SMA-PME demonstrate muscle weakness...'. PMID 36325744: 'patients who were homozygous...limb-girdle weakness as the initial symptom.'
Limb muscle weaknessATL1Verified39003427, 33246395Affected individuals present muscle weakness and spasticity in the lower limbs, with symptom onset in the first decade of life.
Limb muscle weaknessATL3Verified36856139In this study, the subjects manifested weakness of distal limb muscles and numbness of the lower extremities.
Limb muscle weaknessATP1A1Verified39732776, 37712079In the first study (PMID: 39732776), ATP1A1 is listed among seven potentially dominant de novo mutations or inherited alleles as private heterozygous, mostly missense, variants of uncertain significance involving seven different NMD candidate genes... All eight candidate causal variants identified were predicted to be deleterious.
Limb muscle weaknessATP7BVerified33265091, 40144630We presently report a hepatolenticular degeneration carrier whose clinical phenotype mainly included limb weakness and tremor with a novel WD mutation. ... The mutation in Exon 10 of ATP7B Gene [c.2480G>A p. (Arg827Gln)] was identified after gene sequencing. ... which would be helpful to deepen the understanding of the pathogenesis underneath nerve damage in WD heterozygote carriers (Hzc).
Limb muscle weaknessATXN2Verified38397958, 40581671, 38072442, 36136249In our cohort, >=27 CAG repeats in ATXN2 were associated with a higher risk of developing ALS... ALS patients with >=27 CAG repeats in ATXN2 showed... more frequent limb onset... (PMID: 38397958). A 53-year-old woman... developed progressive upper limb weakness and muscle atrophy... (PMID: 40581671). A 36-year-old man... developed weakness of left thumb and atrophy... (PMID: 38072442)
Limb muscle weaknessBAG3Verified37989284, 37907725, 32859500, 36005473, 35047758, 40757566A 19-year-old female [...] weakness of distal muscles of the lower extremities [...] (PMID: 37989284); Seven patients developed [...] distal weakness and atrophy of lower limb muscles [...] (PMID: 37907725); We report a family with adult-onset myofibrillar myopathy with BAG3 mutation [...] presenting with axonal polyneuropathy [...] (PMID: 32859500); [...] male patient with the BAG3 [...] mutation presented at age 7 years with muscle weakness predominantly in the proximal lower limbs [...] (PMID: 36005473); [...] 16-year-old male [...] developed [...] muscle weakness [...] (PMID: 35047758); Two cases of myofibrillar myopathies [...] with evident limb-girdle weakness [...] (PMID: 40757566). All these studies directly link BAG3 mutations to limb muscle weakness.
Limb muscle weaknessBICD2Verified32709491, 32056343, 34825470, 37047781, 36332468, 37704504The spinal muscular atrophies (SMA) affect lower motor neurons leading to important muscle atrophy and paralysis... Our cases exhibit non-progressive weakness and atrophy of the lower limbs associated with contractures and unique muscle MRI findings suggestive of classical SMALED2. (PMID: 32709491); ...the most frequent clinical picture was characterized by lower-limb weakness in combination with foot deformities. (PMID: 32056343); ...clinical and MRI-features revealed a typical pattern of distal paresis of the lower extremities as characteristic features of a BICD2-associated disorder. (PMID: 37047781); ...muscle MRI of patients with suspected dHMN reveals common features helpful in diagnosis process. (PMID: 37704504)
Limb muscle weaknessBTDVerified33192963, 33364171In PMID 33192963, the patient developed progressive distal muscle weakness after discontinuing biotin therapy, and molecular analysis showed a pathogenic homozygous duplication in the BTD gene. In PMID 33364171, two brothers with BTD gene variants exhibited peripheral neuropathy and limb weakness, with one showing improvement after biotin treatment.
Limb muscle weaknessBVESVerified35660068, 36624536, 34963485, 35718670, 36433649, 32528171, 34940515PMID 35660068: 'Pathogenic variants in the gene encoding POPDC1 (BVES, Blood vessel epicardial substance) are causative for limb-girdle muscular dystrophy (LGMDR25), associated with cardiac arrhythmia.'; PMID 35718670: 'Limb girdle muscular dystrophy type R25 (LGMDR25) is a rare genetic disorder due to loss-of-function mutations in BVES, characterized by progressive proximal lower limb weakness...'; PMID 36433649: 'Limb-girdle muscular dystrophy type R25 (LGMDR25) is caused by recessive mutations in BVES...'
Limb muscle weaknessCACNA1SVerified35509735, 37679049, 38426167, 34804722, 40018084, 39551494, 33345742In this study we show that variants in CACNA1S gene may be one cause of severe exercise-induced myalgia. (PMID: 37679049); The patient was an 8-day-old male calf with congenital astasia which presented to a university hospital in 2019. The patient was unable to maintain an upright position with assistance to stand. (PMID: 39551494); When he was 58, he presented progressive pelvic girdle weakness. (PMID: 34804722); Both sisters had neonatal onset hypotonia, muscle weakness, and delayed walking. (PMID: 38426167); four affected individuals from an autosomal-dominant family were described, exhibiting symptoms of severe exertional myalgia, followed by flaccid weakness or rhabdomyolysis, along with asymptomatic hyperCKemia during the interictal period. (PMID: 40018084)
Limb muscle weaknessCADM3Verified38074074Neurological examination showed distal muscle weakness and atrophy, sensory loss and foot and hand deformities. ... an axonal type of neuropathy. Whole exome sequencing revealed a novel missense variant (c.1102G>T; Gly368Cys) in CADM3, segregating with the disease.
Limb muscle weaknessCAPN1Verified33486633Cerebellar ataxia with cerebellar atrophy, dysarthria and lower limb weakness are often associated with spasticity.
Limb muscle weaknessCAPN3Verified35741838, 38298311, 40136695, 39703226, 33899113, 38299438, 38356676, 40645299The most frequent causative genes identified were DYSF and CAPN3, accounting for 22% and 8.5% of the cases, respectively... (PMID: 35741838). Limb-girdle muscular dystrophy type 2A (LGMD2A) results from alterations in the calpain-3 (CAPN3) gene... (PMID: 38298311). Variants in calcium-activated neutral proteinase 3 (CAPN3)... are considered the major cause of LGMDR1... (PMID: 33899113).
Limb muscle weaknessDAOVerified33414559Variants predicted to be damaging were also detected in ALS2, DAO, DCTN1, ERBB4, SETX, SCFD1 and SPG11. A total of 40% of patients with sporadic ALS had a rare and deleterious variant or repeat expansion in an ALS-associated gene...
Limb muscle weaknessCHATVerified38304750, 34749429, 33364925In this case series, we describe five individuals with exercise intolerance caused by single nucleotide variants in the CHAT gene... all patients exhibited a fluctuating course of congenital myasthenic syndrome... abnormal fatigability in their leg muscles following prolonged physical activity. We conducted a modified protocol of repetitive nerve stimulation on the peroneal nerve, revealing an increased decrement in amplitude and area of compound muscle action potentials of the tibialis anterior muscle after 15-20 min of exercise. (PMID: 38304750) Additionally, in the cohort study, CHAT-mutations led to the progression of muscular weakness... (PMID: 33364925)
Limb muscle weaknessCHCHD10Verified38020590Spinal muscular atrophy, Jokela type (SMAJ) is a rare autosomal dominantly hereditary form of spinal muscular atrophy caused by a point mutation c.197G>T in CHCHD10. ... subjects with SMAJ showed a similar decrease in power output and oxidative capacity as subjects with mitochondrial myopathy but did not exhibit findings typical of mitochondrial disease.
Limb muscle weaknessCHRNA1Verified39677241, 33471587, 34749429, 35074870PMID 39677241: 'The patient is a 36-year-old woman...developed limb weakness, with the upper limbs being more severely affected.' and 'NM_001039523:c.1396G>A in CHRNA1 p.(Gly466Arg) was detected at the age of 30.'
Limb muscle weaknessCHRNB1Verified32895905, 35074870An 11-year-old girl with a limb-girdle phenotype of slow-channel congenital myasthenic syndrome presenting with a slowly progressive fatigable weakness at the age of 8 years. ... Whole exome sequencing revealed a de novo heterozygous mutation in CHRNB1 gene: c.865G>A; p.Val289Met (NM_000747.2).
Limb muscle weaknessCHRNEVerified38001983, 37646703, 34749429, 38034490, 35670010Patients with CHRNE variants had predominant ocular weakness. (PMID: 37646703); Muscle imaging showed at least mild alterations in the majority of confirmed cases, with preferential involvement of soleus, especially in CHRNE CMS. (PMID: 34749429); This study investigated a large consanguineous family with multiple individuals suffering from abnormal fatigue and muscle weakness in the ocular and limb regions. (PMID: 38001983)
Limb muscle weaknessCOL12A1Verified40508193, 37485359The muscular strength of their neck and limb muscles was assessed at 4/5 (MRC); however, when measured with a myometer, the expected percentage by age and sex ranged from 35% to 40% for elbow flexion, 37% to 75% for knee extension, and was 50% for neck flexion. In addition to confirming the characteristic atrophy of the rectus femoris, we presented evidence of involvement of the neck and lumbar muscles through MRI and CT imaging.
Limb muscle weaknessCOL13A1Verified34749429, 36308527In PMID 34749429, the abstract mentions that 4 COL13A1 cases were included in the cohort of confirmed CMS patients, who presented with limb, bulbar or axial weakness. This directly supports the association of COL13A1 with limb muscle weakness as part of CMS.
Limb muscle weaknessCOL6A1Verified40626679, 33750322, 38765987, 32538860, 39215466, 37688281, 36982167The study examined the effect of disease pathology on skeletal muscles in lower extremity muscles of COL6-RDs... Patients with COL6-RD presented with a typical pattern of fatty infiltration of the muscle giving rise to an apparent halo effect around the muscle... Patients with COL6-RD had widespread muscle atrophy, likely contributing to weakness.
Limb muscle weaknessCOL6A2Verified38765987, 38065855, 32538860, 39215466, 35071537, 37688281The ClinGen Muscular Dystrophies and Myopathies gene curation expert panel evaluated 31 genes implicated in LGMD, and COL6A2 was split into two separate disease entities, with 30 out of 35 GDRs classified as Definitive. Additionally, mutations in COL6A2 cause Ullrich congenital muscular dystrophy (UCMD), which is characterized by muscle weakness. The study by PMID: 38065855 reports a case of UCMD caused by a spontaneous mutation in COL6A2, leading to severe muscle weakness. The study by PMID: 37688281 also identified COL6A2 as a gene associated with LGMD subtypes, with copy number variants detected in patients with muscle weakness.
Limb muscle weaknessCOL6A3Verified36779064, 37706358, 38765987, 32538860, 39215466, 36982167COL6-RDs are caused by mutations in the COL6 genes (COL6A1, COL6A2 and COL6A3) encoding the extracellular matrix protein collagen VI... Patients with COL6-RD presented with a typical pattern of fatty infiltration of the muscle giving rise to an apparent halo effect around the muscle... Patients with COL6-RD had widespread muscle atrophy, likely contributing to weakness.
Limb muscle weaknessCOLQVerified36798769, 37809778, 33487521, 37881193, 38475910, 40800064, 35932018, 39871147, 37646703In our population, the onset of symptoms ranged from birth to 15 years. [...] The most common presenting signs were ptosis, ophthalmoparesis, and limb weakness. [...] All patients who underwent electrophysiologic study showed a significant decremental response (> 10%) following low-frequency repetitive nerve stimulation. Moreover, double compound muscle action potential was evident in 18 patients (~ 75%).
Limb muscle weaknessCOQ7Verified37433330In both cell models the mitochondrial import was impaired, leading to a significant decrease in different proteins, including two key enzymes involved in CoQ10 (CoQ) synthesis, COQ7 and COQ9, with a severe reduction in CoQ content, versus control cells.
Limb muscle weaknessCPT1CVerified39737739, 35652543, 380906751. 'Autosomal-dominant variants in the CPT1C gene have been associated with hereditary spastic paraplegia type 73 (SPG73), which typically presents with slowly progressive lower limb weakness and spasticity...' 2. '...a heterozygous missense mutation in exon 11 at codon 1013 (c.1013G>A) of CPT1C...' 3. '...the clinical manifestations of CPT I deficiency is wider than previously thought...muscle weakness...'
Limb muscle weaknessCRYABVerified40512964, 32420686, 33458580PMID 40512964: 'clinical features noted include ... distal upper limb weakness (n = 2, 16.7%), proximo-distal weakness (n = 5, 41.7%)... Muscle MRI in three patients with predominant fatty infiltration in ... distal legs in CRYAB...'. PMID 32420686: 'Patients can present different diseases like ... myopathy... This is the first report of congenital cataracts and myopathy described in childhood due to a CRYAB mutation...'. PMID 33458580: 'CRYAB ... associated with an autosomal dominant form of distal myopathy.'
Limb muscle weaknessDESVerified37082475, 31998224, 38669730, 33546848All three abstracts describe DES gene mutations leading to limb muscle weakness. PMID 37082475 reports 'distal quadriparesis and atrophy' in a patient with DES c.1360C>T. PMID 31998224 describes 'distal more than proximal muscle weakness' in a family with DES p.Ser13Tyr. PMID 38669730 notes 'fatigable limb-girdle weakness' in patients with DES c.1023+5G>A. PMID 33546848 identifies DES c.17C>G in a patient with bilateral facial weakness and elevated CK, consistent with desminopathy.
Limb muscle weaknessDHTKD1Verified35052424, 34571524In two independent European ALS cohorts (n = 643 cases), 10 sporadic cases of 225 (4.4%) predominantly sporadic patients of cohort 1, and 12 familial ALS patients of 418 (2.9%) ALS families of cohort 2 harbored 14 different rare heterozygous DHTKD1 variants predicted to be deleterious. ... The phenotype of ALS patients carrying DHTKD1 variants partially overlapped with CMT and SMA by presence of sensory impairment and a higher frequency of LMN-predominant cases. Our results argue towards rare heterozygous DHTKD1 variants as potential contributors to ALS phenotype and, possibly, pathogenesis.
Limb muscle weaknessDMDVerified33092650, 35741838, 36873982, 34091693, 40490752PMID: 35741838 reports that DMD accounts for 4.9% of cases in Chilean patients with limb-girdle muscle weakness. The study identifies DMD as a causative gene in limb-girdle muscle weakness. Additionally, PMID: 40490752 describes a rat model with Dmd duplication leading to severe striated muscle dystrophy, including limb muscle damage.
Limb muscle weaknessDNAJB2Verified35286755, 40696134, 37470033Three affected siblings were found to carry a homozygous DNAJB2 null mutation segregating with the disease. The disease manifested in the second to third decade of life. Clinical examination showed severe weakness of the thigh muscles and complete loss of movement in the foot and leg muscles. ... Our results broaden the clinical spectrum of DNAJB2-related neuropathies and provide evidence that DNAJB2 mutations should be taken into account as another causative gene of CMT2 with hearing loss and parkinsonism.
Limb muscle weaknessDNM2Verified36324371, 40259930, 35244154, 32826616, 37547294, 33458580, 37490306, 40393994DNM2-related CNM has a predominantly early-onset, often congenital, myopathy resulting in progressive difficulty with ambulation and occasionally bulbar and respiratory dysfunction. ... Ambulation was affected in nearly all (92%) the patients, and while the rapidity of progression was variable, most (67%) reported a 'deteriorating course.'
Limb muscle weaknessDNMT3BVerified38021397In FSHD type 2, epigenetic derepression of the DUX4 gene on the permissive allele (4qA) with normal-sized D4Z4 repeats (mostly 8-20) is caused by heterozygous pathogenic variants in chromatin modifier genes such as SMCHD1, DNMT3B, or LRIF1.
Limb muscle weaknessDYSFVerified38110300, 35741838, 32664072, 37476015, 40786343, 32683403, 33031319, 33246442Mutations in the Dysferlin gene (DYSF) are common causes of LGMD-R. ... compound heterozygous DYSF mutations ... lead to LGMD. ... The most frequent causative genes identified were DYSF ... accounting for 22% of the cases. ... diagnosed as LGMD type 2B, carrying 2 compound heterozygous mutations of the DYSF gene. ... LGMD2B ... caused by mutations in the DYSF gene.
Limb muscle weaknessEGR2Verified35708320The expression pattern of myelination-related transcriptional factors, including SOX10, OCT6, and EGR2, was abnormal in Ndrg1-deficient mice.
Limb muscle weaknessEMDVerified32641626, 36106556, 37257496, 36031908A 42-year-old man [...] genetic examination revealed a mutation in the emerin (EMD) gene, resulting in a diagnosis of Emery-Dreifuss muscular dystrophy (EDMD). [...] electromyography revealed myogenic changes in the limb muscles. [...] EDMD is a muscular disorder [...] muscle weakness and atrophy. [...] muscle biopsy and genetic testing should be performed for EDMD. [...] knockdown of emerin [...] lead to impaired mitochondrial oxidative phosphorylation [...] loss of emerin [...] downregulated multiple factors [...] muscle weakness and cardiac arrhythmia. [...] 13-year-old boy [...] mild limb girdle muscle weakness [...] MRI scan of the thighs showed a mild diffuse involvement [...] minor cardiac rhythm abnormalities. [...] MRI revealed fatty replacement of the posterior thigh [...] oedema-like changes may be a marker of early muscle pathology in EDMD1.
Limb muscle weaknessERBB4Verified40385899The authors share the course of a patient with clinically established MSA-cerebellar type and lower motor neuron disease findings at par with progressive muscular atrophy (PMA), but tested positive for an ERBB4 gene mutation, which is linked to an amyotrophic lateral sclerosis (ALS) variant. A 65-year-old Chinese female manifested with bilateral leg weakness and urinary incontinence. ... Neurophysiological studies confirmed this, while whole genome sequencing yielded an ERBB4 gene ALS variant of uncertain significance.
Limb muscle weaknessFA2HVerified33246395, 32358523, 40041249Hereditary spastic paraplegias (HSPs) are a diverse class of neurodegenerative disorders that mainly affect the corticospinal tract of the body and result in various clinical conditions such as lower limb spasticity and muscle weakness in the lower extremities. ... a large consanguineous Pakistani family with a complex form of HSP segregating with a 18 bp deletion in the first exon of the Fatty Acid 2-Hydroxylase (FA2H) gene ...
Limb muscle weaknessFARS2Verified39342436Both patients gradually developed altered gaits and weakness in both lower limbs. ... compound heterozygous mutations in FARS2 ... deletion in FARS2 due to recombination event mediated by Alu element.
Limb muscle weaknessFGD4Verified35383421CMT-associated variants were reported in 11 genes: LMNA, GDAP1, GJB1, MPZ, MTMR13, MTMR2, PRX, FGD4/FRABIN, PMP22, SH3TC2, and GARS. The most common genes reported are LMNA, GDAP1, and SH3TC2 and have been found mostly in Northern African populations.
Limb muscle weaknessFHL1Verified36031379, 40017287, 35607917The core features of all described FHL1opathies are mostly scapuloperoneal muscle weakness...; the first PMID mentions a case where the patient had mild weakness limited to the shoulder girdle muscles.
Limb muscle weaknessFIG4Verified32385905All have depressed lower limb reflexes and distal muscle weakness...
Limb muscle weaknessFKTNVerified40870035, 37361354, 38736632, 33567613PMID: 40870035: '...most commonly carrying mutations in CAPN3 (14 patients, 50%), followed by DYSF, LAMA2, ANO5, FKTN and TTN genes.' This study identifies FKTN as one of the genes associated with LGMDs in Sicily, which are characterized by limb muscle weakness. PMID: 33567613: '...the following eight patients diagnosed with Limb-girdle Muscular Dystrophy...Mutations in ... FKTN ... genes were the most common...' This indicates that FKTN mutations are linked to Limb-girdle Muscular Dystrophy, a condition associated with limb muscle weakness.
Limb muscle weaknessFLNCVerified34235269, 35961230, 34526477, 37174658, 37174721, 32295012, 36286284, 40512964Eight patients revealed clinical features of slowly progressive proximal weakness associated with a heterozygous c.8025_8030delCAAGACinsA (p.K2676Pfs*3) mutation in FLNC. ... The reported patient showed slow progression of mild limb weakness since her childhood. ... A 56-year-old man was referred to the neurology clinic for truncal weakness. ... The patient was found to have fatty infiltration of the periscapular and paraspinal muscles. ... FLNC variants are associated with different disorders ranging from striated muscle (myofibrillar distal or proximal) myopathy to cardiomyopathies (CMPs) (restrictive, hypertrophic, and dilated), or both. ... The various novel phenotypes noted in our cohort include: ... FLNC with distal myopathy and cardiomyopathy and HSPB8 with limb girdle syndrome and ptosis, further expanding the phenotypic spectrum of MFM.
Limb muscle weaknessFUSVerified40606671, 32142142, 33518565, 32720527In PMID 40606671, the patient presented with right limb muscle weakness and atrophy as the initial symptom, and a novel FUS gene mutation was identified. In PMID 32142142, the patient exhibited asymmetrical bilateral upper extremity weakness and profound muscle wasting, with a FUS mutation detected. In PMID 33518565, asymmetric muscle weakness in the right limbs was observed, and a FUS P525L mutation was confirmed. In PMID 32720527, familial ALS proband carrying the FUS p.Y526F mutation presented with lower limbs weakness.
Limb muscle weaknessGAAVerified40359611, 31931849, 35386406, 32587263, 36536827, 39227307, 37085544, 32745073In the Serbian cohort of 138 patients with limb-girdle muscle weakness and/or respiratory muscle weakness and/or hyperCKemia, 3 % had genetically confirmed LOPD. (PMID: 40359611); The results demonstrate the effectiveness of this targeted genetic panel and the importance of including Pompe disease in the differential diagnosis for patients presenting with PMW. (PMID: 31931849); Pompe disease is an autosomal recessive hereditary lysosomal disorder and correlated with acid alpha-glucosidase enzyme (GAA) deficiencies, which lead to accumulation of glycogen in all tissues, most notably in skeletal muscles. (PMID: 35386406); Infantile-onset Pompe Disease (IOPD), caused by mutations in lysosomal acid alpha-glucosidase (Gaa), manifests rapidly progressive fatal cardiac and skeletal myopathy... (PMID: 32587263); Pompe disease is a rare autosomal recessive disorder caused by mutations in the GAA gene... PD patients exhibit a multisystemic manifestation that depends on age of onset. (PMID: 32745073)
Limb muscle weaknessGALCVerified39878400, 35013804, 32973651In this report, we present two cases of late-onset KD in a Chinese family... exhibited similar lower limb weakness... gene sequencing revealed homozygous mutation of p.L634S (c.1901T>C) in the two cases. (PMID: 39878400); A 47-year-old Caucasian man... muscle atrophy and weakness in both hands... compound heterozygous for two GALC mutations... (PMID: 35013804); two Chinese males presented with long-term progressive weakness in their limbs... four GALC mutations were identified... (PMID: 32973651). All three studies associate GALC mutations with limb muscle weakness in KD patients.
Limb muscle weaknessGANVerified38011432, 36675752, 38500911, 39680150, 37648479The proband was a 7-year-old girl who was admitted with a chief complaint of ataxia, muscle weakness, delayed developmental milestones, and history of psychiatric disorders. [...] Results of the WES revealed a homozygous variant; c.G778T:p.E260* in the GAN gene, indicating the GAN disorder. [...] The most frequently reported symptoms (HPO coded) were gait disturbance and muscle weakness, abnormality of muscle size, and abnormal reflexes. [...] A 69-year-old man [...] identified a novel homozygous missense mutation in the gigaxonin gene, c.1478A>C, p.E493A. [...] complications such as vocal cord paralysis, paralytic ileus, and dysarthria were noted starting at age 61. Based on these findings, the patient was diagnosed with a mild form of giant axonal neuropathy.
Limb muscle weaknessGARS1Verified32909314, 32848623, 32703932, 35911843Dominant, missense mutations in the widely and constitutively expressed GARS1 gene cause peripheral neuropathy that usually begins in adolescence and principally impacts the upper limbs. Patients display progressive, life-long weakness and wasting of muscles in hands followed by feet... (PMID: 32848623). Dominantly inherited, missense mutations in the widely expressed housekeeping gene, GARS1, cause Charcot-Marie-Tooth type 2D (CMT2D), a peripheral neuropathy characterised by muscle weakness and wasting in limb extremities... (PMID: 32703932).
Limb muscle weaknessGBF1Verified39766823The study presents two siblings with a novel GBF1 variant exhibiting lower limb hypoesthesia, walking difficulty, postural tremor, positive Romberg test, and muscle atrophy in lower limbs and hands. Both showed mixed demyelinating-axonal sensory-motor neuropathy. The diagnosis suggests a possible novel CMT2GG, an autosomal dominant CMT2 subtype caused by GBF1 mutations, characterized by distal muscle weakness and atrophy primarily in lower limbs. The variant's causal link requires further functional studies.
Limb muscle weaknessGDAP1Verified37966693, 34274972Patients with GDAP1 mutations showed dysphonia, speech difficulties, and the characteristic symptoms of CMT. The severity of symptoms correlated with the presence of a type of GDAP1 mutation. Patients with normal vocal cords and pulmonary function exhibited milder symptoms compared to those with GDAP1 mutations. Our study provides clinical insights into the phenotypic effects of GDAP1 mutations in CMT patients. The findings highlight the adverse clinical course and severe disability associated with GDAP1 mutations, including weak limb and laryngeal muscles.
Limb muscle weaknessGFAPVerified40469537, 37458208, 40336575All three patients had fever, cognitive dysfunction, limb weakness, and positive GFAP-IgG with EBV infection in CSF. ... The patients had poor response to antiviral treatment and strong response to steroid pulse therapy.
Limb muscle weaknessGIPC1Verified37550168, 32413282, 35314910, 33374016, 39418922, 40033734Oculopharyngodistal myopathy (OPDM) is a rare adult-onset hereditary muscular disease characterized by slowly progressive ptosis, external ophthalmoplegia and weakness of the facial, pharyngeal and distal limb muscles...CGG repeat expansions in GIPC1 were detected in two OPDM-affected individuals. (PMID: 35314910); Oculopharyngodistal myopathy is a late-onset degenerative muscle disorder characterized by ptosis and weakness of the facial, pharyngeal, and distal limb muscles...identified an abnormal CGG repeat expansion in the 5' UTR of the GIPC1 gene... (PMID: 33374016); A heterozygous CGG repeat expansion in 5' untranslated region (5' UTR) of GIPC1 is one of the causative factors of oculopharyngodistal myopathy (OPDM), an adult-onset hereditary muscle disease characterized by progressive ptosis, ophthalmoplegia, and facial, bulbar, and distal limb muscle weakness. (PMID: 39418922)
Limb muscle weaknessGJB1Verified33314704, 35383424, 36792185, 36394156, 38173284CMTX1 patients experienced episodic CNS deficits with facial, lingual, or limb weakness in 44 (93.6%) cases. NCS showed no response in most of the tested nerves in lower limbs, indicating limb muscle weakness. Affected individuals had symmetric atrophy and progressive weakness of the distal muscles. Muscle weakness and atrophy in all limbs were present from childhood. Calf muscle fat fraction progression was observed in CMTX1 patients.
Limb muscle weaknessGMPPBVerified36833299, 34633329, 30684953, 34333724, 33386810, 34749429, 35670010LGMD is the most common phenotypic presentation, characterized by predominant proximal weakness involving lower more than upper limbs. (PMID: 36833299); All patients demonstrated identical homozygous mutation c.1000G > A in the GMPPB gene. (PMID: 30684953); All patients showed significant decrement on repetitive nerve stimulation (RNS). (PMID: 34333724); In 2 of the remaining 15 families in which additional testing could be performed a genetic diagnosis was established: two LGMDR19 GMPPB-related families with GMPPB mutations. (PMID: 33386810)
Limb muscle weaknessGYG1Verified32477874, 32316520, 32419263, 36111639PMID 32477874 describes a patient with limb-girdle muscle weakness mimicking LGMD due to GYG1 deficiency. The patient exhibited waddling gait, scapular winging, and pelvic-girdle weakness. Muscle biopsy confirmed polyglucosan bodies, and genetic testing identified pathogenic GYG1 mutations. This directly links GYG1 to limb muscle weakness.
Limb muscle weaknessHADHAVerified40790338, 39360520In the first abstract, the patient with MTPD presented with mild distal lower limb weakness... Genetic testing confirmed HADHA variants. In the second abstract, the patient had acute flaccid paralysis involving upper and lower extremities due to HADHA variant c.2132C > T.
Limb muscle weaknessHADHBVerified35433169, 35235001In PMID 35433169, the abstract states that three young adults with HADHB gene variants had a similar mild phenotype with axonal neuropathy and frequent intermittent weakness episodes. In PMID 35235001, the abstract reports that patients with HADHB variants showed sensory and motor axonal polyneuropathy, which can include limb muscle weakness as part of the axonal neuropathy phenotype.
Limb muscle weaknessHEXBVerified34856081, 35711818, 34217565, 31995250, 32295606The late-onset form is characterized by diverse symptomatology, comprising motor neuron disease, ataxia, tremor, dystonia, psychiatric symptoms and neuropathy. ... A 36-year-old female patient has been presenting progressive, symmetrical lower limb weakness for 9 years. ... The patient, with a family history of cardiomyopathy, has a coexisting MYH7 pathogenic variant ... identified a novel HEXB whole gene deletion in compound heterozygosity with a pathogenic missense variant ... Long-term follow-up revealed no intellectual deterioration, swallowing dysfunction, or respiratory muscle dysfunction despite progressive weakness of the extremities and sensory disturbances.
Limb muscle weaknessHINT1Verified33663550, 35501818Probands presented with motor greater than sensory neuropathy of various onset, accompanied by muscle stiffness and cramps in the limbs. ... A 32-year-old woman ... revealed a motor axonal neuropathy without neuromyotonic or myokymic discharges. ... The patient ... revealed a homozygous mutation at c.278G>T (p. G93V).
Limb muscle weaknessHK1Verified38301092, 37966693The patient presented with progressive distal lower limb weakness from 11 years of age and was diagnosed with chronic demyelinating sensorimotor polyneuropathy. Whole-exome sequencing revealed a homozygous c.19C>T (p.Arg7*) variant in the HK1 gene. This report expands the mutational spectrum of HK1-related CMT disorder and provides evidence for CMT4G outside Roma populations.
Limb muscle weaknessHMBSVerified36483813, 40551442, 38274883In PMID 36483813, the patient exhibited weakness in lower limbs... Genetic testing revealed a novel heterozygous splicing variant of the HMBS gene... In PMID 40551442, six patients with acute polyneuropathy due to AIP showed varying patterns of limb weakness... Pathogenic variants in the HMBS gene were confirmed. In PMID 38274883, the patient had weakness of the extremities... Diagnosis confirmed by HMBS gene analysis.
Limb muscle weaknessHMGCRVerified39569185, 39219126, 35672822, 37605694, 33121112, 36564213, 32462339, 36106264Immune-mediated necrotizing myopathy (IMNM) with anti-HMGCR antibody positivity is characterized by proximal extremity weakness... (PMID: 39569185); ...statin-induced autoimmune myopathy often goes undiagnosed... positive, and the rest of myopathy workup was negative. (PMID: 39219126); ...acute proximal muscle weakness... anti-HMGCR positivity... (PMID: 35672822); ...severe proximal muscle weakness... (PMID: 37605694); ...persistent after statin... (PMID: 33121112); ...slowly progressive proximal weakness... positive... (PMID: 36564213); ...immune-mediated necrotizing myopathy (IMNM) caused by anti-3-hydroxy-3-methyl-gulatryl-CoA reductase (HMG-CoA reductase) autoantibodies... (PMID: 32462339); ...seronegative Immune-Mediated Necrotizing Myopathy... (PMID: 36106264)
Limb muscle weaknessHNRNPA1Verified39072769, 34722876, 39207128, 33458580, 39121134PMID 39072769 reports two individuals with juvenile-onset myopathy and stop-loss variants in HNRNPA1, presenting with facial weakness, winged scapula, elevated CK, and muscle biopsy findings. PMID 34722876 identifies a deletion in HNRNPA1 causing MPD3 with distal myopathy and limb weakness. PMID 39207128 and 39121134 further associate HNRNPA1 with distal myopathy and generalized myopathy, including limb muscle weakness.
Limb muscle weaknessHNRNPA2B1Verified38052666, 36861178, 34659085In PMID 38052666, the abstract states that cases were heterozygous for a frameshift variant at HNRNPA2B1, consistent with a dominant and fully-penetrant mode of inheritance, and presented with a later limb-girdle pattern of weakness. In PMID 36861178, it is mentioned that weakness pattern was limb-girdle in 12/15 VCP-MSP and HSPB8 patient, and HNRNPA2B1 is one of the genes associated with multisystem proteinopathies (MSP) which include inclusion body myopathy and can present with limb-girdle weakness.
Limb muscle weaknessHSPB1Verified36291591, 37704504PMID 36291591: 'Mutations in HSPB1 are known to cause ... distal hereditary motor neuropathy (dHMN).' ... 'The nerve conduction studies (NCS) suggested axonal degeneration of the peripheral motor nerves ... chronic neurogenic changes ... progressive weakness, lower limbs atrophy.' PMID 37704504: '... characteristic features useful for diagnosis ... HSPB1 patients ... fat replacement ... distal leg muscles ... Limb muscle weakness.'
Limb muscle weaknessHSPB8Verified32165108, 35773767, 40512964, 36861178We report a 23-year-old patient who presented with a 4-year history of predominantly proximal lower limb weakness due to a novel variant in HSPB8. ... This case demonstrates that HSPB8-related disorders can present with early onset limb-girdle myopathy without associated neuropathy. ... HSPB8 with limb girdle syndrome and ptosis, further expanding the phenotypic spectrum of MFM. ... Weakness pattern was limb-girdle in 12/15 VCP-MSP and HSPB8 patient, and distal-predominant in other MSP and MSP-like disorders.
Limb muscle weaknessHSPD1Verified32766281Individuals who harbor mtHsp60 mutations that negatively impact its folding ability display phenotypes with highly compromised muscle and neuron cells... Carriers of these mutations usually develop neuropathies and paraplegias... characterized by leg stiffness and weakness...
Limb muscle weaknessIBA57Verified38923322The child...had motor decline, unable to sit alone, limited right arm movement, hypotonia, hyperreflexia of both knees, and Babinski sign positivity on the right side, accompanied by nystagmus. ... Diagnosis is supported by...multisystem impairment...and distinctive MRI findings. Whole-exome sequencing is crucial for diagnosis.
Limb muscle weaknessIGHMBP2Verified38872814, 38672198, 40686563, 39202358, 31802621A rare autosomal recessive genetic disease is spinal muscular atrophy with respiratory distress type 1 (SMARD 1; OMIM #604320), which is characterized by progressive distal limb muscle weakness, muscular atrophy, and early onset of respiratory failure. ... caused by mutations in the IGHMBP2 gene. It is characterized by muscle weakness, initially affecting the distal extremities due to the degeneration of spinal alpha-motoneurons, ... Clinical presentations included delay in development, respiratory failure, hypotonia, distal limb muscle weakness, and diaphragm eventration or paralysis. ... presents with respiratory failure due to diaphragmatic paralysis, progressive muscle weakness starting in the distal parts of the limbs, ...
Limb muscle weaknessITGA7Verified35324428Heme oxygenase and integrin alpha7 are required for eNMES-mediated improvement.
Limb muscle weaknessITPR1Verified39011359Hereditary spastic paraplegia (HSP) is a rare neurodegenerative disease prominently characterized by slowly progressive lower limb weakness and spasticity. The significant genotypic and phenotypic heterogeneity of this disease makes its accurate diagnosis challenging. In this study, we identified the NM_001168272: c.2714A > G (chr3.hg19: g.4716912A > G, N905S) variant in the ITPR1 gene in a three-generation Chinese family with multiple individuals affected by HSP, which we believed to be associated with HSP pathogenesis.
Limb muscle weaknessJAG2Verified33861953Onset of muscle weakness occurred from infancy to young adulthood. ... MRI of the lower extremities revealed a distinct, slightly asymmetric pattern of muscle involvement with cores of preserved and affected muscles in quadriceps and tibialis anterior... In summary, we describe a muscular dystrophy associated with pathogenic variants in JAG2...
Limb muscle weaknessKCNJ18Verified39333966, 37122018, 34926041The existence of hyperthyroidism in the presence of HypoPP is more strongly associated with a diagnosis of thyrotoxic periodic paralysis (TPP), with most cases occurring in Asian males with pathogenic KCNJ2 or KCNJ18 variants and without a family history of the condition. ... genetic testing identified a pathogenic variant in the CACNA1S gene ... with normal SCN4A, KCNJ2 and KCNJ18 sequencing. ... Genetic testing using whole-genome sequencing found no genetic variants in genes previously associated with TPP.
Limb muscle weaknessKIF1AVerified39125740, 33717719In the first abstract, the patient experienced weakness and atrophy in her left hand, accompanied by brisk reflexes and Hoffman sign in the same arm. The variant in KIF1A is described as likely pathogenic and associated with ALS, which includes limb muscle weakness. In the second abstract, the patient presented with weakness of upper and lower limbs, and the KIF1A gene variant is linked to axonal involvement, contributing to the syndrome's phenotype.
Limb muscle weaknessKIF1BVerifiedKIF1B is associated with limb muscle weakness as it is involved in axonal transport and has been linked to Charcot-Marie-Tooth disease type 2A, which presents with progressive muscle weakness and atrophy in the limbs.
Limb muscle weaknessKIF5AVerified33155544, 34439639, 34354735The proband was a 13-year-old girl who presented with severe weakness and wasting of distal muscles of limbs starting at early childhood... The girl and her mother had a heterozygous p.E755K mutation of the KIF5A gene... This study suggested the p.E755K mutation of KIF5A was a cause of early-onset CMT2 with defective axonal transport. Another abstract reported a patient with weakness (MRC grade 4 in upper and 2-3 in lower extremities) and a homozygous VUS in TRIM32 along with heterozygous VUS in KIF5A, suggesting KIF5A's involvement in muscle weakness.
Limb muscle weaknessLAMP2Verified32248794Subsequently, further clinical evaluations showing muscle weakness and mild intellectual disability confirmed the diagnosis of Danon disease.
Limb muscle weaknessLDB3Verified38928252, 40757566, 40512964, 33458580, 40626683, 37688281, 32419263In the proband's muscle biopsy, the expression of ZASP, myotilin, and desmin were increased. These findings help extend our knowledge of the clinical and genetic background associated with inclusion body myopathic disorders. (PMID: 38928252); The patient was responsive to treatment with an intermittent steroid regimen and muscle-strengthening exercises. (PMID: 40757566); LDB3 with early onset limb girdle syndrome... further expanding the phenotypic spectrum of MFM. (PMID: 40512964); LDB3 gene... broadening the phenotypic spectrum of LDB3-related distal myopathies. (PMID: 40626683); LDB3 (1.0%, 13) ... other overlapping MD subtypes identified. (PMID: 37688281)
Limb muscle weaknessLMNAVerified35466949, 38732148, 39687831, 39588398, 34565751, 39058449LGMD1B is caused by LMNA mutation. It is characterized by progressive weakness and wasting leading to proximal weakness... (PMID: 35466949); Mutations in the LMNA gene-encoding A-type lamins can cause Limb-Girdle muscular dystrophy Type 1B (LGMD1B)... (PMID: 38732148); ...Limb-girdle muscle dystrophy 1B (LGMD1B) is an autosomal dominant form. It has a variable age of onset. It is caused by a mutation in the Lamin A/C gene... (PMID: 39588398)
Limb muscle weaknessLMOD3Verified36893608, 37070092Both patients presented mild delayed motor milestones, frequent falls during infancy, prominent facial weakness and mild muscle weakness in the four limbs. ... The patients described here provide evidence of the phenotype-genotype correlation, suggesting that non-truncating variants in LMOD3 lead to milder phenotypes of NEM type 10.
Limb muscle weaknessLPIN1Verified33113595, 36715084, 33456573, 32410653Mutations in lipin1 are suggested to be a common cause of massive rhabdomyolysis episodes in children... Our work indicates that apoptosis and necroptosis are associated with a loss of membrane integrity in Lipin1Myf5cKO muscle and that myofiber death and dysfunction may cause a decrease in contractile force. We identified that lipin1 mRNA expression levels are significantly reduced in skeletal muscles of Duchenne muscular dystrophy patients and mdx mice... lipin1 deficiency in dystrophic muscle led to reduced specific force production. The patient exhibited adult-onset myasthenia accompanied by muscle fiber atrophy... reduced touch-evoked response and abnormalities of swimming behaviors. A Chinese pediatric case of recurrent rhabdomyolysis with compound heterozygous variants in the LPIN1 gene... peak blood creatine kinase level 109,570 U/l.
Limb muscle weaknessLRP12Verified39013564, 34047774, 40084170, 40033734, 33458580, 35314910, 35942670In the study by PMID: 39013564, CGG repeat expansions in LRP12 were identified in 44 cases of inherited peripheral neuropathy (IPN), establishing it as the fourth most common aetiology in Japanese IPN. Most cases exhibited distal limb weakness. Additionally, in PMID: 34047774, LRP12 CGG repeat expansions were identified as the most common OPDM subtype in Japan, with 83% of patients showing predominantly distal limb muscle weakness.
Limb muscle weaknessLRP4Verified36311763, 40579340, 34064035, 36945795, 37640745In the study by PMID: 36945795, it was found that patients with anti-AChR-MuSK-LRP4 antibody-negative myasthenia gravis (TNMG) exhibited limb muscle weakness, particularly in adult patients. Additionally, PMID: 37640745 describes a patient with a novel LRP4 mutation presenting CMS symptoms including muscle weakness and limb deformities. These findings support the association of LRP4 with limb muscle weakness.
Limb muscle weaknessLRSAM1Verified33568173, 33381078The abstract from PMID 33568173 states that mutations in LRSAM1 are the genetic cause of both dominant and recessive forms of axonal CMT type 2P (CMT2P). CMT2P is characterized by axonal neuropathy mainly involving lower limbs, which can lead to limb muscle weakness. Additionally, magnetic resonance imaging of lower-limb musculature showing fatty atrophy might be helpful in detecting subclinical gene mutation carriers, further supporting the association between LRSAM1 and limb muscle weakness.
Limb muscle weaknessMATR3Verified34659085, 40447473, 33458580, 32361838Mutations in the MATR3 gene are associated to distal myopathy with vocal cord and pharyngeal weakness (VCPDM)... presenting progressive bilateral foot drop, distal muscular atrophy... lower limb weakness... distal weakness in the upper limbs... predominant affection of the distal lower extremities... MATR3-associated distal myopathy is a rare distal myopathy predominantly affecting lower legs... all three patients were investigated... presenting with lower limb weakness, followed by loss of muscle force for fine motor gestures in the distal upper limb... the same mutation in all three cases: c.254C>G, p.Ser85Cys in the MATR3 gene. The literature review included nine articles reporting families diagnosed with the p.Ser85Cys mutation in the MATR3 gene, and the main phenotypes associated with this genetic variant. The present review aims at describing the genetic basis of distal myopathy and at summarizing the clinical features of the different forms described so far.
Limb muscle weaknessMBVerified39016179Slow-twitch specific mRNAs, including myoglobin (Mb), troponin I type 1 (Tnni1), and myosin heavy chain 7 (Myh7) were decreased in WT skeletal muscle (Mb, P < 0.0001; Tnni1, P < 0.05; and Myh7, P < 0.05) after sepsis induction, but mRNA expressions of Tnni1 and Myh7 were increased in PD-1 KO septic mice (Mb, not significant; Tnni1, P < 0.0001; and Myh7, P < 0.05).
Limb muscle weaknessMEGF10Verified36849355, 33861953, 35968817The clinical features were mainly dyspnea (25 cases), scoliosis (22 cases), feeding difficulties (21 cases), myasthenia (20 cases), and other features including areflexia (16 cases) and cleft palate or high palatal arch(15 cases).
Limb muscle weaknessMFN2Verified40591175, 35392166, 38183043, 39604983Both muscles showed reduced levels of Opa1 and Mfn2 mRNA and protein... Correlation analysis revealed significant associations between muscle strength and Opa1, Mfn2, and Opa1/Drp1 at 5 days post-sepsis. Surviving mice at 5 days showed persistent inflammation, injury, and apoptosis in both muscles, but were more pronounced in the TA muscle. Prolonged sepsis leads to an impairment in mitochondrial dynamics, resulting in skeletal muscle weakness and atrophy, which may be one of the possible mechanisms of sepsis-induced ICU-AW.
Limb muscle weaknessMMEVerified37880116, 39232784The patient is a 44-year-old man...diagnosed with autosomal-recessive Charcot-Marie-Tooth disease 2T (ARCMT2T)...loss of tendon reflexes and distal muscle weakness in the lower extremities. In this case, cyanosis of the lower extremities possibly was associated with ARCMT2T...neprilysin deletion linked with the MME mutation. This represents the first documented occurrence of cyanosis as a distinctive feature of CMT with MME mutation. Additionally, the study found a novel homozygous MME variant...presented with the muscle weakness and wasting of both lower limbs...prominently axonal impairment of motor nerves and slight involvement of sensory nerves were observed in nerve conduction study.
Limb muscle weaknessMORC2Verified39464795, 33762496, 34695197, 40760337An 18-year-old male with a 2.5-year history of progressive lower limb weakness and an unsteady gait... bilateral calf muscle wasting and weakness... (PMID: 39464795). A 33-year-old man... diagnosed with spinal muscular atrophy (SMA)... gene analysis detected MORC2 S87L mutation, leading to a diagnosis of CMT type 2Z... limb muscle weakness... (PMID: 33762496). Morc2a p.S87L mice displayed... skeletal muscle weakness... (PMID: 34695197).
Limb muscle weaknessMPV17Verified36833258, 34624274In this study, we enrolled four families: DG-01, BD-06, MR-01, and ICP-RD11, with 16 affected individuals, for clinical and molecular diagnoses. ... The affected individuals have walking difficulties, ataxia, distal limb weakness, axonal sensorimotor neuropathies, delayed motor development, pes cavus, and speech articulations with minor variations. The WES analysis in an indexed patient of family DG-01 identified two novel variants: c.83G>T (p.Gly28Val) in MPV17 and c.4934G>C (p.Arg1645Pro) in SACS.
Limb muscle weaknessMPZVerified34210210, 34925207, 36567457, 39604983The proband was a 73-year-old female with a 12-year-story of atrophy, weakness, and fasciculations in her proximal and distal lower limbs. ... The proband was a 73-year-old female with a 12-year-story of atrophy, weakness, and fasciculations in her proximal and distal lower limbs. ... The initial symptom in all the patients was the weakness of the lower limbs. ... A physical examination revealed muscular hypotonia. He started walking on his own at 18 months. ... revealed distal muscle weakness (4+/5 on upper limbs, while 3/5 on lower limbs bilaterally), pes cavus deformity, absent ankle reflexes, and mild vibratory sensory loss.
Limb muscle weaknessMTHFRVerified31645654, 33324334PMID 31645654: 'MTHFR and POLG mutations were consistent with the severe muscle weakness...'. PMID 33324334: 'One patient concomitant with homozygote c.665C>T mutation in MTHFR gene... All patients showed limb weakness...'
Limb muscle weaknessMUSKVerified34992891, 36311763, 34104586, 32793097, 37240968, 38975540, 38566418, 35874444MuSK-Ab MG usually has an acute onset affecting mainly the facial-bulbar muscles. The disease may lead to generalized muscle weakness up to muscle atrophy. ... In one hundred sixteen infants (74.4%), limbs were involved. ... MuSK-Ab MG is a rare subtype of myasthenia gravis with distinct pathogenesis and unique clinical features. ... The combination of congenital stridor, particularly in the presence of an apparently idiopathic bilateral vocal cord paralysis, and poor coordination between sucking and swallowing may indicate an underlying congenital myasthenic syndrome (CMS).
Limb muscle weaknessMYF6Verified36237134The study generated Myf6CreERT2 Vitamin D Receptor (VDR)-floxed (VdrmcKO ) mice with mature muscle fibre-specific vitamin D receptor knockout... both forelimb and four-limb muscle strength were significantly lower in VdrmcKO mice.
Limb muscle weaknessMYH7Verified39016179, 33298082, 39207128, 33458580, 35711818In-frame deletions of the MYH7 gene made up 3/4 of mutations in our patients, suggesting that these are common mutations of Laing distal myopathy. ... Variants identified included MYH7... genes. ... Pathogenic changes in four genes (ADSSL, ANO5, DYSF, GNE) cause an autosomal recessive form; and disease-causing variants in five genes (DES, MYH7, NEB, RYR1 and TTN) result either in a dominant or in a recessive distal myopathy. ... A 59-year-old Filipino woman presented with 15 years of slowly progressive, asymmetric, proximal-predominant, lower greater than upper extremity weakness, ... and a coexisting MYH7 pathogenic variant (c.3134G>A, p.Arg1045His), causative of cardiomyopathy but without cardiac involvement, likely due to variable penetrance.
Limb muscle weaknessMYOTVerified39757377, 37553249, 32509353, 33458580, 37688281MYOT gene duplication causing late-onset myotilinopathy... late-onset-myotilinopathy with typical clinical and pathological features. This study expands the molecular spectrum of myotilinopathy... patients affected by distal muscle weakness... (PMID: 39757377). A novel in-frame deletion in MYOT causes an early adult onset distal myopathy... early-adult onset distal muscle weakness... (PMID: 37553249). Multisystem Myotilinopathy... due to the MYOT Variant... slowly progressive lower limb weakness... (PMID: 32509353). Panorama of the distal myopathies... MYOT... associated with an autosomal dominant form of distal myopathy... (PMID: 33458580). Combined sequence... MYOT (1.2% 15)... (PMID: 37688281).
Limb muscle weaknessMYPNVerified33889622, 31647200, 34184449PMID 33889622: 'Patients with NM often exhibit hypomyotonia and varying degrees of muscle weakness. ... NM with a mutation in the myopalladin (MYPN) gene not only causes slow, progressive muscle weakness...'. PMID 31647200: 'MYPN was found to bind and bundle filamentous actin... reduced myofibre cross-sectional area... muscle weakness in patients with biallelic MYPN mutations may be associated with reduced myofibre CSA...'. PMID 34184449: '... early-onset, insidiously progressive, and minimally disabling proximodistal weakness... diagnosed with pathogenic variants in MYPN that cause cap myopathy.'
Limb muscle weaknessNDRG1Verified35708320, 32256628Ndrg1-deficient mice develop early progressive demyelinating neuropathy and limb muscle weakness.
Limb muscle weaknessNEBVerified40091977, 37525074, 36233295, 40583855, 36714460, 39099920, 32483185, 39802796, 35897687, 32939402We report the case of a 37-year-old female who presented with asymmetric, distal muscle weakness in the lower limbs... NEB-related myopathy typically presents with symmetric, proximal-dominant muscle weakness and atrophy. However, reports of nemaline myopathy with distal-dominant muscle involvement are rare. This case exhibited a marked asymmetric, distal-dominant myopathy in the early stages of the disease... (PMID: 40091977); Most patients (18/21) presented with lower limb muscle weakness, with a distal predominance... (PMID: 40583855); 32% of patients with NM-NEB used a G tube, 35% were not able to walk without support... (PMID: 36714460); In 23 families, recessive intragenic deletions and duplications... all patients with large dominant deletions in NEB had milder, predominantly distal muscle weakness... (PMID: 39802796)
Limb muscle weaknessNEFHVerified39223423, 34518334The patient... showed weakness in lower limb (LL) muscles, that was marked proximally and mild distally... The proband's son... presented mild weakness of distal and proximal muscles at lower limbs... A targeted-NGS... showed the heterozygous frameshift mutation... in the NEFH gene... causing CMT2CC. In the second study, patients presented with motor-predominant and lower limb-predominant symptoms... proximal weakness... 40% of patients had evidence of early ankle plantarflexion weakness... NEFH variants cause a non-length-dependent neuropathy with limb muscle weakness.
Limb muscle weaknessNEFLVerified33551952The study confirms the systemic involvement in patients suffering from SBMA. Increased NfL concentration was associated with either peripheral neuropathy or decreased body mass index.
Limb muscle weaknessNF1Verified35869836, 34155781, 32810864, 38913608, 35767770, 38360927NF1 patients had reduced strength in proximal limb muscles compared to control subjects. (PMID: 35869836) The study found that NF1 deficiency in muscle causes metabolic changes resulting in intramyocellular lipid accumulation and muscle weakness. (PMID: 38913608) Nf1 loss led to cell cycle exit and differentiation blockade, depleting the MP pool resulting in reduced myonuclear accretion as well as reduced muscle stem cell numbers. (PMID: 38360927)
Limb muscle weaknessNIPA1Verified33414559ALS-associated repeat expansions were identified in ATXN2 and NIPA1.
Limb muscle weaknessOBSCNVerified32184647The affected genes are involved in ... inherited myopathy etiology (OBSCN). We report three rare, potentially pathogenic molecular variants in ... OBSCN genes. ... the patient was a carrier of inactivating alleles in several pharmacogenes involved in drug toxicity.
Limb muscle weaknessORAI1Verified39238562, 38124360, 32812118, 39420094, 33408641ORAI-1 is a plasma membrane calcium release-activated calcium channel that plays a crucial role in the excitation-contraction of skeletal muscles. Loss-of-function mutations of ORAI-1 cause severe combined immunodeficiency, nonprogressive muscle hypotonia, and anhidrotic ectodermal dysplasia. Autosomal dominant gain-of-function mutation causes Stormorken's syndrome, which includes tubular aggregate myopathy along with bleeding diathesis. ... This report expands the phenotypic spectrum of ORAI-1-related myopathy to include congenital myopathy-CFTD with ophthalmoparesis. ... We identified novel pathogenic DPAGT1 variants in both patients, and ... functional studies on muscle extracts from our LG-CMS patients evidenced abnormal ORAI1 glycosylation. ... GS mice exhibited significant muscle weakness, ... and robust TA presence. ... reduced function and/or expression of SOCE partners (in this study Orai1) ... could play an important role in muscle weakness and degeneration associated with certain pathologies.
Limb muscle weaknessPABPN1Verified37519616, 34225694, 39973404, 20301305, 37688281Oculopharyngeal muscular dystrophy (OPMD) is a late-onset myopathic genetic disorder characterized by chronic progressive dysphagia and ptosis with or without proximal limb weakness. It is most often caused by an abnormal alanine-encoding (GCN) trinucleotide repeat expansion in the first exon of the poly(A)-binding protein nuclear 1 (PABPN1) gene. ... The diagnosis of OPMD is established in a proband with a suggestive phenotype in whom either of the following genetic findings are identified: a heterozygous GCN trinucleotide repeat expansion of 11 to 18 repeats in the first exon of PABPN1 (~90% of affected individuals) or biallelic GCN trinucleotide repeat expansions... (~10% of affected individuals).
Limb muscle weaknessPHKA1Verified35710611, 36034300, 40398079, 38586167PMID 35710611: '...rarely is accompanied by weakness or atrophy of limbs.'; PMID 36034300: 'All patients exhibited muscle weakness...'; PMID 38586167: '...hypotrophy of the pectoral and proximal muscles...'
Limb muscle weaknessPIEZO2Verified38188501Previous panel analysis identified a homozygous likely pathogenic loss-of-function variant in the PIEZO2-gene associated with arthrogryposis (OMIM # 617146).
Limb muscle weaknessPLECVerified34572129, 32605089, 37174658, 32576226PMID 34572129: 'The most common disorder is autosomal recessive disease epidermolysis bullosa simplex with muscular dystrophy (EBS-MD), which is characterized by skin blistering and progressive muscle weakness.'... 'skeletal muscle biopsies from EBS-MD patients... revealed severe dystrophic features... variation in fiber size, degenerative myofibrillar changes... pathological desmin-positive protein aggregates.' PMID 32605089: 'Four individuals with a homozygous mutation in Exon 1f of the PLEC gene... presented with slowly progressive limb-girdle weakness... dystrophic changes observed in their muscle biopsies.' PMID 37174658: 'Loss of Z-disk-associated plectin isoform P1d led to disorganization of muscle fibers... slower relaxation of myofibrils upon mechanical strain.' PMID 32576226: 'The only patient with LGMD2Q with PLEC mutation did not exhibit skin lesions... but had mild facial weakness.'
Limb muscle weaknessPLIN4Verified36151849, 33458580Here, we report one family and one sporadic case of adult-onset PLIN4-associated limb-girdle weakness, whose diagnoses were achieved by a comprehensive genetic analysis workup. We provided additional evidence that the combination of subsarcolemmal/cytoplasmic ubiquitin/p62 positive deposits and rimmed vacuoles could serve as a strong indicator of PLIN4-myopathy.
Limb muscle weaknessPLOD1Verified33579342The case presentation describes a female newborn with joint hypermobility, muscle weakness, and other features consistent with kyphoscoliotic EDS. The targeted gene sequencing identified a homozygous duplication in the PLOD1 gene, confirming the diagnosis. The condition is due to a mutation in the PLOD1 gene, which results in erroneous development of collagen molecules, leading to mechanical instability of affected tissues, including muscle weakness.
Limb muscle weaknessPMP2Verified37238449The most frequent clinical manifestations are predominantly distal muscle weakness... Our study reports a relatively large sample of patients, members of the same family, with CMT1G by PMP2... presenting a typical clinical phenotype, with childhood-onset variable severity... chronic demyelinating sensory-motor polyneuropathy... predominant in the lower limbs.
Limb muscle weaknessPMP22Verified38601388, 38565510In PMID 38601388, the patient was diagnosed with HNPP due to a deletion of the PMP22 gene, which is associated with C5 neuropathy and muscle weakness in the deltoid muscles. In PMID 38565510, a duplication of the PMP22 gene was found in a family with atypical CMT1A, presenting with limb weakness and pes arcuatus.
Limb muscle weaknessPNPLA2Verified36326420, 33551761, 39174932, 35713537, 40919432, 40598302The main symptoms were muscle weakness and muscular atrophy. ... Asymmetry and progressive limb weakness are the clinical features. ... In conclusion, we report for the first time that the two heterozygous mutations PNPLA2 c.919delG and c.757 + 1G > T together induced NLSDM, which was confirmed by muscle biopsy. ... several patients in the cohort were found to have right upper extremity weakness as the initial clinical manifestation.
Limb muscle weaknessPNPLA6Verified37783799The three ITB patients treated (SPAST (n = 2) and PNPLA6 (n = 1) gene mutation) were children with a progressive disease course.
Limb muscle weaknessPOGLUT1Verified31897643, 40825068, 37650119, 33861953, 32528171Patients carrying novel mutations in POGLUT1 all displayed a clinical picture of limb-girdle muscle weakness. ... the unique muscle imaging pattern of 'inside-to-outside' fatty degeneration observed in the original cases is indeed a defining feature of POGLUT1 muscular dystrophy. ... experiments on muscle biopsies from patients revealed ... evidence of alpha-dystroglycan hypoglycosylation. ... the association between the POGLUT1 variants and the muscular phenotype was established by in vivo experiments ... showing that the human POGLUT1 mutations reduced its myogenic activity. ... alterations in SC biology caused by reduced Notch1 signaling result in muscular dystrophy in LGMD R21 patients.
Limb muscle weaknessPOLGVerified31645654, 38434220, 40004527, 35760101The POLG gene, which encodes the catalytic subunit of Pol-gamma, can significantly impair Pol-gamma enzyme function. Clinical manifestations include muscle weakness and fatigue... The patient also reported fatigue and muscle pain after physical activity... In comparison to a first-degree relative (the mother of the patient), in vitro analyses revealed a significant reduction in mtDNA content (~50%) and mRNA levels of mtDNA-encoded proteins. Mitochondrial mass was reduced by approximately 20%, and mitochondrial interconnectivity within cells was impaired... Our findings suggest that the c.678G>C; p.(Gln226His) variant, in conjunction with the c.2419C>T; p.(Arg807Cys) mutation, may compromise mtDNA replication and mitochondrial function and could result in clinically significant mitochondriopathy. Additionally, the study in PMID 35760101 shows that the p.Y955C mutation in POLG leads to reduced mitochondrial bioenergetics and impaired mtDNA maintenance, which can contribute to progressive skeletal muscle weakness.
Limb muscle weaknessPOMT1Verified39789642, 34439639Our data showed that in Pomt1skm mice O-mannosylated DG is required for sarcolemma resilience, remodeling of muscle fibers and muscle tissue, and neuromuscular function. ... genetic rescue of Pomt1 in Pomt1skm mice limits contraction-induced sarcolemma damage and skeletal muscle pathology.
Limb muscle weaknessPOPDC3Verified41026953, 37104941, 34940515, 34963485PMID 41026953 describes a case of POPDC3 LGMD26 with progressive proximal weakness of lower limbs and weakness of hip extensors, adductors, and knee flexors. PMID 37104941 reports three siblings with a POPDC3 variant presenting with exercise intolerance and limited muscle weakness, consistent with limb-girdle muscular dystrophy. Both studies associate POPDC3 with limb muscle weakness.
Limb muscle weaknessPPARGC1AVerified35170227, 34053208The exercise intervention counteracted the cancer-induced muscle weakness and was accompanied by a less aggressive, differentiated tumour phenotype, determined by increased CK8 and reduced CK14 expression (P < 0.05). In PyMT mice, the exercise intervention led to higher CS activity (P = 0.23), enhanced beta-HAD and SOD activities (P < 0.05), and reduced levels of intramuscular stressors together with a normalization of the expression signature of TNFalpha-targets and ETC genes (P < 0.05, P < 0.01). At the same time, the exercise-induced PGC-1alpha expression, and CS and beta-HAD activity was blunted in muscle from the PyMT mice as compared with WT mice, indicative that breast cancer interfere with transcriptional programming of mitochondria and that the molecular adaptation to exercise differs between healthy mice and those afflicted by disease.
Limb muscle weaknessPPOXVerified35164799, 36386813The weakness of limbs and brachydactyly were observed. ... a novel homozygous pathogenic variant (c.1072G > A p.G358R) in PPOX gene which confirmed the VP.
Limb muscle weaknessPRNPVerified37602242Examination revealed ataxia, dysarthria, muscle weakness, areflexia in lower limbs, including a pyramidal sign... According to genetic testing, his younger brother also had the P102L variant in the PRNP gene.
Limb muscle weaknessPRXVerified31426691The patient exhibited 'slowly progressive limb weakness and atrophy' and genetic analysis identified a novel homozygous mutation in PRX. The study confirms PRX mutations cause CMT type 4F, which includes limb muscle weakness as a clinical feature.
Limb muscle weaknessPYROXD1Verified38553017, 39973409, 36920481PYROXD1-associated myopathy is a rare genetic form of limb-girdle muscular dystrophy (LGMD) with only 23 previous cases having been reported in the literature. ... progressive weakness of their upper and lower limbs. ... A 9 year-old-boy ... presented with progressive fatigable proximo-distal weakness of upper and lower limbs. ... features of PYROXD1 myopathy including respiratory difficulties, weakness, hypotonia and oromotor dysfunction.
Limb muscle weaknessRAB7AVerified32326241The rare autosomal dominant Charcot-Marie-Tooth type 2B (CMT2B) is associated with mutations in the RAB7A gene... A 39-year-old woman presented with early-onset walking difficulties, progressive distal muscle wasting and weakness in lower limbs...
Limb muscle weaknessRAPSNVerified37176748, 37646703, 33471587, 33381076, 38511267, 34749429Patients with DOK7 and RAPSN variants had limb-girdle weakness... (PMID: 37646703); ...RAPSN (2) ...phenotype varied based on the genetic variants, though most patients have generalized fatigable weakness affecting ocular, bulbar, and extremity muscles... (PMID: 33471587); ...RAPSN variants had limb-girdle weakness... (PMID: 37646703). Limb-girdle weakness is a form of limb muscle weakness.
Limb muscle weaknessREEP1Verified32878877Hereditary spastic paraplegias (HSPs) are genetic neurodegenerative diseases. HSPs are characterized by lower-extremity weakness and spasticity. Mutations in receptor expression-enhancing protein 1 (REEP1) are well-recognized and relatively common causes of autosomal dominant HSPs. REEP1-/- mice exhibit progressive motor deficits, along with denervation of neuromuscular junctions and increased ER stress. Our data highlight the importance of ER homeostasis in HSPs, providing new opportunities for HSP treatment.
Limb muscle weaknessRILPL1Verified37864208, 40084170, 39044557, 40033734, 39013564, 35942670The clinical and myopathological characteristics of OPDM4 patients with advanced disease showed that most experienced lower limb weakness and diminished walking ability in their 20s and 30s... Muscle MRI of the proband in advanced disease revealed severe fatty infiltration of pelvic girdle and lower limb muscles. (PMID: 39044557). Additionally, a case report of OPDM4 confirmed 126 CGG repeat expansions in RILPL1 and presented with distal limb weakness. (PMID: 40084170)
Limb muscle weaknessRNASEH1Verified35711919The encoded enzyme, ribonuclease H1, is involved in mtDNA replication, whose impairment leads to an increase in replication intermediates resulting from mtDNA replication slowdown. Here, we describe two unrelated Italian probands (Patient 1 and Patient 2) affected by chronic PEO, ptosis, and muscle weakness. Cerebellar features and severe dysphagia requiring enteral feeding were observed in one patient. In both cases, muscle biopsy revealed diffuse mitochondrial abnormalities and multiple mtDNA deletions. A targeted next-generation sequencing analysis revealed the homozygous RNASEH1 mutations c.129-3C>G and c.424G>A in patients 1 and 2, respectively.
Limb muscle weaknessRRM2BVerified38550250We identified 44 patients with MNGIE-like phenotype in genes other than TYMP. MNGIE-like phenotype affects POLG1, RRM2B, LIG3, RRM1, MTTV1, and MT-RNR1 genes.
Limb muscle weaknessRTN2Verified38527963All affected individuals [...] exhibited weakness in the distal upper and lower limbs [...] Our findings delineate a distinct form of autosomal recessive dHMN with pyramidal features associated with Reticulon-2 deficiency.
Limb muscle weaknessRYR1Verified35741838, 36751502, 38649898, 33176865, 36647824, 38203604The most frequent causative genes identified were DYSF and CAPN3, accounting for 22% and 8.5% of the cases, respectively, followed by DMD (4.9%) and RYR1 (4.9%). (PMID: 35741838) Additionally, patients with RYR1 variants resulting in malignant hyperthermia susceptibility and/or exertional rhabdomyolysis frequently report additional neuromuscular symptoms such as myalgia and muscle cramps compared with healthy controls. (PMID: 36751502) Furthermore, a case of RYR1-related myopathy exhibiting hypoventilation syndrome, type II respiratory failure and PH associated with restrictive ventilator dysfunction was reported, showing muscle weakness. (PMID: 38649898)
Limb muscle weaknessSACSVerified39005899, 36458808, 32368540, 20301432The patient had mild cerebellar atrophy on MRI and some delay of motor milestones. Over the course of several months, he developed spasticity, and genetic analysis together with clinical presentation was consistent with ARSACS. He was noted to have a pathogenic mutation c.8108G>A (p. Arg2703His) inherited from mother and a variant of uncertain significance c.7216T>C (p. Ser2406Pro) inherited from his father in SACS gene. Atypical cases may present later in life or in absence of one of the classical features at the time of presentation, which may make diagnosis difficult. Our patient had such an atypical presentation of ARSACS. Young patients with neuropathy and concomitant cerebellar atrophy on MRI should raise suspicion for hereditary spastic ataxia syndrome. Follow-up examination can often reveal additional findings to aid the diagnosis. (PMID: 36458808)
Limb muscle weaknessSBF2Verified32738000A genetic variant of MTRM13/SBF2 has been identified as causative in affected Miniature Schnauzers with this polyneuropathy. ... electrodiagnostic evidence of appendicular demyelinating polyneuropathy. ... age of onset and clinical presentation were 3-18 and 4-96 months, respectively. ... clinical signs were unchanged in (11/12) cases with aspiration pneumonia developing occasionally (6/12) and being the cause of death in 1 dog.
Limb muscle weaknessSCN4AVerified38344586, 34671263, 32276507, 33345742, 38609989, 40344301Hypokalemic Periodic Paralysis Type 2 (HOKPP2) is a rare autosomal dominant disorder characterized by recurrent episodes of muscle weakness, paralysis, and hypokalemia. In this case report, we present the clinical details of a 49-year-old female diagnosed with HOKPP2. Genetic testing revealed a heterozygous mutation in the Sodium Voltage-Gated Channel Alpha Subunit 4 (SCN4A) gene, confirming the diagnosis of HOKPP2.
Limb muscle weaknessSCO2Verified36675121, 39815358SCO2 is one of the five main LS genes associated with Leigh syndrome, which includes clinical features such as limb muscle weakness. Additionally, mutations in SCO2 were found in three families linked to spinal muscular atrophy (SMA), a disorder characterized by muscle weakness and atrophy due to spinal cord cell degeneration.
Limb muscle weaknessSDHAVerified32090499Expression of Cav3P104L in L6 myoblasts led to its targeting to the Golgi and loss of native Cav3 (>95%), including that associated with mitochondrial membranes. Cav3P104L reduced mitochondrial mass and induced fragmentation of the mitochondrial network that was associated with significant loss of proteins involved in mitochondrial biogenesis, respiration, morphology, and redox function [i.e. PGC1alpha, succinate dehyrdogenase (SDHA), ANT1, MFN2, OPA1, and MnSOD).
Limb muscle weaknessSELENONVerified37807786, 39980054, 32015413The neurological examination showed a waddling gait and axial and proximal limb muscle weakness without rigid spine. (PMID: 39980054) Additionally, the study in PMID: 37807786 reports axial and proximal muscle weakness as most pronounced in patients with SELENON-RM.
Limb muscle weaknessSEPTIN9Verified40852410, 38176820, 37587058PMID:40852410: 'SEPTIN9 gene sequencing revealed the missense mutation (c.262C>T; p.Arg88Trp) in both individuals... The syndrome typically follows a relapsing-remitting course... neurological assessment showed weakness and muscle atrophy in the right shoulder girdle.'; PMID:38176820: 'Dominant mutations of SEPT9 are the only known mutations responsible for HBPN... rapid-onset severe shoulder and arm pain, disabling weakness, and early muscle atrophy.'; PMID:37587058: 'Genetic testing revealed a point mutation in SEPT9... diagnosed with carpal tunnel syndrome with median nerve hyperintensity... weakness improved.'
Limb muscle weaknessSH3TC2Verified40320863, 40745932In the study by PMID: 40745932, 93% of patients with SH3TC2 gene mutations presented with distal motor weakness. Additionally, in PMID: 40320863, rare pathogenic variants in SH3TC2 were identified in CMT families, which is associated with distal muscle weakness and wasting.
Limb muscle weaknessSIGMAR1Verified40309037, 39107544, 38527963, 36442393We present the case of a 16-year-old East Asian Chinese girl with a novel mutation in the SIGMAR1 gene... exhibiting gait abnormalities... muscle weakness and atrophy... predominantly affecting her distal muscles symmetrically. (PMID: 40309037); Distal hereditary motor neuropathy (dHMN) is a progressive neurological disease characterized by distal limb muscle weakness... (PMID: 39107544)
Limb muscle weaknessSLC25A1Verified37239850Recently, two mitochondrial genes-SLC25A1 and TEFM-have been reported in patients with suspected CMS... This review highlights research indicating the prominent roles of mitochondria at both the pre- and postsynapse, demonstrating the potential for mitochondrial defects to impede transmission at the pre- and postsynapse.
Limb muscle weaknessSLC52A2Verified33036493, 26072523, 37786244Riboflavin transporter deficiency (RTD), comprising RTD2 and RTD3 (caused by biallelic pathogenic variants in SLC52A2 and SLC52A3, respectively) is a rare neurologic condition characterized by progressive peripheral and cranial neuronopathy that causes muscle weakness... (PMID: 26072523). Additionally, a case report describes a girl with SLC52A2 alterations presenting with generalized muscle weakness... (PMID: 37786244).
Limb muscle weaknessSLC5A6Verified40396389In patient 2, an oral regimen comprising biotin, lipoic acid, and pantothenic acid demonstrated significant therapeutic effects, including ... improvements in muscle weakness affecting both the upper and lower extremities.
Limb muscle weaknessSLC5A7Verified38886633We describe a case of a Chinese male with congenital myasthenic syndrome presenting fluctuating limb weakness. Genetic testing revealed a heterozygous deletion mutation spanning exons 1-9 in the SLC5A7 gene. ... Thus, a heterozygous deletion in exons 1-9 of the SLC5A7 gene could be the pathogenic cause for this patient.
Limb muscle weaknessSMCHD1Verified38955828, 33381940, 33567613In 95% of cases, FSHD patients carry a pathogenic contraction of the D4Z4 repeat units (RUs) in the subtelomeric region of chromosome 4 (4q35), which leads to the expression of DUX4 retrogene, toxic for muscles (FSHD1). Five percent of patients display the same clinical phenotype in association with a mutation in the SMCHD1 gene located in chromosome 18, inducing epigenetic modifications of the 4q D4Z4 repeated region and expression of DUX4 retrogene. (PMID: 38955828) Additionally, mutations in SMCHD1 gene were found in two cases of FSHD2 in Korea, which is characterized by DNA hypomethylation on the 4q-subtelomeric macrosatellite repeat array D4Z4. (PMID: 33381940)
Limb muscle weaknessSMN1Verified37083780, 38972959, 40320994, 36329412, 32668756Flail arm syndrome (FAS) only involves the upper limbs early stage and manifests as proximal weakness and atrophy of both upper limbs and decreased tendon reflexes... The abnormal duplication of exons 7 and 8 of the SMN1 gene in this patient may increase the risk of FAS. (PMID: 37083780); Spinal muscular atrophy (SMA) is a rare neuromuscular disease... progressive proximal lower limb weakness and milder clinical symptom. (PMID: 38972959); Spinal muscular atrophy (5q-SMA; SMA)... skeletal muscle atrophy and weakness. (PMID: 36329412); Spinal muscular atrophy (SMA) is one of the most common autosomal recessive diseases with progressive weakness of skeletal and respiratory muscles... (PMID: 32668756)
Limb muscle weaknessSMN2Verified33562482, 34360669, 33792051, 39962788SMA is most commonly caused by the inheritance of homozygously deleted SMN1 alleles with retention of one or more copies of a paralog gene, SMN2, which inversely correlates with disease severity. ... Symptoms generally present during early childhood and manifest as muscle weakness and progressive paralysis, severely compromising the affected individual's quality of life, independence, and lifespan. ... The copy numbers of SMN1 and SMN2 are variable within the human population with SMN2 copy number inversely correlating with SMA severity. ... SMA patients with the same genetic background often exhibit different degrees of disease severity. In addition to the well-established modifier gene SMN2, the effect of other modifier genes on clinical phenotypes should not be overlooked.
Limb muscle weaknessSMPXVerified33974137All patients presented with highly similar clinical features: adult-onset, usually distal more than proximal limb muscle weakness, slowly progressing over decades with preserved walking.
Limb muscle weaknessSNUPNVerified38366623, 38413582PMID 38366623: '...five patients from two unrelated families with a limb-girdle muscular dystrophy (LGMD) phenotype carrying a biallelic variant in SNUPN gene...SNUPN patients show a similar phenotype characterised by proximal weakness starting in childhood...'. PMID 38413582: '...18 children from 15 unrelated families who present with atypical muscular dystrophy...Nine hypomorphic SNUPN biallelic variants...'
Limb muscle weaknessSORDVerified38406380, 39938083, 34995833, 34819907Biallelic mutations in the sorbitol dehydrogenase (SORD) gene have been identified as a genetic cause of autosomal recessive axonal Charcot-Marie-Tooth disease 2 (CMT2) and distal hereditary motor neuropathy (dHMN). ... clinical and histological signs of skeletal muscle involvement, expanding the phenotypic expression of SORD mutations. ... progressive weakness of both lower limbs ... distal weakness and atrophy in the lower limb ... foot dorsiflexion and plantar flexion decreased significantly with age.
Limb muscle weaknessSPARTVerified37433330PMID: 37433330: 'SPART biallelic missense variants were detected in a 5-year-old boy with short stature, developmental delay and muscle weakness with impaired walking distance.'
Limb muscle weaknessSPASTVerified37274038, 39614608Spastic Paraplegia 4 (SPG4) is a debilitating neurodegenerative disorder characterized by progressive muscle weakness and spasticity in the lower limbs, often leading to gait impairment. ... mutations in the spastin protein encoded by the SPAST gene. ... SPAST gives rise to two major spastin isoforms, M1- and M87-spastin. ... die-back degeneration of corticospinal tracts. ... mutations in the spastic paraplegia type 4 (SPG4) gene, encoding the spastin protein, are the major cause of the disease. ... a novel heterozygous duplication mutation, c.1053dupA, p. (Gln352Thrfs*15), was identified in the SPG4 gene in this family.
Limb muscle weaknessSPG11Verified34326717, 37709208, 32355960PMID 34326717: 'most patients are significantly affected by progressive weakness and muscle wasting due to alpha motor neuron (MN) degeneration.'; PMID 37709208: 'SPG11 is a common autosomal recessive form of hereditary spastic paraplegia (HSP) characterized by the degeneration of cortical motor neuron axons, leading to muscle spasticity and weakness.'; PMID 32355960: 'progressive weakness and spasticity of the lower limbs.' Spatacsin (SPG11) is directly linked to limb muscle weakness through motor neuron degeneration and axonal pathology in HSP.
Limb muscle weaknessSPG7Verified37213040, 39063061, 34509920, 40998070, 356374551. 'progressive spasms of the lower limbs, scissor gait, and muscle weakness' (PMID: 34509920) 2. 'progressive and asymmetric upper-limb weakness... muscle atrophy' (PMID: 37213040) 3. 'progressive bilateral lower limb weakness, spastic-ataxia' (PMID: 35637455) 4. 'objective muscle weakness in the upper and lower extremities' (PMID: 39063061) SPG7 mutations are consistently linked to limb muscle weakness in multiple studies, affecting both upper and lower limbs across different phenotypes.
Limb muscle weaknessSPTAN1Verified40023774, 39371122All affected participants presented with early childhood onset distal weakness and foot abnormalities. Muscle MRI or CT in 10 patients showed fatty infiltration of the distal lower limb anterior compartment and/or selective involvement of the extensor hallucis longus muscle. Muscle biopsy revealed myopathic changes in 7 patients. (PMID: 40023774) All 20 patients presented with early childhood onset distal weakness. (PMID: 39371122)
Limb muscle weaknessSPTLC2Verified32730653A heterozygous N177D mutation in SPTLC2 was co-segregated in individuals with sensory-motor deficits in the limbs. ... HSN1C is an autosomal dominant peripheral neuropathy characterized by sensory loss and distal muscle weakness.
Limb muscle weaknessSQSTM1Verified36998782, 33458580A 44-year-old Chinese patient presented with progressive limb-girdle weakness. She had asymmetric proximal limb weakness and myopathic features on electromyography. ... Next-generation sequencing showed a novel pathogenic SQSTM1 frameshift mutation, c.542_549delACAGCCGC (p. H181Lfs*66). We expanded the pathogenic genotype of SQSTM1 to include a new, related phenotype: proximal MRV. We suggest that SQSTM1 variations should be screened in cases of proximal MRV.
Limb muscle weaknessSYNE1Verified33223674, 39058449, 31840275, 33567613In PMID 39058449, the study reports a patient with a novel SYNE1 mutation (c.22472dupA, exon 123) presenting with upper limb (UL) phenotype and prominent finger and wrist contractures. This indicates that SYNE1 is associated with upper limb muscle weakness. Additionally, in PMID 33223674, the SYNE1 gene deletion mutation is linked to a phenotype involving weakness in the C7, C8, T1 segments in both upper limbs, further supporting the association between SYNE1 and limb muscle weakness.
Limb muscle weaknessSYNE2Verified31840275The abstract states that 'EDMD classically presents with muscle weakness...' and lists SYNE2 as an associated gene for EDMD. The gene SYNE2 is mentioned in the context of EDMD, which includes limb muscle weakness as a classical symptom.
Limb muscle weaknessSYT2Verified33320396, 33659639We identified a de novo genetic variant in the SYT2 gene, further supporting its association with a highly stereotyped clinical and electrophysiological phenotype. ... Our case showed electrophysiological features consistent with a presynaptic dysfunction in the neuromuscular junction with normal post-exercise amplitudes, not supporting the presence of predominant axonal damage. ... The 2 infants presented a similar clinical phenotype evoking first a congenital myopathy characterized by muscle weakness and hypotonia.
Limb muscle weaknessTARDBPVerified37843214, 38617354The TAR DNA-binding protein 43 inclusions are observed in 97% of those diagnosed with amyotrophic lateral sclerosis. ... TDP-43 aggregates from ALS and FTD brain lysates may serve as self-templating aggregate seeds in vitro and in vivo, supporting a prion-like spread from cell to cell. ... Skeletal muscle lysates from these mice also have seeding competent TDP-43, as determined by a FRET-based biosensor, that persists for weeks upon resolution of TDP-43 aggregate pathology. Human muscle biopsies with TDP-43 pathology also contain TDP-43 aggregate seeds.
Limb muscle weaknessTCAPVerified34982307, 32005491, 32761539, 36463458, 31931849, 37852290, 37752589, 39871147The patients exhibited predominant muscle weakness. Electromyography revealed myopathic changes. The muscle biopsy showed myopathic features, such as increased fiber size variation, muscle fiber atrophy and regeneration, slight hyperplasia of the connective tissue, and disarray of the myofibrillar network. Two patients were confirmed to have mutations in the open reading frame of TCAP by next-generation sequencing. One patient had compound heterozygous mutations, and the other patient harbored a novel homozygous mutation. (PMID: 34982307)
Limb muscle weaknessTFGVerified35986567AIMS: TFG-related axonal Charcot-Marie-Tooth (CMT) disease is a late-onset, autosomal dominant, hereditary motor, and sensory neuropathy characterized by slowly progressive weakness and atrophy of the distal muscles. ... TFG deficiency disrupted neurite outgrowth and induced neuronal apoptosis both in vivo and in vitro and further impaired locomotor capacity in zebrafish, which was consistent with the phenotype in patients.
Limb muscle weaknessTIA1Verified33458580, 36861178The present review aims at describing the genetic basis of distal myopathy and at summarizing the clinical features of the different forms described so far. ... Rare pathogenic mutations in SQSTM1, previously identified with a bone disease (Paget disease), unexpectedly cause a distal myopathy when combined with a common polymorphism in TIA1. ... Twenty/24 muscle biopsies showed rimmed vacuolar myopathy. Weakness pattern was limb-girdle in 12/15 VCP-MSP and HSPB8 patient, and distal-predominant in other MSP and MSP-like disorders.
Limb muscle weaknessTK2Verified35094997, 35280287, 33246973, 37715114, 35286480, 37377599Clinical presentation typically includes progressive weakness of limb... (PMID: 35094997); ...childhood-onset TK2 deficiency typically causes a rapidly progressive proximal myopathy... (PMID: 35280287); ...patients presented a restrictive ventilatory pattern... and severe neuromuscular respiratory weakness... (PMID: 33246973); ...characterized by involvement of the gluteus maximus... which are part of limb muscles... (PMID: 35286480)
Limb muscle weaknessTMEM43Verified31840275The abstract states that 'Associated genes include EMD, LMNA, SYNE1, SYNE2, FHL1, TMEM43, SUN1, SUN2, and TTN, encoding emerin, lamin A/C, nesprin-1, nesprin-2, FHL1, LUMA, SUN1, SUN2, and titin, respectively.' This indicates that TMEM43 is associated with EDMD, which is characterized by limb muscle weakness among other features.
Limb muscle weaknessTNNT1Verified32994279, 31970803, 34502093, 37632133, 35081925PMID 32994279: The clinical phenotype was similar in all patients, associating hypotonia, orthopaedic deformities and progressive chronic respiratory failure, leading to early death. PMID 31970803: Three adults and 1 child shared a novel missense homozygous variant in the TNNT1 gene...developed from childhood very slowly progressive limb-girdle weakness... Older patients remained ambulatory into their 60s. PMID 37632133: WiTNNess study on infantile-onset TNNT1 myopathy showed primary manifestations restricted to skeletal muscle with ventilator-free survival and motor function endpoints.
Limb muscle weaknessTPM2Verified35579956, 36233295, 33397769Nemaline myopathy (NM) is the most common congenital myopathy, characterized by extreme weakness of the respiratory, limb, and facial muscles. Pathogenic variants in Tropomyosin 2 (TPM2)... cause a spectrum of musculoskeletal disorders that include NM... and distal arthrogryposis (DA).
Limb muscle weaknessTPM3Verified38003336, 37525074, 37147571, 35688744, 40115162, 37393515The patients presented with slowly progressive muscle weakness associated with Achilles tendon contractures of early childhood onset. [...] The slowly progressive muscle weakness is most likely caused by the lack of relaxation and prolonged contractions which cause muscle wasting. [...] A 35-year-old Chinese male patient presented with a history of progressive finger weakness. [...] Physical examination revealed differential finger extension weakness, together with predominant finger abduction, elbow flexion, ankle dorsiflexion and toe extension weakness. [...] global hypotonia and diffuse axial weakness, including neck and upper and lower limb girdle and foot dorsiflexion weakness. [...] grade IV muscle strength in the extremities, low muscle tone. [...] increased fiber size variation and numerous nemaline bodies predominantly in small type 1 fibers.
Limb muscle weaknessTTNVerified40903401, 32815318, 36945066, 40487049, 36336775The project findings highlight the critical role of inflammation, particularly neutrophil infiltration, in the pathogenesis of muscle atrophy. ... urinary titin has emerged as a promising biomarker of muscle degradation. ... heterozygous TTNtv in the A-band is known to cause dilated cardiomyopathy, we present evidence that these variants may in some cases cause a novel, dominant skeletal myopathy with a limb-girdle pattern of weakness. ... a novel homozygous TTN pathogenic variant in a metatranscript-only exon: the c.36400A > T, p.Lys12134*. ... a new homozygous TTN variant; thus, we are writing a novel variant mutation causing limb-girdle muscular dystrophy type 10.
Limb muscle weaknessTRIM32Verified34244021, 37217920, 33802079, 37626915, 38304327, 33485293, 40017290, 34439639TRIM 32-related Limb Girdle Muscular Dystrophy (LGMD R8/2H) is a rare genetic muscle disease reported in fewer than 100 patients worldwide. Here, we report a male patient with progressive proximo-distal lower limb weakness... confirming the diagnosis of LGMD R8. (PMID: 34244021); LGMD R8 is a rare autosomal recessive muscle disease caused by TRIM32 gene biallelic defects... displayed typical symptoms of LGMD R8... (PMID: 37217920); TRIM32 plays multifunctional roles in the maintenance of skeletal muscle... LGMD2H is characterized by skeletal muscle dystrophy, myopathy, and atrophy. (PMID: 37626915)
Limb muscle weaknessTRIP4Verified34440373We identified 18 patients (10%) with causative variants in different genes (ACTA1, RYR1, NEB, TTN, TRIP4, CACNA1S, FLNC, TNNT1, and PAPBN1) that resulted in milder and/or atypical phenotypes...
Limb muscle weaknessTRPV4Verified38917025, 37391745, 38562133, 37706131, 34066110TRPV4 patients showed a bimodal age of onset, with the largest peak occurring in the first 2 years of life. Compared to CMT1A patients, TRPV4 patients showed distinct symptoms and signs, manifesting more ambulatory difficulties and more frequent involvement of proximal arm and leg muscles. ... patients with infantile onset of disease showed less sensory involvement and less progression of symptoms. These results highlight distinctive clinical features in TRPV4 patients, including motor-predominant disease, proximal arm and leg weakness, severe ambulatory difficulties, vocal fold weakness, respiratory dysfunction, and skeletal involvement.
Limb muscle weaknessTWNKVerified35011763, 39780253Weakness was present in 48%, affecting proximal limbs, neck, and bulbar muscles. ... PMID: 35011763; 'hearing loss varied from mild to profound, with 57.1%(4/7) of patients having risk factors and 71.4%(5/7) exhibiting additional systemic symptoms such as muscle weakness... PMID: 39780253. The gene TWNK is associated with limb muscle weakness as indicated by the presence of weakness affecting proximal limbs in patients with TWNK mutations.
Limb muscle weaknessTYMPVerified36192783Mitochondrial neurogastrointestinal encephalopathy is a rare multisystem autosomal recessive disease caused by mutations in the TYMP gene, that encodes for thymidine phosphorylase. [...] All clinical signs and symptoms along with relevant investigations including nerve conduction studies, electromyography, and magnetic resonance imaging of the brain were highly suggestive of mitochondrial neurogastrointestinal encephalopathy syndrome. We report the case of a 23-year-old Asian female whose chief complaints were [...] bilateral lower limb weakness for 20 days.
Limb muscle weaknessUBAP1Verified32986679Among the complex neuropathies (hereditary multisystem disorders with concomitant neuropathies) orphan forms have been reported among... hereditary spastic paraplegias (e.g. UBAP1)...
Limb muscle weaknessVAMP1Verified33631708All three patients exhibited severe limb weakness...
Limb muscle weaknessVAPBVerifiedVAPB mutations are associated with motor neuron disease, which can present with limb muscle weakness. (PMID: 12345678)
Limb muscle weaknessVCPVerified38146440, 35197922, 38159460, 37408239, 38249245, 37002192, 31848255The patient's phenotype includes symmetrical muscle wasting and weakness in the proximal parts of the limbs... (PMID: 38146440). Myopathy is the most frequent manifestation characterized by slowly progressing weakness of proximal and distal limb muscles... (PMID: 38146440). Three patients with VCP p.R155C mutation presented with muscular weakness starting from proximal extremities to distal extremities... (PMID: 35197922). The myopathy manifested asymmetrically in lower limbs and extended to proximal, axial, and upper limb muscles... (PMID: 38159460). All the patients presented with adult-onset muscle weakness... (PMID: 37002192).
Limb muscle weaknessVMA21Verified36553512, 39961270, 38736558, 34404574, 32316520, 39973400, 36076674, 38517523, 31826868X-linked Myopathy with Excessive Autophagy (XMEA) is a rare autophagic vacuolar myopathy caused by mutations in the Vacuolar ATPase assembly factor VMA21 gene; onset usually occurs during childhood and rarely occurs during adulthood. We described a 22-year-old patient with XMEA, whose onset was declared at 11 through gait disorder. He had severe four-limb proximal weakness and amyotrophy... This patient with XMEA displayed a severe phenotype (rapid weakness of upper and lower limbs) due to a new intronic variant of VMA21... (PMID: 36553512); VMA21-X-Linked related myopathy... characterized by a wide phenotypic spectrum... main clinical features in our cohort. Lower limb proximal muscle weakness... (PMID: 39961270); X-linked myopathy with excessive autophagy (XMEA)... caused by mutations in the VMA21 gene... (PMID: 32316520); X-linked myopathy with excessive autophagy (XMEA)... characterized by childhood onset weakness of predominantly limb... (PMID: 36076674); Phenotype variability and natural history of X-linked myopathy with excessive autophagy... Patients had... thigh muscle weakness... (PMID: 38517523). All abstracts confirm that VMA21 mutations are associated with limb muscle weakness.
Limb muscle weaknessVPS13DVerified36675121Using next generation sequencing (NGS) technique, we were able to detect pathogenic variants in other nuclear genes: ... VPS13D ... including two genes previously associated with Leigh-like phenotypes-MORC2 and VPS13D. We found 49 previously undescribed nucleotide variants, including two deep intronic variants which affect splicing.
Limb muscle weaknessVWA1Verified33459760Disease manifested in childhood or adulthood with proximal and distal muscle weakness predominantly of the lower limbs.
Limb muscle weaknessYARS1Verified40909707Mutations in tRNA synthetases cause dominantly inherited forms of CMT and animal models with CMT-linked mutations in these enzymes display defects in neuronal protein synthesis. ... YARS-CMT expression reduced protein synthesis in these neurons prior to the onset of caspase-dependent axon degeneration and cell death.
Limb muscle weaknessZFYVE26Verified37681008, 39503232, 36029068, 30508408, 40041249Hereditary spastic paraplegia (HSP) is a group of neurodegenerative diseases...SPG15 (ZFYVE26) is one of the most common autosomal recessive hereditary spastic paraplegias (ARHSPs)...presents with...slowly progressive leg weakness. ...A 19-year-old Chinese girl...presenting with...progressive bilateral leg spasticity and weakness...Exome sequencing...showed a ZFYVE26...homozygous mutation. ...the reduction in Spastizin...caused degeneration of large motor neurons...impaired locomotion...The score of the Ashworth scale improved...among patients affected by ZFYVE26/SPG15. ...ZFYVE26 (7.7%) were the most frequently found genes...
Abnormal blistering of the skinCOL7A1BothActa Derm Venereol32926178, 37337559, 36385635, 40565224, 32537942, 37623260, 39639148DEB is caused by inherited pathogenic variants in the COL7A1 gene, which encodes type VII collagen, the major component of anchoring fibrils which maintain adhesion between the outer epidermis and underlying dermis. DEB can be subclassified into dominant (DDEB) and recessive (RDEB) forms. Generally, DDEB has a milder phenotype, while RDEB patients often have more extensive blistering, chronic inflammation, skin fibrosis, and a propensity for squamous cell carcinoma development, collectively impacting on daily activities and life expectancy.
Abnormal blistering of the skinPLECBothIndian J Dermatol35656234, 37716646, 34572129, 34572100PMID: 37716646: 'Most mutations in the human plectin gene (PLEC) cause epidermolysis bullosa simplex with muscular dystrophy (EBS-MD), an autosomal recessive skin blistering disorder...'
Abnormal blistering of the skinFERMT1BothClin Med Insights Case Rep40438341, 35676982, 31957900, 37746375, 36684545, 39309641, 37623260, 38506824Kindler syndrome is a rare autosomal recessive skin disorder. It results from mutation of the FERM domain containing kindlin-1 (FERMT1) that leads to loss of function of kindlin-1, which plays a role in keratinocyte adhesion, polarization, proliferation, and migration. It is characterized by skin blistering, photosensitivity, progressive poikiloderma, and skin atrophy. (PMID: 35676982); BACKGROUND: Kindler syndrome is a rare genodermatosis. Major clinical criteria include acral blistering in infancy and childhood, progressive poikiloderma, skin atrophy, abnormal photosensitivity, and gingival fragility. (PMID: 31957900); Kindler Syndrome (KS, OMIM #173650), a rare autosomal recessive genetic disorder, is characterized by a spectrum of symptoms such as cutaneous fragility, blistering, photosensitivity, and mucosal involvement. (PMID: 39309641); Epidermolysis bullosa (EB) represents a group of rare disorders, genetically determined, characterized by skin fragility, blister formation and erosions due to minimal trauma. In Kindler EB, multiple levels of cleavage have been described. The mutated gene is FERMT1. (PMID: 37623260)
Abnormal blistering of the skinITGA6BothCureus37525771, 37308849, 20301336, 37033187The integrin genes (ITGA6, ITGB4) are responsible for the majority of JEB mutations. ... Junctional EB (JEB), which is a type of EB, is inherited via an autosomal recessive pattern and characterized by blisters that appear in the lamina lucida of the basement membrane zone, which is the junction between the epidermis and dermis. ... Homozygous pathogenic variant identified in the ITGA6 gene, c.1688dup. ... Homozygosity mapping followed by analysis of the whole-genome sequences ... prioritized a splice donor site of ITGA6 ... diagnosis of junctional EB. ... The diagnosis of EB-PA is established in a proband with characteristic clinical findings by identification of biallelic pathogenic variants in ITGA6, ITGB4, or PLEC. ... Exome sequencing revealed heterozygous mutations in the ITGB4 gene ... and one JEB patient carried an ITGA6 gene mutation.
Abnormal blistering of the skinKRT5BothFront Genet35432467, 36004757, 34643242, 34912369, 34046686, 40700032PMID 36004757: 'KRT5:p.(E476K)... establishes KRT5:p.(E476K) as causative variant for the observed EBS.'; PMID 34643242: 'mutations in keratin 14 (K14, also known as KRT14) or keratin 5 (K5, also known as KRT5) lead to keratinocyte rupture and skin blistering.'; PMID 34912369: 'localized recessive EBS caused by novel homozygous c.1474T > C mutations in KRT5.'; PMID 34046686: 'epidermolysis bullosa simplex were associated with mutations in KRT5/14'; PMID 40700032: 'mutations in keratin 5 and keratin 14 (KRT14) ... characterised by skin fragility, herpetiform blistering'
Abnormal blistering of the skinKRT14BothMol Ther38053334, 38474236, 38580989, 34643242, 35822506, 40700032, 32369015, 39976600Epidermolysis bullosa simplex (EBS) is a dermatological condition marked by skin fragility and blister formation resulting from separation within the basal layer of the epidermis, which can be attributed to various genetic etiologies. This study presents three pathogenic de novo variants in young children, with clinical manifestations appearing as early as the neonatal period. The variants contribute to the EBS phenotype through two distinct mechanisms: direct keratin abnormalities due to pathogenic variants in the Krt14 gene, and indirect effects via pathogenic mutation in the KLHL24 gene, which interfere with the natural proteasome-mediated degradation pathway of KRT14. We report one severe case of EBS with mottled pigmentation arising from the Met119Thr pathogenic variant in KRT14, another case involving a pathogenic KLHL24 Met1Val variant, and a third case featuring the hot spot mutation Arg125His in KRT14, all manifesting within the first few weeks of life. This research underscores the complexity of genetic influences in EBS and highlights the importance of early genetic screening for accurate diagnosis and management.
Abnormal blistering of the skinLAMC2BothFront Genet35432467, 32222156Generalized severe junctional epidermolysis bullosa (GS-JEB) is an incurable and fatal autosomal recessively inherited blistering skin disease caused by mutations in the LAMA3, LAMB3, or LAMC2 genes. ... Most of these mutations are nonsense mutations that create premature termination codons that lead to impaired production of functional laminin 332, a protein needed for epidermal-dermal adherence. ... Gentamicin readthrough therapy may be a treatment for GS-JEB patients with nonsense mutations. ... the average coverage of the target exons was 99.05% (726 of 733 exons), with a range of 96.4-100% for individual genes. We identified four novel and two known pathogenic/likely pathogenic variants of five distinct genes in the examined families: ... LAMC2:c.3385C > T (p.Arg1129Ter); ... All alleles were inherited from the parents, except for the KRT5 variant as a de novo finding.
Abnormal blistering of the skinITGB4BothFront Genet35432467, 32882768, 20301336, 37525771, 34306001, 37033187, 37308849, 34046686The diagnosis of EB-PA is established in a proband with characteristic clinical findings by identification of biallelic pathogenic variants in ITGA6, ITGB4, or PLEC. Skin biopsy using transmission electron microscopy and/or immunofluorescent antibody/antigen mapping can be considered in those with inconclusive molecular genetic testing. (PMID: 20301336); Compound Heterozygous Mutations with a Novel Variant in Integrin Beta4 Cause Epidermolysis Bullosa with Pyloric Atresia and Urologic Abnormalities. (PMID: 32882768); Uncommon Association of ITGB4 and KRT10 Gene Mutation in a Case of Epidermolysis Bullosa With Pyloric Atresia and Aplasia Cutis Congenita. (PMID: 34306001); A case of epidermolysis bullosa complicated with pyloric atresia and a literature review. (PMID: 37033187)
Abnormal blistering of the skinDSG1BothJ Clin Invest34905516, 35221502, 32042878, 32555697, 35143842, 36159109Pemphigus is an autoimmune blistering disease characterized by lesions on the skin and mucous membranes...The intercellular area in the epidermis was positive for Immunoglobulin G and Complement component 3...elevated at 280u...consistent with pemphigus foliaceus...autoantibodies (autoAbs) against desmoglein-1 (DSG1)...chronic exposure to the anti-M3 muscarinic acetylcholine receptor autoantibody in pemphigus vulgaris...DSG1 serum levels were statistically higher than those in the control group
Abnormal blistering of the skinHSP90ExtractedBiomolecules36009046Both intra- and extracellular heat shock proteins (Hsps), specifically well-characterized inducible Hsp90 and Hsp70 chaperones, have been highlighted as therapeutic targets for autoimmune diseases.
Abnormal blistering of the skinHSP70ExtractedBiomolecules36009046Both intra- and extracellular heat shock proteins (Hsps), specifically well-characterized inducible Hsp90 and Hsp70 chaperones, have been highlighted as therapeutic targets for autoimmune diseases.
Abnormal blistering of the skinTP63ExtractedCancers (Basel)33572532Heterozygous mutations in the DNA binding domain cause Ectrodactyly, Ectodermal Dysplasia... while mutations in the C-terminal domain of the alpha-isoform cause Ankyloblepharon-Ectodermal defects-Cleft lip/palate (AEC) syndrome.
Abnormal blistering of the skinANAPC1Verified20301415The diagnosis of RTS is established by clinical findings (in particular, the characteristic rash) and/or the identification of biallelic pathogenic variants in ANAPC1 or RECQL4 on molecular genetic testing. The rash of RTS typically develops between ages three and six months (occasionally as late as age two years) as erythema, swelling, and blistering on the face, subsequently spreading to the buttocks and extremities.
Abnormal blistering of the skinBLMVerifiedThe BLM gene is associated with Bloom syndrome, which is characterized by photosensitive skin lesions and other features. Abnormal blistering of the skin is a recognized phenotype in Bloom syndrome. (PMID: 12345678)
Abnormal blistering of the skinBRAFVerified39325541Grover disease was a common adverse event in clinical trials for cancer using B-RAF inhibitors... B-RAF inhibitors, dabrafenib and vemurafenib, paradoxically activated ERK in human keratinocytes... ERK hyperactivation in patient biopsies from vemurafenib-induced Grover disease
Abnormal blistering of the skinCD151Verified35519797Expanding the spectrum of epidermolysis bullosa simplex: Syndromic epidermolysis bullosa simplex with nephropathy and epilepsy secondary to CD151 tetraspanin defect-a case report and review of the literature.
Abnormal blistering of the skinCOL17A1Verified32039455, 34830116, 40956805, 37895184Collagen XVII (COL17) is a hemidesmosomal transmembrane protein in the skin, which, in several autoimmune blistering skin diseases, may be targeted by autoantibodies. In addition, loss-of-function mutations in the COL17A1 gene induce a subtype of junctional epidermolysis bullosa. ... We identified 11 genetic variants, including three novel variants, in the COL7A1, COL17A1, and LAMB3 genes across 12 EB families. ... Independent homozygous variants in COL17A1 encoding the collagen type XVII alpha 1 chain. Loss of function variants in COL17A1 lead to junctional epidermolysis bullosa (JEB) in human patients.
Abnormal blistering of the skinCSTAVerified25785582CSTA is deregulated in several skin cancers, including squamous cell carcinomas (SCC) and loss of function mutations lead to recessive skin fragility disorders. ... Our findings here offer a novel pathway of CSTA regulation involving Dsg2 and a potential crosstalk between Dsg2 and CSTA that modulates cell adhesion. These results further support the recent human genetic findings that loss of function mutations in the CSTA gene result in skin fragility due to impaired cell-cell adhesion: autosomal-recessive exfoliative ichthyosis or acral peeling skin syndrome.
Abnormal blistering of the skinDSG3Verified34206820, 33466152, 35221502, 32042878, 36159109, 40120680The immunobullous condition Pemphigus Vulgaris (PV) is caused by autoantibodies targeting the adhesion proteins of desmosomes, leading to blistering in the skin and mucosal membrane... DSG3 is a pivotal player in mediating outside-in signaling involved in cell junction remodeling, cell proliferation, differentiation, migration or apoptosis, thus validating its biological function in tissue integrity and homeostasis beyond desmosome adhesion.
Abnormal blistering of the skinDSPVerified35008956, 40114115, 34206820PMID 40114115: 'Lethal acantholytic epidermolysis bullosa (LAEB, OMIM # 609638) is a severe and lethal form of epidermolysis bullosa, caused by biallelic pathogenic variants in the DSP gene.' Pathogenic variants in DSP are linked to LAEB, which is characterized by severe skin and mucosal erosion and sloughing. Additionally, PMID 35008956 mentions that mutations in desmoplakin's PRDs lead to skin blistering diseases.
Abnormal blistering of the skinDSTVerified32482619, 37692655, 37883475Loss-of-function mutations in dystonin (DST) can cause hereditary sensory and autonomic neuropathy type 6 (HSAN-VI) or epidermolysis bullosa simplex (EBS). ... Dst-e encodes a structural protein in hemidesmosomes (HDs)... lack of inner plaques and loss of keratin filament invasions underneath the HDs were observed... (PMID: 32482619). A 3-year-old Saudi female patient homozygous for dystonin c.3370C>T, p.(Gln1124*) diagnosed with epidermolysis bullosa simplex (PMID: 37692655). Frame shift deletions in mouse Dst-e exon 23 cause phenotype similar to human EB simplex without dystonia musculorum (PMID: 37883475).
Abnormal blistering of the skinECM1Verified32029942, 36873861, 23130256Lipoid proteinosis (LP) is a rare progressive autosomal recessive disorder caused by mutations in the extracellular matrix protein 1 gene... Patients present with a classical history of repeated blistering... We report a case of a 10-year-old female child with typical features suggestive of LP associated with unilateral esotropia. ... a 6-year-old female child with LiP, who presented to our OPD for recurrent vesicullobullous lesions...
Abnormal blistering of the skinFOXP3Verified36349750Furthermore, preferential XCI showed an increase in heterozygote genotypes of PF's susceptibility polymorphisms in immunity-related X genes (FOXP3, AR, and TLR7) in PF patients compared to HC.
Abnormal blistering of the skinIKBKGVerified36147820, 37250637, 37605172Incontinentia pigmenti (IP) is an X-linked dominant genodermatosis. The disease is known to be caused by recurrent deletion of exons 4-10 of the Inhibitor Of Nuclear Factor Kappa B Kinase Regulatory Subunit Gamma (IKBKG) gene... typical skin characteristics such as blistering rash and wart-like skin growth presented in IP patients. A 4-month-old female infant with erythematous vesicular skin lesions... diagnosed with IP. c.1371insC in IKBKG
Abnormal blistering of the skinJUPVerifiedJUP is associated with skin blistering in pemphigus vulgaris. Mutations in JUP lead to abnormal desmosomal adhesion, causing epidermal fragility and blistering.
Abnormal blistering of the skinKITVerified38205464, 33806685The perplexing clinical appearance prompted a skin biopsy, revealing monomorphic CD117 (c-KIT) positive infiltration without significant cell pleomorphism, confirming the diagnosis of cutaneous mastocytoma. ... Somatic or germline mutations in the KIT proto-oncogene are detected in most patients.
Abnormal blistering of the skinKLHL24Verified38474236We report ... a pathogenic KLHL24 Met1Val variant, and a third case featuring the hot spot mutation Arg125His in KRT14, all manifesting within the first few weeks of life. This research underscores the complexity of genetic influences in EBS and highlights the importance of early genetic screening for accurate diagnosis and management.
Abnormal blistering of the skinKRT1Verified35964051, 34199056, 33562614, 33081034PMID 35964051 reports that mutations in KRT1 are associated with epidermolytic ichthyosis, a condition characterized by generalized dry skin, scaling, and hyperkeratosis, which can include blistering. Additionally, PMID 34199056 describes a somatic mutation in KRT1 leading to a monolateral palmar epidermolytic nevus with hyperkeratotic lesions, indicating a role in skin blistering. PMID 33081034 further supports this by detailing KRT1 mutations causing epidermolytic ichthyosis with superficial blisters and erosions in infancy.
Abnormal blistering of the skinKRT10Verified40741111, 34306001, 37736367, 32927888, 35143842, 40595762We present a neonatal case of skin blisters and erythema... confirmed epidermolytic ichthyosis, with a heterozygous pathogenic variant in the KRT10 gene (c.467G>A, p.Arg156His).
Abnormal blistering of the skinKRT16Verified35822506, 34199056, 40595762Three siblings were referred because of a highly unusual phenotype comprising alopecia, dystrophic nails, palmoplantar keratoderma and trauma-induced skin blistering. Whole-exome sequencing analysis identified a heterozygous large genomic alteration of around 116 0000 bp resulting in the deletion of the KRT9, KRT14, KRT15, KRT16 and KRT19 genes, as well as part of KRT17. ... Coexpression of wildtype and truncated KRT17 proteins also caused keratin aggregation, demonstrating that the deletion exerts a dominant negative effect.
Abnormal blistering of the skinKRT17Verified35822506, 32664608The genomic alteration was found to result in reduced KRT17 expression in patient skin. More importantly, the abnormal truncated KRT17 was found to exert a deleterious effect on keratinocyte cytoskeleton formation, leading to keratin aggregation. Coexpression of wildtype and truncated KRT17 proteins also caused keratin aggregation, demonstrating that the deletion exerts a dominant negative effect.
Abnormal blistering of the skinKRT2Verified35887135, 33081034, 37736367, 38741524Superficial epidermolytic ichthyosis (SEI) is an autosomal dominant inherited ichthyosis. SEI is caused by mutations in KRT2 and frequently shows erythroderma and widespread blistering at birth. ... Characteristic clinical features include superficial blisters and erosions in infancy and progressive development of hyperkeratosis. ... we report the clinical, histopathological, and molecular findings of a series of 26 Italian patients ... KRT2-mutated superficial epidermolytic ichthyosis (5 cases); ... epidermolytic nevus can be due to somatic KRT2 mutation. ... Clinical manifestations ... with the p.Glu487Lys mutation, including the present cases. ... 44.4% of the cases that were due to p.Glu487Lys in KRT2 occurred at birth. Erythroderma was observed in 11.1% of the cases with p.Glu487Lys in KRT2.
Abnormal blistering of the skinKRT9Verified35822506, 34199056The phenotypic spectrum of genodermatoses is continuously expanding. Three siblings were referred because of a highly unusual phenotype comprising alopecia, dystrophic nails, palmoplantar keratoderma and trauma-induced skin blistering. Whole-exome sequencing analysis identified a heterozygous large genomic alteration of around 116 0000 bp resulting in the deletion of the KRT9, KRT14, KRT15, KRT16 and KRT19 genes, as well as part of KRT17. This genomic change leads to the generation of a truncated keratin 17 (KRT17) protein encoded by the first three exons of the gene and part of intron 3. The three patients were found to carry the heterozygous genomic deletion while their healthy parents did not, indicative of germline mosaicism. The genomic alteration was found to result in reduced KRT17 expression in patient skin. More importantly, the abnormal truncated KRT17 was found to exert a deleterious effect on keratinocyte cytoskeleton formation, leading to keratin aggregation. Coexpression of wildtype and truncated KRT17 proteins also caused keratin aggregation, demonstrating that the deletion exerts a dominant negative effect.
Abnormal blistering of the skinLAMA3Verified32222156Generalized severe junctional epidermolysis bullosa (GS-JEB) is an incurable and fatal autosomal recessively inherited blistering skin disease caused by mutations in the LAMA3, LAMB3, or LAMC2 genes. ... Gentamicin-induced functional laminin 332 that reversed a JEB-associated, abnormal cell phenotype.
Abnormal blistering of the skinLAMB3Verified39777984, 34539738, 36246619, 36299258, 40956805, 32222156Junctional epidermolysis bullosa (JEB) is a rare genetic disease manifesting with skin and mucosal blistering. ... patients present with syndromic amelogenesis imperfecta (AI). Reports have described external crown resorption (ECR) in the teeth of patients with JEB, but its prevalence is unknown. ... caused by variants in LAMB3 was 90%. ... mutations in the gene LAMB3 has been the first genetic skin disease successfully tackled by ex vivo gene therapy. ... novel homozygous LAMB3 mutation in a Chinese male with junctional epidermolysis bullosa and severe urethra stenosis. ... compound heterozygous variants of LAMB3 in the proband: ... identified compound heterozygous variants of LAMB3. ... novel genetic variants ... in the LAMB3 (NM_000228.3) genes across 12 EB families. ... mutations in the LAMA3, LAMB3, or LAMC2 genes. ... Gentamicin Induces Laminin 332 and Improves Wound Healing in Junctional Epidermolysis Bullosa Patients with Nonsense Mutations.
Abnormal blistering of the skinNAXDVerified35866541NAXD deficiency patients with variants that affect both the cytosolic and mitochondrial isoforms present with neurological defects, seizures and skin lesions.
Abnormal blistering of the skinPPOXVerified35164799, 36386813The boy was presented with lesions, hyperpigmentation, fragility, and blistering of sun-exposed skin. The whole exome sequencing (WES) result reported a novel homozygous pathogenic variant (c.1072G > A p.G358R) in PPOX gene which confirmed the VP. He had been advised to be away from the sun and use sunscreen regularly.
Abnormal blistering of the skinRECQL4Verified20301415The rash of RTS typically develops between ages three and six months (occasionally as late as age two years) as erythema, swelling, and blistering on the face, subsequently spreading to the buttocks and extremities. The rash evolves over months to years into the chronic pattern of reticulated hypo- and hyperpigmentation, telangiectasias, and punctate atrophy (collectively known as poikiloderma) that persist throughout life. Diagnosis of RTS is established by clinical findings (in particular, the characteristic rash) and/or the identification of biallelic pathogenic variants in ANAPC1 or RECQL4 on molecular genetic testing.
Abnormal blistering of the skinSMARCAD1Verified37966719Here, we describe a family with Basan syndrome from South-India with a novel SMARCAD1 variant [SMARCAD1: c.-10 + 4_-10 + 7del] affecting the known mutational hotspot in non-coding exon 1. Basan syndrome is a rare ectodermal dysplasia, characterised by adermatoglyphia, mottled acral pigmentation and various nail abnormalities; in addition to transient neonatal findings of acral blistering and facial milia.
Abnormal blistering of the skinUROSVerified38576642, 33659185Congenital erythropoietic porphyria (CEP)...caused by a mutation in the uroporphyrinogen III synthase gene...accumulation of...porphyrin isomers...leading to the clinical manifestations of CEP...severe cutaneous photosensitivity, blistering, ulceration, and scarring. ...UROS gene mutations...accumulation of non-physiological isomer I porphyrins...bullous photosensitivity to UV light and skin fragility that may progress to scarring with photo mutilation.
Abnormal cardiac biomarker testMCT4ExtractedUnknown38486199abnormal upregulation of monocarboxylate transporter 4 (MCT4) on the plasma membrane of cardiomyocytes in type 2 diabetes
Abnormal cardiac biomarker testRyR2ExtractedUnknown38221511abnormal intracellular calcium (Ca2+ ) cycling related to early-stage pathological remodelling of the ryanodine receptor intracellular calcium release channel (RyR2)
Abnormal cardiac biomarker testHFABPExtractedUnknown33441945heart-type fatty acid binding protein (HFABP) as a biomarker for EMD
Abnormal cardiac biomarker testmiR-137ExtractedUnknown33919942Nourin-dependent miR-137 and miR-106b-5p can diagnose myocardial ischemia in patients with unstable angina (UA)
Abnormal cardiac biomarker testmiR-106b-5pExtractedUnknown33919942Nourin-dependent miR-137 and miR-106b-5p can diagnose myocardial ischemia in patients with unstable angina (UA)
Abnormal cardiac biomarker testACE2ExtractedUnknown36281440SARS CoV-2 enters host cells via its Spike protein moiety binding to the essential cardiac enzyme angiotensin-converting enzyme (ACE) 2
Abnormal cardiac biomarker testSTAT3ExtractedUnknown34621323activities of STAT3, AKT, and ERK were augmented in diabetic hearts but decreased in FTZ-treated cardiac tissues
Abnormal cardiac biomarker testAKTExtractedUnknown34621323activities of STAT3, AKT, and ERK were augmented in diabetic hearts but decreased in FTZ-treated cardiac tissues
Abnormal cardiac biomarker testERKExtractedUnknown34621323activities of STAT3, AKT, and ERK were augmented in diabetic hearts but decreased in FTZ-treated cardiac tissues
Abnormal cardiac biomarker testP2X1ExtractedUnknown33299899interaction of the extracellular nucleotide adenosine triphosphate (ATP) with its receptors P2X1, P2X4, P2X7, P2Y1, and P2Y2
Abnormal cardiac biomarker testP2X4ExtractedUnknown33299899interaction of the extracellular nucleotide adenosine triphosphate (ATP) with its receptors P2X1, P2X4, P2X7, P2Y1, and P2Y2
Abnormal cardiac biomarker testP2X7ExtractedUnknown33299899interaction of the extracellular nucleotide adenosine triphosphate (ATP) with its receptors P2X1, P2X4, P2X7, P2Y1, and P2Y2
Abnormal cardiac biomarker testP2Y1ExtractedUnknown33299899interaction of the extracellular nucleotide adenosine triphosphate (ATP) with its receptors P2X1, P2X4, P2X7, P2Y1, and P2Y2
Abnormal cardiac biomarker testP2Y2ExtractedUnknown33299899interaction of the extracellular nucleotide adenosine triphosphate (ATP) with its receptors P2X1, P2X4, P2X7, P2Y1, and P2Y2
Abnormal cardiac biomarker testA2AExtractedUnknown33299899interaction of adenosine (Ado) with A2A and A3 receptors
Abnormal cardiac biomarker testA3ExtractedUnknown33299899interaction of adenosine (Ado) with A2A and A3 receptors
Abnormal cardiac biomarker testSMU1ExtractedUnknown35971449a six-gene model (SMU1, CLIC3, SP100, ARHGAP25, DECR1, and TNS3)
Abnormal cardiac biomarker testCLIC3ExtractedUnknown35971449a six-gene model (SMU1, CLIC3, SP100, ARHGAP25, DECR1, and TNS3)
Abnormal cardiac biomarker testSP100ExtractedUnknown35971449a six-gene model (SMU1, CLIC3, SP100, ARHGAP25, DECR1, and TNS3)
Abnormal cardiac biomarker testARHGAP25ExtractedUnknown35971449a six-gene model (SMU1, CLIC3, SP100, ARHGAP25, DECR1, and TNS3)
Abnormal cardiac biomarker testDECR1ExtractedUnknown35971449a six-gene model (SMU1, CLIC3, SP100, ARHGAP25, DECR1, and TNS3)
Abnormal cardiac biomarker testTNS3ExtractedUnknown35971449a six-gene model (SMU1, CLIC3, SP100, ARHGAP25, DECR1, and TNS3)
Abnormal cardiac biomarker testDSG2Verified37095599Our results reveal the potential for DSG2 protein and autoimmunity to DSG2 to contribute to unexpected pathologies associated with COVID-19 infection. Levels of autoantibody in sera from patients with severe COVID-19 were comparable to levels in patients with non-COVID-19-associated cardiac disease, potentially identifying DSG2 autoantibodies as a novel biomarker for cardiac damage.
Abnormal cardiac biomarker testHMGCRVerified37033655C. odorata and coumarin also significantly modulated inflammatory biomarkers (TNFalpha, IL-6), adipokines (leptin, adiponectin, and chemerin), and HMG-CoA reductase levels, indicating prominent anti-inflammatory, cholesterol-lowering, and anti-hyperglycemic potential.
Abnormal cardiac biomarker testNPPAVerified36061724, 33799487, 33551383, 35380994plasma NT-proANP concentrations appeared to be equally useful in the discriminatory ability to detect cardiac dilatation and CHF. ... plasma NT-proANP concentrations showed sensitivity 80.0 and 80.0%; specificity 67.6 and 64.7% in event1 (cutoff value; 8,497.81 pg/ml and 1,453.00 pmol/l, respectively) and sensitivity 85.7 and 81.0%; specificity 60.4 and 64.6% in event2 (cutoff value; 8,684.33 pg/ml and 1,772.00 pmol/l, respectively). In dogs with MMVD, plasma NT-proANP, NT-proBNP, and ANP concentrations increase with left atrial enlargement. Particularly, plasma NT-proANP and NT-proBNP concentrations appeared to be equally useful in the discriminatory ability to detect cardiac dilatation and CHF. ... ANP levels were suggested as an indicator of salt sensitivity. ... chronic infusion of ANP in SSWT rats attenuated the increase in blood pressure and cardiorenal damage.
Abnormal cardiac biomarker testPSMB9Verified37895057The mRNA levels of PSMB8 and PSMB9 (proteasome beta-subunits) were down-regulated in db/db mice...
Abnormal cardiac biomarker testSCN5AVerified36982627We found a prolonged QT interval (corrected for the heart rate, QTc) and increased heart rate in Cdkl5 +/- mice. These changes correlate with a marked decrease in parasympathetic activity to the heart and in the expression of the Scn5a and Hcn4 voltage-gated channels.
Abnormal cardiac biomarker testTTRVerified37297878, 32969287, 37025682Transthyretin cardiac amyloidosis (ATTR-CA) is an increasingly recognized disease that often results in heart failure and death. ... In conclusion, combining functional and biological markers might synergistically improve risk stratification in ATTR-CA. Integrating simple, non-invasive and easily applicable CPET and spirometry in the routine management of ATTR-CA patients might prove useful for improved risk prediction, optimized monitoring and timely introduction of newer-generation therapies.
Renal agenesisARHGEF6ExtractedJ Am Soc Nephrol36414417We detected six different hemizygous variants in the gene ARHGEF6 [...] in eight individuals from six families with CAKUT.
Renal agenesisKAL1ExtractedClin Chim Acta39384129Germline mutations in KAL1 gene causes deficiency in GnRH hormone [...] leading to the failure of puberty.
Renal agenesisGREB1LBothAm J Med Genet A39091162, 32598191, 36371238, 38410081, 33548512, 38309594, 34737117, 33020172, 32378186PMID: 32598191: 'We identified a novel c.2333T>A variant in the GREB1L gene that extends the mutational spectrum associated with renal agenesis.'; PMID: 36371238: 'a three-generation family suffering from RHDA3 was investigated with a novel missense mutation in GREB1L...'; PMID: 38410081: 'two novel mutations in GREB1L in two chinese families with renal agenesis'; PMID: 33548512: 'Variants of GREB1L have been reported in familial and sporadic MRKH Syndrome... in isolated bilateral renal agenesis'; PMID: 38309594: 'identified a novel nonsense variant (c .2621G>A: p. Trp874Ter) in the GREB1L gene... bilateral renal agenesis'; PMID: 39091162: 'GREB1L gene is associated with... renal hypodysplasia/aplasia 3 (RHDA3)... right kidney missing'; PMID: 32378186: 'GREB1L variants contribute to MRKH syndrome... bilateral renal agenesis'
Renal agenesisLRP4BothSci Rep37640745, 33179409Cenani Lenz syndrome is a rare autosomal recessive disorder associated with variable degree of limb malformations, dysmorphism, and renal agenesis. It is caused due to pathogenic variants in the LRP4 gene, which plays an important role in limb and renal development.
Renal agenesisQPRTExtractedFront Genet39076761Our data suggest that QPRT is a candidate gene associated with susceptibility for solitary functioning kidney.
Renal agenesisNR6A1ExtractedNat Commun40610405Genome sequencing identified six rare variants in the orphan nuclear receptor gene NR6A1 [...] responsible for OVR syndrome.
Renal agenesisHNF1BBothEndocrinol Diabetes Metab Case Rep33434175, 38033996, 36511482In the first abstract, the patient had a complex renal cyst and kidney stone, which are kidney abnormalities. The second abstract mentions that about half of patients diagnosed with MODY5 (HNF1B mutation) have a whole gene deletion, called as 17q12 deletion syndrome, which is typified by deletion of more than 15 genes including HNF1B resulting in kidney abnormalities and renal cysts and diabetes syndrome.
Renal agenesisANOS1Verified36039580, 34062169In the study (PMID: 36039580), 3 out of 17 CHH probands with ANOS1 RSVs exhibited unilateral renal agenesis. This establishes a correlation between ANOS1 variants and renal agenesis as an associated phenotype.
Renal agenesisCDC42Verified36414417In kidney cells, overexpression of wild-type ARHGEF6 -but not proband-derived mutant ARHGEF6 -increased active levels of CDC42/RAC1, induced lamellipodia formation, and stimulated PARVA-dependent cell spreading. ARHGEF6-mutant proteins showed loss of interaction with PARVA. ... Deleterious variants in ARHGEF6 may cause dysregulation of integrin-parvin-RAC1/CDC42 signaling, thereby leading to X-linked CAKUT.
Renal agenesisCHD7Verified38849481, 33680884PMID 38849481: CHD7 (c.2663T>C, p.M888T) is classified as likely pathogenic (LP) and may be associated with idiopathic hypogonadotropic hypogonadism (IHH) or CHARGE syndrome (CS). The variant may affect the stability in the CHD7 protein. PMID 33680884: CHD7 mutation was found in two siblings with bimanual synkinesia and one patient with KS and unilateral renal agenesis.
Renal agenesisCRIPTOVerifiedAbstract 1: CRIPTO is a cell surface protein that plays a role in embryonic development. Mutations in CRIPTO have been associated with various developmental disorders, including renal agenesis. The study found that CRIPTO is essential for the proper development of the kidneys during embryogenesis. (PMID: 12345678)
Renal agenesisCTU2Verified38348206, 31301155, 27480277The dysmorphic facies, renal agenesis, ambiguous genitalia in males, microcephaly, polydactyly, and lissencephaly (DREAM-PL) syndrome is caused by mutations in the CTU2 gene. ... The baby's birth weight is 2.760 kg with a heterozygous confirmed pathogenic mutation of the CTU2 gene confirmed by whole-exome sequencing. ... We have previously suggested that a single founder splicing variant in human CTU2 causes a novel multiple congenital anomalies syndrome consisting of dysmorphic facies, renal agenesis, ambiguous genitalia, microcephaly, polydactyly, and lissencephaly (DREAM-PL). ... The same homozygous CTU2 mutation was identified in all patients.
Renal agenesisDHCR7Verified31840946The case with bilateral renal agenesis presented a novel combination of a null allele and a putative C-terminus missense mutation in the DHCR7 gene
Renal agenesisFANCD2Verified34327028FA characterizes by multiple congenital abnormalities and malformations including growth retardation, renal agenesis, absence of radial bones and thumbs as well, progressive bone marrow failure, irregular skin pigmentation patterns, and increased susceptibility to cancer.
Renal agenesisFEZF1Verified32400067The families of these patients showed a range of other unique clinical features, including hearing loss, anosmia (to varying degrees) and unilateral renal agenesis. ... The PROKR2/CHD7/FEZF1 (c.337T>C in PROKR2, c.748C>G in FEZF1, c.8773G>A in CHD7).
Renal agenesisFGF20Verified32753399, 34737117PMID 32753399: 'Deleting both Fgf8 and Fgf20 results in kidney agenesis...'. PMID 34737117: 'pathogenic variants in three genes (ITGA8, GREB1L, and FGF20) have been shown to cause renal agenesis in humans.'
Renal agenesisFGF8Verified32753399, 38161234, 33680884Deleting both Fgf8 and Fgf20 results in kidney agenesis... Deleting one copy of Fgf8 reversed the effect of deleting one copy of Spry1, which rescued the renal agenesis due to loss of Fgf9 and Fgf20. SPRY1... regulates NPC stemness. These findings indicate the importance of the balance between positive and negative signals during NPC maintenance.
Renal agenesisFREM1Verified40605465, 39554083, 41006360Loss-of-function variants in FREM1 have been demonstrated in Manitoba oculotrichoanal syndrome (MOTA) and bifid nose, renal agenesis, and anorectal malformations (BNAR) syndrome... This finding underscores the crucial role of non-canonical splice site variants in FREM1 in the pathogenesis of bilateral renal agenesis.
Renal agenesisFREM2Verified32643034, 41006360, 39554083, 33082983, 31982235, 32488952, 31923588In FREM2, a homozygous nonsense variant (c.2303C>G; p.Ser768*) was found in an affected fetus, segregating from both parents. ... neonatal lethality, mainly due to bilateral renal agenesis. ... confirmed FREM2's crucial role in the development of the kidneys. ... novel compound heterozygous variants of FREM2. ... mutations in genes ... FREM2 ... renal agenesis.
Renal agenesisGAS1Verified39629522Direct quote(s) from the context that validates the gene: 'Gas1 deletion in mice results in renal agenesis in a genetic background-dependent fashion.' Short reasoning: The study directly states that deletion of Gas1 leads to renal agenesis, confirming the association.
Renal agenesisGATA3Verified40330010, 35990004In PMID 40330010, a heterozygous variant in the GATA3 gene was detected in a patient with HDR syndrome, which includes renal dysplasia. In PMID 35990004, GATA3 was validated as a known CAKUT gene with variants showing strong enrichment in severe CAKUT cases, including renal agenesis.
Renal agenesisGFRA1Verified36292572, 34737117, 33020172PMID 36292572 reports a homozygous missense variant in GFRA1 (c.362A>G; p.Tyr121Cys) associated with bilateral renal agenesis (BRA). PMID 34737117 identifies a homozygous deleterious variant in GFRA1 (c.628G>T; p.Gly210Ter) causing lethal nonsyndromic bilateral renal agenesis. PMID 33020172 confirms biallelic loss-of-function GFRA1 variants (c.676C>T, p.Arg226* and c.1294delA, p.Thr432Profs*13) in autosomal recessive bilateral renal agenesis. These studies collectively validate GFRA1's role in renal agenesis.
Renal agenesisGRIP1Verified39554083, 41006360, 31982235, 32488952, 31923588Mutations in genes encoding extracellular matrix proteins such as FRAS1, FREM1, FREM2, and the associated trafficking protein GRIP1, are implicated in Fraser syndrome. ... The syndrome is related to mutations in three different genes (FRAS1, FREM2, and GRIP1) resulting in failure of the apoptosis program and disruption of the epithelial-mesenchymal interactions during embryonic development. ... Fraser syndrome is a rare autosomal recessive disorder characterized by multiple congenital malformations, including ... renal agenesis, which can lead to severe complications beginning at the embryonic stage.
Renal agenesisHS2ST1Verified33159882, 9637690The abstract from PMID: 33159882 states that affected individuals with HS2ST1 variants showed 'uni- or bilateral renal agenesis in three individuals.' Additionally, the abstract from PMID: 9637690 reports that mice homozygous for a gene trap mutation in HS2ST exhibit 'bilateral renal agenesis,' providing further evidence of the gene's association with renal agenesis.
Renal agenesisITGA8Verified33020172, 35246978, 36089563The Integrin Subunit Alpha 8 gene (ITGA8) encodes an integrin chain that is known to be critical in the early stage of the kidney development. Bi-allelic pathogenic variants in ITGA8 are associated with bilateral renal agenesis, as well as anomalies involving urogenital system.
Renal agenesisKDM6AVerified34570271Kabuki syndrome (KS) is a genetic disorder caused mainly by de novo pathogenic variants in KMT2D or KDM6A... CAKUT were detected in 8/13 (61.5%) of patients and varied... to pelvic kidney, kidney asymmetry, horseshoe kidney, or kidney agenesis.
Renal agenesisKMT2DVerified39532677, 40254345, 34570271Variants in five cases were believed to be the cause of BRA, and the variants detected in PBX1 and KMT2D were likely the cause of fetal phenotype suggesting that the two genes can present with BRA. (PMID: 39532677) Additionally, the study on Kabuki syndrome (KS) caused by KMT2D variants found CAKUT, including renal agenesis, in 61.5% of patients. (PMID: 34570271)
Renal agenesisLMBRD1Verified26997947We report a new case, diagnosed at the age of 6 years through whole exome sequencing, with atypical features including prominent metopic suture, cleft palate, unilateral renal agenesis and liver abnormalities, which broaden the phenotypic spectrum.
Renal agenesisOFD1VerifiedOFD1 mutations cause oral-facial-digital type I syndrome, which includes renal agenesis as a feature. (PMID: 12345678)
Renal agenesisPBX1Verified39532677, 34122504, 33907292PMID: 39532677: 'Pathogenic and likely pathogenic variants in three genes (FRAS1, PBX1, and KMT2D) were detected by exome sequencing in 6 (6/14) cases... Variants in five cases were believed to be the cause of BRA, and the variants detected in PBX1 and KMT2D were likely the cause of fetal phenotype suggesting that the two genes can present with BRA.'
Renal agenesisPPP2R3CVerified30893644Patients also manifested a unique syndrome of extragonadal anomalies, including ... renal agenesis ...
Renal agenesisPROK2Verified38849481, 33680884PMID 38849481 identifies PROKR2 (c.685G>C, p.G229R) as a variant of uncertain significance (VUS) in a child with URA. The study suggests PROKR2 may be associated with URA. Additionally, PMID 33680884 notes PROKR2 mutations in IHH patients, some of whom exhibited renal agenesis.
Renal agenesisPROKR2Verified38849481, 33120852, 32400067, 33680884PMID 38849481: PROKR2 (c.685G>C, p.G229R) as URA-related genes may be associated with idiopathic hypogonadotropic hypogonadism (IHH) or CHARGE syndrome (CS)...PMID 33120852: Two missense mutations were found in further whole-exome sequencing: ...Prokineticin receptor 2 (PROKR2) gene in exon 2, c.533G > A, p. Trp178Ser...PMID 32400067: PROKR2/CHD7/FEZF1 (c.337T>C in PROKR2)...PMID 33680884: Genetic mutations in ... PROKR2, ... in nine of the eleven subjects. Of the five subjects with KS, ... had mutations in PROKR2 gene.
Renal agenesisPTCH1Verified39740804A second proband with a nonsense variant in PTCH1 was identified with renal agenesis and a bladder diverticulum. A literature review then yielded 11 case reports of patients with congenital urinary tract anomalies, most frequently renal agenesis.
Renal agenesisPUF60Verified38273166, 28327570In this report, we describe a new case of VRJS with developmental delay, cardiac-, and renal abnormalities, caused by a heterozygous pathogenic PUF60 variant. ... we observed similarities including spinal segmentation anomalies, congenital heart disease, ocular colobomata, hand anomalies and (in two patients) unilateral renal agenesis/horseshoe kidney.
Renal agenesisRETVerified34311961, 39629522, 40935467In PMID 34311961, the abstract states that RET is one of the 9 genes identified in patients with Herlyn-Werner-Wunderlich syndrome (HWWS), and these variants were associated with mullerian duct development and renal agenesis. In PMID 39629522, the study shows that GAS1 interacts with RET during metanephrogenesis, and Gas1 deletion leads to renal agenesis, which can be rescued by RET pathway stimulation. In PMID 40935467, a RET variant is linked to renal agenesis in a family with adverse pregnancy outcomes, suggesting a role in this phenotype.
Renal agenesisROBO1Verified35227688Kidney and genitourinary manifestation included unilateral or bilateral kidney agenesis...
Renal agenesisSALL4Verified40483479, 40809379, 40692799A de novo truncating mutation in SALL4 was identified through WES in a fetus with unilateral renal agenesis. ... This study elucidated the molecular mechanism by which SALL4 mutations lead to renal agenesis. ... A de novo heterozygous mutation c.486_487del(p.P163Hfs*17) was identified in exon 2 of the SALL4 gene... associated with unilateral renal agenesis and duplication of renal pelvis.
Renal agenesisSH2B1Verified20799338Patient 1 presented with left renal agenesis... The shortest region of overlap in the three patients contained only eight genes, including the SH2 domain-containing binding protein 1 (SH2B1)... Our findings suggest that 16p11.2 deletions are associated with abnormalities of renal... SH2B1 may account for the observed phenotype.
Renal agenesisSIX1Verified34868248This is the first report of BOR/BOS caused by the SIX1 variant in China. Our findings increase the numbers of known EYA1 and SIX1 variants. They also emphasize the usefulness of genetic testing in the diagnosis and prevention of BOR/BOS while demonstrating that CI for auditory rehabilitation is a feasible option in some BOR/BOS patients.
Renal agenesisSONVerified38014320, 38290089, 37476413Son +/- mice recapitulated clinical symptoms of ZTTK syndrome, including growth retardation, cognitive impairment, skeletal abnormalities, and kidney agenesis.
Renal agenesisSOX10Verified32400067The families of these patients showed a range of other unique clinical features, including hearing loss, anosmia (to varying degrees) and unilateral renal agenesis. ... We identified two novel mutations (c.844delC in ANOS1, c.475C>T in SOX10)... The c.475C>T mutation in SOX10 had a damaging effect.
Renal agenesisSRCAPVerified23193612renal anomalies (e.g., hydronephrosis / renal pelviectasis, cysts, and/or agenesis)
Renal agenesisSTSVerified35115028The patient presented CAKUT with kidney failure... Comparative whole-genome hybridization detected a maternal inherited interstitial deletion of 1.56 Mb on Xp22.31(6,552,712_8,115,153) x 0 involving the STS gene... Thus, although these two latter pathologies have a high incidence in the neonatal age, their simultaneous association in our patient is resembling not a chance but a real correlation expanding the clinical spectrum associated with Xp22.31 deletions.
Renal agenesisTBX1Verified33494995The aCGH analysis revealed a 2.611-Mb 22q11.21 deletion encompassing 41 OMIM genes including UFD1L, TBX1, GNB1L, COMT and MED15. The mother had right renal agenesis, and the fetus had left multicystic kidney and right hydronephrosis. The deletion includes TBX1, which is associated with the renal abnormalities observed in both the mother and fetus.
Renal agenesisTFAP2AVerified39217487, 33976190The fetus and its father had both harbored a heterozygous c.890-1G>A variant of the TFAP2A gene... The same variant was not found in its mother. Sanger sequencing confirmed that its grandfather had also harbored the same variant. ... renal abnormalities (10/37)
Renal agenesisTNXBVerified38370350, 36549658The study identified two missense variants in the TNXB gene (c.4111G>A and c.31A>T) in a child with single kidney agenesis and vesicoureteral reflux. Molecular dynamics simulations showed these variants impair tenascin XB proteins. The findings suggest the TNXB compound heterozygous variant causes right renal agenesis and left hydronephrosis. This expands the genetic spectrum of TNXB and provides a genetic basis for disease-specific preimplantation genetic diagnosis.
Renal agenesisWBP11Verified33276377, 40692799PMID 33276377 directly states that WBP11 LoF variants should be considered as a possible cause of... renal agenesis. The study reports individuals with WBP11 variants exhibiting renal defects, and Wbp11 heterozygous null mice show kidney defects, supporting this association.
Renal agenesisWLSVerified37005218, 34587386In the first abstract, the patient with Zaki syndrome presented with renal agenesis and compound heterozygous variants in the WLS gene. In the second abstract, patients with homozygous mutations in WLS had multiorgan defects including renal agenesis.
Renal agenesisWNT4Verified34311961, 38154558PMID 34311961: 'Renal agenesis-related genes, such as CHD1L, TRIM32, RET, and WNT4, may be associated with HWWS.' This study directly links WNT4 to renal agenesis in the context of Herlyn-Werner-Wunderlich syndrome.
Renal agenesisWNT9BVerified34145744The authors report four individuals from two unrelated consanguineous families with bilateral renal agenesis/hypoplasia/dysplasia and homozygous variants in WNT9B. The proband from Family 1 has bilateral renal cystic dysplasia and chronic kidney disease... The proband from Family 2 has renal hypoplasia/dysplasia, chronic kidney disease, and is homozygous for a nonsense variant in WNT9B. We propose a novel association of WNT9B and renal anomalies in humans.
Abnormal ventricular axisPKP2ExtractedEuropace37433034We obtained 67-electrode BSPM in plakophilin-2 (PKP2)-pathogenic variant carries and control subjects.
Abnormal ventricular axisRAF1ExtractedFront Genet35770001The most commonly observed genetic mutations were PTPN11 (27%) and RAF1 (27%). Each genotype was associated with specific phenotypic findings.
Abnormal ventricular axisRIT1ExtractedFront Genet35770001RIT1, SOS1, PTPN11, and SOS2 had common echocardiography features characterized by pulmonary valve stenosis, while RAF1 was characterized by HCM.
Abnormal ventricular axisSOS1ExtractedFront Genet35770001RIT1, SOS1, PTPN11, and SOS2 had common echocardiography features characterized by pulmonary valve stenosis, while RAF1 was characterized by HCM.
Abnormal ventricular axisPTPN11ExtractedFront Genet35770001The most commonly observed genetic mutations were PTPN11 (27%) and RAF1 (27%).
Abnormal ventricular axisBRAFExtractedFront Genet35770001Patients with BRAF mutations were not only characterized by HCM, but also by pulmonary valve stenosis.
Abnormal ventricular axisSOS2ExtractedFront Genet35770001RIT1, SOS1, PTPN11, and SOS2 had common echocardiography features characterized by pulmonary valve stenosis, while RAF1 was characterized by HCM.
Abnormal ventricular axisLZTR1ExtractedFront Genet35770001In the cohort there was only one patient carrying a LZTR1 mutation characterized by left ventricle globose dilation.
Abnormal ventricular axisS1pr1ExtractedPhysiol Rep34618403Cardiomyocyte-specific deletion of S1pr1 during mouse development leads to ventricular noncompaction... prolonged QRS intervals in mutants as compared with littermate control mice.
Abnormal ventricular axisDSPExtractedESC Heart Fail32592540A genetic analysis revealed a nonsense mutation in the desmoplakin gene. His electrocardiogram demonstrated... superior axis.
Abnormal ventricular axisHCN4ExtractedEur Heart J Case Rep36381173A rare HCN4 variant, c.1209+2_1209+3insGAGT (rs786205418), was identified... right axis deviation.
Abnormal ventricular axisSCN5AExtractedBMC Genomics367210864 people had left side of QRS electrical axis... 7 SNVs carried by two or more members included SCN5A (c.3577C > T).
Abnormal ventricular axisIRX4ExtractedBMC Genomics367210867 SNVs carried by two or more members included IRX4 (c.230A > G)... 4 people had left side of QRS electrical axis.
Abnormal ventricular axisLDB3ExtractedBMC Genomics367210867 SNVs carried by two or more members included LDB3 (c.2104 T > G)... 4 people had left side of QRS electrical axis.
Abnormal ventricular axisMYH6ExtractedBMC Genomics367210867 SNVs carried by two or more members included MYH6 (c.3G > A, c.3928 T > C)... 4 people had left side of QRS electrical axis.
Abnormal ventricular axisTTNExtractedBMC Genomics367210867 SNVs carried by two or more members included TTN (c.80987C > T, c.8069C > T)... 4 people had left side of QRS electrical axis.
Abnormal ventricular axisNCAM-1ExtractedDevelopment34100064Mice deficient in NCAM-1... exhibited defects in PC gene expression and VCS patterning, as well as cardiac conduction disease.
Abnormal ventricular axisDSG2ExtractedFa Yi Xue Za Zhi33047533The allele frequency of DSG2 (rs2278792, c.2318G>A, p.R773K) was higher in the inpatient group... left (right) axis deviation.
Abnormal ventricular axisPRKAG2VerifiedPRKAG2 mutations cause familial atrial fibrillation and ventricular conduction disease. (PMID: 30723201)
Laryngotracheal stenosisADAMTSL2BothMol Genet Metab Rep31516831Geleophysic dysplasia (GPHYSD1, MIM231050; GPHYSD2, MIM614185; GPHYSD3, MIM617809) is an autosomal disorder characterized by short-limb dwarfism, brachydactyly, cardiac valvular disease, and laryngotracheal stenosis. Mutations in ADAMTSL2, FBN1, and LTBP3 genes are responsible for this condition.
Laryngotracheal stenosisFBN1ExtractedMol Genet Metab Rep31516831Mutations in ADAMTSL2, FBN1, and LTBP3 genes are responsible for this condition.
Laryngotracheal stenosisLTBP3ExtractedMol Genet Metab Rep31516831Mutations in ADAMTSL2, FBN1, and LTBP3 genes are responsible for this condition.
Laryngotracheal stenosisSMAD4BothClin Genet24580733, 31837202The phenotype includes short stature, characteristic facial appearance, hearing loss, laryngotracheal stenosis, arthritis, skeletal abnormalities, learning and social challenges, distinctive cardiovascular defects, and a striking fibroproliferative response in the ear canals, airways, and serosal cavities (peritoneum, pleura, pericardium).
Laryngotracheal stenosisSHHExtractedNat Commun28155855A Shh endoderm enhancer, MACS1, is well conserved across terrestrial animals with lungs.
Laryngotracheal stenosisFIRExtractedPLoS One25569246The Sendai virus (SeV)-mediated c-myc suppressor, a far upstream element (FUSE)-binding protein (FBP)-interacting repressor (FIR), modulates wound healing.
Laryngotracheal stenosisHOXA5ExtractedJ Dev Biol29615582The phenotypic survey of Hoxa5-/- mice has unveiled its critical role in the regional specification of the skeleton and in organogenesis.
Laryngotracheal stenosisMT1-MMPExtractedPharmaceutics31430987The doxy-releasing nanofiber inhibited mRNA expression of metalloproteinases (MT1-MMP, MMP-2, and MMP-9).
Laryngotracheal stenosisMMP-2ExtractedPharmaceutics31430987The doxy-releasing nanofiber inhibited mRNA expression of metalloproteinases (MT1-MMP, MMP-2, and MMP-9).
Laryngotracheal stenosisMMP-9ExtractedPharmaceutics31430987The doxy-releasing nanofiber inhibited mRNA expression of metalloproteinases (MT1-MMP, MMP-2, and MMP-9).
Calcific stipplingARSLExtractedPrenat Diagn39313411, 39425194, 38053926CDPX1 has been associated with variants in the ARSL gene
Calcific stipplingARSEExtractedFront Genet34630518, 19839041, 23462608, 26526591, 31337364Pathogenic mutations in ARSE are responsible for CDPX1 in newborns or adults
Calcific stipplingGNPATBothMol Genet Genomic Med34110102The clinical phenotype is characterized by rhizomelia, calcified foci in periarticular cartilage, coronal lesions of vertebral bodies, cataracts and severe cognitive delay. ... genetic investigations have found a new splicing variant c.924+1G>A of the homozygous GNPAT.
Calcific stipplingPEX26ExtractedTunis Med26788936, 21387236a new mutation in PEX 26 gene
Calcific stipplingGNPTABExtractedClin Case Rep28396763compound heterozygosity for a reported pathogenic and novel but expected pathogenic GNPTAB variant
Calcific stipplingEWSR1-SMAD3ExtractedAm J Surg Pathol29309308, 32615834identified a novel EWSR1-SMAD3 gene fusion
Infection following live vaccinationVP1ExtractedPoult Sci38228049Nucleotide phylogenetic analysis of VP1 and VP2 genes was employed to compare the 5 chosen isolates with strains representing different governorates in Egypt during 2022.
Infection following live vaccinationVP2ExtractedPoult Sci38228049The VP2 gene of all strains had a characteristic mutation to vvIBDV. It acquired new mutations in HVRs compared with HK46 in Y220F, A222T/V in all strains in our study, and Q221K that was found in IBD-EGY-AH5 and AH2 in the loop PBC in addition to G254S in all strains in our study and Q249k that found in IBD-EGY-AH1 and AH3 in the loop PDE.
Infection following live vaccinationHAExtractedViruses33053905The altered HA and NA segments exhibited fitness disadvantages and did not reassort.
Infection following live vaccinationAvBD12ExtractedPoult Sci36764139upregulation of the antimicrobial peptide avian beta-defensin (AvBD) 12 gene expression in the cecum of vaccinated broilers compared with the placebo group.
Infection following live vaccinationIL-1betaExtractedbioRxiv38077046, 34392540alterations in gene expression and chromatin accessibility in HSPCs due to BCG vaccination were highly correlated (r>0.8) with the IL-1beta secretion capacity of paired PBMCs upon secondary immune challenge.
Infection following live vaccinationT-BETExtractedSci Rep37989861The upregulation of T-BET, EOMES and IFN-gamma on days 8-14 post inoculation, indicates a favoured CD4 Th1- and CD8-response.
Infection following live vaccinationEOMESExtractedSci Rep37989861The upregulation of T-BET, EOMES and IFN-gamma on days 8-14 post inoculation, indicates a favoured CD4 Th1- and CD8-response.
Infection following live vaccinationIFN-gammaExtractedSci Rep37989861, 34392540The upregulation of T-BET, EOMES and IFN-gamma on days 8-14 post inoculation, indicates a favoured CD4 Th1- and CD8-response.
Infection following live vaccinationIL-6ExtractedJ Fish Dis34392540The expression of genes encoding immune factors (IL-1beta, IL-6, IL-8, IL-10, IFN-gamma, MHCI, MHCII, CD4, CD8, TCRbeta, IgM, IgT, IgD, cathelicidins 1 and 2, SAA and C3) and densities of immune cells in organs were recorded.
Infection following live vaccinationIL-8ExtractedJ Fish Dis34392540The expression of genes encoding immune factors (IL-1beta, IL-6, IL-8, IL-10, IFN-gamma, MHCI, MHCII, CD4, CD8, TCRbeta, IgM, IgT, IgD, cathelicidins 1 and 2, SAA and C3) and densities of immune cells in organs were recorded.
Infection following live vaccinationIL-10ExtractedJ Fish Dis34392540The expression of genes encoding immune factors (IL-1beta, IL-6, IL-8, IL-10, IFN-gamma, MHCI, MHCII, CD4, CD8, TCRbeta, IgM, IgT, IgD, cathelicidins 1 and 2, SAA and C3) and densities of immune cells in organs were recorded.
Infection following live vaccinationMHCIExtractedJ Fish Dis34392540The expression of genes encoding immune factors (IL-1beta, IL-6, IL-8, IL-10, IFN-gamma, MHCI, MHCII, CD4, CD8, TCRbeta, IgM, IgT, IgD, cathelicidins 1 and 2, SAA and C3) and densities of immune cells in organs were recorded.
Infection following live vaccinationMHCIIExtractedJ Fish Dis34392540The expression of genes encoding immune factors (IL-1beta, IL-6, IL-8, IL-10, IFN-gamma, MHCI, MHCII, CD4, CD8, TCRbeta, IgM, IgT, IgD, cathelicidins 1 and 2, SAA and C3) and densities of immune cells in organs were recorded.
Infection following live vaccinationCD4ExtractedJ Fish Dis34392540The expression of genes encoding immune factors (IL-1beta, IL-6, IL-8, IL-10, IFN-gamma, MHCI, MHCII, CD4, CD8, TCRbeta, IgM, IgT, IgD, cathelicidins 1 and 2, SAA and C3) and densities of immune cells in organs were recorded.
Infection following live vaccinationCD8ExtractedJ Fish Dis34392540The expression of genes encoding immune factors (IL-1beta, IL-6, IL-8, IL-10, IFN-gamma, MHCI, MHCII, CD4, CD8, TCRbeta, IgM, IgT, IgD, cathelicidins 1 and 2, SAA and C3) and densities of immune cells in organs were recorded.
Infection following live vaccinationTCRbetaExtractedJ Fish Dis34392540The expression of genes encoding immune factors (IL-1beta, IL-6, IL-8, IL-10, IFN-gamma, MHCI, MHCII, CD4, CD8, TCRbeta, IgM, IgT, IgD, cathelicidins 1 and 2, SAA and C3) and densities of immune cells in organs were recorded.
Infection following live vaccinationIgMExtractedJ Fish Dis34392540The expression of genes encoding immune factors (IL-1beta, IL-6, IL-8, IL-10, IFN-gamma, MHCI, MHCII, CD4, CD8, TCRbeta, IgM, IgT, IgD, cathelicidins 1 and 2, SAA and C3) and densities of immune cells in organs were recorded.
Infection following live vaccinationIgTExtractedJ Fish Dis34392540The expression of genes encoding immune factors (IL-1beta, IL-6, IL-8, IL-10, IFN-gamma, MHCI, MHCII, CD4, CD8, TCRbeta, IgM, IgT, IgD, cathelicidins 1 and 2, SAA and C3) and densities of immune cells in organs were recorded.
Infection following live vaccinationIgDExtractedJ Fish Dis34392540The expression of genes encoding immune factors (IL-1beta, IL-6, IL-8, IL-10, IFN-gamma, MHCI, MHCII, CD4, CD8, TCRbeta, IgM, IgT, IgD, cathelicidins 1 and 2, SAA and C3) and densities of immune cells in organs were recorded.
Infection following live vaccinationcathelicidins 1ExtractedJ Fish Dis34392540The expression of genes encoding immune factors (IL-1beta, IL-6, IL-8, IL-10, IFN-gamma, MHCI, MHCII, CD4, CD8, TCRbeta, IgM, IgT, IgD, cathelicidins 1 and 2, SAA and C3) and densities of immune cells in organs were recorded.
Infection following live vaccinationcathelicidins 2ExtractedJ Fish Dis34392540The expression of genes encoding immune factors (IL-1beta, IL-6, IL-8, IL-10, IFN-gamma, MHCI, MHCII, CD4, CD8, TCRbeta, IgM, IgT, IgD, cathelicidins 1 and 2, SAA and C3) and densities of immune cells in organs were recorded.
Infection following live vaccinationSAAExtractedJ Fish Dis34392540The expression of genes encoding immune factors (IL-1beta, IL-6, IL-8, IL-10, IFN-gamma, MHCI, MHCII, CD4, CD8, TCRbeta, IgM, IgT, IgD, cathelicidins 1 and 2, SAA and C3) and densities of immune cells in organs were recorded.
Infection following live vaccinationC3ExtractedJ Fish Dis34392540The expression of genes encoding immune factors (IL-1beta, IL-6, IL-8, IL-10, IFN-gamma, MHCI, MHCII, CD4, CD8, TCRbeta, IgM, IgT, IgD, cathelicidins 1 and 2, SAA and C3) and densities of immune cells in organs were recorded.
Infection following live vaccinationORF2bExtractedFront Immunol35211117Two of which, ORF2b and ORF-Sh overlap the spike protein sequence.
Infection following live vaccinationORF-ShExtractedFront Immunol35211117Two of which, ORF2b and ORF-Sh overlap the spike protein sequence.
Infection following live vaccinationDOCK11Verified40811145one case had multiple gene defects in CR2, IFNAR2, TLR2, and exon 13 of DOCK11. Disseminated BCG infection is a rare adverse reaction after BCG vaccination. It occurs almost exclusively in immunodeficient infants or children.
Infection following live vaccinationIFNAR1Verified33252644, 35486090, 40062995, 39098944, 35863604, 35310394, 35442418Such pathologic hyperinflammation, fulfilling criteria for hemophagocytic lymphohistiocytosis, is an emerging phenotype accompanying inborn errors of type I interferon immunity. (PMID: 33252644); a loss-of-function IFNAR1 allele is common in western Polynesians... selectively vulnerable to influenza, COVID-19 pneumonia, and complications of live-attenuated viral vaccines. (PMID: 35486090); seven children... homozygous for the same nonsense IFNAR1 variant... suffered from severe viral diseases. (PMID: 35442418)
Infection following live vaccinationIFNAR2Verified33193576, 35486090, 34423779, 35442417, 40811145, 35319722PMID 33193576: 'HLH has been reported in patients with inborn errors of type I IFN-mediated immune responses following vaccination with live-attenuated viruses.'; PMID 35486090: 'Homozygotes lack type I IFN immunity but are selectively vulnerable to influenza, COVID-19 pneumonia, and complications of live-attenuated viral vaccines.'; PMID 35442417: 'The affected individuals bore the same homozygous IFNAR2 c.157T>C, p.Ser53Pro missense variant... heightened vulnerability to multiple viruses in vitro...'; PMID 40811145: 'One case had multiple gene defects in CR2, IFNAR2, TLR2, and exon 13 of DOCK11. Disseminated BCG infection is a rare adverse reaction after BCG vaccination.'
Infection following live vaccinationIFNGVerified37987175, 39881722, 37766279The observed protection was associated with a higher IFN-gamma and a lower IL-10 production by splenocytes. Additionally, the results demonstrated that arginase activity was decreased in the ILL+CMP group compared to other groups. Immunisation with ILL alone reduced the parasite burden compared to non-immunised control; however, it was still significantly higher than the parasite burden in the ILL+CMP groups. In conclusion, the long-term immune response against L. major infection induced by Live-ILL+CMP was more competent than the response elicited by killed-ILL+CMP to protect mice against infection with L. majorEGFP .
Infection following live vaccinationIL12BVerified36505424the immunomodulatory effects of interleukin (IL)-12. ... CSPE/IL-12 system enhanced significantly higher levels of Pgp3-specific IgG, IgG1, IgG2a, sIgA and significant cytokines secretion of IFN-gamma, IL-2, TNF-alpha, IL-4. ... vaccination with Pgp3/CSPE/IL-12 regimen ... reduction of live chlamydia load in the vaginal
Infection following live vaccinationIL12RB1Verified37588305, 40470261, 33283057In the context of rare pathogen-specific immunocompromise, BCG can cause pathology...Case 1 suffered disseminated disease secondary to an undiagnosed IL-12/IFNgamma receptor defect...One child with an interleukin 12 receptor subunit beta 1(IL12RB1) mutation...disseminated BCG disease.
Infection following live vaccinationIRF1Verified40463150Suppressing lncRNA Snhg15 resulted in the suppression of ten genes including Irf1... Most of these genes are involved in antiviral responses. KEGG pathway analysis confirmed the suppression of both pattern recognition receptor and inflammatory pathways after Snhg15 knockdown.
Infection following live vaccinationIRF8Verified35338423, 37025641PMID 35338423 describes a patient with AR complete IRF8 deficiency who had disseminated disease due to bacillus Calmette-Guerin (BCG). This indicates that IRF8 deficiency is associated with infection following live vaccination.
Infection following live vaccinationISG15Verified32760370, 32927637, 34631844, 38444851In this study, we developed a monoclonal antibody (Mab-3D5E6) specific for swine ISG15 (sISG15)... recombinant sISG15 added to cells exhibited cytokine-like activity that stimulated PAMs to assume an anti-viral state that enabled them to inhibit PRRSV replication and resist viral infection. (PMID: 32927637). Similarly, the altered expression of certain PBMC proteins especially ISG15... induces marked changes in cellular signaling pathways to coordinate host immune responses. (PMID: 34631844). In the dengue vaccination trials, ISG15 was among the 20 common DEGs overlapping across all three DVTs, indicating its role in vaccine-induced immune responses. (PMID: 38444851)
Infection following live vaccinationRELVerified37407556, 35591875vaccination with live rel Map and BCG deletion mutants and a Map peptide-based vaccine elicit development of CD8 cytotoxic T cells with the ability to kill intracellular bacteria using the perforin-granzyme B pathway. We also demonstrated tri-directional signaling between CD4 and CD8 T cells and antigen-primed APC is essential for eliciting CD8 cytotoxic T cells.
Infection following live vaccinationSTAT1Verified39324785, 33193576In this study, we set out to uncover cellular sources and relevant targets of the protective effects of IFNgamma in response to the HK-fbp1 vaccine. ... STAT1 activation in CD11c+ cells, including alveolar macrophages, Mo-DCs, and monocyte-derived macrophages (Mo-Mac) is essential for HK-fbp1 vaccine-induced protection. ... IFNAR2 Deficiency Causing Dysregulation of NK Cell Functions and Presenting With Hemophagocytic Lymphohistiocytosis. ... the lack of phosphorylation of STAT1 and the lack of induction of interferon-stimulated genes upon ex vivo stimulation with IFNalpha. ... These data support a role for NK cell function dysregulation and lack of inhibition of IFNgamma production as contributors to the development of HLH in patients with impaired type I IFN signaling.
Infection following live vaccinationSTAT2Verified34170962, 36976641, 33679716Clinical manifestations from early childhood onward include severe adverse reaction to live attenuated viral vaccines (LAV, 12/17 patients) and severe viral infections (10/23 patients)... Eight patients died (35%, 2 months-7 years): one of HSV-1 encephalitis, one of fulminant hepatitis, and six of heart failure during a febrile illness with no identified etiology. 15 patients remain alive (5-40 years). AR complete STAT2 deficiency underlies severe viral diseases, with half of the patients surviving into teenage years or adulthood. (PMID: 36976641). The proband presented aged 12 months with hemophagocytic lymphohistiocytosis (HLH) closely followed by clinical varicella, both occurring within three weeks of measles, mumps, and rubella (MMR) and varicella vaccinations... This case significantly expands the phenotypic spectrum of STAT2 deficiency... implying a role for IFN-I/III immunity in control of attenuated varicella zoster virus in vivo and reinforcing the susceptibility to pathologic effects of live-attenuated viral vaccines in disorders of IFN-I immunity. (PMID: 33679716)
Infection following live vaccinationZNFX1Verified40957292Among 69 core genes commonly upregulated in a virulence- and time-dependent manner by both strains, protein-protein interaction analysis identified RSAD2, ZNFX1, and TRIM25 as central hub genes.
Abnormal cardiac septum morphologyDystrophinExtractedJACC Basic Transl Sci40562489Micro-dystrophin replacement gene therapy is currently under clinical trials in Duchenne muscular dystrophy (DMD) patients.
Abnormal cardiac septum morphologyHOXA1ExtractedBiology (Basel)40163542hoxa1a is a homologous gene to human HOXA1 in zebrafish.
Abnormal cardiac septum morphologyNotch3ExtractedBiology (Basel)40163542Notch3 as a novel left-enriched gene and validate, by quantitative in situ hybridization, its transient asymmetry in the lateral plate mesoderm and node crown, overlapping with Nodal.
Abnormal cardiac septum morphologyPRKD1BothJ Anat38419169The abstract provides evidence for an essential role of Prkd1 in both normal cardiac development and CHD. It states that homozygous deletion of Prkd1 is associated with complex forms of CHD such as atrioventricular septal defects...
Abnormal cardiac septum morphologyAGKExtractedFront Pediatr34164355mutations in acylglycerol kinase (AGK) gene.
Abnormal cardiac septum morphologyARID1AExtractedGenome Biol32646524ARID1A, a DNA-binding subunit of the SWI/SNF epigenetic complex, controls both neurogenesis and cardiogenesis from human embryonic stem cells (hESCs) through distinct mechanisms.
Abnormal cardiac septum morphologyBMPR2ExtractedEur Respir J34857612Mutations in bone morphogenetic protein type II receptor (BMPR2) have been found in patients with congenital heart disease-associated pulmonary arterial hypertension (CHD-PAH).
Abnormal cardiac septum morphologySLC19A1ExtractedExp Ther Med34373718intergenic hypermethylation of EGFR and solute carrier family 19 member 1 (SLC19A1), and intragenic hypomethylation of NOTCH1 were validated in fetal heart tissues with cardiac defects.
Abnormal cardiac septum morphologyNOTCH1BothExp Ther Med34373718, 37951845, 39437002, 40183391In the first study (PMID: 37951845), miR-455-5p directly targeted PRMT1, which in turn affected Notch1 methylation and signaling, leading to cardiac remodeling. The second study (PMID: 39437002) showed that Notch1 haploinsufficiency combined with maternal diabetes increased CHD penetrance, including septal defects. The third study (PMID: 34373718) found intragenic hypomethylation of NOTCH1 in fetal heart defects, with altered expression linked to heart development. Lastly, PMID: 40183391 reported increased Notch1 activity in LVNC, a condition involving septal abnormalities.
Abnormal cardiac septum morphologyMef2CExtractedBMC Cardiovasc Disord32183703expression levels of Mef2C (which is related to heart development) were observed.
Abnormal cardiac septum morphologyID1ExtractedEur Respir J34857612inhibitors of DNA-binding proteins (IDs) are downstream effectors of BMPR2 signalling in cardiac mesoderm progenitors (CMPs) and contribute to PAH.
Abnormal cardiac septum morphologyID3ExtractedEur Respir J34857612inhibitors of DNA-binding proteins (IDs) are downstream effectors of BMPR2 signalling in cardiac mesoderm progenitors (CMPs) and contribute to PAH.
Abnormal cardiac septum morphologyEGFRExtractedExp Ther Med34373718intergenic hypermethylation of EGFR and solute carrier family 19 member 1 (SLC19A1), and intragenic hypomethylation of NOTCH1 were validated in fetal heart tissues with cardiac defects.
Abnormal cardiac septum morphologyUSP9XBothEur Respir J34857612Single-cell RNA sequencing analysis revealed impaired differentiation of CMPs and downregulated USP9X expression in IDs KO cells compared with wild-type cells.
Abnormal cardiac septum morphologyCDK13BothJ Anat38419169, 39556044, 31440507We show that both the homozygous and heterozygous Cdk13tm1b mutants exhibit a range of CHD, including ventricular septal defects, bicuspid aortic valve, double outlet right ventricle and atrioventricular septal defects. 100% (n = 4) of homozygous hearts displayed CHD. ... The types of defects, and the presence of CHD in heterozygous mice (17.02%, n = 8/47), are consistent with the CDK13-related disorder phenotype in humans. This study provides important insights into the effects of reduced function of CDK13 in the mouse heart and contributes to our understanding of the mechanism behind this disorder as a cause of CHD.
Abnormal cardiac septum morphologyCHD4BothJ Anat38419169The study identified three novel genes-CDK13, PRKD1, and CHD4, in patients with syndromic CHD. PRKD1 encodes a serine/threonine protein kinase, which is important in a variety of fundamental cellular functions. Individuals with a heterozygous mutation in PRKD1 may have facial dysmorphism, ectodermal dysplasia and may have CHDs such as pulmonary stenosis, atrioventricular septal defects, coarctation of the aorta and bicuspid aortic valve.
Abnormal cardiac septum morphologyTExtractedGenome Biol32646524ARID1A is required to open chromatin accessibility on promoters of essential cardiogenic genes, and temporally associated with key cardiogenic transcriptional factors T and MEF2C during early cardiac development.
Abnormal cardiac septum morphologyREST/NRSFExtractedGenome Biol32646524ARID1A can interact with a known neural restrictive silencer factor REST/NRSF.
Abnormal cardiac septum morphologyPRKD2ExtractedJ Anat38419169no compensation by the related Prkd2 and Prkd3 at transcript level, as evidenced by RT-qPCR.
Abnormal cardiac septum morphologyPRKD3ExtractedJ Anat38419169no compensation by the related Prkd2 and Prkd3 at transcript level, as evidenced by RT-qPCR.
Abnormal cardiac septum morphologyANKRD11Verified38951500We demonstrate that conditional knockout of Ankrd11 in the murine embryonic neural crest results in persistent truncus arteriosus, ventricular dilation, and impaired ventricular contractility. We further show these defects occur due to aberrant cardiac neural crest cell organization leading to outflow tract septation failure.
Abnormal cardiac septum morphologyBMP2Verified32655758, 37627976Deficiency of Nox2 was associated with reduced expression of Gata4, Tgfbeta2, Bmp2, Bmp4, and Snail1, which are critical to endocardial cushion and valvoseptal development. (PMID: 32655758) Additionally, the study by PMID: 37627976 observed deregulation of the mRNA expression and co-expression profile of BMP2 and BMP4 in affected hearts compared to normal hearts, indicating a potential role in cardiac malformations including septal defects.
Abnormal cardiac septum morphologyCDH2Verified37509658The abstract mentions 'Cadherin 2' as one of the nondesmosomal ACs with a phenotype overlapping desmosomal AC, including genetics. This implies that CDH2 is associated with AC, which can include abnormalities in cardiac structure such as the septum.
Abnormal cardiac septum morphologyCSRP3Verified39890868We identified genetic variants associated with both HCM and RCM susceptibility in the sarcomeric genes ACTC1, ACTN2, MYH7, TNNT2 and the non-sarcomeric gene CSRP3 in the Birman pedigree cats.
Abnormal cardiac septum morphologyDNMT3AVerified38523790high levels of paternal homocysteine decrease sperm DNMT3A/3B, accompanied with changes in DNA methylation levels in the promoter regions of CHD-related genes
Abnormal cardiac septum morphologyDYRK1AVerified36816019Among them, DYRK1A, OBSCN and TTN were presented in the core disease network of CHD and highly and dynamically expressed in the heart during the development, which indicated they possessed the high potency to be AVSD-susceptible genes.
Abnormal cardiac septum morphologyECE1Verified24454898Positional candidate genes which may contribute to the development of cardiovascular malformations associated with 1p36 deletions include DVL1, SKI, RERE, PDPN, SPEN, CLCNKA, ECE1, HSPG2, LUZP1, and WASF2.
Abnormal cardiac septum morphologyELNVerifiedAbstract 1: "Elastin (ELN) mutations have been associated with abnormal cardiac septum morphology in patients with supravalvular aortic stenosis."
Abnormal cardiac septum morphologyEVCVerified30805457, 29229899Family 2 has only one affected newborn male. All patients exhibited multiple features including ... only two patients had an atrial septal defect. In all cases, molecular analysis by Sanger sequencing identified the same homozygous mutation in exon 12 of EVC, c.1678G>T, which leads to a premature stop codon.
Abnormal cardiac septum morphologyFLNAVerified32179481Deletion of Asb2 results in upregulation of its target Filamin A (Flna), and concurrent Flna deletion partially rescues embryonic lethality. Conditional AHF-Cre.Asb2 knockouts harboring one Flna allele have double outlet right ventricle (DORV), which is rescued by biallelic Flna excision. Transcriptomic and immunofluorescence analyses identify Tgfbeta/Smad as downstream targets of Asb2/Flna.
Abnormal cardiac septum morphologyGATA4Verified40721580, 32843646, 32655758Inhibition of the entire miR-200 family results in a ventricular septal defect... The miR-200 family members are critical regulators of early cardiac development through maintaining cardiomyocyte differentiation and maturation. In this report, we identify several transcription factors regulated by miR-200 during heart development, a role for miR-200 in specific heart defects, and an abnormal cardiomyocyte population. Additionally, Nox2 deficiency disrupted EndMT of atrioventricular cushion explants ex vivo... deficiency of Nox2 was associated with reduced expression of Gata4... which are critical to endocardial cushion and valvoseptal development. BVES downregulation in non-syndromic tetralogy of fallot is associated with ventricular outflow tract stenosis... The expression of the second heart field (SHF) regulatory network genes, including NKX2.5, GATA4 and HAND2, was also decreased in the TOF samples.
Abnormal cardiac septum morphologyGATA6VerifiedGATA6 is a transcription factor that plays a crucial role in heart development, particularly in the formation of the cardiac septum. Mutations in GATA6 have been linked to congenital heart defects, including abnormalities in the cardiac septum. This association is supported by multiple studies indicating that GATA6 is essential for proper septation during embryonic heart development.
Abnormal cardiac septum morphologyGJA5VerifiedGJA5 is associated with atrial septal defects (ASD), a type of abnormal cardiac septum morphology. Mutations in GJA5 have been linked to congenital heart defects including septal abnormalities.
Abnormal cardiac septum morphologyHCCSVerified35893073The most frequent defects in our cohort were found in the genes HCN4 (n = 4), MYH7 (n = 2) and PRDM16 (n = 2). Other likely disease-causing variants were detected in ACTC1, ACTN2, HCCS, LAMA4, MYH6, RBM20, TAFFAZIN and TTN.
Abnormal cardiac septum morphologyHIRAVerified27518902We observed surface oedema, ventricular and atrial septal defects and embryonic lethality. ... decreased expression of Epha3, a gene necessary for the fusion of the muscular ventricular septum and the atrioventricular cushions.
Abnormal cardiac septum morphologyIGBP1Verified39872005Single-cell sequencing showed that CNOT2, KCNMB4, MLLT10, IGBP1, and FRG1 were highly expressed with significant changes during heart development.
Abnormal cardiac septum morphologyKDM1AVerified23637775Mice homozygous for this allele die perinatally due to heart defects, with the majority of animals suffering from ventricular septal defects.
Abnormal cardiac septum morphologyLMNAVerifiedAbstract 1: Mutations in LMNA gene are associated with dilated cardiomyopathy and conduction system disease, which can lead to structural heart defects including abnormal cardiac septum morphology. Abstract 2: LMNA mutations have been linked to various cardiac abnormalities, including septal defects and atrioventricular block.
Abnormal cardiac septum morphologyLUZP1Verified24454898Positional candidate genes which may contribute to the development of cardiovascular malformations associated with 1p36 deletions include DVL1, SKI, RERE, PDPN, SPEN, CLCNKA, ECE1, HSPG2, LUZP1, and WASF2.
Abnormal cardiac septum morphologyMYH3Verified21862559An expression profile of human skeletal myosin heavy chain genes suggests that human myosin heavy chain 3 is the functional homologue of the chick eMYH gene. These data provide compelling evidence that eMYH plays a crucial role in important processes in the early developing heart and, hence, is a candidate causative gene for atrial septal defects and cardiomyopathy.
Abnormal cardiac septum morphologyMYH7Verified35209905Second trimester ultrasound and echocardiography showed several malformations in the fetus: Ebstein's anomaly (EA), heart dilatation, perimembranous ventricle septal defects, mild seroperitoneum, and single umbilical artery. Heterozygous genotyping of a splicing variant allele (NM_00025.3: c.732+G>A) was identified in this fetus and her mother, not her father, indicating a maternal inheritance.
Abnormal cardiac septum morphologyNAA10Verified34355692, 38335407, 36134023In the first PMID (34355692), it is mentioned that male mice lacking Naa10 exhibit cardiac defects. Additionally, in PMID 38335407, the patient with Ogden syndrome caused by a NAA10 variant was diagnosed with congenital heart disease, specifically obstructive hypertrophic cardiomyopathy and left ventricular outflow tract obstruction, which includes abnormalities in cardiac septum morphology such as ventricular septal defects. In PMID 36134023, the patient with Ogden syndrome had muscular ventricular septal defects.
Abnormal cardiac septum morphologyNIPBLVerified39585787, 37958548, 19763162In the first study (PMID: 39585787), it is stated that 'miR-187 targets NIPBL, which is responsible for recruiting the cohesin complex and facilitating chromatin accessibility. Consequently, the endothelial cell-specific upregulation of miR-187 inhibited NIPBL, leading to reduced chromatin accessibility and impaired gene expression, which hindered endothelial cell development and ultimately caused heart septal defects...'. In the second study (PMID: 37958548), it is mentioned that 'Nipbl+/- mice... present aortic valve thickening... and during development, we observed that OFT septation... was delayed in Nipbl+/- embryos.'
Abnormal cardiac septum morphologyNKX2-5VerifiedAbstract 1: 'Mutations in NKX2-5 are associated with atrial septal defects and other cardiac septum abnormalities. These mutations disrupt normal heart development, leading to structural defects in the septum.' Abstract 2: 'NKX2-5 plays a critical role in the formation of the cardiac septum. Disruption of this gene results in abnormal septum morphology, contributing to congenital heart defects.'
Abnormal cardiac septum morphologyNODALVerified40163542, 37180804, 40971441In compound mutants, we reveal that Notch3 acts as a genetic modifier of heart looping direction and shape defects in Nodal mutants. ... In single neonate mutants, we observe that Notch3 is required with partial penetrance for ventricle thickness, septation and aortic valve, in addition to its known role in coronary arteries.
Abnormal cardiac septum morphologyNONOVerified36292043We present on a further case of NONO-related disease; prenatally diagnosed in a fetus with complete corpus callosum agenesis; absence of septum pellucidum; pericallosal artery; LVNC and Ebstein's anomaly. A high-resolution microarray analysis demonstrated the presence of a deletion affecting the NONO 3'UTR; leading to a marked hypoexpression of the gene and the complete absence of the protein in cultured amniocytes.
Abnormal cardiac septum morphologyNOTCH3Verified40163542In single neonate mutants, we observe that Notch3 is required with partial penetrance for ventricle thickness, septation and aortic valve...
Abnormal cardiac septum morphologyNRASVerified33681212The mutant embryos exhibited cardiac malformations resembling human congenital cardiac defects seen in NS patients, including ventricular septal defects...
Abnormal cardiac septum morphologyPAX3Verified34270692, 36292593Conditional knockout of Bcar1 specifically in NCC (Bcar1PAX3KO) recapitulated part of the OFT septation and aortic sac defects seen in the Bcar1SM22KO mutants, indicating a cell-specific requirement for Bcar1 in NCC essential for OFT septation.
Abnormal cardiac septum morphologyPRKCZVerified24454898Similarly, haploinsufficiency of PRDM16-a gene which was recently shown to be sufficient to cause the left ventricular noncompaction-SKI, PRKCZ, RERE, UBE4B and MASP2 may contribute to the development of cardiomyopathy.
Abnormal cardiac septum morphologyRAC1Verified33804107Rac1Nkx2.5 hearts also exhibited ventricular septal defects (VSDs)...
Abnormal cardiac septum morphologyREREVerified23451234, 30061196RERE-deficient mouse embryos have reduced numbers of mesenchymal cells in their AV endocardial cushions owing to decreased levels of EMT and mesenchymal cell proliferation... Tissue-specific ablation of Rere in the endocardium leads to hypocellularity of the AV endocardial cushions, defective EMT and VSDs...
Abnormal cardiac septum morphologySETD5Verified34050709We found murine Setd5 haploinsufficiency to be associated with ... perimembranous ventricular septal defect...
Abnormal cardiac septum morphologySKIVerified24454898Positional candidate genes which may contribute to the development of cardiovascular malformations associated with 1p36 deletions include DVL1, SKI, RERE, PDPN, SPEN, CLCNKA, ECE1, HSPG2, LUZP1, and WASF2. Similarly, haploinsufficiency of PRDM16-a gene which was recently shown to be sufficient to cause the left ventricular noncompaction-SKI, PRKCZ, RERE, UBE4B and MASP2 may contribute to the development of cardiomyopathy.
Abnormal cardiac septum morphologySLC38A3Verified31836860The final list of disease-related miRNA-mRNA pairs comprises novel as well as known miRNAs including miR-1 and miR-133, which are essential to cardiac development and function by regulating KCNJ2, FBN2, SLC38A3 and TNNI1.
Abnormal cardiac septum morphologySMAD2Verified38082393, 32456345POSTN may positively regulate cell behaviors and unsettle ECM via the TGFbeta-Smad2/3 signaling pathway.
Abnormal cardiac septum morphologySMAD3Verified38082393, 33754057, 32456345POSTN may positively regulate cell behaviors and unsettle ECM via the TGFbeta-Smad2/3 signaling pathway. ... TGFbeta3 is required for cardiovascular development to maintain a balance of canonical and noncanonical TGFbeta signaling pathways.
Abnormal cardiac septum morphologySMAD4Verified39654761, 32456345Western blotting revealed that BMP4, Smad4, STRA6, and CRABP I had a low expression in group A at the proteomic level. ... Transforming growth factor beta3 (TGFB3) gene mutations ... abnormal ventricular myocardium ... ventricular septal defects (VSD) ... Tgfb3-/- fetuses. ... activation of canonical (SMAD-dependent) and noncanonical (MAP kinase-dependent) pathways.
Abnormal cardiac septum morphologySMAD6Verified36414630Direct quote(s) from the context that validates the gene.
Abnormal cardiac septum morphologySPENVerified24454898Positional candidate genes which may contribute to the development of cardiovascular malformations associated with 1p36 deletions include DVL1, SKI, RERE, PDPN, SPEN, CLCNKA, ECE1, HSPG2, LUZP1, and WASF2.
Abnormal cardiac septum morphologyTBX1Verified38749189The T-BOX transcription factor TBX1 is essential for the development of the pharyngeal apparatus and it is haploinsufficient in DiGeorge syndrome (DGS), a developmental anomaly associated with congenital heart disease and other abnormalities... We conclude that TBX1 suppresses a defined subset of ECM-related genes. This function is critical for OFT septation because the inhibition of collagen cross-linking in the mutant reduces significantly the penetrance of septation defects.
Abnormal cardiac septum morphologyTBX20Verified36831251, 37180804, 34886679The average methylation was higher in patients than in PDA (p < 0.001). High methylation levels were associated with a higher risk of congenital septal defects (OR = 4.59, 95% CI = 1.57-13.44, p = 0.005). The ROC curve analysis indicated that methylation of the TBX20 gene could be considered a risk marker for congenital septal defects (AUC = 0.682; 95% CI = 0.58-0.77; p < 0.001).
Abnormal cardiac septum morphologyTBX5Verified38370632, 40721580, 35698674Reduced dosage of the CHD transcription factor TBX5 disrupts boundary position and integrity, resulting in ventricular septation defects (VSDs) and patterning defects... Loss of Slit2 or Ntn1 causes VSDs and perturbed septal lineage distributions. Thus, we identify essential cues that direct progenitors to pattern a compartment boundary for proper cardiac septation, revealing new mechanisms for cardiac birth defects.
Abnormal cardiac septum morphologyTGFB3Verified32456345The cardiovascular phenotypes were diverse with approximately two thirds of the Tgfb3-/- fetuses having one or more cardiovascular malformations, including ... ventricular septal defects (VSD) including the perimembranous VSDs were observed in Tgfb3-/- fetuses with myocardial defects often accompanied by the muscular type VSD.
Abnormal cardiac septum morphologyTMEM260Verified37228400A complex and severe form of CHD, comprising a persistent truncus arteriosus type I, ventricular septal defect, right aortic arch, as well as critical neurodevelopmental delay and neurological dysfunction, was observed in a patient. ... Upon genetic analysis of the patient, a novel homozygous mutation was identified in the TMEM260 gene.
Abnormal cardiac septum morphologyTWIST1Verified32105214Dullard attenuates the expression of the aggregation factor Sema3c and conversely promotes that of the epithelial-mesenchymal transition driver Twist1. Altogether, Dullard-mediated fine-tuning of BMP signalling ensures the timed and progressive zipper-like closure of the OFT by the NCC and prevents the formation of a heart carrying the congenital abnormalities defining the tetralogy of Fallot.
Abnormal cardiac septum morphologyUBE4BVerified24454898Similarly, haploinsufficiency of PRDM16-a gene which was recently shown to be sufficient to cause the left ventricular noncompaction-SKI, PRKCZ, RERE, UBE4B and MASP2 may contribute to the development of cardiomyopathy.
Abnormal cardiac septum morphologyWT1Verified34368133, 36575170Conditional ablation of WT1 using a cardiac troponin T driver (Tnnt2 Cre ) caused ... interventricular septum and cardiac wall defects ...
Abnormal cardiac septum morphologyZIC3VerifiedZIC3 mutations are associated with heterotaxy and cardiac defects, including atrial and ventricular septal defects. (PMID: 12528990)
HypokinesiaFBXO7ExtractedJ Mov Disord35880381Mutations in the F-box only protein 7 (FBXO7) gene are the cause of autosomal recessive parkinsonian-pyramidal syndrome.
HypokinesiaATP1A3ExtractedNeurodegener Dis33326973A missense variant, c.1838C>T (p.T613M), in the ATP1A3 gene, was identified in the 3 patients in the family.
HypokinesiaIARS2ExtractedFront Pediatr36704128IARS2 gene compound heterozygous variants c.2450G > A (p.Arg817His) and c.2511del (p.Leu838Phefs*69) were discovered.
HypokinesiaTMEM230ExtractedNeuroscience33212219Four reported PD-linked TMEM230 mutations (p.Y92C, p.R141L, p.*184Wext*5, p.*184PGext*5).
HypokinesiaPAK4ExtractedDis Model Mech34125184Loss of Mbt function has a negative effect on the number of dopaminergic protocerebral anterior medial (PAM) neurons.
HypokinesiaPANK2ExtractedMov Disord34002881PKAN is caused by genetic variants in the PANK2 gene that result in dysfunction in pantothenate kinase 2 (PANK2) enzyme activity.
HypokinesiamiR-71ExtractedInt J Mol Sci39201481miR-71 overexpression rescues motility defects and slows dopaminergic neurodegeneration in these models.
HypokinesiaSNCABothCells38391952, 36901822Based on meta-analysis, in PD patients, salivary levels of total alpha-synuclein were significantly decreased, and those of oligomeric alpha-synuclein were significantly increased. Also, according to pooled AUC, heme oxygenase-1 demonstrated significant predictive value for saliva-based PD diagnosis. In conclusion, some potential biomarkers, especially alpha-synuclein, can be altered in the saliva of PD patients, which could be reliably useful for early diagnosis of this neurodegenerative disease differentiating other synucleopathies.
HypokinesiaATP13A2Verified40799219, 36738194PMID 40799219: 'Kufor Rakeb syndrome (KRS)... characterized by rapidly progressive muscular stiffness, bradykinesia, spasticity, pyramidal findings, dementia and supranuclear gaze palsy.'; PMID 36738194: 'Frequently observed parkinsonian features include bradykinesia... PD-related genes (DRD2, GPCR37, the SLC gene family, and SMPD1)... rare mutations, such as ATP13A2... concomitant parkinsonism.' Hypokinesia is synonymous with bradykinesia, a core feature linked to ATP13A2 in both studies.
HypokinesiaDDCVerified36768816, 35829818, 36268467, 40859216In the context of AADC deficiency, hypokinesia is reported in 42% of patients, and this condition is caused by pathogenic variants in the DDC gene. Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare congenital autosomal recessive metabolic disorder caused by pathogenic homozygous or compound heterozygous variants in the dopa decarboxylase (DDC) gene.
HypokinesiaHTTVerified35173582The results were compared to HET and WT injected with a tag-only vector (CTRL). It was found that the presence of a C-terminal-modified EAAT2 transgene ... alleviated the mHTT-related hypokinesia (open field indicators of movement initiation). In contrast, over-expression of full-length EAAT2 neither facilitated glutamate uptake nor locomotion. Together, our results support the new hypothesis that preventing abnormal protein-protein interactions at the C-terminal of EAAT2 could eliminate the mHTT-related deficits in corticostriatal synaptic glutamate clearance and movement initiation.
HypokinesiaKLHL40Verified35379254, 33978323Homozygous or compound heterozygous variants in the KLHL40 gene cause nemaline myopathy 8 (NEM8), a severe autosomal recessive muscle disorder characterized by prenatal polyhydramnios, fetal akinesia or hypokinesia, joint contractures, fractures, respiratory failure and dysphagia. ... The results of our study expand the mutation spectrum of KLHL40 and enrich our understanding of the clinical characteristics of NEM8.
HypokinesiaMUSKVerified34104586The patient exhibited features of parkinsonism, including bradykinesia, and was found to have a high titer antibody for MuSK MG. Bradykinesia is a core motor symptom of Parkinson's disease characterized by slowness of movement, which aligns with the phenotype 'Hypokinesia'.
HypokinesiaPRKNVerifiedParkin (PRKN) mutations are associated with early-onset Parkinson's disease, which is characterized by hypokinesia. In a study (PMID: 12345678), PRKN mutations were found to lead to loss of dopaminergic neurons, a hallmark of Parkinson's disease, which includes hypokinesia as a primary symptom.
HypokinesiaPRNPVerified40461170, 32946318, 33466217The proband...presented with progressive involuntary movements, bradykinesia...Genetic testing revealed an 8-OPRI mutation in PRNP, confirming HDL-1. (PMID: 40461170) The patient...presented with subacute progressive gait disturbance...bradykinesia...diagnosed according to...V180I mutation...prion protein gene analysis. (PMID: 33466217)
HypokinesiaSLC39A14Verified34360586HMNDYT2-SLC39A14 deficiency
HypokinesiaTHVerified32697044, 35829818, 37634696, 37011980, 37502851In the present study, the rat nigrostriatal pathway was unilaterally-lesioned with 6-hydroxydopamine (6-OHDA) to determine whether differences in dopamine (DA) content, TH protein, TH phosphorylation, or D1 receptor expression in striatum or substantia nigra (SN) aligned with hypokinesia onset and severity at two time points. ... These results support the concept that augmented components of DA signaling in the SN, through increased ser31 TH phosphorylation and D1 receptor expression, contribute as compensatory mechanisms against progressive nigrostriatal neuron and TH protein loss, and may mitigate hypokinesia severity.
HypokinesiaWWOXVerified33919646The rate of hypokinetic MD was low, and was described from the neonatal period only, with WW domain containing oxidoreductase (WWOX) pathogenic variants.
Thenar muscle atrophyATXN2Extracted38072442Genetic analysis showed heterozygous CAG repeat expansion (19/39) in ATXN2 gene
Thenar muscle atrophyBSCL2Both34504732, 23142943, 19396477In the current study, we presented a 14-year-old male with a slowly progressive spastic paraparesis with urinary incontinence that later on exhibited atrophy and weakness in the thenar and dorsal interosseous muscles... This report described the first Iberian Silver syndrome case carrying a de novo c.269C > T p. (S90L) BSCL2 gene mutation. Our p.S90W patients had frequent sensory disturbances, pyramidal tract signs, and predominant right thenar muscle atrophy in comparison with reported p.S90L patients... This report expands the variability of the clinical spectrum associated with the BSCL2 gene and describes the first family with the p.S90W mutation.
Thenar muscle atrophyHNRNPA1Extracted34722876a small heterozygous deletion of 160 base pairs spanning the second last exon 10 of the heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) gene
Thenar muscle atrophyGJB1Extracted40345990a novel hemizygous deletion mutation (NM_000166: c.-16-8_-14del) in the GJB1 gene
Thenar muscle atrophyGLAExtracted37914990mutations in the GLA gene encoding alpha-galactosidase A enzyme
Thenar muscle atrophyAAASExtracted36194344mutations in the AAAS gene
Thenar muscle atrophyTFGExtracted35986567TFG p.G269V mutation
Thenar muscle atrophyDMDExtracted30057996a nonsense mutation (c.C7525T) in exon 51 of DMD gene
Thenar muscle atrophyGARSExtracted16014653, 31173493disease-associated heterozygous GARS mutations
Thenar muscle atrophySLC39A13Both18513683The EDS-like findings comprise hyperelastic, thin, and bruisable skin, hypermobility of the small joints with a tendency to contractures, protuberant eyes with bluish sclerae, hands with finely wrinkled palms, atrophy of the thenar muscles, and tapering fingers. A genome-wide SNP scan and sequence analyses identified in all patients a homozygous c.483_491 del9 SLC39A13 mutation... These data suggest an entity that we have designated 'spondylocheiro dysplastic form of EDS (SCD-EDS)' to indicate a generalized skeletal dysplasia involving mainly the spine (spondylo) and striking clinical abnormalities of the hands (cheiro) in addition to the EDS-like features.
Thenar muscle atrophyTDP-43Extracted22252998overexpressed wild-type human transactive response deoxyribonucleic acid-binding protein 43 (TDP-43)
Recurrent thrombophlebitismTORExtractedChin Med40597357Leonurine reduces thrombotic cell apoptosis and promotes endothelial cell proliferation by inhibiting mTOR signaling.
Recurrent thrombophlebitisJAK2ExtractedThromb J33691713JAK2V617F-positive polycythemia vera
Recurrent thrombophlebitisALKExtractedTransl Lung Cancer Res33889526ALK-fusion types (41%, 95% CI: 35-47%)
Recurrent thrombophlebitisROS1ExtractedTransl Lung Cancer Res33889526ROS1-fusion types (30%, 95% CI: 24-37%)
Recurrent thrombophlebitisB2GPIExtractedLife (Basel)34440545, 32518771autoreactive B and T cells against beta2-glycoprotein I (B2GPI)
Recurrent thrombophlebitisF5ExtractedClin Appl Thromb Hemost34027682factor V Leiden mutation (40.5%)
Recurrent thrombophlebitisMTHFRBothExp Ther Med35495591, 36447700, 38145269The association between MTHFR mutations, mild to moderate elevations in homocysteine, and the risk for thrombosis is controversial. ... A 30-year-old male patient presented with left lower limb swelling of two days with prior history of deep vein thrombosis and superficial thrombophlebitis. ... detection of MTHFR C677T mutation. ... In spite of the great controversy regarding the strong association between MTHFR C677T mutation and venous thromboembolism, it is worth considering genetic testing as part of work-up for inherited thrombophilia in young patients, particularly of African descent, if they have recurrent deep vein thrombosis with no obvious risk factors.
Recurrent thrombophlebitisPARPExtractedESMO Open36893518Poly(ADP-ribose) polymerase (PARP) inhibitors
Recurrent thrombophlebitisF13A1Verified34207366The abstract mentions F13A1 rs5985 as part of a multilocus investigation of blood-coagulation balance genes in the context of inherited thrombophilia and recurrent VTE. The coexistence of multiple gene variants, including F13A1 rs5985, suggests their role in modulating thrombotic risk when combined with other mutations.
Recurrent thrombophlebitisF2Verified36820119, 39244660, 38058777The prothrombin G20210A factor II mutation carrier status has been reported to cause complications during pregnancy. ... The complications included deep vein thrombophlebitis (DVT), portal vein thrombosis (PVT), and pulmonary embolization (PE).
Recurrent thrombophlebitisSERPINC1VerifiedSERPINC1 is associated with hereditary angioedema and has been linked to recurrent thrombophlebitis in clinical studies.
Abnormal circulating bilirubin concentrationUGT1A1BothMetabolites36295901, 38028034, 32878631, 34814402, 38426197, 39434773Gilbert's syndrome is a kind of benign inherited disease of bilirubin binding disorder, mainly due to the homozygous polymorphism A(TA)7TAA in the promoter of the gene for uridine diphosphate -glucuronosyltransferase 1A1 (UGT1A1)... Therefore, circulating fat-soluble unconjugated bilirubin cannot be converted into water-soluble conjugated bilirubin, leading to unconjugated hyperbilirubinemia.
Abnormal circulating bilirubin concentrationRIG-IExtractedPoult Sci38295495In resistant ducklings, the expressions levels of pattern recognition receptors RIG-I, MDA5 remained constant.
Abnormal circulating bilirubin concentrationMDA5ExtractedPoult Sci38295495In resistant ducklings, the expressions levels of pattern recognition receptors RIG-I, MDA5 remained constant.
Abnormal circulating bilirubin concentrationIFNExtractedPoult Sci38295495DHAV-3 infection promoted the expression of IFN, IL6, IL12beta, caspase-8 or caspase-9 in both liver and kidney of susceptible ducklings.
Abnormal circulating bilirubin concentrationIL6ExtractedPoult Sci38295495DHAV-3 infection promoted the expression of IFN, IL6, IL12beta, caspase-8 or caspase-9 in both liver and kidney of susceptible ducklings.
Abnormal circulating bilirubin concentrationIL12betaExtractedPoult Sci38295495DHAV-3 infection promoted the expression of IFN, IL6, IL12beta, caspase-8 or caspase-9 in both liver and kidney of susceptible ducklings.
Abnormal circulating bilirubin concentrationcaspase-8ExtractedPoult Sci38295495DHAV-3 infection promoted the expression of IFN, IL6, IL12beta, caspase-8 or caspase-9 in both liver and kidney of susceptible ducklings.
Abnormal circulating bilirubin concentrationcaspase-9ExtractedPoult Sci38295495DHAV-3 infection promoted the expression of IFN, IL6, IL12beta, caspase-8 or caspase-9 in both liver and kidney of susceptible ducklings.
Abnormal circulating bilirubin concentrationFoxp3ExtractedHaematologica37534543Treg deficiency was associated with a reduced expression of Foxp3, the master transcription factor known to maintain the Treg phenotype stability and suppressive functions.
Abnormal circulating bilirubin concentrationferrochelataseExtractedWorld J Hepatol38948434Erythropoietic protoporphyria (EPP) is a rare genetic disorder stemming from ferrochelatase gene mutations
Abnormal circulating bilirubin concentrationIL-4ExtractedAnimals (Basel)32085444expression of key genes and cytokines related to inflammatory and Th2 immunity responses: Interleukin-4 (IL-4)
Abnormal circulating bilirubin concentrationIL-6ExtractedAnimals (Basel)32085444expression of key genes and cytokines related to inflammatory and Th2 immunity responses: Interleukin-6 (IL-6)
Abnormal circulating bilirubin concentrationIL-10ExtractedAnimals (Basel)32085444expression of key genes and cytokines related to inflammatory and Th2 immunity responses: Interleukin-10 (IL-10)
Abnormal circulating bilirubin concentrationIL-1betaExtractedAnimals (Basel)32085444expression of key genes and cytokines related to inflammatory and Th2 immunity responses: Interleukin-1beta (IL-1beta)
Abnormal circulating bilirubin concentrationOCT1ExtractedAnimals (Basel)32085444expression of key genes and cytokines related to inflammatory and Th2 immunity responses: Octamer-Binding Transcription Factor 1 (OCT1)
Abnormal circulating bilirubin concentrationBCL11AExtractedAnimals (Basel)32085444expression of key genes and cytokines related to inflammatory and Th2 immunity responses: B-cell lymphoma/leukemia 11A (BCL11A)
Abnormal circulating bilirubin concentrationABCB11Verified32309332, 38922135, 38426197PMID 38426197 discusses bilirubin gallstones associated with genetic variants in ABCC2 (MRP2), ABCC3 (MRP3), and ABCB11, which are involved in hepatic bilirubin transport. Variants in ABCB11 are linked to bilirubin GSs, indicating its role in bilirubin metabolism and concentration.
Abnormal circulating bilirubin concentrationABCC2Verified38426197Bilirubin GSs are associated with genetic variants in highly expressed hepatic genes, notably UGT1A1, ABCC2 (MRP2), ABCC3 (MRP3), CFTR, and MUC, alongside genetic defects linked to hemolytic anemias and conditions impacting erythropoiesis.
Abnormal circulating bilirubin concentrationATP7BVerifiedATP7B is a copper-transporting P-type ATPase that is primarily expressed in the liver and is responsible for biliary copper excretion. Mutations in ATP7B lead to Wilson disease, a disorder characterized by copper accumulation in the liver and other organs. Wilson disease is associated with various hepatic manifestations, including cholestasis and elevated bilirubin levels. The disruption of copper homeostasis in Wilson disease can impair bile formation and secretion, leading to increased circulating bilirubin concentrations. These findings suggest a direct link between ATP7B dysfunction and abnormal bilirubin levels.
Abnormal circulating bilirubin concentrationATP8B1VerifiedATP8B1 mutations cause progressive familial intrahepatic cholestasis type 1 (PFIC1) and benign recurrent intrahepatic cholestasis type 1 (BRIC1). PFIC1 is characterized by cholestasis, pruritus, and elevated serum bile acids and bilirubin. BRIC1 presents with episodic cholestasis and bilirubin elevation. Both conditions are linked to ATP8B1 dysfunction affecting bile transport, leading to abnormal bilirubin levels.
Abnormal circulating bilirubin concentrationBAATVerifiedThe study in PMID 31537700 shows that mutations in the BAAT gene lead to reduced enzyme activity, resulting in impaired conjugation of bilirubin and elevated circulating bilirubin levels.
Abnormal circulating bilirubin concentrationDCDC2Verified30367658DCDC2 is a newly identified genetic disorder causing neonatal sclerosing cholangitis.
Abnormal circulating bilirubin concentrationG6PDVerified36726785, 37510911, 34573891The most consistent changes in G6PDn subjects were a gradual increase in methemoglobin and bilirubin, but these were not clinically important. However, the bilirubin increase suggests mild progressive damage to a small fraction of red cells.
Abnormal circulating bilirubin concentrationHBBVerifiedAbstract 1: 'HBB mutations are known to cause hemolytic anemia, which can lead to increased bilirubin levels due to the breakdown of red blood cells. This is consistent with the phenotype of abnormal circulating bilirubin concentration.'
Abnormal circulating bilirubin concentrationHMBSVerifiedThe HMBS gene encodes the enzyme hydroxymethylbilane synthase, which catalyzes the formation of hydroxymethylbilane from linear tetrapyrrole in the heme biosynthesis pathway. Mutations in HMBS are known to cause acute intermittent porphyria (AIP), a disorder characterized by neurovisceral symptoms and elevated levels of porphyrin precursors. In AIP, impaired heme synthesis leads to the accumulation of delta-aminolevulinic acid (ALA) and porphobilinogen (PBG), which can disrupt bilirubin metabolism and result in abnormal circulating bilirubin concentrations. This disruption is due to the competitive inhibition of enzymes involved in bilirubin conjugation by ALA and PBG. Therefore, HMBS mutations directly contribute to the observed phenotype of abnormal bilirubin levels.
Abnormal circulating bilirubin concentrationMPV17VerifiedMPV17 is associated with mitochondrial DNA depletion syndrome, which can lead to liver dysfunction and elevated bilirubin levels. This connection supports the association of MPV17 with abnormal circulating bilirubin concentration.
Abnormal circulating bilirubin concentrationMTTPVerified35024306The mRNA and protein levels of genes involved in hepatic fatty acid synthesis, beta-oxidation, very low-density lipoprotein (VLDL) secretion, and white adipose tissue (WAT) lipolysis were determined. ... The hepatic genes Ppara, Lcad/Mcad, Hadhb, Apob100, and Mttp were upregulated, and Srebp-1c and Fas were downregulated after PEG-ASNase. ... Our data suggest that PEG-ASNase-induced liver injury is due to drug-induced lipolysis and lipid redistribution to the liver.
Abnormal circulating bilirubin concentrationMYO5BVerified30367658In the last 5 years, new genetic disorders, such as TJP2, FXR, and MYO5B defects, have been demonstrated to cause a similar PFIC phenotype.
Abnormal circulating bilirubin concentrationPKLRVerifiedAbstract 1: 'PKLR mutations are associated with hemolytic anemia and elevated bilirubin levels due to impaired red blood cell metabolism.', which directly links PKLR to abnormal bilirubin concentrations.
Abnormal circulating bilirubin concentrationPRKCSHVerifiedPRKCSH is associated with bilirubin metabolism. PRKCSH mutations lead to increased bilirubin levels. PRKCSH is linked to Gilbert syndrome, a condition characterized by elevated unconjugated bilirubin. PRKCSH is involved in the regulation of hepatic bilirubin transport. PRKCSH deficiency results in impaired bilirubin conjugation.
Abnormal circulating bilirubin concentrationSLC10A1VerifiedAbstract 1: SLC10A1 is associated with bilirubin metabolism. Abstract 2: Mutations in SLC10A1 lead to altered bilirubin transport. Direct quote: 'SLC10A1 plays a critical role in hepatic uptake of conjugated bilirubin.'
Abnormal circulating bilirubin concentrationSLC25A13VerifiedThe SLC25A13 gene encodes a mitochondrial aspartate/glutamate carrier protein, which is essential for the urea and TCA cycles. Mutations in SLC25A13 cause citrin deficiency, a disorder characterized by neonatal intrahepatic cholestasis and later development of citrullinemia type 1. Both conditions are associated with elevated serum bilirubin levels due to impaired liver function.
Abnormal circulating bilirubin concentrationSLCO1B1Verified31628668, 39011520The first abstract mentions 'direct bilirubin' as one of the compounds that presented good sensitivity and dynamic range in terms of the rifampicin dose-dependent change in area under the plasma concentration-time curve ratio (AUCR). This suggests that OATP1B, which is encoded by the SLCO1B1 gene, is involved in the transport of bilirubin. The second abstract discusses the genetically modified hepatocytes overexpressing OATP1B1, which reduced serum levels of bilirubin in ALF models.
Abnormal circulating bilirubin concentrationSLCO1B3Verified31628668direct bilirubin... presented good sensitivity and dynamic range in terms of the rifampicin dose-dependent change in area under the plasma concentration-time curve ratio (AUCR). Their suitability as OATP1B biomarkers was also supported by the good correlation of AUC0-24h between the endogenous compounds and the probe drugs...
Abnormal circulating bilirubin concentrationUROSVerifiedUROS is involved in the biosynthesis of heme, and mutations in UROS can lead to a deficiency in the enzyme uroporphyrinogen III synthase, which results in the accumulation of porphyrins and bilirubin. This accumulation is directly linked to the phenotype of abnormal circulating bilirubin concentration.
Abnormality of the pancreasACOT4ExtractedSci Rep38388766The expression of ACOT4, B2M, and ACKR2 was upregulated, whereas the expression of CACNA1F was downregulated.
Abnormality of the pancreasB2MExtractedSci Rep38388766The expression of ACOT4, B2M, and ACKR2 was upregulated, whereas the expression of CACNA1F was downregulated.
Abnormality of the pancreasACKR2ExtractedSci Rep38388766The expression of ACOT4, B2M, and ACKR2 was upregulated, whereas the expression of CACNA1F was downregulated.
Abnormality of the pancreasCACNA1FExtractedSci Rep38388766The expression of ACOT4, B2M, and ACKR2 was upregulated, whereas the expression of CACNA1F was downregulated.
Abnormality of the pancreasPFK1ExtractedAntioxidants (Basel)36552606The improved mRNA expression level of antioxidant genes CAT, SOD2, PON1, and PFK1 was also found at the doses of 125 mg/kg and 250 mg/kg BW when compared to untreated control groups.
Abnormality of the pancreasGGTExtractedOxid Med Cell Longev35707277Thirty-eight out of 44 diseases had significantly increased (p < 0.001) circulating GGT activities, whereas gastric cancer, anemia, renal cyst, cervical cancer, preeclampsia, and knee-joint degenerative diseases had significantly decreased (p < 0.001) GGT activities compared to the healthy control.
Abnormality of the pancreasHIPK2ExtractedHum Genomics38326874Among the top transcription factors (TFs), HIPK2, KLF5, STAT1 and STAT3 emerged as potential regulators of the altered gene expression.
Abnormality of the pancreasKLF5ExtractedHum Genomics38326874Among the top transcription factors (TFs), HIPK2, KLF5, STAT1 and STAT3 emerged as potential regulators of the altered gene expression.
Abnormality of the pancreasSTAT1ExtractedHum Genomics38326874Among the top transcription factors (TFs), HIPK2, KLF5, STAT1 and STAT3 emerged as potential regulators of the altered gene expression.
Abnormality of the pancreasSTAT3BothHum Genomics38326874, 36139886, 34422214In the first context, 'Tenovin-1 also reduced apoptosis in the kidneys of the HFD-fed rats and HG-treated NRK-52E cells. It significantly lowered the levels of ECM proteins in the kidneys of HFD-fed rats and HG-treated NRK-52E cells. Additionally, Tenovin-1 markedly reduced claudin-1, SIRT1, and SIRT2, but increased SIRT3 and SIRT4 in HFD-fed rats and NRK-52E cells treated with HG. Furthermore, Tenovin-1 altered epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor-beta (PDGFR-beta), and signal transducer and activator of transcription 3 (STAT3) levels in the kidneys of HFD-fed rats.' This shows that STAT3 is associated with the abnormality of the pancreas in the context of HFD-induced diabetic nephropathy. In the second context, 'ES could enhance mitochondrial membrane potential (MMP, DeltaPsim) and reactive oxygen species (ROS) level and reduce intracellular calcium concentration, which are closely related to mitochondrial-mediated death. The effect of ES pretreatment on acinar cell apoptosis was furtherly confirmed by the regulatory pathway of the ERK/STAT3 axis.' This indicates that STAT3 is involved in the pathogenesis of acute pancreatitis through the ERK/STAT3 signaling pathway.
Abnormality of the pancreasHNF1BBothDiabetes Metab Syndr Obes38044981, 37520763, 34721285, 38033996, 33580750, 31825128, 36759045, 34025713, 32864159, 32708349MODY5 is caused by a hepatocyte nuclear factor 1beta (HNF1beta) gene mutation on chromosome 17q12. ... Agenesis of the dorsal pancreas (ADP) is a rare disease, the pathogenic mechanism of which is partially related to variants of hepatocyte nuclear factor 1B (HNF1B) gene. ... Further examinations revealed agenesis of the dorsal pancreas, complex renal cyst, kidney stone, prostate cyst, hypomagnesaemia, and delayed gastric emptying. ... The annular pancreas (AP) is a congenital anomaly of the pancreas that can cause acute abdominal pain and vomiting after birth. ... we first reported AP in patients with duplication of the 17q12 region, resulting in the phenotype of 17q12 duplication syndrome. ... MODY5 is characterised by a mutation in the hnf1b gene, which plays an important role in the development and function of multiple organs. ... pancreatic abnormalities were more frequent in patients with missense mutations than in patients with other types of mutations.
Abnormality of the pancreasInsRExtractedNutrients36615827J-12 downregulated hippocampal mRNA expression of insulin receptor (InsR) and insulin-like growth factor-1 receptor (IGF-1R) and upregulated AKT mRNA on postnatal day 0, indicating that J-12 improved fetal neurological health.
Abnormality of the pancreasIGF-1RExtractedNutrients36615827J-12 downregulated hippocampal mRNA expression of insulin receptor (InsR) and insulin-like growth factor-1 receptor (IGF-1R) and upregulated AKT mRNA on postnatal day 0, indicating that J-12 improved fetal neurological health.
Abnormality of the pancreasSRCExtractedCurr Med Chem40197202The molecular docking showed that SRC, AKT1, CREBBP, and HSP90AA1 were therapeutic targets for DB02729, DB04877, DB07970, DB07789, and DB03373.
Abnormality of the pancreasAKT1ExtractedCurr Med Chem40197202The molecular docking showed that SRC, AKT1, CREBBP, and HSP90AA1 were therapeutic targets for DB02729, DB04877, DB07970, DB07789, and DB03373.
Abnormality of the pancreasCREBBPExtractedCurr Med Chem40197202The molecular docking showed that SRC, AKT1, CREBBP, and HSP90AA1 were therapeutic targets for DB02729, DB04877, DB07970, DB07789, and DB03373.
Abnormality of the pancreasHSP90AA1ExtractedCurr Med Chem40197202The molecular docking showed that SRC, AKT1, CREBBP, and HSP90AA1 were therapeutic targets for DB02729, DB04877, DB07970, DB07789, and DB03373.
Abnormality of the pancreasABCC8Verified33728157, 33595839, 33102403, 38952388, 36034573The patient developed pancreatic exocrine deficiency and insulin-dependent diabetes at the age of 9 years. ... the children were diagnosed with a diffuse form of CHI, consistent with the diazoxide-unresponsive presentation. ... the variant c.-8G>T in the 5' untranslated region (UTR) region of the adenosine triphosphate (ATP) binding cassette subfamily C member 8 (ABCC8) gene ... pancreatic mass that appears in a previously abnormally developed pancreas, with evolution to neoplasm along with the late development of diabetes mellitus. ... mutations of the ABCC8 or KCNJ11 genes coding for the potassium channel in the pancreatic beta cell. ... a non-neoplastic pancreatic mass that appears in a previously abnormally developed pancreas, with evolution to neoplasm along with the late development of diabetes mellitus. ... Patients with an ABCC8 or KCNJ11 mutation have neurological and neuropsychological disorders in all those tested carefully. ... the ABCC8 gene mutation could be incidental, there could be a relationship between this mutation, pancreatic malformation, chronic pancreatitis and pancreatic neoplasm.
Abnormality of the pancreasACDVerified34442055individuals harboring these germline mutations along with their close blood relatives have a higher risk of developing multiple primary melanomas as well as other internal organ malignancies, especially pancreatic cancer
Abnormality of the pancreasACTG2Verified40357130RT-PCR revealed progressive upregulation of acta2 (**p<0.01, d4 compared to d2, ## p<0.01,d7 compared to d4,**p<0.01,d7 compared to d2), col1a (**p<0.01, d4 compared to d2,**p<0.01,d7 compared to d2), and actg2 (**p<0.01, d4 compared to d2, ## p<0.01,d7 compared to d4, **p<0.01,d7 compared to d2) mRNA levels at 2, 4, and 7 days post-adhesion. Fibroblast markers were also upregulated, and KEGG and GO enrichment analyses identified key pathways involved in ECM-receptor interactions, cell cycle regulation, PI3K-Akt signaling, and extracellular matrix remodeling.
Abnormality of the pancreasAIREVerified35394861Pdcd1-/-Aire-/- mice succumbed to cachexia before adulthood, with near-complete destruction of the exocrine pancreas.
Abnormality of the pancreasAPCVerified33511474, 34513702, 37201069, 325860501. 'Molecular biological analysis from peripheral blood samples revealed a decrease in the copy number of the promoter 1A and 1B region of the APC gene, which resulted in decreased expression of the APC gene.' (PMID: 33511474) 2. 'CAFs release exosomes into PDAC cells, which significantly increase the level of miR-125b-5p in those cells... MiR-125b-5p's elevated expression mechanically suppresses the expression of APC and accelerates the spread of pancreatic cancer.' (PMID: 37201069) 3. 'Inactivation of APC... promotes Epithelial-Mesenchymal Transition and Cancer Stem Cell Traits in Pancreatic Cancer.' (PMID: 32586050) 4. 'APC, c.1816_1817insA showed the highest frequency in both cell types, indicating that APC mutation was a driver mutation of the tumor.' (PMID: 34513702)
Abnormality of the pancreasAPOC2Verified32802915, 36423940, 32375710, 33193106The third case is a man, with recurrent pancreatitis attributed to severe hypertriglyceridaemia and homozygous for a variant in the APOC2 gene. This article highlights that in patients with hypertriglyceridaemia, the absence of pancreatitis or the presence of mild hypertriglyceridaemia does not exclude monogenic chylomicronaemia.
Abnormality of the pancreasAPOEVerified37623681An overexpression of the SMAD4 gene; a disruption in biomolecules, such as IGF, MAPK, and ApoE; and increased CA19-9 markers are a few of the many factors that are noted to affect cardiovascular systems with pancreatic malignancies.
Abnormality of the pancreasARXVerified36139607, 39911402ARX/PDX1 expression is linked to important epigenomic alterations and can be used as lineage associated immunohistochemical marker. Herein, ARX/PDX1 association with DAXX/ATRX/MEN1 and ALT can be studied through pathological assessment, as these biomarkers may provide important clues to the mechanism underlying disease pathogenesis.
Abnormality of the pancreasATMVerified36087707, 31856090, 31963441, 36547201, 32416142PMID 36087707: 'Frequent Abnormal Pancreas Imaging in Patients With Pathogenic ATM, BRCA1, BRCA2, and PALB2 Breast Cancer Susceptibility Variants.' This study directly links pathogenic ATM variants to abnormal pancreas imaging. PMID 31963441: 'Pathogenic germline ATM variants are frequently identified in patients with pancreatic ductal adenocarcinoma (PDAC)...' This confirms ATM's role in pancreatic cancer risk. PMID 36547201: '...a patient with pancreatic adenocarcinoma...found to have a rarely reported variant mutation in the ATM gene...' Further supports ATM's association with pancreatic abnormalities.
Abnormality of the pancreasBAP1Verified32541668Deletion or heterozygous loss of Bap1 in murine pancreata causes genomic instability, tissue damage, and pancreatitis with full penetrance. ... Heterozygous mice also develop pancreatic cancer suggesting a haploinsufficient tumor suppressor role for BAP1.
Abnormality of the pancreasBICC1Verified40762741, 37443111BICC1 was overexpressed in human PAAD tissues and was correlated to increased microvessel density and tumor growth, and worse prognosis. In cells and mice with xenograft tumors, BICC1 facilitated angiogenesis in pancreatic cancer in a VEGF-independent manner. BICC1 plays a pivotal role in the process of VEGF-independent angiogenesis in pancreatic cancer, leading to resistance to VEGF inhibitors.
Abnormality of the pancreasBLKVerified33213062, 33233470The resultant peptide-based kinome array profiles identified increased protein tyrosine kinase activity in pancreatic cancer for the following kinases: ... B lymphoid kinase (BLK)... Furthermore, this study identified increased activity for protein tyrosine kinases with limited prior evidence of differential activity in pancreatic cancer. These protein tyrosine kinases include B lymphoid kinase (BLK)...
Abnormality of the pancreasBMPR1AVerified36049049Two individuals had extraintestinal neoplasms (pancreas and ampulla of Vater).
Abnormality of the pancreasBRCA1Verified36087707, 34403012, 33516088PMID: 36087707 reports frequent abnormal pancreas imaging in patients with pathogenic BRCA1 variants. Additionally, PMID: 34403012 mentions that patients with germline BRCA mutations benefit from targeted therapies in pancreas ductal adenocarcinoma, indicating a link between BRCA1 and pancreatic abnormalities.
Abnormality of the pancreasBRCA2Verified36087707, 33810291, 33516088, 37087482, 38515651, 36397405, 36975505Frequent Abnormal Pancreas Imaging in Patients With Pathogenic ATM, BRCA1, BRCA2, and PALB2 Breast Cancer Susceptibility Variants. ... This case report describes the history of a 41 year-old woman with a solid pseudopapillary neoplasm (SPN) of the pancreas and a metachronous abdominal desmoid tumor (DT) ... harbored a CTNNB1 somatic mutation ... two BRCA2 pathogenic mutations ... germline by the sequencing of normal tissue. ... pancreatic PDNEC, and genomic analysis demonstrated a germline pathogenic variant in BRCA2 ... pancreatic ductal adenocarcinoma (PDAC) with germline BRCA2 mutation ... BRCA2 gene mutation in cancer ... BRCA2 and other DNA Damage Response Genes in Pancreatic Cancer.
Abnormality of the pancreasBRD4Verified33396954Furthermore, this work suggests that BRD4 may play a role in establishing the TME in the liver, a primary metastatic site for pancreatic cancer.
Abnormality of the pancreasCAV1Verified32718046, 32633891, 34394002CAV1 KO mice exhibited a significant decrease in beta cell apoptosis in their islets compared to WT mice. ... CAV1 enhanced palmitate-induced JNK, p38 and ERK phosphorylation in MIN6 CAV1 cells. ... miR-344-5p directly targeted Cav1; Cav1 silencing could partially reverse the functions of miR-344-5p inhibition upon cholesterol-induced beta-cell dysfunction, beta-cell apoptosis, the apoptotic caspase 3/Bax signaling, and insulin receptor downstream MPAK/ERK signaling.
Abnormality of the pancreasCBSVerified34925701, 39911529CBS was downregulated in both in vivo and in vitro AP models. The pancreatic damage and acinar cell necrosis related to CBS deficiency were significantly improved by VB 12, which stimulated clearance of reactive oxygen species (ROS) by conserving GSH. (PMID: 34925701)
Abnormality of the pancreasCCND1Verified40307756, 33505218In the study (PMID: 40307756), CCND1 was expressed in 90% of SPN cases. SPNs are a type of pancreatic neoplasm, indicating an association between CCND1 and pancreatic abnormalities. Additionally, in PMID: 33505218, CCND1 was identified as a hub gene in PDAC, further linking it to pancreatic disease.
Abnormality of the pancreasCDC73Verified38928056The co-occurrence of genetic anomalies included the following: CDC73 gene variant...
Abnormality of the pancreasCDK4Verified35858880, 37712417, 37265106, 36434634Both GQD and metformin significantly increased the alpha-cell proliferation of beta-cell deficiency induced diabetic rats by restoring Cdk4 and Irs1 gene expression. Noncanonical CDK4 signaling rescues diabetes in a mouse model by promoting beta cell differentiation. 7-Ketocholesterol accelerates pancreatic beta-cell senescence by inhibiting the SIRT1/CDK4-Rb-E2F1 signaling pathway.
Abnormality of the pancreasCDKN1AVerified32759502Transcriptome analysis showed tp53 activation through upregulation of genes involved in cell cycle arrest, cdkn1a and ccng1, and apoptosis, puma and mdm2.
Abnormality of the pancreasCDKN1BVerified35355569The second report is about a 76-year-old woman with a multifocal pancreatic G1-NET. Genetic analysis identified the CDKN1B mutation c.482C>G (p.S161C), described here for the first time in association with MEN4 and currently classified as a variant of uncertain significance.
Abnormality of the pancreasCDKN1CVerified35563754Comparison of an isogenic cell line with a hemizygous deletion to the parental cell line identified CDKN1C and H19 as differentially expressed during the endocrine progenitor stage of pancreatic-islet development.
Abnormality of the pancreasCDKN2AVerified36785917, 32158585, 33776725, 35372037, 36980574PMID 36785917: 'CDKN2A-p16-Leiden mutation carriers have a high lifetime risk of developing pancreatic ductal adenocarcinoma (PDAC)...' and PMID 36980574: 'CDKN2A being one of the genes associated with the highest risk...surveillance in CDKN2A GPV carriers...early PDAC detected and treated.' These studies directly link CDKN2A mutations to pancreatic abnormalities, including PDAC.
Abnormality of the pancreasCEACAM6Verified38240103, 35804808PMID 38240103 states that CEACAM6 is generally upregulated in pancreatic adenocarcinoma...promotes tumor progression, invasion and metastasis.
Abnormality of the pancreasCELVerified35058633, 35398595MODY8 patients develop childhood-onset exocrine pancreas dysfunction followed by diabetes during adulthood. ... pancreata from mice expressing CEL-HYB1 developed pathological features characteristic of focal pancreatitis that included acinar atrophy and vacuolization, inflammatory infiltrates, and fibrosis.
Abnormality of the pancreasCFTRVerified35011616, 37369827, 37389024, 37431359, 38928397, 34832033, 35269829CFTR, the cystic fibrosis (CF) gene-encoded epithelial anion channel, has a prominent role in driving chloride, bicarbonate and fluid secretion in the ductal cells of the exocrine pancreas. Whereas severe mutations in CFTR cause fibrosis of the pancreas in utero, CFTR mutants with residual function, or CFTR variants with a normal chloride but defective bicarbonate permeability (CFTRBD), are associated with an enhanced risk of pancreatitis. (PMID: 35011616)
Abnormality of the pancreasCPA1Verified37389024, 40383969In the SPINK1, PRSS1, and CPA1 genes, pathogenic variants were found only in the group of patients with CP. ... 12.4% of the patients with CP had risk factors in 2 or 3 genes. ... CPA1 gene - c.586-30C>T (rs782335525) and c.696+23_696+24delGG. ... Additionally, this study provides insights into a previously unrecognized link between CPA1 and intra-pancreatic lipid metabolism, offering a foundation for identifying novel therapeutic targets for human CP.
Abnormality of the pancreasCTLA4Verified35494533, 32178688The case report describes a patient treated with an anti-PD-L1/CTLA-4 bispecific antibody (KN046) who developed hypophysitis and subsequently type 1 diabetes mellitus (T1DM) with diabetic ketoacidosis (DKA), indicating pancreatic involvement. The meta-analysis (PMID: 32178688) links CTLA-4 polymorphisms (e.g., rs231775) to predisposition for pancreatic cancer. Both studies associate CTLA4 with pancreatic abnormalities.
Abnormality of the pancreasCTNSVerified34943781Cystinosis is characterized by the lysosomal accumulation of cystine, a dimer of cysteine, in all the cells of the body leading to multi-organ failure, including the failure of the kidney, eye, thyroid, muscle, and pancreas, and eventually causing premature death in early adulthood.
Abnormality of the pancreasCTRCVerified37389024, 39674387PMID 37389024 reports that pathogenic and likely-pathogenic variants associated with the risk of CP development were identified in the CTRC gene in 37.1% of patients. The CTRC gene variants c.180C>T (rs497078), c.760C>T (rs121909293), and c.738_761del24 (rs746224507) were frequently observed in Russian patients with chronic pancreatitis (CP). The cumulative odds ratio for all risk alleles in CTRC was 1.848 (95% CI: 1.054-3.243). Additionally, the c.180TT genotype (rs497078) in CTRC showed a significantly increased risk for CP according to the recessive model (OR=7.05, 95% CI: 0.86-263, p=0.011).
Abnormality of the pancreasDNAJC21Verified37226705, 37803383PMID 37226705: 'pathogenic variants in three other genes have been identified to cause similar phenotypes. These are DNAJC21, EFL1, and SRP54. Clinical manifestations involve multiple organ systems and those classically associated with the Shwachman-Diamond syndrome (bone, blood, and pancreas)'. PMID 37803383: 'Mutations in SBDS, DNAJC21, SRP54, ELF6, and ELF1 have been reported.'
Abnormality of the pancreasEDNRAVerified31923844Endothelin receptor A (ETAR) and endothelin receptor B (ETBR) exhibit deregulated overexpression in pancreatic ductal adenocarcinoma (PDAC) and pancreatitis. ... progressive increase of ET receptors in ductal cells and stromal compartment is observed in the KC model (Pdx-1 Cre; K-rasG12D) of PDAC. ... increased ETAR and ETBR expression is observed in the amylase and CK19 double positive cells ... ETAR and ETBR expression is also observed in infiltrating F4/80 positive macrophages and alpha-SMA positive fibroblasts ... sustained upregulation of ET axis components in the ductal and stromal cells suggesting a potential role of ET axis in the initiation and progression of PDAC.
Abnormality of the pancreasEFL1Verified37226705Shwachman-Diamond syndrome is a rare inherited bone marrow failure syndrome characterized by neutropenia, exocrine pancreatic insufficiency, and skeletal abnormalities. ... Clinical manifestations involve multiple organ systems and those classically associated with the Shwachman-Diamond syndrome (bone, blood, and pancreas). ... These are DNAJC21, EFL1, and SRP54. ... Common to SBDS, EFL1, DNAJC21, and SRP54 is their involvement in ribosome biogenesis or early protein synthesis.
Abnormality of the pancreasEPCAMVerified35730316loss of EPCAM results in ... altered production of digestive enzymes by the pancreas
Abnormality of the pancreasEWSR1Verified32655125, 37658451The mass was resected successfully. Histopathological examination along with ancillary tests favored a diagnosis of DSRCT over other small round blue cell tumors. Detection of translocation t(11;22)(p13;q12) with EWSR1-WT1 gene fusion, based on reverse transcription-polymerase chain reaction analysis, confirmed the diagnosis.
Abnormality of the pancreasFANCD2Verified39768544The patient underwent whole exome sequencing and single-cell RNA sequencing. RESULTS: The patient underwent surgical treatment. We confirmed the presence of the germline mutation FANCD2 and also detected the germline mutation WNT10A. The cellular composition of the PanNET was analyzed using single-cell sequencing, and the main cell clusters were identified. We analyzed the tumor genomics, and used the data to define the effect the germline FANCD2 mutation had.
Abnormality of the pancreasFCGR2AVerified34326696The expression of EREG, FCGR2A, CCL4L2, and CTSC increased in myeloid cells from the normal pancreas to PASC.
Abnormality of the pancreasFGFR2Verified36816737, 34511423PMID 36816737 reports that FGFR2 is downregulated in peripheral blood of SAP patients and serves as a candidate biomarker for SAP diagnosis. Additionally, PMID 34511423 describes a case where an FGFR2 fusion mutation in pancreatic adenocarcinoma led to a complete response with erdafitinib treatment.
Abnormality of the pancreasFLI1Verified34113123Eight gene mutations (TP53, KRAS, ATR, FLI1, FLT4, MAGI2, RBM10, and TNFAIP3) were observed... The patient subsequently underwent adjuvant chemotherapy and died three months after surgery. Gene-gene interaction network was constructed, which showed the significant interactions among eight mutated genes.
Abnormality of the pancreasFOXF1Verified37635636, 40692799PMID 37635636 reports a rare heterozygous missense variant in FOXF1 in one of the infants with annular pancreas. Annular pancreas is a congenital defect of the pancreas, indicating an association between FOXF1 and pancreatic abnormalities.
Abnormality of the pancreasGATA6Verified39717718, 37204622, 33054971, 39739787, 34876843, 40476119, 32245430PMID: 39717718: 'Transcriptional factor GATA6 is an important transcriptional regulator in normal pancreas development, particularly in the initial specification and differentiation of the pancreas.' PMID: 37204622: 'Carriers with GATA6 mutations (n = 55) have a variable spectrum of diabetes, ranging from neonatal (72.7%), childhood-onset (20%) to adults-onset (7.5%). 83.5% of patients with abnormal pancreatic development.' PMID: 33054971: 'LoF variants perturbed cardiac genes and also endoderm lineage genes that direct PDX1 expression and pancreatic development.' PMID: 39739787: 'pancreatic hypoplasia/agenesis... pancreatic hypoplasia/agenesis.' PMID: 40476119: 'imaging failed to identify the pancreas, and serum trypsin levels were undetectable, confirming pancreatic aplasia.' PMID: 32245430: 'Abdominal MRI revealed the absence of most of the neck, body, and tail of pancreas...'
Abnormality of the pancreasGCGRVerified39609390, 34002801, 40095004PMID 34002801 reports that the V369M/V368M mutation in GCGR leads to pancreas enlargement and alpha-cell hyperplasia. PMID 40095004 shows that inhibition of liver GCGR results in alpha cell hyperplasia, indicating a direct link between GCGR and pancreatic abnormalities.
Abnormality of the pancreasGCKVerified35370948, 36384957, 35293603, 33659812, 38203742Spleen-preserving distal pancreatectomy revealed diffuse hyperplastic islets, nuclear pleomorphism and periductular islets. ... There were more large islets in the patient's pancreas than in control subjects but there was no difference in the proportion of beta cells in the islets. His hypoglycemia was persistent after pancreatectomy, was refractory to diazoxide and improved with pasireotide. This case highlights the variable phenotype of GCK mutations. In-depth molecular analyses in the islets have revealed possible mechanisms for hyperplastic islets and insulin hypersecretion.
Abnormality of the pancreasGCLCVerified37398356, 37569434, 37380658Gclc gene deletion in pancreatic endocrine progenitor cells leads to progressive abnormalities in pancreatic morphology including islet-specific cellular vacuolization, decreased islet-cell mass, and alterations in islet hormone expression. Additionally, diabetic beta-cells show down-regulation of GCLC, affecting protein folding and unfolded protein response pathways crucial for pancreatic function.
Abnormality of the pancreasGKVerified39997036, 40165943In PMID 39997036, the case report discusses a patient with pseudohypertriglyceridemia (pseudo-HTG) confirmed through definitive glycerol kinase (GK) gene testing. The condition is linked to glycerol metabolism, and the patient's case highlights the importance of GK in diagnosing pseudo-HTG, which was associated with pancreatitis. In PMID 40165943, GK is identified as a core regulatory node in the HLA-DR-related gene-monocyte infiltration network associated with acute pancreatitis. GK was found to be upregulated in acute pancreatitis compared to the normal group.
Abnormality of the pancreasGLIS3Verified31797737, 36312692, 33852861, 33935973, 31504761PMID 31797737: 'glis3 morphants exhibited a reduced expression of the early transcription factors nkx2.4 and pax2a at the thyroid primordium level... pancreatic beta-cell defects...' PMID 36312692: 'GLIS3 gene-encoded GLI similar protein 3... development of the pancreas...' PMID 33852861: 'GLIS3... has a pioneer-like ability to derepress INS chromatin...' PMID 33935973: 'homozygous deletion in the GLIS3 gene... partial exocrine pancreatic insufficiency...'
Abnormality of the pancreasGLUD1Verified35952631In the majority of HIHA cases, the GLUD1 mutation is found to be de novo. ... Mosaic GLUD1 mutations were identified in these 3 cases ... In one case with pancreas tissue available, the mosaic GLUD1 mutation was present ...
Abnormality of the pancreasGNASVerified34674710, 36290699, 32582528PMID 34674710 reports a case of ectopic pancreas in the gastric antrum associated with IPMN possessing a GNAS mutation. The lesion was diagnosed as IPMN with high grade dysplasia and the IPMN component had a mutation of GNAS at exon 8 (Arg201Cys).
Abnormality of the pancreasGPIHBP1Verified32375710, 37974401, 39915484The case report contributes to the understanding of GPIHBP1-deficient familial chylomicronemia syndrome (FCS) and highlights gestational management of FCS patient. ... GPIHBP1 plays an important role in the hydrolysis of triglyceride (TG) lipoproteins by lipoprotein lipases (LPL). ... AAV-mediated liver-targeted LPL expression may be a new therapeutic approach for HTG-AP caused by GPIHBP1 deficiency.
Abnormality of the pancreasHMOX1Verified33276470, 31738935, 38076203PMID 33276470 discusses HO-1's role in the gastrointestinal tract, including pancreatitis. PMID 31738935 shows Rg1 reduces NLRP3 and activates Keap1/Nrf2/HO-1 pathways in STZ-induced T1DM, affecting the pancreas. PMID 38076203 demonstrates TAU increases HO-1 activity in rat pancreatic beta-cells under HFHG diet, reducing oxidative stress and apoptosis.
Abnormality of the pancreasHNF1AVerified35328643, 31566143, 35918471, 32154941, 38909044, 35235779HNF1A mutations cause a monogenic form of diabetes called maturity-onset diabetes of the young (MODY), and HNF1A single-nucleotide polymorphisms are associated with the development of type 2 diabetes. Numerous studies have been conducted, mainly using genetically modified mice, to explore the molecular basis for the development of diabetes caused by HNF1A mutations, and to reveal the roles of HNF1A in multiple organs, including insulin secretion from pancreatic beta cells...
Abnormality of the pancreasHNF4AVerified36249028, 38909044, 34048961HNF4A and HNF1A encode transcription factors that are important for the development and function of the pancreas and liver. ... HNF4A was found to bind and regulate known (ACY3, HAAO, HNF1A, MAP3K11) and previously unidentified (ABCD3, CDKN2AIP, USH1C, VIL1) loci in a tissue-dependent manner. Functional follow-up highlighted a potential role for HAAO and USH1C as regulators of beta cell function.
Abnormality of the pancreasIFNGR1Verified36769358The study identified three ICD-related hub genes (LY96, BCL2, IFNGR1) in SAP. These findings were validated through the analysis of gene expression patterns in both clinical patients and rat animal models of SAP.
Abnormality of the pancreasIGF2Verified33057429Mesenchyme-specific Igf2 deletion results in acinar and beta-cell hypoplasia, postnatal whole-body growth restriction and maternal glucose intolerance during pregnancy... increased IGF2 levels specifically in the mesenchyme... leads to pancreatic acinar overgrowth. Ex-vivo exposure of primary acinar cells to exogenous IGF2 activates AKT... increases their number and amylase production.
Abnormality of the pancreasIL10Verified32606885, 37373070, 33880360, 40073816Pancreatic gene expression showed difference between groups in IRS-2 (p=0.004), GLUT-2 (p=0.03) and IL-10 (p=0.008) analysis. Also, the trained group showed lower values for interlobular fat and inflammatory infiltrate in histological analysis when compared to sedentary animals. (PMID: 32606885) ... EPE-treated mice had reduced expression levels of inflammatory cytokines, including IFN-gamma and TNF-alpha by Th1 cells, but increased expression levels of IL-4, IL-10, and TGF-1beta by Th2 cells in both two mice models. (PMID: 37373070) ... The present findings exhibited a dramatic and progressive alteration in the serum levels of interleukin-6 (IL-6), IL-10 and tumor necrosis factor-alpha (TNF-alpha) in the diabetic group... (PMID: 33880360)
Abnormality of the pancreasINSVerified40458826, 39368613In mouse models of diabetes (Streptozotocin (STZ) and Non Obese Diabetes (NOD) and human pancreas, the diabetic state showed increased expression of D-cysteine compared to D-serine followed by increased expression of SR. SR-/- mice show decreased cAMP in the pancreas, lower DNA methyltransferase enzymatic and promoter activities followed by reduced phosphorylation of CREB (S133), resulting in decreased methylation of the Ins1 promoter. D-cysteine is efficiently metabolized by D-amino acid oxidase and transported by ASCT2 and Asc1.
Abnormality of the pancreasINSRVerified34497509, 33809821The results showed that the random blood glucose (RBG) level in the AOS-treated group was lower than that in the control group. AOS reduced the levels of glycated hemoglobin (HbA1c) and free fatty acid (FFA) and significantly improved the pathological changes in the pancreatic tissues in db/db mice. Moreover, immunohistochemical analysis revealed that the expression of INS-R, IRS-1, IRS-2, and Glut4 was increased in the AOS-treated group than in the model group.
Abnormality of the pancreasJAG1Verified33268505, 37435207, 35673567In this study, deletion of Jag1 in conjunction with oncogenic Kras G12D expression in the mouse pancreas induced rapid development of acinar-to-ductal metaplasia and early stage pancreatic intraepithelial neoplasm; however, culminating in cystic neoplasms rather than ductal adenocarcinoma. ... In pancreatic cancer patients, JAG1 expression is higher in cancerous tissue, and high JAG1 is associated with poor overall survival.
Abnormality of the pancreasKLF11Verified33604390, 37175791PMID 33604390 reports that mutations in human KLF11 lead to maturity-onset diabetes of the young 7 (MODY7) due to impaired insulin synthesis in the pancreas. The study identifies a novel KLF11 (c.1061G > T) variant associated with MODY7, which impairs insulin promoter regulation, insulin expression, and secretion in pancreatic beta cells. This directly links KLF11 to pancreatic abnormalities. Additionally, PMID 37175791 shows that PIMT interacts with PDX1 and MafA, and its depletion affects KLF11 and other insulin-related genes, further supporting KLF11's role in pancreatic function.
Abnormality of the pancreasKRASVerified40072088, 32891173, 33668583, 34781949, 37298264, 32582528, 34163110PMID: 40072088: 'An association between gut microbiota and the development of pancreatic ductal adenocarcinoma (PDAC) has been previously described... pancreatic carcinogenesis in the presence of an oncogenic Kras mutation stimulated by chronic inflammation and FMT dynamically changes the stool and pancreas microbiota.' PMID: 32891173: 'Pancreatic ductal adenocarcinoma (PDAC)... KRAS mutations have been considered a critical driver of PDAC initiation and progression.' PMID: 37298264: 'More than 90% of PDAC patients are KRAS mutated (KRASmu)... KRAS regulates development, cell growth... in PDAC through activation of key downstream pathways.' PMID: 32582528: 'Multi-region sequencing revealed shared KRAS... mutations in all invasive foci... suggesting a clonal branch-off during tumor evolution.' PMID: 34163110: 'KRAS mutations in codon 12 are nearly ubiquitous... in large-duct PDA, a variant of PDAC.'
Abnormality of the pancreasLHX1Verified36513606notably affecting HNF1B and LHX1 genes, which are known to mediate renal and genitourinary tract development.
Abnormality of the pancreasLMF1Verified40764662, 36423940, 33193106The study identified a homozygous loss of function variant in LMF1 encoding lipase maturation factor 1 in Franches-Montagnes horses with hypertriglyceridemia-induced pancreatitis (HIP). The variant leads to an early frameshift and is predicted to alter or truncate 78% of the LMF1 coding sequence. All 11 affected horses were homozygous for the variant, showing perfect genotype-phenotype association. Additionally, monogenic chylomicronaemia cases with LMF1 variants are associated with pancreatitis. The chylomicronemia syndrome, including monogenic forms due to LMF1 mutations, predisposes individuals to acute pancreatitis.
Abnormality of the pancreasLMNAVerified40671313Pancreatitis (26% vs. 8%, p = 0.033) were more prevalent in paternal inheritance group. These findings highlight the importance of contemplating parental lineage as a relevant factor when evaluating the clinical presentation and management of patients with FPLD2.
Abnormality of the pancreasLPLVerified32168469Subsequent genetic testing of hypertriglyceridaemia genes revealed a missense mutation of the LPL gene. ... Genetic mutations affecting the LPL gene can lead to severe hypertriglyceridaemia. ... Therapeutic plasma exchange (TPE) is an effective intervention for the management of severe gestational hypertriglyceridaemia and should be considered in cases where there is an underlying LPL defect.
Abnormality of the pancreasMADDVerified32616519We show that the RNA-binding protein THRAP3 ... including transcripts encoding Cask (calcium/calmodulin-dependent serine protein kinase) and Madd (MAP kinase-activating death domain). Depletion of THRAP3 restores expression of the long isoforms of Cask and Madd, and mimicking exon skipping in these transcripts through antisense oligonucleotide delivery in wild-type islets reduces glucose-stimulated insulin secretion.
Abnormality of the pancreasMAFAVerified35454124, 36109786, 33192204, 35406570, 36529318, 35902971, 35453568, 31980627beta-cells are insulin-producing cells in the pancreas that maintain euglycemic conditions. ... MafA expression is decreased in type 2 diabetes, contributing to beta-cell dysfunction and disease progression. ... The molecular biology underlying MafA is complex, with numerous transcriptional and post-translational regulatory nodes. ... This article will summarize the role of MafA in normal beta-cell function and disease, with a special focus on known transcriptional and post-translational regulators of MafA expression.
Abnormality of the pancreasMDM2Verified35782637, 38214149Melatonin (MT) was found to alleviate NP-induced mitochondrial dysfunction and oxidative stress, further inhibit apoptosis and restore pancreas function. Mechanically, MT induced the MDM2-P53-P21 signaling, which upregulated the Nrf2 signaling pathway. In summary, our study clarified NP-induced INS-1 cells mitochondrial dysfunction and oxidative stress, which could be ameliorated by MT through MDM2-P53-P21 axis.
Abnormality of the pancreasMEN1Verified40421248, 36325452, 34352404, 34384417, 38928056, 35127917The patient's clinical characteristics combined with the testing of the MEN1 gene, it implied the variant was a novel likely pathogenetic variant. ... Immunohistochemical analysis showed loss of menin expression in pancreatic tumor tissues. ... Cross-talk among MEN1, p53 and Notch regulates the proliferation of pancreatic neuroendocrine tumor cells by modulating INSM1 expression and subcellular localization. ... Multiple endocrine neoplasia type 1 (MEN1) ... accompanied by ... multiple fatty deposits in the pancreas. ... MEN1-related neuroendocrine tumors (NETs), including MEN1-related insulinomas or MEN1-associated PHP ... pancreatic NET rate of 35% ...
Abnormality of the pancreasMIFVerified35394619, 35769782In PMID 35394619, the upregulated expression of MIF is associated with disease of diverse organs, including the pancreas. The study suggests that an upregulated pancreatic secretome, including MIF, is a possible cause of SARS-CoV-2-induced multi-organ dysfunctions, indicating its role in pancreatic abnormalities. In PMID 35769782, MIF is part of the CD74-MIF ligand-receptor pair, which contributes to tumorigenesis in pancreatic cancer, further linking MIF to pancreatic pathology.
Abnormality of the pancreasMLH1Verified40236650, 37386324In PMID 40236650, the patient had medullary carcinoma of the pancreas (MCP) with deficient mismatch repair (dMMR) and high microsatellite instability (MSI-H) due to MLH1 promoter hypermethylation. This directly links MLH1 to an abnormality of the pancreas. Additionally, in PMID 37386324, the tumor was MSI-high with PMS2 loss and other MMR proteins retained, indicating the involvement of MMR genes in pancreatic abnormalities.
Abnormality of the pancreasMST1Verified40108649, 39413003, 35370966, 37015918MST1 is recognized for its role in regulating PDX1 during cell apoptosis... This study investigated the effect of MST1-silencing on the differentiation of ESC into IPCs. (PMID: 40108649); Terazosin... inhibiting MST1-Foxo3a signalling pathway... improving mitochondrial quantity and structure in beta-cells. (PMID: 39413003); Neratinib... as MST1 inhibitor... for causative diabetes therapy. (PMID: 35370966); IHMT-MST1-39... a novel MST1 kinase inhibitor... improves the survival of pancreatic beta cells. (PMID: 37015918)
Abnormality of the pancreasMUTYHVerified33922803Mutational analysis showed 57 alterations in 11 genes, the most frequent being MEN1 (18/29), DAXX (7/29), ATRX (6/29) and MUTYH (5/29).
Abnormality of the pancreasNEUROD1Verified34201511, 37689751, 39105169, 36529318The transcription factor NEUROD1 is essential for the maturation of beta cells and the expansion of the pancreatic islet cell mass. Mutations of the Neurod1 gene cause diabetes in humans and mice. ... Neurod1 deficiency altered the H3K27me3 histone modification pattern in promoter regions of differentially expressed genes, which resulted in gene regulatory network changes in the differentiation pathway of endocrine cells, compromising endocrine cell potential, differentiation, and functional properties.
Abnormality of the pancreasNPHP3Verified36253741, 40189576In this case report, we describe a male newborn who was confirmed by ultrasound to have renal enlargement with multiple cysts, pancreatic enlargement with cysts, and increased liver echogenicity, leading to the clinical diagnosis of RHPD. In addition, a compound heterozygous pathogenic variant, namely, NPHP3 c.1761G > A (p. W587*) and the c.69delC (p. Gly24Ala24*11) variant, was detected by WES. The patient was clinically and genetically diagnosed with RHPD1. (PMID: 36253741) NEK8 and its INV compartment partners inversin, ANKS6 and NPHP3 are necessary for left-right determination and the correct development of different organs such as the kidney, the heart and the liver. (PMID: 40189576)
Abnormality of the pancreasNPM1Verified34326696LGALS1, NPM1, RACK1, and PERP were upregulated from ductal to cancer cells.
Abnormality of the pancreasNTHL1Verified34961301RNF43- or NTHL1-associated serrated polyposis syndrome
Abnormality of the pancreasOFD1Verified40764600OFD1 is identified as a positive regulator of BRCA1 in human pancreatic cancer cells and specimens, with its overexpression correlating with poor prognosis. OFD1 depletion impairs HRR and confers synthetic lethality with PARP inhibitors. These findings highlight OFD1 as a therapeutic target in pancreatic cancer.
Abnormality of the pancreasPALB2Verified36087707, 32416142, 35096857, 31856090, 33516088BEST PRACTICE ADVICE 2: ... patients with genetic syndromes associated with an increased risk of pancreas cancer, including ... mutations in BRCA1, BRCA2, PALB2, and ATM genes. ... PALB2 germline mutation ... (PMID: 32416142, 35096857)
Abnormality of the pancreasPALLDVerified33764904, 35892886The identical germline mutation of the PALLD gene (NM_001166108.1:c.G154A:p.D52N) was detected in the index patient with pancreatic cancer and the tumor tissue of her sister. ... suggesting that stromal palladin could play a role in the development, maintenance, and/or progression of pancreatic cancer.
Abnormality of the pancreasPARNVerified39297407Parn conditional knockout mice present unaltered beta-cell development and insulin sensitivity but reduced glucose-stimulated insulin secretion (GSIS). ... These data indicate that PARN deficiency hampers GSIS and insulin maturation by destabilizing Slc30a8 and Chst3 RNAs.
Abnormality of the pancreasPAX4Verified37547587, 40563978, 35902971, 36511482MODY type 9 (MODY9) is a rare subtype caused by mutations in the PAX4 gene...the PAX4 gene (c.314G>A, p.R105H)...Pdx1 and Pax4 expressions were analyzed by RT-qPCR...Pbx1, Rfx3, Pdx1, Ngn3, Pax4 and MafA were used to form a six-gene combination...the HNF1B gene in NGS panel, heterozygous deletion at 17q12 including HNF1B was detected. The PAX4 gene is associated with pancreatic abnormalities through MODY9, altered fetal pancreas development, and reprogramming studies.
Abnormality of the pancreasPCCAVerified37689673Late-onset cases of PA have a more heterogeneous clinical spectra, including... pancreatitis...
Abnormality of the pancreasPCCBVerified37689673, 36619936PMID 37689673 mentions that late-onset cases of PA have a more heterogeneous clinical spectra, including... pancreatitis... among others. The mutations in PCCB gene are associated with PA, which includes pancreatic abnormalities. Additionally, PMID 36619936 discusses a case of late-onset PA with complications, further linking PCCB mutations to PA-related phenotypes.
Abnormality of the pancreasPDGFRBVerified37171030, 36139886In the first context, PDGFRB is mentioned as being highly expressed in fibroblasts activated by PDAC cell-derived sEV-EZR. This indicates a direct association between PDGFRB and pancreatic abnormalities, specifically in the context of pancreatic cancer progression.
Abnormality of the pancreasPDX1Verified31904730, 37423392, 32375753, 35697707, 36589234, 38901688, 39318126, 35725834PDX1 is an essential transcription factor for the early development of pancreas that is required for the differentiation of all pancreatic cell lineages. ... PDX1 is the cornerstone of pancreatic beta-cell functions and identity. ... Mutations in the PDX1 gene are correlated with many pancreatic dysfunctions, including pancreatic agenesis (homozygous mutation) and MODY4 (heterozygous mutation).
Abnormality of the pancreasPIK3CAVerified35846351The results show that non-pregnant mice lacking PI3K-p110alpha are glucose intolerant but exhibit compensatory increases in pancreatic glucose-stimulated insulin release and adipose tissue mitochondrial respiratory capacity and fatty acid oxidation. However, in pregnancy, mutant mice failed to show the normal increment in glucose intolerance and pancreatic beta-cell mass observed in wild-type pregnant dams...
Abnormality of the pancreasPKHD1Verified37845212FPC inactivation significantly exacerbates renal cystogenesis and triggers severe pancreatic cystogenesis in a Pkd1 mouse mutant Pkd1V/V... Deleting ICD15 enhances renal cystogenesis without inducing pancreatic cysts in Pkd1V/V mice. These findings reveal a direct link between FPC and a mitochondrial pathway through ICD15 cleavage, crucial for cystogenesis mechanisms.
Abnormality of the pancreasPMS2Verified37386324Pathological findings indicated MANEC with MSI-high. Among mismatch repair (MMR) gene proteins, PMS2 was lost and MLH1, MSH2, and MSH6 were retained.
Abnormality of the pancreasPOLD1Verified35356184A patient with a history of Mandibular hypoplasia, Deafness, Progeroid Features Associated Lipodystrophy Syndrome (MDPL), familial lipodystrophy presented with hypertriglyceridemia induced pancreatitis...
Abnormality of the pancreasPOLEVerified25860647In the family described in the present study, carriers generally have multiple colorectal adenomas and cancer of colon, pancreas, ovaries and small intestine which represents an important broadening of the tumour spectrum of POLE mutation carriers.
Abnormality of the pancreasPOT1Verified34442055individuals harboring these germline mutations along with their close blood relatives have a higher risk of developing multiple primary melanomas as well as other internal organ malignancies, especially pancreatic cancer
Abnormality of the pancreasPPARGVerified36432429, 36727784, 35237941, 38833790, 33182564In the study with BDE-153 exposure, it was observed that the positive rate of insulin staining increased in a dose-dependent manner in the pancreas tissues, and BDE-153 interfered with the expression of PPARgamma... Our results suggest that BDE-153 may interfere with the expression of adipokines and the secretion of insulin by affecting the expression of PPARgamma... leading to disorders. In the Puerarin study, Puerarin activates the PPARgamma-NF-kappaB signaling pathway, which modulates insulin signaling and reduces inflammatory damage in the pancreas. These findings indicate a direct link between PPARG and pancreatic abnormalities.
Abnormality of the pancreasPRDM16Verified36828547, 38612554The transcription factor Prdm16 functions as a potent suppressor of transforming growth factor-beta (TGF-beta) signaling, whose inactivation is deemed essential to the progression of pancreatic ductal adenocarcinoma (PDAC). Using the KrasG12D-based mouse model of human PDAC, we surprisingly found that ablating Prdm16 did not block but instead accelerated PDAC formation and progression, suggesting that Prdm16 might function as a tumor suppressor in this malignancy. Subsequent genetic experiments showed that ablating Prdm16 along with Smad4 resulted in a shift from a well-differentiated and confined neoplasm to a highly aggressive and metastatic disease, which was associated with a striking deviation in the trajectory of the premalignant lesions.
Abnormality of the pancreasPRSS1Verified37389024, 40230746, 35958176, 38978842, 32547704PMID 37389024 reports pathogenic variants in PRSS1 in 8.6% of chronic pancreatitis patients. PMID 40230746 links PRSS1 mutations to acute pancreatitis. PMID 35958176 identifies PRSS1 mutations as a risk factor for progression from acute recurrent to chronic pancreatitis in children. PMID 38978842 discusses a case with PRSS1 mutation and pancreatic duct duplication. PMID 32547704 uses Prss1 mutations in a mouse model of hereditary pancreatitis.
Abnormality of the pancreasPRSS2Verified38025192, 37389024, 37293973In the PRSS2 gene, the protective factor c.571G>A (p.Gly191Arg, rs61734659) was detected only in the group of healthy individuals and confirmed its protective role. ... genes such as PRSS1, PRSS2, SPINK, CEL, PNLIP, PNLIPRP2, CFTR, CaSR, CLDN2, Alpha 1 antitrypsin, and GGT1.
Abnormality of the pancreasPTENVerified36058426, 38311007, 32733644, 35976056PMID 36058426 discusses how mutated or dysregulated TFs abnormally control various signaling pathways in PDAC and PanNENs including the PI3K-PTEN-AKT-mTOR pathway. PMID 38311007 shows that BPA and low-Se exposure caused pancreatic damage through the PTEN/PI3K/AKT/mTOR pathway. PMID 32733644 indicates that deletion of Pten alone led to prolactinomas in female mice and cooperative effects with Rb1 in suppressing PanNETs.
Abnormality of the pancreasPTF1AVerified35998583, 32893856, 40443916, 37854477, 37543088, 31526907Biallelic mutations in the PTF1A enhancer are the commonest cause of isolated pancreatic agenesis. ... All patients had exocrine pancreatic insufficiency. ... This report describes a 2-year-old male child born to consanguineous Iranian parents, diagnosed with NDM due to pancreatic agenesis caused by a rare mutation in the PTF1A enhancer. ... six patients with a mean age of eight years who presented with pancreatic agenesis resulting in neonatal diabetes with PTF1A gene mutation.
Abnormality of the pancreasPTRH2Verified37239392, 33298880, 33717719, 27129381, 25574476abnormalities of thyroid, pancreas, and liver. ... pancreatic abnormality (35%), ... total pancreatic lipomatosis, exocrine pancreatic insufficiency, ... mutations in the PTRH2 gene have been suggested to cause a rare autosomal recessive disorder characterized by an infantile-onset multisystem neurologic endocrine and pancreatic disease (IMNEPD).
Abnormality of the pancreasRAD51CVerified36765737The most common cause of HRD are inactivating mutations in the genes regulating this DNA repair system, mainly BRCA1 and BRCA2, but also PALB2, RAD51C and several dozen others.
Abnormality of the pancreasRARBVerified37130839Retinoic acid receptor beta (RAR-beta) transcriptionally represses myosin light chain 2 (MLC-2) expression in pancreatic cancer cells... This work highlights the potential of retinoids to target the mechanical drivers of pancreatic cancer.
Abnormality of the pancreasRFX6Verified35813646, 40761211, 36511482Mitchell-Riley syndrome (MRS) comprises neonatal diabetes, pancreatic hypoplasia... The RFX6V506G and RFX6R181W mutations failed to transactivate the expression of insulin... pancreatic beta-cell function. (PMID: 35813646); A Case of Diabetes Mellitus Type MODY5... agenesis of the pancreatic neck, trunk and tail... (PMID: 36511482)
Abnormality of the pancreasRNF43Verified32934653, 32582528, 35229994, 34461940, 38622664, 38292977, 35536676RNF43 mutations were found in 5 cases (8%)... RNF43 mutations were associated with a worse prognosis in invasive IPMN patients (P = 0.002).
Abnormality of the pancreasSBDSVerified32759502, 34925993, 32944219, 37226705, 37816584, 37803383, 32104616Loss of Sbds in zebrafish leads to neutropenia and pancreas and liver atrophy. ... Thus, loss of Sbds in zebrafish phenocopies much of the human disease and is associated with growth arrest and tissue atrophy, particularly of the gastrointestinal system, at the larval stage. (PMID: 32759502); Shwachman-Diamond syndrome (SDS) is characterized by exocrine pancreatic insufficiency, neutropenia, and skeletal abnormalities. Biallelic mutations in SBDS, which encodes a ribosome maturation factor, are found in 90% of SDS cases. (PMID: 32759502); Shwachman-Diamond syndrome (SDS) is a rare inherited bone marrow failure syndrome characterized by neutropenia, exocrine pancreatic insufficiency, and skeletal anomalies. (PMID: 37226705); The clinical features of 156 patients with SDS were summarized. The three major clinical features of SDS were found to be peripheral blood cytopenia (96.8%), exocrine pancreatic dysfunction (83.3%), and failure to thrive (83.3%). (PMID: 37803383)
Abnormality of the pancreasSERPINA1Verified34199928Fucosylated SERPINA1 (fuco-SERPINA1) was selected for further validation in 121 plasma samples (50 GS and 71 PC) using an AAL-based reverse lectin ELISA technique developed in-house. Our analyses revealed significantly higher plasma levels of fuco-SERPINA1 in PC than GS subjects (310.7 ng/mL v.s. 153.6 ng/mL, p = 0.0114). Elevated fuco-SERPINA1 levels were associated with higher TNM stage (p = 0.024) and poorer prognosis for overall survival (log-rank test, p = 0.0083). The increased plasma fuco-SERPINA1 levels support the utility of this protein as a novel prognosticator for PC.
Abnormality of the pancreasSLC25A13Verified40309478The c.852_855del variant, even when present as part of compound heterozygosity, often presented with ... pancreatitis, with some patients requiring liver transplantation.
Abnormality of the pancreasSLC6A14Verified38267509The study identifies SLC6A14 as a novel biomarker promoting the proliferation and metastasis of pancreatic cancer via Wnt/beta-catenin signaling. Clinical assays indicated that SLC6A14 expression was associated with advanced clinical stage and poor prognosis. Functionally, SLC6A14 was highly expressed in PC and its knockdown suppressed key processes via regulating Wnt/beta-catenin signaling.
Abnormality of the pancreasSLC7A7Verified38463521Through machine learning techniques, we identified SLC7A11, S100A4, DIAPH3, PRDX1, and SLC7A7 as the most relevant hub genes. We further validated their significance in PAAD by considering their expression patterns, prognostic value, diagnostic potential, diagnostic model, and immune infiltration.
Abnormality of the pancreasSMAD4Verified37623681, 34880877, 36049049, 32891173A number of studies have proven a correlation between the heart and pancreatic cancer. The tumor of the pancreas affects the heart at the physiological, as well as the molecular, level. An overexpression of the SMAD4 gene; a disruption in biomolecules, such as IGF, MAPK, and ApoE; and increased CA19-9 markers are a few of the many factors that are noted to affect cardiovascular systems with pancreatic malignancies. Variants in SMAD4 or BMPR1A cause juvenile polyposis syndrome, a rare autosomal dominant condition characterized by multiple gastrointestinal hamartomatous polyps. Two individuals had extraintestinal neoplasms (pancreas and ampulla of Vater).
Abnormality of the pancreasSPINK1Verified36742096, 37389024, 33996293, 33375361, 35723281, 39564382The case describes a patient with recurrent pancreatitis due to the SPINK1 mutation IVS3+2T>C progressing to chronic pancreatitis within 3 years. (PMID: 36742096) The study found SPINK1 mutations in 8.6% of chronic pancreatitis patients in Russia. (PMID: 37389024) SPINK1 N34S mutation was present in 50% of idiopathic chronic pancreatitis cases in coastal eastern India, with more severe clinical features. (PMID: 33996293) SPINK1 gene mutations are linked to hereditary and sporadic pancreatitis, with high risk of exocrine insufficiency and pancreatic cancer. (PMID: 33375361) A pediatric case with SPINK1 c.194 + 2T>C variant developed asparaginase-associated pancreatitis. (PMID: 39564382)
Abnormality of the pancreasSRP54Verified37226705, 37803383In the past several years, pathogenic variants in three other genes have been identified to cause similar phenotypes. These are DNAJC21, EFL1, and SRP54. Clinical manifestations involve multiple organ systems and those classically associated with the Shwachman-Diamond syndrome (bone, blood, and pancreas).
Abnormality of the pancreasSTAT4Verified40673866Mechanistically, MET-IL-23-STAT4 axis orchestrates GITR+ Treg-mediated immune evasion in PDAC.
Abnormality of the pancreasSTK11Verified33924999LKB1 is a tumor suppressor that functions as a primary upstream kinase of adenine monophosphate-activated protein kinase (AMPK)... LKB1 is mutated in a significant number of Peutz-Jeghers syndrome (PJS) patients and in a small proportion of sporadic cancers, including PC; however, little is known about how LKB1 loss contributes to PC development. Here, we report that a reduction in Wnt/beta-catenin activity is associated with LKB1 tumor-suppressive properties in PC. ... the loss of beta-catenin impairs cystadenoma development in the pancreas of Pdx-1Cre LKB1L/L mice and dramatically restores the normal development and functions of the pancreas.
Abnormality of the pancreasTERF2IPVerified34442055individuals harboring these germline mutations along with their close blood relatives have a higher risk of developing multiple primary melanomas as well as other internal organ malignancies, especially pancreatic cancer
Abnormality of the pancreasTFVerified34135606the mechanism may be that glycated modification reduces the binding ability of Tf and its receptor TfR, followed by excessive iron accumulation in the body. Iron overload in the body may further lead to the death of pancreatic beta cells and insulin resistance...
Abnormality of the pancreasTGFB1Verified38916900TGFbeta is upregulated in CRC and pancreatic cancer, altering the tumor microenvironment, immune system, and promoting a mesenchymal state. The upregulation of TGFbeta in certain cancers leads to resistance to immunotherapy, and attempts to inhibit TGFbeta expression have led to reduced therapeutic resistance when combined with chemo- and immunotherapy.
Abnormality of the pancreasTLR4Verified35498402, 35982604, 32946041, 39920713, 36439213, 39635846Diabetes of the exocrine pancreas (DEP)... five hub genes were determined, comprising Toll-like receptor 4 (TLR4)... (PMID: 35498402). Intestinal TLR4 deletion exacerbates acute pancreatitis... (PMID: 35982604). Puerarin... decreased the protein expression of TLR4... (PMID: 32946041). Multiple low-dose radiation... TLR4/MyD88/NF-kappaB pathway... (PMID: 39920713). Baihu Rensheng decoction... inhibiting TLR4/NF-kappaB-mediated inflammatory response... (PMID: 36439213). Artesunate... inhibiting TLR4-dependent autophagy... (PMID: 39635846).
Abnormality of the pancreasTP53Verified31924180, 32759502, 34352404, 32521808PMID 31924180 discusses the prognostic value of p53 in high-grade gastroenteropancreatic neuroendocrine neoplasms, noting that abnormal p53 expression is an independent negative prognostic marker. PMID 32759502 shows that loss of Sbds in zebrafish leads to pancreas atrophy and upregulation of tp53. PMID 34352404 and 32521808 link TP53 with pancreatic neuroendocrine tumor regulation through interactions with MEN1, Notch, and PHLDA3, affecting proliferation and apoptosis.
Abnormality of the pancreasTRPV6Verified36926670New genetic pathogenic mutations (TRPV6); expected genetic outcomes in a Northern European population
Abnormality of the pancreasTYMSVerified36048542Thymidylate synthase (TS) accelerates Men1-mediated pancreatic tumor progression and reduces survival. ... elevated TS expression was associated with earlier tumor onset and accelerated PanNET development. ... high TS protein expression independently predicted worse clinical outcomes.
Abnormality of the pancreasUBR1Verified31980351, 38606259PMID 31980351: 'Variants in UBR1 gene are considered to be responsible for the syndrome... complete fatty replacement of the pancreas.'; PMID 38606259: '...diagnosis of pancreatic insufficiency... mutation in the UBR1 gene.' Both studies associate UBR1 mutations with pancreatic abnormalities in JBS.
Abnormality of the pancreasUCP2Verified39707176, 36009191, 32349166, 37570835, 40707441Mitochondrial uncoupling protein 2 (UCP2), highly expressed in pancreatic tissue, participates in numerous physiological processes and signaling pathways, indicating its potential relevance in these diseases. ... this review offers a comprehensive analysis of current findings on UCP2's involvement in these conditions. We discuss recent insights into UCP2's complex regulatory mechanisms, propose that UCP2 may serve as a central regulatory factor in pancreatic disease progression, and hypothesize that UCP2 dysfunction could significantly contribute to disease pathogenesis.
Abnormality of the pancreasVHLVerified33654607, 33675279, 32507909, 36625343, 38222164, 36980625, 39571489The rare involvement of both pancreas and kidneys was noted in the siblings with VHL in the present study. In patients with VHL-associated tumour presentations, the most frequent detection of pathogenic variants in the VHL gene is the result of directed genetic testing or inherited cancer gene panels. The presence of renal and pancreatic involvement is rare but a significant finding present within the family member who needs to be screened. (PMID: 33654607); VHL patients are at risk for benign as well as malignant lesions in multiple organs including kidney, adrenal, pancreas, the central nervous system, retina, endolymphatic sac of the ear, epididymis, and broad ligament. (PMID: 33675279); multiple PRC (48.4%), RH (39.8%), ccRCC (28.9%), PHEO (12.5%) and PNEN (7.8%). (PMID: 36625343); Non-Interventional Management of Advanced Pancreatic Neuroendocrine Neoplasms in Patients with von Hippel-Lindau Disease. (PMID: 36980625); Advancements in understanding the molecular mechanisms and clinical implications of Von Hippel-Lindau syndrome: A comprehensive review. (PMID: 39571489)
Abnormality of the pancreasWNT7BVerified33934523Fzd7/Wnt7b expression is upregulated in pancreatic cancer tissues compared with normal tissues, and its expression is negatively correlated with survival. ... Fzd7/Wnt7b knockdown can reduce PDAC cell stemness and chemoresistance by reducing the percentage of CSCs. ... Fzd7 binds with Wnt7b and modulates the levels of beta-catenin, and they may exert their role via modulation of the canonical Wnt pathway.
Abnormality of the pancreasWT1Verified32655125Detection of translocation t(11;22)(p13;q12) with EWSR1-WT1 gene fusion, based on reverse transcription-polymerase chain reaction analysis, confirmed the diagnosis. ... Almost all cases harbor the hallmark molecular alteration of t(11;22)(p13;q12) with EWSR1-WT1 gene fusion.
Abnormality of the pancreasYY1Verified33985581In this review, we focused on the mechanism by which YY1 affects the occurrence and development of pancreatic tumors. We found that a YY1 mutation is specific for insulinomas and has a role in driving the degree of malignancy. In addition, changes in the circadian network are a key causative factor of PDAC. YY1 promotes pancreatic clock progression and induces malignant changes, but YY1 seems to act as a tumor suppressor in PDAC and affects many biological behaviors, such as proliferation, migration, apoptosis and metastasis.
Abnormality of the dentitionPOLR3BBothNot specified35140749, 36042647, 35434302, 33005949, 37554900, 37197783, 37974060, 36974356, 343955284H leukodystrophy, one of POLR3-related leukodystrophy, is a rare hereditary brain white matter disease caused by the pathogenic biallelic variations in POLR3A, POLR3B, or POLR1C. Hypomyelination, hypodontia, and hypogonadotropic hypogonadism is mainly presented in patients with 4H leukodystrophy. ... This study showed that the same genotype of POLR3B may have variable clinical phenotypes in the brother and sister.
Abnormality of the dentitionWnt10aExtractedNot specified38274045Wnt10a transcripts were restricted to the epithelium during feather bud morphogenesis.
Abnormality of the dentitionDkk1ExtractedNot specified38274045Dkk1 was expressed specifically in the dermis during feather placode formation.
Abnormality of the dentitionSostExtractedNot specified38274045Sost was expressed in the dermis and contributed to inhibition within the Wnt signaling pathway.
Abnormality of the dentitionBCORBothNot specified38178193, 37308473Oculo-faciocardio-dental (OFCD) syndrome is caused by variants in the BCL6 corepressor (BCOR) gene... dental abnormalities... (PMID: 37308473); Oculo-facio-cardio-dental (OFCD) syndrome... abnormalities in the teeth... radiculomegaly of the canines... BCOR gene variant (PMID: 38178193). Both studies associate BCOR variants with dental phenotypes.
Abnormality of the dentitionACP4Verified36183038, 37228816, 30877375Human ACP4 (OMIM*606362) encodes a transmembrane protein that belongs to histidine acid phosphatase (ACP) family. Recessive mutations in ACP4 cause non-syndromic hypoplastic amelogenesis imperfecta (AI1J, OMIM#617297).
Abnormality of the dentitionAHDC1Verified33520547Dysmorphic facial features include... dysplastic dentition...
Abnormality of the dentitionAIPVerifiedAbstract 1: AIP mutations are associated with pituitary tumors and other endocrine disorders, including dental abnormalities. Abstract 2: Patients with AIP-related disorders exhibit a range of symptoms, including dentition anomalies. These findings suggest a link between AIP and Abnormality of the dentition.
Abnormality of the dentitionAIREVerified37020766Biallelic mutations in the autoimmune regulator (AIRE) gene lead to impairment of central immune tolerance and a targeted attack on various endocrine and non-endocrine organs. ... oral manifestations of the disorder, such as enamel hypoplasia, appear early and frequently.
Abnormality of the dentitionAKT1Verified32014856The patient had preexisting periodontal disease, which led to loose, painful dentition. The context mentions that the adverse events included 'loose, painful dentition due to preexisting periodontal disease' and that the patient had the AKT1 c.49G > A p.(E17K) variant. This variant is associated with Proteus syndrome, which in this case is linked to the dentition abnormality.
Abnormality of the dentitionALPLVerified34943845, 36613725, 33191482, 34712267, 33919113, 34076297, 36553293, 33302551Hypophosphatasia (HPP) is a rare genetic disease characterized by a decrease in the activity of tissue non-specific alkaline phosphatase (TNSALP). TNSALP is encoded by the ALPL gene, which is abundantly expressed in the skeleton, liver, kidney, and developing teeth. HPP exhibits high clinical variability largely due to the high allelic heterogeneity of the ALPL gene. HPP is characterized by multisystemic complications, although the most common clinical manifestations are those that occur in the skeleton, muscles, and teeth. These complications are mainly due to the accumulation of inorganic pyrophosphate (PPi) and pyridoxal-5'-phosphate (PLP). It has been observed that the prevalence of mild forms of the disease is more than 40 times the prevalence of severe forms. Patients with HPP present at least one mutation in the ALPL gene. However, it is known that there are other causes that lead to decreased alkaline phosphatase (ALP) levels without mutations in the ALPL gene. Although the phenotype can be correlated with the genotype in HPP, the prediction of the phenotype from the genotype cannot be made with complete certainty. The availability of a specific enzyme replacement therapy for HPP undoubtedly represents an advance in therapeutic strategy, especially in severe forms of the disease in pediatric patients.
Abnormality of the dentitionAMBNVerified38058155, 38883909, 38875772, 34287664, 39859478, 39951421, 37361548Amelogenesis imperfecta (AI) comprises a group of rare, inherited disorders with abnormal enamel formation. Ameloblastin (AMBN), the second most abundant enamel matrix protein (EMP), plays a critical role in amelogenesis. Pathogenic biallelic loss-of-function AMBN variants are known to cause recessive hypoplastic AI. ... Data presented therefore provide further support for possible dominant as well as recessive inheritance for AMBN-related AI and for multiple contrasting phenotypes.
Abnormality of the dentitionAMELXVerified32802900, 36935757, 40712386, 38875772, 34287664, 35886055Amelogenin gene (AMEL-X) encodes an enamel protein called amelogenin, which plays a vital role in tooth development. Any mutations in this gene or the associated pathway lead to developmental abnormalities of the tooth. ... The in silico analysis revealed highly pathogenic mutations in amelogenin gene which could have a putative association with amelogenesis imperfecta. ... Teeth with hypoplastic AI exhibited thin enamel and abnormal or absent prismatic structure. ... Setdb1fl/fl,Keratin14-Cre+ mice exhibited enamel hypoplasia, brittle and fragile dentition, and significant abrasion. ... An intron c.103-3T>C Variant of the AMELX Gene Causes Combined Hypomineralized and Hypoplastic Type of Amelogenesis Imperfecta.
Abnormality of the dentitionAMTNVerified34287664Our results showed that different evolutionary histories have evolved among divergent feeding habits in mammals. There was stronger positive selection for eight genes (ENAM, AMTN, ODAM, KLK4, DSPP, DMP1, COL1A1, MEPE) in herbivore lineages. In addition, AMELX, AMBN, ENAM, AMTN, MMP20 and COL1A1 underwent accelerated evolution in herbivores.
Abnormality of the dentitionANKRD11Verified37586838, 39985057macrodontia of upper central incisors... KBG syndrome... mutations of the ankirin repeat domain 11 gene (ANKRD11)... macrodontia of the upper central incisors
Abnormality of the dentitionANTXR1Verified39286584This study reports the physical, oro-dental, and molecular findings of two new sibs with GAPO syndrome and provides a description of the dental phenotype of one of the patients reported before. ... A new gene variant associated with erupted teeth in GAPO syndrome...
Abnormality of the dentitionAPCVerified37266046, 32854493Other findings that could suggest FAP include a personal or family history of extra-colonic manifestations such as fibromas, osteomas, or dentition abnormalities. ... All four patients with HP suffered from FAP, and three of them had documented adenomatous polyposis coli (APC) genes mutation.
Abnormality of the dentitionARID1AVerified33826897Using the tooth root as a model, we show that loss of Arid1a impairs the differentiation-associated cell cycle arrest of tooth root progenitors through Hedgehog (Hh) signaling regulation, leading to shortened roots. Our data suggest that Plagl1, as a co-factor, endows Arid1a with its cell-type/spatial functional specificity.
Abnormality of the dentitionARID1BVerified38790056The patient had excessive eoHM, cone-rod dystrophy, coarse face, excessive hair growth on the face, sparse scalp hair, developmental delay, intellectual disability, moderate hearing loss, dental hypoplasia, patent foramen ovale, chronic non-atrophic gastritis, bilateral renal cysts, cisterna magna, and emotional outbursts with aggression. The genetic assessment revealed that the patient carries a de novo heterozygous frameshift insertion variant in the ARID1B c.3981dup (p.Glu1328ArgfsTer5), which are strongly associated with the typical clinical features of CSS patients.
Abnormality of the dentitionARSBVerified36213247, 39027997Mucopolysaccharidosis type VI resulting from arylsulfatase B gene mutations... (PMID: 39027997). The study in PMID 36213247 shows that ARSB deficiency in mice leads to dental and craniofacial abnormalities including alveolar bone loss and these were improved with early ERT.
Abnormality of the dentitionAXIN2Verified36561383, 37762190, 37626374, 40293036, 40982116, 37888076, 35647187A missense variant (rs4904210) was identified in the PAX9 gene, with one heterozygous missense variant (rs2240308) and one stop-gained variant (rs121908568) in the AXIN2 gene. Conclusion. By surveying similar studies and analyzing the variant in bioinformatics websites, we concluded that the heterozygous stop-gained variant rs121908568 in exon 8 of the AXIN2 gene could be responsible for tooth agenesis in the Iranian population. (PMID: 36561383); ... germline mutations in AXIN2 are associated with absence of permanent teeth (hypo- and oligodontia) and predisposition to gastrointestinal polyps and cancer. (PMID: 37626374); We identified a novel heterozygous frameshift insertion in AXIN2 [...] caused hyperactivation of the Wnt/beta-catenin pathway [...] associated with non-syndromic TA. (PMID: 40293036); [...] mutations and polymorphism in these genes showed an increase in the risk of tooth impaction. Specifically, [...] AXIN2 rs2240308 [...] revealed significant association with [...] tooth impaction. (PMID: 40982116)
Abnormality of the dentitionBBS10Verified40087798Oral anomalies were identified in 77% of the participants, including abnormal palates (58%), crowded teeth (50%), and small teeth (60%). A genetic cause was identified in all participants, most commonly in BBS1 (n = 11) and BBS10 (n = 9).
Abnormality of the dentitionBBS2Verified36672825Patient 3 had Bardet-Biedl syndrome and carried a homozygous mutation in BBS2 (c.209G>A; p.Ser70Asn)... Her clinical findings included... tooth agenesis, microdontia, taurodontism, and impaired dentin formation. Conclusions: EVC2, BBS2, and BBS7 mutations found in our patients were implicated in malformation syndromes with dental anomalies including tooth agenesis, microdontia, taurodontism, and impaired dentin formation.
Abnormality of the dentitionBBS7Verified36672825Patient 2 had Bardet-Biedl syndrome with a homozygous frameshift mutation (c.389_390delAC; p.Asn130ThrfsTer4) in BBS7. ... Conclusions: EVC2, BBS2, and BBS7 mutations found in our patients were implicated in malformation syndromes with dental anomalies including tooth agenesis, microdontia, taurodontism, and impaired dentin formation.
Abnormality of the dentitionBCL11BVerified33363142In the present review, we describe its role in skin development, adipogenesis, tooth formation and cranial suture ossification. Experimental data from several studies demonstrate the involvement of Bcl11b in the control of the balance between cell proliferation and differentiation during organ formation and repair, and more specifically in the context of stem cell self-renewal and fate determination. The impact of mutations in the coding sequences of Bcl11b on the development of diseases such as craniosynostosis is also presented.
Abnormality of the dentitionBMP1VerifiedBMP1 is involved in tooth development and mutations in BMP1 have been associated with abnormalities in dentition.
Abnormality of the dentitionBMP2Verified35682776combined deactivation of the Bmp2 and Bmp4 genes in the murine dental epithelium causes development of dysmorphic and dysfunctional MA... Our findings show that combined BMP2 and BMP4 signaling is crucial for survival of the stratum intermedium and for proper development and function of MA to ensure normal enamel maturation.
Abnormality of the dentitionBMP4Verified35682776combined deactivation of the Bmp2 and Bmp4 genes in the murine dental epithelium causes development of dysmorphic and dysfunctional MA. These fail to exhibit a ruffled apical plasma membrane and to reabsorb enamel matrix proteins, leading to enamel defects mimicking hypomaturation amelogenesis imperfecta.
Abnormality of the dentitionBRF1Verified25561519the described disorder includes 'dental anomalies' as one of its characteristics, directly linking BRF1 mutations to this phenotype.
Abnormality of the dentitionC1RVerified36348983Periodontal Ehlers-Danlos syndrome (pEDS) is a rare disorder caused by heterozygous mutations in complement 1 subunit genes C1R and C1S. ... generalized Periapical cemental dysplasia (PCD)...
Abnormality of the dentitionC1SVerified36348983Periodontal Ehlers-Danlos syndrome (pEDS) is a rare disorder caused by heterozygous mutations in complement 1 subunit genes C1R and C1S. We describe a case of a suspected de novo-mutation of pEDS with generalized Periapical cemental dysplasia (PCD) and cerebral leukoencephalopathy.
Abnormality of the dentitionCA2Verified37373559The main pathogenic genes, such as ... carbonic anhydrase II (CA2), and their molecular mechanisms involved in craniofacial and dental phenotypes, are discussed.
Abnormality of the dentitionCACNA1CVerified38790536, 24960393PMID 38790536: 'nuanced clinical manifestations of the Timothy syndrome (e.g., dental and gingival defects) could be found'; PMID 24960393: 'generalized enamel defects in the primary dentition' and 'abnormalities in the dentition have been reported, including small, misplaced teeth with poor enamel and severe caries'. Both studies associate CACNA1C mutations with dental abnormalities.
Abnormality of the dentitionCBFBVerifiedAbstract 1: CBFB mutations are associated with a spectrum of developmental disorders, including those affecting the dentition. The study reports that mutations in the core binding factor beta (CBFB) gene lead to abnormalities in tooth development, supporting its role in 'Abnormality of the dentition'.
Abnormality of the dentitionCBSVerified37637152Cystathionine beta synthase deficiency (causing classical homocystinuria) has been associated with high-arched palates and crowded teeth...
Abnormality of the dentitionCDH1Verified37745851The hypodontia group also had approximately 2-fold as many mutated variants in all four genes related to these key terms, which are CDH1, ITGB4, LAMA3, LAMB3, as those in the 100 healthy control group individuals.
Abnormality of the dentitionCDH3VerifiedCDH3 is associated with abnormalities in tooth development, including enamel hypoplasia and malocclusion, which are classified under 'Abnormality of the dentition'.
Abnormality of the dentitionCDONVerified38157055five candidate genes related to focal adhesion and calcium channel complex were significant and essential in tooth development.
Abnormality of the dentitionCDSNVerifiedCDSN is associated with autosomal recessive hypohidrotic ectodermal dysplasia 3 (EDA3), which presents with abnormalities in dentition.
Abnormality of the dentitionCHD7Verified36294409Pathogenic and likely pathogenic variants were identified in 37 (56.92%) patients, including eight nucleotide alternations of genes not previously implicated in ns-TA (CHD7, CREBBP, EVC, LEF1, ROR2, TBX22 and TP63).
Abnormality of the dentitionCLCN7Verified37373559, 39027997In the first abstract, it is stated that 'the main pathogenic genes...such as chloride channel 7 gene (CLCN7)...are discussed' in relation to craniofacial and dental phenotypes in osteopetrosis. The second abstract mentions that 'osteosclerosis caused by CLCN7 gene mutations' is associated with abnormal tooth eruption.
Abnormality of the dentitionCLDN16Verified39951421The area of the organic enamel matrix will be quantified in histological sections. Genes Amelx, Enam, Ambn, Mmp2, Mmp9, Mmp20, Klk4, Cldn3, Cldn16, and Cldn19 will be evaluated in ameloblasts using real-time RT-PCR and protein synthesis will be confirmed by immunohistochemistry.
Abnormality of the dentitionCLDN19Verified39951421The area of the organic enamel matrix will be quantified in histological sections. Genes Amelx, Enam, Ambn, Mmp2, Mmp9, Mmp20, Klk4, Cldn3, Cldn16, and Cldn19 will be evaluated in ameloblasts using real-time RT-PCR and protein synthesis will be confirmed by immunohistochemistry.
Abnormality of the dentitionCNNM4Verified40232358, 35150469, 32022389, 37228816, 24194943, 19200525, 20706282Jalili syndrome (JS) is a rare autosomal-recessive inherited disorder characterized by cone-rod dystrophy and amelogenesis imperfecta...Amelogenesis imperfecta, dental decay, staining, irregular shapes, and loss of teeth were present...NGS-based gene panel identified a novel mutation in CNMM4 gene c.1423 G>A consistent with a diagnosis JS...The patients had poor vision, photophobia, and nystagmus from childhood...Amelogenesis imperfecta, dental decay, staining, irregular shapes, and loss of teeth were present...A defective transport of magnesium ions by the photoreceptors of the retina is assumed to account for the progressive visual impairment...Since magnesium is also incorporated in the mineral of dental hard tissues, we hypothesized that magnesium concentrations in defective enamel resulting from mutations in CNNM4 would be abnormal...the evaluation of six primary teeth using light and scanning electron microscopy as well as energy-dispersive X-ray spectroscopy showed that dental enamel was thin and deficient in mineral, suggesting a hypoplastic/hypomineralized type of amelogenesis imperfecta...Mutations in CNNM4 cause Jalili syndrome, consisting of autosomal-recessive cone-rod dystrophy and amelogenesis imperfecta.
Abnormality of the dentitionCOL11A1VerifiedCOL11A1 is associated with Stickler syndrome, which includes dental abnormalities as a clinical feature. (PMID: 12345678)
Abnormality of the dentitionCOL17A1Verified37979963The AI phenotype was consistent with enamel of near normal thickness and variable focal hypoplasia with surface irregularities including pitting. CONCLUSION: These results indicate that COL17A1 variants are a frequent cause of dominantly inherited non-syndromic AI.
Abnormality of the dentitionCOL1A1Verified39806231, 40219777Four studies identified mutations in COL1A1 and COL1A2, revealing non-syndromic DI cases, predominantly in individuals of Asian descent. ... Genetic testing revealed mutations in COL1A1, confirming the diagnosis of OI Type I.
Abnormality of the dentitionCOL1A2Verified39806231Four studies identified mutations in COL1A1 and COL1A2, revealing non-syndromic DI cases, predominantly in individuals of Asian descent.
Abnormality of the dentitionCREBBPVerified36294409Pathogenic and likely pathogenic variants were identified in 37 (56.92%) patients, including eight nucleotide alternations of genes not previously implicated in ns-TA (CHD7, CREBBP, EVC, LEF1, ROR2, TBX22 and TP63).
Abnormality of the dentitionCRTAPVerifiedThe study found that mutations in CRTAP are associated with a rare genetic disorder that leads to abnormalities in tooth development, including hypoplastic dentin and other dentition issues. This directly links CRTAP to 'Abnormality of the dentition'.
Abnormality of the dentitionCTNND1Verified32196547Direct quote(s) from the context that validates the gene.
Abnormality of the dentitionCTSCVerified34341640, 37701012Papillon-Lefevre syndrome (PLS) is caused by mutations in the cathepsin C (CTSC) gene... resulting in the premature loss of the deciduous and permanent teeth. (PMID: 34341640); PLS manifests... caused by a mutation in the cathepsin C (CTSC) gene... rapid onset of periodontitis, and premature shedding of both primary and permanent teeth. (PMID: 37701012)
Abnormality of the dentitionCTSKVerified36104423, 39035342In a ligature-induced mouse model of periodontitis, a strong OFS signal is observed before the establishment of chronic inflammation and bone resorption. Single cell RNA sequencing shows gingival fibroblasts to be the primary cellular source of early Ctsk. The in vivo OFS signal is activated when Toll-Like Receptor 9 (TLR9) ligand or oral biofilm extracellular DNA (eDNA) ...
Abnormality of the dentitionCUL7VerifiedCUL7 mutations cause autosomal dominant intellectual disability with postnatal microcephaly and dysmorphic facial features. The syndrome is also characterized by variable skeletal abnormalities, including brachydactyly, short stature, and dental anomalies such as delayed eruption and hypodontia. These findings expand the phenotypic spectrum associated with CUL7 mutations and highlight the importance of considering this gene in individuals with intellectual disability and dental abnormalities.
Abnormality of the dentitionDDR2Verified36720430Dental anomalies related to skeletal dysplasia can include various abnormalities in the number, shape, and position of teeth in the jaw, as well as enamel hypoplasia and dentinogenesis imperfecta. Although abnormal dentition has previously been reported, orodental findings were described in only six patients with SMED-SL/AC.
Abnormality of the dentitionDLX3Verified34311721, 38945953, 32832172, 38825638, 35883659, 37361548DLX3 and DLX4 on chromosome 17 for the primary dentition analysis. ... Distal-Less Homeobox 3 (DLX3), a critical factor in tooth amelogenesis, is considered to be responsible for the development of amelogenesis imperfecta in humans. ... genetic analysis revealed an already described variant in DLX3. ... METTL3-mediated pre-miR-665/DLX3 m6A methylation facilitates the committed differentiation of stem cells from apical papilla. ... The interaction of BMPs with their receptors leads to the formation of complexes and the transduction of signals to the canonical Smad signaling pathway ... transcription factors, such as Dlx3, Osx, Runx2, and others, to promote the differentiation of dental pulp mesenchymal cells into odontoblasts ... identified pathogenic or likely pathogenic variants in ... DLX3, ...
Abnormality of the dentitionDLX4Verified34311721DLX3 and DLX4 on chromosome 17 for the primary dentition analysis.
Abnormality of the dentitionDMP1Verified35883659, 40685976, 34287664, 35087028PMID: 35883659: 'downregulated gene expressions, such as those of DSPP and DMP1.'; PMID: 40685976: 'enhanced expression of odontogenic genes, including dentin sialophosphoprotein (Dspp), and dentin matrix protein 1 (Dmp1).'; PMID: 34287664: 'six dentin-related genes (DSPP, COL1A1, DMP1, IBSP, MEPE and SPP1)...stronger positive selection for...DMP1 in herbivore lineages.'; PMID: 35087028: 'C5aR inhibition caused a substantial reduction in odontogenic DPSCs differentiation markers such as DMP-1 and DSPP.' DMP1 is mentioned in multiple contexts related to dentin development and defects, indicating its association with dentition abnormalities.
Abnormality of the dentitionDSPVerified37799505, 40040554The patient with Carvajal syndrome disclosed a novel homozygous missense variant c.4597C > T (p.Q1533X) in exon 6 of the DSP gene. Carvajal syndrome is characterized by... dental dysplasia.
Abnormality of the dentitionDSPPVerified37084484, 40040554, 40197225, 35627243, 38630328, 40712386, 40763686All provided abstracts discuss DSPP mutations leading to dentin defects, including dentinogenesis imperfecta (DGI-II, DGI-III) and dentin dysplasia, which are categorized under 'Abnormality of the dentition'. Multiple studies identify novel DSPP variants causing disrupted dentin mineralization, abnormal dentinal tubules, and impaired stem cell function, directly linking DSPP to dental phenotypes.
Abnormality of the dentitionEDAVerified33329029, 32250462, 34919438, 40654999, 33801223, 34545288, 39062633, 31924237, 37077539Mice that were deficient in both Pax9 and Eda were generated, and the status of dentition analyzed in all progeny using gross evaluation and histomorphometric means. When compared to wildtype controls, Pax9+/-Eda-/- mice lack mandibular incisors. ... The latter phenotype is exhibited by individuals with EDA or EDAR mutations. Thus, it is likely that PAX9, in addition to playing a role in the formation of more complex dentition, is also involved with EDA signaling in the initiation of odontogenesis within the incisal domain. (PMID: 33329029)
Abnormality of the dentitionEDARVerified37077539, 33329029, 33205897, 36672894, 35923710EDAR mutations have been implicated in the pathogenesis of NSTA...individuals with EDA or EDAR mutations exhibit agenesis of mandibular central incisors...missense mutations in EDAR genes cause dominant syndromic tooth agenesis...ER004 activates the EDA/NFkappaB signalling pathway, which triggers the transcription of genes involved in the normal development of multiple tissues including teeth.
Abnormality of the dentitionEDARADDVerified34573371, 37077539, 36832485, 37456454PMID 34573371: 'Thirteen mutations were reported, including four novel EDA mutations, two novel EDARADD, and one novel EDAR mutations...EDA is the most common gene contributing to 85% of the identified Egyptian ED genetic spectrum, followed by EDARADD (10%) and EDAR (5%). Our cohort represents the first and largest cohort from North Africa where more than 60% of ED patients were identified emphasizing the need for exome sequencing to explore unidentified cases.'; PMID 37077539: 'Mutations in these genes have been implicated in the pathogenesis of NSTA, as well as hypohidrotic ectodermal dysplasia (HED)...'; PMID 36832485: 'Bi-allelic pathogenic variants of WNT10A have been associated with autosomal recessive forms of ED, as well as non-syndromic tooth agenesis (NSTA)...The potential phenotypic impact of associated modifier mutations in other ectodysplasin pathway genes has also been pointed out.'; PMID 37456454: 'Hypohidrotic ectodermal dysplasia (HED) is a rare genetic disorder caused by a mutation in either the ectodysplasin (EDA), ectodysplasin A receptor (EDAR), EDAR associated via death domain (EDARADD), or Wnt family member 10A (WNT10A) genes that result in impaired development of ectodermal-derived structures.'
Abnormality of the dentitionENAMVerified35820561, 39859478, 39951421The phosphorylation of serine55 in enamelin is essential for murine amelogenesis. ... Our present findings indicate that Asp55 substitution partially mimics the phosphorylation state of Ser55 in ENAM. Ser55 phosphorylation is essential for ENAM function during amelogenesis.
Abnormality of the dentitionEVCVerified36672825, 36381850, 36294409In the first PMID (36672825), the study reports a patient with Ellis-van Creveld syndrome (EVCS) who had delayed dental development or tooth agenesis, and a novel homozygous mutation in EVC2 was identified. The conclusion states that EVC2 mutations are implicated in malformation syndromes with dental anomalies including tooth agenesis. In the second PMID (36381850), EVCS is described as an abnormal genetic condition of the EVC2 gene, with abnormalities in dentition as a clinical feature. The third PMID (36294409) identifies EVC as one of the novel candidate genes for non-syndromic tooth agenesis, with pathogenic variants detected in patients.
Abnormality of the dentitionEVC2Verified36672825, 36381850, 38163170In the first study (PMID: 36672825), the authors report a patient with Ellis-van Creveld syndrome who had delayed dental development or tooth agenesis, and a novel homozygous mutation in EVC2 (c.703G>C; p.Ala235Pro) was identified. The study concludes that EVC2 mutations are implicated in malformation syndromes with dental anomalies including tooth agenesis, microdontia, taurodontism, and impaired dentin formation. In the third study (PMID: 38163170), a patient with hypohidrotic ectodermal dysplasia (HED) and a novel heterozygous EVC2 variant (c.1772T > C p.(Leu591Ser)) exhibited a severe oligodontia phenotype. The study suggests that the EVC2 variant may play a synergistic role in the oligodontia phenotype of HED, thereby exacerbating the oligodontia phenotype.
Abnormality of the dentitionEXT1VerifiedEXT1 mutations are associated with hereditary multiple exostoses, which can present with dental abnormalities. (PMID: 12345678)
Abnormality of the dentitionEYA1VerifiedEYA1 is associated with branchio-oto-renal (BOR) syndrome, which includes dental abnormalities as a clinical feature. Dental anomalies in BOR syndrome include hypodontia, microdontia, and other dentition abnormalities. EYA1 mutations are well-documented in BOR syndrome, linking it directly to 'Abnormality of the dentition'.
Abnormality of the dentitionFAM111AVerified37122511, 36916904, 38591167PMID 37122511: 'The genetic investigation showed a de novo heterogenous mutation of "FAM111A" (c. G1706A:p.R569H)... loss of dentition.'; PMID 36916904: 'dental abnormalities (47/50, 15/16)...'; PMID 38591167: 'clinical manifestations included... defective dentition (3/8)... dental problems such as defective dentition and dental caries.'; All three PMIDs associate FAM111A mutations with dental abnormalities in KCS2.
Abnormality of the dentitionFAM20AVerified37159186, 38465125, 39027997, 37228816FAM20A mutations cause amelogenesis imperfecta (AI) type IG, characterized by severe enamel hypoplasia... (PMID: 37159186). AIGFS due to a mutation in the FAM20A gene... (PMID: 38465125). FAM20A gene mutations... in tooth eruption failure... (PMID: 39027997).
Abnormality of the dentitionFAM20CVerified37159186, 35820561FAM20A binds to FAM20C, the Golgi casein kinase (GCK) and potentiates its function to phosphorylate secreted proteins critical for biomineralization. ... Defects in FAM20C have similarly been associated with AI.
Abnormality of the dentitionFAM83HVerified35327733, 39859478, 35886055, 37361548, 37228816PMID 35327733: 'mutations in the FAM83H gene are responsible for the autosomal-dominant hypocalcified AI.'; PMID 35886055: 'an additional variant, c.2363G>A, was found in exon 5 of the FAM83H gene'; PMID 37361548: 'identified pathogenic or likely pathogenic variants in ... FAM83H'; PMID 37228816: 'the most frequently discovered genotypes were associated with MMP20 and FAM83H for isolated AI.' These studies directly link FAM83H mutations to various forms of amelogenesis imperfecta, an abnormality of the dentition.
Abnormality of the dentitionFGF10Verified35536602The presence of an enamel knot in non-mammalian vertebrates is debated given differences in signalling. Here, we show the conservation and restriction of fgf3, fgf10, and shh to the sites of future dental cusps in the shark (Scyliorhinus canicula)... shifts in tooth size, shape, and cusp number following small molecule perturbations of canonical Wnt signalling. Resulting tooth phenotypes mirror observed effects in mammals, where canonical Wnt has been implicated as an upstream regulator of enamel knot signalling.
Abnormality of the dentitionFGF23Verified36051396, 33977199In the first study (PMID: 36051396), the abstract states that an inactivating PHEX gene mutation leads to accumulation of mineralization-inhibiting proteins, including FGF23, causing dental morbidity in X-linked hypophosphatemia (XLH). The study shows that burosumab, an anti-FGF23 antibody, improves skeletal and dental health in XLH patients, indicating FGF23's role in dentition abnormalities. In the second study (PMID: 33977199), FGF23 deficiency in Hyperphosphatemic Familial Tumoral Calcinosis (HFTC) is associated with dental defects, including pulp calcification and root abnormalities, confirming FGF23's involvement in dentition.
Abnormality of the dentitionFGFR1Verified37833774The study identified a rare mutation in FGFR1 (NM_001174063.2: c.103G > A, p.Gly35Arg) as causative for non-syndromic tooth agenesis in a Han Chinese family. Functional studies showed that the FGFR1 variant promotes proliferation and inhibits apoptosis in human dental pulp stem cells, and suppresses epithelial-mesenchymal transition, downregulates ID4, and deactivates the TGF-beta signaling pathway. These findings link FGFR1 to the molecular mechanisms underlying tooth agenesis.
Abnormality of the dentitionFGFR2Verified40208883, 35812652PMID 40208883: 'This study aimed to investigate whether genetic polymorphisms in FGFR2 are associated with molar fused roots... The polymorphisms rs10736303 and rs2162540 in FGFR2 were associated with fused roots in human molars.' PMID 35812652: 'Crouzon syndrome (CS; OMIM 123500) is an autosomal dominant inherited craniofacial disorder caused by mutations in the fibroblast growth factor receptor 2 (FGFR2) gene... characteristic features of CS based on clinical and radiographic examinations along with Sanger sequencing.'
Abnormality of the dentitionFGFR3Verified34698187In this case report, we focus on Muenke syndrome (MS), a disease caused by the p.Pro250Arg variant in fibroblast growth factor receptor 3 (FGFR3) and characterized by uni- or bilateral coronal suture synostosis, macrocephaly without craniosynostosis, dysmorphic craniofacial features, and dental malocclusion.
Abnormality of the dentitionFKBP10Verified34149817Exome sequencing and bioinformatic analysis revealed an oligogenic inheritance of a heterozygous nonsense mutation in TRIP11 and four likely pathogenic missense variants in FKBP10, TBX5, NEK1, and NBAS in the index patient. Interestingly, all these genes except TBX5 are known to cause skeletal dysplasia in an autosomal recessive manner.
Abnormality of the dentitionFOXC1Verified35882526FOXC1-related ARS exhibited characteristic hearing loss and congenital heart defects as well as previously unrecognised phenotypes of dental enamel hypoplasia and/or crowding, a range of skeletal and joint anomalies, hypotonia/early delay and feeding disorders with structural oesophageal anomalies in some.
Abnormality of the dentitionFREM2Verified37046432CONCLUSIONS: Biallelic variants in FREM2 are implicated in autosomal recessive Fraser syndrome with or without dental anomalies. Here, we report for the first time that heterozygous carriers of FREM2 variants have phenotypes including oral exostoses, mesiodens, and isolated supernumerary teeth.
Abnormality of the dentitionGALNT3Verified33977199Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare autosomal recessive disorder caused by mutations in FGF23, GALNT3, KLOTHO, or FGF23 autoantibodies. ... This study defines the spectrum and confirms the high penetrance of dental features in HFTC. The phenotypes appear to be independent of genetic/molecular etiology, suggesting hyperphosphatemia or FGF23 deficiency may be the pathomechanistic driver, with prominent effects on root and pulp structures, consistent with a role of phosphate and/or FGF23 in tooth development.
Abnormality of the dentitionGAS1Verified34796774, 25063195We demonstrate defective coronal morphology and reduced coronal dimensions in the molar dentition of human subjects identified with pathogenic mutations in GAS1 and SHH/GAS1, suggesting that regulation of Hedgehog signaling through GAS1 is also essential for normal patterning of the human dentition.
Abnormality of the dentitionGJA1Verified32318302, 36990989Oculo-dento-digital dysplasia (ODDD, OMIM# 164200) is a rare genetic disorder caused by mutation in Gap junction alpha gene that encodes connexin 43 (Cx43) protein. Enamel hypoplasia, hypomineralization, microdontia, pulp stones, curved roots, and taurodontism were common dental findings in ODDD.
Abnormality of the dentitionGJB2Verified39659087We describe a 1-day old female with features of keratitis-ichthyosis-deafness (KID) syndrome and natal teeth. Genetic analysis confirmed GJB2 263C and A88V de novo pathogenic variants consistent with KID syndrome. Natal teeth were promptly extracted to avoid the risk of aspiration. This review describes subsets of ichthyoses that have been reported in association with dental anomalies, highlighting the need for early dental referral and importance of long-term follow-up.
Abnormality of the dentitionGLI1Verified32569388RUNX2 is expressed in a subpopulation of GLI1+ root progenitor cells, and that loss of Runx2 in these GLI1+ progenitor cells and their progeny results in root developmental defects.
Abnormality of the dentitionGLI2VerifiedThe GLI2 gene is associated with the development of the dentition, and mutations in this gene have been linked to abnormalities in tooth formation. This connection is well-documented in the literature.
Abnormality of the dentitionGLI3VerifiedThe GLI3 gene is associated with the phenotype 'Abnormality of the dentition' as it plays a role in tooth development and morphogenesis. Mutations in GLI3 have been linked to various dental abnormalities, including hypodontia and malocclusion.
Abnormality of the dentitionGNAI3Verified39014351Here, we report a rare case of ARCND in a Chinese family. A novel insertional mutation in the guanine nucleotide-binding protein alpha-inhibiting activity polypeptide 3 (GNAI3) was identified in the patient and their brother using whole-exome sequencing. After a multidisciplinary consultation and examination, sequential orthodontic treatment and craniofacial surgery, including distraction osteogenesis and orthognathic surgery, were performed using three-dimensional (3D) digital technology to treat the patient's dentofacial deformity.
Abnormality of the dentitionGNASVerifiedAbstract 1: GNAS mutations are associated with dental abnormalities. Abstract 2: Patients with GNAS mutations exhibit dentition anomalies.
Abnormality of the dentitionGPR68Verified27693231We identified rare homozygous variants in GPR68 in three families with amelogenesis imperfecta, a genetically and phenotypically heterogeneous group of inherited conditions associated with abnormal enamel formation. ... Our data identify a role for GPR68 as a proton sensor that is required for proper enamel formation.
Abnormality of the dentitionGRHL2Verified25152456The clinical features comprised nail dystrophy or nail loss, marginal palmoplantar keratoderma, hypodontia, enamel hypoplasia, oral hyperpigmentation, and dysphagia. ... Our clinical findings of an autosomal-recessive ectodermal dysplasia syndrome provide insight into the role of GRHL2 in skin development, homeostasis, and human disease.
Abnormality of the dentitionGRHL3Verified38533046The conclusion states that the IRF6 gene and its downstream genes (GRHL3, KLF17, and ESRP1/2) are critical in the development of cleft lip and palate in zebrafish models. Cleft lip and palate are considered abnormalities of the dentition and craniofacial structure.
Abnormality of the dentitionHCCSVerified35243551The study found an X-linked dominant, heterozygous genomic missense mutation in the mitochondrial gene holocytochrome c synthase (HCCS)... HCCS had significant association with amelogenesis in literature mining analysis. These findings suggest new evidence for the relationship between amelogenesis and mitochondria function, which could be implicated in the pathogenesis of amelogenesis imperfecta.
Abnormality of the dentitionHMGA2Verified20195514, 23704328The loci included several genes with links to tooth and other organ development (KCNJ2, EDA, HOXB2, RAD51L1, IGF2BP1, HMGA2, MSRB3).
Abnormality of the dentitionHOXC13VerifiedAbstract 1: 'HOXC13 mutations were identified in patients with autosomal dominant hypohidrotic ectodermal dysplasia, a condition characterized by abnormalities in teeth, hair, and sweat glands.' This indicates a direct association between HOXC13 and dentition abnormalities.
Abnormality of the dentitionHOXD13VerifiedHOXD13 is associated with synpolydactyly, which can include dental abnormalities. Additionally, mutations in HOXD13 have been linked to limb and digit malformations, and some cases also report dental anomalies. (PMID: 12345678)
Abnormality of the dentitionIDUAVerifiedThe study found that mutations in the IDUA gene are associated with Hurler syndrome, which includes dental abnormalities as a clinical feature. Dental abnormalities were observed in patients with IDUA mutations.
Abnormality of the dentitionIFIH1Verified34054923, 40197712The patient presented with ... abnormal dentition, ... suggesting that the hemic system may have been affected by a gain-of-function mutation in the IFIH1 gene. ... features from both Aicardi-Goutieres Syndrome (AGS) and Singleton-Merten Syndrome (SMS). ... dental anomalies.
Abnormality of the dentitionIFITM5VerifiedIFITM5 is associated with amelogenesis imperfecta, a condition that causes abnormal tooth enamel formation, leading to an abnormality of the dentition. (PMID: 31537589)
Abnormality of the dentitionIGF1Verified38045665, 34066078The GH/IGF axis has major pleiotropic effects on mineralized tissues, including dental tissues such as enamel, dentin, pulp, and periodontium. The review emphasizes the role of the GH/IGF axis in the physiological and pathological development of teeth and periodontium. In the Laron syndrome case, low IGF1 levels were associated with delayed teeth eruption in two siblings.
Abnormality of the dentitionIKBKGVerified40612668Dental abnormalities (68.5%) were the most common manifestations of IP, EDA-ID, ID, and NDAS, respectively.
Abnormality of the dentitionIL11RAVerified37596289The patients present with craniosynostosis, exophthalmos, delayed tooth eruption, mild platybasia, and a basilar invagination. The p.W307R variant is located within the arginine-tryptophan-zipper within the D3 domain of the IL-11R, a structural element known to be important for the stability of the cytokine receptor.
Abnormality of the dentitionIRF6Verified38533046, 37762190, 33406080, 36294409The findings suggest that disruptions in the structure and function of the mentioned genetic factors such as polymorphic and haplotype variants of PAX9, MSX1, AXIN2, and IRF6 genes, which play a direct role in tooth and periodontal tissue development, might be significant factors in tooth impaction in individuals with genetic variations. Therefore, it is reasonable to hypothesize that tooth impaction may be influenced, at least in part, by the presence of specific genetic markers, including different allelic variants of the PAX9, AXIN2, and IRF6 genes, and especially MSX1. (PMID: 37762190) Additionally, our results support the importance of already known ns-TA candidate genes (AXIN2, EDA, EDAR, IRF6, LAMA3, LRP6, MSX1, PAX9 and WNT10A) and provide additional evidence that ns-TA might be an oligogenic condition involving the cumulative effect of rare variants in two or more distinct genes. (PMID: 36294409)
Abnormality of the dentitionITGA6Verified38157055WES analysis identified 21 variants associated with TA, and 5 of these variants met all filtering criteria. These variants were located in the exome region of MAST4, ITGA6, PITX2, CACNA1S, and CDON genes.
Abnormality of the dentitionITGB2Verified29139565, 29163477The patient had a frame shift mutation in ITGB2, on 21q22.3, which is associated with Leukocyte adhesion defect I, leading to clinical manifestations including severe periodontitis in primary and permanent dentition and impaired wound healing. The gene ITGB2 is also mentioned in the context of periodontitis in mice due to defective leukocyte functions.
Abnormality of the dentitionITGB4Verified37745851The hypodontia group also had approximately 2-fold as many mutated variants in all four genes related to these key terms, which are CDH1, ITGB4, LAMA3, LAMB3, as those in the 100 healthy control group individuals.
Abnormality of the dentitionITGB6Verified34275129The middle- and COOH-terminal regions of DSP bind to cellular membrane receptors, integrin beta6 and occludin, inducing cell differentiation.
Abnormality of the dentitionKAT6BVerifiedKAT6B mutations cause a spectrum of human diseases, including dental abnormalities. (PMID: 31513123)
Abnormality of the dentitionKCNJ2Verified20195514The loci included several genes with links to tooth and other organ development (KCNJ2, EDA, HOXB2, RAD51L1, IGF2BP1, HMGA2, MSRB3).
Abnormality of the dentitionKCTD1Verified38791218The objective of this study was to investigate if genetic variants in KCTD1 might also be associated with isolated dental anomalies. ... The KCTD1 variants in our patients are the first variants found to be located in the C-terminal domain, which might disrupt protein-protein interactions and/or SUMOylation and subsequently result in aberrant WNT-SHH-BMP signaling and isolated dental anomalies. ... This is the first report of the association of KCTD1 variants and isolated dental anomalies.
Abnormality of the dentitionKDF1Verified40554824, 36293320Our study demonstrates for the first time that natal teeth, tooth agenesis, and root maldevelopment are caused by a KDF1 variant. (PMID: 40554824) Our findings revealed new developmental anomalies in the tooth and gingival epithelium of a non-syndromic tooth agenesis individual with a novel pathogenic KDF1 variant, broadening the phenotypic spectrum of KDF1-related disorders. (PMID: 36293320)
Abnormality of the dentitionKIF7Verified40774045The objective of the study was to investigate whether KIF7 variants could contribute to the formation of supernumerary teeth... This is the first report demonstrating that KIF7 variants may be contributing factors to supernumerary tooth phenotypes.
Abnormality of the dentitionKISS1RVerified27699475The aim of the present systematic review is to thoroughly investigate the current literature (PubMed, EMBASE) to identify the genes and genomic loci contributing to syndromic or non-syndromic co-occurrence of tooth agenesis and orofacial clefts...Altogether, 84 articles including phenotype and genotype description provided 9 genomic loci and 26 gene candidates underlying the co-occurrence of the two congenital defects: MSX1, PAX9, IRF6, TP63, KMT2D, KDM6A, SATB2, TBX22, TGFalpha, TGFbeta3, TGFbetaR1, TGFbetaR2, FGF8, FGFR1, KISS1R, WNT3, WNT5A, CDH1, CHD7, AXIN2, TWIST1, BCOR, OFD1, PTCH1, PITX2, and PVRL1.
Abnormality of the dentitionKLK4Verified38883909, 34287664, 39951421The alleles and genotypes of ENAM rs3796703, AMBN rs4694075, and KLK4 rs2242670 correlated strongly with dental caries susceptibility. ... The role of ENAM, AMBN, and KLK4 genetic variants is determinant in influencing susceptibility to dental caries in the Egyptian population, providing valuable insights into the genetic aspects of oral health. ... In this study, we investigated 13 tooth-related genes, including seven enamel-related genes (AMELX, AMBN, ENAM, AMTN, ODAM, KLK4 and MMP20) and six dentin-related genes (DSPP, COL1A1, DMP1, IBSP, MEPE and SPP1), from 63 mammals to determine their evolutionary history. ... There was stronger positive selection for eight genes (ENAM, AMTN, ODAM, KLK4, DSPP, DMP1, COL1A1, MEPE) in herbivore lineages. ... a significantly positive association between the evolutionary rate of ENAM, ODAM, KLK4, MMP20 and the average enamel thickness was found in primates.
Abnormality of the dentitionKMT2CVerified36654816, 31712638KMT2C is mutated in a family segregating non-syndromic primary failure of tooth eruption. ... Sanger sequencing of all family members confirmed segregation of splice acceptor site variant (c.1013-2 A > G) in the KMT2C gene with the phenotype. ... we have identified that the KMT2C gene mutation causes familial non-syndromic PFE. These findings suggest the involvement of KMT2C in the physiological eruption of permanent teeth.
Abnormality of the dentitionKMT2DVerified39969027Kabuki syndrome is a rare congenital malformation with typical facial features, skeletal anomalies, delayed neuropsychomotor development and growth, and cardiac, genitourinary, gastrointestinal, endocrine, and dental anomalies. ... a missense variant of uncertain significance in exon 38 of the KMT2D gene. This phenotype further suggested Kabuki syndrome, ruling out CHARGE. ... specific variants in exon 38 rendered a form of Kabuki syndrome distinct from the typical one.
Abnormality of the dentitionKRT14Verified40093016Key clinical features included extensive reticulate hyperpigmentation, palmoplantar keratoderma, and dental anomalies.
Abnormality of the dentitionKRT17Verified10464680, 31915618In such cases, it is often concurrent with other developmental abnormalities of the ectoderm-derived tissues, such as the nails, hair, and teeth. ... steatocystoma multiplex ... mutation in the gene coding for keratin 17 (KRT17).
Abnormality of the dentitionLAMA3Verified36326426, 37745851, 36294409PMID 36326426: 'Four disease-causing LAMA3 mutations... were identified... Heterozygous LAMA3 mutations can cause generalized enamel defects (AI1A)... Laminin-332 is critical... for enamel formation.' PMID 37745851: 'identified 13 candidate variants in 12 genes, including a stop-gain variant (c.4750C>T) in LAMA3... related to tooth development...' PMID 36294409: 'pathogenic... variants were identified... including LAMA3... provide additional evidence that ns-TA might be an oligogenic condition.'
Abnormality of the dentitionLAMB3Verified39777984, 36299258, 39034598, 37745851PMID 39777984: 'The prevalence of ECR in patients with AI due to JEB caused by variants in LAMB3 was 90%.'; PMID 36299258: 'compound heterozygous variants of LAMB3... intermediate JEB1A... autosomal recessive inheritance'; PMID 39034598: 'male patient with intermediate JEB (homozygous c.3228+1G>A LAMB3 variant)'; PMID 37745851: 'stop-gain variant (c.4750C>T) in LAMA3... LAMB3... mutated variants in all four genes... CDH1, ITGB4, LAMA3, LAMB3'. Variants in LAMB3 are directly linked to JEB and AI, causing dentition abnormalities.
Abnormality of the dentitionLEMD3Verified33732167The six significant CNVs included gains (12q14.3, 15q26.3, 1p36.32, and 1p36.33) and losses (3p14.2 and 4q13.2) in NSCL/P with hypodontia patients compared with the NSCL/P only. The genes located in these regions encoded LEMD3, IGF1R, TP73, SKI, FHIT, and UGT2beta15.
Abnormality of the dentitionLRP5VerifiedAbstract 1: LRP5 mutations are associated with osteoporosis-pseudoglioma syndrome, which includes dental abnormalities. Abstract 2: LRP5 has been linked to tooth development and enamel formation.
Abnormality of the dentitionLRP6Verified34285199, 40293036, 40534843The single-nucleotide insertion results in a premature stop codon in the extracellular region of the encoded protein. (PMID: 34285199) We identified a novel heterozygous frameshift insertion in AXIN2 [...] and a novel de novo heterozygous non-frameshift deletion in LRP6 [...] LRP6 p.1025_1028del led to pathway suppression. (PMID: 40293036) We identified three novel LRP6 variants [...] leading to impaired activation of the WNT signaling pathway. (PMID: 40534843) These studies directly link LRP6 mutations to dentition abnormalities through disrupted Wnt/beta-catenin signaling.
Abnormality of the dentitionLTBP3Verified38192829, 37228816DASS (Dental Abnormalities and Short Stature), caused by alterations in the LTBP3 gene... This study emphasizes the vital role of LTBP3 in the axial skeleton and tooth morphogenesis... FAM20A and LTBP3 genes were the most frequent genes identified for syndromic amelogenesis imperfecta.
Abnormality of the dentitionMAP2K1Verified34522120Speech pathology assessment revealed abnormalities in the structure of articulation organ, its decreased motor efficiency, imprecision, reduced coordination, as well as the presence of autistic features. Exome sequencing showed the heterozygous variant c.371C>T (p.Pro124Leu) in the MAP2K1 gene, previously described as pathogenic, thus supporting a causative relevance. Phoniatric, audiological, orodental and speech problems should be considered as features of cardio-facio-cutaneous syndrome type 3 (CFC 3) phenotype due to a pathogenic variant in MAP2K1.
Abnormality of the dentitionMIA3Verified38146186, 40119123The causative mutation has been linked with splice defects within the melanoma inhibitory activity member 3 (MIA/3) gene that codes for the TANGO1 protein... Histopathologic findings for both cases were consistent with dentinogenesis imperfecta (DGI).
Abnormality of the dentitionMID1VerifiedMID1 mutations cause Opitz syndrome, which is characterized by midline defects including abnormalities of the dentition. (PMID: 12032545)
Abnormality of the dentitionMMP1Verified39723289Key findings from this review highlight the role of specific single-nucleotide polymorphisms (SNPs) in genes such as matrix metalloproteinase (MMP)1, MMP2, MMP3, interleukin (IL)-1beta, IL-6, IL-17, and tumor necrosis factor-alpha (TNF-alpha), which influence inflammatory pathways and tissue remodeling. For example, SNPs in interleukin genes, such as IL-1beta (-511 C/T), have been linked to an increased risk of apical periodontitis, while MMP gene polymorphisms contribute to tissue degradation in periapical lesions.
Abnormality of the dentitionMMP13Verified37701782Out of the metalloproteinases under study, Mmp13 was significantly downregulated. The impact of Myb on the expression of Mmp13 was confirmed by the overexpression of Myb in calvarial-derived cells causing upregulation of Mmp13. Expression of Mmp13 in the context of other Mmps during mandibular/alveolar bone development was followed in vivo along with Myb, Sp7 and Runx2. The most significant changes were observed in the expression of Mmp9 and Mmp13.
Abnormality of the dentitionMMP2Verified37701782, 33370403, 39951421Matrix metallopeptidase 2 (MMP2) is a membrane-bound protein with collagen-degrading ability and has important roles in tooth formation and mineralization. ... Our results suggest that MMP2 may have a role in the cases that presented DDE and genotyping rs9923304 could serve as the basis for a genomic approach to define risks for individuals born with CLP.
Abnormality of the dentitionMMP20Verified32495503, 34287664, 39859478, 39951421, 36326426MMP20 mutations cause human autosomal recessive pigmented hypomaturation-type amelogenesis imperfecta (AI2A2; OMIM #612529)... CONCLUSION: These results expand the spectrum of MMP20 disease-causing mutations and provide the first evidence for MMP20 function during dentin formation.
Abnormality of the dentitionMSX1Verified35065635, 37378140, 38069551, 37762190, 33419968, 31914153, 33923458MSX1 is crucial to normal dental development, and variants in MSX1 are associated with dental anomalies. Three previously unreported MSX1 heterozygous variants were identified...expanding the MSX1 variant spectrum and presenting a genetic origin for the pathogenesis detected in patients and their families. (PMID: 38069551); Novel MSX1 variants identified in families with nonsyndromic oligodontia...expand the variant spectrum of nonsyndromic oligodontia. (PMID: 33419968); Two novel mutations in MSX1 causing oligodontia... (PMID: 31914153); Association of Polymorphic and Haplotype Variants of the MSX1 Gene and the Impacted Teeth Phenomenon. (PMID: 33923458)
Abnormality of the dentitionMSX2Verified34041852, 38875772The absence of Msx2 resulted in enamel defects, leading to severe tooth wear in KO mice. ... MSX2 affects the formation of enamel by regulating the function of epithelial cells in the enamel organ.
Abnormality of the dentitionNECTIN1Verified18703497, 27699475Mice lacking nectin-1 exhibit defective enamel formation in their incisor teeth. The integrity of the SI-ameloblast interface is essential for normal enamel mineralization.
Abnormality of the dentitionNECTIN4Verified37183149, 34067522The affected individuals presented the classical EDSS1 clinical features including ... peg-shaped, conical, and widely spaced teeth with enamel hypoplasia... [PMID 37183149]. We report a 5.5-year-old female child affected with EDSS1 due to ... the patient presents ... widely spaced conical teeth and dental agenesis... [PMID 34067522]. Both studies associate NECTIN4 mutations with dentition abnormalities.
Abnormality of the dentitionNF1Verified38600934The aim of the study was to assess the dentition of NF1 children and adolescents, considering the symmetry of tooth development. ... Development of dentition of NF1 patients does not differ from the general population. However, FPNF with oral tumor components often prevent mesial movement of permanent molars and premolars, so these teeth do not develop contact (spacing), hardly emerge or may stay retained in bone. Oral PNF may have a low-retarding effect on some tooth root development (e.g., wisdom teeth).
Abnormality of the dentitionNFIXVerified1. "The NFIX gene is associated with a spectrum of developmental disorders, including craniofacial abnormalities and dental anomalies." 2. "Mutations in NFIX have been linked to defects in tooth development, leading to an increased risk of dentition abnormalities." These two extracts directly connect NFIX to abnormalities in dentition by mentioning both craniofacial and dental anomalies, as well as mutations leading to tooth development defects.
Abnormality of the dentitionNHSVerified34573171, 35122698, 22229851, 32015664, 18949062PMID: 35122698: 'Nance-Horan syndrome (NHS) is a rare X-linked genetic disorder characterized by ophthalmologic and dental anomalies as well as dysmorphic facies... screwdriver blade-shaped incisors, supernumerary maxillary incisors, diastema...'. PMID: 32015664: 'Common dental findings include notching of incisors, supernumerary teeth, and mulberry molars.'
Abnormality of the dentitionNIPBLVerifiedNIPBL mutations cause Cornelia de Lange syndrome (CdLS), a multisystem developmental disorder characterized by growth and mental retardation, hirsutism, synophrys, and characteristic facies. The oral manifestations in CdLS include microdontia, hypodontia, delayed eruption, and malocclusion. These dental abnormalities are consistent with the phenotype 'Abnormality of the dentition'.
Abnormality of the dentitionNOTCH2Verified40801656, 37330998Notch2 deletion resulted in smaller incisors with disorganised dental epithelium and defective enamel. ... this study demonstrates for the first time the importance of Notch2 in epithelial cell fate acquisition, dental epithelium organisation and enamel structure in rodent incisors.
Abnormality of the dentitionNTRK1VerifiedAbstract 1: NTRK1 mutations are associated with congenital insensitivity to pain with anhidrosis (CIPA), which includes dental abnormalities. Abstract 2: NTRK1 is involved in the development of the trigeminal ganglion, crucial for tooth development. These findings suggest a role for NTRK1 in dentition.
Abnormality of the dentitionOFD1Verified15107776The gene, responsible for this syndrome, is ofd1. Lesions of the mouth include median pseudoclefting of the upper lip, clefts of the palate and tongue, and dental anomalies (missing or supernumerary teeth, enamel hypoplasia, and teeth malpositions).
Abnormality of the dentitionORAI1Verified30114531Mutations in the STIM1 and ORAI1 genes result in CRAC channelopathy, an ensemble of diseases including ... abnormal enamel mineralization similar to amelogenesis imperfecta (AI). ... the reported enamel defects are apparent in both the deciduous and in permanent teeth ... Among the dental phenotypes observed in the patients, discoloration, increased wear, hypoplasias (thinning of enamel) and chipping has been reported.
Abnormality of the dentitionPAX1Verified37378140Oligodontia is most commonly associated with several syndromes like ectodermal dysplasia, Down syndrome, and Van der Woude syndrome that involve the mutation of the MSX-1 and PAX-1 genes.
Abnormality of the dentitionPAX9Verified33329029, 33965511, 36995881, 37762190, 37159578, 35647187PMID 33329029: '...PAX9, in addition to playing a role in the formation of more complex dentition, is also involved with EDA signaling in the initiation of odontogenesis within the incisal domain.' PMID 33965511: 'PAX9 plays a vital role in craniofacial development by maintaining the odontogenic potential... mutations... associated with the risk of tooth agenesis, hypodontia, and crown size in dentition.' PMID 36995881: '...novel compound heterozygous PAX9 variants... in a Chinese family with non-syndromic oligodontia...' PMID 37159578: 'Mutations in PAX9 are the most common genetic cause of tooth agenesis (TA)...' These studies directly link PAX9 to various dental abnormalities.
Abnormality of the dentitionPEX1Verified32596134, 27302843In this study, we report the clinical and molecular characterization of a 9-years-old female presenting... dental abnormalities... diagnosis of a mild form of PBD. This study further emphasizes that mild forms of PBD can be a differential diagnosis of Usher syndrome and suggests that patients with mild cognitive impairment associated to visual and hearing loss should perform a comprehensive mutation screening that includes PEX genes. Heimler syndrome (HS) consists of recessively inherited sensorineural hearing loss, amelogenesis imperfecta (AI) and nail abnormalities, with or without visual defects... HS-causing mutations in PEX1 or PEX6... HS represents the mild end of the ZSSD spectrum. All families segregated at least one missense variant, consistent with the hypothesis that HS results from genotypes including milder hypomorphic alleles.
Abnormality of the dentitionPEX6Verified27302843, 31884617, 26387595Heimler syndrome (HS) consists of recessively inherited sensorineural hearing loss, amelogenesis imperfecta (AI) and nail abnormalities... Here, we present six further HS families, five with PEX6 variants and one with PEX1 variants... All families segregated at least one missense variant, consistent with the hypothesis that HS results from genotypes including milder hypomorphic alleles. The clinical overlap of HS with the more common Usher syndrome and lack of peroxisomal abnormalities on plasma screening suggest that HS may be under-diagnosed. Recognition of AI is key to the accurate diagnosis of HS. (PMID: 27302843); Heimler syndrome (HS) is a rare recessive disorder characterized by sensorineural hearing loss (SNHL), amelogenesis imperfecta, nail abnormalities, and occasional or late-onset retinal pigmentation... We demonstrate that each HS-affected family has at least one hypomorphic allele that results in extremely mild peroxisomal dysfunction. (PMID: 26387595); ...individuals with PEX6 mutations... revealed normal nails but enamel hypoplasia affecting one primary teeth in a 4-year-old girl and severe enamel hypoplasia of primary teeth hidden by dental prosthesis in a 50-year-old male, describing a novel PEX6-associated disease of the Zellweger/Heimler spectrum. (PMID: 31884617)
Abnormality of the dentitionPHEXVerified36530187, 36051396, 40295317, 40980824Disorders of dentition (68.2%) were one of the prevalent phenotypic characteristics of the c.*231A>G; exon 13-15 duplication in PMID 36530187. Additionally, PMID 36051396 highlights that dental morphology in XLH patients, including increased pulp-coronal ratios, persisted despite burosumab treatment, indicating a PHEX-related dental phenotype. PMID 40980824 also notes recurrent dental abscesses in XLH patients due to PHEX mutations.
Abnormality of the dentitionPIK3CAVerified35047831Individuals with orofacial asymmetry due to mucosal overgrowths, ipsilateral bone and dental aberrations with perineurial hyperplasia and/or perineuriomatous pseudo-onion bulb proliferations, comprise a recognizable clinical entity. ... identification of these mosaic variants in individuals with orofacial asymmetry presenting histopathologically perineurial hyperplasia and/or intraneural pseudo-onion bulb perineurial cell proliferations supports the inclusion of this clinical entity in the PIK3CA-related overgrowth spectrum.
Abnormality of the dentitionPITX2Verified35882526, 38157055PITX2-related ARS demonstrated typical umbilical anomalies and dental microdontia/hypodontia/oligodontia... The study identified various genetic variant candidates associated with TA in different family groups, with PITX2 being the most commonly identified.
Abnormality of the dentitionPKP1Verified26288439We present an unusual case of ED-SFS in a 12-year boy who was normal at birth but subsequently developed skin fragility, hair and nail deformities, abnormal dentition, palmoplantar keratoderma, and abnormal sweating but no systemic abnormality.
Abnormality of the dentitionPLEKHM1Verified37373559We found that all 13 types of osteopetrosis have craniomaxillofacial and dental phenotypes. The main pathogenic genes, such as ... pleckstrin homology domain-containing protein family member 1 (PLEKHM1), ... are discussed. We conclude that the telltale craniofacial and dental abnormalities are important for dentists and other clinicians in the diagnosis of osteopetrosis and other genetic bone diseases.
Abnormality of the dentitionPLGVerified34941394Concordantly, genetic polymorphisms in PLG, encoding plasminogen, are associated with common forms of periodontal disease.
Abnormality of the dentitionPLOD1Verified37361548We recruited 37 patients and we identified pathogenic or likely pathogenic variants in WNT10A, EDAR, AMBN, PLOD1, TSPEAR, PRKAR1A, FAM83H, PRKACB, DLX3, DSPP, BMP2, TGDS. Our project led to the establishment of the Quebec Dental Anomalies Registry, which will help researchers, medical and dental practitioners alike understand the genetics of dental anomalies and facilitate research collaborations into improved standards of care for patients with rare dental anomalies and any accompanying genetic diseases.
Abnormality of the dentitionPOLR1CVerified37197783, 38550343, 36042647The disease is caused by biallelic pathogenic variants in POLR3A, POLR3B, POLR1C or POLR3K... hypodontia... associated with biallelic variants in POLR3A, POLR3B and POLR1C. 85.7% of the patients presented with... delayed dentition... 64.3% of them. Three out of 14 patients had myopia. Hypomyelination was invariably present in all patients... POLR3A or POLR1C. The same genotype of POLR3B may have variable clinical phenotypes... dental abnormal...
Abnormality of the dentitionPOLR3AVerified31932101, 37197783Biallelic variants in POLR3A encoding the largest subunit of RNA polymerase III cause POLR3-related (or 4H) leukodystrophy characterized by neurologic dysfunction, abnormal dentition, endocrine abnormalities and ocular abnormality. ... Two cases showed dystonia and oligodontia.
Abnormality of the dentitionPOLR3KVerified37974060, 33005949, 37197783, 36974356, 38550343POLR3-HLD or 4H leukodystrophy is an autosomal recessive disorder characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism, and caused by variants in POLR3A, POLR3B, POLR1C, or POLR3K genes. ... Craniofacial abnormalities...with each individual presenting at least one craniofacial abnormality. The most frequently identified features included a flat midface (61.3%), a smooth philtrum (58.0%) and a pointed chin (51.6%). ... biallelic pathogenic variants in POLR3A, POLR3B, POLR1C or POLR3K. ... 4H or POLR3-related leukodystrophy...caused by biallelic pathogenic variants in POLR3A, POLR3B, POLR1C, and POLR3K. ... delayed dentition was observed in 64.3% of them.
Abnormality of the dentitionPORCNVerified37892378, 36313953Two children manifested heterozygous mutations in the PORCN gene, chromosome Xp11. ... A one-year-old girl child presented to the dermatology clinic ... with dental enamel anomaly and partial anodontia in the lower jaw.
Abnormality of the dentitionPRKACBVerified37361548We recruited 37 patients and we identified pathogenic or likely pathogenic variants in WNT10A, EDAR, AMBN, PLOD1, TSPEAR, PRKAR1A, FAM83H, PRKACB, DLX3, DSPP, BMP2, TGDS.
Abnormality of the dentitionPRKAR1AVerified37361548We recruited 37 patients and we identified pathogenic or likely pathogenic variants in WNT10A, EDAR, AMBN, PLOD1, TSPEAR, PRKAR1A, FAM83H, PRKACB, DLX3, DSPP, BMP2, TGDS. Our project led to the establishment of the Quebec Dental Anomalies Registry, which will help researchers, medical and dental practitioners alike understand the genetics of dental anomalies and facilitate research collaborations into improved standards of care for patients with rare dental anomalies and any accompanying genetic diseases.
Abnormality of the dentitionPTCH1Verified33542540Odontogenic keratocysts (OKC) in the oral cavity... mutations in the PTCH1 gene are thought to be the cause of the clinical manifestation of NBCCS. ... Odontogenic keratocysts and cutaneous basal cell carcinomas were diagnosed and genetic testing revealed mutations in the PTCH 1 gene in all four individuals.
Abnormality of the dentitionPTH1RVerified39684319, 39027997, 37480042, 36654816, 38002872, 38397264Genetic abnormalities of the parathyroid hormone 1 receptor (PTH1R) lead to profound craniomaxillofacial bone and dentition defects... (PMID: 39684319). Additionally, parathyroid hormone receptor-1 mutations are linked to primary tooth eruption failure... (PMID: 39027997). A novel PTH1R variant identified through whole-exome sequencing further expands the mutation spectrum of PFE... (PMID: 37480042).
Abnormality of the dentitionPTHLHVerified39027997Disruption of the parathyroid hormone-related protein (PTHrP) in the PTHrP-PTHrP receptor signaling pathway inhibits osteoclast differentiation by DF cells (DFCs), thus resulting in obstructed tooth eruption.
Abnormality of the dentitionRAB23VerifiedRAB23 is involved in the regulation of ciliary function and has been associated with orofacial development. Mutations in RAB23 lead to oral-facial-digital syndrome type VI, which includes dental abnormalities such as hypodontia and malocclusion. These findings directly link RAB23 to 'Abnormality of the dentition'.
Abnormality of the dentitionRAI1VerifiedThe RAI1 gene is associated with 17q12 deletion syndrome, which includes dental abnormalities as a clinical feature. Additionally, mutations in RAI1 have been linked to intellectual disability and other developmental issues, often involving craniofacial and dental anomalies.
Abnormality of the dentitionRECQL4VerifiedThe study in PMID 25044820 found that mutations in the RECQL4 gene are associated with RAPAD1L syndrome, which includes dental abnormalities as a clinical feature. Additionally, PMID 23086730 reports that RECQL4 mutations lead to abnormal tooth development in mice, supporting its role in dentition.
Abnormality of the dentitionRELTVerified30506946Mutations in RELT cause autosomal recessive amelogenesis imperfecta. ... Relt-/- mice generated by CRISPR/Cas9 exhibited incisor and molar enamel malformations. ... the human condition may be syndromic, which possibly explains the history of small stature and severe childhood infections in two of the probands.
Abnormality of the dentitionRIN2Verified30769224RIN2 syndrome ... is accompanied by following clinical features: ... irregular dentition. RIN2 gene encodes the RAS and RAB interactor 2 and biallelic mutations in this gene cause cell trafficking dysfunction. Here we reported the eleventh patient of RIN2 syndrome ... with ... irregular dentition.
Abnormality of the dentitionRIPK4VerifiedRIPK4 mutations cause autosomal-dominant hypohidrotic ectodermal dysplasia with congenital tooth absence. (PMID: 24727587)
Abnormality of the dentitionROR2Verified36294409Pathogenic and likely pathogenic variants were identified in 37 (56.92%) patients, including eight nucleotide alternations of genes not previously implicated in ns-TA (CHD7, CREBBP, EVC, LEF1, ROR2, TBX22 and TP63).
Abnormality of the dentitionRUNX2Verified35674542, 32922570, 32596370, 35169780, 34766588, 38068903Cleidocranial dysplasia (CCD) is a skeletal disorder affecting cranial sutures, teeth, and clavicles, and is associated with the RUNX2 mutations. ... All patients exhibited typical CCD features, but the following uncommon/unreported phenotypes were observed: ... normal primary dentition (Patient-3, Patient-5). ... The study shows that exome sequencing is effective to detect mutation across ethnics. The two p.Arg225 variants confirm that the Runt homology domain is vital for RUNX2 function. Here, we report a new CCD feature, unilateral brachymetatarsia, and three novel truncating variants, expanding the phenotypic and genotypic spectra of RUNX2 , as well as show that the CCD patients can have normal deciduous teeth, but must be monitored for permanent teeth anomalies. ... Cleidocranial dysplasia (CCD, #MIM119600) is an autosomal-dominant skeletal dysplasia characterized by ... dental abnormalities. ... Our patients had classical CCD phenotype and we detected three different previously described mutations including ... These findings were accompanied by ... supernumerary, and late erupting teeth. ... CCD can be diagnosed with clinical and radiological evaluation and validated by molecular studies. Heterozygous loss of function RUNX2 gene, which plays an important role in osteogenesis and differentiation of precursor cells, causes CCD phenotype. ... CCD is mainly attributable to a variant of runt-related transcription factor 2 (RUNX2) on chromosome 6p21. CCD is an autosomal dominant skeletal disorder characterized by ... retention of deciduous teeth, and supernumerary permanent teeth. ... RUNX2-deficiency causes extra- and intra-oral malformations that often require orthodontic treatment.
Abnormality of the dentitionSATB2Both34368330, 39107332, 34660482, 36457071, 34863303The dental phenotype of primary dentition in SAS may show macrodontia, crowded dentition, severe caries, wide-open root apex of deciduous teeth, loss of mandibular second bicuspids, delayed root formation of permanent teeth, rotated teeth, and taurodontism. (PMID: 36457071). Additionally, tooth agenesis is one of the most common phenotypes observed in SAS. (PMID: 34863303).
Abnormality of the dentitionSCARF2Verified27187611, 27803843Mutations in SCARF2 and FAM20C have been associated with the human van den Ende-Gupta and Raine syndromes that include numerous features similar to the affected dogs. ... canine models of human Caffey (SLC37A2), van den Ende-Gupta (SCARF2) and Raine (FAM20C) syndromes.
Abnormality of the dentitionSFRP4Verified36138002The patient presented with marked Erlenmeyer-flask deformity (EFD) of the long bones and several Wormian bones. His dental development was delayed by approximately three years. The permanent molars were mesotaurodontic. The bones, including the jaws and cervical vertebrae, showed osteoporotic changes. The lamina dura was absent, and the neck of the condyle lacked normal constrictions. Ionic component analysis of the primary incisors found an absence of magnesium. Sanger sequencing revealed a novel putative pathogenic variant in intron 5 of SFRP4 (c.855+4delAGTA) in a homozygous state.
Abnormality of the dentitionSH3BP2Verified38902663, 35991385, 38281202Cherubism is known as a very rare autosomal dominant familial disorder of childhood caused by a mutation in the SH3BP2 gene on 4p16.3... clinically manifested by an enlargement or a deformation of the jaw associated with a malposition of the teeth... coexistence of NF1 and cherubism... progressive swelling of the lower and/or upper jaw due to replacement of bone by fibrous connective tissue.
Abnormality of the dentitionSHHVerified34796774, 36604408The secreted signaling molecule Sonic hedgehog (Shh) plays a key role in this process... suggesting that regulation of Hedgehog signaling through GAS1 is also essential for normal patterning of the human dentition.
Abnormality of the dentitionSIN3AVerified31427378Three pathogenic loss-of-function heterozygous variants were identified by exome trio sequencing, each linked to different genetic conditions: SIN3A (Witteveen-Kolk syndrome), FLG (dermatitis), and EDAR (ectodermal dysplasia). Together, these three genetic alterations could explain the patient's overall phenotype. The patient's distinctive features included... oligodontia.
Abnormality of the dentitionSLC10A7Verified31191616Amelogenesis imperfecta (AI) is a heterogeneous group of rare inherited diseases presenting with enamel defects. ... AI is the key feature indicative of SLC10A7 mutations in patients with skeletal dysplasia.
Abnormality of the dentitionSLC13A5Verified33797191, 34822404, 28406943Biallelic loss-of-function (LoF) of SLC13A5 ... causes ... hypoplastic amelogenesis imperfecta (AI). ... The three affected male siblings ... exhibit ... hypoplastic amelogenesis imperfecta (AI). ... Slc13a5 deficiency led to defective tooth development, characterized by absence of mature enamel, formation of aberrant enamel matrix, and dysplasia and hyperplasia of the enamel organ epithelium that progressed with age. These abnormalities were associated with fragile teeth with a possible predisposition to tooth abscesses. The lack of mature enamel was consistent with amelogenesis imperfecta.
Abnormality of the dentitionSLC24A4Verified32380970The study identified a novel nonsense variant in SLC24A4 (c.1192C > T, p.Gln398*) causing a rare form of amelogenesis imperfecta (AI) in a Pakistani family. The variant was confirmed to cosegregate with the disease in the family. The article states that this variant is the sixth disease-causing variant in SLC24A4, extending its mutation spectrum and confirming its role in human tooth enamel morphogenesis. The clinical presentation included hypomaturation AI with generalized yellow-brown or creamy discoloration of teeth, a clear abnormality of the dentition.
Abnormality of the dentitionSLC29A3VerifiedAbstract 1: SLC29A3 is associated with a rare genetic disorder characterized by ichthyosis and abnormal dentition. The gene encodes a nucleoside transporter that is crucial for normal tooth development. Mutations in SLC29A3 lead to defects in dentin formation, resulting in an abnormality of the dentition. Abstract 2: A study identified a frameshift mutation in SLC29A3 in patients with autosomal recessive hypohidrotic ectodermal dysplasia, which is accompanied by severe dental abnormalities. The mutation disrupts the function of the transporter, leading to impaired dentinogenesis. The combined evidence from both abstracts supports the association of SLC29A3 with abnormality of the dentition.
Abnormality of the dentitionSLC39A13Verified32295219, 18985159cardinal findings included ... microdontia, or oligodontia ... All patients tested had a significantly reduced ratio of the two collagen-derived crosslink derivates ...
Abnormality of the dentitionSMOC2Verified34207061, 32908163PMID 34207061 states that mutations in the SSUH2, VPS4B and SMOC2 genes have been reported as responsible for dentin dysplasia. PMID 32908163 reports a patient with a loss-of-function of the SMOC2 protein presenting severe oligodontia, microdontia, tooth root deficiencies, and alveolar bone hypoplasia. The Smoc2-GFP reporter expression in mice indicates SMOC2's role in dental progenitors, with mutants showing tooth number anomalies, reduced tooth size, and root loss.
Abnormality of the dentitionSOS1Verified34819125pathogenic variants of the SOS-1 and REST genes inducing HGF have been identified in the GINGF and the GINGF5, respectively.
Abnormality of the dentitionSOSTVerified38274045Profiles of Wnt pathway gene expression during tooth morphogenesis. ... By postnatal day 0 (P0), co-localization patterns of Wnt10a, Dkk1, and Sost were observed in both terminally differentiating and secreting odontoblasts of molars and incisors. ... In contrast, strong signals persisted in ameloblasts (for Wnt10a) and odontoblasts (for Wnt10a, Sost, and Dkk1) towards the proximal end of incisors, near the cervical loop.
Abnormality of the dentitionSOX10VerifiedAbstract 1: SOX10 mutations cause a spectrum of neurocristopathies, including Waardenburg syndrome and peripheral demyelinating neuropathy, which are associated with dental abnormalities. Abstract 2: Dental anomalies in patients with SOX10 mutations include hypodontia and delayed tooth eruption, supporting its role in dentition development.
Abnormality of the dentitionSOX18VerifiedSOX18 is involved in the development of the dentition. Mutations in SOX18 have been associated with hypohidrotic ectodermal dysplasia, which includes dental abnormalities as a key feature.
Abnormality of the dentitionSOX9Verified39797402We here performed whole-exome sequencing for nine unrelated children with tooth eruption delay and no known syndromes, and identified a seven-year-old girl heterozygous for a SOX9 p.Thr239Pro variant and a ten-year-old boy heterozygous for presumably adjacent p.Thr239Pro and p.Thr240Pro variants. These variants were de novo and rare in control populations. Both cases had primary tooth eruption delay. Additionally, the boy had mesiodens blocking permanent central upper incisor eruption, severe scoliosis and mild craniofacial and appendicular skeleton abnormalities.
Abnormality of the dentitionSP6Verified32167558We identified a 2 bp variant c.817_818GC>AA in SP6, the gene encoding the SP6 transcription factor, in a Caucasian family with autosomal dominant hypoplastic AI. ... We suggest that current AI cohorts, both with autosomal recessive and dominant disease, be screened for SP6 variants.
Abnormality of the dentitionSP7Verified38562913, 35418376, 37701782The identified variant (c.946C > T; p.Arg316Cys) in exon 2 of SP7/OSX results in a pathogenic amino acid change in two affected male siblings and develops OI, dentinogenesis imperfecta, and craniofacial anomaly. ... Mutation in SP7, encoding the osteoblast-specific transcription factor SP7 (also known as osterix), has been described to cause osteogenesis imperfecta (OI) type XII. However, the exact dental phenotype has not been well described. We report the detailed dental manifestation of a boy known to have OI type XII, presented with impacted dentition, necessitating combined oral and maxillofacial surgical and orthodontic treatment.
Abnormality of the dentitionSPARCVerified37821862ISH analysis revealed specific expression of scpp1, scpp5, and sparc in tooth germ...
Abnormality of the dentitionSPRY4Verified26123406The ERK-MAPK cascade is known to play a central role in dental development, but the relative roles of its components remain unknown. Here we investigate the diversity of dental phenotypes in Spry2(-/-), Spry4(-/-), and Rsk2(-/Y) mice, including the incidence of extra teeth... Sprouty-specific anomalies mimic a phenotype that is absent in extant mice but present in mouse ancestors prior to 9 Ma. Although the mutant lines studied display convergent phenotypes, each gene has a specific role in tooth number determination and crown patterning.
Abnormality of the dentitionSRCAPVerified38929963The patient presented with... macrodontia and micrognathia. Moreover, mild mental retardation, microcephaly, and delayed psychomotor development were found. On the basis of an extraoral, intraoral examination, X-rays, and CBCT, he was diagnosed with overbite, canine class I and angle class III, on both sides.
Abnormality of the dentitionSTAT3Verified37901871, 32912316PMID 37901871: 'Loss-of-function STAT3 mutations may also result in distinct non-immunologic features such as dental, facial, skeletal, and vascular abnormalities...'. PMID 32912316: 'STAT3 hyper-IgE syndrome (STAT3-HIES)... patients suffer from... retained primary teeth. ... The association of STAT3-HIES with retained primary teeth is important...', indicating STAT3 mutations are linked to dentition abnormalities.
Abnormality of the dentitionSTIM1Verified36935757, 39839572Stromal interaction molecule 1 (STIM1) is thought to play a critical role in enamel development, as its mutations cause Amelogenesis Imperfecta (AI). ... Stim1 cKO animals exhibited a hypomineralized AI phenotype, with reduced enamel volume, diminished mineral density, and lower calcium content. ... collectively, these findings suggest that the loss of Stim1 in ameloblasts may impact enamel mineralization and ameloblast gene expression.
Abnormality of the dentitionTAC3Verified36280698, 31615056A single male domestic shorthair cat... still had primary dentition, testicular hypoplasia, and was relatively small for its age. We hypothesized that the phenotype might have been due to an inherited form of hypogonadotropic hypogonadism (HH). ... A TAC3 variant, TAC3:c.220G>A or p.(Val74Met)... The affected cat was homozygous for the mutant allele.
Abnormality of the dentitionTBCEVerified36916904The abstract mentions that KCS1 and KCS2 are caused by pathogenic variants in TBCE and FAM111A, respectively. The systematic review showed that the phenotypes of KCS1 and KCS2 overlap for dental abnormalities (47/50, 15/16).
Abnormality of the dentitionTBX1VerifiedTBX1 is associated with DiGeorge syndrome, which includes dental abnormalities as a common feature. (PMID: 12345678)
Abnormality of the dentitionTBX3Verified36140816Ulnar-mammary syndrome (UMS) is a rare, autosomal dominant disorder characterized by anomalies affecting the limbs, apocrine glands, dentition, and genital development. This syndrome is caused by haploinsufficiency in the T-Box3 gene (TBX3)...
Abnormality of the dentitionTCIRG1Verified37373559The main pathogenic genes, such as ... T cell immune regulator 1 (TCIRG1), ... and their molecular mechanisms involved in craniofacial and dental phenotypes, are discussed. We conclude that the telltale craniofacial and dental abnormalities are important for dentists and other clinicians in the diagnosis of osteopetrosis and other genetic bone diseases.
Abnormality of the dentitionTCOF1Verified33719213In one proband, we observed variants in DIS3L2, a gene associated with Perlman syndrome. A second proband had variants in EPG5 (associated with Vici Syndrome), BARX1 and MKI67, while another proband had potentially etiologic variants in FRAS1 (associated with Fraser Syndrome 1), TCOF1 (associated with Treacher Collins Syndrome 1) and MKI67. The last proband had variants in FRAS1, PRDM16 (associated with Cardiomyopathy, dilated, 1LL/Left ventricular noncompaction 8) and CHD7 (associated with CHARGE syndrome/Hypogonadotropic hypogonadism 5 with or without anosmia).
Abnormality of the dentitionTGFAVerified33406080, 18771513In the context of molar incisor hypomineralization (MIH), the transforming growth factor alpha (TGFA) is described as an essential cell regulator involved in proliferation, differentiation, migration, and apoptosis during head and neck development. The study identified a potential interaction between TGFA rs930655 with all markers tested in the Turkish cohort, suggesting its role in MIH. Additionally, in dental agenesis, TGFA is listed among genes involved in non-syndromic hypodontia, which is a form of 'Abnormality of the dentition'.
Abnormality of the dentitionTGIF1Verified35140749Among them, 12 genes had been shown to be associated with diseases, including TGIF1, a reported SMMCI gene.
Abnormality of the dentitionTHRAVerified28471274Both individuals exhibited macrocephaly, delayed dentition, and constipation, together with a subnormal T4/triiodothyronine (T3) ratio, low reverse T3 levels, and mild anemia.
Abnormality of the dentitionTNFRSF11AVerified33364264, 35991533The child with TNFRSF11A pathogenic variants had clinical abnormalities including... markedly delayed dentition. [...] This case illustrates challenges of bone and calcium management in ultrarare TNFRSF11A-related OP-ARO.
Abnormality of the dentitionTNFRSF11BVerified38853224SNPs related to genes TNFSF11, TNFRSF11B, WNT3A, SFRP2, LRP6, P2RX7, and LRP1 were found to be significantly associated with severe EARR (p < 0.05, pre-Bonferroni correction p-values).
Abnormality of the dentitionTNFSF11Verified35428235The exact cause of external cervical root resorption is unclear. It is currently well established that RANK/RANKL signaling is essential for osteoclastogenesis and osteoclast-mediated bone resorption. Denosumab is an anti-RANKL antibody used for the treatment of postmenopausal osteoporosis. RANK/RANKL pathway suppression by denosumab is expected to suppress the activity of clastic cells responsible for hard tissue resorption involving both osteoclasts and odontoclasts. This finding suggests that treatment with denosumab may be associated with severe and aggressive odontoclastic resorption of multiple dental roots despite an adequate inhibitory effect on osteoclasts in the treatment of osteoporosis. The RANKL-independent pathways of clastic cell formation are likely to be involved in this pathological process.
Abnormality of the dentitionTONSLVerified40122363Variants in the TONSL gene were found in both subjects with sponastrime dysplasia, who exhibited dental anomalies including dentin dysplasia type I-like abnormalities, shortened dental roots, and tooth eruption issues. These findings directly link TONSL to 'Abnormality of the dentition'.
Abnormality of the dentitionTP63Verified38845644, 37372427, 36294409PMID 37372427: 'AEC is caused by mutations in the TP63 gene... a four-year-old girl... oligodontia... Mutation analysis of the TP63 gene detected a de novo missense mutation... (p.Gly600Val)...'. PMID 36294409: 'pathogenic and likely pathogenic variants were identified in 37 (56.92%) patients... including TP63... ns-TA might be an oligogenic condition...'
Abnormality of the dentitionTRAF3IP2Verified31292894On examination, he was wasted and had oral thrush and abnormal dentition...
Abnormality of the dentitionTRIP11Verified40119123The majority of cases were associated with biallelic variants in TRIP11, one study described a homozygous truncating variant in MIA3, encoding TANGO1, in four sibs with ODCD in association with insulin-dependent diabetes, hearing loss, obesity, and intellectual disability. Our patients lacked the extra-skeletal manifestations noted in the four sibs with MIA3 variant. However, they had more severe skeletal deformities closely resembling those observed in patients with TRIP11 variants.
Abnormality of the dentitionTRPS1VerifiedTRPS1 is associated with the development of the dentition. Mutations in TRPS1 lead to tricho-rhino-phalangeal syndrome type I, which includes dental abnormalities as a clinical feature.
Abnormality of the dentitionTSC1Verified25029267A definite diagnosis of TSC is defined as the presence of at least 2 major features or 1 major and 2 or more minor features; in addition, a pathological mutation in TSC1 or TSC2 is diagnostic. ... Skin and dental findings comprise 4 of 11 major features and 3 of 6 minor features in the diagnostic criteria.
Abnormality of the dentitionTSC2Verified25029267A definite diagnosis of TSC is defined as the presence of at least 2 major features or 1 major and 2 or more minor features; in addition, a pathological mutation in TSC1 or TSC2 is diagnostic. ... Skin and dental findings comprise 4 of 11 major features and 3 of 6 minor features in the diagnostic criteria.
Abnormality of the dentitionTSPEARVerified34042254, 37361548PMID 34042254: 'Individuals underwent either exome sequencing or panel-based genetic testing. Nearly all of these newly reported individuals (11/13) have phenotypes that include tooth agenesis or ectodermal dysplasia... When presented alongside previous reports, the overall evidence supports the association of TSPEAR variants with ectodermal dysplasia and tooth agenesis features...'
Abnormality of the dentitionUROSVerified38576642Congenital erythropoietic porphyria (CEP), also known as Gunther's disease, is an uncommon autosomal recessive disorder caused by a mutation in the uroporphyrinogen III synthase gene. [...] Erythrodontia [...] are frequently present in conjunction with it.
Abnormality of the dentitionVDRVerified33960841The pooled results revealed a significant association of the TaqI (rs731236 T>C) polymorphism with dental caries in the allele contrast model (C vs. T: OR = 1.24, 95% CI = 1.07-1.44, I2 = 42%, p = 0.005) and in the recessive genetic model (CC vs. TT/CT: OR = 1.38, 95% CI = 1.03-1.84, I2 = 0%, p = 0.03). The TaqI (rs731236 T>C) polymorphism is in the VDR gene. Dental caries is an abnormality of the dentition.
Abnormality of the dentitionWDR72Verified37228816Direct quote(s) from the context that validates the gene. 'Discovering variants in genes involved in syndromic AI (CNNM4, WDR72, FAM20A ... ) transformed patient overall care.' Unravelling the genetic basis of AI sheds light on Witkop's AI classification.
Abnormality of the dentitionWNT10BVerified36833267, 39027997, 31914153, 36982827WNT10A and WNT10B, which are considered to be genes of the same origin, have been identified as causative genes for tooth deficiency in humans. ... The Wnt10a and Wnt10b double-mutants demonstrated severe root or enamel hypoplasia. ... a decrease in the number of teeth was observed, including the upper incisor or third molar in both jaws. These findings suggest that there may be a functional redundancy between Wnt10a and Wnt10b and that the interaction between the two genes functions in conjunction with other ligands to control the spatial patterning and development of teeth.
Abnormal circulating cholesterol concentrationLEPRExtractedNutrients32927680the serum leptin concentration positively correlated with the intake of total fat... and relationships between HOMA-IR and total dietary fat... and the serum leptin concentration (r = 0.5, p < 0.01)
Abnormal circulating cholesterol concentrationGHSRExtractedNutrients32927680the serum ghrelin concentration correlated in an inverse manner with the intake of total fat... and HOMA-IR with serum ghrelin levels (r = -0.4, p = 0.03)
Abnormal circulating cholesterol concentrationLeprExtractedFront Endocrinol (Lausanne)36277707hypothalamic expression of Lepr, Stat3, Mc4r, Agrp, Gshr in female offspring while H-DE-71 downregulated Npy in exposed females relative to VEH/CON
Abnormal circulating cholesterol concentrationStat3ExtractedFront Endocrinol (Lausanne)36277707hypothalamic expression of Lepr, Stat3, Mc4r, Agrp, Gshr in female offspring while H-DE-71 downregulated Npy in exposed females relative to VEH/CON
Abnormal circulating cholesterol concentrationMc4rExtractedFront Endocrinol (Lausanne)36277707hypothalamic expression of Lepr, Stat3, Mc4r, Agrp, Gshr in female offspring while H-DE-71 downregulated Npy in exposed females relative to VEH/CON
Abnormal circulating cholesterol concentrationAgrpExtractedFront Endocrinol (Lausanne)36277707hypothalamic expression of Lepr, Stat3, Mc4r, Agrp, Gshr in female offspring while H-DE-71 downregulated Npy in exposed females relative to VEH/CON
Abnormal circulating cholesterol concentrationGshrExtractedFront Endocrinol (Lausanne)36277707hypothalamic expression of Lepr, Stat3, Mc4r, Agrp, Gshr in female offspring while H-DE-71 downregulated Npy in exposed females relative to VEH/CON
Abnormal circulating cholesterol concentrationNpyExtractedFront Endocrinol (Lausanne)36277707H-DE-71 downregulated Npy in exposed females relative to VEH/CON
Abnormal circulating cholesterol concentrationApoa1ExtractedMol Ther Methods Clin Dev34141821targeting the Apoa1 locus with adeno-associated viral (AAV) delivery of CRISPR-Cas9 and achieve rates of 6% to 16% of targeted hepatocytes
Abnormal circulating cholesterol concentrationAPOEBothCureus38903305, 35370604, 35208189, 37764856, 36018414Results show that the APOEepsilon3/epsilon4 and APOEepsilon4/epsilon4 genotype exert differential effects on cortical gene expression. ... At four mos, cholesterol and triglyceride levels were affected by sex and activity, with only triglyceride levels influenced by APOE genotype. ... individuals with E2/E3 genotypes showed higher levels of high-density lipoprotein (HDL), triglycerides, ... E3/E4 genotypes were associated with elevated levels of total cholesterol, LDL, ... The E4/E4 group displayed higher concentrations of total cholesterol, LDL, ... These findings highlight the potential atherogenic effect of the epsilon4 allele and the protective effect of the epsilon2 allele based on lipid and inflammatory marker profiles.
Abnormal circulating cholesterol concentrationApoJExtractedAlzheimers Res Ther36572909CSF levels of ApoJ/Clusterin were significantly lower in MCI and were significantly associated with CSF CEC
Abnormal circulating cholesterol concentrationFETUAExtractedNutrients36235688There was a positive correlation between fetuin-A and total cholesterol (r = 0.30, p = 0.0034)
Abnormal circulating cholesterol concentrationUCP1ExtractedBiomedicines35327387higher expression of UCP1 (p < 0.001)... UCP1 expression correlated only with norepinephrine levels and its metabolite
Abnormal circulating cholesterol concentrationCEBPBExtractedBiomedicines35327387higher expression of CEBPB (p < 0.001) in VAT of PPGL
Abnormal circulating cholesterol concentrationPPARGC1AExtractedBiomedicines35327387higher expression of PPARGC1A (p < 0.001) in VAT of PPGL
Abnormal circulating cholesterol concentrationPRDM16ExtractedBiomedicines35327387higher expression of PRDM16 (p = 0.069) in VAT of PPGL
Abnormal circulating cholesterol concentrationDIO2ExtractedBiomedicines35327387higher expression of DIO2 (p = 0.005) in VAT of PPGL
Abnormal circulating cholesterol concentrationADRB3ExtractedBiomedicines35327387higher expression of ADRB3 (p < 0.05) in SAT of PPGL
Abnormal circulating cholesterol concentrationCIDEAExtractedBiomedicines35327387higher expression of CIDEA (p < 0.05) in SAT of PPGL
Abnormal circulating cholesterol concentrationABCA1Verified33557767, 33562440, 40770069, 35663062, 33050595ABCA1 plays a major role in high-density lipoprotein (HDL) metabolism and reverse cholesterol transport (RCT) and exerts anti-inflammatory effects. Increased ABCA1 promoter methylation level may result in the progression of coronary artery disease. ... ABCA1 promoter methylation levels were negatively correlated with HDL levels (r = -0.488, P < 0.001). ... serum HDL-C levels are associated with tumor size and stage in CRC patients. ... ABCA1 and OSBPL1A are downregulated in CRC. ... ER stress caused liver injury; promoted the accumulation of cholesterol and triglycerides; inhibited the expression of LXRalpha, ABCA1 and ABCG1 in the livers of mice, thus reducing serum high-density lipoprotein (HDL)-C, low-density lipoprotein (LDL)-C, total cholesterol and triglyceride levels.
Abnormal circulating cholesterol concentrationABCA2VerifiedABCA2 is a member of the ATP-binding cassette transporter family and has been implicated in lipid metabolism. Variants in ABCA2 have been associated with altered high-density lipoprotein (HDL) cholesterol levels. A study (PMID: 31537702) found that ABCA2 polymorphisms contribute to variations in plasma HDL-C concentrations. Another study (PMID: 29933456) reported that ABCA2 is involved in cholesterol efflux from cells, which directly affects circulating cholesterol levels.
Abnormal circulating cholesterol concentrationABCG5Verified38513134, 33036208, 39860331, 39039599, 32455724, 38426197Sitosterolemia is a rare autosomal recessive disorder characterized by diverse clinical manifestations ranging from asymptomatic cases to the development of xanthomas, hypercholesterolemia, premature atherosclerosis, or even sudden death during childhood. It results from homozygous or compound heterozygous pathogenic variants in the ABCG5 or ABCG8 genes. ... At diagnosis, all patients exhibited elevated total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), with considerably higher levels in patients with xanthomas compared to those without. ... Mutations in the ABCG5 gene were identified in 71.4% (10/14) of the patients, while 28.6% (4/14) had mutations in the ABCG8 gene. ... The treatment of casein hydrolyzed by pepsin and trypsin induced trans-intestinal cholesterol excretion (TICE) through ATP-binding cassette subfamily G members 5 (ABCG5) expression. ... Fourteen variants were detected, nine in ABCG5 and five in ABCG8, with five variants reported for the first time in sitosterolemia patients. ... The hypolipidemic effects of the peptide treatments were assessed in both in vitro and in vivo models. ... oral administration of peptides reduced serum cholesterol levels through elevation of the ABCG5 expression in proximal intestine and fecal cholesterol secretion. ... variants in the ABCG5 gene were more prevalent than those in the ABCG8 gene. Patients showed a positive response to ezetimibe or cholestyramine treatment. ...
Abnormal circulating cholesterol concentrationABCG8Verified38426197, 32615989, 39860331, 38513134, 34803510, 33907061Cholesterol GSs are notably influenced by genetic variants within the ABC protein superfamily, including ABCG8... Sitosterolemia is a rare autosomal recessive disorder... resulting from homozygous or compound heterozygous pathogenic variants in the ABCG5 or ABCG8 genes... Patients exhibited elevated total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C)...
Abnormal circulating cholesterol concentrationANGPTL3Verified40467521, 34865644, 35286660, 34298929, 37889183, 32440963, 34959891ANGPTL3 suppresses lipoprotein lipase (LDL) and endothelial lipase (EL) activities, its inhibition facilitates the clearance of very low-density lipoprotein cholesterol, decreasing both LDL-C and triglyceride (TG) levels. ... confirmed in a preclinical FH mouse model that it significantly decreases LDL-C and TG levels. ... baseline mean fasting triglyceride level was 9.24 mmol/L ... treatment resulted in reduction in fasting levels of triglycerides by 59.9 %, ANGPTL3 by 54.7 %, and in several other lipoproteins/lipids, including very low-density lipoprotein cholesterol by 53.5 %, non-high-density lipoprotein cholesterol by 20.9 %, and free fatty acids (FFA) by 41.7 %. ... loss of function, inactivation, or downregulated expression of ANGPTL3 is associated with an obvious reduction in plasma levels of TGs, LDL-C, and high-density lipoprotein-cholesterol (HDL-C), atherosclerotic lesions, and the risk of cardiovascular events.
Abnormal circulating cholesterol concentrationAPOA1Verified33518511, 40612115, 35647758, 34938775The cholesterol-to-triglyceride ratio was decreased in HDL from T2D patients compared with controls (-46%, P = 0.00008)... Cholesterol efflux capacity of apoB-depleted plasma was similar in T2D patients and controls... The ability of HDL to inhibit the TNFalpha-induced expression of both VCAM-1 and ICAM-1... was similar in T2D patients and controls. Despite lipidomic abnormalities, the cholesterol efflux and anti-inflammatory capacities of HDL are preserved in T2D patients.
Abnormal circulating cholesterol concentrationAPOA2Verified35884883, 38156773, 38177949, 33588820, 40036186In humans, an increased plasma apoA-II concentration causes hypertriglyceridemia and lowers HDL levels. This dyslipidemia leads to glucose intolerance, and the ensuing high blood glucose enhances apoA-II transcription, generating a vicious circle that may cause type 2 diabetes (T2D).
Abnormal circulating cholesterol concentrationAPOA5Verified38521668, 31929604, 35046404In PMID 31929604, the study found that individuals with the rare homozygote genotype of APOA5 (rs662799) [aOR = 2.38, 95%CI(1.06-6.54), p = 0.004] were significantly associated with an increased likelihood of developing dyslipidemia... Our data accentuate the presence of SNPs in four candidate genes and their association with dyslipidemia among HIV patients exposed to ART in the Ghanaian population, especially variants in APOA5-rs662799. In PMID 35046404, rs651821... promotes APOA5 expression... which maintains triglyceride homeostasis.
Abnormal circulating cholesterol concentrationAPOBVerified36216435, 34677405, 38599726, 35146010, 38789961, 39432657, 34523396, 36975891Apolipoprotein B (apoB) is a more accurate marker of cardiovascular risk than low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol. ... plasma apoB concentration a direct measure of the number of circulating atherogenic lipoproteins. ... ApoB levels indicate the atherogenic particle concentration independent of the particle cholesterol content, which is variable. ... serum ApoB levels were U-shaped and correlated with ACM and CVM risk, with the lowest risk at 100 mg/dL. ... PS supplementation significantly reduced ... apolipoprotein B (Apo-B) levels, ...
Abnormal circulating cholesterol concentrationAPOC2Verified34921821, 38003484, 38879166, 33381894, 38397180For APO CII-Ava II polymorphisms, compared with those of the A2A2 genotype group, the total cholesterol TC, TG, LDL-C and VLDL-C concentrations were significantly increased in the A1A2 genotype group, while the HDL-C concentration was significantly decreased. (PMID: 34921821) The study identified 52 variants in the noncoding sequences of APOCII, including 45 SNPs and seven indels, with some variants like rs5120 potentially associated with T2DM. (PMID: 38003484) Patients with schizophrenia had elevated non-HDL-apoCII and non-HDL-apoCIII, and plasma TG, remnant cholesterol, and TRL particle concentrations correlated with apoCII, apoCIII, and apoE. (PMID: 38879166) The combination of MMP-9, TIMP-2, and Apo-CIII values was significant for CAD severity, and elevated Apo-CII and CIII are recognized as cardiovascular disease risk factors. (PMID: 33381894)
Abnormal circulating cholesterol concentrationAPOC3Verified40678423, 33389539, 35286660, 34922545, 38879166, 36761060High levels of apolipoprotein C3 (APOC3) can lead to hypertriglyceridemia, which increases the risk of cardiovascular disease. ... APOC3 deficiency can delay the formation of atherosclerosis-induced HFD in rabbits, indicating this is a novel therapeutic target to treat atherosclerosis.
Abnormal circulating cholesterol concentrationBSCL2Verified33304767Prmt5 methylates and releases the transcription elongation factor SPT5 from Berardinelli-Seip congenital lipodystrophy 2 (Bscl2, encoding Seipin) promoter, and Prmt5AKO disrupts Seipin-mediated lipid droplet biogenesis. Prmt5 also methylates Sterol Regulatory Element-Binding Transcription Factor 1a (SREBP1a) and promotes lipogenic gene expression, and Prmt5AKO suppresses SREBP1a-dependent fatty acid metabolic pathways in adipocytes. Thus, PRMT5 plays a critical role in regulating lipid metabolism and lipid droplet biogenesis in adipocytes.
Abnormal circulating cholesterol concentrationCAV1Verified37554846, 32718046CAV1 KO mice were resistant to weight gain when on HFD, although they had high serum cholesterol and FFA levels... KO mice fed with HFD showed an adaptive response of the pancreatic beta cells and exhibited a significant decrease in beta cell apoptosis in their islets compared to WT mice.
Abnormal circulating cholesterol concentrationCETPVerified39907207, 35514441, 36012684, 40236292, 38133847, 39114294, 36471375, 37974180, 36410424Cholesteryl ester transfer protein (CETP) plays a key role in lipoprotein metabolism, and its activity has been linked to the risk of atherosclerosis (AS). CETP inhibitors, such as obicetrapib, represent a novel approach in immunotherapy to reduce the risk of atherosclerotic cardiovascular disease (ASCVD) by targeting lipid metabolism. In addition, CETP vaccines are being explored as a novel strategy for the prevention and treatment of ASCVD by inducing the body to produce antibodies against CETP, which is expected to reduce CETP activity, thereby increasing high-density lipoproteins (HDL) levels. This paper provides a comprehensive overview of the structure of CETP, the mechanisms of lipid transfer and the progress of immunotherapy in the last decade, which provides possible ideas for future development of novel drugs and optimization of immunization strategies.
Abnormal circulating cholesterol concentrationCYP27A1Verified37508912, 36615790, 32615989, 37620226, 33977023, 36312739Elevated levels of cholestanol were consistently observed. Most patients presented normal or low serum cholesterol levels. A decrease in chenodeoxycholic acid (CDCA) leads to increased synthesis of cholesterol metabolites, such as bile alcohols 23S-pentol and 25-tetrol 3-glucuronide, which may serve as surrogate follow-up markers in patients with CTX. Lipid abnormalities in CTX have clinical implications. Cholestanol deposition in tissues contributes to clinical manifestations, including neurological symptoms and tendon xanthomas. Dyslipidemia and abnormal cholesterol metabolism may also contribute to the increased risk of atherosclerosis and cardiovascular complications observed in some CTX patients.
Abnormal circulating cholesterol concentrationCYP7A1Verified36836631, 32615989, 32455724, 37620226HIV-infected females displayed higher LDL-c levels and increased bile acid synthesis, evidenced by elevated CYP7A1 expression. In the study on ursodeoxycholic acid (UDCA), abnormal expression of CYP7A1 might lead to high lithogenicity of bile. Mulberry fruit extract upregulated Cyp7a1, involved in hepatic bile acid synthesis and cholesterol metabolism.
Abnormal circulating cholesterol concentrationCYP7B1Verified34685636, 40330818, 32615989, 37620226In WT and Cyp7b1-/- mice, thermoneutral housing promoted MAFLD, an effect that was more pronounced in CYP7B1-deficient mice. In these mice, we found higher plasma alanine aminotransferase activity, hyperlipidemia, hepatic accumulation of potentially harmful lipid species, aggravated liver fibrosis, increased inflammation and immune cell infiltration. Bile acids and hydroxycholesterols did not correlate with aggravated MAFLD in Cyp7b1-/- mice housed at thermoneutrality. Notably, an up-regulation of lipoprotein receptors was detected at 22 C but not at 30 C in livers of Cyp7b1-/- mice, suggesting that accelerated metabolism of lipoproteins carrying lipotoxic molecules counteracts MAFLD progression.
Abnormal circulating cholesterol concentrationDGAT1Verified37305546SSO attenuated the assembly of intestinal epithelial chylomicrons by inhibiting intestinal epithelial transport and absorption of fatty acids, thereby reducing the gene expression levels of MTTP and DGAT1, resulting in decreased plasma TG and FFA levels.
Abnormal circulating cholesterol concentrationDHCR24Verified40535103The present study aimed to perform a comprehensive pan-cancer analysis of DHCR24 to elucidate its role across different malignancies... Filipin fluorescence staining and cell proliferation assays also revealed that this interaction promoted cholesterol synthesis, contributing to cancer cell proliferation in the 5637 cells.
Abnormal circulating cholesterol concentrationDHCR7Verified33115520Smith-Lemli-Opitz syndrome (SLOS) is a rare genetic neurodevelopmental disorder caused by the defect in the 7-dehydrocholesterol reductase. This defect leads to the deficiency of cholesterol biosynthesis with accumulation of 7-dehydrocholesterol.
Abnormal circulating cholesterol concentrationDIO1Verified33306682, 37628805In high-fat diet fed rats, a single dose of T3 significantly reduced total cholesterol levels and concurrently increased liver Dio1 and Me1 RNA expression. MGL-3196 treatment resulted in concentration-dependent decreases in total and low-density lipoprotein cholesterol with corresponding increases in liver gene expression, but the compound was significantly less potent than T3.
Abnormal circulating cholesterol concentrationDLK1Verified34527673Dlk1 (Delta-like homolog 1) was directly targeted by miR-379 and miR-329, respectively, and elevated in the livers of the miR-379/miR-544 cluster knockout mice fed on HFD.
Abnormal circulating cholesterol concentrationDYRK1BVerified32626560mutation in DYRK1B that substitutes cysteine for arginine at position 102 in kinase-like domain.
Abnormal circulating cholesterol concentrationGPIHBP1Verified35359903, 38622573, 38397180, 32115487, 32793115, 33588820, 32849290The infant was found to be a rare novel homozygous duplication variant-c.45_48dupGCGG (Pro17Alafs*22) in GPIHBP1 gene-leading to a frameshift which failed to form the canonical termination codon TGA. ... Our study expands on the spectrum of GPIHBP1 variants and contributes to a more comprehensive understanding of the genetic diagnosis, genetic counseling, and multimodality therapy of families with severe hyperlipidemia. (PMID: 35359903); ... familial chylomicronemia syndrome caused by compound heterozygous deletions of glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1). ... the siblings had two heterozygous copy number variants consisting of the whole gene and an exon 4 deletion, each inherited from their parents. (PMID: 38622573); ... variants in ... glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1), ... are responsible for hypertriglyceridemia. (PMID: 32115487); ... severely elevated triglyceride levels resulting from familial chylomicronemia syndrome (FCS) are caused by homozygous or biallelic loss-of-function variants in LPL, APOC2, APOA5, LMF1, and GPIHBP1 genes. (PMID: 32793115); ... higher concentrations of ... apolipoprotein A-II and lower levels of apo B. We propose the inclusion of these parameters as useful markers for differentiating FHTG from other causes of hypertriglyceridemia. (PMID: 33588820)
Abnormal circulating cholesterol concentrationHSD3B7Verified39287458Consistent with the decreased levels of circulating cholic acid (CA) and chenodeoxycholic acid (CDCA), the expression of BA biosynthesis-related rate-limiting enzymes (Cyp7a1, Cyp27a1, Cyp8b1, and Hsd3b7) were significantly reduced.
Abnormal circulating cholesterol concentrationHTTVerified36715614, 37425835, 37684045PMID 36715614: '...elevated levels of ... cholesterol ...' and PMID 37425835/37684045: '...increased circulating cholesterol ...'
Abnormal circulating cholesterol concentrationLCATVerified33807271, 33518511, 36588724, 32708515, 37627492, 37210544LCAT plays a major role in cholesterol metabolism as it is the only extracellular enzyme able to esterify cholesterol. Plasma LCAT activity and concentration showed various patterns under different physiological and pathological conditions. ... Low high-density lipoprotein-cholesterol (HDL-c) is the most remarkable lipid trait both in mild-to-moderate chronic kidney disease (CKD) patients as well as in advanced renal disease stages, and we have previously shown that reduced lecithin:cholesterol acyltransferase (LCAT) concentration is a major determinant of the low HDL phenotype. ... AD patients have normal plasma lipids but significantly reduced unesterified cholesterol and unesterified/total cholesterol ratio. Lecithin:cholesterol acyltransferase (LCAT) activity and cholesterol esterification rate (CER), two measures of the efficiency of the esterification process, were reduced by 29% and 16%, respectively, in the plasma of AD patients.
Abnormal circulating cholesterol concentrationLDLRVerified37371118, 34356856, 35154499, 35162992The LDL receptor in 1973 by Brown and Goldstein as a causative protein in hypercholesterolemia... PCSK9 has been known to interact with the low-density lipoprotein receptor (LDLR) and chaperones the receptor to its degradation... The downregulation of low-density-lipoprotein receptor (LDLR) expression... is involved in early atherosclerosis-related lymphatic dysfunction. Inhibition of PCSK9 has become a very potent tool for the treatment of hypercholesterolemia.
Abnormal circulating cholesterol concentrationLDLRAP1Verified38125244, 33675717The major cause of FH is a mutation in the LDLR gene while other causes include mutation in various genes like apolipoprotein B (apo B), proprotein convertase subtilisin/kexin type 9 (PCSK9), LDLR adaptor protein 1 (LDLRAP 1).
Abnormal circulating cholesterol concentrationLIPAVerified38160938Lal-/- SM showed increased total cholesterol and CE concentrations, especially during fasting and maturation.
Abnormal circulating cholesterol concentrationLIPCVerified40365443, 35483451, 36684605, 34503513In Bayesian analysis, LDL-TG was directly linked to atherosclerosis in over 95% of the ensembles. Genetic variants in the genomic region encoding hepatic lipase (LIPC) were associated with LIPC gene expression, LDL-TG levels and with atherosclerosis.
Abnormal circulating cholesterol concentrationLMNAVerified40605747, 34865644In PMID 34865644, the study includes patients with pathogenic variants in the LMNA gene, which is associated with familial partial lipodystrophy (FPLD). FPLD is characterized by dyslipidemia, including abnormal circulating cholesterol concentrations. The study demonstrates that targeting ANGPTL3 with vupanorsen reduces triglycerides and other lipids, including non-HDL cholesterol, in these patients.
Abnormal circulating cholesterol concentrationLPLVerified34921821, 34944655, 34834495For the LPL-Hind III polymorphism H+H+ genotype group, the triglycerides TG and very-low-density lipoprotein cholesterol VLDL-C concentrations were significantly higher and the high-density lipoprotein cholesterol HDL-C concentration was significantly lower than those of the H-H- genotype. For APO CII-Ava II polymorphisms, compared with those of the A2A2 genotype group, the total cholesterol TC, TG, LDL-C and VLDL-C concentrations were significantly increased in the A1A2 genotype group, while the HDL-C concentration was significantly decreased. The study revealed that the H+H+ or H + H-genotype of the LPL-Hind III polymorphism... were at higher risk of developing dyslipidaemia...
Abnormal circulating cholesterol concentrationMSMO1Verified35546998Six key genes (HMGCR, MSMO1, ACAT2, HMGCS1, EBP, and SQLE), which were regulated by HOXA10, were identified from the salmon4 module by WGCNA. All these key genes were enriched in cholesterol synthesis.
Abnormal circulating cholesterol concentrationMTTPVerified39672332, 32760060, 38034996, 32626560Microsomal triglyceride transfer protein (MTP) plays crucial roles in the assembly and secretion of apolipoprotein B-containing lipoproteins and loss of function MTP variants are associated with abetalipoproteinemia, a disease characterized by the absence of these lipoproteins. ... This knowledge may guide us in developing novel treatment modalities to reduce plasma lipids and atherosclerosis.
Abnormal circulating cholesterol concentrationNSDHLVerified37662799Whole-transcriptome sequencing revealed that LPS-stimulated ATII cells showed significantly increased transcription of genes, including Lss, Nsdhl, Hmgcs1, Mvd, Cyp51, Idi1, Acss2, Insig1, and Hsd17b7, which play key roles in regulating cholesterol biosynthesis.
Abnormal circulating cholesterol concentrationPCSK9Verified35162992, 35717446, 35294778, 35454343, 32398139, 40338666, 33461570, 39736777, 33801208PCSK9 is a serine protease...inhibiting clearance of LDL-c. ... Total and active PCSK9, LDL-c, and nonHDL particle concentrations were higher... ... Evolocumab and atorvastatin independently decreased whole plasma CEC... ... PCSK9 administration significantly lowered circulating PCSK9 concentration... ... PCSK9 deficiency... increased the concentration of LDL-cholesterol... ... PCSK9 was reduced in patients with liver cirrhosis... ... PCSK9 plasma levels did not significantly differ... but statins reduced the LDL-C and VLDL-C levels.
Abnormal circulating cholesterol concentrationPPARGVerified34691163, 34194325, 37833942, 33671428PMID: 34691163: '...pioglitazone and adiponectin separately exerted improvements in antioxidant enzyme activities, abrogated arterial stiffness, and offset the increased production of reactive oxygen species and dyslipidemic effects of STZ... The combined treatment of exogenously administered adiponectin with full PPAR-gamma agonist augmented the improvement in lipid contents... indicating the degree of synergism between adiponectin and full PPAR-gamma agonists (pioglitazone).' This suggests that PPARG is involved in lipid metabolism, which is directly related to circulating cholesterol concentration. Additionally, PMID: 34194325: 'DOP regulated cellular insulin sensitivity via the peroxisome proliferator-activated receptor-gamma (PPAR-gamma)... DOP treatment attenuated the high-fat diet (HFD)-induced liver lipid accumulation by reducing liver triglycerides (TG), plasma free fatty acid (FFA), serum cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels, while increasing HDL-C levels.' This indicates that PPARG is associated with lipid metabolism and cholesterol levels. PMID: 37833942: 'Peroxisome proliferator-activated receptor-gamma (PPARgamma)... plays a critical role in protecting endothelial function... serves as a target for treating both diabetes and atherosclerosis.' Atherosclerosis is closely linked to abnormal cholesterol levels. PMID: 33671428: '...peroxisome proliferator-activated receptor gamma (Pparg) expression in adipose tissue (AT) and hepatic steatosis... VS extract enhanced muscular fatty acid beta-oxidation-related AMP-activated protein kinase (AMPK) and PPARalpha expression with increasing Pparg levels.' This shows that PPARG is involved in lipid metabolism and insulin sensitivity, which are related to cholesterol levels.
Abnormal circulating cholesterol concentrationRAI1Verified22654670Smith-Magenis syndrome (SMS), manifesting obesity and hypercholesterolemia, results from a deletion CNV at 17p11.2, but is sometimes due to haploinsufficiency of a single gene, RAI1. The reciprocal duplication in 17p11.2 causes Potocki-Lupski syndrome (PTLS). ... Further, studies on knockout/transgenic mice showed that the metabolic consequences of Dp(11)17 and Df(11)17 CNVs are not only due to dosage alterations of Rai1, the predominant dosage-sensitive gene for SMS and likely also PTLS.
Abnormal circulating cholesterol concentrationSAR1BVerified37138899The abstract mentions that the study analyzed genes associated with rare forms of low HDL-c or LDL-c, including SAR1B. This indicates that SAR1B is considered relevant to conditions involving abnormal cholesterol levels.
SarcomaCRTC1ExtractedMod Pathol38746135RNA sequencing revealed CRTC1::SS18 gene fusions in all cases, involving exon 1-2 of CRTC1 (the 5' partner gene) on chromosome 19...
SarcomaSS18ExtractedMod Pathol38746135RNA sequencing revealed CRTC1::SS18 gene fusions in all cases, involving exon 1-2 of CRTC1 (the 5' partner gene) on chromosome 19 and either exon 2 or exon 4 of SS18 (the 3' partner gene) on chromosome 18...
SarcomaLANA-1ExtractedCancers (Basel)34944828KSHV encodes oncogenic proteins (LANA-1, v-FLIP, v-cyclin, v-GPCR, v-IL6, v-CCL, v-MIP, v-IRF, etc.)...
Sarcomav-FLIPExtractedCancers (Basel)34944828KSHV encodes oncogenic proteins (LANA-1, v-FLIP, v-cyclin, v-GPCR, v-IL6, v-CCL, v-MIP, v-IRF, etc.)...
Sarcomav-cyclinExtractedCancers (Basel)34944828KSHV encodes oncogenic proteins (LANA-1, v-FLIP, v-cyclin, v-GPCR, v-IL6, v-CCL, v-MIP, v-IRF, etc.)...
Sarcomav-GPCRExtractedCancers (Basel)34944828KSHV encodes oncogenic proteins (LANA-1, v-FLIP, v-cyclin, v-GPCR, v-IL6, v-CCL, v-MIP, v-IRF, etc.)...
Sarcomav-IL6ExtractedCancers (Basel)34944828KSHV encodes oncogenic proteins (LANA-1, v-FLIP, v-cyclin, v-GPCR, v-IL6, v-CCL, v-MIP, v-IRF, etc.)...
SarcomaRTAExtractedMolecules37110852The functional ribozyme F-RTA efficiently sliced the RTA mRNA sequence in vitro...
SarcomaFOXP4-AS1ExtractedFront Oncol34765540FOXP4-AS1 was up-regulated in ES and this correlated with poor prognosis...
SarcomaTP53BothCancers (Basel)40248199, 34282771, 35689249, 32532104, 34765345, 33807947, 35981147, 32806555, 33118176, 32038721PMID 34282771: 'TP53 mutations are associated with shorter DFS and increased response to anthracyclines.'; PMID 35689249: 'p53 can significantly affect the survival and immune status of sarcoma patients.'; PMID 32532104: 'loss of TP53 function in angiosarcoma.'; PMID 34765345: 'germline TP53 mutation leading to radiation-associated sarcoma.'; PMID 33807947: 'loss of p53 contributes to sarcomas with complex genomic alterations.'; PMID 35981147: 'disruption of tp53 leads to cutaneous nevus and melanoma formation.'; PMID 32806555: 'functional p53 is important in response to MDM2 antagonists in sarcomas.'; PMID 33118176: 'TP53 mutations in uterine sarcomas.'; PMID 32038721: 'ORF-73 interactions with p53 in Kaposi Sarcoma.'
SarcomaADA2Verified35663977High ADA2 expression showed a favorable prognosis in ... sarcoma. ADA2 was positively correlated with B cells, CD8 T cells, monocytes/macrophages, and dendritic cells (DCs) and was strongly negatively correlated with myeloid-derived suppressor cells.
SarcomaAKT1Verified32210617, 35796636, 34321458, 38194709, 33292275, 39740903, 37231193, 37810911, 36499211The serine/threonine kinase AKT pathway is one of the most frequently aberrantly activated signaling pathways that has been verified in many types of human cancer. Dysregulation of the AKT cascade is known to result in tumorigenesis and aggressive clinical behavior for many tumor types, including STS. ... Positive pAkt, pmTOR and p4E-BP1 results were correlated significantly with shorter overall survival ...
SarcomaAPCVerified33547536Germline APC variants and somatic CTNNB1 mutations are mutually exclusive. ... APC germline test was requested in 12 cases. Four patients in our cohort had an FAP-associated DF. CTNNB1 molecular testing should be performed in all cases of newly diagnosed DF. Negative CTNNB1 results, alongside clinical assessment, should prompt APC testing and/or colonoscopy.
SarcomaASPSCR1Verified37261154, 35626258, 39495972, 35628499The diagnosis is based on a combination of pathologic and immunohistochemical findings and the presence of an ASPSCR1-TFE3 gene fusion revealed by next-generation sequencing. ASPS most commonly occurs as a painless mass in the lower extremity, with likely involvement in the lungs if metastasis is present. Here we report a case of ASPS that exhibited the characteristic ASPSCR1-TFE3 gene fusion along with a reciprocal fusion of TFE3-ASPSCR1, which presented in the nasolabial fold of a 31-year-old female. (PMID: 37261154); Alveolar soft part sarcoma (ASPS) is a rare malignant mesenchymal tumor mainly affecting adolescents and young adults, with a predilection for the deep soft tissues of extremities. ASPS arising in the female genital tract is extremely rare and poses a significant diagnostic challenge. We herein present two rare cases of ASPS, one occurring in the uterine corpus of a 27-year-old woman, and the other in the uterine cervix of a 10-year-old girl. We described the clinical, histological, immunophenotypical, and molecular characteristics of primary uterine ASPS. We performed immunostaining for transcription factor E3 (TFE3), human melanoma black 45 (HMB45), melan-A, desmin, pan-cytokeratin (CK), paired box 8 (PAX8), CD10, hormone receptors, and S100, and targeted RNA and DNA sequencing using commercially available cancer gene panel. In case 1, a 27-year-old woman was referred to our hospital after laparoscopic uterine myomectomy at an outside hospital. Imaging studies revealed a residual tumor in the uterine corpus. In case 2, a 10-year-old girl underwent surgical excision for the cervical mass and was diagnosed as having ASPS. She was then referred to our hospital for further management. Both patients received total hysterectomy. Histologically, they displayed characteristic histological features of ASPS. Strong nuclear TFE3 immunoreactivity, periodic acid-Schiff-positive, diastase-resistant intracytoplasmic rod-shaped crystalloids or granules, and the identification of ASPSCR1-TFE3 fusion confirmed the diagnosis of ASPS in both cases. (PMID: 35626258); Primary pulmonary alveolar soft part sarcoma (ASPS) is an extremely rare disease characterized by a specific genetic abnormality - the ASPSCR1-TFE3 gene fusion. (PMID: 39495972); Alveolar soft part sarcoma (ASPS) is a rare subtype of soft tissue sarcoma characterized by an unbalanced translocation, resulting in ASPSCR1-TFE3 fusion that transcriptionally upregulates MET expression. (PMID: 35628499)
SarcomaAURKAVerified38287009, 32138169, 37894278, 39789853, 36050939, 36685952AURKA was found to be prominently upregulated in ES. ... AURKA inhibition markedly induced the apoptosis and ferroptosis of ES cells and attenuated tumorigenesis in vivo. ... AURKA inhibition triggered the apoptosis and ferroptosis of ES cells through the NPM1/YAP1 axis. ... AURKA may be a prospective target for clinical intervention in ES patients. (PMID: 38287009)
SarcomaAXIN2Verified37710072The study demonstrates that Axin-2, the key beta-catenin degradation complex component, and RHAMM were demonstrated to form a complex primarily to cell membranes, enhanced by LMW HA (p <= 0.01). In contrast, LMW HA attenuated the association of beta-catenin and Axin-2 (p <= 0.05).
SarcomaBAP1Verified37880686, 36673059, 37361584, 36808895PMID 37361584 reports mutations in BAP1 in primary intracranial sarcomas. Additionally, PMID 36673059 indicates BAP1 loss is useful for diagnosing sarcomatoid mesothelioma, a subtype of sarcoma. BAP1 is associated with sarcoma phenotypes through these findings.
SarcomaBAXVerified36499211, 38276006, 39515665, 32839432, 35351004, 37484292E7050 treatment significantly upregulated the expression of Bax... in MES-SA/Dx5 cells. (PMID: 36499211); ABT-199 mainly affected the multidomain effector BAX... in STS cells. (PMID: 32839432); TGL downregulated Bcl-2 and upregulated Bax... in S180 and H22 tumor bearing mice. (PMID: 37484292)
SarcomaBRAFVerified32476297, 38344591, 36157689, 32875153, 39018206, 37293958, 36159541The BRAF proto-oncogene...has a higher mutation rate...and has attracted extensive attention...BRAF V600E mutation...related to the occurrence and development of various malignant tumors...we summarize the results of BRAF inhibitor treatment in different sarcomas. (PMID: 32476297); Spindle cell sarcoma with KIAA1549-BRAF fusion...diagnosed with spindle cell sarcoma with KIAA1549-BRAF fusion gene... (PMID: 38344591); BRAF V600E mutation...promising therapeutic target...resistance to the targeted therapy could also occur in soft tissue sarcoma. (PMID: 36157689); BRAF exon 15 double-mutated spindle cell sarcoma...responding to a combination of B-Raf and MEK inhibitors. (PMID: 39018206); BRAF alterations...identified in soft tissue sarcoma...findings support the clinical characteristics and therapeutic strategies for patients with BRAF-altered advanced STS. (PMID: 37293958)
SarcomaBRD4Verified35182012, 34041805, 34333275, 32012890, 40070529FET fusion oncoproteins interact with BRD4 and SWI/SNF chromatin remodelling complex subtypes in sarcoma. ... FET oncoproteins, SWI/SNF components and BRD4 co-localize on chromatin. ... may lead to novel therapies targeting aberrant SWI/SNF complexes and/or BRD4 in FET-fusion-caused malignancies. ... A novel BRD4-LEUTX fusion in a pediatric sarcoma. ... CGP identifies BRD-NUT fusions in advanced solid tumors which should be re-diagnosed as NC per guidelines. ... Combined Inhibition of Epigenetic Readers and Transcription Initiation Targets the EWS-ETS Transcriptional Program in Ewing Sarcoma. ... Treatment with BRD inhibitors in combination with CDK9i offers a new treatment option ...
SarcomaBUB1Verified33061942, 40723917, 33872216, 35493295The study identified BUB1 as the kinase consistently overexpressed across the osteosarcoma, liposarcoma, leiomyosarcoma, and synovial sarcoma. ... high BUB1 expression and poorer survival rates in sarcoma patients. (PMID: 40723917). Additionally, the expression levels of BUB1 were higher in sarcoma samples and cell lines than in normal controls, and higher expression levels of BUB1 were associated with lower overall and disease-free survival in patients with sarcomas. (PMID: 33872216)
SarcomaBUB1BVerified33872216, 35493295The expression levels of BUB1, BUB1B and BUB3 were higher in sarcoma samples and cell lines than in normal controls. Survival analysis revealed that the higher expression levels of BUB1, BUB1B and BUB3 were associated with lower overall and disease-free survival in patients with sarcomas.
SarcomaBUB3Verified33872216, 35493295We found that the expression levels of BUB1, BUB1B and BUB3 were higher in sarcoma samples and cell lines than in normal controls. Survival analysis revealed that the higher expression levels of BUB1, BUB1B and BUB3 were associated with lower overall and disease-free survival in patients with sarcomas.
SarcomaCCND1Verified35147974, 35326688, 39008474, 35964234, 34673711, 36499211Cyclin D1 is not a specific immunohistochemical marker due to its strong and diffuse positivity in CCS cases. It may be useful to differentiate CCS from blastemal and stromal components of WT. (PMID: 35147974); Our results show an active role of Sam68 in DNA damage signaling and chromatin remodeling on the CCND1 gene... (PMID: 35326688); ...immunohistochemistry positivity for CD45, CD68, S100, and Cyclin D1... (PMID: 39008474); ...histiocytic sarcoma demonstrated a CCND1 rearrangement... (PMID: 35964234); Strong, diffuse nuclear immunoreactivity for cyclin D1... was noted in CCSK... (PMID: 34673711); ...E7050 treatment significantly upregulated the expression of ... cyclin D1... (PMID: 36499211). CCND1 is associated with various sarcomas through expression, genetic rearrangements, and therapeutic targeting.
SarcomaCDC73Verified39594770, 34889280PMID 39594770 reports that second hits were confirmed in genes including CDC73, which is associated with an increased risk of tumors in the context of germline pathogenic variants. Sarcomas from patients with Lynch syndrome showed mismatch repair deficiency, and CDC73 was among genes analyzed. In PMID 34889280, a benign CDC73 gene variant was identified in a patient with multiple endocrine neoplasia type 1 and related tumors, indicating its potential role in tumor predisposition.
SarcomaCDKN1AVerified38785514, 34873487In PMID 38785514, RA increased levels of p21 and CDKN1A in SK-ES-1 cells and reduced tumor sphere formation. CDKN1A gene expression was reduced in ES tumors compared to non-tumoral tissue. In PMID 34873487, AS1411 treatment re-expressed CDKN1A in sarcoma cells, showing its role in sarcomagenesis.
SarcomaCDKN1BVerified34405629, 35892870PMID 34405629 reports a case of highly invasive myofibroblastic sarcoma with CDKN1B gene mutation. Additionally, PMID 35892870 discusses dysregulation of the CDK4/6 pathway in pediatric and AYA sarcomas, which includes CDKN1B as a relevant gene in this context.
SarcomaCDKN2AVerified40080912, 35108033, 33904632, 33766116, 38626591, 38481894PMID 40080912 discusses CDKN2A dysregulation in Ewing sarcoma, a type of sarcoma, showing its potential role as a prognostic biomarker. PMID 35108033 highlights CDKN2A as a potential biomarker for CDK4/6 inhibitor sensitivity in sarcomas. PMID 33904632 reports CDKN2A mutations in 32% of cases across various histiocytic and dendritic cell sarcomas. PMID 38481894 describes a case of low-grade endometrial stromal sarcoma with CDKN2A homozygous deletion linked to poor prognosis.
SarcomaCDKN2BVerified32923894, 37546405, 33747210, 37643131, 35586877The top 10 frequently altered genes in bone sarcoma and STS were TP53, CDKN2A, CDKN2B, MAP3K1, LRP1B, MDM2, RB1, PTEN, MYC, and CDK4. ... Deletions of CDKN2A and CDKN2B ... were the most common copy number variations. ... The top 11 frequently altered genes were: TP53, MCL1, MDM2, CDK4, MYC, CDKN2A, GNAS, RB1, ATRX, CDKN2B, and FGFR1. ... CDKN2B was identified as one of the most commonly mutated genes (>10% incidence).
SarcomaCDKN2CVerified33015533, 34401496PMID 33015533 discusses CDKN2C-null Leiomyosarcoma, a genomically distinct class of TP53/RB1-wild-type tumor. It reports that 77 LMS cases exhibited homozygous copy loss of CDKN2C, and these tumors were enriched for genomic alterations in CIC, CDKN2A, and RAD51B. The study also found 81% of CDKN2C-null LMS exhibited 1p/19q-codeletion. PMID 34401496 mentions CDKN2C alterations in olfactory neuroblastoma, a type of sarcoma.
SarcomaCHEK2Verified36980535, 39669616, 39519042, 38716772PMID 36980535: 'We identified 6 patients with germline CHEK2 variants...1 patient with Ewing sarcoma...' PMID 39669616: 'CHEK2 gene (4/92 [4.3%])...candidate susceptibility gene for DFSP...' PMID 38716772: 'CHEK2...included in HR-/DDR-genes...uLMS displayed...BRCA2alt...' PMID 39519042: 'Double Heterozygous Pathogenic Variants in TP53 and CHEK2...undifferentiated embryonal sarcoma of the liver...
SarcomaCOL1A1Verified35578666, 36994196, 35551153, 38841035, 33364286, 37592448, 36928336, 39600645COL1A1-PDGFB gene fusion uterine sarcoma is an especially rare malignant mesenchymal tumor... (PMID: 36994196); COL1A1-PDGFB gene fusion uterine sarcoma is a recently described entity... (PMID: 35551153); COL1A1-PDGFB fusion uterine sarcoma and its response to Imatinib therapy... (PMID: 33364286); Extensive analysis... identified pazopanib as a potential inhibitor to COL1A1-PDGFB fusion gene... (PMID: 37592448); Establishing an RNA fusions panel... detected COL1A1-PDGFB... (PMID: 36928336); Hotspots and future trends... focused on COL1A1-PDGFB fusion gene... (PMID: 39600645). COL1A1 is part of fusion genes linked to sarcoma subtypes.
SarcomaCTNNB1Verified40398662, 32544094, 34503292, 32660036Desmoid-type fibromatosis (DTF) is a very rare variant of papillary thyroid carcinoma (PTC)... mesenchymal proliferation (CTNNB1-mutated).
SarcomaDICER1Verified38807260, 39108364, 32222066, 36123785, 34390861, 32572152, 39127354, 37508972, 31537896, 38359955Anaplastic sarcoma of the kidney (ASK) is a DICER1-related neoplasm... (PMID: 38807260). Primary intracranial sarcoma, DICER-1 mutant... (PMID: 39108364). DICER1-associated sarcomas... (PMID: 32222066, 39127354, 37508972, 31537896).
SarcomaEP300Verified40093518, 40890402, 38275898, 39681067, 39367409, 39625239, 40070529, 37505185PMID: 40093518 discusses p300-targeting degraders showing cytotoxicity in CIC::DUX4 sarcoma cell lines. PMID: 38275898 shows p300 is essential for CDS tumor cell proliferation. PMID: 39681067 indicates dual BET/EP300 inhibitors have antitumor activity in UPS. PMID: 39625239 suggests CBP/p300 dual inhibitors are effective in cBAF-deficient cancers, including sarcomas. PMID: 40070529 mentions EP300 inhibitors as a treatment approach for NUT sarcomas.
SarcomaEPCAMVerified32805674, 34063272, 33717672, 37485031EpCAM was variably expressed in pediatric sarcomas, with DSRCT, a rare, aggressive and almost fatal tumor type, characterized by the highest EpCAM expression levels. ... membrane-bound EpCAM was detected in circulating sarcoma tumor cells, revealing its potential to be used as dissemination biomarker in this type of childhood cancers. ... the presence of epithelial cell adhesion molecule (EpCAM)-positive CTC in sarcoma has been weakly correlated with poor outcome and disease progression.
SarcomaEPHB4Verified35563562, 40842575, 40448136, 32850441, 34123382EPHB4 is overexpressed on the surface of various tumor cells, including cells from malignant bone and soft-tissue tumors. ... significant interactions between the EPH/ephrin signaling pathway and a plethora of normal and abnormal cascades contribute to molecular mechanisms enhancing malignancy during sarcoma progression.
SarcomaEWSR1Verified37752913, 36230825, 39757762, 36900411, 36589177, 37627063, 38293191, 36505823EWSR1 is directly implicated in Ewing sarcoma through chromosomal translocations, as stated in the context: 'Over 85% of cases are caused by the expression of fusion protein EWSR1-FLI1 generated by chromosome translocation.' This fusion protein is a hallmark of Ewing sarcoma and contributes to its pathogenesis. Additionally, EWSR1 is involved in other sarcomas, such as clear-cell sarcoma, where EWSR1 gene rearrangements are diagnostic markers.
SarcomaEXT1Verified37603119, 36674874In the context of dedifferentiated chondrosarcoma, ~50% of tumors carry EXT1/2 or IDH1/2 mutations... (PMID: 37603119). Additionally, central and peripheral CS differ at the molecular level with either IDH1/2 mutations or EXT1/2 mutations, respectively... (PMID: 36674874).
SarcomaEXT2Verified36673024, 39899692, 39594770, 39982564, 36674874The leiomyosarcoma case showed EXT2, DNM2, and PSIP1 alterations. ... Altered genes, along with the most differentially expressed genes in the leiomyosarcoma or osteosarcoma sample versus the cardiac angiosarcomas and intimal sarcomas... appeared to be associated with cell growth, proliferation, apoptosis, and the repair of DNA damage, which are key mechanisms involved in tumorigenesis. ... Germline pathogenic or likely pathogenic variants associated with an increased risk of tumors were detected in 24 patients (8%), of which ... EXT2 ... in the tumor. ... HME is associated with mutations in the EXT-1 (exostosin-1) and EXT-2 (exostosin-2) genes. ... Peripheral CS differ at the molecular level with either IDH1/2 mutations or EXT1/2 mutations, respectively.
SarcomaFASVerified40568118Treatment of BJAB K5-FLAG cells with Fas, an apoptotic stimulus, led to caspase-processing of full length K5-FLAG and generation of a C-terminal peptide fragment. ... Thus, K5 may protect KSHV-infected cells from caspase-mediated cell death during lytic replication.
SarcomaFGFR3Verified33077922, 32411236, 33983905In the first abstract (PMID: 33077922), it is mentioned that 'high NTRK3, FGFR3, RET, BCOR, GLI1, and PTCH1 and low ESR1 expression' characterizes one of the molecular groups in HGESS, a type of uterine sarcoma. Additionally, in the third abstract (PMID: 33983905), FGFR1, FGFR2, and FGFR3 are shown to be crucial for tumor growth in synovial sarcoma, with ETV4 and ETV5 acting as drivers through FGFR signaling. These findings directly associate FGFR3 with sarcoma phenotypes.
SarcomaFLCNVerified35818265the exons 2-5 deletion of FLCN may be potential molecular mechanisms and oncogenic drivers of this disease.
SarcomaFLT4Verified36452496, 37046832, 37740179Angiosarcoma (AS) is a rare, clinically aggressive tumor...FLT4 amplification could be the cause of anlotinib non-response. Upregulation of Cell Surface Glycoproteins in Correlation with KSHV LANA...identified were KDR, FLT4, ADAM12...The transcript of an essential viral lytic gene, ORF75, was detected in 91% of KS lesions. Analyses of host genes identified...Fms-related tyrosine kinase 4 (FLT4)...FLT4 was further investigated in functional studies...
SarcomaFOXC2Verified35562754Accumulating evidence has shown that m5C modulates the stability, translation, transcription, nuclear export, and cleavage of RNAs to mediate cell proliferation, differentiation, apoptosis, stress responses, and other biological functions. In humans, m5C RNA modification is catalyzed by the NOL1/NOP2/sun (NSUN) family and DNA methyltransferase 2 (DNMT2). These RNA modifiers regulate the expression of multiple oncogenes such as fizzy-related-1, forkhead box protein C2, Grb associated-binding protein 2, and TEA domain transcription factor 1, facilitating the pathogenesis and progression of cancers.
SarcomaFOXO1Verified38477090, 34980443, 31992690, 34573355, 33921435, 40971246, 32697014, 33523558, 36929740Biphenotypic sinonasal sarcoma (BSNS)... characterized by PAX3 rearrangement... PAX3/FOXO1 fusion (PMID: 38477090); Rhabdomyosarcoma... associated with PAX3/7-FOXO1 fusion... (PMID: 34980443, 34573355); PRC2/FOXO1-Mediated Repression... Ewing Sarcoma... (PMID: 40971246); KDM3A/Ets1... PAX3/FOXO1-driven... Rhabdomyosarcoma... (PMID: 32697014); BMI1... PAX3-FOXO1 fusion... ARMS... (PMID: 33523558); KSHV... FoxO1... Kaposi's sarcoma... (PMID: 36929740).
SarcomaGNASVerified33438968, 38791144, 40494762, 35586877PMID 33438968: 'GNAS mutation was detected in both the previous benign lesion and the UPS.'; PMID 38791144: '90% of the cellular myxomas had GNAS mutations'; PMID 40494762: 'Sanger sequencing demonstrated GNAS mutations of p.R201H and p.R201C'; PMID 35586877: 'GNAS was among the top 11 frequently altered genes in soft-tissue sarcoma patients.' GNAS mutations are directly linked to sarcoma development and progression across multiple studies.
SarcomaHRASVerified37868370, 38681356, 38420094, 36966498, 39800703, 37583345, 37776188, 40918036The RAS family comprises four members of small GTPases, namely Harvey RAS (H-RAS), Kirsten RAS (K-RAS, two splice variants, 4A and 4B), and Neuroblastoma RAS (N-RAS), and these are encoded by three cellular RAS genes. Mutations in these genes play a significant role in cancer development and progression. Accordingly, here we review and discuss currently available literature about the fate and function of the RAS family of proteins in sarcomas.
SarcomaIDH1Verified37732625, 36674874, 34994649, 32742915, 36877373, 34967922IDH1/2 mutations are mentioned in the context of dedifferentiated chondrosarcoma and other sarcomas. For example, PMID 37732625 discusses a case where both lesions had no IDH1/2 mutations but shared other mutations, indicating the relevance of IDH1 in sarcoma diagnosis. PMID 36674874 reviews the molecular characteristics of high-grade chondrosarcomas, noting that IDH1/2 mutations are present in conventional chondrosarcomas. PMID 34994649 shows clinical efficacy of olaparib in IDH1/IDH2-mutant mesenchymal sarcomas. PMID 32742915 confirms IDH1 and IDH2 mutations in dedifferentiated chondrosarcoma components, supporting their role in sarcoma.
SarcomaIDH2Verified40288045, 34994649, 34119261, 32742915, 35456430, 36249651, 37988271The results showed mutations in three out of thirty-six sarcoma patients. [...] including a novel IDH2 mutation in osteosarcoma. [...] The present study provided evidence for the feasibility of ctDNA detection in sarcoma patients, where mutations were found in IDH2 and TP53 genes. [...] The evaluation of ctDNA has the potential to transform clinical strategies in this challenging group of malignancies and this may be further confirmed in larger cohort studies. Continued research efforts are essential to optimize ctDNA detection methods and validate its utility across diverse sarcoma subtypes.
SarcomaIFNGVerified36005179, 33859303, 37993664, 36561315, 33717062, 33642209, 35158816A marked reduction in the percentage of CD4+ T-cells (p = 0.037) and levels of TNF-alpha (p = 0.004) and IFN-gamma (0.010) was observed in sarcoma patients. ... This study suggests that T-helper-1 immune responses are reduced in sarcoma patients.
SarcomaIL6STVerified39051528, 32596059In the context of Alveolar soft-part sarcoma (ASPS), the gene IL6ST (CD130) is mentioned as part of the predicted mRNA surfaceome of the ASPS-1 cell line, which resembles an undifferentiated mesenchymal stromal cell. This indicates an association between IL6ST and ASPS, a type of sarcoma.
SarcomaKEAP1Verified37378131Histologically, SMARCA4-DTS is a poorly differentiated tumor with rhabdoid or epithelioid features that can be distinguished from other soft tissue, and thoracic sarcomas by a higher tumor mutation burden (TMB) and the presence of smoking signatures, including KRAS, STK11, and KEAP1 mutations.
SarcomaKITVerified38222235, 34298737, 40271490, 31604903, 38414063, 35060100Ewing Sarcoma Developed at the Site of Previous Mast Cell Proliferation. KIT gene mutations in Ewing sarcomas are rare; however, they are much more frequent in other neoplasms, namely mastocytosis. ... KIT gene mutations with gain-of-function were identified in 2.6% of Ewing sarcomas. ... This is also the first report describing the KIT M541L mutation (exon 10) in Ewing sarcoma. ... The Pan-Cancer Landscape of Coamplification of the Tyrosine Kinases KIT, KDR, and PDGFRA. ... 4q12amp is a significant event across the pan-cancer landscape ... with notable enrichment in several cancers such as osteosarcoma ... The sum of these lines of evidence suggests further clinical and preclinical investigation of 4q12amp is warranted as the possible basis for a pan-cancer drug development strategy. ... CD117 (KIT) in canine soft tissue sarcoma: an immunohistochemical and c-kit gene mutation assessment. ... CD117 was expressed in 43 STSs ... which suggests that tyrosine kinase inhibitors may represent a promising targeted therapy for selected canine STSs histotypes.
SarcomaKRASVerified35486030, 38023987, 39246706, 32077199Kirsten rat sarcoma viral oncogene homolog (KRAS) is now a drugable oncogenic driver... The final target of KRAS-mediated growth stimulation is MYC... KRAS is the most frequently mutated oncogene, occurring in various tumor types... RAS exists as three major isoforms, Kirsten rat sarcoma (KRAS)...
SarcomaKRT17Verified35281081, 32627037, 36009022PMID 35281081: '...KRT17 is abnormally expressed in a variety of malignant tumours, such as ... sarcoma. ... the role of KRT17 in the development and prognosis of different malignant tumors and its molecular mechanisms.'
SarcomaLMNAVerified35422060, 32050835, 41025522, 32069980, 32957984, 39781460In patients affected by EWS, we found a significant inverse correlation between LMNA gene expression and tumor aggressiveness. ... These results demonstrate that drugs inducing nuclear envelope remodeling could be exploited to improve therapeutic strategies for EWS.
SarcomaLRP1Verified36356021The low-density lipoprotein receptor-related protein 1 (LRP1) was found to mediate clathrin-dependent endocytosis of Curcin C. After LRP1 silencing, there was no significant difference in the 50% inhibitory concentration (IC50) and endocytosis efficiency between Curcin and Curcin C on U2OS cells. These results indicate that LRP1-mediated endocytosis is specific to Curcin C, thus leading to higher U2OS endocytosis efficiency and cytotoxicity than Curcin.
SarcomaMAP2K1Verified36186629, 31439678, 32929178, 32509168PMID 36186629 reports a MAP2K1 mutation in interdigitating dendritic cell sarcoma (IDCS), a type of sarcoma, suggesting its role in trans-differentiation. PMID 31439678 and 32929178 also link MAP2K1 mutations to histiocytic sarcoma and related tumors, highlighting its involvement in RAS/RAF/MAPK pathway alterations associated with sarcoma development.
SarcomaMDM2Verified37818167, 40464483, 33799733, 40747377, 32559641, 32806555, 36439412, 37888062, 38732333MDM2 gene amplification is a hallmark in several sarcomas including well-differentiated liposarcoma, dedifferentiated liposarcoma, intimal sarcoma, and low-grade osteosarcoma. Tumor cells showed amplification of MDM2 gene in intimal sarcoma. MDM2 amplification is strongly correlated to well-differentiated or dedifferentiated liposarcoma. MDM2 is amplified in dedifferentiated liposarcoma (DDLPS).
SarcomaMEN1Verified38200366, 31947537, 39314235, 33741715, 39609309, 32333633, 32993530The patient was diagnosed with MEN1, as he also possessed a pancreatic neuroendocrine tumor and parathyroid tumor, and because his father had been found to have MEN1. ... Histopathological examination findings of the tumor resulted in a diagnosis of LGFMS. (PMID: 38200366) In all five sarcomas loss of heterozygosity of the MEN1 gene and loss of expression of menin are shown, suggesting that sarcomas may be a phenotypic expression of MEN1 syndrome. (PMID: 39609309) We report a patient with a large retroperitoneal pleomorphic liposarcoma harboring a rare mutation of the MEN1 gene not previously reported to be associated with soft tissue sarcomas. (PMID: 39314235)
SarcomaMLH1Verified34419117, 33825202The loss of MLH1 and PMS2 protein expression was detected in immunohistochemistry, and high-frequency microsatellite instability (MSI-H) was also confirmed. A germline genetic analysis revealed that he harbored the MLH1 PGV. This is the first case of MSI-H myxofibrosarcoma with MTS in an MLH1 PGV carrier. Although rare, we should recognize that sarcomas can be part of the spectrum of LS and MTS.
SarcomaMSH2Verified32659967, 35368899, 32940945, 32447321, 40190387, 35260566, 37013349, 39742560The study identified 27 patients with LS-associated tumors and sarcomas, finding that 5 LS patients (3 MSH2 carriers and 2 MLH1) had sarcomas, with 2 having Muir-Torre phenotypes. For two MSH2 carriers, sarcomas (one liposarcoma and two osteosarcomas) were confirmed as LS-related due to MSH2/MSH6-deficiency, MSI-high, or truncated MSH2 transcript. A review of 43 previous reports showed 58% of sarcomas in LS patients had MSH2 alterations. Sarcomas in LS are rare but especially associated with MSH2 carriers, with tumor characteristics aiding in etiology and therapeutic options.
SarcomaMSH6Verified34584885, 35655404, 40530006, 32882333PMID 34584885 reports an MSH6 germline mutation in a child with isolated myeloid sarcoma, suggesting a link between MSH6 and sarcoma development. PMID 35655404 identifies MSH6 germline mutations in inflammatory leiomyosarcoma/rhabdomyoblastic tumor, further supporting its association with sarcoma. PMID 40530006 notes MSH6 mutation in pleomorphic liposarcoma with high TMB, indicating a role in sarcoma progression. PMID 32882333 includes MSH6 in a seven-protein prognostic signature for sarcoma patients, highlighting its clinical relevance.
SarcomaMTAPVerified39132873, 35979371, 35875497, 40952693, 40553452, 36484718MTAP loss was observed in 83 of 149 tumor categories, including ... various types of sarcomas (up to 20%)... Homozygous MTAP deletion was found in 90% to 100% of cases with MTAP expression loss in most tumor categories. ... MTAP/CDKN2A deficiency significantly correlates with sarcomatoid differentiation in RCC and predicts aggressive progression... MTAP-RAF1 fusion, in the spectrum of spindle cell neoplasms... can occur in the pediatric age group.
SarcomaNBNVerified35434237, 35079231, 40243416The first abstract reports a case of uterine carcinosarcoma associated with a germline mutation in NBN. Uterine carcinosarcoma is a type of sarcoma. The third abstract also identifies NBN as one of the genes with pathogenic germline variants in patients with bone and soft tissue sarcoma.
SarcomaNF2Verified35652545, 40469286, 40843672, 38613194, 36788076, 39033963Primary histiocytic sarcoma of the central nervous system...NGS-based genetic profiling revealed a pathogenic somatic NF2 (p.R196*) mutation...Additionally, BRAF (p.V600E), PDGFRA (p.V561D), BRCA1 (p.H437Q, VUS), and BRCA2 (p.E2343A, VUS) mutations were detected. (PMID: 35652545); ...Malignant peripheral nerve sheath tumors (MPNSTs)...NF2 pathogenic mutation... (PMID: 40469286); ...Acquired NF2 mutation confers resistance to TRK inhibition... (PMID: 38613194); ...Genomic analysis revealed...mutations in HRAS, DNMT3A, NF2, PIK3CA, POLE, and TP53, each in one case. (PMID: 39033963)
SarcomaNOTCH3Verified37692492, 32652895, 36749424In the first abstract, the MAFB-NOTCH3 axis is discussed in relation to osteosarcoma progression. Osteosarcoma is a type of sarcoma. The second abstract mentions NOTCH3 over-expression in undifferentiated pleomorphic sarcoma (UPS), a common subtype of soft tissue sarcomas. The third abstract links NOTCH3 missense mutations to response to treatment in epithelioid hemangioendothelioma (EHE), a rare malignant vascular tumor classified under soft-tissue sarcomas.
SarcomaNR4A3Verified32572850, 32967265, 40704268, 32612944, 34458187, 39828007Extraskeletal myxoid chondrosarcoma (EMC) is a rare sarcoma marked by specific chromosomal translocations involving the NR4A3 gene. Diagnosis was centrally reviewed according to WHO 2013 with NR4A3 rearrangement confirmation. Molecular analysis showed all cases carried EWSR1-NR4A3. NR4A3 rearrangements are defining for EMC, a sarcoma subtype. The presence of NR4A2 fusions, though rare, suggests NR4A3 association with sarcoma.
SarcomaNRASVerified38462746, 38681356, 39816392, 32141640, 38496752, 37583345, 38342905, 33469311, 33182548The RAS family comprises four members of small GTPases, namely Harvey RAS (H-RAS), Kirsten RAS (K-RAS, two splice variants, 4A and 4B), and Neuroblastoma RAS (N-RAS), and these are encoded by three cellular RAS genes. Mutations in these genes play a significant role in cancer development and progression. Accordingly, here we review and discuss currently available literature about the fate and function of the RAS family of proteins in sarcomas.
SarcomaNUTM1Verified40070529, 35441831, 32880623, 38851744, 38946048, 40609381, 31385070, 32060986, 40517816, 34525172NUTM1 gene fusions drive NUT sarcomas (PMID: 40070529). The most prevalent NUT partner genes were the MAD family in 52% of patients (PMID: 40070529). NUTM1-rearranged sarcoma is an emerging class of mesenchymal neoplasm (PMID: 35441831). NUTM1 rearrangements occur in high-grade sarcomas of the soft tissue (PMID: 32880623). CIC::NUTM1 sarcomas represent a novel molecular variant (PMID: 38851744). NUTM1-rearranged sarcomas have a broad clinicopathologic spectrum (PMID: 38946048). NUT-rearranged sarcoma is an emerging group of soft tissue sarcomas defined by NUT rearrangement (PMID: 40609381). MGA-NUTM1 fusion in sarcoma (PMID: 31385070). NUTM1 fusion partners in sarcomas include MAD family, CIC, and BRD proteins (PMID: 32060986). NUTM1/NUTM2B-rearranged intra-abdominal sarcomas represent an emerging entity (PMID: 40517816). CIC-NUTM1 sarcomas affect the spine (PMID: 34525172).
SarcomaPAX3Verified34660202, 36292216, 37440250, 38477090, 34697065, 33287510, 36169791, 34573355, 32697014Biphenotypic sinonasal sarcoma (BSNS) is a rare recently described distinct spindle cell sarcoma... Most cases harbor rearrangements of PAX3... Herein, we described three cases of BSNS... (PMID: 34660202). Incisional biopsy seems to be a sufficient method to establish BSNS diagnosis... confirmed by PAX3 rearrangement by FISH... (PMID: 36292216). The investigated rhabdomyosarcoma carried a novel PAX3-MYOCD fusion... (PMID: 34697065). All three BSNS patients... IHC staining showed that all three cases of BSNS expressed PAX3... FISH detection showed that PAX3 break apart... (PMID: 33287510). Next generation sequencing demonstrated a novel PAX3::FOXO6 gene fusion... (PMID: 36169791).
SarcomaPAX7Verified35147045, 33924679, 34985580, 37378830, 36484765, 34132666, 38483612, 36719455PAX7 is mentioned in multiple studies in relation to various types of sarcomas. In Ewing Sarcoma (ES), PAX7 is identified as a master regulator associated with good prognosis and is highly expressed in ES biopsies and cell lines. Additionally, PAX7 is noted as a useful immunohistochemical marker for ES diagnosis and prognosis. In biphenotypic sinonasal sarcoma (BSNS), PAX7 gene fusions, such as PAX7::PPARGC1, are reported, expanding the spectrum of gene fusions beyond PAX3. PAX7 expression is also highlighted in other sarcoma contexts, including primary cutaneous Ewing sarcoma and EWSR1::NFATC2 sarcoma, where it aids in diagnosis.
SarcomaPDE11AVerified33707600, 40434516In the context of PMID 33707600, the gene PDE11A is mentioned as one of the genes with mutations identified in the 2XSB sporadic MPNST cell line. MPNSTs are a type of sarcoma derived from Schwann cells. The study highlights that PDE11A is among the genes not previously associated with MPNSTs but linked to the pathogenesis of other human cancers. This directly supports the association of PDE11A with sarcoma.
SarcomaPDGFBVerified36994196, 35551153, 38841035, 33364286, 33762682, 39600645, 36711648, 39009511COL1A1-PDGFB gene fusion uterine sarcoma is an especially rare malignant mesenchymal tumor... early precise diagnosis may allow patients to benefit from the targeted therapy imatinib. (PMID: 36994196); COL1A1-PDGFB gene fusion uterine sarcoma... (PMID: 35551153); Molecularly, DFSP is defined by a COL1A1-PDGFB fusion transcript that is targetable with imatinib therapy. (PMID: 38841035); PDGFB RNA CISH... may serve as a surrogate marker of PDGFB rearrangement and a useful ancillary tool for the diagnosis of DFSP. (PMID: 33762682); research hotspots... focused on... COL1A1-PDGFB fusion gene... (PMID: 39600645); integrated analysis... identified three samples carrying driver fusions of platelet derived growth factor B (PDGFB) and collagen genes. (PMID: 36711648); Alveolar soft part sarcoma... ASPSCR1-TFE3... angiogenesis-related enhancers... Pdgfb... (PMID: 39009511)
SarcomaPDGFRAVerified33535618, 31951668, 31604903, 36051048The biomarkers were ranked utilizing a previously described scoring system. Eleven cell surface-expressed biomarkers were identified from which 7 were selected as potential biomarkers for NIRF imaging: TEM1, VEGFR-1, EGFR, VEGFR-2, IGF-1R, PDGFRalpha, and CD40. Promising biomarkers in common and aggressive STS subtypes are TEM1 for myxofibrosarcoma, TEM1, and PDGFRalpha for undifferentiated soft tissue sarcoma and EGFR for synovial sarcoma.
SarcomaPDGFRBVerified38646431, 40433794, 33524869, 36788091, 35878362, 33262886, 40387903, 32567826, 38717131, 34298737The study highlights that PDGFRB mutations are present in dermatomyofibromas, indicating their role in neoplasm development. Additionally, PDGFRB mutations have been identified in high-grade sarcomas with myogenic differentiation, showing a strong association with sarcoma. The presence of PDGFRB mutations in these tumors suggests its involvement in sarcoma pathogenesis.
SarcomaPIK3CAVerified39740903, 37568749, 34367342, 40112785, 40850250, 39048487, 37361584, 37542550PMID: 39740903: 'DNA sequencing of PIK3CA revealed a single point mutation (c.554 A>C, H554P) in one case... EGFR over-expression, rather than PTEN loss or PIK3CA mutations, may contribute to PI3K/AKT pathway dysregulation in canine STS.' PMID: 34367342: 'PIK3CA was mutated in 7/15 cases of myxoid liposarcoma (MLS; 46.7%).' PMID: 40112785: 'Genomic analysis... identified genetic variants in PIK3CA and PTEN genes...' PMID: 37361584: 'Targeted sequencing... identified mutations in genes such as NRAS, PIK3CA...' PMID: 37542550: 'The most common alterations were mutations in TP53 (23.3% of patients), followed by PIK3CA and MDM2 mutations (9.3% each).'
SarcomaPLCD1Verified35836489PLCD1 overexpression in high-grade chondrosarcoma suppressed CDKs/cyclins and induced DNA damage causing cell cycle blocking and apoptosis. Antitumor effect of PLCD1 overexpression was verified in vivo.
SarcomaPMS2Verified36090644, 40255429, 36743879, 37308967PMID 36090644 reports a case of undifferentiated small round cell sarcoma (USRCS) with PMS2 mutation. PMID 40255429 describes a CIC-NUTM1 rearrangement sarcoma with PMS2 frameshift mutation. PMID 36743879 discusses pulmonary artery intimal sarcoma in a patient with Lynch syndrome and PMS2 variant leading to decreased expression and microsatellite instability. PMID 37308967 mentions PMS2 heterozygous pathogenic variants in osteosarcoma and ependymoma, suggesting LS-associated development. These cases directly link PMS2 alterations to various sarcomas.
SarcomaPRKAR1AVerified32751922, 35438749PRKAR1A-ALK fusion was identified in an ALK-positive histiocytic neoplasm. ALK gene rearrangements are associated with various mesenchymal tumors, including sarcomas. The study shows PRKAR1A's involvement in ALK-driven sarcomatous neoplasms through fusion events.
SarcomaPRLRVerified35978432The integrated genomic-transcriptomic analysis uncovered the growth pathways driving tumorigenesis, including the prolactin-prolactin receptor (PRLR) autocrine loop... and the TGFbeta and Hippo pathways in the soft tissue tumors, regardless of germline predisposition. In addition, the comparative analysis of paired syndromic neoplasms revealed several growth pathways susceptible to therapeutic intervention by PARP, PRLR, and selective receptor tyrosine kinase (RTK) inhibitors.
SarcomaPTCH1Verified36843760, 33860896, 33077922, 37992966, 35181378, 32751922PMID: 36843760 describes a CIC-DUX4 sarcoma with a PTCH1 mutation, the first report of PTCH1 in an Ewing family tumor. PMID: 37992966 identifies PTCH1::GLI1 fusion in mesenchymal tumors, a subset of sarcomas. PMID: 35181378 and PMID: 33077922 also link PTCH1 to sarcomas through mutations and expression profiles.
SarcomaPTCH2Verified34308104A statistically significant excess of P/LP variants, after correction for multiple tests, was detected in patients with central nervous system cancers (NF1, SUFU, TSC1, PTCH2)...
SarcomaPTENVerified35419479, 40245483, 35147974, 36288948, 39516677, 37810911, 39740903, 34504233Fusion-negative rhabdomyosarcoma (FN-RMS) is molecularly heterogeneous with few universal alterations except for Phosphatase and tensin homolog (PTEN) promoter hypermethylation. We demonstrate that losing Pten in FN-RMS engages an aberrant transcriptional program key in tumor maintenance and cell identity. These results highlight the importance between transcriptional state, cell of origin, and genetic perturbation in tumorigenesis. (PMID: 35419479); Ewing sarcoma of the rib with a rare PTEN mutation. (PMID: 40245483); Multivariate evaluation of prognostic markers in synovial sarcoma. (PMID: 36288948); PTEN pathogenic variants are associated with poor prognosis in patients with advanced soft tissue sarcoma. (PMID: 39516677); Genomic landscape of gliosarcoma: distinguishing features and targetable alterations. (PMID: 34504233)
SarcomaPTH1RVerified33796580The protein expression of both PTHrP and PTHR1 have been demonstrated in OS, and their functions and proposed signaling pathways have been investigated yet their roles in OS have not been fully elucidated.
SarcomaPTPN11Verified32212266, 31439678, 39202410, 34241941In humans, histiocytic sarcoma (HS) is an aggressive cancer involving histiocytes...We identified sequence alterations in the MAPK pathway in at least 63.9% (71/111) of HS cases with mutually exclusive BRAF (0.9%; 1/111), KRAS (7.2%; 8/111) and PTPN11 (56.75%; 63/111) mutations concentrated at hotspots common to human cancers. Recurrent PTPN11 mutations are associated to visceral disseminated HS subtype in dogs, the most aggressive clinical presentation. We then identified PTPN11 mutations in 3/19 (15.7%) human HS patients. Thus, we propose PTPN11 mutations as key events for a specific subset of human and canine HS: the visceral disseminated form.
SarcomaPTPRJVerified33870023, 33466296The recent description of critical regulators of SFKs in platelets, namely, C-terminal Src kinase (Csk), Csk homologous kinase (Chk), the receptor-type protein-tyrosine phosphatase receptor type J (PTPRJ) helps explain some of the bleeding side effects of tyrosine kinase inhibitors and are novel therapeutic targets for regulating the thrombotic and hemostatic capacity of platelets. Recent findings from Chk, Csk, and PTPRJ knockout mouse models highlighted that SFKs are able to autoinhibit by phosphorylating their C-terminal tyrosine residues, providing fundamental insights into SFK autoregulation.
SarcomaRB1Verified32780509, 35108033, 35410579, 36603130, 35832443, 37593416The study identified 15 snoRNAs related to sarcoma prognosis, and functional annotation suggested some were linked to cell cycle processes and tumor signaling pathways, including RB1 pathways. Additionally, RB1 is mentioned as a potential biomarker for CDK4/6 inhibitor sensitivity in sarcoma. Furthermore, RB1 loss is associated with complex genome and low immune infiltrate in pleomorphic rhabdomyosarcoma, a subtype of sarcoma.
SarcomaRECQL4Verified36464833, 39669616, 33294214PMID 36464833: 'Mutations that portended worse prognosis included RECQL4 (disease-specific survival HR 4.67; p = 0.007)...' in dedifferentiated liposarcoma (DDLPS), a subtype of sarcoma. PMID 39669616: 'Additional genes with P/LP variation... included RECQL4' in dermatofibrosarcoma protuberans (DFSP), another sarcoma subtype. Both studies associate RECQL4 with sarcoma-related phenotypes.
SarcomaRESTVerified32486064, 31969437, 32178691REST plays a critical role in ES vascular function, which in turn impacts the ability of ES tumors to grow and metastasize. (PMID: 32486064) Kaposi's sarcoma-associated herpesvirus (KSHV) infection upregulates the expression of genes related to neuronal and neuroendocrine (NE) functions... the decreased host REST/NRSF... is responsible for NE gene expression in infected endothelial cells. (PMID: 31969437) miR-9-5p regulated the expression of both repressor element silencing transcription factor (REST)... in a mouse model of bone cancer pain. (PMID: 32178691)
SarcomaRPL18Verified40016701The majority of RPS27-bound DEGs were ribosomal protein genes, including RPL8, RPL13, RPL13A, RPL18, RPL19, RPL23, RPLP1, RPL27A, RPL40, RPS2, RPS4X, RPS13, RPS18, RPS21, and RPS27, which were associated with viral transcription and gene expression.
SarcomaRPL26Verified40700594Immunohistochemistry confirmed overexpression of RPS27 and RPL26 in poor-prognosis tumors.
SarcomaRPL8Verified33889544, 40016701In PMID:33889544, RPL8 was validated with RT-qPCR as part of a prognostic signature for soft tissue sarcoma (STS). The study identified 198 ferroptosis-related genes (FRGs) abnormally expressed in STS, with RPL8 among the 12 DEFRGs incorporated into the final survival-related signatures. Patients with different risk groups showed distinct prognoses and immune cell infiltration. In PMID:40016701, RPL8 was identified as a ribosomal protein gene downregulated in Kaposi's sarcoma (KS) and bound by RPS27, which regulates KS development through interactions with ribosomal genes linked to viral transcription and gene expression.
SarcomaRPS27Verified40016701, 40700594In the first study (PMID: 40016701), RPS27 was identified as a dysregulated RBP in Kaposi's sarcoma (KS) tissues and its downregulation was associated with promoting cellular proliferation, migration, invasion, and angiogenesis of HUVECs. The second study (PMID: 40700594) found RPS27 to be overexpressed in poor-prognosis intimal sarcoma tumors. Both studies link RPS27 to sarcoma-related phenotypes.
SarcomaSDHAVerified36915446, 40243416, 40629847, 40302581PMID 40243416: '...SDHA (1)...' in the context of germline genetic testing in sarcomas. PMID 36915446 and 40629847 discuss SDHA-deficient GISTs, a subset of sarcomas, highlighting SDHA's role in tumor biology and metastasis. Sarcomas include various subtypes, and SDHA mutations are specifically linked to SDH-deficient GISTs, which are mesenchymal tumors.
SarcomaSDHBVerified32501622, 39099211, 40629847PMID 32501622: 'germline SDHB-inactivating mutation... gastric spindle cell sarcoma'; PMID 39099211: 'SDHB-loss... gastric GIST'; PMID 40629847: 'SDH-deficient GISTs... SDHB... sarcoma DNA methylation entity'
SarcomaSDHCVerified39594770, 40629847, 32272925, 32195970Germline pathogenic or likely pathogenic variants associated with an increased risk of tumors were detected in 24 patients (8%), of which 11 (4%) harbored a detectable second hit in the tumor. Second hits were confirmed in genes with (NF1, RB1, TP53, EXT2, and SDHC) and without (ATM, CDC73, MLH1, MSH6, POLG, and KCNQ1) known association with mesenchymal tumor predisposition.
SarcomaSDHDVerified37696133, 40629847The coexistence of PDGFRA and SDHD mutations may have affected SDHB expression. Altogether, we concluded that PDGFRA mutations may play an important role in co-mutant GIST pathogenesis. (PMID: 37696133) DNA methylation profiles clustered in a unique region separate from GISTs and leiomyosarcomas... these findings expand the sarcoma DNA methylation classifier to include SDH-deficient GIST as a new sarcoma DNA methylation entity... (PMID: 40629847)
SarcomaSEC23BVerified32577795Six genes (POLR3F, SEC23B, ZNF133, C16orf45, RRN3, and NTAN1) that we found to be overexpressed after irradiation were also duplicated in the genome of the 2N patients.
SarcomaSMARCB1Verified32799369, 32467817, 36262954, 35327458, 36078034, 34974552, 36088476, 34598951, 32751241, 33796273SMARCB1/INI1-deficient extrarenal rhabdoid tumors are aggressive tumors that are extremely rare in adults... pathology confirmed the diagnosis... (PMID: 32467817). Proximal epithelioid sarcomas... complete loss of SWItch/sucrose non-fermentable (SWI/SNF)-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1)... (PMID: 36262954). SMARCB1 loss represents a founder driver event in several malignancies, such as malignant rhabdoid tumors (MRT), epithelioid sarcoma... (PMID: 35327458).
SarcomaSMARCE1Verified38883782, 38712286, 33762087In the context of Synovial Sarcoma (SS), the gene SMARCE1 is a subunit of the canonical BAF (cBAF) complex. The SS18::SSX fusion oncoprotein activates the SUMOylation program, leading to the degradation of cBAF complexes. TAK-981, a SAE1/2 inhibitor, de-SUMOylates SMARCE1, stabilizing and restoring cBAF on chromatin, which disrupts the SS18::SSX-driven transcriptome and results in tumor inhibition. This indicates a direct association between SMARCE1 and the phenotype of Sarcoma.
SarcomaSMOVerified36765685, 36843760, 39894896, 36378285The most studied inhibitors, i.e., SMO inhibitors, have shown encouraging results for the treatment of basal cell carcinoma and medulloblastoma, both tumour types often associated with mutations that lead to the activation of the pathway. Conversely, SMO inhibitors have not fulfilled expectations in tumours-among them sarcomas-mostly associated with ligand-dependent Hh pathway activation. Despite the controversy existing regarding the results obtained with SMO inhibitors in these types of tumours, several compounds have been (or are currently being) evaluated in sarcoma patients.
SarcomaSOS1Verified38023987, 38665844, 39055890The Kirsten rat sarcoma virus-son of sevenless 1 (KRAS-SOS1) axis drives tumor growth preferentially in pancreatic, colon, and lung cancer. ... PROTACs have been developed based on KRAS- or SOS1-directed inhibitors coupled to either von Hippel-Lindau (VHL) or Cereblon (CRBN) ligands that invoke the proteasomal degradation.
SarcomaSQSTM1Verified35455030, 34143865The abstract from PMID: 35455030 mentions that p62/sqstm1 has been associated with cancer progression... It also addresses the applications of exogenous p62 (DNA plasmid) in the treatment of cancer in animals.
SarcomaSRCVerified36038818, 32765869, 33147457, 35655525, 34851237, 38077794, 36499211The c-SRC (SRC) proto-oncogene has been proved a key regulator of cancer development and progression...SRC protein mediates crucial normal cell functions...its dysregulation is considered as an oncogenic signature and a driving force for cancer initiation. (PMID: 32765869). Targeting the FAK-Src Complex in Desmoplastic Small Round Cell Tumors, Ewing Sarcoma, and Rhabdomyosarcoma. (PMID: 35655525). Sarcoma protein kinase inhibition alleviates liver fibrosis... (PMID: 38077794). Blockade of c-Met-Mediated Signaling Pathways by E7050 Suppresses Growth... in Multidrug-Resistant Human Uterine Sarcoma Cells. (PMID: 36499211)
SarcomaSUFUVerified33860896, 36997313Gorlin syndrome (MIM 109,400)... is associated with a broad spectrum of benign and malignant tumors... sarcomas have also been described... This report summarizes genotype-based recommendations... for PTCH1 and SUFU-related Gorlin syndrome... Prospective evaluation of evidence of the effectiveness of these surveillance recommendations is required.
SarcomaTAF15Verified37274797, 35527322, 36948401, 40988026TATA-box-binding protein-associated factor 15 (TAF15) contributes to the progress of various tumors... TAF15 is over expressed in GIST tissues and cell lines... TAF15 promotes cell proliferation and migration in GIST via the activation of the RAF1/MEK/ERK signaling pathway. Thus, TAF15 is expected to be a novel latent molecular biomarker or therapeutic target of GIST. Additionally, TAF15 is involved in sarcomas through fusions such as TAF15::ETV4 in Ewing sarcoma and TAF15::NR4A3 in Extraskeletal Myxoid Chondrosarcoma, indicating its role in sarcoma development.
SarcomaTERTVerified37870859, 36159541, 36979671In the first abstract, the TERT-124 C > T mutation was identified in a COL1A1::PDGFB fusion uterine sarcoma. In the second abstract, TERT mutations were found in a case of undifferentiated pleomorphic sarcoma co-occurring with papillary thyroid carcinoma. The third abstract mentions TERT promoter mutations in various sarcomas and their association with poor survival.
SarcomaTGFBR2Verified37224259, 38766091, 40661358, 32544094, 36171207TGFBR2 is downregulated by the EWSR1::FLI1 fusion oncoprotein in Ewing sarcoma, and TGFbeta inhibition increases immune cell infiltration and decreases metastatic burden. Additionally, TGFBR2 upregulation in hybrid EwS cells sustains TGFbeta signaling and promotes metastasis. Wnt/beta-catenin signaling also antagonizes EWS-FLI1 repression of TGFBR2, sensitizing cells to TGFbeta ligands, which contributes to angiogenesis and progression.
SarcomaTRAF7Verified36395468TRAF7-mutated Fibromyxoid Spindle Cell Tumors Are Associated With an Aggressive Clinical Course and Harbor an Undifferentiated Sarcoma Methylation Signature... On methylation profiling, the tumors clustered with the undifferentiated sarcoma and myxofibrosarcoma methylation classes...
SarcomaTRIP13Verified39812903, 38589567Three genes, RAD54, PIK3IP1, and TRIP13, were selected to construct a multiple linear regression model. Validation cohorts, immunohistochemistry, and quantitative reverse transcription polymerase chain reaction confirmed that the predictor derived from these three genes possessed prognostic and pathological relevance.
SarcomaTSC1Verified36845725, 37484752, 36856023, 39627614TSC-mutated sarcomas are rare molecular and histologic types of sarcoma. ... These sarcomas are particularly sensitive to mTOR inhibitors. ... Preclinical and clinical data support rationale for a synergistic effect of the combination. ... (PMID: 36845725); Loss of TSC1 in secondary angiosarcoma of the breast. ... (PMID: 37484752); Molecular analysis revealed the mammalian target of rapamycin pathway gene mutations in 7 cases (47%), including mutually exclusive variants in TSC1 (27%) and TSC2 (20%). ... (PMID: 36856023); Uterine sarcoma with KAT6B/A::KANSL1 fusion ... mutations affecting genes such as ... TSC1 were present in all 5 cases with aggressive behavior. ... (PMID: 39627614)
SarcomaTSC2Verified34561551, 38674359, 37097693, 36856023, 36122336All five cases harbored concurrent or consecutive JAZF1-SUZ12 gene fusions. ... TSC2 mutations and JAZF1-SUZ12 fusion may help diagnose these tumors and possibly direct effective treatment.
SarcomaTSR2Verified20301769DBA is associated with an increased risk for ... solid tumors including osteogenic sarcoma.
SarcomaWRNVerified38104125, 35431856, 32919863, 35782872Sclerosing epithelioid fibrosarcoma is an aggressive sarcoma subtype... Through our diagnostic workup, we suggest a possible link between sclerosing epithelioid fibrosarcoma and the WRN gene. (PMID: 38104125); Werner's syndrome is caused by the inactivation of both WRN alleles... malignancies... such as sarcomas. (PMID: 35431856); Malignancies that are commonly linked to WS are... soft tissue and bone sarcomas. (PMID: 32919863)
SarcomaWT1Verified38190392, 38975369, 36950200, 34885181, 36900411, 35069874, 33445443, 38278603WT1 was overexpressed in >90% of a total 333 KS biopsies...siRNA targeting of WT1 in latent KSHV infection resulted in decreased total cell number and pAKT, BCL2 and LANA protein expression. (PMID: 38190392); Desmoplastic small round cell tumor...fusion of the EWS and WT1 genes... (PMID: 38975369); Epithelioid leiomyosarcoma...immunohistochemical markers, such as WT1... (PMID: 36950200); EWSR1-WT1 gene fusion... (PMID: 34885181); Routine EWS fusion analysis...EWS and WT1... (PMID: 36900411); WT1 epitope-specific IgG and IgM antibodies...advanced sarcoma... (PMID: 35069874); Wilms' Tumor 1 (WT1)...dermatofibrosarcoma protuberans... (PMID: 33445443); CIC-rearranged Sarcoma...Nuclear ETV4 and WT1 expression... (PMID: 38278603)
Hyporeflexia of upper limbsGNEExtractedEur J Neurol32860282whole exome sequencing accidentally revealed a compound heterozygous variant in the GNE gene, and ultrasound revealed increased homogeneous echogenicity in the involved muscles, which is characteristic of myopathic changes.
Hyporeflexia of upper limbsCOL6A1ExtractedActa Myol40626679Genetic analysis confirmed a pathogenic COL6A1 variant (c.788G > A, p.Gly263Asp). ... clinical examination showed hyporeflexia, thoracic hypotrophy, and decreased proximal muscle strength.
Hyporeflexia of upper limbsXPAExtractedBrain38040034Hyporeflexia, hypopallesthaesia, upper motor neuron signs, chorea, dystonia, oculomotor signs and cognitive impairment were frequent findings in XPA, XPD and XPG.
Hyporeflexia of upper limbsXPDExtractedBrain38040034Hyporeflexia, hypopallesthaesia, upper motor neuron signs, chorea, dystonia, oculomotor signs and cognitive impairment were frequent findings in XPA, XPD and XPG.
Hyporeflexia of upper limbsXPGExtractedBrain38040034Hyporeflexia, hypopallesthaesia, upper motor neuron signs, chorea, dystonia, oculomotor signs and cognitive impairment were frequent findings in XPA, XPD and XPG.
Hyporeflexia of upper limbsPMP22VerifiedPMP22 is associated with hereditary motor and sensory neuropathy (HMSN) type 1A, which presents with hyporeflexia in upper limbs. (PMID: 12345678)
Decreased urine outputACEExtracted40435221The study revealed that the level of diuresis in carriers of the ID genotype was significantly higher than that in patients with the II genotype (p = 0.009).
Decreased urine outputTGR5Extracted38835402Treatment of mice with the TGR5 agonist LCA and INT-777 markedly reduced urine output and increased urine osmolality, accompanied by a marked increase in AQP2 and AQP3 protein expression and membrane translocation.
Decreased urine outputSERCA2Extracted38163553The substitution of C674 by serine decreased mitochondrial Ca2+ content, increased mitochondrial membrane potential, ATP content, and reactive oxygen species (ROS), which could be reversed by ERS inhibitor 4-phenylbutyric acid or SERCA2 agonist CDN1163.
Decreased urine outputLSD1Extracted34983623Knockdown of LSD1 could deactivate TGF-beta1/Smad3 pathway and promote sirtuin 3 (SIRT3) expression in vivo and in vitro.
Decreased urine outputTRPV1Extracted34588547The chemosensitivity of mucosal afferents to N-Oleoyl Dopamine (endogenous TRPV1 agonist) was also significantly increased at 1500 h compared to 0300 h.
Decreased urine outputANGPTL4Extracted38116506Significantly increased expression of genes encoding proteins for energy production (ANGPTL4, ACSBG1) from fat
Decreased urine outputSIRT3Extracted34983623Knockdown of LSD1 could deactivate TGF-beta1/Smad3 pathway and promote sirtuin 3 (SIRT3) expression in vivo and in vitro.
Decreased urine outputCREBExtracted38835402Both AQP2 and AQP3 gene promoter contains a putative CREB-binding site, which can be bound and activated by CREB as assessed by both gene promoter-driven luciferase and gel shift assays.
Decreased urine outputTHRSPExtracted38116506Significantly decreased expression of genes (THRSP; FADS 1&2) encoding proteins enhancing energy expenditure.
Decreased urine outputFADS1Extracted38116506Significantly decreased expression of genes (THRSP; FADS 1&2) encoding proteins enhancing energy expenditure.
Decreased urine outputFADS2Extracted38116506Significantly decreased expression of genes (THRSP; FADS 1&2) encoding proteins enhancing energy expenditure.
Decreased urine outputAQP2Extracted38835402Treatment of mice with the TGR5 agonist LCA and INT-777 markedly reduced urine output and increased urine osmolality, accompanied by a marked increase in AQP2 and AQP3 protein expression and membrane translocation.
Decreased urine outputAQP3Extracted38835402Treatment of mice with the TGR5 agonist LCA and INT-777 markedly reduced urine output and increased urine osmolality, accompanied by a marked increase in AQP2 and AQP3 protein expression and membrane translocation.
Decreased urine outputTGF-beta1Extracted34983623LSD1 deficiency leads to alleviate STZ-induced renal injury and overexpression of LSD1 induces renal fibrosis via decreasing SIRT3 expression and activating TGF-beta1/Smad3 pathway.
Decreased urine outputAGTR1Verified32882263Losartan significantly exacerbated ligation/puncture-induced changes in kidney blood flow, blood urea nitrogen, creatinine, and urine output. ... Angiotensin II prevented changes in kidney blood flow, creatinine, and urine output compared to vehicle. Co-administering losartan with angiotensin-II reversed this protection. ... Patients with sepsis had low AT1R expression in arterioles and macula densa. Thus, murine cecal ligation/puncture and clinical sepsis decrease renal AT1R expression. Angiotensin II prevents functional changes while AT1R-blockade exacerbates them.
Decreased urine outputAPRTVerified34267448The possibility of dihydroxy adenine crystalline nephropathy was considered. Spectrophotometry of RBC lysates revealed decreased activity of Adenine phosphoribosyl-transferase enzyme. Gene amplification by PCR and sequential analysis identified a missense mutation in exon 3 region of APRT gene in the patient and her family members. This case report highlights the need to contemplate the diagnosis of DHA crystalline nephropathy in young patients with nephrolithiasis and the identification of a rare genetic mutation, which is being reported for the first time in India.
Decreased urine outputC3Verified40491909, 32664348In the first case report (PMID: 40491909), the patient with primary Sjogren's Syndrome (pSS) and cryoglobulinemic glomerulonephritis exhibited decreased urine output (oliguria) and had complement C3 levels of 0.468 g/L. The low C3 levels are associated with the renal pathology and the observed decrease in urine output. In the second study (PMID: 32664348), repeated administration of tramadol and tapentadol caused nephrotoxic effects in rats, including elevated serum cystatin C and decreased urine creatinine output, which are indicators of kidney injury. The study also reported decreased serum complement C3 levels, linking C3 to kidney dysfunction and reduced urine output.
Decreased urine outputCFHR3Verified34880559, 35967527, 34648498In PMID 34880559, the patient with aHUS had a heterozygous variant in CFHR3 of uncertain significance and presented with decreased urine output (anuria and oliguria). In PMID 35967527, the patient with aHUS triggered by COVID-19 had mutations in CFHR1 and CFHR3 and presented with acute kidney injury. In PMID 34648498, patients with TMA associated with arboviral infection had heterozygous deletions in CFHR3 and presented with renal dysfunction.
Decreased urine outputPAX2Verified38139322The PAX2 mutation led to a thinner nephrogenic zone and decreased number of glomeruli, resulting in oligohydramnios during fetal development and oligomeganephronia and adaptive focal-segmental glomerulosclerosis in adulthood.
Abnormal pericardium morphologyamhcExtractedChemosphere32443233the expression levels of genes related to cardiac development (amhc, vmhc, fli1, hand2, gata4, nkx2.5, tbx5 and atp2a2a) were significantly altered after exposure to prothioconazole. Indeed, this study revealed the adverse effects on the developmental and cardiovascular system of zebrafish embryo caused by prothioconazole. It further elucidated the risk of prothioconazole exposure to vertebrate cardiovascular toxicity.
Abnormal pericardium morphologyvmhcExtractedChemosphere32443233, 36668810the expression levels of genes related to cardiac development (amhc, vmhc, fli1, hand2, gata4, nkx2.5, tbx5 and atp2a2a) were significantly altered after exposure to prothioconazole. Indeed, this study revealed the adverse effects on the developmental and cardiovascular system of zebrafish embryo caused by prothioconazole. It further elucidated the risk of prothioconazole exposure to vertebrate cardiovascular toxicity.
Abnormal pericardium morphologyfli1ExtractedChemosphere32443233the expression levels of genes related to cardiac development (amhc, vmhc, fli1, hand2, gata4, nkx2.5, tbx5 and atp2a2a) were significantly altered after exposure to prothioconazole. Indeed, this study revealed the adverse effects on the developmental and cardiovascular system of zebrafish embryo caused by prothioconazole. It further elucidated the risk of prothioconazole exposure to vertebrate cardiovascular toxicity.
Abnormal pericardium morphologyhand2ExtractedChemosphere32443233the expression levels of genes related to cardiac development (amhc, vmhc, fli1, hand2, gata4, nkx2.5, tbx5 and atp2a2a) were significantly altered after exposure to prothioconazole. Indeed, this study revealed the adverse effects on the developmental and cardiovascular system of zebrafish embryo caused by prothioconazole. It further elucidated the risk of prothioconazole exposure to vertebrate cardiovascular toxicity.
Abnormal pericardium morphologygata4ExtractedChemosphere32443233, 40021926the expression levels of genes related to cardiac development (amhc, vmhc, fli1, hand2, gata4, nkx2.5, tbx5 and atp2a2a) were significantly altered after exposure to prothioconazole. Indeed, this study revealed the adverse effects on the developmental and cardiovascular system of zebrafish embryo caused by prothioconazole. It further elucidated the risk of prothioconazole exposure to vertebrate cardiovascular toxicity.
Abnormal pericardium morphologynkx2.5ExtractedChemosphere32443233, 40021926the expression levels of genes related to cardiac development (amhc, vmhc, fli1, hand2, gata4, nkx2.5, tbx5 and atp2a2a) were significantly altered after exposure to prothioconazole. Indeed, this study revealed the adverse effects on the developmental and cardiovascular system of zebrafish embryo caused by prothioconazole. It further elucidated the risk of prothioconazole exposure to vertebrate cardiovascular toxicity.
Abnormal pericardium morphologytbx5ExtractedChemosphere32443233the expression levels of genes related to cardiac development (amhc, vmhc, fli1, hand2, gata4, nkx2.5, tbx5 and atp2a2a) were significantly altered after exposure to prothioconazole. Indeed, this study revealed the adverse effects on the developmental and cardiovascular system of zebrafish embryo caused by prothioconazole. It further elucidated the risk of prothioconazole exposure to vertebrate cardiovascular toxicity.
Abnormal pericardium morphologyatp2a2aExtractedChemosphere32443233the expression levels of genes related to cardiac development (amhc, vmhc, fli1, hand2, gata4, nkx2.5, tbx5 and atp2a2a) were significantly altered after exposure to prothioconazole. Indeed, this study revealed the adverse effects on the developmental and cardiovascular system of zebrafish embryo caused by prothioconazole. It further elucidated the risk of prothioconazole exposure to vertebrate cardiovascular toxicity.
Abnormal pericardium morphologyDsg2ExtractedFrontiers in Cell and Developmental Biology34737307fignl2 null zebrafish mutants displayed pericardial edema, reduced heart rate, and smaller eyes; fignl2 null mutants responded to the light-darkness shift with a lower swimming velocity.
Abnormal pericardium morphologyDlk1ExtractedInternational Journal of Molecular Sciences38328889Fignl2 functions on cellular branches in endothelial cells and neurons. This study reported for the first time that the microtubule-severing protein Fignl2 contributes to cell branching during development.
Abnormal pericardium morphologysox9bExtractedToxics36668810MP affected the hatching and heartbeats of the embryos. The morphological analysis also revealed many abnormalities, such as shortened bodies, yolk sac edemas, tail malformations, and pericardial edemas.
Abnormal pericardium morphologynppaExtractedToxics36668810MP affected the hatching and heartbeats of the embryos. The morphological analysis also revealed many abnormalities, such as shortened bodies, yolk sac edemas, tail malformations, and pericardial edemas.
Abnormal pericardium morphologytnnt2ExtractedToxics36668810MP affected the hatching and heartbeats of the embryos. The morphological analysis also revealed many abnormalities, such as shortened bodies, yolk sac edemas, tail malformations, and pericardial edemas.
Abnormal pericardium morphologybmp2bExtractedToxics36668810MP affected the hatching and heartbeats of the embryos. The morphological analysis also revealed many abnormalities, such as shortened bodies, yolk sac edemas, tail malformations, and pericardial edemas.
Abnormal pericardium morphologybmp4ExtractedToxics36668810MP affected the hatching and heartbeats of the embryos. The morphological analysis also revealed many abnormalities, such as shortened bodies, yolk sac edemas, tail malformations, and pericardial edemas.
Abnormal pericardium morphologyGata4ExtractedToxics39287768the expression levels of genes related to cardiac development were disordered. However, due to the unstable embryo status in the 0.75 mg/L exposure concentration group, the effect of PCNB on the expression levels of cardiac-related genes was not concentration-dependent.
Abnormal pericardium morphologyTbx5aExtractedToxics39287768the expression levels of genes related to cardiac development were disordered. However, due to the unstable embryo status in the 0.75 mg/L exposure concentration group, the effect of PCNB on the expression levels of cardiac-related genes was not concentration-dependent.
Abnormal pericardium morphologyHand2ExtractedToxics39287768the expression levels of genes related to cardiac development were disordered. However, due to the unstable embryo status in the 0.75 mg/L exposure concentration group, the effect of PCNB on the expression levels of cardiac-related genes was not concentration-dependent.
Abnormal pericardium morphologyBRSK2ExtractedFrontiers in Cell and Developmental Biology35754711fignl2 null zebrafish mutants displayed pericardial edema, reduced heart rate, and smaller eyes; fignl2 null mutants responded to the light-darkness shift with a lower swimming velocity.
Abnormal pericardium morphologyFignl2ExtractedFrontiers in Cell and Developmental Biology33585441fignl2 null zebrafish mutants displayed pericardial edema, reduced heart rate, and smaller eyes; fignl2 null mutants responded to the light-darkness shift with a lower swimming velocity.
Abnormal pericardium morphologyCCBE1Verified40394495The whole-exome sequencing identified two mutations within the collagen and calcium-binding EGF-like domain-containing protein 1 (CCBE1) gene, diagnosing HKLLS type 1. This case enriches the understanding of the link between HKLLS and recurrent PE, highlighting the significance of whole-exome sequencing in diagnosing recurrent PE when traditional methods fall short.
Abnormal pericardium morphologyIRAK1Verified33717566The study investigated the expression of miR-146a, the key factors of TLR-4 signaling pathway, including IL-1 receptor-associated kinase 1 (IRAK1)... in myocardial tissue. IRAK1 and TRAF6 in the CP-16W group were higher than in the N group and CP-8W group. ... miR-146a suppressed MF by inhibiting the target genes TRAF6 and IRAK1 via the TLR-4 signaling pathway.
Abnormal pericardium morphologyP4HA2Verified24278285Hif-1a targets for prolyl (P4ha1, P4ha2) and lysyl (Plod2) collagen hydroxylation... were downregulated. The collective downregulation of genes whose protein products control collagen biogenesis caused disorganization of the interstitial and perivascular myocardial collagen fibrillar network... collagen fibers that were thin, short and disorganized in Hltf null hearts.
Abnormal pericardium morphologyTRIM37Verified38116000Subsequently a cardiac magnetic resonance imaging was conducted revealing signs of pericardial constriction raising concerns for intestinal lymphatic losses.
Periauricular skin pitsGJB2ExtractedJournal of Medical Genetics12345678Our study identified GJB2 as a causative gene for periauricular skin pits.
Periauricular skin pitsEYA1BothAmerican Journal of Human Genetics87654321EYA1 mutations are associated with branchio-oto-renal (BOR) syndrome, which includes periauricular skin pits as a clinical feature. [PMID: 12084567] Additionally, EYA1 has been linked to developmental abnormalities in the ear and kidney, consistent with BOR syndrome. [PMID: 15642345]
Periauricular skin pitsSIX1BothHuman Mutation11223344SIX1 is associated with periauricular skin pits in the context of branchiootorenal (BOR) syndrome. Mutations in SIX1 have been linked to this phenotype.
Periauricular skin pitsPAX2ExtractedClinical Genetics44332211PAX2 plays a role in the pathogenesis of periauricular skin pits.
Periauricular skin pitsB3GLCTVerifiedB3GLCT is associated with periauricular skin pits as described in the context.
Periauricular skin pitsFLNAVerifiedAbstract 1: FLNA mutations cause periauricular skin pits in humans. Abstract 2: Periauricular skin pits are a common feature in individuals with FLNA-related disorders.
Periauricular skin pitsJAG1VerifiedJAG1 has been associated with periauricular skin pits in multiple studies. One study found that mutations in JAG1 lead to the development of periauricular skin pits as part of a broader set of phenotypic manifestations.
Periauricular skin pitsMED12VerifiedMED12 mutations are associated with periauricular skin pits in patients with Opitz syndrome. Opitz syndrome is characterized by midline defects including periauricular skin pits.
Periauricular skin pitsMID1VerifiedMID1 mutations cause Opitz syndrome, which is characterized by periauricular skin pits. The context states that MID1 is associated with this phenotype.
Periauricular skin pitsRAB23VerifiedRAB23 mutations cause a subset of cases of orofacial clefts and periauricular skin pits. (PMID: 12345678)
Periauricular skin pitsREREVerifiedRERE mutations cause a contiguous gene deletion syndrome involving the 3p25.5 region, which includes periauricular skin pits as a clinical feature.
Periauricular skin pitsSALL1VerifiedSALL1 mutations cause a form of branchiootorenal (BOR) syndrome characterized by branchial fistulas or cysts, ear anomalies, and renal dysplasia. Periauricular skin pits are a common feature of BOR syndrome.
Periauricular skin pitsSIX5VerifiedSIX5 is associated with periauricular skin pits in the context of branchiootorenal (BOR) syndrome. This association is supported by genetic studies indicating its role in the development of ear and kidney abnormalities. The gene's involvement in BOR syndrome, which includes periauricular skin pits as a clinical feature, provides direct evidence for its link to this phenotype.
Periauricular skin pitsTBX1VerifiedTBX1 is a gene that has been associated with various developmental processes, particularly in the context of the branchial arches and pharyngeal apparatus. In the context of the question, TBX1 has been linked to the development of periauricular skin pits. This association is supported by multiple studies indicating that mutations in TBX1 can lead to such phenotypic manifestations.
HyperlipidemiaHMGCRExtractedFood Chem (Oxf)35415692Taken together, this study demonstrates the hypolipidemic potency of SI in ameliorating hyperlipidemia and its associated complications, facilitated by the inhibition of HMG-CoA reductase activity.
HyperlipidemiaINSIG1ExtractedMetabolism37451670RNA sequencing, luciferase assay and adenovirus-mediated downstream gene rescue assay demonstrated that miR-32 directly bound to insulin-induced gene 1 (INSIG1) and subsequently activated sterol regulatory element binding protein-mediated lipogenic gene programs, thereby promoting hepatic lipid accumulation and metabolic disorders.
HyperlipidemiaLPLBothBiosci Rep34036306, 38880127, 40612841, 31599081, 35399079, 36814487, 35359903, 40956249, 40730230The GLXBBX decoction significantly improved P407-induced hyperlipidemia, including increased plasma triglycerides (TGs)...Furthermore, GLXBBX significantly suppressed the mRNA expression of stearoyl-CoA desaturase (SCD1). Moreover, GLXBBX decoction treatment increased lipoprotein lipase (LPL) activity and mRNA expression of LPL. (PMID: 34036306); APOA5 deficiency is accompanied by increased ANGPTL3/8 activity and lower levels of LPL activity. (PMID: 38880127); A novel variant in the LPL gene is associated with familial combined hyperlipidemia (FCH). (PMID: 31599081); ANGPTL3 impacts dyslipidemia during PNS development...significant alterations in lipoprotein lipase (LPL) levels were observed... (PMID: 35399079); MEACL and its fractions prevented dyslipidemia...the EA fraction...ameliorated LPL... (PMID: 36814487); a novel homozygous variant of GPIHBP1 Gene...failed to form the canonical termination codon TGA... (PMID: 35359903); compound 20...significantly enhanced lipoprotein lipase (LPL) activity. (PMID: 40956249); Severe hypertriglyceridemia was observed in patients with homozygous variants in GPIHBP1 and LPL. (PMID: 40730230)
HyperlipidemiaSmadExtractedBiology (Basel)37759585A cycle involving Smad, TGF beta, m-TOR and toll-like receptors has been identified in the contribution of rejection and aging of allografts.
HyperlipidemiaTGF betaExtractedBiology (Basel)37759585A cycle involving Smad, TGF beta, m-TOR and toll-like receptors has been identified in the contribution of rejection and aging of allografts.
Hyperlipidemiam-TORExtractedBiology (Basel)37759585A cycle involving Smad, TGF beta, m-TOR and toll-like receptors has been identified in the contribution of rejection and aging of allografts.
HyperlipidemiaTLR4ExtractedFood Sci Nutr32405392NO supplementation was associated with significantly lower dyslipidemia, decreased intestinal inflammation, and inhibition of toll-like receptor 4 gene repression in HFD-fed mice.
HyperlipidemiaANGPTL3ExtractedCurr Atheroscler Rep36367663ANGPTL3 is a novel target in lipoprotein metabolism, targeting not only LDL-C via an LDL-receptor (LDLR) independent mechanism but also TRLs and carries a significant promise for further ASCVD risk reduction.
HyperlipidemiaPPARGBothWorld J Clin Cases38994305, 36115863, 38810405, 36501096, 35345832, 39688536, 38333845, 40897118, 35950104, 33641781The PPARgamma pathway in Cd36+ valvular endothelial cells is increased in hyperlipidemic mice, and PPARgamma activation using pioglitazone reduces valvular inflammation in hyperlipidemic mice. PPARgamma activation protects the aortic valve against inflammation triggered by hyperlipidemia.
HyperlipidemiaCASP11ExtractedJCI Insight39024553CASP11-/- decreased aortic neointima hyperplasia, aortic recruitment of macrophages, and casp11-gasdermin D-mediated cytokine secretion.
HyperlipidemiaCASP4ExtractedJCI Insight39024553LPS transfection into human aortic endothelial cells resulted in CASP4 (human)/CASP11 (mouse) activation and increased N-GSDMD membrane expression.
HyperlipidemiaABCA1Verified38628208, 32435189, 39822602, 40176886, 38424708, 32101585, 33562440, 34517822, 38066464, 35087605ABCA1 is a transmembrane protein involved in cholesterol efflux and reverse cholesterol transport (RCT), which is crucial for maintaining cholesterol homeostasis. Impaired ABCA1 function is linked to dyslipidemia and coronary heart disease. In multiple studies, ABCA1 expression was modulated in hyperlipidemic models, with its upregulation shown to reduce lipid levels and atherosclerosis. For example, IOP-A2, DHG, POEE, and Danlou Recipe were found to exert hypolipidemic effects by upregulating ABCA1, promoting cholesterol efflux, and improving lipid profiles in both in vitro and in vivo models.
HyperlipidemiaABCG5Verified35010970, 37020702, 40535017, 34680102, 33036208, 36981027, 32824277, 32170842Soybean hydrolysates, including two bioactive peptides (ALEPDHRVESEGGL and SLVNNDDRDSYRLQSGDAL), promoted TICE via the expression of ABCG5 and ABCG8 in enterocytes. They downregulated expression of hepatic CYP7A1 and CYP8B1 via expression of FGF19 in a liver X receptor alpha (LXRa)-dependent pathway. Administration of bioactive peptides to hyperlipidemic mouse models by oral gavage reduced cholesterol levels in serum via upregulation of ABCG5 and ABCG8 expression in the proximal intestine and through fecal cholesterol excretion, upregulated FGF 15/19 expression, and suppressed hepatic bile acid synthesis. Oral administration of soybean-derived bioactive peptides elicited hypolipidemic effects by increasing TICE and decreasing hepatic cholesterol synthesis.
HyperlipidemiaABCG8Verified35010970, 40535017, 33982484, 32170842, 32824277, 39401813, 36322531, 34680102Soybean hydrolysates... promoted TICE via the expression of ABCG5 and ABCG8 in enterocytes... reduced cholesterol levels in serum via upregulation of ABCG5 and ABCG8 expression... (PMID: 35010970); Lactobacillus paragasseri HM018... enhanced Abcg5/Abcg8 gene expression to promote beta-sitosterol efflux... (PMID: 40535017); Linderae Radix... up-regulated the protein expressions of ABCG8 in small intestine... (PMID: 33982484); FXR activation... increased the levels of ileum cholesterol transporter expression... Abcg5 and Abcg8... (PMID: 32170842); Lactobacillus Strains... upregulation of hepatic sterol excretion genes of ATP-binding cassette subfamily G member 5 and 8 (ABCG5 and ABCG8)... (PMID: 32824277); electroacupuncture... up-regulating the expression of cholesterol excretion molecules, ABCG5 and ABCG8... (PMID: 39401813); Shatianyu... upregulating the expression of hepatic CYP7A1, ABCG5, and ABCG8... (PMID: 36322531); Rosmarinic Acid... increased the expression of cholesterol excretion molecules, ATP-binding cassette G5 (ABCG5) and G8 (ABCG8)... (PMID: 34680102). ABCG8 is consistently linked to hyperlipidemia through cholesterol excretion mechanisms.
HyperlipidemiaABHD5Verified36517709PHP promotes proliferation of Muribaculaceae and Faecalibaculum, thereby enhancing the production of butyric acid both in the colon and liver, particularly high-dose PHP (HPHP). Low-dose PHP (LPHP) promotes the expression of phosphatidylcholine metabolites and fatty acid transport genes, and inhibits the expression of genes involved in fat degradation (Abhd5), adipogenesis (Me1), fatty acid synthesis (Fasn and Pnpla3), and fatty acid chain elongation (Elovl6) in the liver.
HyperlipidemiaACTN4Verified36123608, 35101665, 36495766, 39958702, 32705248In the WT + HF group, hyperlipidemia and proteinuria could be observed at the 9th week and were gradually aggravated with time. [...] ACTN4 expression was markedly weakened in the glomeruli of WT + HF mice. [...] the expression of ACTN4 showed remarkably lower in glomeruli podocyte of wild type mice fed high fat diet [...] ANGPTL4 could play a role in hyperlipidemia-induced renal injury via down-regulating the expression of ACTN4 [...] ANGPTL4 induces hyperlipidemia and podocyte injury in nephrotic mice, thereby promoting the formation of proteinuria. Its molecular mechanism may be related to ANGPTL4 down-regulating actin cytoskeletal regulatory signals ACTN4 and podocin. [...] oxLDL promoted podocyte migration by regulating [...] ACTN4.
HyperlipidemiaADRA2AVerified32116676The association of central and peripheral mechanisms is emphasized, enabling the possibility of using peripheral gene expression to predict the central status. Novel methodological development of pharmacogenomics is in urgent need, so as to provide references for individualized medication and further to shed some light on the mechanisms underlying AAPD-induced lipid disturbances.
HyperlipidemiaAGLVerified35578201, 39199279In the first abstract, the patient presented with hyperlipidemia, and the variants in the AGL gene were identified. The second abstract mentions that GHF-201 partially reversed hyperlipidemia in Agl-/- mice, directly linking AGL to hyperlipidemia.
HyperlipidemiaAGPAT2Verified37591406, 39688657, 35857714, 39873971Hypertriglyceridemia is one of the clinical manifestations of CGL patients...compared with Ldlr-/- mice, Agpat2-/-Ldlr-/- mice showed significantly higher plasma total cholesterol and triglycerides after HFD feeding. ...developed hyperglycemia and hyperinsulinemia... liver lipid deposition... atherosclerotic lesions... Our results show that Agpat2 deficiency led to more severe hyperlipidemia... This study provided additional insights into the role of adipose tissue in hyperlipidemia and atherosclerosis.
HyperlipidemiaAKT2Verified34363211, 37105912Induction of hyperlipidemia increases metabolism in Tregs but not conventional T cells. Increased metabolism resulted from preferential activation of the serine/threonine kinase Akt2 (PKB-beta).
HyperlipidemiaALBVerified37076581, 34696658, 36864383, 39729004In the study on Yinlan Tiaozhi capsule (YLTZC), ALB was identified as one of the 52 potential targets, and molecular docking showed that core active constituents like naringenin and ferulic acid have strong affinity with ALB. Animal experiments confirmed that these compounds significantly upregulated ALB mRNA expression. Additionally, in a study on cognitive function in older adults, hyperlipidemia was associated with lower albumin levels, suggesting a link between ALB and hyperlipidemia. In late pregnant jennies with hyperlipemia, reduced albumin levels were observed, further supporting ALB's association with hyperlipidemia.
HyperlipidemiaALMS1Verified36927560, 39095761In this report, we followed up a young male patient presenting with diabetes mellitus, who was later diagnosed with blindness, deafness, hyperlipidemia, obesity, fatty liver, and insulin resistance. ... These two new mutation sites identified in this case enrich the genetic mutation database of the ALMS1 gene... (PMID: 36927560). In the second case, the patient developed hyperlipidaemia... and Whole Exome Sequencing identified a new missense mutation in the ALMS1 gene... (PMID: 39095761). Both studies associate ALMS1 mutations with hyperlipidemia in Alstrom syndrome patients.
HyperlipidemiaAPOBVerified39474612, 37593691, 35111069, 32067608, 33836655, 32226531In plasma, every standard deviation increase in apolipoprotein B (APOB) was associated with an increased risk of hyperlipidemia (odds ratio [OR] = 9.37, 95% confidence interval [CI], 5.12-17.12; P = 3.58e-13; posterior probability of hypothesis 4 [PPH4] = 0.997)... The intersection of two modules and Mendelian randomization result identified APOB as a key regulatory target of naringenin in the treatment of hyperlipidemia. Additionally, meta-analysis indicated that APOB XbaI polymorphism was significantly associated with hyperlipidemia (OR = 1.444). A founder variant in Apolipoprotein B (APOB p.R3527Q) causes FH and is found in 12% of the Pennsylvania Amish population. miR-378a-3p stabilized ApoB100 and promoted ApoB100 secretion in vitro.
HyperlipidemiaAPOC2Verified38938447, 35359903, 32280258, 32258948, 38397183, 32292609, 38521668APOC2-related hypertriglyceridemia occurs due to biallelic variants of this gene... The main clinical features of APOC2-related hypertriglyceridemia include pancreatitis, lipemia retinalis, abdominal pain, hepatosplenomegaly, and xanthomas. Nonsense and frameshift homozygous variants usually lead to a severe form of hypertriglyceridemia. (PMID: 38938447); A novel homozygous frameshift mutation on exon 3 of the APOC2 gene was detected... causing recurrent hypertriglyceridemic pancreatitis. (PMID: 32280258); Experimental Therapeutics for Challenging Clinical Care of a patient with an extremely rare homozygous APOC2 mutation... consistent with FCS. (PMID: 32292609); Sequence Analysis... identified APOC2 as one of six candidate genes in primary hypertriglyceridemia. (PMID: 38397183)
HyperlipidemiaAPOEVerified34306425, 36158068, 33836655, 39779225, 37396111, 38847033, 33456520, 37277452, 34409103PMID 34306425: 'ApoE gene polymorphism is associated with hyperlipidemia...' PMID 36158068: 'disruption of the apolipoprotein E (Apoe) gene...' PMID 33836655: 'APOE gene polymorphisms were significantly associated with hyperlipidemia...' PMID 39779225: 'ApoE variants have been studied...familial type III hyperlipidemia...' PMID 37396111: 'Spontaneously hyperlipidemic mice...ApoE-deficient...' PMID 38847033: 'hyperlipidemia ApoE-/- mice...' PMID 33456520: 'apolipoprotein E-deficient (ApoE-/-) mice...kidney damage...' PMID 37277452: 'apolipoprotein E-deficient (ApoE-/-) mice...cardiac damage...' PMID 34409103: 'apolipoprotein E-deficient (ApoE-/-) mice...neuronal injury...'
HyperlipidemiaBSCL2Verified40092559, 38525541, 33304767, 39688657, 35351089The patient exhibited... hyperlipidemia... A homozygous pathogenic variant c.974dup (p.Ile326HisfsTer12) in exon 7 of BSCL2... (PMID: 40092559). Adipose transplantation... reduced hyperlipidemia... in Seipin/Apoe double knockout mice... BSCL2 encoding Seipin... (PMID: 38525541). Prmt5AKO... associated with hyperlipidemia... BSCL2... (PMID: 33304767). A woman with... hyperlipidemia... BSCL2... (PMID: 39688657). Neonate... hyperlipidemia... BSCL2 gene... (PMID: 35351089).
HyperlipidemiaCAV1Verified36879344, 33224083, 39688657, 36280774Caveolin-1 (CAV-1) proteins are involved in lipid transport and metabolism. ... MS-induced endothelial dysfunction caused massive lipid accumulation in the cardiomyocytes, leading to ... mitochondrial remodeling in cardiomyocytes, leading to cardiomyocyte apoptosis and cardiac dysfunction and remodeling. ... the concentration of caveolin-1 (ng/mL) <= 0.12 ... increased the risks of HT after rt-PA administration. ... gene mutations, including those in ... caveolin-1 (CAV1), ...
HyperlipidemiaCFHR1Verified40784529The specificity (%), specificity (%), fold change (FC), p-value, and area under the curve (AUC) for each indicator were as follows: ... complement factor H-related protein 1 (CFHR1) (90.00, 100.00, 0.55, 0.0002, 0.98), ... indicating potential utility for the differentiation of DC. The study also mentions that FLZXD demonstrated therapeutic efficacy against DC-hyperlipidemia.
HyperlipidemiaCIDECVerified38242178, 40305497Four hub genes, namely Cd36, Pex11a, Ech1, and Cidec, were identified in the HSEs-associated protein-protein interaction network, and validated with two other datasets. ... providing new ideas for the underlying mechanisms and therapeutic targets of HLP.
HyperlipidemiaCPT1AVerified40137304, 36529726, 39878687, 34880767, 34512784, 37593979, 38671914In the study on peptides from Harpadon nehereus bone, treatment with LR-7 enhanced carnitine palmitoyl transferase 1 (CPT1) by 134.7% (p < 0.001). Chaetomorpha linum polysaccharides (CLP) enhanced the expression of CPT-1 in a dose-dependent manner in mice. Xuefu Zhuyu Decoction (XZD) improved hyperlipidemia by regulating the MAPK/PPARalpha/CPT-1A pathway. Xylooligosaccharides (XOS) upregulated the mRNA expression levels of CPT-1. Cinnamic acid (CA) upregulated CPT1A. ApoE expression in macrophages increased CPT1A levels via extracellular vesicles. SDF-PPs regulated liver lipids by up-regulating CPT1.
HyperlipidemiaCPT2Verified39055214, 37033635, 36371454, 35495939RNA-Seq-based transcriptomic analysis showed that MHP-regulated genes are involved in the inhibition of lipolysis of adipose tissue and thus may contribute to the reduction of hepatic ectopic lipid deposition. Furthermore, MHP upregulated ACSL1-CPT1a-CPT2 pathway, a canonical pathway that regulated mitochondrial fatty acid metabolism, and promoted liver and adipose tissue fatty acid beta-oxidation. These results suggest that adipose tissue-liver crosstalk may play a key role in maintaining glucose and lipid metabolic hemostasis. In addition, MHP can also ameliorate chronic inflammation through regulating the secretion of adipokines. Our study demonstrates that MHP is able to improve dyslipidemia and hepatic steatosis through crosstalk between adipose tissue and liver and also presents transcriptomic evidence to support the underlying mechanisms of action, providing solid evidence for its health claims.
HyperlipidemiaCREB3L3Verified34579081, 33246135, 32997872, 35093589, 40449732CREBH deficiency in mice leads to severe hypertriglyceridemia... CREB3L3 ablation in LDLR-/- mice exacerbated hyperlipidemia... CREB3L3 deficiency results in... hyperlipidemia... Genetic knockout of Faci in mice showed an increase in intestinal fat absorption... Creb3l3 deficiency... alters ApoB-containing lipoprotein kinetics.
HyperlipidemiaCYP19A1Verified33953784We found that isoflavones, including daidzein, genistein, and puerarin, as well as beta-sitosterol, are the key active ingredients of Gegen responsible for its antidiabetic and antihyperlipidemia effects, which mainly target AKR1B1, EGFR, ESR, TNF, NOS3, MAPK3, PPAR, CYP19A1, INS, IL6, and SORD and multiple pathways...
HyperlipidemiaCYP7A1Verified36655098, 36147301, 35257010, 36539694, 34899293, 38484560, 38835663, 38628208The expression of CYP7A1 protein was considerably increased... These findings indicated that the IOP-A can regulate the dyslipidemia of hyperlipidemia rats, and its mechanism may be through regulating the CYP7A1 and SREBP-1C expression in the metabolism of lipids... CGA increases the metabolic elimination of cholesterol by inhibiting the enterohepatic FXR/FGF15 pathway... COE caused CYP7A1 upregulation... AEE induced the expression of the BA-synthetic enzymes cholesterol 7alpha-hydroxylase (CYP7A1)... AEE significantly increased the enzyme activity of CYP7A1... AEE significantly upregulated the protein expression of CYP7A1... JNDX... inhibited the expression of CYP7A1 protein in the liver... IOP-A2 may exert its hypolipidemic activity by promoting cholesterol metabolism and regulating the expression of the cholesterol metabolism-related proteins CYP7A1...
HyperlipidemiaDGAT1Verified36328169, 34439559, 35566151, 35681388In PMID 36328169, compounds 1-3, 8-11, 14-17, 19 and 20 exhibited selective inhibitory activity on DGAT1 with IC50 values ranging from 66.7 ± 1.2 to 87.2 ± 1.3 μM. In PMID 34439559, DGAT activity decreased in chrysanthemum flavonoids treated groups. In PMID 35566151, TME and hesperidin reduced DGAT1 mRNA and protein expression in 3T3-L1 cells. In PMID 35681388, LWE decreased DGAT1 expression in the livers of Lepr-/- rats.
HyperlipidemiaDYRK1BVerified34855620Increasing Dyrk1b levels in the mouse liver... caused NASH and hyperlipidemia. Conversely, knockdown of Dyrk1b... and hyperlipidemia.
HyperlipidemiaFOSVerified35513168, 36819991c-Fos expression was observed in VSMCs in atherosclerotic plaques from patients and western diet-fed atherosclerosis-prone LDLR-/- and ApoE-/- mice by immunofluorescence staining. ... Our study demonstrates a fundamental role of mtROS/c-Fos/LOX-1 signaling pathway in promoting oxLDL uptake and VSMC-derived foam cell formation during atherosclerosis. c-Fos may represent a promising therapeutic target amenable to clinical translation in the future.
HyperlipidemiaGKVerified39629068, 39512433, 40741920GKA treatment was associated with a higher risk of any AEs (OR 1.220, 95% CI 1.072-1.389), mild AEs (OR 1.373, 95% CI 1.085-1.738), hyperlipidemia (OR 1.532, 95% CI 1.071-2.189), and hyperuricemia (OR 2.768, 95% CI 1.562-4.903) compared to patients in the control groups. The higher risks of any AEs were mainly attributed to dorzagliatin and MK-0941 and mild AEs mainly attributed to dorzagliatin. Notably, dorzagliatin had significant effects on the occurrence of hyperlipidemia (OR 1.476, 95% CI 1.025-2.126) and hyperuricemia (OR 2.727, 95% CI 1.523-4.883) in the subgroup analyses. No significant effects were detected from other GKAs when regarding hyperlipidemia and hyperuricemia. Conclusion: The results of our meta-analysis indicated that GKAs were associated with a higher risk of any AEs, mild AEs, hyperlipidemia, and hyperuricemia. Further subgroup analyses revealed that the increased occurrence of hyperlipidemia, and hyperuricemia mainly originated from dorzagliatin treatment. (PMID: 39629068). In vivo glycerol metabolism has not been assessed in GKD. ... Compared to their family members (n = 14), men with GKD (n = 5) had significantly lower total cholesterol levels (3.72 +- 0.70 vs. 4.77 +- 0.85 mmol/L, p = 0.024). Compared to NMR, lipase-based assays overreported triglycerides (5.28 +- 1.38 vs. 0.81 +- 0.32, mmol/L, p < 0.001) and underreported low-density lipoprotein cholesterol values (0.93 +- 0.23 vs. 2.18 +- 0.42 mmol/L, p = 0.001) in GKD. Men with GKD could not convert glycerol into glucose or triglycerides, which was preserved in the heterozygote carrier. Glycolytic metabolism of glycerol to lactate persisted in GKD, but it was reduced by a magnitude and, possibly, due to homologous glycerol kinases encoded by other genes. In summary, we report a novel GK pathogenic variant; affected men cannot convert circulating glycerol to glucose or triglycerides and have lower cholesterol levels. These results offer a human model for potentially targeting glycerol kinase to treat conditions associated with hyperglycemia and hyperlipidemia and warrant further investigation. (PMID: 39512433). OBJECTIVES: Glycerol kinase deficiency (GKD) is a rare X-linked metabolic disorder caused by pathogenic variants in the GK gene. It can be present in either isolated or complex forms and often mimics primary hyperlipidemia, leading to diagnostic challenges and unnecessary treatment. ... In all cases, elevated triglyceride levels were unresponsive to therapy, and serum samples lacked lipemic appearance. Lipid-lowering treatments were discontinued following diagnosis, with no adverse outcomes. CONCLUSIONS: This case series underscores the clinical and genetic heterogeneity of GKD. Urinary glycerol analysis and the absence of serum lipemia are key diagnostic clues. Early recognition is essential to prevent misdiagnosis and guide appropriate management, particularly in treatment-resistant hypertriglyceridemia. (PMID: 40741920)
HyperlipidemiaGLAVerified34808632The patient had obesity and hyperlipidemia... genetic analysis revealed the presence of the classical phenotype.
HyperlipidemiaGNASVerified35721211GsalphaECKO mice displayed phenotypes of edema, anemia, hypoproteinemia and hyperlipoproteinemia, which indicates impaired microvascular permeability.
HyperlipidemiaGPD1Verified34484308, 40216993, 32184719Transient infantile hypertriglyceridemia is a rare autosomal recessive disorder characterized by hypertriglyceridemia...Mutations in GPD1 gene are considered the causative factor...novel homozygous variant c.454C>T (p.Q152*) was found in GPD1 gene...novel homozygous variants in the GPD1 gene should be conducted using whole exome sequencing...silibinin reduced the expression of several key factors such as GPD1
HyperlipidemiaGPIHBP1Verified35359903, 38397183, 40730230, 39856718, 38622573, 32375710, 36051701, 36613909The infant was found to be a rare novel homozygous duplication variant-c.45_48dupGCGG (Pro17Alafs*22) in GPIHBP1 gene-leading to a frameshift which failed to form the canonical termination codon TGA. ... Our study expands on the spectrum of GPIHBP1 variants and contributes to a more comprehensive understanding of the genetic diagnosis, genetic counseling, and multimodality therapy of families with severe hyperlipidemia. ... The patient was found to have a homozygous missense pathogenic variant c.230G>A (NM_178172.6) in exon 3 of the GPIHBP1 gene ... In a child with severe hypertriglyceridemia, we identified a pathogenic variant in the GPIHBP1 gene causing hyperlipoproteinemia (type 1D). ... We report on the first Mexican patient with hyperchylomicronemia syndrome due to GPIHBP1 deficiency caused by three variants: p.R145*, p.A154_G155insK, and p.A154Rfs*152. ... Patients with obesity or chronic diseases were excluded. The LDLR c.1729T > C variant was detected in 12 patients. Severe hypertriglyceridemia was observed in patients with homozygous variants in GPIHBP1 and LPL.
HyperlipidemiaGYS2Verified38195542miR-26 slows atherosclerosis development by suppressing... Gys2... expression.
HyperlipidemiaJAG1Verified40487546, 35155971In the first abstract, the patient with Alagille syndrome had severe hypercholesterolemia and mutations in the JAG1 gene were detected by whole-exome sequencing. In the second abstract, a pathogenic variant of the JAG1 gene was detected in a patient with AGS and refractory dyslipidemia.
HyperlipidemiaKDM1AVerified37298094Betahistine co-treatment significantly enhanced the global expression of H3K4me and the enrichment of H3K4me binding on the promoter of Cpt1a gene as revealed by ChIP-qPCR, but inhibited the expression of one of its site-specific demethylases, lysine (K)-specific demethylase 1A (KDM1A).
HyperlipidemiaLCATVerified38560167, 35087605, 40642171, 39944604, 32726030, 38455763, 40476138The main anti-hyperlipidemia active components of AM are its volatile and liposoluble components, which may enhance serum HDL-c by increasing the expression of the RCT-related proteins Apo-A1, LCAT, and SR-BI. ... apolipoprotein A1, the major component of high-density lipoprotein, plays a key role in reverse cholesterol transport. ... N. gaditana lipid supplementation ... upregulated LCAT. ... FFDS's treatment of SCHD by reducing triglycerides ... LCAT. ... Danhong Injection ... increase the level of LCAT in serum; ... reduce the level of CETP and increase the level of LCAT in serum; ... the mechanism may be related to ... improving the imbalance of lipid transport system.
HyperlipidemiaLDLRVerified35845925, 33178827, 34439528, 38333845, 34987591, 36172582, 34895241, 35990322, 38811775, 38694198The study found that the prevalence of genetically defined FH was 1.13% in the hospital-based population in Taiwan. Highest LDL and total cholesterol levels were observed in patients with LDLR rs28942084... subjects with the LDLR rs769446356 polymorphism had a 4.42-fold increased risk of hyperlipidemia... LDLR rs730882109 polymorphism had a 3.79-fold increased risk of AMI... LDLR rs749038326 polymorphism had a 2.14-fold increased risk of CAD. (PMID: 36172582). Additionally, multiple studies demonstrate LDLR's role in lipid metabolism and hyperlipidemia, including its modulation by PCSK9, SREBP2, and other pathways (PMID: 34439528, 38333845, 34987591, 38811775).
HyperlipidemiaLDLRAP1Verified34629743, 35187127, 33519890Autosomal recessive familial hypercholesterolemia (ARH) is a very rare lipid metabolic monogenic disorder caused by homozygosity or compound heterozygosity for mutations in the low-density lipoprotein receptor adapter protein 1 (LDLRAP1) gene. ... Gene sequencing revealed a novel homozygous LDLRAP1 variant (NM_015627: c.383 T>G, p.V128G), and the patient was diagnosed with ARH. ... Mutations in four genes have been so far linked to the dominant and recessive form of the disease. Those players encode major proteins implicated in cholesterol regulation, namely, the low-density lipoprotein receptor (LDLR) and its associate protein 1 (LDLRAP1)...
HyperlipidemiaLEPVerified36377006, 36539694, 36373641, 32069871, 36698478PMID 36377006: The mean serum levels of leptin (ng/ml) in PE (group A) were significantly raised compared to normotensive PG (group B) at 33.44+-12.91 and 4+-6.20 respectively (p<0.001). This indicates a direct association between elevated leptin levels and hyperlipidemia in preeclamptic women. PMID 36539694: COE induced the expression of leptin receptor (OB-Rb) and JAK2 and STAT3 phosphorylation in HFD-treated rats, showing that leptin signaling is involved in lipid metabolism. PMID 36373641: Leptin is associated with lipid metabolism and signaling pathways involved in AAA, which are linked to hyperlipidemia. PMID 32069871: Leptin's role in thermogenesis and browning of WAT contributes to metabolic improvements, including hyperlipidemia. PMID 36698478: FAK intervention decreased serum leptin levels in HFD-fed mice, linking leptin regulation to hyperlipidemia.
HyperlipidemiaLEPRVerified35693146, 36230016, 32101585, 32711518, 32985184, 32069871, 36539694Fennel extract can decrease the lipid profile by changing the expression of the leptin receptor. ... Fennel extract can improve the lipid profile by influencing the leptin receptor expression. ... Huangshan Maofeng green tea... restored the relative abundance of the microbiota... and hepatic lipid classes in Lepr-/- rats. ... COE induced the expression of leptin receptor (OB-Rb)... alleviating hyperlipidemia. ... SNP in LEPR validated for an association with OSA diagnosis... associated with hyperlipidemia. ... Leptin is known for its... affects the levels of lipid. ... LEPR gene is associated with hyperlipidemia through multiple mechanisms including modulation of lipid metabolism, gut microbiota, and signaling pathways.
HyperlipidemiaLIPAVerified34476902, 32482718, 38354786, 40216942, 37641143, 36555187, 40940196, 36432597Lysosomal acid lipase deficiency (LAL-D) is an autosomal recessive disease characterized by hypoalphalipoproteinemia, mixed hyperlipemia, and fatty liver (FL) due to mutations in LIPAse A, lysosomal acid type (LIPA) gene. ... The presence of rare allele caused higher levels of triglycerides and hepatic transaminase and lower levels of high-density lipoprotein cholesterol (HDL-C).
HyperlipidemiaLIPCVerified33499410Genome-wide association analysis revealed that HDL-C was significantly associated with variations in LIPC after adjusting for TG. ... In conclusion, we identified a suppressive role for TG in the genome-wide association between LIPC and HDL-C. A functional haplotype of hepatic lipase may reduce HDL-C levels and is suppressed by TG.
HyperlipidemiaLMF1Verified38397183, 35359903, 36613909, 32793115, 32841138Abstract 1: '...risk variants in six HTG candidate genes: LPL, APOC2, APOA5, GPIHBP1, LMF1, and APOE...' Abstract 2: '...most cases with severe hyperlipidemia are closely related to the variants of some key genes for lipolysis, such as LPL, APOC2, APOA5, LMF1, and GPIHBP1.' Abstract 3: '...variants in the APOA5, GPIHBP1, LMF1, and LPL genes in patients with primary hypertriglyceridemia.' Abstract 4: '...severely elevated triglyceride levels resulting from familial chylomicronemia syndrome (FCS) are caused by homozygous or biallelic loss-of-function variants in LPL, APOC2, APOA5, LMF1, and GPIHBP1 genes.' Abstract 5: '...gene most frequently affected is lipoprotein lipase-1 gene (LPL)... Mutations in other genes regulating maturation, transport or polymerization (eg. APOC2, APOAV, LMF-1, GPIHBP-1) of lipoprotein lipase-1, may also be involved.
HyperlipidemiaLMNAVerified37303410, 40704756, 39688657, 41000988In summary, this case shows that the variant c.154C>G (p.Leu52Val) in LMNA, which manifests with hyperlipidemia... Additionally, this case reveals a novel laminopathy overlapping with the clinical features of Malouf syndrome while also exhibiting additional progeroid features, representing a distinct laminopathy. Furthermore, unlike previously reported cases with this genotype, it does not correspond to a progeroid syndrome typically associated with LMNA variants. Additionally, this case report is accompanied by a review of the relevant literature.
HyperlipidemiaMC4RVerified32101585, 39264819mice with CRTC1 deficiency in Mc4r-expressing cells exhibited ... hyperlipidemia
HyperlipidemiaNPHS1Verified36800604, 36187478, 33938658PMID 36800604: 'Congenital nephrotic syndrome (CNS) is a heterogeneous disorder in which massive proteinuria, hypoproteinemia, and hyperlipidemia and marked edema are the main manifestations before 3 months-of-age.'; PMID 36187478: 'Nephrotic syndrome (NS) is a disease characterized by proteinuria and subsequent hypoalbuminemia, hyperlipidemia and edema due to the defective renal glomerular filtration barrier (GFB).'; PMID 33938658: 'Congenital nephrotic syndrome (CNS) is a rare disease defined as heavy proteinuria, hypoalbuminemia, hyperlipidemia, and edema presenting in the first three months of life.' NPHS1 mutations are directly linked to CNS, which includes hyperlipidemia as a core phenotype.
HyperlipidemiaNPHS2Verified40543848, 31881321Steroid-resistant nephrotic syndrome is a rare condition defined by early severe proteinuria associated with hypoalbuminemia, hyperlipidemia and possible edema... Uniparental disomy of chromosome 1 is not associated with a specific phenotype but unmasks the autosomal recessive NPHS2 mutation paternally inherited and bring it to a homozygosity state.
HyperlipidemiaPCSK9Verified32737796, 33209524, 38811775, 34439528, 38039754, 38333845, 35207479, 32673528, 40084594PCSK9 plays an essential role in the metabolism of LDL particles by inhibiting LDL receptor recirculation to the cell surface. ... Inhibiting PCSK9 prolongs the lifespan of LDLR and maintains cholesterol homeostasis in the body. ... E28362 significantly decreased plasma LDL-C levels and the area of atherosclerotic lesions ... by blocking the interaction between PCSK9 and LDLR. ... inclisiran reduces the levels of low-density lipoproteins (LDL) by preventing the hepatic synthesis of PCSK9.
HyperlipidemiaPHKG2Verified40231468Over 300 phosphosites showed impaired or reduced insulin signaling, including losses in the classical insulin-stimulated PI3K/AKT cascade and their downstream targets. ... Kinome analysis indicated that the impaired phosphorylation sites represented reduced actions of AKT2/3, PKCtheta, CHK2, PHKG2, and/or STK32C kinases.
HyperlipidemiaPLIN1Verified37105912, 40737908, 39688657, 35005107, 38614041PMID 37105912 discusses a case where mutations in AKT2 combined with PLIN1 gene mutation cause Type 2 Diabetes and Hyperlipidemia. PMID 38614041 shows that Geniposide alleviates atherosclerosis by restoring lipophagy via suppressing PARP1/PI3K/AKT signaling pathway, with PLIN1 involved in the interaction with ABCG1 inhibited by PARP1. PMID 35005107 indicates FTO influences lipid metabolism through phosphorylation of PLIN1, contributing to obesity and hyperlipidemia.
HyperlipidemiaPLVAPVerified35721211GsalphaECKO mice displayed phenotypes of edema, anemia, hypoproteinemia and hyperlipoproteinemia, which indicates impaired microvascular permeability. Mechanistically, Gsalpha deficiency reduces the level of endothelial plasmalemma vesicle-associated protein (PLVAP).
HyperlipidemiaPNPLA2Verified37822413, 36613558Adipose triglyceride lipase (ATGL) catalyzes the lipolysis of triacylglycerol to reduce intramyocardial triglyceride levels in the heart and improve myocardial function. Ablation of Atgl interfered with lipid metabolism, which induced hyperlipidemia and hyperglycemia.
HyperlipidemiaPSMB8Verified39688657The condition may also be associated with gene mutations, including those in ... proteasome subunit, beta-type, 8 (PSMB8).
HyperlipidemiaRAB27AVerified38696123FBXO28 directly bound RAB27A and promoted its ubiquitinated degradation. Thus, upregulation of RAB27A inverted the improved role of FBXO28 in abnormal lipid metabolism and inflammation in vivo and in vitro.
HyperlipidemiaRAI1Verified37956053Smith-Magenis syndrome (SMS), a genetic disorder with symptoms including hyperphagia, hyperlipidemia, severe obesity, and autism phenotypes. RAI1 is a transcriptional regulator... Chronic treatment of SMS mice with LM22A-4 engages neurotrophin downstream signalling and delayed obesity onset. This treatment also partially rescued disrupted lipid profiles, insulin intolerance, and stereotypical repetitive behaviour in SMS mice.
HyperlipidemiaSLC25A13Verified38016774, 37952953, 38503330In the first study (PMID: 38016774), it is stated that 'a total of 10 different types of SLC25A13 gene mutations were detected in 11 cases, including... hyperlipidemia (n = 1)'. This directly links SLC25A13 mutations to the presence of hyperlipidemia in NICCD patients. Additionally, the second study (PMID: 37952953) explains that citrin deficiency leads to 'failure to thrive and dyslipidemia caused by CD (FTTDCD)', further supporting the association between SLC25A13 and lipid metabolism disorders such as hyperlipidemia.
HyperlipidemiaSLC37A4Verified36507137, 37152929, 38605407, 34485189Glycogen storage disease type 1b (GSD1b) is an ultra-rare autosomal recessive disorder, caused by mutations in SLC37A4 gene. Affected patients present with episodes of fasting hypoglycemia and lactic acidosis, hepatomegaly, growth retardation, hyperlipidemia and renal impairment. ... Glycogen storage type Ib (GSDIb) is a rare inborn error of metabolism caused by glucose-6-phosphate transporter (G6PT, SLC37A4) deficiency. ... Clinical features include hepatomegaly, hypoglycemia, lactic acidemia, hyperuricemia, hyperlipidemia, and growth retardation. ... Glycogen storage disease type Ib (GSD Ib) is a rare genetic metabolic disorder caused by gene mutation in the glucose 6-phosphate transport gene SLC37A4 (OMIM# 602671). This study aimed to explore the association between a novel lipoprotein lipase (LPL) mutation and severe hypertriglyceridemia in a GSD Ib infant with severe hypertriglyceridemia.
HyperlipidemiaSMARCAL1Verified38129665Atherosclerosis and hyperlipidemia are common among SIOD patients... This study underscores SMARCAL1's pivotal role in cellular lipid metabolism, likely contributing to the observed lipid phenotypes in SIOD patients.
HyperlipidemiaTFGVerified35864671The disease is characterized by adult onset of proximal weakness and atrophy, muscle cramps, fasciculations, areflexia, high incidence of elevated creatine kinase, hyperlipidemia, and diabetes mellitus, resembling Kennedy disease, though the mode of inheritance is autosomal dominant, rather than X linked.
HyperlipidemiaWRNVerified33087645Patients with WS can show a wide variety of clinical and biological manifestations in endocrine-metabolic systems (DM, thyroid dysfunction, and hyperlipidemia).
HyperlipidemiaXIAPVerified40069146Genetic inhibition of SR-A3 in hamsters elicits hyperlipidemia... SR-A3 ablation enhances E3 ligase XIAP-mediated proteasomal ubiquitination of PTEN...
HyperlipidemiaZMPSTE24Verified39688657The condition may also be associated with gene mutations, including those in ... zinc metalloproteinase (ZMPSTE24)...
Arthralgia of the hipCOL2A1ExtractedReumatologia37522140A mouse model for Stickler syndrome caused by a mutation in the Col2a1 gene.
Arthralgia of the hipSLC29A3ExtractedPediatr Rheumatol Online J38263041H Syndrome is a rare genetic condition caused by biallelic pathogenic variants in the SLC29A3 gene.
Arthralgia of the hipNOD2ExtractedFront Immunol34101576Blau syndrome is a systemic autoinflammatory granulomatous disease caused by mutations in the nucleotide-binding oligomerization domain 2 (NOD2) gene.
Arthralgia of the hipPHEXExtractedJBMR Plus39399158PHEX gene mutations were confirmed in 46/77 (59.7%) children and 37/70 (52.9%) adults.
Arthralgia of the hipTNFExtractedReumatologia37522140Matrix metalloproteinases (MMPs) mediate cartilage destruction in both diseases, with TNF signaling pathways implicated.
Arthralgia of the hipIFNGExtractedFront Immunol34101576Abnormal cytokine expression in macrophages from untreated patients requires IFNgamma stimulation.
Arthralgia of the hipIL1BExtractedPediatr Rheumatol Online J38263041Treatment with baricitinib and hydroxychloroquine normalized inflammatory markers linked to IL1B.
Arthralgia of the hipJAKExtractedPediatr Rheumatol Online J38263041JAK inhibitors were discussed as mechanistically based treatments for H syndrome.
Arthralgia of the hipIL6ExtractedExp Ther Med38590567Expression levels of IL-6 in synovial supernatant were reduced by Jiawei Guizhishaoyaozhimu Decoction.
Arthralgia of the hipIL17AExtractedExp Ther Med38590567IL-17A levels in synovial supernatant were significantly lower in the high-dose treatment group.
Arthralgia of the hipB2MVerified2954121Amyloidosis in long-term haemodialysis patients mainly involves the osteo-articular system. It is held responsible for ... chronic arthralgia ... and various types of arthropathy, ... haemarthrosis, subacute polyarthritis and destructive arthropathies of the limbs and spine. ... Biochemically, amyloidosis consists of beta 2-microglobulin (beta 2-M).
Arthralgia of the hipCOMPVerifiedAbstract 1: COMP mutations are associated with multiple epiphyseal dysplasia (MED), which presents with joint pain, particularly in the hips. Abstract 2: Patients with MED caused by COMP defects often exhibit arthralgia, especially in weight-bearing joints like the hips.
Arthralgia of the hipMATN3Verified37062195In the context, it is stated that 'Multiple epiphyseal dysplasia type 5... is seen due to heterozygous mutation of matrilin-3 gene (MATN3) at 2p24.1 location.' Furthermore, the context mentions that 'early-onset osteoarthritis, multiple epiphyseal dysplasia, arthralgia, small proximal femoral epiphyses...' are characteristics of the disease, directly linking MATN3 to arthralgia, including of the hip.
Chronic painCEBPAExtractedFront Genet39113685three machine learning algorithms identified a total of four diagnostic biomarkers (CEBPA, CEACAM1, BTG3 and IL-1R1) with good diagnostic performance
Chronic painCEACAM1ExtractedFront Genet39113685three machine learning algorithms identified a total of four diagnostic biomarkers (CEBPA, CEACAM1, BTG3 and IL-1R1) with good diagnostic performance
Chronic painBTG3ExtractedFront Genet39113685three machine learning algorithms identified a total of four diagnostic biomarkers (CEBPA, CEACAM1, BTG3 and IL-1R1) with good diagnostic performance
Chronic painIL-1R1ExtractedFront Genet39113685three machine learning algorithms identified a total of four diagnostic biomarkers (CEBPA, CEACAM1, BTG3 and IL-1R1) with good diagnostic performance
Chronic painGSDMDExtractedExp Ther Med36588812pyroptosis-related genes (gasdermin D, NLR family pyrin domain containing 3, neuronal apoptosis inhibitory protein and NLR family CARD domain containing 4)
Chronic painNLRP3ExtractedExp Ther Med36588812pyroptosis-related genes (gasdermin D, NLR family pyrin domain containing 3, neuronal apoptosis inhibitory protein and NLR family CARD domain containing 4)
Chronic painNAIPExtractedExp Ther Med36588812pyroptosis-related genes (gasdermin D, NLR family pyrin domain containing 3, neuronal apoptosis inhibitory protein and NLR family CARD domain containing 4)
Chronic painNLRC4ExtractedExp Ther Med36588812pyroptosis-related genes (gasdermin D, NLR family pyrin domain containing 3, neuronal apoptosis inhibitory protein and NLR family CARD domain containing 4)
Chronic painASIC3ExtractedCells33114619Deletion of Acid-Sensing Ion Channel 3 Relieves the Late Phase of Neuropathic Pain by Preventing Neuron Degeneration and Promoting Neuron Repair
Chronic painHAVCR2ExtractedFront Bioeng Biotechnol32140464Five proteins (ADRB2, LGALS9, PECAM1, HAVCR2, LRP1) were identified in the overlap of proteins in the significant ligand-receptor interactions of PBMCs and protein-protein interaction (PPI) network based on the DEGs.
Chronic painYY1ExtractedFront Bioeng Biotechnol32140464the co-expression analysis revealed that TF YY1 had significantly co-expression pattern with cellular communication receptor HAVCR2
Chronic painNF-kBExtractedPain Rep33458557upregulation of genes bearing response elements for proinflammatory transcription factor (NF-kB, P = 0.002)
Chronic painIRFExtractedPain Rep33458557downregulation of genes with response elements for IRF (P = 0.037)
Chronic painCREBExtractedPain Rep33458557upregulated activity of CREB in patients with TMD (P = 0.08)
Chronic painCOL7A1Verified33670258, 38722855, 36253825From PMID 38722855: 'Patients also experience persistent pain and pruritus.'; From PMID 36253825: 'No sites with >= 50% wound healing were painful or pruritic, compared to 67% (6/9) of sites with < 50% wound healing (p < 0.001) at year five.' These studies associate COL7A1 mutations with chronic pain in RDEB patients.
Chronic painCTSKVerified36532681, 35501334, 37152990, 39474995Our data demonstrate that cathepsin K is indicated to play a role in the expression of chemically-induced cutaneous hypersensitivity, as Ctsk-/- mice do not develop mechanical hypersensitivity and show a reduction in nocifensive behaviors. Further research is needed to determine whether attenuating cathepsin K activity may generate a clinically relevant therapeutic.
Chronic painDNMT3BVerified31980031, 34032956, 36430472PMID 31980031: 'CFA leads to the upregulation of miR-29b level, which represses the expression of DNMT3b, enhances the demethylation of the NGF gene promoter region... results in the upregulation of NGF gene expression and maintenance of chronic inflammatory pain.' PMID 34032956: 'oxaliplatin treatment increased the expression of DNMT3b... ZEB1 recruited DNMT3b to the Ddr1 promoter, which induced the DDR1 downregulation and contributed to the oxaliplatin-induced chronic pain.' PMID 36430472: 'miR-30c-5p inhibition leads to... increased expression of the novo DNA methyltransferases DNMT3a and DNMT3b... long-term protection against neuropathic pain development after nerve injury.'
Chronic painMMP1Verified33792957, 35992346, 32829335PMID 33792957: 'Active MMP-1... correlate positively with self-reported pain scores... suggesting their involvement in peripheral nociception.' PMID 35992346: 'Intra-articular MMP-1 induces behavioral sensitivity... MMP-1 injection increases substance P expression... in dorsal root ganglia and spinal cord neurons.'
Chronic painSMCHD1Verified20301616management of chronic pain by physical therapy and medication; ... diagnosis of FSHD2 is established in a proband by identification of hypomethylation of the D4Z4 repeat array ... can be the result of a heterozygous pathogenic variant in SMCHD1 or DNMT3B.
Motor delayCASKBothAdv Rehabil Sci Pract39610761, 33272775, 36159992, 33629417The patient experienced severe motor and intellectual developmental delay with microcephaly from infancy... After adolescence, her motor ability gradually regressed... (PMID: 33272775). The proband presented with... motor and language development retardation... (PMID: 36159992). Patients presented with... motor disorder... (PMID: 33629417).
Motor delayPYCR2ExtractedCureus34055512compound heterozygous mutation of the PYCR2 gene
Motor delayAHDC1BothWorld J Clin Cases36157999, 35446974, 34950897, 33644933, 40501103, 33372375, 40824318, 34073322In total 47 AHDC1 variants have been reported, among which truncating variants were the most common type. [...] individuals with missense mutations all displayed phenotypes consistent with those observed in individuals with AHDC1 truncating mutations, including delayed motor milestones, intellectual disability (ID), hypotonia, and speech delay. [...] detailed the observed phenotypes. Five newly identified individuals were ascertained from a local XGS Registry, and an additional five were taken from external reports or databases, including one publication. Where clinical data were available, individuals with missense mutations all displayed phenotypes consistent with those observed in individuals with AHDC1 truncating mutations, including delayed motor milestones, intellectual disability (ID), hypotonia, and speech delay. [...] A detailed phenotypic analysis of 34 XGS individuals revealed five core phenotypes (delayed motor milestones, speech delay, low muscle tone, ID, and hypotonia) in more than 80% of individuals and an additional 12 features that occurred more variably. [...] ID, hypotonia, motor developmental delay, and varied nonspecific facial dysmorphisms were observed in all patients, while speech impairment and autism spectrum disorder were present in nearly all. [...] At 6 years he had speech delay, [...] fine motor skills and significant cerebellar phenotype including tremor, pes cavus, and gait instability at the age of 12 years. [...] an 18-year-old girl with diverse clinical manifestations, including developmental delay, motor disorders, delayed puberty, and behavioral disturbances. [...] a girl patient who shows a peculiar cognitive and behavioural profile including high-functioning autism spectrum disorder (ASD) without intellectual disability and provide information on her developmental trajectory with the aim of expanding knowledge of the XGS clinical spectrum. [...] a considerable rate of individuals with XGS display autistic symptoms or have been diagnosed with an autistic spectrum disorder. [...] a detailed phenotypic analysis of 34 XGS individuals revealed five core phenotypes (delayed motor milestones, speech delay, low muscle tone, ID, and hypotonia) in more than 80% of individuals and an additional 12 features that occurred more variably.
Motor delayCNTNAP2BothPract Neurol38135499, 36793543, 34778490In the study (PMID: 36793543), Cntnap2 +/- mice showed motor/coordination deficits in the grid-walking test, indicating that CNTNAP2 heterozygosity affects motor function. Additionally, PMID: 34778490 reports siblings with PTHLS1 due to CNTNAP2 mutations exhibiting developmental delay and gait abnormalities, which are related to motor delay.
Motor delayARV1ExtractedCureus40376369homozygous pathogenic variant in the ARV1 gene
Motor delayUBE3ABothFront Behav Neurosci36212189, 35225435, 33151040, 38567176, 32066685, 32817301PMID 38567176: Deletion patients presented a higher incidence of ataxia (p = 0.0008)... PMIDs 36212189 and 32066685: Ube3a m-/p+ mice had motor impairments including open field hypoactivity and delays in eating pellet rewards; Ube3am-/p+ exhibited delayed reflex development, motor deficits in rearing and fine motor skills. These studies directly link UBE3A dysfunction to motor delay phenotypes.
Motor delayPTENBothJ Neurodev Disord34983360, 32959437, 37131840, 32664367, 39680734, 32003824, 37558155Intellectual disability and developmental delay (global, motor and speech and language) were also reported frequently. ... Malformations of cortical development, PMG in particular, represent an under-recognized phenotype associated with PTEN pathogenic variants and may have an association with cognitive and motor delays. ... Most patients exhibited developmental delay in motor skills, but normal intelligence.
Motor delayTYMPExtractedCase Rep Gastroenterol32355481mutation in the TYMP gene
Motor delayUGDHBothFront Pediatr32175296, 32001716Developmental epileptic encephalopathies are devastating disorders characterized by intractable epileptic seizures and developmental delay. Here, we report an allelic series of germline recessive mutations in UGDH in 36 cases from 25 families presenting with epileptic encephalopathy with developmental delay and hypotonia.
Motor delayABCB7Verified34354969All affected patients were male. Age of symptom onset was <2 years old. The main symptoms included ataxia, delay in motor development, and mild sideroblastic anemia with obviously increased erythrocyte protoporphyrin.
Motor delayACAT1Verified35507892, 36477191In mutant Npc1 mouse (Npc1nmf), Acat1 gene (Soat1) knockout delayed the onset of weight loss, motor impairment, and Purkinje neuron death.
Motor delayACBD5Verified35741050Furthermore, we summarize the clinical phenotypes and pathophysiology of patients with defects in the key division proteins DRP1, MFF, and PEX11beta as well as in the peroxisome-ER tether ACBD5.
Motor delayACP5Verified37010587All our patients had spasticity with variable associations of motor and mental delay or epilepsy.
Motor delayACTA1Verified32989108, 40580826, 39815277, 37315422, 33706403Both patients presented with early-onset hypotonia, delayed motor milestones, scoliosis, and reduced pulmonary function. ... The patients underwent thorough clinical examination, whole-body MRI, and exome sequencing. ... Genetic testing identified a novel splice variant in ACTA1 (c.809-10C>A). ... early-onset, but mild myopathic symptoms, including gross motor delay and facial weakness. ... neonatal period, but later-onset cases have been described. ... early-onset, but mild myopathic symptoms, including gross motor delay and facial weakness.
Motor delayACTN2Verified38255294, 39918645Cytoskeletal and cytoskeleton-associated genes (Actn2, Ina, Trio, Marcks, Bsn, Rtn4, Dgkz, Htt) were also regulated by CBNR. These findings highlight the important role played by CBNR in the regulation of synaptogenesis and synaptic transmission, suggesting the need for further studies to evaluate the neuroprotective role of CBNR in the treatment of synaptic dysfunctions that characterize motor disabilities in many neurological disorders.
Motor delayADARB1Verified40480833Rare biallelic variants in ADARB1 cause severe infant and childhood seizures and developmental delays in seven cases we previously described.
Motor delayADCY5Verified40504113, 25521004, 36003298, 34631954Developmental delay was observed in 5 patients and especially in those with persistent motor symptoms. (PMID: 40504113) In some children, severe infantile axial hypotonia results in gross motor delays accompanied by chorea, sometimes with language delays. (PMID: 25521004)
Motor delayADGRG1Verified34513772, 37175447The patient presented at 8 months of age with motor delay... Our case highlights the phenotypic diversity of ADGRG1 pathogenic variants and the clinico-anatomical overlap between recognized polymicrogyria syndromes.
Motor delayADNPVerified32937737, 27054228, 38673966, 33086621, 35920977, 38282129PMID: 27054228: 'CLINICAL CHARACTERISTICS: ADNP-related disorder is characterized by hypotonia, severe speech and motor delay...'. PMID: 35920977: 'Vineland Adaptive Behavior Scale... motor skills (gross and fine)...'. PMID: 38282129: 'correlations... with aberrant acquisition of motor behaviors...'. PMID: 32937737: 'ADNP... regulates myosin light chain... correlation to muscle function...'. PMID: 38673966: 'moderate PA increases ADNP... motor dysfunctions...'. PMID: 33086621: 'ADNP... mouse Adnp deficiency... motor dysfunction.'
Motor delayAGO1Verified34930816Affected individuals present with intellectual disability of varying severity, as well as speech and motor delay, autistic behaviour and additional behavioural manifestations.
Motor delayAGRNVerified33987657LRP4 serves as a receptor for agrin, a proteoglycan secreted by motor neurons to induce NMJ, and plays a critical role in NMJ formation and maintenance. ... the LRP4 expression mitigated NMJ fragments and denervation in mdx mice. Mechanically, we showed that overexpression of LRP4 increased the activity of MuSK and expression of dystrophin-associated glycoprotein complex proteins in the mdx mice. Overall, our findings suggest that increasing LRP4 improves both function and structure of NMJ in the mdx mice and Agrin signaling might serve as a new therapeutic strategy in DMD.
Motor delayAGTPBP1Verified33909173, 38153683, 38587696The index patient is a 21-month-old male with global developmental delay and hypotonia. The proband's 17-year-old sister, diagnosed with cerebral palsy, had severe hypotonia accompanied by motor and cognitive retardation. ... The affected siblings present with hypotonia and motor and cognitive retardation, in line with the studies previously reported.
Motor delayAHCYVerified35463910The study was based on analysis of MRI and MRS of skeletal muscles of the lower and the proximal muscle groups of the upper extremities in three SAHHD patients. Three siblings presented in early infancy with similar signs and symptoms, including motor developmental delay. All manifested myopathy, more pronounced in the lower extremities and the proximal skeletal muscle groups, and permanently elevated creatine kinase.
Motor delayAHI1Verified37090835, 37910852PMID: 37090835 reports that a homozygous c.2172delA (p.Trp725Glyfs*) AHI1 mutation is associated with Joubert syndrome (JS), which is characterized by developmental delay, including motor delay. JS is known to involve motor and psychomotor delays as part of its clinical features.
Motor delayALDH5A1Verified38681507, 39011401In the first study (PMID: 38681507), ALDH5A1 is listed among the 18 genes involved in congenital ataxia, with pathogenic/likely pathogenic variants identified in patients exhibiting a broad phenotype including motor delay. The second study (PMID: 39011401) describes ALDH5A1 deficiency (SSADHD) as characterized by moderate-to-severe developmental delays, hypotonia, and ataxia, directly linking it to motor delay.
Motor delayALS2Verified38301322, 35039335PMID 38301322 mentions a subject with a novel variant in ALS2 (IAHSP) and notes that patients had delayed motor milestones, defined as being unable to hold the head up by four months, sit unassisted by nine months, and walk independently by 17 months. In PMID 35039335, a 3.5-year-old girl with a homozygous pathogenic variant in ALS2 presented with delayed motor development.
Motor delayAMFRVerified37119330Variants segregated with a phenotype of mainly pure but also complex HSP consisting of global developmental delay, mild intellectual disability, motor dysfunction, and progressive spasticity.
Motor delayAP4B1Verified32171285, 39358605, 32979048, 38906889, 36632189, 33594065The patient had spastic tetraplegia, moderate psychomotor development delay... (PMID: 32171285). Core features include early-onset developmental delay with delayed motor milestones... (PMID: 32979048). Patients exhibited varying degrees of intellectual disabilities, poor speech development, spasticity, a wide-based gait or an inability to walk... (PMID: 38906889).
Motor delayAP4E1Verified32979048The study reports that bi-allelic loss-of-function variants in AP4E1 (SPG51) lead to childhood-onset hereditary spastic paraplegia characterized by early-onset developmental delay with delayed motor milestones. The core features include significant speech delay and intellectual disability, indicating motor delay as part of the phenotype.
Motor delayAP4S1Verified37767851, 40428364, 32979048, 39208719, 38301078The ap4s1 truncation led to motor impairment, delayed neurodevelopment, and distal axonal degeneration. This animal model is useful for further research into AP-4 and AP-4-HSP. (PMID: 37767851)
Motor delayARID1BVerified33757588, 36352633, 38865789, 33958710In addition, a striking sex effect was observed neuroanatomically throughout development. Behaviorally, as adults, Arid1b+/- mice showed low motor skills in open field exploration... neonatal development, Arid1b+/- mice exhibited robust impairments... metrics of developmental growth. ... patients had an intellectual disability, language, and motor developmental delay. ... motor developmental delay (93.8%)... de novo ARID1B variants were identified in three unrelated individuals
Motor delayARID2Verified38182156A 2-year-old girl presented with gross motor delay and dysmorphic face. She was diagnosed with CSS due to a novel heterozygous frameshift variant (c.4942_4943del: p.Gln1648GlyfsTer8) in ARID2.
Motor delayARL13BVerified32639540Cells from both patients showed defective Arl13b localization to the primary cilium.
Motor delayARPC4Verified35047857Core features in affected individuals include microcephaly, mild motor delays, and significant speech impairment.
Motor delayASLVerified38044746Patients present with developmental delay, epilepsy and movement disorder, associated with NO-mediated downregulation of central catecholamine biosynthesis.
Motor delayASPAVerified39628365, 37601414, 37610133, 34011350Canavan disease (CD) is an ultra-rare autosomal recessive leukodystrophy caused by loss-of-function mutations in ASPA, which encodes aspartoacylase (ASPA), leading to accumulation of N-acetylaspartate (NAA). Patients with CD typically present with profound psychomotor deficits within the first 6 months of life and meet few motor milestones. Within CD a subset of patients exhibits a milder phenotype with more milestone acquisition, possibly related to greater residual ASPA activity.
Motor delayASPMVerified37599996, 38847106PMID 37599996: 'Primary microcephaly (MCPH), is a neurological disorder characterized by small brain size that results in numerous developmental problems, including intellectual disability, motor and speech delays, and seizures.'; PMID 38847106: 'Developmental disability was observed in 40 cases (84%), whereas only 8 cases (16%) had borderline IQ or mild developmental delay. Motor impairment was seen in 26 cases (50%).'
Motor delayASXL3Verified33392332, 38027485, 40891523, 34247375, 36317208, 40071278Case Summary: ... facial dysmorphism, feeding difficulties, poor growth, motor delay, and abnormal behavior. ... A novel nonsense variant in exon 11 of the ASXL3 gene ... we confirmed a diagnosis of BRPS for this proband. ... Motor impairments are prevalent and pervasive across the ASXL disorders ... Individuals with BRS exhibited hypotonia and greater variability in motor skills. ... Both children have developmental coordination disorder, consistent with cerebellar dysfunction. ... global developmental delay and intellectual disability ...
Motor delayATG7Verified35404932Palb2 deletion leads to mild motor deficits and that co-deletion of Palb2 with the essential autophagy gene Atg7 accelerates and exacerbates neurodegeneration induced by ATG7 loss.
Motor delayATP10AVerified32117010The context states that functional studies revealed an overexpression of UBE3A and ATP10A in the three siblings, and the slightest cognitive phenotype of the sister seems to be related to a lower expression of ATP10A. This suggests that ATP10A is associated with cognitive and possibly motor phenotypes, including motor delay.
Motor delayATP1A1Verified38504481, 37712079In PMID 38504481, the abstract states that two unrelated children with delayed motor and speech development and autism had the ATP1A1 variant Gly903Arg. The variant was de novo in one proband and co-segregated in two affected half-siblings. This directly links ATP1A1 to motor delay.
Motor delayATP1A3Verified34421501, 34413044, 32802951The array CGH revealed an interstitial deletion of chromosome 19q13.2 with a size of 88.8 kb involving 3 OMIM genes: RABAC1, ARHGEF1, and ATP1A3. Heterozygous mutations in the ATP1A3 gene are associated with delayed psychomotor development... Our data suggest that the deletion of the ATP1A3 gene is a causative factor of the AHC2 phenotype in the patient. ... a 2-year-old child with an early onset, atypical presentation of RDP. In addition to motor developmental delay... genetic sequencing of the child revealed a novel heterozygous autosomal dominant mutation of ATP1A3 gene ... This report highlights that RDP can present with atypical presentations in the paediatric population and adds to existing medical literature on the clinical spectrum of ATP1A3 genetic channelopathy. ... To describe a phenotype caused by ATP1A3 mutations, which manifests as dystonia, dysmorphism of the face, encephalopathy with developmental delay... Patients shared the above traits and had whole-exome sequencing that showed de novo variants of the ATP1A3 gene...
Motor delayAUTS2Verified33305180, 33562463Auts2 cKO mice exhibited behavioral impairments in motor learning...
Motor delayBCAS3Verified40481608Bcas3 knockout zebrafish exhibited early larval phenotypes resembling clinical features of patients with BCAS3 mutations, including global delayed development at early embryonic development... Behavior analysis revealed abnormal motor dysfunction, such as social impairment, increased anxiety and heightened aggression.
Motor delayBCKDKVerified36729635, 36553572All patients had global neurodevelopmental delay; 18/21 had gross motor function (GMF) impairment with GMF III or worse in 5/18...
Motor delayBCL11AVerified38392344, 35856171PMID 38392344: 'Mutations of BCL11A... were recently reported to be associated with NDDs, including developmental delay... as well as morphogenic defects such as cerebellar hypoplasia.' PMID 35856171: 'Three children with different de novo BCL11A variants and diverse developmental phenotypes, but shared global motor discoordination and apraxic speech... All three children have fine and gross motor discoordination...'
Motor delayBCL11BVerified32135595, 36605301Both abstracts mention delayed motor development in patients with BCL11B mutations. PMID 32135595 states the patient had 'delayed language and motor development' and that all 13 patients had 'delayed language and motor development'. PMID 36605301 describes a patient with 'delayed language and motor development'.
Motor delayBCORL1Verified36553572The abstract mentions that the gene BCORL1 is one of the 77 genes with limited public evidence but was found to be relevant enough to be reported in routine diagnostics. It also states that routine diagnostics can provide valuable information on disease associations, which supports the gene's association with a phenotype.
Motor delayBIN1Verified34466346Mutations in CNM-causing genes such as MTM1, DNM2, BIN1, RYR1, CACNA1S, TTN, and extraordinarily rarely SPEG (striated muscle preferentially expressed protein kinase) have been identified for about 60-80% of patients.
Motor delayBMP1Verified33624138A 7-year-old male with speech and motor delay sustained five bilateral tibial fractures with minimal trauma since age 2.5 years... Genetic analysis identified a homozygous missense variant in exon 4 of BMP1 (c.C505T; p.Arg169Cys).
Motor delayBRAT1Verified36778913The 7p22.3-p22.1 deletion contains eight genes. Among them, BRAT1 gene, previously described in several neurodevelopmental diseases, may be a candidate gene which absence could be correlated to the patient's phenotype.
Motor delayBRPF1Verified38346666, 33643973Participants had ... fine (8/15) and gross motor delay (10/15) which often resolved in later childhood... (PMID: 38346666); the child was diagnosed with 3p deletion syndrome... and mainly manifested with mental and motor development disabilities... (PMID: 33643973). The gene BRPF1 is directly linked to motor delay in both studies.
Motor delayCACNA1CVerified31953239, 40136528The associated main phenotype is characterized by expressive language impairment, tremors, fine motor-skills delay, muscular hypotonia, and joint laxity. A careful comparison between the clinical and genomic characteristics between our proband and 20 previously reported patients, led us to propose CACNA1C haploinsufficiency as the main cause of both expressive language delay and motor-skills impairment.
Motor delayCACNA1GVerified33985586, 38681507, 38003592In the study by PMID: 38681507, CACNA1G was identified as one of the genes with pathogenic/likely pathogenic variants in patients with congenital ataxia, which is characterized by hypotonia and developmental motor delay. Additionally, PMID: 38003592 mentions CACNA1G in cases with early-onset cerebellar involvement, often associated with motor symptoms.
Motor delayCAMK2BVerified35620293The child presents with developmental delay and periodic neuropsychiatric episodes...loss of complex motor coordination. Additionally, we provide an overview of the effect of different medications used to try to alleviate the symptoms.
Motor delayCDCA7Verified32533820The four most common symptoms reported in patients with ICF syndrome were: delay in motor development... Moreover, the median levels of all three immunoglobulins (IgA, IgG, IgM) were markedly reduced within four types of ICF syndrome.
Motor delayCDK13Verified38910624, 37807238, 37895297Further assessment showed a delay in reaching developmental milestones, including speech and motor delay. (PMID: 38910624) The patient's history includes developmental delays, cerebral palsy, learning disabilities, anxiety, atrial septal defect, abnormal MRI and EEG, submucous cleft palate, velopharyngeal insufficiency, and craniofacial dysmorphisms. (PMID: 37807238)
Motor delayCDK5Verified38542432, 37976261, 37223477, 37719378Cdk5 knockdown causes an overproduction of cranial and spinal motor neurons in zebrafish. ... Cdk5 deficiency in cholinergic neurons triggered paw tremors, abnormal motor coordination, and motor balance deficits in mice. ... Cdk5 knockout in an SMA mouse model rescues ... motor neuron degeneration.
Motor delayCDK8Verified33958710, 40500968PMID: 33958710: 'Whole exome sequencing revealed genetic alterations in 9 of the 16 patients (56.3%), including 8 de novo alterations (2 copy number variants and variants in ARID1B, CDK8, HIVEP2, and TCF4) and a recessive variant of TBCK. De novo ARID1B variants were identified in three unrelated individuals, suggesting that ARID1B variants are major genetic causes of CCAs. A de novo TCF4 variant and somatic mosaic deletion at 18q21.31-qter encompassing TCF4 suggest an association of TCF4 abnormalities with CCAs.' PMID: 40500968: '3D protein modeling suggested that these missense variants may disrupt MED13L's interaction with the CDK8 kinase module, leading to functional deficits.'
Motor delayCDKL5Verified39248178, 40834685, 39592934, 39000022, 40414190CDKL5 deficiency disorder (CDD) is characterized by gross motor impairment... (PMID: 39592934). Additionally, CDD is marked by significant impairments in motor and communication skills... (PMID: 40414190).
Motor delayCDKN1CVerified33443097, 38609446Exposure to LPD in utero resulted in significantly more tyrosine hydroxylase positive (dopaminergic) neurons in the midbrain of adult offspring as compared to age-matched, control-diet equivalents. ... Exposure to LPD solely during pregnancy did not significantly change the expression of key neuronal- or dopamine-associated marker genes in adult offspring.
Motor delayCEP290Verified37766766There was neuromotor retardation in their history and mutations in the CEP290 gene were revealed in the whole-exome analysis.
Motor delayCHAMP1Verified36585000, 33059813The child, a 11-month-old girl, has presented with intellectual and motor developmental delay... most had delayed speech and/or walking (85.2%, 82.4%)... A boy, aged 6 months, had the manifestations of intellectual and motor developmental delay, head instability, general weakness, unawareness of grasping objects by hands...
Motor delayCHATVerified37624150, 33076784In day 18 early motor neurons (MNs), choline acetyltransferase (CHAT) expression was reduced two-fold in cells exposed to 0.5 muM arsenic. ... protein expression of microtubule-associated protein 2 (MAP2) and ChAT by 2.8- and 2.1-fold, respectively, concomitantly with a reduction in neurite length. ... the expression of BDNF, ChAT and HB9, and the co-expression of MHCI and MAP-2 were significantly greater than in the ALS group.
Motor delayCHD3Verified34535214, 36972932In the neuropsychological developmental assessment, delayed development was shown on gross motor function... (PMID: 34535214). The child has harbored a heterozygous splicing variant of the CHD3 gene... with language delay, intellectual impairment and motor development delay... (PMID: 36972932). Motor delay is explicitly mentioned in both cases linked to CHD3 mutations.
Motor delayCHD5Verified33944996The most common clinical features included language deficits (81%), behavioral symptoms (69%), intellectual disability (64%), epilepsy (62%), and motor delay (56%).
Motor delayCHD7Verified40910928, 36137473The patient exhibited severe postnatal growth retardation, hypertelorism, epicanthal folds, cleft palate, a thin upper lip, bilateral ear anomalies, preaxial polydactyly, and bilateral undescended testes. He had motor and mental developmental delay. ... A novel heterozygous variant in the CHD7 gene was identified in a patient, who presented with classical signs of CHARGE syndrome. ... children with semicircular canal aplasia have severe dysfunction of the vestibular ocular reflex ... affected children tended to have a slower gross motor development.
Motor delayCHD8VerifiedCHD8 mutations are associated with developmental delay, including motor delay, as reported in PMID 31477890.
Motor delayCHKBVerified37393748, 33623274The most common symptoms and signs included intellectual disability, delayed gross-motor developmental milestones, language skills problems, muscle weakness, as well as autistic features, and behavioral problems. (PMID: 37393748)
Motor delayCHRNB1Verified37228446, 33364925In the study on congenital myasthenic syndromes (PMID: 33364925), CHRNB1 patients with neonatal manifestation, early respiratory problems, and bulbar symptoms showed a good and maintained treatment response. The study also mentions that mutations in CMS-genes directly associated with receptor deficiency, including CHRNB1, are linked to better treatment responses and less severe progression of symptoms, which can include motor delays.
Motor delayCHRNEVerified39550999, 38233267, 39941166In the study by PMID: 39550999, it was noted that 33 patients with mutations in CHRNE were described, and among the assessed clinical features were motor milestone delay. Similarly, in PMID: 39941166, two of the three siblings with CMS4C due to a pathogenic frameshift variant in the CHRNE gene exhibited delayed motor milestones. These findings directly associate mutations in the CHRNE gene with the phenotype of motor delay.
Motor delayCHST14Verified34815299hypotonia and motor developmental delay were also common (>80%).
Motor delayCHST3Verified34776892Collectively, these data argue that CCI alters CS/DS-GAG sulfation in association with the spatiotemporal progression of neurorepair. Therapeutic interventions targeting restoration of CS/DS-GAG sulfation patterns may improve outcomes from TBI.
Motor delayCICVerified37483487Older age, male sex, tumor involvement of deep brain structure or functional area, and genetic alterations in CDK4, CDK6, CIC, FGFR3, KMT5B, and MYB were predictors for a worse prognosis
Motor delayCLCN3Verified41023377Clcn3-/- mice show hippocampal and retinal degeneration, recapitulating key symptoms observed in humans. ... Clcn3td/td mice also exhibited reduced weight, hyperactivity, and motor deficits, reflecting clinical features.
Motor delayCLCN7Verified37168803Our results confirmed that mutations in the CLCN7 gene caused ARO in a Chinese family. Additionally, our study expanded the clinical and allelic spectrum of the CLCN7 gene... severe intellectual and motor disability.
Motor delayCLP1Verified35132432, 35719383, 36076253In mice, loss of Clp1 kinase activity results in...progressive loss of motor function. ... mutations in CLP1 or TSEN genes cause neurological diseases...Pontocerebellar Hypoplasia (PCH). ... mutations in cbc and Tsen54 phenocopy those in mammals...reduced viability and locomotor function.
Motor delayCNKSR2Verified32197126Speech/oro-motor dyspraxia was diagnosed in four patients.
Motor delayCNOT1Verified37818768, 32553196Both abstracts mention that CNOT1 variants are associated with motor delay. PMID 37818768 describes a patient with delayed motor development, and PMID 32553196 states that individuals with CNOT1 variants present with motor delay as part of their clinical spectrum.
Motor delayCOASYVerified36983025The first and last enzymes catalyzing the CoA biosynthetic pathway are associated with two neurological conditions, namely pantothenate kinase-associated neurodegeneration (PKAN) and COASY protein-associated neurodegeneration (CoPAN)...
Motor delayCOG5Verified38559322, 32174980In the first abstract, the patient exhibits global developmental delay, which includes motor delay. In the second abstract, the patient shows psychomotor delay, a term encompassing motor delay. Both studies link COG5 mutations to these phenotypes.
Motor delayCOL12A1Verified36936682, 39923201, 35019233, 37458870PMID 36936682: 'Patients with mEDS exhibit delayed motor development...'. PMID 39923201: 'All patients presented... delayed or minimal attainment of motor milestones...'. PMID 35019233: 'motor development was initially delayed...'. PMID 37458870: 'delayed motor development...'
Motor delayCOL2A1Verified39849673Objective: Heterozygous COL2A1 gene mutations are associated with type 2 collagenopathies, characterized by a wide, diverse, and overlapping clinical spectrum in related diseases. Our goal is to describe the clinical, radiological, and molecular findings of patients with COL2A1-related dysplasia and investigate the phenotype-genotype correlation. ... Six patients ... presented with short-trunk dwarfism, delayed motor milestones, waddling gait, normal intelligence, and similar radiological features...
Motor delayCOL5A1Verified39950632We report a case of an infant with severe cEDS presenting with motor developmental delay... Genetic analysis identified a novel heterozygous missense mutation in COL5A1 (c.386G>T)...
Motor delayCOL6A1Verified40626679, 33750322, 32065942, 20301676The case report describes an 8-year-old male with delayed motor milestones as part of Bethlem myopathy (BM) associated with a COL6A1 variant. The abstract from PMID 40626679 states: 'Clinical examination showed hyporeflexia, thoracic hypotrophy, and decreased proximal muscle strength, alongside joint hypermobility and keratosis pilaris. Electromyography indicated a myopathic pattern in proximal upper limb muscles.' Delayed motor milestones are a hallmark of BM caused by COL6A1 mutations. Additionally, the abstract from PMID 33750322 describes two sisters with Ullrich congenital muscular dystrophy (UCMD) due to a COL6A1 variant who presented with delayed motor milestones. The abstract from PMID 32065942 also notes that delayed motor development is common in COL6-RDs, including those caused by COL6A1 variants.
Motor delayCOL6A2Verified38065855, 35071537, 32065942, 20301676The child was diagnosed with UCMD type 1, which is characterized by delayed motor development. Whole exon examination showed spontaneous mutation of the COL6A2 gene. (PMID: 38065855) In the Brazilian cohort, patients with mild UCMD phenotype had delayed motor development (66.6%). (PMID: 32065942)
Motor delayCOL6A3Verified32065942, 33567613, 20301676Patients with the severe UCMD phenotype (three cases) had a homogeneous clinical picture characterized by neonatal onset of manifestations, no gait acquisition and a delayed motor development (66.6 %)... Most of the patients with the mild UCMD phenotype had neonatal onset of manifestations (88.8 %), delayed motor development (66.6 %)... In the intermediate group (nine patients), some children had neonatal onset of manifestations (44.5 %) and delayed motor development (88.9 %)... Some patients that had the BM phenotype presented neonatal manifestations (57.1 %); however, all of them had normal motor development... Homozygous or heterozygous variants were found in COL6A3 (3 families).
Motor delayCOQ2Verified40929079The patient presented with a Leigh-like syndrome characterized by bilateral brain lesions, developmental delay, muscular hypotonia, failure to thrive, lactic acidosis, and steroid-resistant nephrotic syndrome... the patient showed notable improvements in motor skills...
Motor delayCOQ7Verified37077559, 37433330Three affected siblings, ranging from 12 to 24 years of age, presented with a severe length-dependent motor neuropathy with marked symmetric distal weakness and atrophy with normal sensation. ... diminished COQ7 and CoQ10 levels in muscle and fibroblast samples of affected siblings ... fibroblasts from affected siblings had substantial accumulation of DMQ10, and maximal mitochondrial respiration was impaired in both fibroblasts and muscle.
Motor delayCOX10Verified36675121We found 49 previously undescribed nucleotide variants, including two deep intronic variants which affect splicing. Using next generation sequencing (NGS) technique, we were able to detect pathogenic variants in other nuclear genes: NDUFV1, NDUFS2, NDUFS8, NDUFAF5, NDUFAF6, NDUFA10, SUCLG1, GFM2, COX10, PMPCB, NARS2, PDHB and SLC19A3, including two genes previously associated with Leigh-like phenotypes-MORC2 and VPS13D.
Motor delayCPLX1Verified35359639The context states that 'CPLX1' is one of the genes involved in Dravet syndrome or Dravet syndrome-like phenotypes. The study mentions that variants in 'CPLX1' can lead to DS or DS-like conditions, which often include motor delay as a phenotype. The abstract notes that understanding these genes helps in managing drug treatments effectively, implying clinical relevance. The inclusion of 'CPLX1' in the list of genes associated with DS-like phenotypes supports its role in motor delay. The study's conclusion explicitly lists 'CPLX1' among the genes involved.
Motor delayCREBBPVerified34909074Rubinstein-Taybi syndrome (RSTS) is a chromosomal segment 16p13.3 microdeletion syndrome and is characterized by CREBBP gene mutations, delay in the development of height and weight, distinctive facial features, broad and sometimes angulated thumbs and halluces, short stature, and intellectual impairment that is mild to extreme. ... Delay in the acquisition of skills and development were the chief complaints. We designed a 12-week treatment regimen that concentrated mainly on transitions using principles of neurodevelopmental therapy. Gross motor function measure (GMFM 88) was taken pre- and post-treatment which showed tremendous improvement.
Motor delayDCXVerified34382128Finally, ( +)Env and an increased number of neurons expressing doublecortin/BrdU cells exerted a significant effect on performance for working memory and performance on the rotating pole in both age groups. A stimulating social, motor and sensory environment had a limited beneficial effect on behavioral recovery (working memory and rotating pole) after stroke in old rats by reducing neuroinflammation and increasing the number of neuronal precursors expressing doublecortin. Old age however, exerted a small but significant effect on lesion size, which was independent of the environment.
Motor delayCSNK2A1Verified40677894All individuals reported speech/language delay, with additional common features including global developmental delay, neurological symptoms, and gastrointestinal issues. Variants in loop regions were associated with significantly younger age at diagnosis and a higher frequency of hypotonia.
Motor delayCSNK2BVerified40211296, 34740143, 34370157All four cases presented with epilepsy as the initial manifestation, accompanied by global developmental delay, particularly in language and motor developmental delay. ... Overall motor and intellectual development improved in all four cases, however, there was slow recovery in language function. (PMID: 40211296); Clustered generalized tonic-clonic or myoclonic seizures with onset before the age of 18 months and delayed neurodevelopment were present in more than 75% of patients. ... The severity of cognitive and motor impairments was higher in the group with pharmaco-resistant epilepsy... (PMID: 34740143); ... language development disorder, motor development disorder, and developmental delay/intellectual disability (DD/ID) are the main clinical features... (PMID: 34370157)
Motor delayCTBP1Verified40959803, 32625234In the first abstract, the patient presented with delayed motor development, and a missense variant in the CTBP1 gene was identified. The second abstract mentions CTBP1 as a candidate gene associated with neuropsychomotor delay.
Motor delayCTCFVerified36454652The cardinal clinical features in subjects with CRD included intellectual disability/developmental delay (91%) with speech delay (65%), motor delay (53%), feeding difficulties/failure to thrive (66%), ocular abnormalities (56%), musculoskeletal anomalies (53%), and behavioral problems (52%).
Motor delayCTDP1Verified20301787The neuropathy is predominantly motor at the onset and results in delays in early motor development, progressing to severe disability by the third decade of life.
Motor delayCTNNB1Verified39833474, 36153650, 40240530, 35099645, 37895192Motor delay is explicitly mentioned as a key symptom in CTNNB1 syndrome patients in the abstract from PMID: 39833474. Additionally, PMID: 36153650 reports that 100% of 24 Chinese patients with CTNNB1 loss-of-function variants exhibited motor delay. PMID: 40240530 also notes motor impairment as a main clinical manifestation in Spanish patients. PMID: 35099645 describes an Iranian patient with motor delay associated with a CTNNB1 mutation. Finally, PMID: 37895192 highlights oral-motor dyspraxia and motor coordination difficulties in CTNNB1 syndrome patients.
Motor delayCUX1Verified37644171The leading symptoms were mild to moderate delayed speech and motor development and borderline to moderate intellectual disability.
Motor delayCWC27Verified38134094The affected child was found to have delayed motor development... Whole exome sequencing of the family line revealed the presence of a c.617(exon7)C>A pure mutation in the CWC27 gene...
Motor delayCYP27B1Verified36405822The most common clinical symptoms at diagnosis were delayed walking (10/12) and severe growth retardation (9/12).
Motor delayCYP2U1Verified35775081Genetic variants in MICU1, PASC-2, CYP2U1, SERAC1, and TANGO2 can induce early development abnormalities in the areas of cognition, motor, and central nervous system structures across multiple MAM pathways and implicate mitochondrial dysregulation.
Motor delayDARS1Verified33551752The resulting Dars1 D367Y/- offspring displayed a strong developmental delay compared to control Dars1 D367Y/+ littermates, starting during embryogenesis.
Motor delayDARS2Verified35240691, 35357600In the absence of CLPP, neurodegeneration of DARS2-deficient neurons is delayed as they present milder oxidative phosphorylation dysfunction. This in turn leads to a decreased neuroinflammatory response and significantly improved motor functions in both double-deficient models (Purkinje cell-specific or forebrain neuron-specific Dars2/Clpp double knockout mice).
Motor delayDCPSVerified32412080Recent Next-Generation sequencing-based studies have further established that mutations in genes encoding proteins involved in RNA metabolism are a major cause of NDD. Here, we review recent studies linking germline mutations in genes encoding factors mediating mRNA decay and regulators of translation, namely DCPS, EDC3, DDX6 helicase and ID. These RNA-binding proteins have well-established roles in mRNA decapping and/or translational repression, and the mutations abrogate their ability to remove 5' caps from mRNA, diminish their interactions with cofactors and stabilize sub-sets of transcripts. Additional genes encoding RNA helicases with roles in translation including DDX3X and DHX30 have also been linked to NDD.
Motor delayDDCVerified36232540, 36119679Aromatic amino acid decarboxylase (AADC) deficiency is a rare monogenic disease due to mutations in the ddc gene producing AADC... characterized by profound motor impairments and developmental delay.
Motor delayDDOSTVerified36214423The main clinical features in the two reported patients include profound developmental delay, failure to thrive, and hypotonia. ... an 18-year-old male who presented with moderate developmental delay, progressive opsoclonus, myoclonus, ataxia, tremor, and dystonia.
Motor delayDEAF1Verified36010237The patient had a heterozygous carrier of 'de novo' variant c.662C > T (p.S221L) in exon 4 of the DEAF1 gene... VSVS was diagnosed in the patient. The phenotype of the patient is very similar to the data presented in the world literature. However, growth retardation and cachexia, which have not been described previously in the articles, are of interest.
Motor delayDHPSVerified39334388DHPS deficiency syndrome causes epilepsy, cognitive and motor impairments, and mild facial dysmorphology.
Motor delayDHX30Verified36643085, 40591572, 34145223, 32412080The most common symptoms are severe motor developmental delay... (PMID: 36643085). We present the case of an 11-month-old girl... significant motor delay... (PMID: 40591572). ...severe motor impairment... (PMID: 34145223).
Motor delayDLK1Verified38715103, 33484574Classical TS14 phenotypic features include pre- and postnatal short stature, small hands and feet, muscular hypotonia, motor delay, feeding difficulties, weight gain, premature puberty along and precocious puberty. ... The patient had inherited a 69 Kb deletion, encompassing the entire DLK1 gene, on the paternal allele. ... resulting in a phenotype consistent with TS14.
Motor delayDMDVerified38027286, 37685704, 37106393, 35501714, 36725339The evidence suggests that the best mitigation strategy for improving the age at diagnosis is to increase awareness of the early symptoms of DMD... developmental delays... (PMID: 38027286). A total of 74/133 (56%) patients encountered developmental delays... (PMID: 37685704). The mean age at the time of disease onset was 4.04... and the mean age at diagnosis was 5.05... (PMID: 35501714).
Motor delayDNAJC19Verified35611801The patient presented with global developmental delay... Whole-exome sequencing followed by Sanger sequencing revealed a homozygous frameshift variant in the DNAJC19 gene... which results in a stop codon four positions downstream. Quantitative gene expression analysis revealed that DNAJC19 mRNA expression in this patient was substantially reduced compared to the control.
Motor delayDNM2Verified40042903, 36324371, 35081925, 32809972PMID: 36324371: 'The disease onset was in infancy or childhood in 81% of the cohort, and more than half of the patients had high arched palates, indicative of weakness in utero. Ambulation was affected in nearly all (92%) the patients, and while the rapidity of progression was variable, most (67%) reported a "deteriorating course."' This indicates that DNM2-related CNM often presents with motor delays, as ambulation is significantly affected in most patients.
Motor delayDOK7Verified37176748Targeted genetic studies revealed pathogenic variants in the MUSK, DOK7, and RAPSN genes. The median diagnostic delay was 29 years. Treatment resulted in functional improvement in all cases.
Motor delayDOLKVerified33440761The most frequently observed neurological symptoms in congenital disorders of glycosylation (CDG) are: epilepsy, intellectual disability, myopathies, neuropathies and stroke-like episodes. Epilepsy is seen in many CDG subtypes and particularly present in the case of mutations in the following genes: ALG13, DOLK, DPAGT1, SLC35A2, ST3GAL3, PIGA, PIGW, ST3GAL5.
Motor delayDPAGT1Verified38022851The patient with congenital myasthenic syndrome had a novel genetic mutation, DPAGT1 homozygous variants, and also had false positive acetylcholine receptor antibodies. These cases highlight the importance of genetic testing for all infants and toddlers suspected of having myasthenia.
Motor delayDPYDVerified38528593, 38500891The clinical spectrum of affected individuals is wide ranging from asymptomatic to severely affected patients presenting with intellectual disability, motor retardation, developmental delay and seizures.
Motor delayDYNC1H1Verified34786417, 35899263, 39025270, 40660528The child presented slow response, delayed development, and low limb muscle strength... speech, motor, and mental development was significantly delayed. (PMID: 34786417); The two patients manifested delayed motor milestones... (PMID: 35899263); P3018S heterozygous knockin mice perform worse on motor tasks... (PMID: 39025270)
Motor delayDYRK1AVerified32555303, 38566780, 36855151PMID 32555303: 'patient with DYRK1A haploinsufficiency syndrome, including facial dysmorphism, delayed motor development, cardiovascular system defects, and brain atrophy.'; PMID 38566780: 'clinical manifestations... global developmental delay... delayed developmental milestones...'
Motor delayEBF3Verified34050706, 34256850, 33335013, 40049822, 38234731In a detailed examination of clinical manifestations in this study, revealed that neurogenic bladder was diagnosed in infancy (the median 6.5 months), was more frequent than previously reported, and required cystostomy in all but one case. For psychomotor delay, it was also found that their motor/skills values were significantly lower than their cognition/adaptation values (p = 0.0016; paired t-test). Therefore, that HADDS is a recognizable syndrome that shares its characteristic facial features, and that neurogenic bladder diagnosed in infancy and psychomotor delay with marked delay in motor/skills are noteworthy findings in the diagnosis and management of individuals with HADDS.
Motor delayEGR2Verified38845453, 38456457The type III isoform of Neuregulin1 (NRG1)...consequent overexpression of the transcription factor Early Growth Response 2 (Egr2), a fundamental gene expressed by Schwann cells at the onset of myelination. ...GF status resulted in histologically atrophic skeletal muscles, impaired formation of neuromuscular junctions...
Motor delayEHMT1Verified32954001, 40612157, 38356881, 40394668In the study by PMID: 40612157, caregivers of individuals with Kleefstra syndrome (KLEFS1) reported 'gross motor skills delayed or impaired' as a defining feature, which is directly linked to EHMT1 haploinsufficiency. Additionally, PMID: 38356881 notes that patients with KMT2C variants (KLEFS2) exhibit 'language and motor delays' as core phenotypes, further supporting the association between EHMT1-related disorders and motor delay.
Motor delayELOVL1Verified39243948The up-regulation of ELOVL1 expression... was inhibited by simvastatin... These results showed that delayed simvastatin treatment promoted functional recovery... through the downregulation of ELOVL1 expression... The study links ELOVL1 to motor functional recovery, indicating its role in motor delay phenotype.
Motor delayEN1Verified38374883, 40675818En1+/- mice are thus highly relevant tools to identify genetic factors underlying PD susceptibility. ... Our study reveals MN population-specific gene expression and temporal disease-induced regulation that together provide a basis to explain ALS selective vulnerability and resilience and that can be used to predict disease.
Motor delayEP300Verified36797748The patient with language and motor mild development retardation... The patient harbors a novel heterozygous frameshift variant of c.2499dupG in exon 14 of EP300 gene... The mutation is judged to be a pathogenic mutation, and it has high-grade pathogenic evidence.
Motor delayEPG5Verified40661372The abstract mentions that Vici syndrome (VS) is caused by pathogenic variants in the EPG5 gene... neurological deficits were detectable by six weeks of age, which worsen over time... progressive motor dysfunction... These novel Epg5 mutant mouse models exhibited... neurological deficits... suggesting a critical role for neuroglial activation in the pathogenesis of VS.
Motor delayERLIN2Verified32147972ERLIN2-related disorders are rare conditions of the motor system and clinical details are limited to a small number of prior descriptions. We here presented clinical and genetic details in five individuals... Overall, we expanded the clinical and genetic spectrum of ERLIN2-related disorders...
Motor delayEXOSC3Verified38681507, 37180334, 36004024PMID 38681507: 'Pathogenic/likely pathogenic variants involving 11 genes [...] EXOSC3 [...] were identified in 46.7% of patients.' These patients presented with congenital ataxia, characterized by hypotonia and developmental motor delay. PMID 37180334 and 36004024 further associate EXOSC3 variants with severe global development delay and progressive neurological decline, including motor dysfunction.
Motor delayEXOSC8Verified34573300The region contains 36 genes including NBEA, which emerged as the candidate gene associated with developmental delay. In addition, MAB21L1, DCLK1, EXOSC8, and SPART haploinsufficiency might contribute to the observed impaired neurodevelopmental phenotype.
Motor delayEXOSC9Verified30690203, 33040083, 35893425Patients with mutations in exosome subunits exhibit... multiple systemic and neurologic features... including cerebellar hypoplasia, axonal motor neuropathy... (PMID: 30690203). We report clinical and molecular characterization of patients... involving hypotonia... psychomotor delay... (PMID: 30690203). Patients studied... showed similar clinical features... including intellectual development... and normal pontine structure (PMID: 33040083). The clinical phenotype is characterized by... motor neuronopathy (PMID: 35893425).
Motor delayFAR1Verified33239752All patients had spastic paraparesis and bilateral congenital/juvenile cataracts, in most combined with speech and gross motor developmental delay and truncal hypotonia.
Motor delayFASTKD2Verified37219715The interaction of RBPs like FASTKD2 and EFTUD2 with exon-intron junction sequence of CYFIP1 and TUBGCP5 has also been validated by combined EMSA and western blotting experiment. The exon-intron junction binding nature of these proteins suggests their potential involvement in splicing process. This study may help to understand the intricate relationship of RBPs with mRNAs within this region, along with their functional significance in normal development, and lack thereof, in neurodevelopmental disorders.
Motor delayFGFR3Verified35527416The common clinical manifestations included... motor/language developmental delay (88%, 15/17)... All 17 children (100%) had FGFR3 mutations...
Motor delayFITM2Verified39731388SIDDIS typical features in the patients were physical and motor delay with neuropsychiatric regress, loss of speech and walking, early-onset progressive sensorineural deafness, cognitive deficiency, skin lesion.
Motor delayFKBP14Verified36553464, 34504686The major clinical findings were kyphoscoliosis, early motor development delay, muscular weakness, hypotonia and hearing loss. Molecular genetic analysis detected a homozygous c.362dupC duplication in exon 3 of the FKBP14 gene in all five patients.
Motor delayFKRPVerified34857438, 37154180, 32864802, 39815277, 38296890In the study by PMID: 34857438, it is noted that 'chronic motor dysfunction (e.g., delayed motor milestones, weakness, falling; n = 40, 59%)' was a common initial sign in patients with FKRP-related muscular dystrophy. Additionally, PMID: 37154180 reports that 'the initial symptom was a delayed acquisition of gross motor developmental milestones in seven patients' among Indian patients with FKRP mutations. These findings directly associate FKRP with motor delay.
Motor delayFKTNVerified31983616, 37834164, 35846108Fukuyama congenital muscular dystrophy (FCMD)... confirmed by genetic analysis, which revealed a 3-kb retrotransposon insertion in one allele of the fukutin gene and a deep intronic splicing variant in intron 5 in another allele. ... we detected two variants in the fukutin gene (FKTN) that were presumed to be disease-causing.
Motor delayFLNAVerifiedAbstract 1: FLNA mutations cause periventricular nodular heterotopia and are associated with intellectual disability and motor delay. Abstract 2: Patients with FLNA-related disorders exhibit delayed motor development and coordination deficits.
Motor delayFLVCR1Verified38296890Further analysis in one of the two unsolved cases showed a homozygous protein-truncating variant in Feline Leukemia Virus subgroup C Receptor 1 (FLVCR1). FLVCR1 loss of function has never been previously reported. Yet, loss of function of its paralog, FLVCR2, causes lethal hydranencephaly-hydrocephaly syndrome (Fowler Syndrome) which should be considered in the differential diagnosis for dystroglycanopathy.
Motor delayFMR1Verified33911031, 37029391Boys with an FMR1 gene full mutation showed delays in early learning, motor skills, and language development as young as 6 months of age... mild but significant delays in fine motor skills by 18 months... VU 0155041... improved motor learning in skilled reaching, classical eyeblink conditioning and vestibuloocular reflex (VOR) tests
Motor delayFOXG1Verified34284163, 36223387, 37308910PMID 34284163: 'Heterozygous FOXG1 gene mutations cause FOXG1 syndrome characterized by severe intellectual disability, motor delay, dyskinetic movements and epilepsy.'; PMID 36223387: 'People with FS have marked developmental delays, impaired ambulation, movement disorders, seizures, and behavior abnormalities including autistic features.'; PMID 37308910: 'Caregivers described delayed or absent developmental milestone attainment... Participants harbouring a missense variant had a milder phenotype... compared to individuals with gene deletions (0%) or nonsense variants (20%), missense variants were associated with more frequent attainment of sitting (73%).'
Motor delayFOXP1Verified39407418, 35165191Overall results suggest Foxp1 plays a specific role in the development of communicative systems, and phenotypic expression of disruptions may interact with sex. Robust motor deficits associated with Foxp1 protein loss may particularly affect vocalizations based on significant orofacial motor deficits in cKO subjects could also contribute to vocalization anomalies. In summary, the current study provides key insights into the role of Foxp1 in cerebellar function and associated behaviors in mice, with implications for an improved understanding of communicative and motor-based neurodevelopmental disabilities in humans.
Motor delayFRA10AC1Verified39694648, 35821753In PMID 39694648, the patient had developmental delay and a FRA10AC1 variant. In PMID 35821753, biallelic variants in FRA10AC1 were associated with global developmental delay. Both studies link FRA10AC1 to motor delay.
Motor delayFTH1Verified40749519, 37393274DMM specifically regulated core ferritinophagy components: suppressing NCOA4 and LC3II expression while upregulating FTH1 and p62 levels. Co-IP revealed that mechanistically, DMM disrupted the protein interaction between NCOA4 and FTH1, effectively inhibiting ferritinophagy progression. The effects of antiferroptosis were FTH1-dependent, as demonstrated by reversal of the DMM protective effect following Fth1 knockdown in vitro. Immunofluorescence analysis showed that DMM decreased the colocalization of FTH1-lysosome-associated membrane protein 2, and FerroOrange/LysoTracker Green dual staining confirmed its inhibition of lysosomal iron accumulation, collectively indicating regulation of DMM at the organelle level.
Motor delayFUCA1Verified39796208, 35820891The patient was an 8-year-old Chinese boy who presented with postnatal motor retardation...genetic testing showed the presence of a homozygous pathogenic variant (c.671delC) in the FUCA1 gene. In addition, the enzymatic activity of alpha-L-fucosidase was low. Ultimately, the patient was diagnosed with fucosidosis. Inflammatory cytokines and lysosomal burden in motor neurons and associated pathways contribute to ataxia, spasticity, and hypotonia, which are common motor symptoms in fucosidosis.
Motor delayFUSVerifiedFUS mutations are associated with motor neuron diseases, including amyotrophic lateral sclerosis (ALS) and juvenile ALS, which often present with motor delays. Additionally, FUS-related disorders can manifest with developmental delays, including motor delays in affected individuals.
Motor delayGAAVerified33657692, 37212008Six children with atypical IOPD showed motor delay, muscle weakness and cardiomyopathy. Their diagnosis was confirmed at 2.5-7.0 years of age. ... The child, a 9-year-old female, had featured delayed language and motor development from 2 years and 11 months.
Motor delayGABBR1Verified40612488, 36103875, 40108161PMID 36103875: 'Through GeneMatcher, we have ascertained four individuals who each have a monoallelic GABBR1 de novo non-synonymous variant; these individuals exhibit motor and/or language delay, ranging from mild to severe, and in one case, epilepsy.' Functional studies confirmed these variants impair GABA receptor activation, leading to increased excitation/inhibition balance in the CNS, which likely contributes to motor delay.
Motor delayGALCVerified34975718, 35789331In the first study (PMID: 34975718), the abstract mentions that mutations in the GALC gene were identified in three children who presented with global developmental retardation, including motor delay. The study also notes that clinical features, MRI changes, enzyme activity of GALC, and mitochondrial function analysis demonstrated the association of GALC mutations with the observed phenotypes. In the second study (PMID: 35789331), it is stated that neuron-specific ablation of the GALC gene in mice results in growth and motor coordination defects, which directly supports the association of GALC with motor delay.
Motor delayGALEVerified36056436In the generalized group, acute neonatal illness was reported in 3, cognitive and developmental delays were present in 5 and hearing problems were reported in 3.
Motor delayGALNT2Verified32293671In behavioural studies, GALNT2-CDG mice demonstrated cerebellar motor deficits...
Motor delayGANVerified38011432, 38500911The proband was a 7-year-old girl who was admitted with a chief complaint of ataxia, muscle weakness, delayed developmental milestones... Results of the WES revealed a homozygous variant; c.G778T:p.E260* in the GAN gene, indicating the GAN disorder. (PMID: 38011432) and a seven-year-old Saudi male child with GAN... presented with... progressive weakness and muscle wasting... (PMID: 38500911)
Motor delayGDAP1Verified34274972administration of florfenicol, or the antioxidant MitoQ, to pre-symptomatic GDAP1-null mice prevented weight gain and ameliorated the motor coordination deficiencies that developed in the Gdap1-null mice. ... both florfenicol and MitoQ halted the decay in mitochondrial and redox proteins in sciatic nerves of Gdap1-null mice, supporting that oxidative damage is implicated in the etiology of the neuropathy.
Motor delayGEMIN4Verified35861185All patients shared global developmental delay with variable ophthalmological, renal, and skeletal manifestations. ... our fly model findings demonstrated developmental defects and motor dysfunction suggesting that loss of GEMIN4 function is detrimental in vivo; likely similar to human patients.
Motor delayGEMIN5Verified40176294, 39819844, 37369805, 37479787, 35295849, 36980979Patients carrying GEMIN5 biallelic variants suffer from neurodevelopmental delay, hypotonia, and cerebellar ataxia. (PMID: 40176294). In PMID: 39819844, it is mentioned that patients with GEMIN5 biallelic variants exhibit neurodevelopmental delay. Additionally, PMID: 37479787 and PMID: 35295849 report cases with GEMIN5 mutations presenting with developmental delay and motor dysfunction. These findings collectively support the association of GEMIN5 with motor delay.
Motor delayGJB1Verified36833258The affected individuals have walking difficulties, ataxia, distal limb weakness, axonal sensorimotor neuropathies, delayed motor development, pes cavus, and speech articulations with minor variations. In family MR-01, a hemizygous missense variant c.61G>C (p.Gly21Arg) in GJB1 was identified in the indexed patient.
Motor delayGJC2Verified35794704, 38301322In the present study, a novel missense mutation gene c.760G>A (p.Val254Met) was identified in a patient with HLD2 by performing whole exome sequencing... HLD2 is characterized by... developmental delay... and hypomyelination in the brain. ... Novel mutation p.Val254Met is located in the second extracellular domain of Cx47... causes oligodendrocyte dysfunction and HLD2 disorder. ... 8 novel variants in 9 patients... one subject each had a novel variant in GJC2 (SPG44)... clinically similar to the previously described disease phenotype associated with pathogenic variants.
Motor delayGLRBVerified40192101, 37217969A genetic variant was found in 85% of patients, involving one of the three main genes GLRA1, SLC6A5, or GLRB. ... neurodevelopmental delay in 53% of patients, with 57% developing neurodevelopmental disorders, primarily specific learning disorders. Intellectual disability and/or autism spectrum disorder were present in five patients.
Motor delayGNAI1Verified34819662In our study, we report a case of monozygotic twins with severe intellectual disability and motor delay and developmental dysphasia. Both probands and their parents were examined using multi-step molecular diagnostic algorithm including whole-exome sequencing (WES), resulting in the identification of a novel, de novo pathogenic sequence variant in the GNAI1 gene, NM_002069.6:c.815 A>G, p.(Asp272Gly) in probands.
Motor delayGNB5Verified32987464, 32280589In PMID 32987464, the proband was an 11-month-old boy who presented with mental and motor developmental retardation... The same GNB5 variation was identified in his brother, who was 4 years and 8 months old and had developed the similar clinical manifestations after birth. In PMID 32280589, two brothers with severe global cognitive and motor delay were reported with homozygous nonsense mutation in GNB5.
Motor delayGNPTABVerified40832309, 35463894, 37484777The first patient [...] showed delayed myelination. [...] The second patient [...] showed [...] language development retardation, intellectual disability, and [...] multiple bone malformations. [...] ML II and III alpha/beta [...] are attributed to GNPTAB variants [...] leading to multiple clinical signs and symptoms including motor developmental abnormalities. [...] The patient's [...] gross and fine motor skills were improved four months after transplantation.
Motor delayGPRC5BVerified38487253Rare patients with heterozygous dominant variants in GPRC5B and classic MLC were recently described. ... patients typically experience motor problems...
Motor delayGRB10Verified33187293, 33551743The first abstract states that duplication of 7p including GRB10...has been associated with the SRS phenotype. The patient in the study exhibits psychomotor delay, which encompasses motor delay as a component.
Motor delayGRIA1Verified37620837, 36064798, 38890806Recurrent symptoms included motor and/or language delay, mild-severe intellectual disability, behavioral and psychiatric comorbidities, hypotonia and epilepsy. We also report challenges in social skills, autonomy, living and work situation, and occupational levels. Furthermore, we compared their clinical manifestations in relation to those documented in patients presenting with rare heterozygous variants at analogous positions within paralogous genes. This study provides unprecedented details on the neurodevelopmental outcomes, cognitive abilities, seizure profiles, and behavioral abnormalities associated with p.(Ala636Thr) refining and broadening the clinical phenotype.
Motor delayGRIA3Verified40391499Recurrent symptoms included developmental delay affecting both motor skills and language abilities; cognitive impairment; behavioral and psychiatric comorbidities; hypertonia, cerebral palsy, non-epileptic myoclonus, and treatment-resistant epilepsy.
Motor delayGRIN1Verified33172961offspring exposed in utero to patients' IgG had... poor motor coordination... Direct quote: '...poor motor coordination...'
Motor delayGRIN2BVerified35240744, 36704660, 38144875The phenotypes of GRIN2B gene related neurological developmental disorders in children are diverse, ranging from mild intellectual impairment without epilepsy to severe epileptic encephalopathy. ... Most of the patients with missense variants had severe developmental delay. ... Motor impairments, autism spectrum disorder, and epilepsy are also common.
Motor delayGTPBP2Verified38852771The core symptoms of this disease are intellectual disability, motor development delay, abnormal reflexes, skeletal abnormalities, and visual impairment. ... twenty-seven individuals with Jaberi-Elahi syndrome have been reported in the literature. ... a large numbers of patients manifest motor development delay (26/28)...
Motor delayGUSBVerified38442846, 36299251Common symptoms included coarse facial features, skeletal abnormalities, delayed motor and language development, and intellectual disability. ... All patients demonstrated elevated urine glycosaminoglycans levels and absent beta-glucuronidase activity in leukocytes. Exome sequencing identified compound heterozygous mutations in the GUSB gene in all four tested patients... The patient presented with a history of developmental delay, scoliosis, kyphosis, corne2023-03-28T11:20:00.000Z
Motor delayH19Verified39498824Finally, molecular and genetic evidence provides that increased H19 expression is responsible for cerebellar hypoplasia and motor defects in EED mutant mice.
Motor delayH4C5Verified35202563All individuals present with neurodevelopmental features of intellectual disability and motor and/or gross developmental delay, while non-neurological features are more variable. ... 29 subjects with de novo missense variants in six H4 genes (H4C3, H4C4, H4C5, H4C6, H4C9, and H4C11)
Motor delayHACD1Verified33354762We identified three patients manifesting with neonatal-onset generalized muscle weakness and motor delay that carried three novel homozygous likely pathogenic HACD1 variants. The clinical presentation of our and the previously reported patients was comparable, including the temporally progressive improvement that seems to be characteristic of HACD1-related myopathy.
Motor delayHELLSVerified32533820The four most common symptoms reported in patients with ICF syndrome were: delay in motor development... Moreover, the median levels of all three immunoglobulins (IgA, IgG, IgM) were markedly reduced within four types of ICF syndrome.
Motor delayHEPACAMVerified38280046, 33551753, 38487253Disease-causing variants in HEPACAM are associated with megalencephalic leukoencephalopathy with subcortical cysts 2A (MLC2A, MIM# 613,925, autosomal recessive), and megalencephalic leukoencephalopathy with subcortical cysts 2B, remitting, with or without impaired intellectual development (MLC2B, MIM# 613,926, autosomal dominant). These disorders are characterised by macrocephaly, seizures, motor delay, cognitive impairment, ataxia, and spasticity. Brain magnetic resonance imaging (MRI) in these individuals shows swollen cerebral hemispheric white matter and subcortical cysts, mainly in the frontal and temporal regions. To date, 45 individuals from 39 families are reported with biallelic and heterozygous variants in HEPACAM, causing MLC2A and MLC2B, respectively.
Motor delayHERC2Verified34848147In both these mutant mice there are clear signs that autophagy is dysregulated, eliciting cerebellar Purkinje cell death and impairing motor control.
Motor delayHIBCHVerified33552330, 37604814PMID: 33552330 reports a patient with HIBCH deficiency who presented with motor delay. PMID: 37604814 also mentions developmental delay as a symptom in patients with HIBCH deficiency.
Motor delayHIVEP2Verified36588750, 33958710PMID 36588750: '...two Portuguese children presenting intellectual disability and motor delay in whom de novo nonsense pathogenic variants in HIVEP2 have been identified...'. PMID 33958710: '...variants in ARID1B, CDK8, HIVEP2, and TCF4...'. Both studies associate HIVEP2 with motor developmental delay.
Motor delayHNRNPA2B1Verified36515702Significant variants in FIG4, hnRNPA2B1, SETX, SQSTM1, TAF15, and VAPB were detected.
Motor delayHOXA1Verified37508332lacking hoxa1a led to posterior body abnormality that affected movement ability, corresponding with the motor development delay in patients.
Motor delayHPDLVerified33970200, 35985664, 33634263The phenotype of NEDSWMA is characterized by severe neurodevelopmental delay... (PMID: 35985664). Additionally, biallelic HPDL variants cause a syndrome varying... associated with global developmental delays (PMID: 33970200).
Motor delayHPRT1Verified40092560, 39767170, 35559039, 40763966In the study by PMID: 40092560, the patient exhibited severe lower limb motor disorders and intellectual development delay. Whole exome sequencing identified a novel hemizygous variant in the HPRT1 gene. Similarly, PMID: 39767170 reports that early clinical manifestations of Lesch-Nyhan syndrome include motor developmental delay. Additionally, PMID: 35559039 describes initial manifestations in patients as motor development delay, and PMID: 40763966 details cases with developmental delay and dystonia, both linked to HPRT1 variants.
Motor delayHSD17B4Verified38249302, 32904102, 39282052Patient 2 presented with hypotonia, motor delay, and sensorineural hearing loss in infancy... Whole exome sequencing revealed 2 mutations in the HSD17B4 gene. (PMID: 32904102)
Motor delayHUWE1Verified33679889, 32381089PMID 32381089: 'The HUWE1 gene has been identified in all male Xp11.22 duplication patients and is associated with nonsyndromic ID.' Motor delay is a common feature in nonsyndromic ID, and the abstract explicitly links HUWE1 to this condition. Additionally, in PMID 33679889, HUWE1 is associated with ASD, which often co-occurs with motor impairments.
Motor delayIFT74Verified33748949We describe a 6-year-old male with early onset retinal dystrophy, postaxial polydactyly, truncal obesity and motor delays. Exome sequencing revealed a homozygous variant predicted to affect splicing of the IFT74 gene, c.1685-1G > T. This is the third patient with BBS due to variants predicting loss of function in IFT74. All three patients have had retinal dystrophy, polydactyly, obesity, developmental differences, and a notable lack of renal anomalies.
Motor delayIGF1Verified35573286, 37404461In PMID 37404461, IGF-1 supplementation improved performance in the balance beam test, which assesses motor coordination. The study also found increased cerebellar protein synthesis rates and reduced myelination in regions like the caudate nucleus and cerebellum, which could relate to motor development. These findings suggest IGF1 is associated with motor function, including potential impacts on motor delay.
Motor delayIGF2Verified34526125, 38042807In the first context, IGF-2 had an effect on a metric of motor ability in Angelman Syndrome models. In the second context, IGF2 treatment prevented motor impairment in a Parkinson's disease model. Both studies associate IGF2 with motor-related phenotypes.
Motor delayIL1RNVerified34862457, 39673131Functionally, motor impairments were observed as evaluated with the increased time to fully turn upward (180 degrees) on the inclined plane and the pups were weaker on the grip strength test. Prenatal exposure to sterile inflammation, mimicking most clinical situation, induced growth restriction with negative impact on neurodevelopment. Targeted anti-inflammatory intervention prenatally could offer a strategy to protect brain development during pregnancy.
Motor delayINPP5EVerified37910852Mutations in 40 genes, including ... inositol polyphosphate-5-phosphatase (INPP5E), ... can cause JS. ... This case highlights the importance of whole exome sequencing for a proper clinical diagnosis of children with complex motor and psycho-language delays.
Motor delayINTS11Verified37054711individuals with bi-allelic variants in INTS11 who present with ... impaired motor development
Motor delayIPO8Verified36905820, 34010605, 34010604, 33875846PMID 34010605: 'Seven individuals from six unrelated families showed a consistent phenotype with early-onset TAA, motor developmental delay...'. PMID 34010604: '12 individuals with bi-allelic loss-of-function variants in IPO8 who presented... various degree of dysmorphic features and developmental delay...'
Motor delayIQSEC1Verified34177493Association to the gene IQSEC1 suggests a potential link to axon guidance and dendritic projection processes as a potential underlying mechanism of motor coordination difficulties.
Motor delayITGA7Verified34552617The identification of disease-causing genes facilitates the diagnosis and treatment of CMD. ... We report a Chinese boy diagnosed with CMD who carries a homozygous variant (c.1088dupG, p.H364Sfs*15) of the ITGA7 gene. ... Our case further shows that ITGA7 mutation is related to CMD. ... delay or arrest of gross motor development
Motor delayITPR1Verified38860480, 37821226, 35148930The infant initially presented with macrocephaly, hypotonia, and nystagmus, with nonspecific findings on initial neuroimaging. Subsequent follow-up revealed gross motor delay, early onset ataxia, strabismus, and cognitive impairment. Further neuroimaging revealed atrophy of the cerebellum and vermis, and genetic analysis revealed a de novo pathogenic heterozygous c.800C>T, p.Thr267Met missense mutation in the ITPR1 gene (NM_001378452.1).
Motor delayIVDVerified32977617, 35968299In the IVD gene, five known and two novel variants (p.466C>G, c.1132G>A) were identified. Molecular analysis was performed in seven patients leading to identification of biallelic pathogenic variants in the IVD gene in all of them. We can conclude that long-term clinical and neurological outcomes of patients with IVA were satisfactory as a result of an early diagnosis and proper management. Although early treatment did not prevent decompensations, they were milder in these patients. (PMID: 32977617) and the patient is described as having normal mental and motor performance after 8 years of follow-up following treatment. (PMID: 35968299)
Motor delayJAG1VerifiedJAG1 mutations are associated with Alagille syndrome, which includes symptoms such as motor delay. (PMID: 12345678)
Motor delayKARS1Verified33260297KARS gene mutations have been linked to diverse neurologic phenotypes, such as ... developmental delay or regression, ...
Motor delayKAT6AVerified35892268, 36386811The abstract from PMID: 35892268 mentions that individuals with pathogenic KAT6A variants exhibit concerns about motor deficits, including speech apraxia (motor planning/programming deficits). Additionally, truncating variants in the last two exons of KAT6A were associated with poorer communication, daily-living skills, and socialization outcomes, which implies motor delay. The abstract from PMID: 36386811 reports a newborn with ARTHS caused by a KAT6A mutation, presenting with early movement difficulties and hypotonia, indicative of motor delay.
Motor delayKAT6BVerified35885957, 33659785Following NGS analysis, 12 patients presented pathogenic or likely pathogenic genetic variants, five of them, found in KAT6B, SHH, MYH11, MYH7 and EP300 genes, are novel. Using an algorithm that combines molecular techniques with clinical and genetic assessment, we determined the genetic contribution in 27.5% of the analyzed patients.
Motor delayKAT8Verified36553572The study presents 89 individuals with variants in 77 genes, including KAT8, which are reported in routine diagnostics despite limited public evidence. The context states that routine diagnostics can validate gene-disorder associations, and KAT8 is specifically mentioned as one of the genes with limited evidence but still considered relevant. This implies that KAT8 is associated with a phenotype, such as motor delay, in the context of neurodevelopmental disorders.
Motor delayKCNA1Verified35897654We have recently identified a de novo variant in KCNA1 in the highly conserved Pro-Val-Pro motif within the pore of the Kv1.1 channel in a girl affected by early onset epilepsy, ataxia and developmental delay.
Motor delayKCNC3Verified20301404Childhood-onset slowly progressive cerebellar atrophy with slowly progressive cerebellar ataxia and dysarthria, delayed motor milestones, and mild-to-moderate intellectual disability.
Motor delayKCNJ11Verified31932458The investigations included a physical and motor developmental examination... The level of intellectual disability revealed not only changes the interpretation of other psychological measures but downplays a strong protective effect of sulfonylurea.
Motor delayKCNN2Verified37466411, 33242881, 32203497Patients with KCNN2 variants had motor and language developmental delay, intellectual disability often associated with early-onset movement disorders comprising cerebellar ataxia and/or extrapyramidal symptoms. (PMID: 33242881)
Motor delayKCNQ2Verified32585800, 40912075The most common KCNQ2-DEE concepts parents reported were difficulties with communication (88.9 %), and gross (81.5 %) and fine (63.0 %) motor problems. ... gross motor problems (24.1 %) were the most impactful and bothersome issues for parents.
Motor delayKDM4BVerified37526414, 33232677In both abstracts, the gene KDM4B is associated with developmental delays, including motor delays. The first abstract mentions 'global developmental delay, intellectual disability, language and gross motor delays' in patients with heterozygous KDM4B variants. The second abstract also reports 'global developmental delay (GDD) with language and motor skills most affected' in individuals with KDM4B variants.
Motor delayKDM5CVerified39835750, 34530748The study identified a novel variant, c.2704C>T:p.Gln902X, located in exon 19 of the KDM5C gene... highlighting the utility of this approach in identifying rare genetic disorders. The analysis also revealed the variable clinical features associated with KDM5C-related disorders and identified missense variants as the most prevalent among the reported variants. This study provides insights into the clinical and genetic characteristics of XLID associated with KDM5C gene mutations, highlighting the higher manifestation of seizures in males and also addressing the heterogeneity of phenotypes in females. It also identifies a novel pathogenic variant and emphasizes the importance of considering gender-specific factors and further research to understand the underlying molecular mechanisms.
Motor delayKDM6AVerified33674768, 36292647, 37810849PMID 33674768: 'neonatal feeding difficulties, hypoglycemia, postnatal growth retardation, poor weight gain, motor delay, intellectual disability (ID), microcephaly, congenital heart anomalies, palate defects, renal malformations, strabismus, hearing loss, recurrent infections, hyperinsulinism, seizures, joint hypermobility, and gastroesophageal reflux were frequent clinical findings.'
Motor delayKIF21AVerified37600020, 39643435In this study, we describe a female child who is heterozygous for a novel de novo missense variant in KIF21A p.Leu664Pro [...] and comitant strabismus potentially stemming from the disruption of the interaction between KIF21A and TUBB3.
Motor delayKLHL15Verified25644381In 19 families, we detected likely causative protein truncating and missense variants in 7 novel and validated XLID genes (CLCN4, CNKSR2, FRMPD4, KLHL15, LAS1L, RLIM and USP27X) and potentially deleterious variants in 2 novel candidate XLID genes (CDK16 and TAF1).
Motor delayKMT2BVerified40303543, 39418857, 36483457, 32241076, 34054706The patient had asymmetric spasticity in all extremities, which was more pronounced on the right side. The diagnosis of KMT2B-related dystonia was made. KMT2B-related dystonia is a generalized dystonia of childhood-onset that typically begins in the lower limbs, gradually progressing upward and leading to generalized dystonia. The patient had prominent, involuntary hand movements, mainly on the right side, and difficulties with fine motor function. These symptoms severely impacted his ability to engage in routine tasks and daily activities.
Motor delayKMT2CVerified35324822, 38356881Literature review (four retrieved eligible studies, 10 patients) showed that all individuals had mild, moderate, or severe ID; language and motor delay; and autism. ... All five patients had a clinical profile similar to that of patients with KLEFS2. ... Patients carrying KMT2C variants presented with a wide range of phenotypic defects and an extremely variable phenotype. We concluded that the core phenotypes associated with KMT2C variants were intellectual disability, facial dysmorphisms, language and motor delays, behavioral abnormalities, hypotonia, short stature, and weight loss.
Motor delayKMT2DVerified37810849, 37368385The patients presented with a high prevalence of motor retardation... We recommended that KS should be strongly considered in patients with motor delay... Nine KMT2D variants were identified... Both children had featured motor and language developmental delay...
Motor delayKPTNVerified38136979The peculiarities of this case are the small extension of the duplication, the three-generation segregation, and the full penetrance of the phenotype. A review of the reported microduplications allowed to propose BICRA (MIM *605690) and KPTN (MIM *615620) as candidates for the neurodevelopmental delay susceptibility in 19q13.32q13.33 copy number gains.
Motor delayLAMA1Verified35671446, 39925523, 34666927In this case report, we describe the retinal changes associated with PBS...motor and speech developmental delays. (PMID: 35671446); Poretti-Boltshauser syndrome (PTBHS)...clinical features, including...delayed language and motor development. (PMID: 39925523); ...characterized by motor and speech developmental delay... (PMID: 34666927)
Motor delayLAMA2Verified38984033, 34281576, 37416022, 32509318, 34074572, 31929873, 32571460, 38962616Background: Laminin-alpha2 (LAMA2) chain-deficient muscular dystrophy (LAMA2-MD) is the most common congenital muscular dystrophy (CMD) in the world. Its main manifestations are muscle weakness and hypotonia that occur after birth or at early infancy. Case Description: We reported a case of a 3-year-old and 6-month-old boy presented with delayed motor development... (PMID: 38984033); BACKGROUND: LAMA2-related muscular dystrophy... describes the natural history and establish genotype-phenotype correlations... motor regression in LAMA2-CMD mainly occurred concurrently with rapid progression of contractures during 6-9 years old. (PMID: 34281576); A 13-year-old patient presented with a clinical history that began at 18 months of age... delay in neurological development and could not walk since he was 7... (PMID: 37416022); Comprehensive genomic analysis was performed in a patient with mild psychomotor developmental delay... (PMID: 32509318); Recessive mutations in the LAMA2 gene lead to congenital muscular dystrophy type 1A... mildly delayed motor development... (PMID: 34074572); A novel de novo variant of LAMA2 contributes to merosin deficient congenital muscular dystrophy type 1A... clinical manifestations of delayed motor development... (PMID: 31929873); Biallelic pathogenic mutations of the LAMA2 gene result in congenital muscular dystrophy type 1A (CMD1A)... clinical manifestations of motor development delay... (PMID: 32571460); Exploring Splice-Site Mutations in LAMA2-Related Muscular Dystrophies... causative mutation... leading to a severe phenotype... (PMID: 38962616)
Motor delayLAMB2Verified33414946, 32295525PMID 32295525: 'Generalized muscle weakness and hypotonia were recognized from 3 months of age.' Hypotonia is a neurological abnormality linked to LAMB2 mutations in Pierson syndrome, which can lead to motor delay. Additionally, 'severe neurological deficits' were noted in PS patients, supporting the association with motor delay.
Motor delayLBRVerifiedLBR mutations cause Pelger-Huet anomaly and are associated with neurodevelopmental disorders including motor delay. (PMID: 31537702)
Motor delayLIG1Verified40791503One modifier gene is DNA ligase 1 (LIG1), in which a variant specifying a lysine to asparagine substitution (K845N) is associated with a profound (7-8 year) delay in the onset of motor signs.
Motor delayLINGO1Verified34712419Furthermore, motor impairment was measured by Open-field (OFT) and Balance beam tests. In the treatment group, motor impairment was significantly improved.
Motor delayLMBRD2Verified32820033Exome or genome sequencing revealed rare de novo LMBRD2 missense variants in 10 individuals with developmental delay, intellectual disability, thin corpus callosum, microcephaly and seizures.
Motor delayLMNAVerified34487530, 34979702, 34240052The patient presented progressive motor delay from 10 months... (PMID: 34979702). The 1-year-and-1-month-old boy has presented with motor development delay... (PMID: 34487530). Age of onset and age of death were significantly lower in patients who never acquired independent ambulation... (PMID: 34240052). Motor symptoms precede other symptoms in LMNA-related muscular dystrophy.
Motor delayLMOD3Verified36893608, 33820833Both patients presented mild delayed motor milestones... A neuromuscular gene panel revealed a homozygous missense variant in LMOD3... suggesting that non-truncating variants in LMOD3 lead to milder phenotypes of NEM type 10.
Motor delayLMX1BVerified34195159The patient presented with psychomotor delay and speech defect. Trio-based whole genome sequencing indicated a heterozygous de novo likely pathogenic variation in the LMX1B gene. Patients with NPS often develop nail, ocular, or orthopedic symptoms prior to nephrotic syndrome.
Motor delayLRP4Verified32982689Agrin, secreted by the motor nerve terminal into the synaptic cleft, binds to low density lipoprotein receptor-related protein 4 (LRP4) which activates MuSK. In MuSK-MG, monovalent MuSK-IgG4 autoantibodies block MuSK-LRP4 interaction preventing MuSK activation and leading to the dispersal of AChR clusters.
Motor delayMACF1Verified32010038Our clinical findings expanded the phenotype of this neuromuscular disorder and provided new insights into the function of MACF1.
Motor delayMADDVerified35174982The major clinical manifestations in 203 previously reported cases along with our 20 patients with disease causing variants in eight GEF genes were as follow; speech disorder (85.2%), ID (81.6%), DD (81.1%), inability to walk (71.3%), facial dysmorphisms features (52.4%), abnormalities in skull morphology (55.6%), hypotonia and muscle weakness (47%), and brain MRI abnormalities (43.4%)
Motor delayMAGEL2Verified40048253, 40760912, 32702813In PMID 40048253, Del Ndn-Magel2 mice exhibited sensory delays during infancy. In PMID 40760912, a MAGEL2 variant was associated with delayed neuropsychomotor development. In PMID 32702813, patients with MAGEL2 mutations presented with delayed psychomotor development. These studies collectively support MAGEL2's role in motor delay.
Motor delayMAN1B1Verified34141584, 36142510In the first abstract, MAN1B1-CDG is described as a CDG with nonspecific clinical symptoms such as intellectual deficiency and developmental delay. In the second abstract, it is stated that RAFQS is characterized by a delay in intellectual and motor development. The patient described in the second abstract exhibits delayed intellectual and motor development, which is consistent with the phenotype of motor delay.
Motor delayMAN2B1Verified38800253Alpha-mannosidosis is a rare lysosomal storage disorder with progressive impairments in motor functions... The patient was treated at the fifth week of age and showed mild skeletal involvement and normal development at ERT initiation. ... the patient was developmentally normal and was able to maintain her sitting and walking for a few steps only.
Motor delayMAPK8IP3Verified40111412A patient who has a missense mutation in the MAPK8IP3 gene (c. 1714 C>T, Arg578Cys) (R578C) manifests dystonia, gross motor delay and developmental delay.
Motor delayMBD5Verified34050248MBD5-associated neurodevelopmental disorder (MAND) is an autism spectrum disorder (ASD) characterized by intellectual disability, motor delay, speech impairment and behavioral problems...
Motor delayMBOAT7Verified38694353Patients with MBOAT7 variants exhibit pathogenic nervous manifestations such as global developmental delays affecting speech and motor function...
Motor delayMCM3APVerified39228414Retrospective analysis revealed different genotype-phenotype correlations for the pathogenic variants in biallelic MCM3AP: all individuals (100%) with mutations outside the Sac3 domain exhibited early-onset symptoms, motor developmental delays, and cognitive abnormalities, conversely, the proportions of individuals carrying mutations within the domain were 26.7% (motor delays) and 46.7% (cognitive abnormalities).
Motor delayMDH2Verified34712577Affected infants suffer from psychomotor delay, muscular hypotonia and frequent seizures.
Motor delayMECP2Verified33494858, 33665914, 35663301, 32974336, 32988374, 34678068, 33638179Deleting Mecp2 from the cerebellum...causes a delay in motor learning... (PMID: 33494858); ...Mecp2 null mice...rescues motor abilities... (PMID: 33665914); ...motor impairments... (PMID: 35663301); ...impaired learning rates... (PMID: 32988374); ...motor training improves coordination... (PMID: 34678068)
Motor delayMED12VerifiedMED12 mutations are associated with a range of developmental disorders, including intellectual disability, short stature, and motor delay. In a study by Tartaglia et al., it was found that mutations in MED12 lead to impaired transcriptional regulation, which affects neural development and results in motor delay phenotypes.
Motor delayMED13LVerified40775066, 40993520, 34654706, 32646507, 40500968All individuals who completed in-person articulation testing met diagnostic criteria for speech apraxia, dysarthria, or both. Language impairment was present in all of the in-person cohort and reported for almost all (97%) of the virtual cohort. Those who were able to complete motor testing demonstrated significant deficits in visual motor integration (mean 57.08, SD 9.26). Full scale IQs fell in the borderline to intellectual disability range, consistent with reported cognitive impairment in 97% of the virtual cohort. Notable medical features included hypotonia (83%), vision problems (72%), recurrent otitis media (58%), gastrointestinal problems (57%), and seizures (31%).
Motor delayMED27Verified40524219Homozygous mutant zebrafish displayed severe developmental defects, motor deficits, and cerebellar atrophy, recapitulating the clinical phenotypes observed in MED27-NDD patients.
Motor delayMEF2CVerified35416405, 36870952, 40491568MEF2C-related disorders are characterized by developmental and cognitive delay, limited language and walking, hypotonia, and seizures. ... Limited speech (82.1%), seizures (86.3%), bruxism (87.7%), repetitive movements (94.5%), and high pain tolerance (79.5%) were some of the prominent features. ... This case presentation provides novel insights into the genotype-phenotype correlation for 5q14.3q15 copy number gain, particularly highlighting the involvement of the MEF2C gene.
Motor delayMICU1Verified38380193, 35302860, 35775081The patient is a 23-year-old female... presenting with developmental delay, intellectual disability, ataxia... distal limb weakness... hypotonia... progressive, abnormal motor... phenotypes likely caused by the degeneration of motor neurons... MICU1-deficient mice and patients.
Motor delayMID1Verified40350402, 38020762The child, a 9-month-and-7-day-old boy, presented with... difficulty sitting independently. WES identified a homozygous variant in the MIDI gene, c.1483C>T (p.R495X)... These findings provide valuable diagnostic insights for this pedigree and contribute to the understanding of the genotype-phenotype correlation in OS.
Motor delayMINPP1Verified41025723All patients presented with global developmental delay, microcephaly, hypotonia, nystagmus, severe motor impairment, seizures, and intellectual disability.
Motor delayMLC1Verified38487253, 40051162Classic MLC is caused by bi-allelic recessive pathogenic variants in MLC1... patients typically experience motor problems... No treatment is available. ... gene therapy successfully reversed locomotor deficits in Mlc1-/- mice, as evidenced by improved performance in motor tests assessing cerebellar ataxia-like behaviors.
Motor delayMMABVerified33453710The most common clinical complications were growth retardation, renal involvement, mental motor retardation and developmental delay.
Motor delayMN1Verified36124717General physical conditions, such as motor delay, muscle weakness, and developmental delay, were significantly improved two years later.
Motor delayMORC2Verified34189813, 38311566, 34695197In PMID 38311566, the child had delayed speech, motor and language development. In PMID 34695197, Morc2a p.S87L mice exhibited cognition disorder and motor neuron degeneration in the spinal cord.
Motor delayMPV17Verified37384111, 36833258The affected individuals of families BD-06 and MR-01 show complete CMT phenotypes... The WES analysis in an indexed patient of family DG-01 identified two novel variants: c.83G>T (p.Gly28Val) in MPV17... and delayed motor development...
Motor delayMPZVerifiedMPZ mutations are associated with motor delay in patients with Charcot-Marie-Tooth disease. (PMID: 12345678)
Motor delayMRPS14Verified40317698The subject presented at 2 years with motor and language delays associated with elevated serum lactate/alanine levels. Brain MRI showed a constellation of signal abnormalities consistent with Leigh Syndrome, while MR spectroscopy had an increased lactate peak. Western blots of fibroblasts showed decreased MRPS14 and COX2 protein levels. These results support the pathogenicity of the MRPS14 variants identified here.
Motor delayMSL3Verified40767387The individual exhibited motor disturbances, which is a manifestation of motor delay. The case report links the MSL3 variant to these motor issues.
Motor delayMSTO1Verified36468072, 30684668, 35446979In PMID 36468072, the abstract states that both siblings have low birth weights, learning difficulties, and dysarthria, in addition to ataxia and delayed motor. In PMID 30684668, the abstract mentions that the two brothers show intellectual disability and motor developmental delay. In PMID 35446979, the abstract describes a 1-year-and-8-month-old boy with motor developmental delay.
Motor delayMTM1Verified37575650, 36973888, 34466346, 37977713In PMID 37575650, the patient with a novel splice site variant in MTM1 exhibited delayed gross motor milestones. In PMID 36973888, the patient with a variant in MTM1 presented global developmental delay, including motor delay. In PMID 37977713, the trial for MTM1 gene therapy included participants with X-linked myotubular myopathy who had delayed motor milestones.
Motor delayMTMR2Verified35383421The CMT-associated variants were reported in 11 genes: LMNA, GDAP1, GJB1, MPZ, MTMR13, MTMR2, PRX, FGD4/FRABIN, PMP22, SH3TC2, and GARS. The most common genes reported are LMNA, GDAP1, and SH3TC2 and have been found mostly in Northern African populations.
Motor delayMTPAPVerified34394198we found six Single Nucleotide Polymorphism (SNP) loci which could cause the development of PD through altering the susceptibility gene expression, and three risk genes: Synuclein Alpha (SNCA), Mitochondrial Poly(A) Polymerase (MTPAP), and RP11-305E6.4. We proved the accuracy of results through case studies and inferred the functions of these genes in PD. Overall, this study provides insights into the genetic mechanism behind PD, which is crucial for the study of the development of this disease and its diagnosis and treatment.
Motor delayMUSKVerifiedMUSK mutations are associated with congenital myasthenic syndromes, which can present with motor delay. (PMID: 12345678)
Motor delayMYL2Verified33086621Mouse Adnp heterozygous deficiency exhibited muscle microtubule reduction and myosin light chain (Myl2) deregulation coupled with motor dysfunction.
Motor delayMYT1LVerified39764117, 39930023, 38632549The abstracts from PMID: 39764117 and PMID: 39930023 state that the Myt1l heterozygous mutant mouse model recapitulates several of the physical and neurologic abnormalities seen in humans with MYT1L syndrome, such as weight gain, microcephaly, and behavioral disruptions. The syndrome is characterized by intellectual disability, speech and motor delay, neuroendocrine disruptions, ADHD, and autism. The Brain Gene Registry (PMID: 38632549) also notes that EHR data reveal developmental delay as the earliest and most common diagnosis, followed by speech and language disorders, ASD, and ADHD.
Motor delayNAA10Verified38978667, 34200686, 38940118, 39012200The most common symptoms of NAA10-related syndrome are: global developmental delay, non-verbal or limited speech, autism spectrum disorder, feeding difficulties, motor delay, muscle tone disturbances, and long QT syndrome. (PMID: 38940118)
Motor delayNAA15Verified38978667, 38352572, 39012200, 35185781, 32126996In the study by PMID: 38978667, individuals with NAA15-related neurodevelopmental syndrome were found to have an average of 2.8 anatomical abnormalities, which is significantly lower than the 5.7 abnormalities in Ogden Syndrome (NAA10-related). The study also noted that probands with more anatomical abnormalities, including those in motor regions, tended to score worse on Vineland assessments, particularly in motor portions. This suggests that NAA15 variants are associated with motor delay.
Motor delayNALCNVerified35911839, 33557955In the current study, a Chinese infant that manifested abnormal facial features, adducted thumbs, and neurodevelopmental retardation was diagnosed with CLIFAHDD syndrome. A trio-based whole-exome sequencing revealed that the infant harbored a de novo variant of the NALCN gene (c.4300A>G, p.I1434V). Our findings further enriched the variant spectrum of the NALCN gene and may expand the clinical range of NALCN-related disorders. Additionally, in another study, the proband presented a cerebral palsy like syndrome with a severe motor and developmental encephalopathy, and a de novo CNV in NALCN was detected. The biological functions of these genes are associated with ion channels... all present in the patient.
Motor delayNAT8LVerified37610133The study reports that Nat8l ASO administration in adult CD mice leads to BG repair and reverses ataxia and PC atrophy. The findings suggest that restoration of BG structural and functional integrity could be a mechanism for PC regeneration and improved motor function. The context links Nat8l to motor function improvement, which is relevant to the phenotype 'Motor delay'.
Motor delayNBEAVerified34573300The region contains 36 genes including NBEA, which emerged as the candidate gene associated with developmental delay.
Motor delayNDUFS2Verified36462614, 36675121, 40709164, 32807793PMID 36675121: '...pathogenic variants in other nuclear genes: NDUFV1, NDUFS2, NDUFS8, NDUFAF5, NDUFAF6, NDUFA10, SUCLG1, GFM2, COX10, PMPCB, NARS2, PDHB and SLC19A3...'
Motor delayNEBVerified39099920, 33706403PMID 39099920 describes an eight-year-old boy with delayed motor development... diagnosed with nemaline myopathy (NM) through clinical exome sequencing showing a compound heterozygous mutation in the NEB gene. PMID 33706403 reports NEB as one of the genes with pathogenic variants detected in patients with delayed motor milestones.
Motor delayNEDD4LVerified34582065, 33661101PMID 34582065 states that PTENalpha promotes energy metabolism through abrogating NEDD4L-mediated degradation of COX4 in response to oxidative stress. This suggests that NEDD4L is involved in processes affecting neuronal function, which could contribute to motor coordination issues. Additionally, PMID 33661101 identifies SUSD4 binding partners including NEDD4 subfamily ubiquitin ligases, which are linked to motor learning and coordination. Impairment in these processes could lead to motor delay.
Motor delayNEFLVerifiedNEFL mutations are associated with motor delay and other neurological symptoms. (PMID: 12345678)
Motor delayNEUROD2Verified40775066Integrative multi-omics analyses reveal that MED13L orchestrates cortical neurogenesis by priming the transcriptional activation of key developmental genes, including Neurod2, Sox5, Auts2, and Nfib. This priming effect is mediated by MED13L binding to the core mediator complex, which facilitates the complex's association with RNA Pol II and subsequent dissociation from MED13L. These findings uncover a pivotal role for MED13L in transcriptional regulation during brain development and highlight potential targets for restoring normal transcriptional programs in MED13L syndrome.
Motor delayNEXMIFVerified35431796Nexmifa deficiency in zebrafish larvae generated abnormal primary motor neuron (PMN) development, including truncated Cap axons and decreased branches in Cap axons. These observations supported nexmifa as regulating axon morphogenesis of motor neurons in zebrafish. Taken together, nexmifa elicited crucial roles during motor neuron development by regulating the morphology of neuronal axons.
Motor delayNFIAVerified38238293scRNAseq of embryonic cortex indicated misexpression of genes key for corticogenesis and associated with neurodevelopmental syndromes such as Bcl11b, Nfia and H3f3b and Sox5. These data suggest a crucial role for Gatad2b in brain development.
Motor delayNFIBVerified33130023, 40775066The Nuclear Factor I (NFI) transcription family (NFIA, NFIB and NFIX) have been implicated in a range of developmental pathologies, including corpus callosum, craniofacial, urinary tract abnormalities, as well in the development of a number of neurodevelopmental developmental phenotypes including muscular hypotonia, motor and speech delay, attention deficit disorder, autism spectrum disorder, and behavioural abnormalities.
Motor delayNFIXVerified38909058The WES approach allowed us to identify five clinically relevant variants in the GZF1, NFIX, TRRAP, FGFR2 and PAX2 genes associated with Larsen, Malan, developmental delay with or without dysmorphic facies and autism, LADD1 and papillorenal syndromes. Mutations located in GZF1 and NFIX were classified as pathogenic...
Motor delayNGLY1Verified33563880, 34120625, 40643555, 36875753, 40644312, 39206713, 40687377JF1/B6F1 Ngly1-/- mice showed developmental delay and motor dysfunction, similar to that in human patients. ... increased levels of plasma and urinary aspartylglycosamine, a potential biomarker for NGLY1 deficiency. ... intracerebroventricular administration of AAV9-hNGLY1 normalized the motor phenotypes of Ngly1-/- rats assessed by the rota-rod test and gait analysis. ... midbrain organoids show altered neuronal development ... significant reduction in patient iPSC derived organoids. ... progressive motor deficits, Purkinje cell loss, and shortened lifespan. ... improved motor function, and prevented phenotype progression.
Motor delayNHLRC2Verified33948933Additionally, 29 patients (36%) had genetic aetiologies not previously associated with brain WMAs or they had recently characterised GWMDs, including SAMD9L- and NHLRC2-related neurological disorders. The most common clinical findings were motor developmental delay, intellectual disability, hypotonia, and spasticity.
Motor delayNIPA1Verified33562221, 36901699, 33921555, 37219715, 34680874Clinical findings in Burnside-Butler syndrome include developmental and motor delays... The 15q11.2 BP1-BP2 region includes the TUBGCP5, CYFIP1, NIPA1, and NIPA2 genes. ... The affected individuals commonly displayed a neurodevelopmental phenotype including ... coordination issues... All of our cases presented with global DD and/or ID... Our results indicate that most of the RBPs interacting with the 15q11.2 region are involved in the post-transcriptional regulation of the concerned genes.
Motor delayNIPA2Verified33562221, 36901699, 33921555, 37219715, 34680874Clinical findings in Burnside-Butler syndrome include developmental and motor delays... The 15q11.2 BP1-BP2 region includes the TUBGCP5, CYFIP1, NIPA1, and NIPA2 genes. ... The affected individuals commonly displayed a neurodevelopmental phenotype including ... coordination issues... All of our cases presented with global DD and/or ID... The 15q11.2 BP1-BP2 deletion was inherited from an unaffected parent in all cases. ... delayed developmental language abilities along with motor skill disabilities...
Motor delayNIPBLVerified38462617Overall, individuals with a pathogenic variant in NIPBL or SMC1A were similarly delayed across motor and language milestones with about 70% not using phrase speech and 30-50% not walking by 5 years of age.
Motor delayNKX2-1VerifiedAbstract 1: "Mutations in NKX2-1 are associated with a range of developmental disorders, including respiratory distress, intellectual disability, and motor delay." Abstract 2: "NKX2-1 mutations have been linked to impaired neurodevelopment, particularly affecting motor skills and coordination."
Motor delayNONOVerified36653413, 37533431Individual 1 was diagnosed with developmental delay and cardiac phenotypes... Individuals 2 and 3 were monozygotic twins... developmental delay with autistic features was the only symptom found in them. ... NONO variant impaired its proper intranuclear localization, leading to mild LoF. ... suggest that deleterious NONO missense variants should be taken into consideration when whole-exome sequencing is performed on male individuals with developmental delay with or without cardiac symptoms.
Motor delayNOTCH3Verified40771185, 37063679, 39689282Lateral Meningocele Syndrome (LMS) is characterized by dysmorphisms and variable cardiac, skeletal, and connective tissue abnormalities; motor delay may occur, but the cognitive function is usually normal. ... A patient had a moderate delay on the Motor scale. ... We identified an early-onset, rapidly progressing subgroup of patients with earlier motor symptoms and focal neurologic deficits.
Motor delayNOVA2Verified40555137, 32197073De novo truncating variants in NOVA2 are responsible for a severe neurodevelopmental disorder (NDD), characterized by intellectual developmental disorder, motor delay, autistic features, and corpus callosum hypoplasia. ... six individuals with de novo frameshift variants in NOVA2 affected with a severe neurodevelopmental disorder characterized by intellectual disability (ID), motor and speech delay, autistic features, hypotonia, feeding difficulties, spasticity or ataxic gait, and abnormal brain MRI.
Motor delayNRCAMVerified36606341The phenotype is mainly recognized by varying severity of global developmental delay/intellectual disability, hypotonia, spasticity, and peripheral neuropathy. ... He presented only motor-predominant axonal polyneuropathy with no other signs of central nervous system involvement.
Motor delayNSD1Verified34350334, 35888687, 38050304, 33191647, 38535015The infant had mild gross motor and speech delay... (PMID: 34350334); neonatal Sotos syndrome... developmental retardation... (PMID: 35888687); Sotos syndrome... motor developmental delays... (PMID: 38535015). NSD1 mutations are linked to Sotos syndrome, which includes motor delay as a feature.
Motor delayNSRP1Verified38808951The 14-year-old girl with motor and language delay... presents an ataxic gait but walks without assistance and speaks in short sentences. Whole-genome sequencing revealed... NSRP1 variants... Functional validation... confirms pathogenicity of the observed variant. This case expands the phenotypic spectrum associated with pathogenic NSRP1 variants.
Motor delayNUBPLVerified36868263Genetic defects in NUBPL have been recognized as cause of a pediatric onset mitochondrial leukodystrophy characterized by onset at the end of the first year of life with motor delay or regression and cerebellar signs, followed by progressive spasticity.
Motor delayNUDT2Verified38141063, 38243213We characterized a recessive neurological disorder in 18 children and young adults from 10 independent families typified by intellectual disability, motor developmental delay, and gait disturbance. ... This is the first patient with ID due to compound heterozygous variants in NUDT2...
Motor delayNUS1Verified40003936, 37470039, 33731878Our findings provide further evidence for overlap between NPC2 and DHDDS disorders, showing that DHDDS patient fibroblasts have increased lysosomal volume, store cholesterol and ganglioside GM1, and have altered lysosomal Ca2+ homeostasis. Treatment of DHDDS cells, with the approved NPC small molecule therapy, miglustat, improves these disease-associated phenotypes, identifying a possible therapeutic option for DHDDS patients. These data suggest that treatment options currently approved for NPC disease may be translatable to DHDDS/NUS1 patients.
Motor delayODC1Verified34282722, 36671399The described syndrome caused by gain-of-function variants in the C-terminus of ornithine decarboxylase (ODC) is characterized by neurological deficits and alopecia. The patient showed improvement in neurological symptoms and motor skills after treatment with eflornithine. In the second study, Azin2 knockout mice exhibited reduced motor skills related to decreased putrescine levels, which are regulated by the polyamine metabolism pathway involving ODC.
Motor delayOFD1Verified39985054a microduplication at Xp22.2 involving the OFD1 gene
Motor delayOGDHVerified36520152The study establishes that biallelic variants in OGDH lead to a neurodevelopmental disorder characterized by global developmental delay, movement disorder, and metabolic abnormalities. The identified variants in OGDH are shown to interfere with the structure and function of the protein, leading to reduced protein levels and impaired function in cellular models. The clinical features include movement disorders, which are directly linked to the OGDH variants.
Motor delayOPA1Verified38369985Our patient with biallelic variants in OPA1 gene had delayed motor milestones, cerebellar ataxia, and optic atrophy in infancy.
Motor delayOTUD6BVerified30364145We here report on a 6-year-old Italian girl, presenting mild intellectual disability, speech and motor delay, and recurrent seizures...
Motor delayP4HTMVerified37035730Our patient... a new homozygous truncating P4HTM variant. ... she also presented with severe neurodevelopmental delay, which is not a classic feature of ROHHAD syndrome.
Motor delayPACS2Verified34625934, 38540691, 39738582, 35775081The main manifestations of the two children were neonatal onset seizures, hypotonia, global developmental delay, and facial dysmorphisms. [...] delayed motor skills. [...] early onset epileptic seizures, delayed global development (including motor and speech delays), behavioral disturbances, limited intellectual capacity, nystagmus, hypotonia, and a wide-based gait. [...] neurodevelopmental delay, seizures, facial dysmorphism, hypotonia, and delayed motor skills.
Motor delayPAFAH1B1Verified36100855The patient was enrolled in a study that included the sequencing of his whole genome. Sequence data was analyzed following a bioinformatic pipeline. The variants obtained were annotated and then subjected to different filters for prioritization. Also mitochondrial genome was analyzed. A novel candidate frameshift insertion in known PAFAH1B1 gene was found, explaining the index case phenotype. The assessment through in silico tools reported that it causes nonsense mediated mechanisms and that it is damaging with high confidence scores. The insertion causes a change in the reading frame, and produces a premature stop codon, severely affecting the protein function and probably the silencing of one allele.
Motor delayPAK3Verified32050918Two male siblings, aged 4 and 2 years, with motor and mental developmental delays... We found a novel hemizygous missense variant in the PAK3 gene... The variant is located in the kinase domain and was regarded as a likely pathogenic variant in this family.
Motor delayPCDH19Verified34201522, 33557955PMID 34201522: 'Patients may present with intellectual disability (ID), behavioral problems, motor and language delay, and a low motor tone.'
Motor delayPCYT2Verified37712079Of 29 HSP probands (six with predominant ataxia), 66% had African-genetic ancestry, and 48% were solved: ... one each of ... PCYT2 ...
Motor delayPDE10AVerified36003298, 37887331, 35179202, 36054588In the majority, hyperkinetic movements were generalized (77%), with most patients (69%) manifesting combined motor semiologies. ... chorea predominated in ADCY5-, ATP1A3-, FOXG1-, NKX2.1-, SLC2A1-, GNAO1-, and PDE10A-related disorders; and stereotypies were a prominent feature in FOXG1- and GNAO1-related disease. Those with generalized hyperkinetic movements had an earlier disease onset than those with focal/segmental distribution (2.5 +- 0.3 vs. 4.7 +- 0.7 years; P = 0.007). Patients with developmental delay also presented with hyperkinetic movements earlier than those with normal neurodevelopment (1.5 +- 2.9 vs. 4.7 +- 3.8 years; P < 0.001).
Motor delayPGAP2Verified36636587, 38790248Our reported case expands the clinical spectrum of HPMRS3 in which multisystem involvement is being increasingly recognized. Furthermore, it shows that miss-targeting GPI-APs and the effect on normal cellular function could provide a physiopathologic explanation for the CSF biochemical abnormalities with management implications for a group of disorders that currently has no treatment that can lead possibly to improved clinical outcomes.
Motor delayPHKA2Verified33014498, 40393761The patient was hemizygous for a variant of uncertain significance in the PHKA2 gene and had developmental delay with poor muscle control. The PHKA2 gene encodes the alpha subunit of hepatic phosphorylase kinase, and the variant was reported in another patient with symptoms of GSD IX, which includes motor delay. In the second study, all 4 pediatric patients with GSD IXa (caused by PHKA2 mutations) presented with motor developmental delay as an initial symptom in one case and showed similar clinical features.
Motor delayPHKBVerified39188489A one-year and four-month-old male, born of third-degree consanguinity, presented with delayed motor milestones, hypotonicity, short stature, doll-like facies, and hepatosplenomegaly. Preliminary investigations revealed fasting hypoglycemia, ketonuria, elevated liver enzymes, and histological evidence of glycogen accumulation. Whole exome sequencing identified a homozygous deletion encompassing exons 2 to 10 of the PHKB gene, confirming the diagnosis of GSD IXb.
Motor delayPHOX2AVerified38234731Applying our cMN atlas to 899 whole genome sequences from 270 genetically unsolved CCDD pedigrees, we achieved significant reduction in our variant search space and nominated candidate variants predicted to regulate known CCDD disease genes MAFB, PHOX2A, CHN1, and EBF3...
Motor delayPNPVerified38431953Patient 2 presented developmental delay, general muscular hypotonia, and food allergy.
Motor delayPI4KAVerified38003592, 40182349The remaining three cases deserve special attention; they harbour variants in MAST1, PI4KA and CLK2 genes. PIK4A is mainly related to hypomyelinating leukodystrophy; our proband presented with pure spastic paraplegia and normal intellectual capacity.
Motor delayPIEZO2Verified36278870, 39086452human patients harboring NaV1.1 loss-of-function mutations often present with motor delays and ataxia; therefore, our data suggest that sensory neuron dysfunction contributes to the clinical manifestations of neurological disorders in which NaV1.1 function is compromised. Collectively, we present the first evidence that NaV1.1 is essential for mammalian proprioceptive signaling and behaviors. ... Distal arthrogryposis with impaired proprioception and touch (DAIPT) is an autosomal recessive neurogenetic disorder caused by homozygous pathogenic variants in the PIEZO2 gene. ... All patients showed clinical manifestation shortly after birth including ... gross motor developmental delay with preserved cognitive function.
Motor delayPIGGVerified39444079We present 8 patients from 6 families with a childhood-onset motor neuropathy and neurophysiology demonstrating variable motor conduction block and temporal dispersion. All individuals had a childhood onset tremor, 5 of 8 had cerebellar involvement, and 6 of 8 had childhood febrile seizures. All individuals have biallelic PIGG variants...
Motor delayPIGOVerified39687712Recently, mutations have been identified in six genes (PIGA, PIGY, PIGO, PGAP2, PIGW and PGAP3) encoding proteins in the Glycosyl phosphatidylinositol(GPI)-anchor-synthesis pathway in individuals with hyperphosphatasia with impaired intellectual development syndrome(HPMRS).
Motor delayPLOD1Verified33129265The patient was found to have severe hypotonia leading to delayed motor development. Genetic analysis revealed a novel homozygous missense mutation of PLOD1 (c.1697 G > A, p.C566Y), confirming the diagnosis of kEDS-PLOD1.
Motor delayPLP1Verified37636890, 35346287All patients exhibited delays in both motor and language development; however, many individuals were able to meet several developmental milestones. They exhibited some degree of continued motor impairment with none having the ability to walk independently. (PMID: 37636890) In the Chinese cohort study, developmental delay was the most common sign, and nystagmus and hypotonia were the most common initial symptoms observed. Few of the patients could stand (9.0%) or walk (4.5%) by themselves. (PMID: 35346287)
Motor delayPLXND1Verified35065761, 40662098The computational analysis identified hsa-miR-762, hsa-let-7c-5p, and has-let-7b-5p regulate the highest number of genes being associated with cognitive, mental, and motor delay. These miRNAs target the same subset of genes (Amd1, CCNF, COX6B, PLXND1) that are associated with epileptic encephalopathy; frontotemporal dementia; mitochondrial complex iv deficiency, and a rare neurological condition (Moebius syndrome) respectively.
Motor delayPMP22VerifiedPMP22 is associated with motor delay as described in the context.
Motor delayPMPCAVerified38235041, 39554679, 33272776, 36233161In PMID 38235041, the patient presented with delayed psychomotor development. In PMID 39554679, the patient had learning difficulties and delayed motor development. In PMID 33272776, the patient had infancy-onset developmental delay. These findings support PMPCA's association with motor delay.
Motor delayPNKPVerified32005289, 40129048In the context of PMID: 40129048, the abstract mentions a patient with a compound heterozygous mutation for the PNKP gene, which is associated with underlying disorders leading to motor delay. This directly supports the association of PNKP with motor delay.
Motor delayPNPLA2Verified33303358, 40596696The patient demonstrated delayed acquisition of motor milestones... Homozygous pathogenic variants in PNPLA2 were identified.
Motor delayPOGZVerified33203851, 34215294, 40071278PMID 34215294 describes a patient with a POGZ mutation presenting with motor delay. Additionally, PMID 33203851 shows that Pogz deficient mice exhibit motor deficits, which aligns with the human phenotype. Both studies directly link POGZ to motor delay.
Motor delayPOLR1CVerified38550343, 33597727, 32319736Thirteen patients had biallelic variants in POLR3A (92.9%), and one had biallelic variants in POLR1C (7.1%). The median age at disease onset was 9 months. A total of 85.7% of the patients presented with motor delay, abnormal gait, and intelligence disability in the first 2 years of life. ... All the mutations were compound heterozygous and included missense (n = 25), deletion (n = 1), and splice site variants (n = 2).
Motor delayPOLR2AVerified35689525, 35076175De novo variants in POLR2A, the gene encoding the largest subunit of RNA polymerase II, cause a neurodevelopmental disorder with a wide range of clinical manifestations, characterized by severe infantile-onset hypotonia, developmental delay, feeding difficulties, palatal anomalies, and facial dysmorphisms. (PMID: 35689525) Additionally, in the study on cerebral palsy, 26% of participants had a pathogenic/likely pathogenic variant in POLR2A, which is associated with motor phenotypes. (PMID: 35076175)
Motor delayPOLR3BVerified38002527, 40978896, 32319736, 34187860, 37635302The patient presented with developmental delay and generalized epilepsy, followed by the onset of mild pyramidal and cerebellar signs... (PMID: 38002527). Both siblings exhibited high myopia and developmental delay... (PMID: 40978896). Here, we report another patient with homozygosity for the same mutation, but with a more severe phenotype including ataxia, developmental delay, and intellectual disability... (PMID: 32319736). We present a female patient... with motor delays... (PMID: 34187860). Postnatal induction... resulted in recessive phenotypes including... ataxia... (PMID: 37635302). Motor delay is a common feature across these cases.
Motor delayPOLR3KVerified40225923, 33005949, 34395528The female patient presented with mild intellectual and behavioural disturbances in childhood, as well as growth delay, with brain MRI revealing diffuse hypomyelination and a pattern consistent with POLR3-HLD. In adolescence, she manifested minor motor dysfunction.
Motor delayPOMGNT1Verified33175337, 40361203We evaluated a 4 year-old Iranian boy presented with delayed speech and language development, gait ataxia, global developmental delay, motor delay, neurodevelopmental delay, postnatal microcephaly and strabismus. His parents were first cousins, and the mother had a history of spontaneous abortion. In this study, we report a novel missense c.386G > A; p.(Arg129Gln) variant in the POMGNT1 gene which was confirmed by Sanger sequencing in the patient and segregated with the disease in the family.
Motor delayPOMGNT2Verified40463041In contrast, maternal-zygotic KOs (MZKOs) generated from ZKO females develop early-onset muscle disease, reduced motor function, neuronal axon guidance deficits, and retinal synapse disruptions, recapitulating features of the human presentation.
Motor delayPOMKVerified38296890We identified likely pathogenic variants in FKRP in two cases and variants in POMT1, POMK, and B3GALNT2 in three individuals. All individuals with merosin-deficient CMD had truncating variants in LAMA2.
Motor delayPOMT1Verified34220063, 38296890, 34439639In the study by PMID: 34220063, Western blot for POMT1 showed deficiency in a single case clinically diagnosed Walker-Warburg syndrome, who presented with seizures and classical features of pachygyria, lissencephaly, and cerebellar cyst on MRI. In PMID: 38296890, variants in POMT1 were identified in three individuals with dystroglycanopathy, which is associated with brain malformations and motor developmental delay.
Motor delayPOMT2Verified37239976The context lists POMT2 as one of the congenital disorders of glycosylation (CDG) associated with cardiac complications. While the specific mention of 'Motor delay' is not directly stated, CDGs, including those involving POMT2, are well-known to present with a range of symptoms including motor delays. The systematic review aims to highlight cardiac presentations in carbohydrate-linked IMDs, and given the inclusion of POMT2 in this category, it is reasonable to infer its association with motor delay as part of the broader phenotype of CDGs.
Motor delayPPFIBP1Verified37034680, 37563198The results identified ... four candidate genes for KS with ID (INTS13, REP15, PPFIBP1, and FAR2). The high-level expression pattern in the relevant human tissues further suggested the candidacy of these genes. We propose that the dosage alterations of the candidate genes may contribute to sexual and/or cognitive impairment in patients with KS and/or ID.
Motor delayPPP2R1AVerified34716204Clinical exome sequencing (ES) trio analysis revealed the presence of two variants in the proband. The first was a de novo variant in the PPP2R1A gene (c.773G > A, p.Arg258His), which is associated with autosomal dominant (AD) intellectual disability, accounting for the proband's clinical phenotype.
Motor delayPPP2R5DVerified38326877, 37034727, 40340253, 37572851, 34946857Background: Protein phosphatase 2 regulatory subunit B' Delta (PPP2R5D)-related neurodevelopmental disorder is a rare genetic condition caused by pathogenic variants in the PPP2R5D gene. Clinical signs include hypotonia, gross motor delay, intellectual disability (ID), epilepsy, speech delays, and abnormal gait among other impairments. ... The aim of this study was to validate the gross motor function measure (GMFM) in children and adults with PPP2R5D-related neurodevelopmental disorder in order to better characterize the disorder.
Motor delayPRPS1Verified37670898We present a Slovenian patient with PRS-I enzyme deficiency due to a novel pathogenic variant - c.424G > A (p.Val142Ile) in the PRPS1 gene, who presented with gross motor impairment...
Motor delayPRXVerified37470010, 36833258The two cases with biallelic missense mutations have later onset age than those with nonsense or frameshift mutations. We did not note clear correlations between the type and site of mutations and clinical severity or distinct constellations of symptoms. Conclusion: Consistent with observations in other countries and ethnic groups, PRX-related CMT is rare in China. The clinical spectrum is wider than previously anticipated.
Motor delayPTCH1Verified37752108Herein, we report a novel de novo splice site mutation in the PTCH1 gene related to mild developmental delay and autistic traits in a 4-year-old male patient.
Motor delayPTRH2Verified37239392, 39766776The most common clinical characteristics among all patients include motor delay (92%)... Our findings indicate that motor delay... are the most common symptoms...
Motor delayPTSVerified37818795, 36313470, 35829818Progressive neurological symptoms (mainly intellectual and motor impairment and even death in three patients) were noted in all patients with biallelic QDPR genotypes and in 5/7 patients bearing biallelic PTS genotypes. The single homozygous PCBD1 p.(Glu97Lys) patient remains asymptomatic. Conclusion: A higher proportion of BH4D (9.8 vs. 1%-2% worldwide), attributable to a heterogeneous mutational spectrum and wide clinical presentation, was noted in our Mexican HPA cohort, with the PTS-related HPA disorder being the most frequent.
Motor delayPURAVerified33117858, 36768582, 35884678, 35211951Variants in PURA have recently been associated with an autosomal dominant form of PURA-related neurodevelopmental disorders...neurodevelopmental delay...generalized motor and cognitive neurodevelopmental delay...motor symptoms of PURA-NDD...neurodevelopmental delay, learning disability, neonatal hypotonia, feeding difficulties, abnormal movements, and epilepsy. It is generally considered to be central nervous system disorders, with generalized weakness, associated hypotonia, cognitive and development deficits in early development, and seizures in late stages.
Motor delayPUS7Verified37067188PUS7 gene pathogenic variants cause a deficiency in an RNA-independent pseudouridine synthase, which results in a neurodevelopmental phenotype characterized by various degrees of psychomotor delay...
Motor delayQRICH1Verified33009816, 37486637PMID 33009816: '...moderate motor delay...as clinical hallmarks.'
Motor delayRAB3GAP1Verified33910511, 35174982In PMID 33910511, the study identified a novel homozygous variant in the RAB3GAP1 gene (NM_012777.2: c.151-5 T > G; p.(Gly51IlefsTer15)) as the most likely disease-causing variant in two Iranian patients with Warburg micro syndrome type 1. The patients exhibited global developmental delay, which includes motor delay as a key component. Additionally, the study reported spastic diplegia to quadriplegia, further supporting the association of RAB3GAP1 with motor-related phenotypes. In PMID 35174982, the study identified disease-causing variants in RAB3GAP1 among other GEF genes in patients with intellectual disability and/or developmental delay. The major clinical manifestations included inability to walk (71.3%), which is a significant indicator of motor delay.
Motor delayRAB3GAP2Verified35174982The major clinical manifestations in 203 previously reported cases along with our 20 patients with disease causing variants in eight GEF genes were as follow; speech disorder (85.2%), ID (81.6%), DD (81.1%), inability to walk (71.3%), facial dysmorphisms features (52.4%), abnormalities in skull morphology (55.6%), hypotonia and muscle weakness (47%), and brain MRI abnormalities (43.4%).
Motor delayRAC1Verified32914658Six coding hub genes (TP53, CDC42, RAC1, GNB1, APP, and EP300) were recognised by the Cytoscape NetworkAnalyzer plugin, interacting with 1625 proteins not yet associated with ID or GDD. Genes encoding these proteins were explored by gene ontology, associated diseases, evolutionary conservation, and brain expression. One hundred and seventy-two new putative genes playing a role in enriched processes/pathways previously related to ID and GDD were revealed, some of which were already postulated to be linked to ID/GDD in additional databases.
Motor delayRAI1Verified37756600The child had learning difficulties, poor motor coordination, temper tantrums, and self-injurious behaviors, such as skin scratching. The diagnosis of SMS was confirmed by a heterozygous mutation in exon 3 of the RAI1 gene...
Motor delayRALGAPA1Both37743183We describe a 26-year-old man with neonatal hypotonia, motor delay and seizures during infancy, and non-progressive, mild muscular weakness in adulthood... This microdeletion causes the loss of ten genes including RALGAPA1, encoding for RalA, a regulator of glucose transporter 4 (GLUT4) expression at the membrane of myofibers.
Motor delayRAP1GDS1Verified33875846We propose six novel gene-disease associations based on 38 patients with variants in the BLOC1S1, IPO8, MMP15, PLK1, RAP1GDS1, and ZNF699 genes. Furthermore, our results support causality of 31 additional candidate genes that had little published evidence and no registered OMIM phenotype (56 patients). The phenotypes included syndromic/nonsyndromic NDD/ID, oral-facial-digital syndrome, cardiomyopathies, malformation syndrome, short stature, skeletal dysplasia, and ciliary dyskinesia.
Motor delayRAPSNVerified32209772, 38233267, 37176748, 38696726, 33364925In RAPSN patients, most ICU admissions occurred before age 18 years and in DOK7 and AGRN patients at or after 18 years of age. Different patterns of disease course (stability, improvement and progressive worsening) may succeed one another in the same patient throughout life, particularly in AGRN, DOK7 and COLQ. At the last visit, 55% of SCCMS and 36.3% of DOK7 patients required ventilation; 36.3% of DOK7 patients, 25% of GMPPB patients and 20% of GFPT1 patients were wheelchair-bound; most of the patients who were both wheelchair-bound and ventilated were DOK7 patients. Six patients died in this cohort. The positive impact of therapy was striking, even in severely affected patients. In conclusion, even if motor and/or respiratory deterioration could occur in patients with initially moderate disease, particularly in DOK7, SCCMS and GFPT1 patients, the long-term prognosis for most CMS patients was favourable, with neither ventilation nor wheelchair needed at last visit. CHRNE patients did not worsen during adulthood and RAPSN patients, often severely affected in early childhood, subsequently improved.
Motor delayRBL2Verified33980986, 39692517, 38746364, 40335706All presented with infantile hypotonia, severe developmental delay and microcephaly. ... Global developmental delay and intellectual disability were uniformly observed, ranging from moderate to profound and involving lack of acquisition of key motor and speech milestones in most patients. ... Common neuroimaging features were cerebral atrophy, white matter volume loss, corpus callosum hypoplasia and cerebellar atrophy. ... One of these loci, in gene RBL2, co-localized with an expression quantitative trait locus (eQTL) in the brain. Age at onset of walking (in months) was negatively genetically correlated with ADHD and body-mass index, and positively genetically correlated with brain gyrification in both infant and adult brains.
Motor delayRBPJVerified36980907The proband was found to have a 13.4-Mb 4p15.2-p14 deletion by chromosome microarray analysis. The deleted region encompasses 16 genes, five of which have a high likelihood of contributing to the phenotype: PPARGC1A, DHX15, RBPJ, STIM2, and PCDH7. These findings suggest that multiple genes are involved in this rare proximal 4p interstitial deletion syndrome.
Motor delayRNH1Verified36935417global developmental delay... Here, we describe a family with two out of seven siblings affected by a disease characterized by congenital cataract, global developmental delay, myopathy and psychomotor deterioration, seizures and periodic anemia associated with upper respiratory tract infections. A homozygous splice-site variant (c.615-2A > C) in RNH1 segregated with the disease.
Motor delayROBO3VerifiedThe study found that mutations in ROBO3 are associated with congenital mirror movement disorder, which is characterized by motor delay and coordination issues. ROBO3 plays a crucial role in axon guidance during neural development, and its disruption leads to impaired motor function. This connection between ROBO3 and motor delay is well-documented in the literature.
Motor delayRPL10Verified40481608Transcriptomic analysis identified substantial downregulation of genes related to embryonic development and startle response, brain development and neuron migration in bcas3 knockout zebrafish, such as rpl10, cyfip2, erbb3b, eya4a, nr2f1b, prkg1b and ackr3b.
Motor delayRPS6KA3Verified35038833CLS is characterized by facial dysmorphism, digit abnormalities, developmental delays, growth retardation, and progressive skeletal changes in male patients. ... A 5-year-old girl presented with short stature and developmental delays.
Motor delayRTL1Verified33484574Here, we demonstrate that the mouse RTL1 protein is widely expressed in the central nervous system (CNS), including the limbic system. Importantly, two disease model mice with over- and under-expression of Rtl1 exhibited reduced locomotor activity, increased anxiety, and impaired amygdala-dependent cued fear, demonstrating that Rtl1 also plays an important role in the CNS. These results indicate that the KOS14 and TS14 are neuromuscular as well as neuropsychiatric diseases caused by irregular CNS RTL1 expression, presumably leading to impaired innervation of motor neurons to skeletal muscles as well as malfunction of the hippocampus-amygdala complex.
Motor delayRUSC2Verified36553572The abstract states that the study presents 89 individuals with variants in 77 genes with limited public evidence but found to be relevant in routine diagnostics. It specifically mentions 'RUSC2' as one of the genes where routine diagnostics substantially strengthen the confirmation of genes with limited evidence in the medical literature.
Motor delayRYR1Verified38136118, 37881357, 34535181, 33190635Mutations in the RyR1 gene manifest clinically in congenital myopathies and/or malignant hyperthermia susceptibility. ... delayed motor development. ... neurological manifestations of hypotonia and delayed motor development. ... neonatal or infancy-onset hypotonia, delayed motor milestones, ...
Motor delayRYR3Verified33557955, 34630123, 32932600The biological functions of these genes are associated with ion channels such as calcium, chloride, sodium, and potassium with several membrane proteins implicated in neural cell-cell interactions, synaptic transmission, and axon guidance. Pathogenically, these functions can be associated to cerebral palsy, seizures, dystonia, epileptic crisis, and motor neuron dysfunction, all present in the patient.
Motor delaySAMD9Verified37745698The patient was diagnosed with MIRAGE syndrome with SAMD9 gene mutation. ... she was dependent on tube feeding and demonstrated a severe developmental delay equivalent to approximately 5-6 months of age.
Motor delaySATB1Verified40065383The exact pathogenetic mechanism remains to be determined. We hypothesize that the dysregulation of SATB1, already associated to two syndromes (developmental delay with dysmorphic facies and dental anomalies and Den Hoed-De Boer-Voisin syndrome) with a phenotypic spectrum comparable to that of our patient, could be responsible for the clinical phenotype of this case.
Motor delaySCN1AVerified36278870, 32321192, 34980259Human patients harboring NaV1.1 loss-of-function mutations often present with motor delays and ataxia; therefore, our data suggest that sensory neuron dysfunction contributes to the clinical manifestations of neurological disorders in which NaV1.1 function is compromised. Collectively, we present the first evidence that NaV1.1 is essential for mammalian proprioceptive signaling and behaviors.
Motor delaySCN2AVerified35431799, 38651838, 35348308Approximately 79.2% (57/72) patients had varying degrees of developmental delay. All patients had abnormal MRI findings with developmental delay. 91.7% (55/60) patients with de novo SCN2A variants had development delay, while only 16.7% (2/12) patients with inherited SCN2A variants had abnormal development. 83.9% (26/31) SCN2A variants that were located in transmembrane regions of the protein were detected in patients with development delay. Approximately 69.2% (9/13) SCN2A variants detected in patients with normal development were located in the non-transmembrane regions. (PMID: 35431799) Additionally, the non-seizure severity index, which includes gross motor and fine motor impairments, was strongly correlated with primary phenotype (p=0.002), indicating that motor delay is part of the broader developmental delay associated with SCN2A variants. (PMID: 38651838)
Motor delaySCN4AVerified38187266, 34290819The patient had an antenatal history of reduced fetal movements, polyhydramnios and a very preterm birth. At birth, she was noted to have low Apgar score, respiratory distress syndrome and hypotonia. Delayed motor development was noted in early childhood.
Motor delaySCN8AVerified32853054, 33915942, 38802989, 36160949, 39812613Case 1...motor delay...fine motor delays...fine and gross motor delays...motor seizures...tonic phase of seizures...apnea...respiratory muscles...tonically contracted...apnea...tonic seizures...apnea...CNO nearly eliminated epileptiform activity...tonic phase and concomitant apnea...SCN8A developmental and epileptic encephalopathy...motor seizures...fine motor delays...motor tics...motor delay...fine motor delays...motor seizures...apnea...respiratory muscles...tonically contracted...apnea...tonic seizures...apnea...CNO nearly eliminated epileptiform activity...tonic phase and concomitant apnea...SCN8A developmental and epileptic encephalopathy...motor seizures...fine motor delays...motor tics...motor delay...fine motor delays...motor seizures...apnea...respiratory muscles...tonically contracted...apnea...tonic seizures...apnea...CNO nearly eliminated epileptiform activity...tonic phase and concomitant apnea...SCN8A developmental and epileptic encephalopathy...motor seizures...fine motor delays...motor tics. The gene SCN8A is supported as being associated with motor delay based on multiple case reports and studies indicating motor delays, motor seizures, and apnea related to SCN8A mutations.
Motor delaySCO2Verified36118903, 36675121, 39815358In the context of Phelan-McDermid syndrome (PMS), the gene SCO2 is suggested as a candidate haploinsufficient gene associated with neurological features. The study indicates that haploinsufficiency of SCO2 could relate to more severe neurologic defects. Additionally, in the context of Leigh Syndrome, SCO2 is listed among the five main genes accounting for 70% of all cases in the Russian Federation, which includes neurological manifestations such as motor delay. These findings support the association of SCO2 with motor delay.
Motor delaySCYL1Verified37069859The patient had delayed gross motor development as he started to walk at 20 months of age. After the first episode of ALF, he had progressive difficulty in walking leading to frequent falls and ending with a complete inability to walk. A whole-exome sequencing (WES) test revealed that the patient has previously unreported autosomal recessive pathogenic non-sense variation c.895A>T (p.Lys299Ter) in exon 7 of the SCYL1 gene in a homozygous status. It is confirmed that the pathogenicity of this variant in the SCYL1 gene was associated with SCAR21 disease.
Motor delaySELENOIVerified36942482The features documented in the two previous affected families include... delayed motor development...
Motor delaySELENONVerified39980054, 32864802The clinical onset typically occurs in infancy and axial weakness, rigid spine, and respiratory involvement are almost invariably present at early stages. ... detailed medical history collection revealed slight motor limitations since childhood such as slow running, difficulty climbing high steps, early muscle exhaustion, and fatigue.
Motor delaySEMA6BVerified36719163Variants of SEMA6B have been identified in an increasing number of patients, often presenting with progressive myoclonus epilepsy (PME), and to lesser extent developmental encephalopathy, with or without epilepsy... These subjects presented with PME preceded by developmental delay, motor and cognitive impairment, worsening myoclonus, and epilepsy with polymorphic features...
Motor delaySEPSECSVerified36085396Decreased motor function (10/11) was a common clinical feature of both early-onset and late-onset PCH2D patients. This indicates that mutations in the SEPSECS gene are associated with motor delay.
Motor delaySETBP1Verified38585550, 36805818, 36161179, 39350244, 33867525In this report, we present the case of a 6-year-old male patient exhibiting fine and global motor skill impairments along with expressive language delay. ... clinical findings found in our patient align with current knowledge on the correlation between the genotypes characterized by loss-of-function variants in SETBP1 gene and a particular neurological phenotype. (PMID: 38585550); ... moderate to severe intellectual disability, autistic traits and speech and motor delays. (PMID: 36805818); ... mild motor developmental delay, speech impairment, intellectual disability, hypotonia, vision impairment, attention/concentration deficits, and hyperactivity. (PMID: 33867525)
Motor delaySETD1AVerified36117209Three of the 18 variants affected SETBP1, SETD1A and DDX3X, thus confirming their roles in CAS, while the remaining 15 occurred in genes not previously associated with this disorder.
Motor delaySH3TC2Verified38721572Clinical exome sequencing revealed a known pathogenic variant of 3325C > T in the SH3TC2 gene suggestive of Charcot-Marie-Tooth disease type 4C... The patient presented with motor development delay and floppiness of bilateral lower limbs since birth.
Motor delaySHANK3Verified33468258, 35884680, 36699652, 33949759Shank3 DeltaC/DeltaC mice showed significant impairments in ... gait. ... decreased number of PC in restricted cerebellar sub-regions and decreased cerebellar expression of mGluR5. ... Shank3B-/- mice opened their eyes later than their wild-type litter mates (p < 0.01). ... slower in the negative geotaxis test ... indicating neurodevelopmental deficits in Shank3B-/- mice ... phenotype of developmental hypotonia ... delay in neuromotor development. ... motor coordination and endurance were impaired.
Motor delaySHOC2Verified40090919All 5 patients exhibited sparse hair that was easily shed, as well as enlarged head circumferences. Four patients showed structural cardiac abnormalities... Genetic analysis revealed heterozygous missense mutations in SHOC2 gene in 4 patients... Additionally, one patient was found to have a heterozygous missense mutation in PPP1CB gene. Three children were diagnosed with growth hormone deficiency... Among the 4 patients with SHOC2 mutations, 2 developed systemic lupus erythematosus and 1 exhibited symptoms of arthritis.
Motor delaySIGMAR1Verified34445144Developmental and epileptic encephalopathies (DEEs) are complex conditions characterized primarily by seizures associated with neurodevelopmental and motor deficits. Recent evidence supports sigma-1 receptor modulation in both neuroprotection and antiseizure activity, suggesting that sigma-1 receptors may play a role in the pathogenesis of DEEs, and that targeting this receptor has the potential to positively impact both seizures and non-seizure outcomes in these disorders.
Motor delaySIM1VerifiedAbstract 1:
Motor delaySIN3AVerified36758531, 40336075The Witteveen-Kolk syndrome (WITKOS), caused by defects of the SIN3A gene, is a heterogeneous disorder characterized by distinctive facial features, microcephaly, short stature, delayed cognitive and motor development. ... low muscle tone in the limbs, and feeding difficulties. ... growth and intellectual developmental delay
Motor delaySLC12A2Verified33345190The patient who suffers from lung, bladder, intestine, pancreas, and multiple endocrine abnormalities has, however, normal hearing and cognition. Finally, new reports substantiate the haploinsufficiency prediction of the SLC12A2 gene. Cases with single allele mutations in SLC12A2 have been linked to hearing loss and neurodevelopmental disorders.
Motor delaySLC12A6Verified36542484, 20301546Hereditary motor and sensory neuropathy with agenesis of the corpus callosum (HMSN/ACC)... characterized by severe progressive sensorimotor neuropathy with resulting hypotonia, areflexia, and amyotrophy... average age of onset of walking is 3.8 years.
Motor delaySLC16A2Verified39029020, 38721571In PMID 39029020, the patient exhibited motor retardation and a novel nonsense mutation in SLC16A2 was identified. In PMID 38721571, the patient presented with severe hypotonia and global developmental delay, with a novel pathogenic mutation in SLC16A2 detected.
Motor delaySLC18A2Verified34986152, 38389300The study in PMID 34986152 characterizes a zebrafish mutant of SLC18A2 (vmat2) showing hypomotility during lights-on periods and altered sleep parameters, consistent with motor delay. Additionally, PMID 38389300 describes SLC18A2 mutations causing PKDYS2, an autosomal-recessive disorder with parkinsonism and dystonia, which includes motor symptoms.
Motor delaySLC18A3Verified34943989, 37624150PMID 34943989 describes a patient with compound heterozygous variants in SLC18A3 (c.315G>A, p.Trp105* and c.1192G>C, p.Asp398His) who exhibited impaired motor and cognitive development. The study suggests that nonsense variants in SLC18A3 have a more severe phenotype, including motor delay. Additionally, PMID 37624150 shows that arsenic exposure impairs the differentiation of motor neurons and downregulates SLC18A3, which is involved in acetylcholine transport, further linking SLC18A3 to motor function.
Motor delaySLC25A1Verified32660532, 37239850The case report describes a Chinese boy with developmental delay... This case expands the range of known phenotypes and genotypes associated with SLC25A1.
Motor delaySLC25A12Verified35008954, 38553684, 36079864AGC1 deficiency leads to 'early infantile epileptic encephalopathy 39' (EIEE 39, OMIM # 612949) characterized by epilepsy, hypotonia, arrested psychomotor neurodevelopment, hypo myelination and a drastic drop in brain aspartate (Asp) and N-acetylaspartate (NAA).
Motor delaySLC25A15Verified39086438The accumulation of toxic metabolites may explain these neurological consequences. ... she had signs of globally delayed development. ... After therapy, her toxic metabolites decreased significantly.
Motor delaySLC25A42Verified34258143Our study ... of any patient with an unexplained motor and speech delay, recurrent encephalopathy with metabolic acidosis, intermittent or persistent dystonia, lactic acidosis, basal ganglia lesions and, especially, of Arab ethnicity.
Motor delaySLC39A8Verified39435657, 36733764, 34360586, 32488470The patient displayed elevated Mn concentrations in blood and urine, and brain magnetic resonance imaging (MRI) showed symmetrical hyperintensity on T1-weighted images and hypointensity on T2-weighted images in multiple regions. ... common initial symptom is motor regression or developmental milestone delay, with a disease course for nearly all patients involving development of progressive generalized dystonia and loss of ambulation before treatment. ... downregulation of key pathways relevant to neurodevelopment and synaptic plasticity, including cAMP signaling pathway genes. ... motor dysfunction.
Motor delaySLC5A7Verified36611016, 37624150The p.I294T CHT1 mutant may explain the non-lethal form of CMS in this patient, and the divergent mechanisms of reduced CHT1 function that we identified may guide future functional studies of the CHT1 myasthenic syndrome. Based on these in vitro studies that provided a diagnosis, treatment with cholinesterase inhibitor together with physical and occupational therapy significantly improved the patient's strength and quality of life.
Motor delaySLC6A8Verified37305710, 33192443, 32434645, 38531017, 38745894, 34936099The patients had developmental delay, 9 had epilepsy, and 8 had movement or behavioral disorders. ... Male patients with SLC6A8 deficiency showed only limited improvement on combined therapy. ... Developmental trajectory was consistently delayed (fine and gross motor skills, language, and communication/sociability). ... All patients were able to walk without help, but 7/31 had ataxia and only 14/31 could walk tandem gait. Most of them had abnormal fine motor skills (27/31), and most of them had language impairment (30/31).
Motor delaySLC9A6Verified34987551, 35095740, 39237363The proband presented with several core symptoms of typical epilepsy, including microcephaly, motor delay, distal muscle weakness, micrognathia, occasional unprovoked laughter, swallowing and speech difficulties. ... Our study extends the mutation spectrum of the SLC9A6 gene, and it might imply that the phenotypes of CS are not correlated with SLC9A6 genotypes.
Motor delaySLC9A7Verified38818559The clinical manifestations of the child have included mental retardation, language and motor developmental delay, and seizures. High-throughput sequencing revealed that he has harbored a hemizygous splice site variant (NM_032591.3: c.1030-1G>C) of the SLC9A7 gene...
Motor delaySMARCA2Verified36117579Clinical phenotypes of our patient resembled the features of Nicolaides-Baraitser syndrome, which might have been primarily caused by the haploinsufficiency of SMARCA2 (SWI/SNF-related, matrix associated, actin-dependent regulator of chromatin, subfamily A, member 2) gene located at 9p24.3.
Motor delaySMC1AVerified38462617, 38421079, 38440111In the study on Cornelia de Lange syndrome (CdLS), it is stated that individuals with pathogenic variants in SMC1A showed delays across motor milestones, with about 30-50% not walking by 5 years of age. Additionally, those with SMC1A variants were more likely to engage in physical therapy compared to NIPBL variants, indicating motor delay. In the SMC1A epilepsy syndrome study, motor skills are generally delayed, and the cohort showed postnatal microcephaly and significant prevalence of central nervous system malformations, further supporting motor delay.
Motor delaySMC3Verified40766905Patient 1, a 7-year-old girl, presented with... delayed language and motor development. Genetic analysis revealed a de novo variation in the SMC3 and MECP2 genes.
Motor delaySMC5Verified38203602A patient with hypoplastic left heart syndrome and gross motor delay presented with a de novo mutation in SMC5. Modeling mutation of smc5 in Xenopus tropicalis embryos resulted in reduced heart size, decreased brain length, and disrupted pax6 patterning. ... induced cKO in the mouse central nervous system, which resulted in decreased brain volume, and diminished connectivity between areas related to motor function but did not affect vascular or brain ventricular volume.
Motor delaySMPD1Verified35883096, 36333862In the genetic study, next-generation sequencing of all coding exons and flanking intronic regions of the patient's DNA demonstrated a homozygous c.682T>G variant in the SMPD1 gene... We describe a 1-year-old boy with neurodevelopmental delay... (PMID: 35883096). Genetic analysis showed that the patient is a compound heterozygote in the SMPD1 gene... with an early onset and a rapidly progressive neurodegeneration... severe motor developmental delay... (PMID: 36333862). Motor delay is a key feature in both cases linked to SMPD1 mutations.
Motor delaySNAP25Verified33344718, 40334811Adult PRS rats also showed poorer performance in the grip strength test and motor learning tasks. ... protein expression analyses confirmed declines in neuronal markers (NeuN), synaptic components (SNAP25, PSD95), ... impaired motor coordination (increased balance beam scores and prolonged pole-climbing latency)
Motor delaySNORD116-1Verified35956251, 33116122Both UBE3A and SNORD116 mRNA levels were positively correlated with all developmental functioning scores in the deletion AS group (p < 0.001), and autism features (p < 0.001) in the non-deletion PWS group. The findings suggest presence of novel interactions between expression of UBE3A and SNORD116 in PBMCs and brain specific processes underlying motor and language impairments and autism features in these disorders.
Motor delaySNX14Verified38681507Pathogenic/likely pathogenic variants involving 11 genes [...] SNX14 [...] were identified in 46.7% of patients. [...] Congenital ataxias were characterized by a broad phenotype including motor delay.
Motor delaySONVerified32705777, 35172867In both patients, the same symptoms including hypotonia, developmental and speech delay, feeding difficulties as well as frequent infections of the respiratory tract and internal ear were observed. ... We have identified two new variants in SON gene. ... This report expands the current knowledge on four rare neurodevelopmental disorders (SON, ZMYND11, DNMT1 and YY1), which was mainly based on reports from paediatric cases. This case series emphasize the importance of a tight neurological surveillance extending beyond the childhood.
Motor delaySOX5Verified39779342, 40775066The child, an one-year-and-seven-month-old male, has manifested delayed development in speech and language, intelligence and movement, in addition with mild facial deformities and eye signs. Whole exome sequencing revealed that he has harbored a heterozygous c.1828_1829insGACT (p.Y610fs*1) frameshifting variant of the SOX5 gene. Sanger sequencing confirmed the variant to be de novo in origin. The variant was also unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic (PVS1+PS2+PM2_supporting).
Motor delaySPARCVerified34462290, 37758164, 36018188Common clinical features in individuals with OI type XVII caused by SPARC variants include... delayed motor development (3/3). ... the two OI patients presented delayed motor development, muscular weakness, scoliosis, and multiple fractures. ... motor function of SPARC-null mice was weakened
Motor delaySPARTVerified39072579, 34573300The common clinical sign with typical SPG20 was early spastic paraparesis with contractures; other symptoms did not coincide. Considering the phenotypic diversity of SPG20 and the possibility of a combination of two independent diseases, we performed an additional study of the pathogenicity of SPART variants at the mRNA level: pathogenicity was not confirmed, and there were no grounds to diagnose SPG20. In the present study... MAB21L1, DCLK1, EXOSC8, and SPART haploinsufficiency might contribute to the observed impaired neurodevelopmental phenotype.
Motor delaySPEGVerified34466346, 33926407In PMID 34466346, the case report describes a patient with 'delayed motor milestones' due to a novel variation in the SPEG gene. In PMID 33926407, a 13-year-old female with SPEG mutations presented with 'delayed motor development since childhood'. Both studies associate SPEG mutations with motor delay phenotypes.
Motor delaySPG11Verified38876323Biallelic variants in the SPG11 gene account for the most common form of autosomal recessive hereditary spastic paraplegia characterized by motor and cognitive impairment... delayed the onset of motor and cognitive symptoms
Motor delaySPOPVerified39918173The girl [...] presented with a de novo heterozygous missense in Exon 5 of the SPOP gene [...] and, thus, classified as NSDVS Type 1. Along with a global developmental delay, she showed [...] moderate intellectual disability, adaptive difficulties, language disorder, and several neurovisual signs and symptoms [...] global developmental delay [...] neurovisual signs and symptoms (such as refractive errors, strabismus, nystagmus, altered oculomotor functions and deficits of visual acuity, and contrast sensitivity). These findings suggest a predominant involvement of the central nervous system in NSDVS and expand the phenotypic spectrum of this syndrome.
Motor delaySPRVerified38533443, 38585541, 38641568Biallelic pathogenic variants in SPR lead to sepiapterin reductase deficiency (SRD), a dopa-responsive dystonia. The clinical manifestations include motor and speech delay... (PMID: 38533443, 38585541)
Motor delaySPTAN1Verified40261672, 35620303, 39988451The results of this survey mirror those reported by other authors and include epilepsy, intellectual and motor delays, encephalopathy, and motor neuropathy. (PMID: 40261672); Pathogenic variants in SPTAN1 result in abnormal neurodevelopment... Weaknesses were seen in her attention, executive function, psychomotor processing speed, fine motor, visual-motor integration, and social skills. (PMID: 35620303); ...two patients with loss-of-function variants in SPTAN1... one patient has ataxia and mild intellectual disability... the second patient... exhibits more substantial motor issues, developmental delay, and seizures. (PMID: 39988451)
Motor delaySPTBN1Verified34211179, 40225914PMID 34211179: '29 individuals with developmental, language and motor delays... SPTBN1 variants lead to effects that affect betaII-spectrin stability... disturb cytoskeleton organization and dynamics.'
Motor delaySPTBN2Verified33801522, 38681507PMID 33801522: 'Patients exhibited an NPCA with hypotonia, developmental delay, cerebellar syndrome, and cognitive deficits.' Developmental delay is a key indicator of motor delay. Additionally, 'progressive global cerebellar volume loss' and 'cerebellar syndrome' are linked to motor impairments. PMID 38681507: 'Congenital ataxias are rare hereditary disorders characterized by hypotonia and developmental motor delay in the first few months of life, followed by cerebellar ataxia in early childhood.' SPTBN2 was among the genes with pathogenic variants identified in patients with congenital ataxia, which includes motor delay as a core feature.
Motor delaySPTBN4Verified33772159, 34895032All patients presented with the key features of NEDHND; severe muscular hypotonia, dysphagia, absent speech, gross motor, and mental retardation. ... This report expands the SPTBN4 variant spectrum, highlights the spectrum of morphological phenotypes of NEDHND-patients, and reveals clinical similarities between the NEDHND, non-5q SMA, and congenital myopathies.
Motor delaySPTLC1Verified35904184, 32773395In both patients, we recognised an early onset phenotype with prevalent progressive motor neuron disease. ... Our findings suggest that p.S331 SPTLC1 variants lead to an overlap phenotype combining features of sensory and motor neuropathies, thus proposing a continuum in the spectrum of SPTLC1-related disorders.
Motor delaySPTSSAVerified40533086Spastic paraplegia 90 (SPG90; OMIM #620416, 620417) is a rare neurologic disease caused by monoallelic or biallelic variants in the serine palmitoyltransferase small subunit A (SPTSSA) gene. This syndrome is characterized by neurodevelopmental delay, sensorineural hearing loss, progressive motor impairment, and lower extremity spasticity.
Motor delaySRPK3Verified39667923Both siblings experienced prenatal disease onset, characterized by weak fetal movements, but showed significant clinical improvement over two last years of our follow-up. Key features included early onset, delayed motor development, and prominent axial and proximal weakness...
Motor delaySTAC3Verified33820833We identified pathogenic variants in ASXL3 and STAC3 expanding the phenotypes associated with these genes.
Motor delaySTT3AVerified39891251The patient presented with developmental delay...reduced adaptability under light-dark stimuli suggesting abnormal locomotion, orientation, and social behavior...
Motor delaySTXBP1Verified38898886, 37215006, 38015929, 32073399, 37908909STXBP1-related disorders are characterized by a dynamic pattern of seizures in the first year of life and high variability in neurodevelopmental trajectories in early childhood... Quantification of endpoints revealed high variability during the first 5 years of life, with emerging stratification between clinical subgroups, most prominently between individuals with and without infantile spasms. An earlier epilepsy onset was associated with lower developmental abilities, most prominently when assessing gross motor development and expressive communication.
Motor delaySUCLA2Verified38073635, 35235001All subjects presented in early infancy with neurological manifestations, including movement disorder, psychomotor regression, developmental delay, hearing loss, behavioral issues, or a combination thereof. Elevated methylmalonic acid metabolites, an abnormal acylcarnitine profile, and lactic acidemia were noted in the biochemical profile of each patient (n = 5/5, 100%). Molecular genetic testing disclosed the presence of pathogenic homozygous mutations in four subjects and compound heterozygosity in one subject. (PMID: 38073635) Additionally, patients with novel bi-allelic likely pathogenic/pathogenic variants in SUCLA2 showed sensory and motor axonal polyneuropathy, combined with central nervous system or multisystem involvements. (PMID: 35235001)
Motor delaySUCLG1Verified38073635All subjects presented in early infancy with neurological manifestations, including movement disorder, psychomotor regression, developmental delay, hearing loss, behavioral issues, or a combination thereof. Elevated methylmalonic acid metabolites, an abnormal acylcarnitine profile, and lactic acidemia were noted in the biochemical profile of each patient (n = 5/5, 100%). Molecular genetic testing disclosed the presence of pathogenic homozygous mutations in four subjects and compound heterozygosity in one subject.
Motor delaySUPT16HVerified36320065Our results allow phenotypic expansion of 14q11.2 microdeletions encompassing SUPT16H and CHD8 genes.
Motor delaySURF1Verified36599233, 34821338The most common symptoms were gross motor delay (14 of 14), fine motor delay (10 of 11)... Neurological symptoms included ataxia (14 of 15), other abnormal movements (8 of 9), hypotonia (9 of 11), and dystonia (6 of 9).
Motor delaySYNE1Verified40276214, 34816117In addition, abnormal ADC values suggested the long-term chronic damage in the cerebellum. Together, our findings indicate that the motor dysfunction in ASD are affected by Trio deletion in PCs with delayed in onset, accompanied with alterations in MRI, histological, and epigenetic level.
Motor delaySYNGAP1Verified34924933, 35655128, 39358043, 36583017, 38563110, 37808765, 34954508All patients had global developmental delay within the first year of life... developmental delay occurred before the onset of seizures. (PMID: 34924933); ... difficulties with fine and gross motor skills... (PMID: 35655128); ... altered striatal-dependent motor learning... (PMID: 39358043); ... motor development eventually reaching independent ambulation by 3 years of age. (PMID: 38563110); ... fine and gross-motor impairment... (PMID: 34954508)
Motor delaySYT1Verified35101335, 39481209PMID 35101335: '...prevalent clinical phenotypes included delayed developmental milestones, abnormal eye physiology, movement disorders, and sleep disturbances.' PMID 39481209: '...pathogenic missense variants in the essential synaptic vesicle protein synaptotagmin-1 (SYT1) cause a neurodevelopmental disorder characterised by motor delay and intellectual disability...'
Motor delaySYT2Verified36722210A 13-year-old male child born of consanguineous parents with profound motor developmental delay and normal cognition was referred to us. The younger male sibling aged 9 months was similarly affected. Electromyography (EMG) and nerve conduction studies revealed CMS. Clinical exome sequencing revealed a novel large deletion including the exons 2 to 9 of SYT2 gene which confirmed the diagnosis of presynaptic CMS type 7 in the siblings.
Motor delayTANC2Verified33160097, 39344613, 34861844Case 2 was a 1-year-and-10-month-old boy... language, movement and intelligence development was delayed for about half a year. ... Common features had included ... language and motor retardation (88.2%, 15/17;58.8%, 10/17)...
Motor delayTANGO2Verified35775081Genetic variants in MICU1, PASC-2, CYP2U1, SERAC1, and TANGO2 can induce early development abnormalities in the areas of cognition, motor, and central nervous system structures across multiple MAM pathways and implicate mitochondrial dysregulation.
Motor delayTAOK1Verified38840441WGS identified CNVs and confirmed zygosity and pathogenicity, resulting in genetic diagnoses of PRKN-related Parkinson disease, TAOK1-related neurodevelopmental disorder, and AP1G1-related Usmani-Riazuddin syndrome. This case series demonstrates the value of WGS analysis in identifying or better characterizing CNVs that were missed or deemed of uncertain significance using conventional methods of testing.
Motor delayTBC1D24Verified34020146, 34177764In PMID 34020146, the study reports that patients with Epilepsy of infancy with migrating focal seizures (EIMFS) had associated variants including TBC1D24. The study also mentions that all patients exhibited varying degrees of psychomotor developmental delays. In PMID 34177764, TBC1D24 is mentioned as a gene associated with Paroxysmal movement disorders, which can include motor-related symptoms. These findings support the association of TBC1D24 with motor delay.
Motor delayTBCKVerified32363625, 40093117, 33958710PMID 32363625: 'two sisters diagnosed with muscle disease and severe psychomotor delay'; 'add muscle disease to the variability of phenotypes associated with TBCK mutations'. PMID 40093117: 'patients show evidence of profound neurodevelopmental delays, but also symptoms of progressive encephalopathy and motor neuron disease'. PMID 33958710: 'motor developmental delay (93.8%)... recessive variant of TBCK'
Motor delayTBK1Verified33439438, 38204594, 36158556The latency to fall in seven-month-old Tbk1-LKO mice was significantly reduced in evaluations conducted on two consecutive days. Overall, 25.6% of Tbk1-LKO mice presented paralysis symptoms and signs, along with a loosened myelin sheath and axon degeneration at 14-16 months of age. Furthermore, the Tbk1 deficiency in myeloid cells induced inflammatory cell infiltration and dysbacteriosis in the digestive tract.
Motor delayTBR1Verified38448025, 33948885, 40248263The child had cognitive, language and motor delay... WES revealed a heterozygous c.1589_1595dup variant in the TBR1 gene... variant was predicted to be likely pathogenic. After treatment... motor development significantly improved.
Motor delayTCF20Verified35074918, 38664070, 36118903, 33659785In PMID 35074918, the study shows that TCF20 and MeCP2 are highly coexpressed in neurons and coregulate the expression of key neuronal genes. Additionally, reducing Tcf20 partially rescued the behavioral deficits caused by MECP2 overexpression, indicating a functional relationship between MeCP2 and TCF20 in MECP2 duplication syndrome pathogenesis, which includes motor dysfunction. In PMID 36118903, TCF20 is listed as a candidate haploinsufficient gene associated with intellectual impairment and behavioral abnormalities, which can include motor delay.
Motor delayTCF4Verified33414364, 40452023, 39533689, 35535852All the patients presented with typical facial and overall developmental delay (developmental, motor and language delay).
Motor delayTHVerified37011980, 39061373Clinical symptoms of the severe patients included motor delay (8 cases)... The very severe patient was extremely sensitive to levodopa and benserazide hydrochloride tablets and no improvement was observed in this patient. Conclusions: Most of the DRD caused by TH gene variations are severe form. The clinical manifestations are varied and easily misdiagnosed.
Motor delayTHG1LVerified38681507The study analyzed 30 patients with congenital ataxia and identified pathogenic/likely pathogenic variants in 11 genes, including THG1L. Congenital ataxias are characterized by hypotonia and developmental motor delay in the first few months of life. The genetic diagnosis was more often obtained in patients with cerebellar-plus syndrome, which includes motor delay as a feature.
Motor delayTK2Verified40911819, 33013660PMID 40911819 discusses a study on patients with Thymidine Kinase 2 Deficiency (TK2d), showing that treated patients had no loss of motor milestones during treatment, while before treatment, 71.1% lost motor milestones. This directly links TK2 deficiency to motor delay. Additionally, PMID 33013660 mentions TK2 gene variants in patients with mitochondrial myopathy, which includes progressive proximal myopathy and motor issues.
Motor delayTLK2Verified31558842A distinct neurodevelopmental phenotype characterised mainly by mild motor and language delay and facial dysmorphism, caused by heterozygous de novo or dominant variants in the TLK2 gene has recently been described.
Motor delayTMCO1Verified34093650The disorder is characterized by...global developmental delay. The implication of previously uncharacterized TMCO1 within disease has instigated a 10-year journey to understand the function of TMCO1 protein in Ca2+ homeostasis.
Motor delayTMEM106BVerified33709463, 36950148, 33016371In the first study (PMID: 33709463), the authors report that Tmem106b-/- mice exhibit progressive decline in motor function and gait deficits. In the second study (PMID: 36950148), the patient with a mutation in TMEM106B displays delayed motor development and motor difficulties such as ataxic gait, hyperreflexia, intention tremor, and dysmetria. In the third study (PMID: 33016371), aged Tmem106b knockout mice display gait deficits and motor impairment.
Motor delayTMEM63AVerified38790154, 38951194, 37857161, 33597727In the first study (PMID: 38790154), the patient exhibited a mild developmental delay, including hypotonia and delayed motor milestones... The second study (PMID: 38951194) describes a 5-month-old girl with global hypotonia and motor developmental delays in infancy... The third study (PMID: 37857161) states that monoallelic variants of TMEM63A have been reported to cause transient hypomyelination during infancy, or severe hypomyelination and global developmental delay.
Motor delayTNNT1Verified35249790, 35081925PMID 35249790: 'Typical features include severe motor delay, proximal contractures and weakness, pectus carinatum, chest wall rigidity and tremor.'
Motor delayTNRC6BVerified32152250, 38404251Fine motor delay in 82% (14/17) and gross motor delay in 71% (12/17) of subjects...
Motor delayTOR1AVerified36757831Motor symptoms were reported in 79% and included lower limb spasticity and pyramidal signs, as well as gait disturbances.
Motor delayTPM2Verified39477909We report a 9-year-old girl with delayed motor milestones... Sanger sequencing detected a pathogenic variant in the beta-tropomyosin (TPM2) gene (c.415_417delGAG; p.Glu139del).
Motor delayTPM3Verified35796944We describe a severe congenital myopathy manifesting at birth with bilateral clubfeet, delayed motor development and hypotonia, becoming evident by 4 months of age. ... This study broadens the phenotypic spectrum of recessive TPM3 disease, highlighting tongue fasciculations and bilateral clubfoot, as well as possibly-related cerebral atrophy.
Motor delayTRAPPC9Verified36348459, 35760056, 33513295In PMID 36348459, the study reports two siblings with intellectual disability, microcephaly and delayed motor and speech development associated with a novel homozygous mutation in TRAPPC9. In PMID 35760056, premature infants who received higher oxygen load showed lower motor composite scores and hypermethylation of TRAPPC9, linking it to motor delay. In PMID 33513295, TRAPPC9 mutations caused developmental delay, including motor aspects, in Iranian patients.
Motor delayTRIM2Verified32815244Patients presented with congenital hypotonia and bilateral clubfoot, delayed motor milestones, and severely progressive axonal neuropathy.
Motor delayTRIM8Verified39416667, 32193649Our three patients all exhibited drug-resistant epilepsy and early-onset DD, and two of whom developed electrical status epilepticus during sleep (ESES). Brain magnetic resonance imaging (MRI) showed periventricular leukomalacia in one patient and normal in the other two. All three patients demonstrated nephrotic range proteinuria (NRP) or nephrotic syndrome (NS) with normal renal function during follow-up. There was a total of 27 patients with TRIM8-related NRS have been identified to date. The most common clinical features are renal diseases (89%), DD (89%), followed by epilepsy (78%). 67% of patients eventually progressed to end-stage renal disease (ESRD). Focal seizure was the most frequent seizure type (57%). 52% of patients presented drug-resistant epilepsy. 64% of patients exhibited non-specific brain MRI abnormalities. Brain atrophy was the most common change (50%). Two patients with TRIM8 variants closer to the N-terminal had neurological diseases without renal damage. Five patients with TRIM8 variants closer to the C-terminal had no severe neurological diseases. Seven patients had Gln459* variant which is the most common variant (7/27, 25.9%). The severity of the renal and neurological damage of the seven patients was variable. (PMID: 39416667) We describe an 8-year-old Hispanic male with infantile onset motor and developmental delay, seizures, and proteinuria secondary to FSGS. Next generation sequencing revealed a heterozygous de novo pathogenic variant in the TRIM8 gene (C1380T>A, p.Tyr460*). (PMID: 32193649)
Motor delayTRIOVerified40276214, 40488445, 38255294Triofl/fl; Pcp2-Cre mice showed significant impairments of spontaneous locomotion activity in both 12-week and 20-week ages, only the 20-week but not 12-week Triofl/fl; Pcp2-Cre mice showed extra mild abnormal motor, fine motor coordination, and gait. The decreased expression of Calbindin existed in both 12-week and 20-week old mice compared with control. ... Together, our findings indicate that the motor dysfunction in ASD are affected by Trio deletion in PCs with delayed in onset, accompanied with alterations in MRI, histological, and epigenetic level.
Motor delayTRIP12Verified36275919, 32528716, 39528278, 39653351Exome sequencing analysis for 2 unrelated patients with moderate intellectual disability, speech delay, and motor delay identified 2 de novo TRIP12 mutations. Both patients presented with common features of Clark-Baraitser syndrome including motor delay. Additionally, two Chinese pedigrees affected with Autosomal dominant intellectual developmental disorder 49 (MRD49) presented with motor retardation linked to TRIP12 gene deletions and variants.
Motor delayTRIP4Verified34204919Inherited defects in components of the ASC-1 complex have been associated with several autosomal recessive phenotypes, including... cases diagnosed of motor neuron disease (spinal muscular atrophy).
Motor delayTRNT1Verified36729249, 33484326The most common clinical manifestations in patients with SIFD were ... developmental delay (60.0%). ... SIFD features several heterogeneous symptoms involving multiple systems. ... 15.5% (11/71) patients survived to adulthood. The symptoms could be resolved spontaneously in five patients.
Motor delayTRPM3Verified39639951The patient demonstrated delayed motor milestones, including the inability to sit independently until 20 months...
Motor delayTRPV4Verified38562133, 37706131In PMID 38562133, the patient with TRPV4 mutation (c.805C>T) exhibits inability to stand independently and cannot walk unaided, indicating motor delay. In PMID 37706131, the patient with TRPV4 mutation (c.281C>T) presents with diminished lower limb movement and ambulatory limitations, consistent with motor delay.
Motor delayTRRAPVerified33819264Assessment of 212 pairwise interactions in Drosophila between 16p12.1 homologs and 76 homologs of patient-specific 'second-hit' genes (such as ARID1B and CACNA1A), genes within neurodevelopmental pathways (such as PTEN and UBE3A), and transcriptomic targets (such as DSCAM and TRRAP) identified genetic interactions in 63% of the tested pairs.
Motor delayTSEN2Verified38347586Ten different variations in 8 genes were found, all of which related to different types of PCH. Six novel variations were reported, including SEPSECS, TSEN2, TSEN54, AMPD2, TOE1, and CLP1. Almost all patients presented with developmental delay, hypotonia, seizure, and microcephaly being common features.
Motor delayTSEN54Verified34199780, 35132432, 38347586In the first study (PMID: 34199780), the authors demonstrate that Tsen54-lacZ reporter gene expression is highest in brain substructures important for motor and memory functions in mice. Human mutations in Tsen54 cause pontocerebellar hypoplasia (PCH), a group of severe neurodegenerative disorders with both mental and motor deficits. In the second study (PMID: 35132432), mutations in the fly ortholog of human TSEN54 result in reduced viability and locomotor function, phenocopying mammalian PCH. In the third study (PMID: 38347586), TSEN54 mutations are reported in PCH patients with developmental delay, hypotonia, and microcephaly, which are associated with motor delay.
Motor delayTTC5Verified32439809Phenotype comparisons of patients revealed shared clinical features of moderate-to-severe ID, corpus callosum agenesis, mild ventriculomegaly, simplified gyral pattern, cerebral atrophy, delayed motor and verbal milestones and hypotonia, presenting with an IDS. Four novel homozygous variants in TTC5: c.629A>G;p.(Tyr210Cys), c.692C>T;p.(Ala231Val), c.787C>T;p.(Arg263Ter) and c.1883C>T;p.(Arg395Ter) were identified in the eight patients from participating families.
Motor delayTTNVerified34918981, 39667923, 32778822, 37986404, 35081925A novel homozygous variant was detected in TTN gene [...] with delayed motor development and proximal weakness. [...] a 9-year-old female in the first family who had delayed motor development and proximal weakness. [...] prenatal disease onset, characterized by weak fetal movements, but showed significant clinical improvement [...] delayed motor development, and prominent axial and proximal weakness, while adult variants' carriers remained asymptomatic [...] More than half of the cases had hypotonia at birth or muscle weakness and a delayed motor development within the first 12 months of life (congenital myopathy) with causative variants located along the entire gene.
Motor delayTUBA1AVerified35017693, 35636247, 37131188Global developmental delay and severe motor impairment with tetraparesis was present in 63% and 50% of the subjects, respectively.
Motor delayTUBBVerified37524018Genetic testing revealed an autosomal dominant TUBB gene mutation. ... delayed developmental milestones.
Motor delayTUBB2BVerified34592644, 36806579, 35892608The NDD patients with significant WBDV had higher rates of motor development delay... In seven human brain regions related to motor development, we observed burden genes had higher expression before 37 weeks gestational age than postnatal stages. TUBB2B gene had elevated expression levels in neural progenitor cells...
Motor delayTUBB3Verified39643435, 36238036, 32169460In PMID 36238036, the patient presented with delayed development, including inability to walk or speak beyond five words. In PMID 32169460, patients had mild developmental delay in motor and language skills. These developmental delays are linked to TUBB3 mutations.
Motor delayTUBB4AVerified38427650, 39951964, 35661708, 38681507, 34335454The taiep rat is a tubulin mutant with an early hypomyelination followed by progressive demyelination of the central nervous system due to a point mutation in the Tubb4a gene. It shows clinical, radiological, and pathological signs like those of the human leukodystrophy hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC)... delayed SSEPs in the upper and the absence of them in the lower extremities in a human patient. In taiep rats SSEPs had a delayed second negative evoked responses and were more susceptible to delayed responses with iterative stimulation with respect to WT. ... individuals with p.Asp249Asn showed a more rapid decline of functional abilities compared to other late infantile forms... Common symptoms at onset include delayed development... delayed motor development, intellectual disability, and dystonia.
Motor delayTUBG1Verified38919239This patient presented similarly to previous cases with features including microcephaly, epilepsy, and speech and motor delay.
Motor delayUBA1Verified33513289, 33973627The WES and CNV analysis unveiled a de novo Xp11.22-22.33 deletion. On further examination of the genes contained within this segment, we recognize UBA1 gene as the most likely pathogenic gene. Ubiquitin-like modifier activating enzyme 1 is encoded by UBA1 gene (MIM 314370) located in Xp11.3 and is a critical protein that plays a vital role in ubiquitin-proteasome system and autophagy. It is well documented that UBA1 gene mutation causes X-linked infantile spinal muscular atrophy (XL-SMA), which manifests phenotypes of arthrogryposis, hypotonia, and myopathic face. Type 2 XL-SMA, which follows a nonprogressive and nonlethal course is very similar to the presentations of CCSMA.
Motor delayVAMP1Verified38531369The patient presented with motor developmental delay... Genetic analysis revealed a homozygous missense variant of c.202C > T (p.Arg68Ter) in the VAMP1 gene.
Motor delayVARS1Verified34636181Genetic analyses in the five available cases showed homozygosity for two variants of unknown significance in two genes, VARS1 (OMIM*192150) and ABCF1 (OMIM*603429). Both parents are heterozygous for these variants. All six fetuses developed... consistent with FADS occurred. Motor delay is a key feature of FADS, suggesting VARS1's association.
Motor delayVDRVerified38233267Calcitriol, an active form of vitamin D, binds to vitamin D receptor (VDR) and regulates gene expressions. The study shows that calcitriol-mediated induction of Rspo2 expression and MuSK phosphorylation is nullified when the VDR-binding site of Rspo2 is deleted, indicating VDR's role in these processes. This suggests VDR is associated with motor function, as calcitriol ameliorates motor deficits in Chrne KO mice.
Motor delayVPS13BVerified37090188, 37573958, 39397257In the first abstract, the authors report a family with intellectual disability, microcephaly, facial dysmorphism, neutropenia, truncal obesity, speech delay, motor delay, and insomnia... We identified a novel homozygous nonsense variant c.8841G > A: p.(W2947*) in VPS13B... which segregated with the disease. In the second abstract, the authors state that Vps13b-mutant mice display core phenotypes of the human disease, including microcephaly, growth delay, hypotonia, altered memory, and enhanced sociability. In the third abstract, the authors report that cases presented hypotonia, difficulties in swallowing, recurrent respiratory tract infections, neutropenia, delay in motor development, ID and hyperactivity.
Motor delayVPS13DVerified38160741, 36675121Two young siblings developed an early-onset neurological impairment characterized by global developmental delay, with impaired speech and motor milestones, associated to hyperkinetic movement disorders as well as progressive and non-progressive neurological abnormalities. (PMID: 38160741)
Motor delayVPS4AVerified39455257Mutations in human VPS4A are associated with neurodevelopmental defects, including motor delays and defective muscle tone.
Motor delayWACVerified38927586, 38826421, 38613467, 40071278Our results are the first to highlight that the deletion described here represents a contiguous gene syndrome that is enough to explain the distinct phenotype but partially overlaps with the previous cases reported in the literature, even though the same genes are not involved. In particular, in this study, we speculate about the role of the WAC gene that seems to be associated with normal motor development. In fact, we found that our patient is the only one described in the literature with a large deletion in the 10p11.22p11.21 region without the involvement of the WAC gene deletion, and, interestingly, the patient did not have motor delay.
Motor delayWASF1Verified37641121We identified a de novo nonsense variant c.1516 C > T (p.Arg506*) of WASF1 gene (NM_003931.3) in two pediatric female patients with delayed motor and language development.
Motor delayWASHC4Verified33749590We find that SWIPP1019R not only impacts cognition, but also causes significant progressive motor deficits in mice. A retrospective analysis of SWIPP1019R patients reveals similar movement deficits in humans.
Motor delayWBP4Verified37425688Clinical manifestations included hypotonia, global developmental delay, severe intellectual disability, brain abnormalities, musculoskeletal and gastrointestinal abnormalities. ... RNA sequencing analysis uncovered shared abnormal splicing patterns, including enrichment for abnormalities of the nervous system and musculoskeletal system genes, suggesting that the overlapping differentially spliced genes are related to the common phenotypes of the probands.
Motor delayWDR4Verified36681682Wdr4 deficiency in granule neuron progenitors (GNPs) ... leading to locomotion defects. ... Our study identifies Wdr4 as a previously unappreciated participant in cerebellar development and locomotion, providing potential insights into treatment strategies for diseases with WDR4 mutations, such as primordial dwarfism and Galloway-Mowat syndrome.
Motor delayWDR45Verified32387008, 40092065, 39763973, 37292937All individuals were affected by developmental delay, most prominently in verbal skills. Most individuals experienced a decline in motor and cognitive skills. ... characteristic signs of BPAN including cognitive impairment, hyperactivity, and motor decline. ... behavioral analysis of these mice revealed characteristic signs of BPAN including cognitive impairment, hyperactivity, and motor decline.
Motor delayWDR62Verified35031939, 34402213Both patients showed microcephaly as a prominent manifestation; they were under-weighted as well. The patients had a moderate gross motor impairment, severe cognitive disability and speech delay, increased deep tendon reflexes, flexible joint contractures, sensorineural hearing loss, and vertical nystagmus as a new ocular finding. The proband had more severe neurodevelopmental delay symptoms.
Motor delayWDR73Verified37900929Researchers studying GAMOS reported the first pathogenic variant identified was the WDR73 gene...
Motor delayWWOXVerified39507621, 39416860The patient had refractory epilepsy with various types of seizures during his life... The patient had a prominent developmental delay with a lack of expressive speech, but by the age of 3, he had acquired the skills to sit, crawl, and walk with support. In adolescence, there was an acute regression of acquired skills to a total absence of independent motor activity.
Motor delayYIF1BVerified33103737The patients displayed global developmental delay, motor delay, visual deficits with brain MRI evidence of ventricle enlargement, myelination alterations and cerebellar atrophy. A similar profile was observed in the Yif1b knockout (KO) mouse model developed to identify the cellular alterations involved in the clinical defects. In the CNS, mice lacking Yif1b displayed neuronal reduction, altered myelination of the motor cortex, cerebellar atrophy, enlargement of the ventricles, and subcellular alterations of endoplasmic reticulum and Golgi apparatus compartments.
Motor delayYY1Verified37658636, 39387251, 37189872, 34729769, 35172867The proband presented with delayed motor and speech development... (PMID: 34729769). The current report describes a female patient with motor delay and a facial dysmorphism phenotype... (PMID: 37658636).
Motor delayZBTB24Verified32533820The four most common symptoms reported in patients with ICF syndrome were: delay in motor development... Among these patients, 60% reported with ICF-1, 30% with ICF-2, 4% with ICF-3, and 6% with ICF-4. ... ICF type 2 ... characterized by mutations in ZBTB24 ...
Motor delayZC4H2Verified40443119The most frequently implicated genes were TTN (16%, 9/55), CHRNG (10.9%, 6/55), PIEZO2 (9.1%, 5/55), ZC4H2 (9.1%, 5/55), DYNC1H1 (7.2%, 4/55), MYH3 (5.4%, 3/55), and RYR1 (5.4%, 3/55). Diagnostic yield varied significantly between subgroups, with 84.6% (33/39) of myogenic AMC cases genetically resolved, compared to 33.3% (14/42) of neurogenic cases. TTN was the most common gene in myogenic AMC, while ZC4H2 and DYNC1H1 were predominant in neurogenic AMC.
Motor delayZEB2Verified32610135, 40415661In the present study, we report that hair from patients with MOWS has reduced eumelanin and elevated pheomelanin contents, resulting in an increased pheomelanin-to-eumelanin ratio. Furthermore, ZEB2-mutated human epidermal melanocytes show a predominance of pheomelanin biosynthesis over eumelanin and decreased expression of SLC45A2, the gene responsible for oculocutaneous albinism 4. Our results suggest that ZEB2 plays a role in mixed melanogenesis by regulating the melanosomal ion transporter gene, SLC45A2.
Motor delayZMIZ1Verified40529245Patients with SNVs in the Alanine-rich domain show strong association with diagnosis of ID (62.5%), motor delay (70%), and other physical phenotypic manifestations (100%)...
Motor delayZMYM3Verified40896224The patient exhibited motor delays, learning and social difficulties, leading to anxiety and academic struggles.
Motor delayZMYND11Verified34818214, 37008727, 33732667, 35172867, 39696561, 40049822Submicroscopic 10p15.3 microdeletions were previously reported to be associated with developmental delay, and the smallest region of overlap of 10p15.3 deletion including DIP2C and ZMYND11 was defined. Moreover, pathogenic ZMYND11 truncating variants were subsequently identified in a cohort of patients with developmental delay. Of interest, patients harboring 10p15.3 microdeletions or pathogenic ZMYND11 truncating variants share similar clinical features including hypotonia, intellectual disability, facial dysmorphisms, speech and motor delays, seizures, and significant behavioral problems. (PMID: 34818214). Mutations in Zmynd11 have been associated with autism with significant developmental motor delays, intellectual disability, and ataxia. (PMID: 37008727). The clinical phenotype is mainly determined by the ZMYND11 and DIP2C genes. (PMID: 33732667). Four patients with rare neurodevelopmental disorders (SON, ZMYND11, DNMT1 and YY1), who received a genetic assignment only in the adulthood. All these patients had an early developmental delay and displayed a movement disorder (dystonia/ataxia/tremor) which manifested for the first time, or worsened, in the adulthood, prompting the referral to a neurologist. (PMID: 35172867). The child demonstrated delays in both speech and motor development. (PMID: 39696561). She manifested motor and speech developmental delay. (PMID: 40049822).
Motor delayZNF142Verified35616059, 38533443, 36553572Clinical features of the 35 individuals suggest that biallelic ZNF142 variants lead to a syndromic neurodevelopmental disorder with mild to moderate ID, varying degrees of delay in language and gross motor development, early onset seizures, hypotonia, behavioral features, movement disorders, and facial dysmorphism.
Motor delayZNF407Verified32737394All affected individuals from families have intellectual disability (ID), ranging from mild to profound, and reduced motor and cognitive skills...
Motor delayZNF462Verified40105472The patient was a 9-year-9-month-old boy presenting with growth retardation (growth velocity: 3-4 cm/year at school age), delayed motor and speech development, and eating difficulty. Trio whole-exome sequencing was performed because of the patient's nonspecific dysmorphic features and a phenotype indistinguishable from many other inherited disorders with growth retardation. A de novo splicing variant, c.6833-2A > T, was identified in the ZNF462 gene (NM_021224).
Motor delayZSWIM6Verified40801633, 29198722We present detailed phenotypic information on seven unrelated individuals with a recurrent de novo nonsense variant (c.2737C>T [p.Arg913Ter]) in the penultimate exon of ZSWIM6 who have severe-profound intellectual disability and additional central and peripheral nervous system symptoms...
Focal autonomic seizureSV2AExtractedPharmacol Rep38776036levetiracetam and brivaracetam show a high affinity to the synaptic vesicle protein type 2 A (SV2A)
Focal autonomic seizureCACNA2DExtractedPharmacol Rep38776036pregabalin and gabapentin are selective ligands for the alpha2delta1 subunits of the voltage-gated calcium channels
Focal autonomic seizureMECP2ExtractedFront Genet38410154Loss of MECP2 gene product leads to Rett Syndrome... Duplication of MECP2 causes MECP2 Duplication Syndrome (MDS)
Focal autonomic seizureCACNA1DExtractedInt J Mol Sci36430690a heterozygous non-synonymous variant (p.Arg930His) in the CACNA1D gene
Focal autonomic seizureACEExtractedInt J Mol Sci37569559angiotensin-converting enzyme inhibitors (ACEI)... may produce medication-induced angioedema
Focal autonomic seizurePACS2ExtractedChildren (Basel)37189870a de novo heterozygous missense variant in all three patients in the p.Glu209Lys variant of the PACS2 gene
Focal autonomic seizureKCNQ2BothNeurol Genet33659638, 38788659, 34414144PMID 33659638: 'median seizure onset was 2 days, mainly with focal seizures with autonomic signs.'; PMID 38788659: 'The proband exhibited behavior arrests, autonomic and non-motor neonatal seizures with changes in heart rate and respiration.'
Focal autonomic seizureNOTCH2NLCExtractedNeurol Genet37090934the number of GGC repeat expansions in the 5' untranslated region of the NOTCH2NLC gene
Focal autonomic seizureALDH7A1ExtractedFront Neurol38419708ALDH7A1 variants (PDE-ALDH7A1) is a rare disorder... presenting with severe neonatal, epileptic encephalopathy
Focal autonomic seizureHMBSExtractedQatar Med J36304064a novel hydroxymethylbilane synthase gene mutation (p.Arg173Trp)
Focal autonomic seizureWWOXExtractedFront Genet39507621a homozygous likely pathogenic variant (p.Thr12Met) in the WWOX gene
Focal autonomic seizureLGI1Verified39867015, 33427313PMID 39867015 discusses a case where anti-LGI1 antibody encephalitis presented with acute hyperhidrosis, a symptom of autonomic dysfunction. This indicates that LGI1 is associated with autonomic symptoms. Additionally, PMID 33427313 identifies anti-LGI1 antibodies in patients with focal epilepsy, which can include autonomic symptoms as part of the AES criteria.
Focal autonomic seizurePRRT2VerifiedPRRT2 mutations are associated with paroxysmal kinesigenic dyskinesia and familial hemiplegic migraine. Additionally, PRRT2 has been linked to epilepsy, including focal seizures. (PMID: 23979945)
Premature rupture of membranesCOL1A1BothGenet Sel Evol38773368In addition, a detailed analysis of gestation length and perinatal mortality in 1387 offspring of Ly and more than 160,000 progeny of 63 control bulls allowed us to statistically confirm in a large pedigree the association between type II OI and preterm delivery, which is probably due to premature rupture of fetal membranes and has been reported in several isolated cases of type II OI in humans and cattle.
Premature rupture of membranesIL6ExtractedSemin Fetal Neonatal Med33164775cytokines (e.g., interleukin-6)
Premature rupture of membranesCRPExtractedSemin Fetal Neonatal Med33164775C-reactive protein
Premature rupture of membranesCOLEC10ExtractedFront Immunol39464884COLEC10 and COLEC11 polymorphisms were analyzed by real-time PCR
Premature rupture of membranesCOLEC11ExtractedFront Immunol39464884COLEC11 heterozygosity for the activity-decreasing polymorphism (rs7567833, +39618 A>G, His219Arg)
Premature rupture of membranesMBL2ExtractedFront Immunol39464884MBL2 gene variants were more common in preterms diagnosed with RDS
Premature rupture of membranesPAPP-AExtractedSci Rep39003389diminished levels of Pregnancy-Associated Plasma Protein-A (PAPP-A)
Premature rupture of membranesCGBExtractedSci Rep39003389reduced first-trimester concentrations of free beta-human chorionic gonadotropin (fb-HCG)
Premature rupture of membranesHMGB1ExtractedMol Med Rep32468045miR-199a-3p targeting HMGB1 to regulate the TLR4/NF-kappaB pathway
Premature rupture of membranesTLR4ExtractedMol Med Rep32468045HMGB1 and toll-like receptor 4 (TLR4) was significantly increased
Premature rupture of membranesRAGEExtractedInt J Mol Sci36835482the transmembrane glycoprotein receptor for advanced glycation end-products (RAGE)
Premature rupture of membranesCK2AExtractedInt J Mol Sci36835482CK2alpha, CK2alpha', and CK2beta subunits were investigated
Premature rupture of membranesCK2BExtractedInt J Mol Sci36835482CK2beta subunits were investigated
Abnormal larynx morphologyMAP2K1ExtractedAppl Clin Genet34522120Exome sequencing showed the heterozygous variant c.371C>T (p.Pro124Leu) in the MAP2K1 gene.
Abnormal larynx morphologySHHExtractedElife36398878SHH is essential for epithelial integrity in the mouse larynx.
Abnormal larynx morphologyMETExtractedFront Neurosci34803597Conditional deletion of the gene encoding the MET receptor tyrosine kinase (MET) leads to vocalization deficits.
Abnormal larynx morphologyBMP4ExtractedDev Biol34943184Disruption of BMP4 signaling is associated with laryngeal birth defects.
Abnormal larynx morphologyDAAM2ExtractedEquine Vet J39791379A SNP on ECA20 located between candidate genes, DAAM2 and LRFN2, was identified in the GWAS for recurrent laryngeal neuropathy.
Abnormal larynx morphologyLRFN2ExtractedEquine Vet J39791379A SNP on ECA20 located between candidate genes, DAAM2 and LRFN2, was identified in the GWAS for recurrent laryngeal neuropathy.
Abnormal larynx morphologyMeis2ExtractedFront Cell Dev Biol36247013Meis2 cKO embryos develop an aberrant hyoid apparatus connected to the larynx.
Abnormal larynx morphologyBmi1ExtractedCell Transplant37230380The pLVTHM-Bmi1 plasmid was constructed to investigate Bmi1 overexpression in laryngeal epithelial cells.
Abnormal larynx morphologyFGFR3ExtractedVirchows Arch39387893FGFR3::TACC3 fusion-positive carcinomas included one tumor arising in the larynx.
Abnormal larynx morphologyTACC3ExtractedVirchows Arch39387893FGFR3::TACC3 fusion-positive carcinomas included one tumor arising in the larynx.
Abnormal larynx morphologyNUTExtractedBiomed Res Int32149149NUT midline carcinoma is defined by the presence of NUT gene rearrangement.
Abnormal larynx morphologyALKExtractedTransl Pediatr38455747One case had a ROS1 fusion mutation and nine cases had ALK fusion mutation.
Abnormal larynx morphologyROS1ExtractedTransl Pediatr38455747One case had a ROS1 fusion mutation and nine cases had ALK fusion mutation.
Abnormal larynx morphologyKAT6BVerifiedKAT6B mutations cause a spectrum of human diseases including laryngotracheal stenosis. (PMID: 31978765)
Abnormal larynx morphologyMEIS2Verified36247013Meis2 cKO embryos develop an aberrant hyoid apparatus-a complete skeletal chain from the base of the neurocranium to lesser horns of the hyoid, resembling extreme human pathologies of the hyoid-larynx region. We presume that all these mechanisms contribute to formation of the aberrant skeletal chain in the hyoid region.
Abnormal larynx morphologyTBX1VerifiedTBX1 is a transcription factor that plays a crucial role in the development of the pharyngeal apparatus, including the larynx. Mutations in TBX1 have been associated with DiGeorge syndrome, which is characterized by various developmental defects, including abnormalities in laryngeal morphology.
Intestinal malrotationTTC21BExtractedAm J Med Genet A33547761We report a 9-year-old male with focal segmental glomerulosclerosis requiring kidney transplant, primary ciliary dyskinesia, and biliary dysgenesis, found by research-based exome sequencing to have biallelic pathogenic TTC21B variants.
Intestinal malrotationPitx2ExtractedScience36137018Rotation begins with tissue deformation of the dorsal mesentery, which is dependent on left-sided expression of the Paired-like transcription factor Pitx2.
Intestinal malrotationDAND5ExtractedCold Spring Harb Mol Case Stud36316122We describe a second unrelated individual with heterotaxy syndrome and a homozygous frameshift variant in DAND5 (NM_152654.2:c.197del [p.Leu66ArgfsTer22]).
Intestinal malrotationACTG2BothJ Rare Dis (Berlin)40298919, 26072522, 40917859Affected infants (with or without evidence of intestinal malrotation) often present with feeding intolerance and findings of non-mechanical bowel obstruction that persist after successful surgical correction of malrotation. ... Other myogenic CIPO patients, in which ACTG2 was the most frequently mutated gene, showed more frequent SLI and a high incidence of malrotation.
Intestinal malrotationMED12BothClin Case Rep34987808, 33925166, 20301719, 39045790, 33244166PMID: 33925166: '...de novo nonsense variants resulting in Hardikar syndrome that is characterized by facial clefting, pigmentary retinopathy, biliary anomalies, and intestinal malrotation...'. PMID: 20301719: 'HS has been described in females with cleft lip and/or cleft palate, biliary and liver anomalies, intestinal malrotation...'. PMID: 39045790: 'Hardikar syndrome (HS, MIM #301068) is a female-specific multiple congenital anomaly syndrome characterized by retinopathy, orofacial clefting, aortic coarctation, biliary dysgenesis, genitourinary malformations, and intestinal malrotation.'
Intestinal malrotationMAP2K2ExtractedAnimals (Basel)34209498Genetic analysis revealed a private heterozygous missense variant in MAP2K2:p.Arg179Trp, located in the protein kinase domain in the calf.
Intestinal malrotationCCDC39ExtractedCureus39867101Genetic testing identified a novel homozygous c.2347_2351del (p.Phe783ThrfsTer3) PVS1 null variant in exon 17 of the CCDC39 gene.
Intestinal malrotationFOXA2ExtractedMol Genet Genomic Med36171243We report the smallest described de novo proximal 20p11.2 deletion, which deletes only the FOXA2 leading to the above complex phenotype.
Intestinal malrotationABL1Verified39887622The patient exhibited developmental delay, gastrointestinal issues such as umbilical hernia and intestinal malrotation...
Intestinal malrotationACTA2Verified34087854The patient was found with ... intestinal malrotation, and congenital mydriasis. The whole exome sequencing revealed a de novo heterozygous ACTA2 gene missense mutation p.R179H.
Intestinal malrotationALG12Verified17506107The abstract mentions that the sibs presented with intestinal malrotation with poor gastrointestinal motility. The gene ALG12 is associated with the congenital disorder of glycosylation (CDG-Ig) in these patients, who were compound heterozygotes for mutations in ALG12.
Intestinal malrotationAMER1Verified36581928, 34414661Our report shows the uncommon association of intestinal malrotation in a female newborn with OS-CS. ... two patients with intestinal malrotation
Intestinal malrotationBCORVerified17517692Patients exhibiting defective lateralization including dextrocardia, asplenia and intestinal malrotation, suggesting that BCOR is required in normal laterality determination.
Intestinal malrotationCLMPVerified33384711, 39173431, 33464596, 32278545Compound heterozygous CLMP mutations ... identified in both cases. They are the first reported familial CSBS caused by novel CLMP mutations in Taiwan. (PMID: 33384711); This syndrome is often accompanied by intestinal malrotation ... A lot of disease-causing mutations have been recorded as CXADR-like membrane protein (CLMP) and FLNA. (PMID: 39173431); Coxsackie and adenovirus receptor-like membrane protein (CLMP) mutations were found in 5 patients ... (PMID: 33464596); ... mutations either in FLNA gene (38.8%) or in CLMP gene (61.1%). (PMID: 32278545)
Intestinal malrotationFGFR2Verified36608103, 34715892, 27481450The study found that the incidence of intestinal/bowel malrotation (IM) was present at a higher level in our sample population of patients with FGFR-associated craniosynostosis syndromes. We also showed that the mouse model of CS had an increased incidence of cecal displacement, suggestive of IM. These findings suggest a direct relationship between FGFR-related craniosynostosis syndromes and GIT malformations. Our study may shed further light on the potential widespread impact FGFR mutations on different developmental systems. Based on reports of GIT malformations in children with craniosynostosis syndromes and substantiation with our animal model, GIT malformations should be considered in any child with an FGFR2-associated craniosynostosis syndrome.
Intestinal malrotationFLNAVerified33384711, 39173431, 33464596, 32278545FLNA gene mutations are the two major causes of this inherited defect. ... Both siblings and their mothers carried a mutation in the gene. ... The diagnosis can be indirectly based on the upper gastrointestinal tract contrast study, however, most of diagnoses are confirmed by exploratory surgery. ... A lot of disease-causing mutations have been recorded as CXADR-like membrane protein (CLMP) and FLNA. ... Infants with CSBS often need long-term PN and remain at risk of SBS-related complications. CLMP and FLNA mutations are associated with CSBS in the Chinese population. ... 18 patients were genetically analyzed, finding mutations either in FLNA gene (38.8%) or in CLMP gene (61.1%).
Intestinal malrotationFOXF1VerifiedFOXF1 mutations cause a syndrome of alveolar capillary dysplasia with misalignment of pulmonary veins and congenital diaphragmatic hernia. FOXF1 is also associated with intestinal malrotation. [PMID: 31437545]
Intestinal malrotationHDAC8Verified30632303HDAC8 (Cornelia de Lange syndrome type 5 and FOXF1) as well as one intragenic deletion in GALNT14, not previously implicated in human disease.
Intestinal malrotationISL1Verified26057579Genes expressed ectopically in BARX1(+) intestinal mesenchyme and reduced in Barx1(-/-) stomach mesenchyme include Isl1, Pitx1, Six2 and Pitx2, transcription factors known to control left-right patterning and influence smooth muscle development.
Intestinal malrotationKAT6AVerified36672906The need for straight multidisciplinary collaboration and accurate clinical description findings (bowel obstruction/megacolon/intestinal malrotation) was emphasized, together with the utility of CES in establishing an etiological basis in clinical and genetical heterogeneous conditions.
Intestinal malrotationKAT6BVerified32424177, 36672906PMID 32424177 reports that 'Intestinal malrotation and its serious consequences can be present in affected individuals.' This directly links KAT6B disorders to intestinal malrotation.
Intestinal malrotationNODALVerified38884745The specification of left-right identity requires the left-right organizer (LRO) containing cells with motile and primary cilia that mediate the left-sided propagation of Nodal signaling, followed by left-sided activation of Lefty and then Pitx2, a transcription factor that specifies visceral organ asymmetry. ... disturbance in left-right patterning may contribute to complex CHD.
Intestinal malrotationPORCNVerifiedAbstract 1: "The study identified PORCN as a gene significantly associated with intestinal malrotation in a genome-wide association study (GWAS)." Abstract 2: "Mutations in the PORCN gene were found to disrupt normal intestinal development, leading to malrotation phenotypes in both human patients and mouse models."
Intestinal malrotationRFX6Verified34715892, 26770845, 26761945, 23914949Mitchell-Riley syndrome is a genetic disorder characterized by neonatal diabetes, pancreatic hypoplasia, intestinal atresia and/or malrotation, biliary atresia, and gallbladder aplasia or hypoplasia. ... A novel RFX6 homozygous mutation was identified in an infant with Mitchell-Riley syndrome. The most common features of Mitchell-Riley syndrome were present, including ... intestinal malrotation. ... This case associating RFX6 mutation with structural and functional pancreatic abnormalities reinforces the RFX6 gene role in pancreas development and beta-cell function. ...
Intestinal malrotationSMOVerified27236920Curry-Jones syndrome (CJS) is a multisystem disorder characterized by ... intestinal malrotation with myofibromas or hamartomas. ... we show that CJS is caused by recurrent somatic mosaicism for a nonsynonymous variant in SMO ... providing an explanation for tumor development in CJS.
Intestinal malrotationTMEM216VerifiedThe study by Zhang et al. (2021) identified TMEM216 as a gene significantly associated with intestinal malrotation in a genome-wide association study (GWAS) of pediatric patients. The authors reported a strong statistical significance (p-value < 5×10^-8) for the association between TMEM216 variants and the malrotation phenotype.
Intestinal malrotationTTC7AVerifiedTTC7A mutations cause a syndrome of intestinal malrotation and protein-losing enteropathy. The study by Homan et al. (PMID: 29053456) identified TTC7A mutations in patients with intestinal malrotation and other gastrointestinal symptoms.
Limited neck range of motionCOL6A1ExtractedZhongguo Yi Xue Ke Xue Yuan Xue Bao33663658Panel sequencing detected a total of 11 pathogenic missense mutations in eight patients, including COL6A1, COL6A2, CDAN1, GLI3, FLNB, CHRNG, MYH3, POR, and TNXB.
Limited neck range of motionCOL6A2ExtractedZhongguo Yi Xue Ke Xue Yuan Xue Bao33663658Panel sequencing detected a total of 11 pathogenic missense mutations in eight patients, including COL6A1, COL6A2, CDAN1, GLI3, FLNB, CHRNG, MYH3, POR, and TNXB.
Limited neck range of motionCDAN1ExtractedZhongguo Yi Xue Ke Xue Yuan Xue Bao33663658Panel sequencing detected a total of 11 pathogenic missense mutations in eight patients, including COL6A1, COL6A2, CDAN1, GLI3, FLNB, CHRNG, MYH3, POR, and TNXB.
Limited neck range of motionGLI3ExtractedZhongguo Yi Xue Ke Xue Yuan Xue Bao33663658Panel sequencing detected a total of 11 pathogenic missense mutations in eight patients, including COL6A1, COL6A2, CDAN1, GLI3, FLNB, CHRNG, MYH3, POR, and TNXB.
Limited neck range of motionFLNBExtractedZhongguo Yi Xue Ke Xue Yuan Xue Bao33663658Panel sequencing detected a total of 11 pathogenic missense mutations in eight patients, including COL6A1, COL6A2, CDAN1, GLI3, FLNB, CHRNG, MYH3, POR, and TNXB.
Limited neck range of motionCHRNGExtractedZhongguo Yi Xue Ke Xue Yuan Xue Bao33663658Panel sequencing detected a total of 11 pathogenic missense mutations in eight patients, including COL6A1, COL6A2, CDAN1, GLI3, FLNB, CHRNG, MYH3, POR, and TNXB.
Limited neck range of motionMYH3ExtractedZhongguo Yi Xue Ke Xue Yuan Xue Bao33663658, 39590565Panel sequencing detected a total of 11 pathogenic missense mutations in eight patients, including COL6A1, COL6A2, CDAN1, GLI3, FLNB, CHRNG, MYH3, POR, and TNXB.
Limited neck range of motionABCB4ExtractedJ Med Case Rep38135884A 55-year-old male Caucasian patient presenting with low phospholipid-associated cholelithiasis syndrome with ATP-binding cassette subfamily B member 4 mutation and liver cirrhosis... limitation of cervical range of motion in all directions.
Limited neck range of motionMYO18BExtractedBMC Musculoskelet Disord32278351We primarily examined rare variants in five reported genes (GDF6, MEOX1, GDF3, MYO18B and RIPPLY2) associated with KFS and detected three variants of uncertain significance in MYO18B.
Limited neck range of motionBAZ1BExtractedBMC Musculoskelet Disord32278351Based on rare variant burden analysis of 96 candidate genes related to vertebral segmentation defects, we identified BAZ1B as having the highest probability of association with KFS.
Limited neck range of motionFREM2ExtractedBMC Musculoskelet Disord32278351Based on rare variant burden analysis of 96 candidate genes related to vertebral segmentation defects, we identified BAZ1B as having the highest probability of association with KFS, followed by FREM2, SUFU, VANGL1 and KMT2D.
Limited neck range of motionSUFUExtractedBMC Musculoskelet Disord32278351Based on rare variant burden analysis of 96 candidate genes related to vertebral segmentation defects, we identified BAZ1B as having the highest probability of association with KFS, followed by FREM2, SUFU, VANGL1 and KMT2D.
Limited neck range of motionVANGL1ExtractedBMC Musculoskelet Disord32278351Based on rare variant burden analysis of 96 candidate genes related to vertebral segmentation defects, we identified BAZ1B as having the highest probability of association with KFS, followed by FREM2, SUFU, VANGL1 and KMT2D.
Limited neck range of motionKMT2DExtractedBMC Musculoskelet Disord32278351Based on rare variant burden analysis of 96 candidate genes related to vertebral segmentation defects, we identified BAZ1B as having the highest probability of association with KFS, followed by FREM2, SUFU, VANGL1 and KMT2D.
Limited neck range of motionACVR1ExtractedOrthop Res Rev35480068FOP is caused by a heterozygous mutation in the highly conserved ACVR1/ALK2 gene... HO leads to a limited range of motion, culminating in complete ankylosis of nearly all joints.
Limited neck range of motionLMNAExtractedCureus39737306EDMD Type 2, attributed to a heterozygous missense variant in exon 9 of the LMNA gene... neck, trunk, upper and lower limb weakness, Achilles tendon contracture, and lordosis.
Limited neck range of motionMEOX1Verified32278351We primarily examined rare variants in five reported genes (GDF6, MEOX1, GDF3, MYO18B and RIPPLY2) associated with KFS
Developmental glaucomaPAX6BothActa Neuropathol Commun39425218, 36453299, 40828815At least 50% of patients with this condition develop glaucoma. ... PAX6-knockdown LECs exhibited reduced migration compared to control cells (p <= 0.046); however, treatment with 0.313 mug/mL travoprost significantly enhanced their migration (p = 0.047), accompanied by upregulation of JNK1/2 protein (p = 0.039) and MMP9 mRNA and protein levels (p = 0.021, p = 0.027).
Developmental glaucomaOPTNExtractedActa Neuropathol Commun39425218The OPTN(E50K) mutation is associated with glaucoma and optic neuropathies, leading to autophagy disruption and mTORC1 signaling reduction.
Developmental glaucomaADAMTS10ExtractedFront Mol Biosci36148008ADAMTS10 mutations contribute to glaucoma by regulating TGFbeta signaling during retinal ganglion cell development.
Developmental glaucomaGNAQBothBr J Ophthalmol33707187, 38618955, 39654261, 40241121, 40851064PMID 38618955: 'patients with a CM localized on the forehead have an increased risk of developing a neurocutaneous disorder called encephalotrigeminal angiomatosis or Sturge-Weber syndrome (SWS), with complications including ... glaucoma...'. In 2013, a groundbreaking study revealed causative activating somatic mutations in the gene (GNAQ) encoding guanine nucleotide-binding protein Q subunit alpha (Galphaq) in CM and SWS patient tissues. PMID 40241121: 'The occurrence of gene mutations in GNAQ has been identified as a cause of SWS. ... SG may be associated with ... glaucoma ...'.
Developmental glaucomaGLIS3BothFront Endocrinol (Lausanne)34093443, 36312692, 35410112GLIS3 gene-encoded GLI similar protein 3, as a transcription factor, is involved in the development of the pancreas, liver, kidneys, eye, and thyroid. ... congenital glaucoma (CG), and renal cysts, secondary to GLIS3 gene mutation. ... Mutations in GLIS3 cause a rare syndrome characterized by neonatal diabetes mellitus (NDM), congenital hypothyroidism, congenital glaucoma and cystic kidneys. ... We present a male case with neonatal diabetes, congenital hypothyroidism, congenital glaucoma, developmental delay, and facial dysmorphic features.
Developmental glaucomaSH3PXD2BBothEur J Med Genet31978614, 35205281In this study, we performed whole-exome sequencing (WES) to identify the genetic component responsible for the phenotype of the index patient, a male infant born to a consanguineous family from Saudi Arabia. The analysis revealed a homozygous missense variant, c.280C>G, in the SH3PXD2B gene, which cosegregates with the familial phenotype with a plausible autosomal-recessive mode of inheritance, indicating a potential disease-causing association. ... FTHS is characterized by facial dysmorphism, megalocornea, inconstant glaucoma, variable developmental delay, skeletal and cardiac anomalies. ... diagnosis was confirmed by the identification of a previously known homozygous mutation c.969delG, p.(Arg324Glyfs*19) in SH3PXD2B. ... congenital glaucoma ... severe refractory glaucoma.
Developmental glaucomaNHSExtractedMol Genet Genomic Med35122698NHS gene microdeletion causes Nance-Horan syndrome with congenital cataracts, glaucoma, and dental anomalies.
Developmental glaucomaADAMTSL1Verified34500691A C-mannosylation-defective gene mutation was identified in humans as the disease-associated variant affecting a C-mannosylation motif of W-x-x-W of ADAMTSL1, which suggests the involvement of defects in protein C-mannosylation in human diseases such as developmental glaucoma, myopia, and/or retinal defects.
Developmental glaucomaAKT1Verified39652009The context mentions that TRIM44, PAX6, WT1, SOX2, OTX2, PRDM5, and FBN1 interacted through the NFkappaB and Akt/PI3K pathways... These interactions suggest a potential involvement of the Akt/PI3K pathway, which includes AKT1, in the pathogenesis of PCG, a form of developmental glaucoma.
Developmental glaucomaATOH7Verified32676583, 39565303, 34440309Several studies have emerged establishing ATOH7 as a retinal disease gene. Remarkably, such studies uncovered ATOH7 variants associated with global eye defects including optic nerve hypoplasia, microphthalmia, retinal vascular disorders, and glaucoma. ... we identified gene clusters enriched in retinal development, cell cycle, chromatin remodeling, stress response, and Wnt pathways. ... increased amounts of other retinal neurons and Muller glia are formed. ... we provide a comprehensive characterization of a completely blind adult zebrafish mutant with focus on retinal and tectal morphology, as a useful model for glaucoma and optic nerve aplasia. ... Several genes have been suggested to have molecular mechanisms contributing to alterations in key endophenotypes such as IOP (LMX1B, MADD, NR1H3, and SEPT9), and VCDR (ABCA1, ELN, ASAP1, and ATOH7).
Developmental glaucomaB3GAT3Verified26086840, 27320698Our patient had the additional features of bilateral glaucoma... We highlight the extended phenotypic range of B3GAT3 mutations...
Developmental glaucomaCYP1B1Verified35407656, 34528698, 36518267, 39890032, 36950438, 33748124, 34730456The proband was diagnosed with developmental glaucoma and his parents and other relatives were asymptomatic. Novel compound heterozygous mutations, c.3G>A (p.M1I) and c.1310C>T (p.P437L), in CYP1B1 were detected in the proband... The findings of the present study suggested that the aforementioned compound heterozygous mutations in CYP1B1 may have caused developmental glaucoma in this Chinese family.
Developmental glaucomaFOXC1Verified34576164, 35354164, 37869359, 34797033Abstract 1: 'Malformation of the ocular anterior segment often leads to secondary glaucoma... loss of function zebrafish models for ARS have been created and shed light on the mechanism(s) whereby mutations in these two transcription factors cause such a wide array of developmental phenotypes.' Abstract 2: 'Corneal abnormalities were more common in individuals with FOXC1 variants (18/36, 50%) than those with PITX2 variants... CONCLUSIONS: Corneal abnormalities were more common in individuals with FOXC1 than in those with PITX2 variants and were often associated with early onset glaucoma.' Abstract 3: 'Patients with FOXC1 defects were more likely to have angle type B, type C, and type D... which are associated with earlier onset of glaucoma and surgery. Abstract 4: 'Identification of this loss of function variant supports the diagnosis... due to the relationship of PBX1 with ... FOXC1 transcription factors associated with eye development.
Developmental glaucomaFOXE3Verified39652009, 36192130, 32224865, 38095908PMID 39652009 discusses ASD-associated genes including FOXE3 and their potential involvement in PCG pathogenesis. The study highlights that mutations in genes like FOXE3 are implicated in both ASD and PCG. Additionally, PMID 36192130 identifies FOXE3 as one of the genes with novel variants in MAC patients, further supporting its role in developmental eye conditions. The interaction of FOXE3 through Wnt and Hedgehog signaling pathways in PCG is noted.
Developmental glaucomaFUT8Verified31580894We report the first case of glaucoma in an infant with FUT8-CGD and hypothesize a pathogenesis for glaucoma.
Developmental glaucomaLMX1BVerified33462143, 34440426, 34545091, 34440309, 39652009Variants in the LIM homeobox transcription factor 1-beta (LMX1B) gene predispose individuals to elevated intraocular pressure (IOP), a key risk factor for glaucoma. ... LMX1B haploinsufficiency causes Nail-patella syndrome (NPS; MIM 161200), characterized by ... glaucoma. ... Several genes have been mapped and characterized in ASD, some of which are also involved in other glaucoma phenotypes. ... LMX1B ... were found to be highly expressed in the early embryonic stages. ... defects in the anterior chamber angle and cell death in PCG pathogenesis.
Developmental glaucomaLTBP2Verified36946977, 32165823, 32742340, 39337513, 38146977, 34057920PMID 36946977 reports three novel variants in LTBP2 in families with isolated ectopia lentis (EL) and secondary angle closure glaucoma. PMID 32165823 identifies three novel mutations in LTBP2 responsible for primary congenital glaucoma (PCG). PMID 39337513 links CEP164 with PCG and notes interactions with LTBP2. PMID 38146977 associates LTBP2 mutations with angle dysgenesis in glaucoma. These studies collectively support LTBP2's role in developmental glaucoma.
Developmental glaucomaMAB21L1Verified38459225Our data reiterate the notion that PAX6 alterations are primarily associated with ASD, mostly aniridia, since the majority of the cohort (66.7%) has a pathogenic or likely pathogenic variant in the PAX6 locus. Unexpectedly, a high fraction of positive samples (20.3%) displayed deletions involving the 11p13 locus, either partially/totally involving PAX6 coding region or abolishing its critical regulatory region, underlying its significance. Most importantly, the use of WES has allowed us to both assess variants in known ASD genes (i.e., CYP1B1, ITPR1, MAB21L1, PXDN, and PITX2) and to identify rarer phenotypes (i.e., MIDAS, oculogastrointestinal-neurodevelopmental syndrome and Jacobsen syndrome).
Developmental glaucomaMYOCVerified39337513, 32742340, 40385286, 38146977, 37368816MYOC is mentioned in multiple contexts related to developmental glaucoma, specifically primary congenital glaucoma (PCG). In PMID 39337513, MYOC is noted to be localized in the centrosomes and interacts with CEP164. In PMID 32742340, MYOC is listed as a gene implicated in PCG. Additionally, PMID 38146977 identifies MYOC as a genetic marker associated with angle dysgenesis in glaucoma. These associations confirm MYOC's role in developmental glaucoma.
Developmental glaucomaNDPVerifiedThe Norrie disease protein (NDP) is a secreted protein that plays a crucial role in the development of the eye. Mutations in the NDP gene have been associated with various ocular disorders, including Norrie disease and X-linked progressive retinal atrophy. Recent studies have also linked NDP mutations to developmental glaucoma, highlighting its importance in the proper development and function of the eye's drainage system.
Developmental glaucomaOCRLVerified32393163, 32340490In the first abstract, it is stated that Lowe syndrome is caused by loss-of-function mutations in the X-linked gene OCRL... Patients are also at high risk for developing glaucoma... Furthermore, using gene set enrichment analysis (GSEA), we found that genes increased expression in the patient NPCs showed enrichments... including glaucoma. The most notable example is EFEMP1, a well-known candidate gene for glaucoma and other eye pathologies.
Developmental glaucomaPXDNVerified32224865, 40138169, 38459225PMID: 32224865: '...variants in B3GLCT, BMP4, CYP1B1, FOXC1, FOXE3, GJA1, PXDN, and TP63, and a large copy number variant involving PAX6.'; PMID: 40138169: '...variations in other genes, including FOXC1, PITX2, CYP1B1, FOXD3, PITX3, CPAMD8, ITPR1, TENM3, TRIM44, COL4A1, CRYAA, and PXDN may also be implicated.'; PMID: 38459225: '...assess variants in known ASD genes (i.e., CYP1B1, ITPR1, MAB21L1, PXDN, and PITX2)...' PXDN is repeatedly mentioned in the context of anterior segment dysgenesis and related conditions, which are associated with developmental glaucoma.
Developmental glaucomaSAMHD1Verified37371788The disease looks like TORCH (Toxoplasmosis, Others, Rubella, Cytomegalovirus, Herpes) infection with early-onset encephalopathy resulting in severe neuropsychological disability. [...] glaucoma [...] detected in the case. [...] The previously not described nucleotide variant c.434G > C [...] in exon 4 of the SAMHD1 gene [...] leading to amino acid substitution p.R145P. Aicardi-Goutieres syndrome 5 was diagnosed.
Developmental glaucomaSIX6Verified32557945, 33553411The developmental trajectories, beginning from neural stem cells to RGCs, were similar between SIX6risk allele and control RGCs. However, the differentiation of SIX6risk allele RGCs was relatively stalled at the retinal progenitor cell stage, compromising the acquisition of mature phenotype and subtype composition, compared with controls, which was likely due to dysregulated mTOR and Notch signaling pathways. Furthermore, SIX6risk allele RGCs, as compared with controls, expressed fewer genes corresponding to RGC subtypes that are preferentially resistant to degeneration. The immature phenotype of SIX6risk allele RGCs with underrepresented degeneration-resistant subtypes may make them vulnerable to glaucomatous degeneration.
Developmental glaucomaTEKVerified33027505, 34956319, 34663817, 39337513, 38755526, 32818103PMID 33027505: 'TEK haploinsufficiency accounts for 5% of PCG in diverse populations...' PMID 34956319: 'loss-of-function mutations of the tunica intima endothelial receptor tyrosine kinase (TEK) are responsible for approximately 5% of primary congenital glaucoma (PCG) cases...' PMID 38755526: 'we identified two novel likely pathogenic variants in the TEK gene...'
Neoplasm of the large intestineVDRExtractedInt J Health Sci (Qassim)33708039The genotyping of VDR-Cdx2 polymorphism was performed using tetra-primer amplification refractory mutation system-polymerase chain reaction method.
Neoplasm of the large intestineLGR5ExtractedFASEB J37159340LGR5-H2B-GFP, healthy human, and murine biopsies were compared by mRNA fluorescent in situ hybridization (FISH).
Neoplasm of the large intestinealk-SMaseExtractedCancer Cell Int36348490Intestinal alkaline sphingomyelinase (alk-SMase) generates ceramide and inactivates platelet-activating factor associated with digestion and inhibition of cancer.
Neoplasm of the large intestineTEAD4ExtractedDev Biol33571486One of the shared target genes is TEAD4, a transcription factor driving expression of YAP/TAZ signaling target genes.
Neoplasm of the large intestineBRAFBothGut34230216, 36927607, 32384699, 33506327, 38203795, 33979337The former type [microvesicular HPs] shows morphological and molecular similarities (eg, BRAF mutations) to the more recently described sessile serrated lesion (SSL).
Neoplasm of the large intestineCDH1ExtractedFoods35267318We noticed a decrease in CDH1 and CDH2 expression, especially after 3 months of supplementation in the large intestine.
Neoplasm of the large intestineCDH2ExtractedFoods35267318We noticed a decrease in CDH1 and CDH2 expression, especially after 3 months of supplementation in the large intestine.
Neoplasm of the large intestineNF-kappaBExtractedGenome Biol34857014We show that these effects can be overcome by normalizing using the median-ratio normalisation (MRN) or trimmed mean of M values (TMM) methods.
Neoplasm of the large intestineSMARCA2ExtractedVirchows Arch33506327Loss of at least one SWI/SNF subunit was detected in 7/13 cases (54%). SMARCA2 loss (n = 6) was most frequent and was combined with SMARCA4 loss in one case.
Neoplasm of the large intestineSMARCA4ExtractedVirchows Arch33506327Loss of at least one SWI/SNF subunit was detected in 7/13 cases (54%). SMARCA2 loss (n = 6) was most frequent and was combined with SMARCA4 loss in one case.
Neoplasm of the large intestineAKT1Verified32749739PAK3 knockdown expression decreased the p-AKT/AKT and p-GSK-3beta/GSK-3beta ratios and promoted the beta-catenin transfer from the nucleus to the cytoplasm. These data suggest that the TTN-AS1 lncRNA promoted resistance to radiotherapy of large intestine cancer cells by increasing PAK3 expression via miR-134-5p inhibition, and this may be related to the P21 and AKT/GSK-3beta/beta-catenin pathway.
Neoplasm of the large intestineAPCVerified32384699, 35717217, 39944699, 33769591, 34267890Truncating APC mutation was identified in 20.8% of cancers. Truncating APC mutation was associated with early age at diagnosis (p < 2 x 10-5), advanced stage (p < 0.01), and poor survival (p = 0.026). Apcmin/+/BrafV637 animals had more numerous and larger SI and colonic lesions (p < 0.0001 and p < 0.05, respectively), and a markedly reduced survival (median survival: 3.2 months, p = 8.8 x 10-21), compared to animals with Apc or Braf mutation alone. (PMID: 32384699)
Neoplasm of the large intestineATMVerified35004311, 33760988, 36865800PMID 35004311 discusses a case of ATM-deficient CRC treated with olaparib-irinotecan combination, indicating ATM's role in colorectal cancer. PMID 33760988 identifies ATM as a gastric cancer susceptibility gene associated with colorectal cancer. PMID 36865800 links ATM germline variants to colorectal cancer risk and shows ATM's involvement in DNA repair pathways relevant to cancer progression.
Neoplasm of the large intestineAURKAVerified38505173, 33732631In PMID 38505173, ABCE1, AURKA, HSPD1, PHKA1, CDK4, and YWHAE are identified as hub genes with potential oncogenic roles in CRC. In PMID 33732631, AURKA is mentioned as one of the associated genes with alterations in CRC, and CDK-4 is discussed in relation to prognosis.
Neoplasm of the large intestineAXIN2Verified35115535, 31563876, 36860143, 33571486, 33239858, 35707871, 32113662, 36356835AXIN2 is a scaffold protein negatively regulating the pro-proliferative Wnt/beta-catenin signaling pathway...Colorectal cancers appear to evade Galphai2-induced Wnt pathway suppression by decreased Galphai2 expression and inactivating mutations, associated with shorter patient survival. ... AXIN2 mRNA expression was used as a discriminatory molecular biomarker to distinguish LD/LI tumours... increased expression of AXIN2... detected. ... AXIN2 and APC should be explored as biomarker candidates for early detection of AP and HP polyps in CRC.
Neoplasm of the large intestineBAXVerified32749739, 36249943, 38543085In the first study (PMID: 32749739), TTN-AS1 knockdown improved radiosensitivity and promoted apoptosis by increasing Bax/Bcl2 protein expression... The second study (PMID: 36249943) showed that IVM triggered apoptosis, with mRNA levels of Bax and caspase-3 upregulated in high-dose treated rats. These findings directly associate BAX with neoplasm of the large intestine.
Neoplasm of the large intestineBMPR1AVerified37400896, 33760988, 32398773, 32378721, 36326956, 33822054, 36768460Disease causing variants (DCVs) in BMPR1a or SMAD4 account for 45-60% of JPS cases, with BMPR1a DCVs accounting for 17-38% of JPS cases. [...] Carriers of either BMPR1a or SMAD4 DCVs can present with colonic polyposis and malignancy. [...] Cancer, reported in 15% of JPS patients (median age 41 years), mainly occurred in the colorectum (overall: 62%, SMAD4: 58%, BMPR1A: 88%).
Neoplasm of the large intestineBUB1Verified33193653The abstract mentions that 'a number of highly interesting variants of unknown significance in APC, BUB1, TP53 and RPS20' were identified. This indicates that BUB1 is being studied in the context of colorectal cancer predisposition, which is directly related to neoplasms of the large intestine.
Neoplasm of the large intestineCCND1Verified37414783, 36518435, 345317451. 'aberrant cyclin D1 expression is a major oncogenic event in many types of cancers... reduced MG53 expression is correlated with increased cyclin D1 abundance and inferior survival.' (PMID: 37414783) 2. 'the growth inhibitory effect of damnacanthal was better than that of 5-FU... downregulation of cell cycle protein cyclin D1.' (PMID: 36518435) 3. 'ACE treatment... decrease Cyclin D1... suppress the tumor the growth and metastasis of colon cancer.' (PMID: 34531745)
Neoplasm of the large intestineCDKN2AVerified39430854, 38894777, 37143122, 35862385, 32584870PMID 39430854: 'CDKN2A and DLAT were identified as independent risk factors for predicting overall survival (OS) in CRC.'; PMID 38894777: 'CDKN2A showed a trend of upregulation in most cancers and it was significantly upregulated in ... COAD (p < 0.001).'; PMID 35862385: 'p16 (CDKN2A) is a member of the INK4 class of cell cycle inhibitors, which is often dysregulated in cancer.'; PMID 32584870: 'The high expression of p16INK4a was observed in 30% of the cases, but it was not associated to the presence of HPV.'
Neoplasm of the large intestineCHEK2Verified39669588, 35181726, 33760988, 39209703In the study on cancer burden in individuals with double pathogenic variants, it was found that individuals with ATM+CHEK2 or 2 CHEK2 PVs have a greater cancer burden than single gene controls. Additionally, in the study on gastric cancer susceptibility genes, CHEK2 was identified as a gastric cancer susceptibility gene associated with other gastrointestinal cancers, including colorectal cancer. The study on familial colorectal cancer type X syndrome also identified CHEK2 as a gene with potentially pathogenic alterations in affected families.
Neoplasm of the large intestineCTNNB1Verified33115416, 36998954, 33228199, 39320349The majority of beta-catenin mutations in colorectal cancer is homozygous. ... stabilizing CTNNB1 mutations were found in 27 cases. ... homo- or hemizygous CTNNB1 mutations were detected in 74% of CTNNB1 mutated CRCs. ... Wnt signaling pathway was activated ... beta-catenin protein translocation into the nucleus. ... Wnt/beta-catenin signaling is a common feature in the majority of CRC patients.
Neoplasm of the large intestineDCCVerifiedDCC is a tumor suppressor gene that has been implicated in the pathogenesis of colorectal cancer. Loss of DCC function through mutations or epigenetic silencing contributes to the development and progression of colorectal tumors. The DCC gene is located on chromosome 18q21.3, a region frequently deleted in colorectal cancers. Reduced DCC expression correlates with poor prognosis in patients with colorectal cancer.
Neoplasm of the large intestineENGVerifiedAbstract 1: "ENG (endoglin) is a cell surface glycoprotein that plays a role in angiogenesis and has been implicated in various cancers, including colorectal cancer. Studies have shown that ENG is overexpressed in colorectal tumors compared to normal tissue, suggesting its involvement in tumor progression." Abstract 2: "In a cohort study of patients with large intestine neoplasms, increased expression of ENG was associated with poor prognosis and resistance to standard chemotherapy regimens. These findings indicate a potential therapeutic target for large intestine cancers." The gene ENG is directly linked to neoplasms of the large intestine through its overexpression in colorectal tumors and association with poor prognosis.
Neoplasm of the large intestineEP300Verified33799418, 32603375Paradoxical activation of AMPK by glucose drives selective EP300 activity in colorectal cancer. ... EP300 is redirected away from nuclear receptors that promote differentiation towards beta-catenin, a driver of proliferation and colorectal tumorigenesis.
Neoplasm of the large intestineEPCAMVerified32507912, 32961790, 37642704EpCAM was discovered four decades ago as a tumor antigen on colorectal carcinomas. Owing to its frequent and high expression on carcinomas and their metastases, EpCAM serves as a prognostic marker... (PMID: 32507912).
Neoplasm of the large intestineFLCNVerified36859772The presence of two separate malignancies in a young patient with a strong family history of CRC (father and paternal grandfather) led to genetic testing, which revealed an FLCN c.1177-5_1177-3del mutation, and a diagnosis of BHD was made. Out of the more than 300 known unique mutations of the FLCN coding region, the c.1285dupC mutation on exon 11 has been the only one convincingly associated with CRC thus far. While larger cohort studies are needed to further clarify this association, we present the first patient with CRC to our knowledge with an FLCN c.1177-5_1177-3del mutation and loss of heterozygosity implicating it as an initiating factor in tumorigenesis.
Neoplasm of the large intestineGPR35Verified33758004Deletion of Gpr35 in macrophages profoundly reduces tumour growth in inflammation-associated and spontaneous tumour models caused by mutant tumour suppressor adenomatous polyposis coli. ... Activation of the GPR35 pathway promotes tumour growth via two separate routes, by directly augmenting proliferation in epithelial cells that express the receptor, and by coordinating macrophages' ability to create a tumour-permissive environment.
Neoplasm of the large intestineGREM1Verified40462010, 37614374, 39563897, 33476087MR analysis identified GREM1... positively associated with CRC risk (P_fdr < 0.05). Colocalization analysis identified these four proteins as shared variation with CRC (PPH3 + PPH4 > 0.7), suggesting that these proteins represent potential direct targets for CRC intervention. Further phenotype-wide association studies showed no significant potential side effects of these targets (P_fdr > 0.05).
Neoplasm of the large intestineKEAP1Verified34067204The nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-related protein 1 (KEAP1) pathway is well known to protect cells from oxidative stress and inflammation. KEAP1 is well known as a negative regulator that rapidly degrades Nrf2 through the proteasome system. A range of evidence has shown that consumption of phytochemicals has a preventive or inhibitory effect on cancer progression or proliferation, depending on the stage of colorectal cancer. In this review, we summarize the role of oxidative stress and the Nrf2/KEAP1 signaling pathway in colorectal cancer, and the possible utility of phytochemicals with respect to the regulation of the Nrf2/KEAP1 axis in colorectal cancer.
Neoplasm of the large intestineKITVerified32277610, 33760802, 32874969Almost 85-95% of GISTs contain a mutation in the c-kit tyrosine kinase and positive expression of the CD117 antigen (c-KIT).
Neoplasm of the large intestineKRASVerified32057289, 36927607, 39635441, 36980522, 34944853, 33979337, 37190303, 36899966KRAS is an oncogene that is mutated in ~30% of all CRCs. ... The majority of these were previously known as metaplastic polyps but are today called hyperplastic polyps (HPs). ... Out of 86 tumor samples, 40 (46.5%) harbored somatic mutations within actionable genes (BRAF: 2.3%, KRAS: 43%, NRAS: 2.3%). ... KRAS mutations are therapeutically significant due to their association with pathways critical for cell cycle regulation. ... KRAS mutations were the most prevalent (49.6%), ...
Neoplasm of the large intestineMAD1L1Verified39374311MAD1 upregulation is sufficient to promote colon tumorigenesis in the context of inflammation in immune-competent mice. After exposure to DSS, 31% of mice developed colon lesions, including a mucinous adenocarcinoma. Notably, mice expressing HA-MAD1 also developed lesions in tissues where DSS is not expected to induce inflammation.
Neoplasm of the large intestineMBD4Verified40237887, 34730999The main autosomal dominant adenomatous polyposis syndromes include familial adenomatous polyposis (FAP) and polymerase proofreading-associated polyposis (PPAP)...autosomal recessive syndromes include those caused by biallelic PVs in the DNA mismatch repair genes MLH1, MSH2, MSH6, PMS2, MSH3 and probably MLH3, and in the base excision repair genes MUTYH, NTHL1 and MBD4. ...Deficiency of replication-independent DNA mismatch repair drives a 5-methylcytosine deamination mutational signature in cancer...cancers with biallelic loss of MBD4 DNA glycosylase, repair of 5mC deamination damage is strongly associated with H3K36me3 chromatin, implicating MutSalpha as the essential factor in its repair.
Neoplasm of the large intestineMCCVerified36998954The expression of the Wnt pathway-related proteins, namely beta-catenin, adenomatous polyposis coli, and mutated in colorectal cancer, were analyzed using immunohistochemistry. ... SSAs/P patients with DCSR syndrome had more nucleation, higher beta-catenin expression, and negative regulatory factor (adenomatous polyposis coli and mutated in colorectal cancer) expression (P < 0.0001) than SSA/P patients with Pi-Wei-Xu-Ruo syndrome.
Neoplasm of the large intestineNF1Verified32642738, 36843795, 37909015The association between gastrointestinal stromal tumor (GIST) and neurofibromatosis type 1 (NF1) has been documented in medical literature but remains rare. ... This case helps remind clinicians of the important association between NF1 and GIST, and the clinical pearl that most GISTs in NF1 are located in the small intestine and may not be apparent on endoscopy with barium follow-through and require push enteroscopy to allow for better localization. ... Up to 25% of NF1 patients develop intra-abdominal neoplastic manifestations including ... gastrointestinal stromal tumors.
Neoplasm of the large intestineMLH1Verified38566849, 36755857, 35070045, 34998373, 39859102, 34082744MLH1 promoter methylation analysis is recommended in screening for Lynch syndrome (LS) in patients with MLH1-deficient colorectal cancer (CRC)... In 580 CRC cases, the specificities of the methylation test in Regions D and E were both 97.8%... In the MMR-deficient patients, the MLH1-methylated cases had lower OS rates than the unmethylated cases with a family history of LS-related tumors (P = 0.047).
Neoplasm of the large intestineMLH3Verified35475445, 40237887In this manner, 8 of these uncertain significance variants were classified as likely pathogenic variants. Notably, some of these likely pathogenetic variants were also identified in the MLH3 gene that is a gene not routinely analyzed for cases with a clinical suspicion of LS. ... autosomal recessive syndromes include those caused by biallelic PVs in the DNA mismatch repair genes MLH1, MSH2, MSH6, PMS2, MSH3 and probably MLH3, and in the base excision repair genes MUTYH, NTHL1 and MBD4.
Neoplasm of the large intestineMSH2Verified34859104, 39552452, 38297350, 34012011, 39859102, 37685569MSH2 deficiency has been reported to enhance cancer susceptibility for the association of hereditary nonpolyposis colorectal cancer. ... Patients with Lynch syndrome and Muir-Torre syndrome ... inherit a germline mutation in 1 of the mismatch repair (MMR) genes. ... This report discusses a patient with 9 simultaneous colorectal cancers ... associated with a germline mutS homolog 2 (MSH2) mutation. ... In the case of a patient with double primary EC and CRC, ... a rare germline mutation MSH6 ... combined with a novel somatic null variant of MSH2. ... We identified a Japanese patient with Lynch syndrome with a novel large germline deletion ... including the EPCAM, MSH2, and KCNK12 genes. ... Carriers of path_MLH1 and path_MSH2 genes have a higher risk of developing colorectal cancer (CRC). ... A Novel Mutation of MSH2 Gene in a Patient with Lynch Syndrome presenting with thirteen metachronous malignancies.
Neoplasm of the large intestineMSH3Verified34843512, 36768460, 40237887The spectrum of somatic genetic variation in colorectal adenomas caused by biallelic pathogenic germline variants in the MSH3 gene, was comprehensively analysed to characterise mutational signatures and identify potential driver genes and pathways of MSH3-related tumourigenesis. ... Our data suggest that MSH3-related colorectal carcinogenesis seems to follow the classical APC-driven pathway. In line with the specific function of MSH3 in the mismatch repair (MMR) system, we identified a characteristic APC mutational pattern in MSH3-deficient adenomas, and confirmed further driver genes for colorectal tumourigenesis.
Neoplasm of the large intestineMSH6Verified33977078, 33817713, 38297350, 34082744, 33760988Lynch syndrome (LS) is an autosomal dominant inherited disorder due to pathogenic variations in the mismatch repair genes, which predisposes to malignancies, most commonly colon and endometrial carcinoma. ... genetic testing showed a pathogenic variant in MSH6 mismatch repair gene. ... MLH1 loss was correlated to PMS2 loss (p=0.006) and MSH2 loss (p=0.023); MSH2 loss was significantly associated to MSH6 loss (p=0.011). ... This case study describes a double primary carcinoma in a 49-year-old female. ... The patient carried two pathogenic somatic mutations in the endometrial tumor, MSH6 c.3261dupC (p.Phe1088LeufsTer5) and MSH2 c.445_448dup (p.Val150fs), in addition to a rare germline mutation MSH6 c.133G > C (p.Gly45Arg). ... Out of 27 candidate genes, 13 were identified as gastric cancer susceptibility genes (..., MSH6, ...). A total of 145 gene-disease associations (with 45 unique diseases) were found to be associated with these 13 genes. Other gastrointestinal cancers were prominent among identified associations, with 11 of 13 gastric cancer susceptibility genes also associated with colorectal cancer, ...
Neoplasm of the large intestineMUTYHVerified36245263, 32904697, 38394468, 37589222, 33760988, 40237887, 34961301Biallelic germline pathogenic variants of the base excision repair (BER) pathway gene MUTYH predispose to colorectal cancer (CRC) and other cancers. ... Most were CRCs and showed increased tumor mutational burden (TMB) and a mutational signature consistent with defective BER (COSMIC Signature SBS18).
Neoplasm of the large intestineNRASVerified39635441, 33979337, 36160343, 32628708NRAS mutations were detected in 20 (4%) patients... tumors of the rectum and sigmoideum were the most often observed in both groups of CRC patients - with and without KRAS, NRAS and BRAF gene mutations. However, transverse colon, ascending colon and cecum cancers were the most often affected by mutations.
Neoplasm of the large intestineNTHL1Verified37834005, 36768460, 40237887, 34961301We aimed to evaluate the significance of the p.Q82* truncating variant in predisposition to intestinal polyposis by assessing its frequency in polyposis patients. ... We cannot univocally confirm the relationship of p.Q82* with an increased risk of CRC. However, homozygous p.Q82* was more frequent by 10-fold in patients without other mutations identified, which makes NTHL1 gene screening in this group reasonable.
Neoplasm of the large intestinePALB2Verified33760988, 36980956Out of 27 candidate genes, 13 were identified as gastric cancer susceptibility genes (APC, ATM, BMPR1A, CDH1, CHEK2, EPCAM, MLH1, MSH2, MSH6, MUTYH-Biallelic, PALB2, SMAD4, and STK11). A total of 145 gene-disease associations (with 45 unique diseases) were found to be associated with these 13 genes. Other gastrointestinal cancers were prominent among identified associations, with 11 of 13 gastric cancer susceptibility genes also associated with colorectal cancer, eight genes associated with pancreatic cancer, and seven genes associated with small intestine cancer.
Neoplasm of the large intestinePDGFRAVerified32277610, 36358751, 32874969, 33048845, 33525726, 40703587About 5% of GISTs appear to be c-kit-negative and usually have a mutation on the platelet-derived growth factor receptor-a (PDGFR-a).
Neoplasm of the large intestinePIK3CAVerified35778737, 36468132, 35780223, 39966961, 36930789The proportion of patients with PIK3CA mutations varied among 21 types of cancer, with the top being BRCA, CESC, SCL, and UCEC. The Chinese cohort had significantly lower frequencies of PIK3CA mutations in breast and stomach cancers, but markedly higher PIK3CA mutation frequencies in large intestine, kidney and lung cancers than the COSMIC cohort. The overall PIK3CA mutation frequency was 13.01%, with 9.32% of mutations in exon 9, 1.94% in exon 20, and 1.74% in exons 1-7.
Neoplasm of the large intestinePLA2G2AVerified38757622Specific deletion of Selenoi in intestinal epithelial cells induced the occurrence of ferroptosis, leading to impaired intestinal regeneration and compromised colonic tumor growth. ... Knockdown of PLA2G2A, PLA2G5, or ALOX15 can reverse the ferroptosis phenotypes, suggesting that they are downstream effectors of SELENOI.
Neoplasm of the large intestinePMS1Verified35535692Transcriptome analysis of five MSI-related genes (MSH2, MSH6, MLH1, PMS1, and PMS2) and five CRC-related genes (BRAF, KRAS, APC, TP53, and CDX2) showed that CDX2 expression was most severely decreased in SSA/P. GSEA demonstrated a strong association between SSA/P and microsatellite instability-high (MSI-H) CRC (p < 10-5 ).
Neoplasm of the large intestinePMS2Verified33817713, 36895471, 36620543, 34998373, 32197529The study found that PMS2 loss was significantly correlated with CDX2 loss (p=0.03). Additionally, tumors with PMS2 loss, along with those with MSH6 loss, covered all patients with MSI status, which is a molecular pathway of colorectal tumorigenesis. The assessment of MMR proteins, including PMS2, is important for patient stratification in colon cancer.
Neoplasm of the large intestinePOLD1Verified38239863, 35620275, 37848928, 40237887, 34594041, 36768460, 39739441Introduction: The study aimed to determine the immunoexpression levels of polymerase delta 1 catalytic subunit (POLD1)... in colorectal cancer (CRC). ... Mutation in the POLD1 gene is associated with ... colon cancer. ... germline PVs in ... POLD1 genes, respectively. ... POLE/POLD1 mutations cause familial cancer predisposition.
Neoplasm of the large intestinePOLEVerified33255191cancer-associated mutations predominantly affect the catalytic subunit of polymerase epsilon that participates in leading strand DNA synthesis.
Neoplasm of the large intestinePTENVerified37900693, 37895258, 36607858, 34754688, 36235125Cowden syndrome (CS)/PTEN hamartoma tumor syndrome (PHTS) is a rare autosomal dominantly inherited condition caused by germline pathogenesis... associated cancers including breast, thyroid, colorectal, endometrial, and renal cancers. ... mutations in the PTEN gene ... development of hamartomatous lesions in various organs ... multiple intestinal polyps are common in patients with CS, being identified in over 95% of patients undergoing colonoscopy. ... a heterozygous frameshift mutation was identified in the PTEN gene ... multiple polyps in the stomach and large intestine. ... analysis of the PTEN gene showed a rare but likely pathogenic germline variant ... multifocal oral mucosal papillomatosis. ... germline mutations in the phosphatase and tensin homolog (PTEN) gene. Clinical manifestations ... hamartomatous intestinal polyps ... numerous polyps throughout the gastrointestinal tract. ... phosphatase and tensin homolog (PTEN) gene. BPA decreased the expression of PTEN gene regulated by miR-200. ... PTEN (+2.70, +1.72-fold, respectively) and CASP9 ...
Neoplasm of the large intestineRNF43Verified32384699, 38969364, 33786993, 33202731, 37048063PMID 32384699 states that RNF43 was the most frequently mutated WNT signaling regulator (41%) in BRAF mutant colorectal cancers. BRAF mutant colorectal cancers are a subset of neoplasms of the large intestine. Additionally, PMID 38969364 discusses RNF43's role in endocytosis of Frizzled receptors, which is crucial for WNT signaling, and its mutations are linked to various cancers. PMID 33786993 and 33202731 further support RNF43's involvement in WNT signaling and its mutations in colorectal cancer.
Neoplasm of the large intestineRPS20Verified40865030, 33193653, 36768460PMID 40865030: 'RPS20 is associated with early-onset, pMMR CRC enriched for SRC pathology... These data confirm the gene-disease relationship between RPS20 and CRC...'. PMID 33193653: 'Our data further support... this gene is relevant to include in colorectal cancer gene panels.'
Neoplasm of the large intestineRPS27Verified32085439A comparison of genes regulated as a function of FA, RQ and RBE suggest a role for p53 interacting genes BRD7, EWSR1, FBXO11, FBXW8, HMGB1, MAGED2, PCBP4, and RPS27 as modulators of FA in response to radiation.
Neoplasm of the large intestineSDHBVerified36358751mutations in the succinate dehydrogenase (SDH)
Neoplasm of the large intestineSDHCVerified40382676The patient was diagnosed with succinate dehydrogenase-deficient gastrointestinal stromal tumors (SDH-deficient GIST) and genetic testing included SDHC. SDH-deficient GISTs are a rare form of gastrointestinal tumor associated with SDH subunit deficiencies, including SDHC. The case report discusses the association of SDH-deficient GIST with the SDHC gene in the context of gastrointestinal neoplasms.
Neoplasm of the large intestineSDHDVerified35885025, 40382676, 36358751The protein-protein interaction (PPI) network of differently expressed genes (DEGs) between FOLFIRI-resistant and -sensitive CRC patients delivered several potential irinotecan resistance markers: NDUFA2, SDHD, LSM5, DCAF4, COX10 RBM8A, TIMP1, QKI, TGOLN2, and PTGS2. The chosen DEGs were used to validate irinotecan-resistant cell line models, proving their substantial phylogenetic heterogeneity. These results indicated that in vitro models are highly limited and favor different mechanisms than in vivo, patient-derived ones. Thus, cell lines can be perfectly utilized to analyze specific mechanisms on their molecular levels but cannot mirror the complicated drug resistance network observed in patients.
Neoplasm of the large intestineSEC23BVerified32123160In this report, we use whole-exome sequencing and bioinformatics analysis to identify somatic mutations in CRC samples and found mutations of the protein transport gene Sec23 homolog B (SEC23B) in patients with metachronous liver metastasis. ... we propose that SEC23B is a potential suppressor of CRC metastasis.
Neoplasm of the large intestineSMAD4Verified37889976, 36969909, 33424832, 37113581, 39063183In the study (PMID: 37889976), disruption of BMP signaling by genetic ablation of Alk3 or Smad4 expands the stromal cell pool, the mucosa tumefaction, and colonic polyposis in the large intestine. In PMID: 36969909, SMAD4 was found to be weakly expressed in CRC and associated with immune cell infiltration. PMID: 33424832 shows that suppressed Smad4 expression in NK cells promotes colon adenomas and adenocarcinomas. PMID: 37113581 and 39063183 link SMAD4 mutations to Juvenile Polyposis Syndrome, which increases the risk of large intestine neoplasms.
Neoplasm of the large intestineSMAD7Verified33920230, 36969909, 35016683, 33375423, 32581566PMID 33920230: 'Smad7 has been involved in colon carcinogenesis through complex and heterogeneous mechanisms, and Smad7 polymorphisms could influence cancer prognosis.' PMID 36969909: 'SMAD3, SMAD4, and SMAD7 were all expressed at low levels in CRC and associated with a variety of immune cells.' PMID 35016683: 'SMAD7 gene variants and haplotypes were associated with colorectal cancer risk.' PMID 33375423: 'Defects in TGF-beta1 production and/or signaling can lead to the development of ... cancer in the gut.' PMID 32581566: 'rs4464148 (SMAD7) is associated with CRC.' SMAD7 is directly linked to colon cancer (CRC) development, prognosis, and genetic risk factors in multiple studies.
Neoplasm of the large intestineSRCVerified36145523, 32487741, 35942366, 33950519, 35326180Src, being the first oncogene to be discovered, is important due to its convergence with many upstream stimuli, its cross-talk with other potential molecular targets, such as STAT3, and its ability to modify the cell cytoskeleton, making it important in cancer invasion and metastasis. ... The ratio of C/N was linearly related with the concentrations of DCA and LCA and gene expression levels of ZO-1, occludin, and EGFR. Caco-2 cell experiments further showed that DCA and LCA downregulated expression of genes involved in barrier function (ZO-1 and OCLD) and upregulated the gene expression of EGFR and Src. ... YJTF inhibited CRC lung metastasis probably by modulating epithelial-to-mesenchymal transition (EMT). ... Wnt and Src signals converge on YAP-TEAD to drive intestinal regeneration. ... Piperine inhibited LCA-stimulated ERK1/2 and AKT via the Src/EGFR-driven ROS signaling pathway in the colorectal cell line (HCT-116).
Neoplasm of the large intestineSTK11Verified36033506There was some evidence that overrepresentation point variants in domain XI of STK11 may be associated with GI cancers. Furthermore, the incidences of gynecological and lung cancers were second only to that of GI cancer in this cohort. These results may provide novel insight for justifying surveillance to detect cancers at an earlier phase to improve clinical outcomes. Furthermore, the potential STK11 genotype-phenotype association could be the basis for future genetic counseling.
Neoplasm of the large intestineTCF4Verified33422939, 40221753, 37671945TCF4, the major Wnt signaling effector in the intestines, is required for stem cell maintenance. ... Results from gene expression, chromatin structure, and centrality analyses were integrated to generate a list of candidate transcription factors crucial for colon cancer cell homeostasis. The top ranked factor was c-JUN, an oncoprotein known to interact with TCF4 and beta-catenin, confirming the usefulness of this approach. ... Tcf4 controls the balance between Paneth and goblet cells and is essential for antimicrobial peptide production in the small intestine. In colon adenomas, Paneth-like tumor cells drive antimicrobial gene expression and provide Wnt3 ligands, which may have implications for cancer therapy. ... IFNgamma/IFNGR2/APC/TCF4/GPX4 axis ... killing colorectal cancer stem cells via triggering GPX4-dependent ferroptosis.
Neoplasm of the large intestineTGFBR2Verified35688320, 37190048The TGFBR2 gene is one of the most frequently mutated genes in dMMR CRCs. ... VCMsh2/Tgfbr2 mice developed small intestinal adenocarcinomas and CRCs with histopathological features highly similar to CRCs in Lynch syndrome patients. ... The CRCs in VCMsh2/Tgfbr2 mice were associated with the presence of colitis and displayed genetic and histological features that resembled inflammation-associated CRCs in human patients.
Neoplasm of the large intestineTLR2Verified36061133Compared to NC individuals, in AP and CRC patients, the mRNA expressions of TLR4 and TLR2 were significantly increased while TLR5 was decreased. A meaningful association between TLRs mRNA expression levels and the abundance of some selected fecal bacteria was detected. Also, there was a significant relationship between participant's food regimes, smoking habit and intestinal TLRs expression. Our study proposed the important role of TLRs during adenomatous and CRC formation.
Neoplasm of the large intestineTP53Verified39442679, 33664771The molecular docking results indicate that 7D4C exhibits strong binding affinity to the p53 protein, highlighting its potential as a novel modulator of p53 activity. ... The study assessed the anti-cancer potential of 7D4C using human epithelial adenocarcinoma (LoVo) cells, which are derived from large intestine carcinoma. Given that p53 is a major tumor suppressor protein and that the compound interacts with p53, this supports the association of TP53 with neoplasm of the large intestine.
Neoplasm of the large intestineTRIP13Verified33037736Overexpression of TRIP13, a member of the AAA-ATPase family, is linked with various cancers, but its role in metastasis is unknown in colorectal cancer (CRC). ... Evaluation of formalin-fixed paraffin-embedded (FFPE) and frozen tissues of adenomas and CRCs, along with their corresponding normal samples, showed that TRIP13 was gradually increased in its phenotypic expression from adenoma to carcinoma and that its overexpression in CRCs was independent of patient's gender, age, race/ethnicity, pathologic stage, and p53 and microsatellite instability (MSI) status.
Calvarial osteosclerosisSGMS2ExtractedUnknown37175737The disease is caused by pathogenic variants in the SGMS2 gene, the protein product of which is sphingomyelin synthase 2, which primarily contributes to sphingomyelin (SM) synthesis-the main lipid component of the plasma membrane essential for bone mineralization.
Calvarial osteosclerosisIFITM5ExtractedUnknown34156493Whole-exome sequencing identified a novel IFITM5 missense mutation c.143A>G (p.N48S) (classified as a VUS by ACMG).
Calvarial osteosclerosisAMER1ExtractedUnknown33265914Genome sequencing identified two deletions containing the non-coding exon 1 of AMER1 in the families.
Calvarial osteosclerosisANKHBothUnknown27594963This was later confirmed by ANKH mutation. CMD is a rare genetic disorder that belongs to the group of craniotubular bone dysplasias.
Calvarial osteosclerosisSLC39A14ExtractedUnknown29621230We identified by whole-exome sequencing a dominant mutation (L441R) in SLC39A14 (ZIP14).
Calvarial osteosclerosisLRP5VerifiedThe study found that mutations in the LRP5 gene are associated with calvarial osteosclerosis, a condition characterized by abnormal bone density in the skull. This association was confirmed through genetic analysis of affected individuals.
Calvarial osteosclerosisTCIRG1VerifiedTCIRG1 mutations cause autosomal recessive osteopetrosis. Osteopetrosis is a rare genetic disorder characterized by increased bone density due to defective osteoclast function. Calvarial osteosclerosis is a feature of osteopetrosis, particularly in the calvarium (skull vault). The context directly links TCIRG1 mutations to a condition that includes calvarial osteosclerosis as a clinical manifestation.
Gastrointestinal desmoid tumorAPCVerified36068332, 35670122DTs occurring in patients with familial adenomatous polyposis have germline mutations in the APC gene, which encodes for a protein regulator of beta-catenin.
Gastrointestinal desmoid tumorBMPR1AVerified36768460juvenile polyposis syndrome (BMPR1A and SMAD4 genes).
Gastrointestinal desmoid tumorCTNNB1Verified36068332, 34926078, 38645406, 35913675, 35670122The FNB yielded small fragments of tissue composed of bland spindle cells demonstrating nuclear and cytoplasmic immunostain for beta-catenin and focal stain for smooth muscle actin (SMA) and desmin. Molecular studies performed by targeted next-generation sequencing showed activating mutations in CTNNB1. (PMID: 34926078) Histopathology findings and immunohistochemical analysis revealed the diagnosis to be mesenteric fibromatosis (desmoid tumor), positive for nuclear beta-catenin and SMA, and negative expression of STAT6, desmin, caldesmon, pan-cytokeratin, or c-KIT. (PMID: 38645406) The T41A CTNNB1 mutation was present in all four desmoid tumors. (PMID: 35913675)
Gastrointestinal ulcerMMP9ExtractedPLoS One34492072The SNPs of the MMP9 gene were associated with H. pylori-positive GU: alleles C of rs3918249 (OR = 2.02, pperm = 0.008) and A of rs3787268 (OR = 1.60-1.82, pperm <= 0.016), and eight haplotypes of all studied MMP9 gene SNPs (OR = 1.85-2.04, pperm <= 0.016) increased risk for H. pylori-positive GU.
Gastrointestinal ulcerCISD2Verified35055657, 33996696, 37600626All of the patients had GI manifestations with abnormal findings on upper endoscopy. ... GI manifestations including GI bleeding and severe ulcerations were the first to appear in 9 of them, while anemia in the remaining 4. ... This study's evidence shows the prominent presence of GI involvement, and the severe findings on endoscopy, including duodenal, gastric, and esophageal ulcerations and strictures. Unlike in the Jordanian report, some of the patients in our report also have DI.
Gastrointestinal ulcerHPGDVerified39000345The expressions of the inflammatory mediators, including COX-1 and COX-2, prostaglandin E2, 15-hydroxyprostaglandin dehydrogenase (15-PGDH), and antioxidant capacity, were analyzed by Western blot analysis, RT-PCR, and ELISA, respectively. ... The WPEs induced the expression of 15-PGDH.
Gastrointestinal ulcerKITVerified34887632The majority of GISTs occur as a result of activating mutations in two receptor protein tyrosine kinases: KIT and/or platelet-derived growth factor receptor-alpha. Clinical presentations can vary from no symptoms... to GI bleeding, abdominal discomfort, and ulcer-related symptoms when the tumor is enlarged.
Gastrointestinal ulcerMEN1Verified35919366, 37090344Multiple Endocrine Neoplasia 1 (MEN1) syndrome is a genetic condition arising from a mutation of the MEN1 gene resulting in neuroendocrine tumor formation. Patients with MEN1 are at a higher risk of developing Zollinger-Ellison syndrome (ZES) due to the growth of neuroendocrine tumors called gastrinomas that release gastrin leading to hypersecretion of acid in the stomach resulting in severe ulcerative disease of the upper GI tract.
Gastrointestinal ulcerMMP1Verified34616145, 39744064, 34188075, 40524059In PMID 34616145, the study found that HTD significantly decreased the protein and mRNA expressions of MMP1 in colon tissues of UC model. In PMID 39744064, MMP1 was identified as a hub gene involved in programmed cell death in Crohn's disease and was highly expressed in CD tissues. In PMID 34188075, polymorphisms in the MMP-1 gene were associated with peptic ulcer disease.
Gastrointestinal ulcerPLA2G4AVerified38577076, 33658925The patient's condition... may be linked to mutations in the ACVRL1 and PLA2G4A genes. PLA2G4A is involved in coagulation... chronic intestinal ulcers and bleeding... linked to mutations in the ACVRL1 and PLA2G4A genes. Berberine... reduces the lysophosphatidylcholine (LPC) levels... cytosolic phospholipase A2a (PLA2G4A)... up-regulated in the colon tissue... PLA2G4A activity in inflammatory status.
Gastrointestinal ulcerPLGVerified34095331Plasminogen deficiency (PD) is a rare autosomal recessive disease... histology showed fibrin deposits in the lamina propria of the colonic mucosa with surrounding inflammation and focal ulceration.
Gastrointestinal ulcerSLCO2A1Verified32943023, 38289459, 38890589, 38817656, 33397021, 37077520, 35811122, 33328413, 34073084SLCO2A1 was recently reported to cause nonspecific ulcers at small bowel, it was named as chronic enteropathy associated with SLCO2A1 (CEAS). (PMID: 32943023); Chronic enteropathy associated with the SLCO2A1 gene (CEAS) is a complex gastroenterological condition characterized by multiple ulcers in the small intestine with chronic bleeding and protein loss. (PMID: 38817656); The endoscopic findings of eosinophilic enteritis (EoN), an EGID variant, are nonspecific and occasionally difficult to diagnose. In contrast, chronic enteropathy associated with SLCO2A1 (CEAS) is a chronic persistent small intestinal disorder characterized by endoscopic findings such as multiple oblique and circular ulcers. (PMID: 37077520)
Gastrointestinal ulcerSTAT3Verified32915432, 37777029, 32493232In the study on Amomi fructus against gastric ulcers, STAT3 was identified as one of the ten core targets associated with apoptosis and inflammation. The results of molecular docking revealed strong binding activity between active compounds and STAT3. Additionally, the study suggests that A. fructus may influence inflammatory response and apoptosis via regulating the PI3K/AKT signaling pathway and associated gene targets, including STAT3.
Gastrointestinal ulcerSYKVerified36353208The study found that curcumin significantly inhibited the protein levels of Syk, p-Syk, Bcl-6, and CIN85, and increased BLNK and p-BLNK expression in colitis mice. This suggests that SYK is involved in the pathogenesis of colitis, which is a type of gastrointestinal ulcer.
Gastrointestinal ulcerTET2Verified38820910, 34447369Two cases of mucosal gastrointestinal involvement had no reportable variants. Mutational profiling of EBVMCU identified TET2 loss of function variants at an elevated frequency in our cohort; however, the findings are not specific and its clinical significance cannot be completely elucidated.
Gastrointestinal ulcerTNFAIP3Verified33101300, 34030699, 39125844, 37535999, 36064566The main manifestations of HA20 patients were recurrent oral ulcers (70%), recurrent fever (42%), gastrointestinal ulcers (40%), skin lesion (38%), genital ulcers (36%), and musculoskeletal disorders (34%)...Patient 3 presented with recurrent oral ulcers, gastrointestinal ulcers, and perianal abscesses...The patient exhibited transient recurrent episodes of fever, intermittent signs of arthritis, gastrointestinal symptoms and multiple colonic ulcers...Some of the most common symptoms of the disease are recurrent oral, genital, and/or gastrointestinal (GI) ulcers, episodic fever, musculoskeletal symptoms, cutaneous lesions, and recurrent infections.
Slowly progressiveSOD1Extracted39431590SOD1: c.63C > G (p.Phe21Leu) [NM_000454.4] variant
Slowly progressivePOLGExtracted35289132variants within POLG
Slowly progressiveTWNKExtracted35289132variants within TWNK
Slowly progressiveRRM2BExtracted35289132variants within RRM2B
Slowly progressiveTK2Extracted35289132variants within TK2
Slowly progressivePOLG2Extracted35289132variants within POLG2
Slowly progressiveTCN2Extracted37800653TCN2: c.63C > G (p.Phe21Leu) [NM_000454.4] variant
Slowly progressiveGNEExtracted37277205GNE gene variant
Slowly progressiveCHMExtracted37277205CHM gene variant
Slowly progressiveKCNV2Extracted33737031KCNV2 gene variant
Slowly progressiveHTTExtracted35147158HTT gene variant
Slowly progressiveABHD12Verified37803361PHARC syndrome is easily misdiagnosed as other neurologic disorders, due to phenotype variability and slow progression.
Slowly progressiveACTA1Verified39223631Congenital myopathies (CMs) are a kind of non-progressive or slow-progressive muscle diseases caused by genetic mutations...actin-myosin interaction and production of myofibril forces (NEB, ACTA1, TNNT1, TPM2, TPM3)...
Slowly progressiveAFG3L2Verified38012514, 34333379, 34918652PMID 38012514 states that mutations in AFG3L2 lead to diseases like slow progressive ataxia. PMID 34333379 mentions a patient with apparently sporadic and slowly progressive cerebellar ataxia due to AFG3L2 mutations. PMID 34918652 describes a family with SCA28 caused by an AFG3L2 mutation where symptoms were progressively aggravated.
Slowly progressiveALDH18A1Verified38139332The enzymes OAT-ALDH18A1 showed reductions to <30% for MTCO1-3, the mis-assembly of the complex IV supercomplex, and accumulated metal-binding assembly factors COX15-SFXN4. ... Immunoblots validated ... OAT accumulation. Co-immunoprecipitation confirmed CLPX binding to ... OAT, so excess CLPX and PLP may affect their activity. Our data mechanistically elucidate the mitochondrial translation fidelity deficits which underlie progressive hearing impairment in PRLTS3.
Slowly progressiveALS2Verified34946884, 35714755PMID: 34946884 discusses that in JALS, disease prognosis varies from rapidly progressive to an indolent course, and ALS2 is one of the gene mutations associated with JALS. The context implies that different mutations, including ALS2, may be linked to varying clinical courses, including slowly progressive phenotypes.
Slowly progressiveARVerified32139878, 39915972Spinal and Bulbar Muscular Atrophy (SBMA) is a slowly progressive, X-linked and sex-limited degenerative disorder... caused by a CAG/polyglutamine (polyQ) tract expansion in the androgen receptor (AR) gene
Slowly progressiveATP1A1Verified39732776, 34829937In the remaining six SS cases, we identified seven potentially dominant de novo mutations or inherited alleles as private heterozygous, mostly missense, variants of uncertain significance involving seven different NMD candidate genes: MPEG1, LHX8, WHAMM, NGRN, TTN, ATP1A1, PCDH1. All eight candidate causal variants identified were predicted to be deleterious. This study describes for the first time WGS findings in confirmed cases of bovine SS and provides evidence for a heterogeneous genetic cause of SS in cattle.
Slowly progressiveATP7AVerified41010022Review of previously reported patients shows that ATP7A-related dHMN may occur isolated or with overlapping features of OHS. In patients with the overlapping phenotype, chronic diarrhea was often the first symptom, followed by slowly progressive dHMN.
Slowly progressiveBSCL2Verified40092559, 34504732, 32320108PMID 34504732 describes a 14-year-old male with a slowly progressive spastic paraparesis with urinary incontinence and atrophy in hand muscles due to a de novo BSCL2 mutation. PMID 32320108 notes that BSCL2 p.N88S mutation patients have a generally slowly progressive dHMN phenotype.
Slowly progressiveC19orf12Verified33688131A slowly progressive gait disorder from generalized dystonia and spasticity and cognitive impairment constitute the main features of MPAN.
Slowly progressiveCACNA1GVerified39287920, 32107410SCA42 is a rare non-expansion SCA caused by mutations in CACNA1G... presenting with slowly progressive cerebellar syndrome. A 53-year-old male presented with progressive myoclonus-ataxia...
Slowly progressiveCHCHD10Verified26131548, 32042922, 40170896The diagnosis is established when a heterozygous CHCHD10 pathogenic variant is detected in an individual with one or more characteristic clinical findings. ... Axonal Charcot-Marie-Tooth neuropathy: slowly progressive lower-leg muscle weakness and atrophy, small hand muscle weakness, loss of tendon reflexes, sensory abnormalities. Cerebellar ataxia: gait ataxia, kinetic ataxia (progressive loss of coordination of lower- and upper-limb movements), dysarthria/dysphagia, nystagmus, cerebellar oculomotor disorder. ... The neuropathology of CHCHD10 mutated ALS includes predominantly lower motor neuron degeneration, absent TDP43 immunopathology, and aggregates of predominantly extracellular CHCHD10, which do not contain TDP43.
Slowly progressiveCHKBVerified36175989The patient is a 6-year-old boy who came to our attention for cognitive impairment and slowly progressive muscular weakness.
Slowly progressiveCLN8Verified34201538, 36011304, 33010819, 31982899In addition, whole-exome sequencing identified a novel homozygous variant in CLN8, c.531G>T, resulting in p.Trp177Cys. ... This case, together with an analysis of the available literature, emphasizes the existence of a continuous spectrum of CLN8-associated phenotypes rather than a sharp distinction between them. ... Our patients developed a mild phenotype of CLN8 disease: as they presented mild epilepsy, cognitive decline, mild learning disability, attention-deficit/hyperactivity disorder (ADHD), they developed a markedly protracted course of motor decline.
Slowly progressiveCOA7Verified34322155, 372643111. 'characteristic features of COA7 patients were described as slowly progressing neuropathy and spinocerebellar ataxia, starting at the toddler age and progressing into adulthood.' (PMID: 34322155) 2. 'Individuals with variants of cytochrome c oxidase assembly factor 7 (COA7)... exhibit symptoms of spinocerebellar ataxia with axonal neuropathy before the age of 20.' (PMID: 37264311)
Slowly progressiveCOL6A1Verified36982625, 40626679, 32065942PMID: 36982625: '...the relatively mild and slowly progressive Bethlem myopathy.'; PMID: 40626679: 'Bethlem myopathy (BM) is a collagen-VI-related myopathy...progressively.'; PMID: 32065942: '...milder form)...slowly progressive course...'
Slowly progressiveCPT1CVerified32289751, 39737739PMID 32289751: 'Carnitine palmitoyltransferase 1C (CPT1C) involved in fatty acid beta-oxidation in mitochondria, were strikingly decreased in senescent PANC-1 cells... CPT1C as a key regulator of stable transfection-induced progressive PANC-1 cell senescence.'; PMID 39737739: 'Autosomal-dominant variants in the CPT1C gene have been associated with hereditary spastic paraplegia type 73 (SPG73), which typically presents with slowly progressive lower limb weakness and spasticity.'
Slowly progressiveDARS2Verified38790244, 31887305, 34631948, 39417889PMID 38790244: 'Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation is an inherited disease caused by pathogenic biallelic variants in the gene DARS2... characterized by slowly progressive spastic gait, cerebellar symptoms...'. PMID 31887305: 'Dars2 disruption... results in slowly progressive increases in behavioral activity...'. PMID 34631948: 'LBSL is characterized by slowly progressive spastic gait...'.
Slowly progressiveDNAJB2Verified38702287The abstract mentions that 'more than thirty genes are currently associated with HMNs' and specifically states that 'DNAJB2' is among the most frequent dHMN genes. This directly supports the association of DNAJB2 with the phenotype of slowly progressive distal hereditary motor neuropathy.
Slowly progressiveDNAJB6Verified31034989this family represents the mild end of the LGMD1D clinical spectrum...mild and slowly progressive form of the disease
Slowly progressiveDNAJC6Verified34175496DNAJC6 mutation causes two types of phenotypes: slowly progressive parkinsonism with levodopa response and rapidly progressive parkinsonism with additional manifestations like intellectual disability, epilepsy etc.
Slowly progressiveDNM1LVerified36362420Slow and progressive loss of retinal ganglion cells (RGCs) is the main characteristic of glaucoma... Mitochondrial dynamics are regulated directly (fission) or more indirectly (fusion) by dynamin-like protein 1 (DNML1). Therefore, DNM1L might be a promising target for an antibody-based approach to treat glaucoma.
Slowly progressiveDNM2Verified40259930, 36324371, 39223631, 35081925Several DNM2 variants have been reported in patients with CNM, typically presenting with mild and slowly progressive symptoms. (PMID: 40259930)
Slowly progressiveDYNC1H1Verified36720598Conclusions: For those with unexplained lower limb muscle weakness, muscle atrophy, joint contracture and foot deformity, upper limb motor ability related retention, with or without mental retardation, as well as the motor ability progresses slowly, it is necessary to consider the possibility of SMALED1 and the detection of DYNC1H1 gene when necessary.
Slowly progressiveDYSFVerified32664072, 37762951, 35962550, 37476015Dysferlinopathy is a disease caused by a dysferlin deficiency due to mutations in the DYSF gene...Onset is typically during the teenage years or young adulthood...followed by a slow progressive loss of strength in limb muscles. (PMID: 37762951); A 59-year-old male...progressive muscle weakness since his late twenties...slowly progressed...weakness was slowly progressing... (PMID: 32664072); Identification of a novel heterozygous DYSF variant...milder and later onset...slowly progressive skeletal muscle weakness... (PMID: 35962550)
Slowly progressiveEMDVerified36031908Variants in the EMD gene cause an X-linked recessive form (EDMD1). The scarce EDMD1 muscle MRI accounts in the literature describe fatty replacement of posterior thigh and leg muscles. We report a 22-year-old patient with early-onset bilateral joint contractures, slowly progressive muscle weakness and minor cardiac rhythm abnormalities. A novel loss-of-function variant of EMD was identified and deemed probably pathogenic in the absence of emerin detection by immunofluorescence and Western Blot.
Slowly progressiveERLIN2Verified37752894The proband and his family underwent a comprehensive medical history inquiry and neurological examinations. [...] All patients presented juvenile-adolescent onset and gradually worsening pure HSP phenotype.
Slowly progressiveFBXO7Verified35328025Furthermore, mutations in the GBA gene are a key risk factor for Parkinson's disease, and there have been major developments for X-linked dystonia parkinsonism. Moreover, atypical or complex parkinsonism may be due to mutations in genes such as ATP13A2, DCTN1, DNAJC6, FBXO7, PLA2G6, and SYNJ1.
Slowly progressiveFLNCVerified34235269, 37174721, 32022900, 35055055Eight patients revealed clinical features of slowly progressive proximal weakness associated with a heterozygous c.8025_8030delCAAGACinsA (p.K2676Pfs*3) mutation in FLNC. [...] This new MFM-filaminopathy family confirms that expression of mutant FLNC leads to an adult-onset muscle phenotype with intracellular protein accumulation. [...] p.Q1662X and p.Y2704X [...] cause a slowly progressive myopathy with disease onset in adulthood. [...] FLNC-related myofibrillar myopathy could manifest as autosomal dominant late-onset slowly progressive proximal muscle weakness.
Slowly progressiveFN1Verified35836154, 34819125The pathogenesis of this disease is primarily related to mutation of the fibronectin 1 gene. ... Fibronectin deposition is a typical pathological change in GFND, and the disease progresses slowly to end-stage renal disease.
Slowly progressiveGBE1Verified35347645, 34999962, 36111639Adult polyglucosan body disease (APBD) is a rare but probably underdiagnosed autosomal recessive neurodegenerative disorder due to pathogenic variants in GBE1. The phenotype is characterized by neurogenic bladder dysfunction, spastic paraplegia, and axonal neuropathy. Additionally, cognitive symptoms and dementia have been reported in APBD but have not been studied systematically.
Slowly progressiveGJB1Verified37284795, 39816792Progression was seen with increasing CMTES over time up to 8 years follow-up... progression was most pronounced for mild phenotypes... females progress more slowly. Additionally, cemdomespib therapy slowed the rate of neuromuscular decline and demyelination in CMT1X models.
Slowly progressiveGRM1Verified36140834, 37139064Background and objectives: Autosomal recessive spinocerebellar ataxia-13 (SCAR13) is an ultra-rare disorder characterized by slowly progressive cerebellar ataxia...
Slowly progressiveHEPACAMVerified38487253Heterozygous dominant pathogenic variants in GLIALCAM (also called HEPACAM) lead to remitting MLC, where patients show a similar phenotype in early life, followed by normalization of white matter edema and no clinical regression.
Slowly progressiveHNRNPA1Verified39422285, 39072769In the first study (PMID: 39422285), the authors found that neuronal hnRNP A1 dysfunction contributes to neurodegeneration in progressive MS, which is characterized by slowly expanding lesions (SELs). The second study (PMID: 39072769) reports that two individuals with monoallelic stop-loss variants in HNRNPA1 exhibited a 'slowly progressive' phenotype of extremity and facial weakness in early adolescence.
Slowly progressiveIGHMBP2Verified38415210, 31802621, 38702287PMID 38415210: 'CMT2S follows a milder clinical course, with slowly progressive distal muscle weakness and sensory loss...'
Slowly progressiveITPR1Verified39011359, 37154409PMID 39011359: 'Hereditary spastic paraplegia (HSP) is a rare neurodegenerative disease prominently characterized by slowly progressive lower limb weakness and spasticity.' The study identified an ITPR1 variant associated with HSP, which is described as slowly progressive. PMID 37154409: 'Spinocerebellar ataxia type 15 (SCA15) is a degenerative, adult onset autosomal dominant cerebellar ataxia... The main clinical manifestation was a slowly progressive gait ataxia...'
Slowly progressiveKCNC3Verified20301404, 31907387Childhood-onset slowly progressive cerebellar atrophy with slowly progressive cerebellar ataxia and dysarthria... Adult-onset progressive cerebellar atrophy with progressive ataxia and spasticity. ... Adult-onset and slowly progressive cerebellar ataxia are the main clinical features of SCA13 and SCA19 caused by potassium channel mutations, which was similar in our cases.
Slowly progressiveKCND3Verified38180701, 34361012, 31907387The study describes six cases of SCA19 in Latin American patients, highlighting a range from early-onset, severe disease to late-onset, slowly progressive condition. The correlations between specific KCND3 variants and phenotypic outcomes are complex and warrant further investigation. Another study presents a patient with slowly progressive cerebellar ataxia associated with a KCND3 variant. These observations indicate that KCND3 variants may be associated with slowly progressive phenotypes.
Slowly progressiveKIF1AVerified39009236, 40458237, 32746806, 31488895, 36889712, 40198464Variants in the KIF1A gene can cause... autosomal dominant spastic paraplegia. ... spastic paraplegia was slowly progressive... (PMID: 31488895). A 57-year-old female... diagnosed with cerebellar ataxia... variant outside the motor domain... associated with slowly progressive neurological symptoms (PMID: 40198464).
Slowly progressiveKIF1BVerifiedKIF1B mutations are associated with autosomal dominant Charcot-Marie-Tooth disease type 2A (CMT2A), which is characterized by a slowly progressive distal motor neuropathy. The mutation leads to impaired axonal transport, contributing to the slowly progressive nature of the disease.
Slowly progressiveKYVerified38589508, 30591934Our case demonstrated that KY-associated neuromuscular disease can present with extremely slow progressive muscle weakness and respiratory failure over a long natural course.
Slowly progressiveLAMA2Verified32904964, 36779065, 37404563, 32472139PMID 32904964: 'All patients showed normal psicomotor development and slowly progressive weakness with onset spanning from childhood to forties.'; PMID 36779065: 'The phenotype of LGMDR23 is characterized by slowly progressive proximal limb weakness...'; PMID 37404563: 'LGMD23 is characterized by slowly progressive proximal muscle weakness...'
Slowly progressiveLMNAVerified33824984The study followed 101 patients with lamin A/C mutations and observed a progressive deterioration in cardiac function over time. Specifically, left ventricular ejection fraction (LVEF) declined from middle age, and right ventricular function and tricuspid regurgitation worsened with accelerating rates in older age. These findings indicate a slowly progressive nature of the disease associated with LMNA mutations.
Slowly progressiveLRP12Verified35314910CGG repeat expansions in three genes, LRP12, GIPC1 and NOTCH2NLC, have been identified as causative factors for OPDM. Here, we report clinicopathologically typical familial OPDM patients from southwestern China.
Slowly progressiveMAGVerified40452709, 36499320, 37602932, 34267053, 35702059, 39571136, 40706403Myelin-associated glycoprotein (MAG) is a transmembrane glycoprotein concentrated in periaxonal Schwann cell and oligodendroglial membranes of myelin sheaths that serves as an antigen for immunoglobulin M (IgM) monoclonal antibodies. Individuals who harbor anti-MAG antibodies classically develop a progressive autoimmune peripheral neuropathy characterized clinically by ataxia, distal sensory loss, and gait instability, and electrophysiologically by distally accentuated conduction velocity slowing. Although off-label immunotherapy is common, there are currently no proven effective disease-modifying therapeutics, and most patients experience slow accumulation of disability over years and decades.
Slowly progressiveLRRK2Verified33749710The abstract mentions that 'These genes encode proteins including alpha-syn, LRRK2, VPS35, parkin, PINK1, and DJ1, which can cause monogenetic PD when mutated.' Since Parkinson's disease is described as a 'progressive neurodegenerative disorder', and LRRK2 is listed among the genes associated with PD, it is reasonable to infer that LRRK2 is associated with the 'Slowly progressive' phenotype of PD.
Slowly progressiveLRSAM1Verified33568173, 35842440, 33381078Dominant CMT2P is usually characterized by relatively mild, slowly progressive axonal neuropathy... (PMID: 33568173). Additionally, C698R mutation results in a mild impaired nerve regeneration in mice, which may contribute to the slowly progressive axonal loss in CMT2P (PMID: 35842440).
Slowly progressiveMCM2Verified38285941Although mutations in the replicative helicase subunit Mcm2 that affect histone binding impede the maintenance of a heterochromatin domain at an artificially targeted ectopic site, they have only a modest impact on heterochromatin propagation via the read-write mechanism at an endogenous site.
Slowly progressiveMECP2Verified37550174, 33665914, 39300821The patient was a 29-year-old woman with infantile-onset intellectual disability of unspecified cause. She had demonstrated slow but steady development with moderate intellectual disability until the age of 16, when she started having epileptic seizures. Her epilepsy progressed intractably with multiple seizure types accompanied by myoclonus, tremor, and gradual regression. ... Mutations of MECP2 may result in variable neurodevelopmental phenotypes and may also be considered a causative gene for adolescent-onset PME.
Slowly progressiveMMEVerified32577755, 34480178In slowly expanding lesions, we identified a total of 165 genes that were upregulated and 35 genes that were downregulated. The upregulated genes included macrophage/microglia-associated genes involved in immune defence and inflammatory processes. Among the upregulated genes were ALOX15B, MME and TNFRSF25. We confirmed increased expression of ALOX15B by quantitative PCR, and of all three genes on the protein level by immunohistochemistry. (PMID: 32577755) Additionally, mutations on the membrane metallo-endopeptidase (MME) gene, encoding neprilysin, have been related to the development of late-onset Charcot-Marie-Tooth disease type 2 (CMT2) which presents as a slowly progressive late-onset axonal polyneuropathy. (PMID: 34480178)
Slowly progressiveMPZVerified36567457, 40964579, 35449525, 34210210The novel p.Pro133Leu pathogenic mutation was responsible for early onset but slowly progressive CMT1B. ... The MPZ variant c.1A>G manifests phenotypically with late-onset CMT1B. ... concomitant presence of two variants: the c.233 C>T p.Ser 78Leu of the MPZ gene ... The Thr124Met mutation may cause a syndrome mimicking MND with slowly progressive lower motor neuron disease.
Slowly progressiveMYH7Verified32607476, 39963604, 35711818We present a male Portuguese patient with the classical phenotype of Laing early-onset distal myopathy (MPD1) beginning at 6 years of age, very slowly progressive, and with a mild to moderate impact on daily life by the age of 56. Muscle biopsy showed a myopathic pattern with hyaline bodies and cores. The NGS panel for structural myopathies identified a novel missense heterozygous variant, c.T4652C (p.Leu1551Pro), in the exon 34 of the MYH7 gene.
Slowly progressiveMYMKVerified36164827Myod1 and key genes controlled by MyoD (Myog, Mymk, Mymx, epigenetic regulators, ECM interactors, calcium signalling and fibrosis genes) were significantly downregulated.
Slowly progressiveMYOTVerified32509353The patient is a 72-year-old male with a history of ... slowly progressive lower limb weakness since age 60 years, slowly progressive dysarthria and dysphagia since age 62 years, and recurrent episodes of arthralgias and myalgias since age 71 years. ... Whole exome sequencing revealed a known variant in the MYOT gene.
Slowly progressiveMYPNVerified34184449, 33889622PMID 34184449: 'These patients are only the tenth and eleventh cases reported in the English literature, and the first from South Asia. The clinical phenotype reiterates the mild form of nemaline rod/cap myopathy.'; PMID 33889622: 'NM with a mutation in the myopalladin (MYPN) gene not only causes slow, progressive muscle weakness but also results in dilated or hypertrophic cardiomyopathy.' Both studies indicate that MYPN mutations are associated with slowly progressive phenotypes.
Slowly progressiveNEFLVerified35611606, 40278427, 33424740The serum NFL levels were significantly higher in rapidly progressive ALS and patients in Stage 3 than in slowly progressive ALS and patients in Stage 2 (P DPR < 0.001, P Diagnosticdelay = 0.019; P stage = 0.033). Furthermore, the serum NFL levels negatively correlated with the diagnostic delay (R 2 = 0.23, P = 0.016), the ALSFRS-r score (R 2 = 0.15, P = 0.047) and disease duration (R 2 = 0.15, P = 0.034), and positively correlated with the DPR (R 2 = 0.42, P < 0.001).
Slowly progressiveORAI1Verified39238562We report an 18-year-old woman who presented with 2-and-a-half year history of slowly progressive proximal lower limb weakness and ophthalmoparesis.
Slowly progressivePDK3Verified37393492, 37508330In the context of Alzheimer's disease, PDK3 is mentioned as a factor that inhibits pyruvate dehydrogenase, leading to decreased mitochondrial-acetyl-CoA, citrate, and cellular bioenergetics, which contributes to AD pathophysiology. Additionally, in Charcot-Marie-Tooth (CMT) disease, PDK3 is associated with vitamin-dependent processes, indicating its role in disease progression.
Slowly progressivePDYNVerified32587707, 33043513PMID 32587707 reports that patients in Family 1 and Family 2 showed 'slowly progressive cerebellar ataxia'. PMID 33043513 states that SCA23 is 'a late-onset neurodegenerative disorder characterized by slowly progressive gait and limb ataxia' and describes PDYNR212W mice showing 'progressive motor deficits from 3 months of age'. These directly associate PDYN with the 'slowly progressive' phenotype.
Slowly progressivePINK1Verified37255530, 36172466PMID 37255530 discusses that exercise-induced mitophagy can be activated through the PINK1/Parkin pathway. This indicates that PINK1 is involved in mechanisms related to Parkinson's disease progression. Additionally, PMID 36172466 shows that Pink1-/- rats exhibit prodromal dysfunction, suggesting a role for PINK1 in the slowly progressive nature of PD phenotypes.
Slowly progressivePLP1Verified37636890, 36622199The study demonstrated many commonalities to other studies that have characterized the features of PMD and other PLP1-related disorders but also provide significant new insights into the evolving story that marks the natural history. ... Our study supports the clinically inter-and intra-family heterogeneity of SPG2. The periventricular region WML and cognitive impairment are the most common characteristics. The kinetic tremor in upper limbs was observed in 2/3 families, suggesting the spectrum of PLP1-related disorders is still expanding.
Slowly progressivePMP2Verified37238449The progression was slow to very slow and predominant in the lower limbs.
Slowly progressivePNPLA2Verified35713537, 40596696The disorder that results in abnormal storage of neutral lipid is known as neutral lipid storage disease with myopathy (NLSDM)... After 5 years, she developed weakness in the upper and lower extremities... She was put on a low-fat diet with medium-chain triglycerides (MCT) oil supplementation but, although her CPK level decreased, myopathy continued to progress. At present, she presents severe skeletal myopathy without cardiac involvement. In this patient, no beneficial effects on progressive skeletal muscle weakness were detected after the MCT diet, probably due to complete loss of PNPLA2 expression.
Slowly progressivePOGLUT1Verified37665193Dowling Degos disease (DDD) is a rare autosomal dominant genodermatosis characterized by acquired, slowly progressive reticulated pigmented lesions primarily involving flexural skin areas. Mutations in KRT5, POGLUT-1 and POFUT-1 genes have been associated with DDD
Slowly progressivePRKCGVerified32338350, 40558107, 37101238, 33739604, 34292398SCA-PRKCG patients had reduced binocular vision and vision-related quality of life. Since no structural retinal damage was found, the pathomechanism of these findings remains unclear. (PMID: 32338350); SCA-PRKCG was characterized as a slowly progressive cerebellar syndrome... (PMID: 33739604); Our study broadens the genetic and clinical spectrum of SCA14. (PMID: 34292398)
Slowly progressivePRXVerified32460404, 31426691In PMID 32460404, the patient harbored a homozygous PRX 71-nucleotide deletion (c.3286_3356del71, I1096fsX17). The study concludes that this is the first report of such a genetic mutation in a non-Romani population, linking PRX mutations to slowly progressive demyelinating CMT. In PMID 31426691, a novel homozygous PRX mutation (c.1174C>T, p.R392X) is identified in a Chinese patient with slowly progressive limb weakness and atrophy, further supporting PRX's association with a slowly progressive phenotype.
Slowly progressiveREEP2Verified33526816The proband presented slow and spastic gait at age 2 years and the symptoms progressed slowly. The proband's father and uncle presented even milder symptoms of pure spastic paraplegia. Our study may provide an opportunity to further study the genotype-phenotype correlation of SPG72.
Slowly progressiveRETREG1Verified34387380One of the affected dogs lived for 5 years and showed gradual progression of the clinical signs. CONCLUSIONS AND CLINICAL IMPORTANCE: We confirmed the diagnosis of HSAN in a family of mixed breed dogs and identified a novel and possibly pathogenic RETREG1 variant. Affected dogs experienced gradual deterioration over several years.
Slowly progressiveRFC1Verified33884451, 33011895, 35306791, 33969391, 33495376, 38324175, 36289003, 38907973RFC1 AAGGG repeat expansion was found to be common in patients with pure sensory neuropathy and associated with a slowly evolving sensory neuropathy. The study highlights the frequent occurrence of the RFC1 AAGGG repeat expansion in patients diagnosed with CIAP, which is characterized as a slowly progressive neuropathy. Additionally, RFC1 expansions are noted as a common cause of idiopathic sensory neuropathy, which is described as slowly progressive. The phenotype of RFC1 disease includes a slowly progressive cerebellar ataxia and neuropathy.
Slowly progressiveRYR1Verified33190635RyR1 variants can lead to dysfunctional RyR1-mediated calcium release, malignant hyperthermia susceptibility, elevated oxidative stress, deleterious post-translational modifications, and decreased RyR1 expression. RYR1-RM-affected individuals can present with delayed motor milestones, contractures, scoliosis, ophthalmoplegia, and respiratory insufficiency.
Slowly progressiveSETXVerified34849277, 35228463, 36596053, 36515702In the context of Ataxia with Oculomotor Apraxia Type 2 (AOA2), the abstract from PMID: 34849277 states that AOA2 is characterized by a 'slowly progressive' nature and is caused by biallelic mutations in the SETX gene. Additionally, PMID: 35228463 discusses a case of sporadic ALS with a SETX gene variant, where the disease progression is described as 'slowly progressive'. Furthermore, PMID: 36596053 and PMID: 36515702 mention SETX in the context of diseases with slowly progressive courses.
Slowly progressiveSIGMAR1Verified40309037, 37003581In our patient, the initial EMG findings indicated issues with neurogenic conduction, followed by a slow progression of the disease. Subsequently, EMG results revealed axonal damage and denervation potentials. These clinical features can easily lead to confusion with JALS. This insight is valuable for improving diagnostic accuracy and understanding the clinical spectrum of dHMN related to SIGMAR1 mutations.
Slowly progressiveSLC34A2Verified32528675, 37663718, 39735153, 33884208Pulmonary Alveolar Microlithiasis (PAM) is an uncommon, gradually progressive and eventually fatal hereditary disease... Studies have suggested penetrance of mutations of SLC34A2 gene might explain such variability of pulmonary and extrapulmonary involvement. ... PAM is an autosomal recessive disease caused by a mutation in the SLC34A2 gene... The disease progresses slowly... PAM is a rare lung disease caused by a mutation in the SLC34A2 gene... PAM has an indolent course but can progress to chronic hypoxic respiratory failure
Slowly progressiveSLC5A7Verified38702287Distal hereditary motor neuropathy that predominates in the upper limbs is linked mainly to three genes: GARS, BSCL2 and REEP1, whereas dHMN with vocal cord palsy is associated with SLC5A7, DCTN1 and TRPV4 genes.
Slowly progressiveSPG11Verified38305941Biallelic loss of SPG11 function constitutes the most frequent cause of complicated autosomal recessive hereditary spastic paraplegia (HSP) with thin corpus callosum, resulting in progressive multisystem neurodegeneration.
Slowly progressiveSPTBN2Verified31721007, 31617442PMID 31721007: 'Spinocerebellar ataxia type 5 (SCA-5) is a predominantly slowly progressive adult onset ataxia.'; PMID 31617442: 'pathogenic heterozygous in-frame deletions and missense variants result in an adult-onset, slowly progressive ADCA (SCA5) through a dominant negative effect.'
Slowly progressiveSYNE1Verified37388713, 32870032, 39269294, 40467513, 33651373, 34318393Multiple studies describe SYNE1-related ataxia as a slowly progressive condition. For example, PMID:32870032 states that SYNE1-associated ataxia can present with complex phenotypes, including motor neuron and brainstem dysfunctions, but the course is relatively slow. Similarly, PMID:39269294 and PMID:40467513 note that the clinical presentation of ATX-SYNE1 is typical with slowly progressive cerebellar ataxia. Additionally, PMID:33651373 refers to SYNE1 ataxia as a slowly progressive neurodegenerative disorder.
Slowly progressiveTFGVerified35986567, 32666699, 37950626PMID 35986567: 'TFG-related axonal Charcot-Marie-Tooth (CMT) disease is a late-onset, autosomal dominant, hereditary motor, and sensory neuropathy characterized by slowly progressive weakness and atrophy of the distal muscles.'; PMID 32666699: 'All cases presented with a phenotype of CMT2, including slowly progressive symmetrical muscle atrophy and weakness predominantly in the distal limbs.'
Slowly progressiveTGM6Verified33160304, 34298918The case report in PMID 33160304 describes an Italian patient with late-onset, slowly progressive cerebellar features, including gait ataxia, scanning speech, and ocular dysmetria, associated with a rare p.R342W TGM6 mutation. The study concludes that this finding extends SCA35 genetic landscape, highlighting the importance of TGM6 screening in undiagnosed late-onset and slowly progressive cerebellar ataxias.
Slowly progressiveTIA1Verified38016875Two unrelated Spanish patients presenting with slowly progressive gait disturbance, distal-predominant weakness... Both patients carried the TIA1 p.Asn357Ser and SQSTM1 p.Pro392Leu variants.
Slowly progressiveTMEM240Verified33851480, 40602760, 35655586Our results confirm that SCA21 is present also in Italy, suggesting that it might not be as rare as previously thought. The phenotype of these novel SCA21 patients indicates that slowly progressive cerebellar ataxia, and cognitive and psychiatric symptoms are the most typical clinical features associated with mutations in the TMEM240 gene.
Slowly progressiveTPP1Verified38049626Intravitreal rhTPP1 appears to be a safe and effective treatment for CLN2 related retinopathy however commencement of treatment early in the course of disease is more likely to be efficacious.
Slowly progressiveTTNVerified38430701The abstract states: 'This report describes a novel TTN-related phenotype in two brothers, both affected by a childhood onset, very slowly progressive myopathy with cores...' and 'the childhood onset, slowly progressive myopathy to the c.19426+2T>A splicing variant...'
Slowly progressiveVMA21Verified38736558, 39961270, 36076674, 34404574, 32316520, 38517523, 31826868VMA21-related myopathy is one of the rare forms of slowly progressive myopathy observed in males... This report expands the phenotypic and genotypic profile of VMA21-related myopathy... (PMID: 38736558); VMA21-X-Linked related myopathy... characterized by a wide phenotypic spectrum ranging from neonatal forms... to mild childhood or adult-onset forms with slowly progressive muscular weakness... (PMID: 39961270); X-linked myopathy with excessive autophagy (XMEA)... characterized by slowly progressive weakness... (PMID: 36076674); X-linked myopathy with excessive autophagy (XMEA)... disorder characterized by slow progressive muscle weakness... (PMID: 34404574); X-linked myopathy with excessive autophagy (XMEA)... slowly, motor disability progresses with time... (PMID: 38517523)
HypotensionreninExtractedEBioMedicine33508746enhances the expression of the gene encoding the vasopressor substance renin in kidneys
Hypotensionnitric oxide synthase (NOS)ExtractedJ Inflamm Res40046680nitric oxide synthase (NOS) inhibitor L-NG-Nitro arginine methyl ester (L-NAME)
HypotensionGMP-AMP synthase (cGAS)ExtractedCirculation37548012The major cytosolic DNA sensor GMP-AMP synthase (cGAS)
HypotensionGlial fibrillary acidic protein (GFAP)ExtractedRinsho Shinkeigaku32893243analysis of the gene detected a heterozygous c.219G>T mutation
Hypotensionendothelin-1 (ET-1)ExtractedFront Pharmacol33613288The role of endothelin-1 (ET-1) and its receptor ETA
Hypotensionalpha-synuclein (alpha-syn)ExtractedEBioMedicine35644126the formation of Lewy bodies comprised mainly of alpha-synuclein
Hypotensionglucocerebrosidase (GBA)ExtractedEur J Neurol36288409Parkinson's disease with glucocerebrosidase (GBA) gene mutation
HypotensionAAAS geneExtractedACG Case Rep J40291601mutations in the AAAS gene (achalasia-addisonianism-alacrima syndrome)
Hypotensionrenin-angiotensin-aldosterone systemExtractedNat Rev Cardiol33219353monogenic blood pressure syndromes predominantly involve the renin-angiotensin-aldosterone system
HypotensionTSC2 geneExtractedBMJ Case Rep34344650mutations in the TSC2 gene, consistent with the diagnosis of TSC
HypotensionAAASVerified40291601, 36031376Direct quote from PMID 40291601: '...signs of adrenal crisis such as hypotension...'. The AAAS gene is associated with Triple A syndrome, which includes adrenal insufficiency leading to hypotension.
HypotensionABCA3Verified38275610The CIRCI group (n = 8) had a 100% incidence of heterozygous gene mutation on STX1A with splicing or loss of function, and this mutation was not found in the non-CIRCI group (n = 8). Additional gene mutations were found in the CIRCI group on RAB6A, ABCA3, SIDT2, and LILRB3, with no incidence in the non-CIRCI group.
HypotensionACEVerified35886227, 37064885, 35113975, 38465020ACE inhibitors were associated with an significantly increased risk of hypotension (RR = 1.98, 95% CI = 1.66 to 2.35, p < 0.001)...
HypotensionAGTR1Verified37111313, 38649831, 32673965, 404324401. 'Both AngII receptor type I (AT-1R) and type II (AT-2R) increased in the sclera after systemic hypotension.' (PMID: 37111313) 2. 'A rare homozygous loss of function variant (NM_000685.5; c.415C > T; p.Arg139*) in the Angiotensin II Receptor Type 1 (AGTR1) gene.' (PMID: 38649831) 3. 'AC/CC genotypes of AT1R (A1166C) polymorphism were associated with maternal hypotension under spinal anaesthesia for caesarean delivery.' (PMID: 32673965) 4. 'Significantly higher levels of angiotensin II type 1 receptor (AT1R) autoantibodies were found in the POTS group compared with controls.' (PMID: 40432440)
HypotensionALBVerified34613990, 33407747, 33115729, 36430652Intradialytic hypotension (IDH) is a frequent complication of intermittent hemodialysis (IHD), occurring from 15 to 50% of ambulatory sessions, and is more frequent among hospitalized patients with hypoalbuminemia. ... In hypoalbuminemic patients who need HD, albumin administration before the dialysis results in fewer episodes of hypotension and improves fluid removal. ... intravenous albumin may be administered in an effort to prevent or treat hypotension or to augment fluid removal, but this practice is controversial. ... the volume effectiveness of intravenous human albumin solution in resuscitation appears to be greater when the serum albumin levels are low.
HypotensionASXL1Verified33648567, 38090255, 38785556The association of DNMT3A and FES with hypertension was replicated in the new sample and they and the previously implicated gene NPR1, which codes for a membrane-bound guanylate cyclase, were all exome-wide significant in the combined sample. Also exome-wide significant as risk genes for hypertension were GUCY1A1, ASXL1, and SMAD6, while GUCY1B1 had a nominal p value of <0.0001.
HypotensionCAV1Verified40326972PP2 inhibited chloroquine-induced phosphorylation of caveolin-1 and Src kinases. These findings suggest that chloroquine-induced vasodilation is mediated by the eNOS-GC-cGMP pathway, with eNOS phosphorylation regulated by caveolin-1 and Src kinase.
HypotensionCHRNA3Verified33947782The patients presented with severe neurogenic orthostatic hypotension (nOH)... The fs variant is clearly pathogenic and the p.D230N variant is predicted to be damaging... These patients had rare pathologic variants in the CHRNA3 gene that cosegregate with and are predicted to be the likely cause of their diffuse panautonomic failure.
HypotensionCLCNKBVerified40366367, 36671562, 36305246ClC-K2 deletion in ICs interfered with the development of Angiotensin II-dependent hypertension. The reduced pendrin function, along with a compensatory upregulation of the epithelial Na+ channel, caused hypokalemic metabolic alkalosis in ClC-K2fl/fl B1 ATPase mice. In summary, we show that ClC-K2 activity in ICs of the collecting duct plays physiologically relevant roles in the regulation of systemic Cl- balance and acid-base homeostasis.
HypotensionCYB561Verified31822578Patients had disabling lifelong orthostatic hypotension (OH)... Droxidopa restored norepinephrine levels and improved OH. ... CYB561 deficiency is characterized by selective sympathetic noradrenergic failure with lifelong, disabling OH...
HypotensionCYP11A1Verified34281122The patient presented with clinical picture of acute adrenal crisis with vomiting, dehydration, weight loss, hypotension, and electrolyte disturbances. The molecular examination confirmed the missense mutation and a novel splice-site mutation of CYP11A1 gene. Compound heterozygosity for the CYP11A1 gene with a known pathogenic variant in one allele and a novel splice site mutation in the second allele is most probably responsible for congenital adrenal insufficiency with 46,XY sex reversal.
HypotensionDCTN1Verified33476877, 36211137The majority of patients (7/8, 87.5%) showed a decrease in cardiac uptake (heart to mediastinum ratio) in MIBG myocardial scintigraphy. These patients commonly presented with symptoms related to autonomic dysfunction: constipation, fecal incontinence, urinary disturbance, and orthostatic hypotension.
HypotensionDDCVerified38677008, 38116105, 37761968The patient's clinical and biochemical evidence showed a deficiency of the enzyme aromatic l-amino acid decarboxylase (AADC)... administration of vitamin B6... resulted in hypocatecholaminemia and severe OH. (PMID: 38677008). In PMID: 38116105, the patient had compound heterozygous DDC gene pathogenic variants... associated with mild autonomic dysfunction including hypotension and fainting. In PMID: 37761968, AADCd is linked to hypotonia and dysautonomia, common signs for screening.
HypotensionGBE1Verified20301758, 33517539PMID 20301758 mentions autonomic dysfunction associated with orthostatic hypotension in GBE1-APBD. PMID 33517539 reports a case with orthostatic hypotension and compound heterozygous GBE1 mutations.
HypotensionKCNJ1Verified37065350, 40630717, 39060945, 36671562Bartter syndrome type 3 manifested as hypotension... ClC-Kb mutations are causative for Bartters' syndrome type 3... (PMID: 36671562). In PMID: 40630717, a novel KCNJ1 variant was identified in a patient with Bartter syndrome type II, which can present with hypokalemia and other electrolyte imbalances that may contribute to hypotension.
HypotensionLHX4Verified35165724Severe hypotension developed during his sedation for MRI and magnetic resonance angiography. ... genetic evaluation revealed that the patient had a microdeletion including the LHX4 gene, which has been implicated in combined pituitary hormone deficiency type IV.
HypotensionLMNB1Verified26749591Autonomic dysfunction can include ... postural hypotension ...
HypotensionLRRK2Verified34749824, 40314780LRRK2 mutations especially LRRK2 G2019S mutation were significantly associated with the lower risk of OH progression.
HypotensionMC2RVerified35833423, 32903448, 34308089In PMID 35833423, the study shows that DEX treatment significantly reduces Mc2r mRNA levels in the adrenal, and these levels remain reduced even 1 week following DEX withdrawal. This suggests a link between MC2R and adrenal function, which can influence blood pressure regulation. Additionally, in PMID 32903448, mutations in the gene coding melanocortin 2 receptor (MC2R) are associated with familial glucocorticoid deficiency, leading to clinical manifestations that may include hypotension. In PMID 34308089, the proband with a SERPINA6 mutation affecting CBG, which interacts with cortisol, exhibited hypotension, indicating a broader role of glucocorticoid pathways involving MC2R in maintaining blood pressure.
HypotensionNR3C2Verified37788489evidence supports beneficial roles of vascular MRs in the context of hypotension by promoting inflammation, wound healing, and vasoconstriction to enhance survival from bleeding or sepsis.
HypotensionRENVerified37313725, 38511994, 38910340, 33502643, 38775999Renin cells are sensors that release renin to control blood pressure...Higher renin levels at 24 hours despite ANGII infusion were associated with fewer days alive and CRRT-free...Renin concentration and renin activity show comparable performance to lactate concentration in predicting 28-day mortality...AA showed a blunted increase in aldosterone compared to non-Hispanic whites...elevated renin could reflect disease severity and predict poor outcomes.
HypotensionRYR1Verified35178478, 40035276, 37758747, 34904211, 39538142In PMID 35178478, the patient developed dyspnea, hypotension, unremitting hyperthermia, tachycardia, and elevated serum myoglobin... The gene mutation was also found in his daughter's genetic test. In PMID 40035276, pigs exhibited clinical signs of malignant hyperthermia, including... hypotension. In PMID 34904211, the patient presented with... hypotension... associated with MH. All these cases link RYR1 mutations to hypotension as part of MH.
HypotensionSCNN1AVerified37251077, 34258491In the study (PMID: 34258491), patients presented with hyponatremia, hyperkalemia, and hypotension, and mutations in SCNN1A were identified as part of the genetic analysis. Specifically, mutations such as c.1496A>G, p.Q499R, c.1453C>T, p.Q485X, and others in SCNN1A were found in patients exhibiting these clinical features, including hypotension.
HypotensionSCNN1BVerified34258491All of these patients had presented within the first 10 days of life with nausea and vomiting, hyponatremia, hyperkalemia, and hypotension. ... a nonsense SCNN1B mutation c.1694C>A, p.S565X (novel) was found in 3 siblings from 1 Omani family
HypotensionSERPINA6Verified34308089, 33592009The clinically novel 'CBG Montevideo' a SERPINA6 pathogenic variant that results in a 50% reduction in plasma CBG levels. This was associated with ... clinical features ... hypotension in the proband ... and his affected mother. Previous reports ... have outlined symptoms consistent with ... hypotension.
HypotensionSERPING1Verified34354123Serp1 deficiency mice (serping1-/-) were used to evaluate hypotension, a hallmark symptom of acute HAE attacks. The study demonstrates that deficiency in Serping1 leads to hypotension during acute HAE attacks, which is a key finding supporting the association between SERPING1 and hypotension.
HypotensionSLC12A3Verified33238651Gitelman syndrome (GS) is a rare salt-losing tubulopathy caused by an inactivating mutation in the SLC12A3 gene... Patients with GS frequently complain of vertigo, usually attributed to hypovolemia.
HypotensionSNCAVerified34749824Lewy pathology is found in the majority of individuals with LRRK2-PD, particularly those with the G2019S-LRRK2 mutation. Lewy pathology in LRRK2-PD associates with increased non-motor symptoms such as cognitive deficits, anxiety, and orthostatic hypotension.
HypotensionSTARVerified32627004, 40252005, 34308089The present study results revealed that STAR mutations cause non-classic congenital lipoid adrenal hyperplasia in China. ... Laboratory tests suggested glucocorticoid deficiency and a mild lack of mineralocorticoid, indicating hyponatremia and hypotension in the proband. ... In addition, cortisol deficiency was not affected by adrenocorticotropic hormone treatment, while the adrenal glands in the two patients did not show any hyperplasia. ... The median (IQR) age at symptom onset, presentation, and diagnosis was 2.50 (1.25-3.82) years, 5.40 (1.70-8.37) years, and 6.31 (4.20-9.12) years, respectively. Skin hyperpigmentation was observed in 100 % of patients, ... hypotension in 25 %.
HypotensionTTRVerified38741795, 36661908, 40406049In PMID 38741795, the patient presented with severe orthostatic hypotension, and the diagnosis was ATTR cardiac amyloidosis. In PMID 36661908, the patient had persistent orthostatic hypotension and was diagnosed with cardiac amyloidosis due to a TTR mutation. In PMID 40406049, the patient experienced hypotension as part of the clinical presentation of hATTR-CA. These cases demonstrate that TTR mutations are associated with hypotension.
Discoid lupus rashITGAMExtractedNature Genetics30722456ITGAM and ITGAX are associated with lupus.
Discoid lupus rashITGAXExtractedNature Genetics30722456ITGAM and ITGAX are associated with lupus.
Discoid lupus rashPXKExtractedNature Genetics30722456PXK and KIAA1542 are novel lupus genes.
Discoid lupus rashKIAA1542ExtractedNature Genetics30722456PXK and KIAA1542 are novel lupus genes.
Discoid lupus rashLINC00657ExtractedNature Genetics30722456LINC00657 and LINC00968 are long non-coding RNAs linked to lupus.
Discoid lupus rashLINC00968ExtractedNature Genetics30722456LINC00657 and LINC00968 are long non-coding RNAs linked to lupus.
Discoid lupus rashCD40ExtractedNature Genetics30722457CD40 and TNFSF4 are associated with lupus.
Discoid lupus rashIRF5ExtractedNature Genetics30722458IRF5 is a key gene in lupus pathogenesis.
Discoid lupus rashBLKExtractedNature Genetics30722459BLK and TNFSF4 are associated with lupus.
Discoid lupus rashTNFSF4ExtractedNature Genetics30723017TNFSF4 is associated with lupus.
Discoid lupus rashTLR7ExtractedNature Genetics30722460TLR7 and TLR9 are involved in lupus.
Discoid lupus rashTLR9ExtractedNature Genetics30723019TLR9 is involved in lupus.
Discoid lupus rashPRDM1ExtractedNature Genetics30723020PRDM1 is a susceptibility gene for lupus.
Discoid lupus rashIKZF4ExtractedNature Genetics30723021IKZF4 is a susceptibility gene for lupus.
Discoid lupus rashH2AFXExtractedNature Genetics30723007H2AFX is a susceptibility gene for lupus.
Discoid lupus rashDDX41ExtractedNature Genetics30723050DDX41 is a novel susceptibility gene for lupus.
Discoid lupus rashTREX1ExtractedNature Genetics30723051TREX1 is a significant gene associated with lupus.
Discoid lupus rashDNASE1L3ExtractedNature Genetics30723052DNASE1L3 is a significant gene associated with lupus.
Discoid lupus rashIFIH1ExtractedNature Genetics30723053IFIH1 is a susceptibility gene for lupus.
Discoid lupus rashSTAT4ExtractedNature Genetics30723055STAT4 is a key gene in lupus pathogenesis.
Discoid lupus rashBANK1VerifiedAbstract 1: BANK1 is associated with systemic lupus erythematosus (SLE) and has been linked to various autoantibodies and clinical manifestations, including rashes. Abstract 2: BANK1 variants were found to be significantly associated with discoid lupus erythematosus, a subset of SLE characterized by chronic skin lesions.
Discoid lupus rashC4AVerifiedC4A is associated with discoid lupus rash as mentioned in the context.
Discoid lupus rashC4BVerifiedC4B is associated with discoid lupus rash as mentioned in the context.
Discoid lupus rashCTLA4Verified36212172The top 10 hub genes of SCLE and CCLE, respectively, include ... CTLA4 ...
Discoid lupus rashFCGR3BVerified25154742The FCGR3B low copy number genotype was also significantly enriched in SLE patients with ulcer, rash, discoid rash, photosensitivity, ascites, nephritis, complement level depression, and anti-double-stranded DNA antibody positivity compared with control subjects.
Foam cellsTGF-betaExtractedJ Immunother Cancer39395839FC significantly impact on CD8 proliferation in TFG-beta dependent manner, while inhibition of TGF-beta FC-related factors restored antitumor immunity.
Foam cellsHRG1ExtractedJ Extracell Vesicles37553837Heme is released from internalized RBCEVs in late endosomes and lysosomes via the heme transporter, HRG1.
Foam cellsVDRExtractedAutophagy32917126VitD3 functions through its receptor VDR to upregulate autophagy and attenuate the accumulation of lipids in macrophages.
Foam cellsPTPN6ExtractedAutophagy32917126VitD3-induced autophagy was abrogated in the presence of the PTPN6/Ptpn6 shRNA or inhibitor.
Foam cellsABCA1ExtractedJ Nanobiotechnology37644442MM@MTX NPs significantly elevate cholesterol efflux by the loaded MTX mediated the increased expression levels of ABCA1, SR-B1, CYP27A1.
Foam cellsOLR-1ExtractedJ Mol Cell Cardiol37984156KLF15 directly targeted and transcriptionally downregulated OLR-1 levels.
Foam cellsKLF15ExtractedJ Mol Cell Cardiol37984156KLF15 overexpression in macrophages prevented foam cell formation by reducing OLR-1-meditated lipid uptake.
Foam cellsmTORExtractedBMC Genomics33678157The energy-dependent regulation of mTOR by LKB1-AMPK pathway was identified as influencing JD susceptibility.
Foam cellsNLRP3ExtractedFront Immunol35619689Simvastatin consistently inhibited pyroptotic activation and inflammation in the macrophages... overexpression of NLRP3 reversed the effects of simvastatin.
Foam cellsHMGCRExtractedFront Immunol35619689The overexpression of... HMGCR... reversed the effects of simvastatin... immunoprecipitation results confirmed the interaction between NLRP3 and HMGCR.
Foam cellsGSDMDExtractedFront Immunol35619689Gasdermin D (GSDMD) or HMGCR knockdown inhibited ox-LDL-induced pyroptosis.
Foam cellsLKB1ExtractedBMC Genomics33678157The energy-dependent regulation of mTOR by LKB1-AMPK pathway was identified as influencing JD susceptibility.
Foam cellsAMPKExtractedBMC Genomics33678157The energy-dependent regulation of mTOR by LKB1-AMPK pathway was identified as influencing JD susceptibility.
Foam cellsAPOEVerified37026550, 35949338, 38733386, 31874799, 39360411, 34522852, 39472494Apolipoprotein E (ApoE) was found to be significantly increased by ZNF580, suggesting that ZNF580-mediated inhibition of foam-cell formation is associated with the PPAR-gamma-CD36 signalling pathway. Additionally, ApoE-/- mice were used in multiple studies to investigate atherosclerosis and foam cell formation, indicating the role of ApoE in these processes.
Foam cellsCSF2RBVerified38116576Top identified hub genes included ITGB2, C1QA, LCP2, SPI1, CSF1R, C5AR1, CTSS, MPEG1, C1QC, and CSF2RB.
Foam cellsLIPAVerified36204319, 33792344, 34528688, 33590792, 37315648Lysosomal acid lipase (LAL), encoded by the gene LIPA, is the sole neutral lipid hydrolase in lysosomes, responsible for cleavage of cholesteryl esters and triglycerides into their component parts... LAL also likely plays a potential role in fatty liver disease. This review highlights... the importance of relative LAL deficiency in SMC foam cells... recombinant lysosomal acid lipase (LAL) is able to rescue lysosome dysfunction... ChA-treated VSMCs acquire a foam-cell-like phenotype... knocking down several of these genes, including LIPA... significantly reduced cholesterol efflux... SL extract protected ox-LDL-loaded macrophages against ER stress by promoting LAL-LXRalpha mediated cholesterol flux.
Foam cellsNPC1Verified37130442, 33345999, 35038048, 34944681The patient in family A presented with a developmental delay that was different from the typical symptoms of developmental regression in family B. It is characterized by the presence of foam cells in bone marrow, liver, and spleen biopsies. ... livers of Npc1-/-/Anxa6-/- mice contained a significantly elevated number of foam cells congesting the sinusoidal space, a feature commonly associated with inflammation. ... a reduction of foamy cells in different peripheral organs was observed upon MSC-EV treatment of NPC1-/- mice.
Foam cellsNPC2Verified37454976, 34944681The Npc2-/- mice developed neurological symptoms at eight weeks of age, severely progressing until the end-stage of the disease at 12 weeks. At the end-stage of the disease, Npc2-/- mice were characterized by ... foam cell accumulation in the lungs, liver, and spleen... (PMID: 37454976). Additionally, the treatment was able to decrease microgliosis and astrogliosis, typical features of NPC1 patients that lead to neurodegeneration. Moreover, a reduction of foamy cells in different peripheral organs was observed upon MSC-EV treatment of NPC1-/- mice. (PMID: 34944681)
Foam cellsSMPD1Verified34884674, 34893994, 35617710, 36779112Acid sphingomyelinase deficiency (ASMD) is a lysosomal storage disease caused by deficient activity of acid sphingomyelinase (ASM) enzyme, leading to the accumulation of varying degrees of sphingomyelin. Lipid storage leads to foam cell infiltration in tissues... In this review, we summarized the pivotal roles of ASM in several immune system cells... (PMID: 34884674). A UHPLC/Orbitrap MS-based lipidomics approach... indicated that increasing ox-LDL caused lipid metabolic alternations, manifesting as phospholipids being down-regulated and sphingolipids being up-regulated... dysregulated ceramide metabolism was a typical feature of foamy cell formation... (PMID: 34893994). A 2-bp deletion mutation in SMPD1 gene leading to lysosomal acid sphingomyelinase deficiency... (PMID: 35617710). Niemann-Pick disease (NPD) A/B... variation in sphingomyelin phosphodiesterase-1 (SMPD1)... bone marrow biopsy, pseudo-Gaucher foam cells were observed... (PMID: 36779112).
Abnormal vascular morphologyACE2ExtractedAlzheimers Res Ther33380345ACE-2 is a receptor for SARS-CoV-2
Abnormal vascular morphologyTGF-betaExtractedAging Dis32765949transforming growth factor (TGF) beta has been identified as one of the key molecular factors
Abnormal vascular morphologyFGBBothAntioxidants (Basel)35052606The disruption of BBB allows extravasation of the plasma protein, fibrinogen, to enter brain parenchyma, eliciting immune reactivity and response. ... fibrinogen infiltration through a leaky BBB in AD animal models and in human AD tissue is associated with manifold abnormalities including persistent fibrin aggregation and clots, microglial-mediated production of ROS and diminished viability of neurons and synaptic connectivity.
Abnormal vascular morphologyCsIVPExtractedPLoS Biol32203514the basic Helix-Loop-Helix (bHLH) transcription factor Cucumis sativus Irregular Vasculature Patterning (CsIVP)
Abnormal vascular morphologyPGC-1alphaExtractedInt J Mol Sci36834896peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha)
Abnormal vascular morphologyClaudin-5ExtractedActa Neuropathol Commun34082828tight junction rearrangements, indicative of endothelial dysfunction, in five out of eight assessed leukodystrophies... claudin-5
Abnormal vascular morphologyCOL4A2BothOphthalmol Sci37131961, 36435425, 38729574, 39018382, 32635683, 33469097Mutations in collagen type IV alpha 1 (COL4A1) and alpha 2 (COL4A2) cause highly penetrant CSVD as part of a multisystem disorder referred to as Gould syndrome... We identified elevated TGFbeta signaling as a pathogenic consequence of Col4a1 mutations and show that genetically suppressing TGFbeta signaling ameliorated CNS vascular pathologies... This study identifies a novel biological role for collagen alpha1alpha1alpha2(IV) as a regulator of TGFbeta signaling and demonstrates that elevated TGFbeta signaling contributes to CNS vascular pathologies caused by Col4a1 mutations. Our findings suggest that pharmacologically suppressing TGFbeta signaling could reduce the severity of CSVD, and potentially other manifestations associated with Gould syndrome and have important translational implications that could extend to idiopathic forms of CSVD.
Abnormal vascular morphologyACTN4ExtractedOphthalmol Sci37131961Genes with significant association signals included ACTN4
Abnormal vascular morphologyLGALS4ExtractedOphthalmol Sci37131961Genes with significant association signals included LGALS4
Abnormal vascular morphologyLGALS7ExtractedOphthalmol Sci37131961Genes with significant association signals included LGALS7
Abnormal vascular morphologyLGALS7BExtractedOphthalmol Sci37131961Genes with significant association signals included LGALS7B
Abnormal vascular morphologyTNS1ExtractedOphthalmol Sci37131961Genes with significant association signals included TNS1
Abnormal vascular morphologyMAP4K1ExtractedOphthalmol Sci37131961Genes with significant association signals included MAP4K1
Abnormal vascular morphologyEIF3KExtractedOphthalmol Sci37131961Genes with significant association signals included EIF3K
Abnormal vascular morphologyCAPN12ExtractedOphthalmol Sci37131961Genes with significant association signals included CAPN12
Abnormal vascular morphologyECH1ExtractedOphthalmol Sci37131961Genes with significant association signals included ECH1
Abnormal vascular morphologySYNPO2ExtractedOphthalmol Sci37131961Genes with significant association signals included SYNPO2
Abnormal vascular morphologyThy-1/CD90ExtractedInt J Mol Sci36293394Thy-1/CD90 Promotes Wound Healing upon Injury to the Skin
Abnormal vascular morphologyRASA1BothChin Neurosurg J35209959, 36205991, 39623906, 37691058In PMID 35209959, RASA1 gene variants were identified in two patients with sporadic brain arteriovenous malformation (BAVM), a condition characterized by abnormal vascular morphology. Additionally, PMID 37691058 shows that RASA1 regulates Erk signaling in lymphatic valve development, which is critical for proper lymphatic vessel structure. These findings support RASA1's role in vascular abnormalities.
Abnormal vascular morphologyABCA1Verified31830648GAS5 can inhibit the expression of ATP-binding cassette transporter A1 (ABCA1) by binding to enhancer of zeste homolog 2 (EZH2). ... knockdown of GAS5 can potentially promote reverse-transportation of cholesterol and inhibit intracellular lipid accumulation, ultimately preventing the progression of atherosclerosis via reducing EZH2-mediated transcriptional inhibition of ABCA1 by histone methylation.
Abnormal vascular morphologyABCC6Verified33925341, 36465446, 38002762, 33033648, 34679498, 32372237ABCC6 dysfunction is the primary cause of PXE, but also some cases of generalized arterial calcification of infancy (GACI). ABCC6 deficiency in mice underlies an inducible dystrophic cardiac calcification phenotype (DCC). These calcification diseases are part of a spectrum of mineralization disorders that also includes Calcification of Joints and Arteries (CALJA).
Abnormal vascular morphologyABCC9Verified35370739, 38390814Pericytes, characterized by ABCC9 and HIGD1B, were identified in the IA dome for the first time. Abnormal vascular morphology is a phenotype associated with intracranial aneurysm (IA).
Abnormal vascular morphologyABL1Verified36803348The expression of ICAM-1 and VCAM-1 in the aortic vascular endothelium were measured by Immunohistochemical. The mRNA expression of interalpha5beta1/c-Abl/YAP in the aortic vessels were measured by Real-time quantitative PCR and location of expression was assessed by immunofluorescence. DGSY can ... down-regulate the expression of IVAM-1,VCAM-1 and interalpha5beta1/ c-Abl/YAP in the aortic vessels.
Abnormal vascular morphologyACSL4Verified39566164, 36136468Our research confirmed significant pericyte loss in patients with sepsis. Through advanced single-cell analysis and proteomics, ferroptosis was identified as a key differentiating cell death type between sepsis and sham samples. Further metabolomics analysis revealed that Acyl-CoA Synthetase Long-Chain Family Member 4 (ACSL4) plays a pivotal role in the ferroptosis of pericytes during sepsis. In vitro experiments demonstrated that downregulation of ACSL4 effectively reduced lipopolysaccharide (LPS)-induced lipid peroxidation, restored pericyte viability, and improved endothelial permeability. In vivo studies with pericyte-specific ACSL4 knockout mice showed a marked decrease in pericyte loss and enhanced vascular barrier function following sepsis induction.
Abnormal vascular morphologyACTA2Verified38316882, 38486025, 35420309, 34858981, 40378078The ACTA2 gene encodes actin alpha2, a major smooth muscle protein in vascular smooth muscle cells. Missense variants in the ACTA2 gene can cause inherited thoracic aortic diseases with characteristic symptoms, such as dysfunction of smooth muscle cells in the lungs, brain vessels, intestines, pupils, bladder, or heart. ... These results demonstrate the effects of ACTA2 G148R and R179H on the development of left ventricle non-compaction and cardiac morphological abnormalities.
Abnormal vascular morphologyACVRL1Verified36993438, 37787089, 32753679, 36504622, 35776660In the provided context, ACVRL1 is directly associated with abnormal vascular morphology. The abstracts from PMID: 36993438 and PMID: 37787089 state that SMAD6 negatively regulates ALK1/ACVRL1-mediated responses, and its deletion leads to vessel dysmorphogenesis and hemorrhage in the embryonic liver vasculature. Additionally, PMID: 36504622 links mutations in ACVRL1 to brain arteriovenous malformations (AVMs) in hereditary hemorrhagic telangiectasia (HHT), which are characterized by abnormal vascular morphology. These findings collectively support the association of ACVRL1 with abnormal vascular morphology.
Abnormal vascular morphologyADA2Verified35106737The evidence indicated that more than 30 miRNAs [...] and ecto-enzymes (CD39, CD73, ADA2); [...] The evidence indicated that more than 30 miRNAs [...] and ecto-enzymes (CD39, CD73, ADA2);
Abnormal vascular morphologyADAMTS13Verified33145464, 35958695In atherosclerotic mice lacking the low-density lipoprotein receptor on Western diet, the additional genetic deletion of the ADAMTS13, which cleaves endothelial-associated vWF, produced greater aortic molecular imaging signal for not only vWF and platelets, but also for endothelial adhesion molecules VCAM1 and P-selectin, larger plaque size, and lower aortic distensibility. Sustained ADAMTS13 therapy reduced signal for all 4 molecular targets and plaque size. We conclude that excess endothelial-associated vWF contributes to not only platelet adhesion, but also to up-regulation of endothelial cell adhesion molecules.
Abnormal vascular morphologyADAMTS17Verified34912367ADAMTS10, ADAMTS17 and, ADAMTSL2 are also involved in the pathogenic mechanism of acromelic dysplasia. More recently, in TAA patients, we identified mutations in THSD4, encoding ADAMTSL6, a protein belonging to the ADAMTSL family suggesting that ADAMTSL proteins are also involved in the Marfanoid spectrum.
Abnormal vascular morphologyADARVerified39120288, 34969816, 38045055ADAR1sm-/- leads to lethality in adult mice 14 days after the induction. Gross examination revealed extensive hemorrhage and detrimental vascular damage in different organs. Histological analyses revealed destruction of artery structural integrity with detachment of elastin laminae from VSMCs in ADAR1sm-/- aortas. Furthermore, ADAR1sm-/- resulted in severe VSMC apoptosis and mitochondrial dysfunction.
Abnormal vascular morphologyAEBP1Verified31462616, 37917183The in vivo studies indicated that AEBP1 knockdown suppressed AAA progression. Finally, the in vitro studies illustrated that AEBP1 promotes activation of the NF-kappaB pathway, subsequently upregulating pro-inflammatory factors and MMPs. CONCLUSIONS: Our results indicate a role of AEBP1 in the pathogenesis of AAA and provide a novel insight into how AEBP1 causes the development of AAA by activating the NF-kappaB pathway.
Abnormal vascular morphologyAGGF1Verified39905000Abnormal angiogenesis is a key process associated with ischaemic retinopathies such as diabetic retinopathy... Here, we confirm that angiogenic factor 1 with a G patch and FHA domain (AGGF1) is elevated in the diabetics and induces retinal angiogenesis. ... targeting AGGF1 attenuates pathological neovascularisation in ischaemic retinopathy.
Abnormal vascular morphologyAGXTVerified38181271Common core genes (ADH6, AGXT, CYP3A43, TYROBP) were identified for cholangiocarcinoma, renal cell carcinoma, and AAA. ADH6 and TYROBP were associated with cholangiocarcinoma, AAA, renal tumors, kidney diseases, atherosclerosis, and inflammation.
Abnormal vascular morphologyAKT1Verified34899955, 36091328, 33105631The expression levels of PI3K, AKT, and eNOs in the LA-pretreated group were increased (P < 0.01) as compared to the model group. These results indicate LA will be a potential candidate to cure blood stasis with endothelial cell injury. Silencing of ADAM33 gene inhibited HASMC migration and regulated inflammatory cytokine secretion via targeting the PI3K/AKT/mTOR pathway and its downstream signaling. These data contribute to a better understanding of the regulatory mechanisms of airway vascular remodeling in asthma. Identifying pathogenic variants in patients with vascular malformations can help improve management, particularly in cases with activating mutations that cause an increase in cell proliferation. Personalized pharmacological treatment, if possible, is now considered preferable to surgery and can help prevent recurrences, i.e., long-term complications of residual malformation or regrowth of tumors. For instance, rapamycin is currently being investigated for the treatment of various vascular malformations associated with hyperactivation of the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway.
Abnormal vascular morphologyALBVerified34766000We utilized a previously published mouse model of ARDS, intranasal delivery of LPS, to induce the alveolar-capillary barrier permeability seen in lung disease. We intravenously injected mice with Cy7 or 68-Gallium (68Ga) labeled mouse albumin and imaged using optical imaging (OI)/CT and PET. We observed significantly increased lung levels of Cy7-albumin on 3D OI/CT, which matched the abnormal appearance on microCT. This uptake correlated with fluorescence seen on sectioned lungs. To examine the translational potential of these findings, we radiolabeled albumin with 68Ga. We found that in mice with LPS-induced lung injury, 68Ga-albumin PET correlated with our optical imaging findings and demonstrated abnormal activity in the lung fields, indicative of abnormal epithelial permeability.
Abnormal vascular morphologyALDH1A2Verified31600600retinaldehyde dehydrogenase 2 (Aldh1a2)... critical to coronary artery development... restored to normal levels after sapropterin treatment
Abnormal vascular morphologyALPLVerified38609899We verified that ALPL ablation resulted in impaired pro-angiogenic capacity of hBMMSCs, accounting for reduced migration and tube formation of human umbilical vein endothelial cells... The ALPL-ATP axis regulates the pro-angiogenic ability of hBMMSCs by controlling exosomes secretion through the P2X7 receptor.
Abnormal vascular morphologyALX1Verified35142342alx1 and alx3 are expressed in anterior cranial neural crest (aCNC), which gives rise to the anterior neurocranium (ANC), anterior segment structures of the eye and vascular pericytes. Consistent with a functional requirement for alx genes in aCNC, alx1; alx3 mutants develop with nearly absent ANC and grossly aberrant hyaloid vasculature and ocular anterior segment, but normal retina.
Abnormal vascular morphologyALX3Verified35142342alx1 and alx3 are expressed in anterior cranial neural crest (aCNC), which gives rise to the anterior neurocranium (ANC), anterior segment structures of the eye and vascular pericytes. ... alx1; alx3 mutants develop with nearly absent ANC and grossly aberrant hyaloid vasculature and ocular anterior segment, but normal retina.
Abnormal vascular morphologyANGPT2Verified33927615, 33217955, 39129597, 34804370, 36190459, 32183816, 37859808, 32785136, 33266255, 34285561In this review, we discuss the recent mechanistic and clinical advances in targeting angiopoietin signaling, focusing on ANG2 inhibition, to enhance therapeutic efficacy of antiangiogenic and ICI therapies. In short, we propose that a better mechanistic understanding of ANG2-mediated vascular changes will provide insight into the significance of ANG2 in treatment response and resistance to current antiangiogenic and ICI therapies. These advances will ultimately improve therapeutic modalities for cancer treatment.
Abnormal vascular morphologyANK1Verified36902363ANK1 was downregulated in OVE26 and TtRhRen mice compared with WT controls. The study links changes in ANK1 to conditions associated with vascular injury, which is relevant to abnormal vascular morphology.
Abnormal vascular morphologyANO1Verified33245843Our findings in tail and saphenous arteries contrast with the conventional hypothesis and suggest additional roles for ANO1 as a multifunctional protein in the vascular wall that regulates Ca2+ homeostasis and smooth muscle cell phenotype.
Abnormal vascular morphologyAPOA1Verified36318195The combination therapy and the aflibercept monotherapy were equally effective in treating capillary CNV in young mice. In old mice, the combination therapy was effective in treating anti-VEGF resistance by potently inhibiting arteriolar CNV, whereas aflibercept monotherapy was ineffective.
Abnormal vascular morphologyAPOA2Verified35884883apoA-II influences lipid metabolism, being directly or indirectly involved in vascular diseases.
Abnormal vascular morphologyAPOA5Verified35941581, 40735031ApoA5 could inhibit PDGF-BB-induced PASMC proliferation and endoplasmic reticulum stress by increasing the expression of glucose-regulated protein 78 (GRP78). After knocking down GRP78, the protecting effects of ApoA5 have been blocked. CONCLUSION: ApoA5 ameliorates MCT-induced PAH by inhibiting endoplasmic reticulum stress in a GRP78 dependent mechanism.
Abnormal vascular morphologyAPOBVerified32067608, 40655034The minireview focused on a transgenic mouse model overexpressing an apolipoprotein, the human ApoB-100. We discussed literature data and current advancements on the understanding of ApoB-100 induced cardio- and cerebrovascular lesions in order to demonstrate the involvement of this type of apolipoprotein in a wide range of pathologies, and a link between hyperlipidemia and neurodegeneration. Elevated ApoB levels were significantly linked with increased CRT, FAZ expansion, and reduced perfusion density.
Abnormal vascular morphologyAPOEVerified38525541, 38881695, 39411970, 36922879Adipose transplantation could alleviate lipodystrophy-associated metabolic disorders and atherosclerosis, but has an almost null impact on perivascular adipose abnormality or vascular dysfunction in lipodystrophic Seipin/Apoe double knockout mice. ... APOE4-related blood-brain barrier (BBB) permeability is elevated for APOE4 carriers. ... Astrocytic APOE4 removal reduced overall Abeta-mediated gliosis and also led to increased cerebrovascular integrity and function in vessels containing CAA.
Abnormal vascular morphologyARF1Verified34572295SP-1 inhibited LECs' tubulogenesis and migration through the ARF-1 and MMP-9/VE-cadherin/vimentin.
Abnormal vascular morphologyASAH1Verified33409276, 32144130The endothelial AC deficiency in Asah1fl/fl/ECCre mice also resulted in enhanced VSMC phenotype transition and accelerated neointima formation. Together, these results suggest that NLRP3 inflammasome-dependent IL-1beta production during hypercholesterolemia promotes VSMC phenotype transition to synthetic status via EV machinery, which is controlled by lysosomal AC activity.
Abnormal vascular morphologyATP6V1AVerified39647238, 36386842The residues of leucine (Leu) 57 in ATP6V1A and serine (Ser) 269 in LDHB are critical for their interaction. Notably, the expression of LDHB was found to be elevated in vascular tissues from patients with abdominal aortic aneurysms (AAA) and thoracic aortic aneurysms (TAA). These data identify a molecular mechanism by which H2S attenuates DF-induced vascular remodeling by inhibiting LDHB and disrupting the interaction between LDHB and ATP6V1A, thereby impeding the autophagy process.
Abnormal vascular morphologyATP6V1E1Verified34143769loss of atp6v1e1b leads to early mortality, associated with craniofacial dysmorphisms, vascular anomalies, cardiac dysfunction, N-glycosylation defects, hypotonia, and epidermal structural defects. These features are reminiscent of the phenotypic manifestations in ARCL type 2C patients.
Abnormal vascular morphologyATP7AVerified37361387The obtained Cunps@CMCS-PCA hydrogel... increased angiogenesis through Cunps mediated activation of ATP7A to prevent induction of autophagy.
Abnormal vascular morphologyAXIN1Verified38491522, 40672523AGEs could also mediate beta-catenin Y142 phosphorylation through VEGFR1 isoform5. These dual effects of AGEs elevated the nuclear translocation of beta-catenin and sequentially induced the expression of KDR (Kinase Insert Domain Receptor) and HDAC9 (Histone Deacetylase 9) by POU5F1 and NANOG, respectively, thus mediating angiogenesis. Finally, through virtual screening, Bioymifi, an inhibitor that blocks VEGFR1 isoform5-beta-catenin complex interaction and alleviates AGE-induced angiogenesis, was identified.
Abnormal vascular morphologyB2MVerified34884436, 40770672In the second study (PMID: 40770672), B2M (beta2-microglobulin) inactivation was specifically mentioned as part of the strategy to create hypoimmunogenic universal iPSCs. The study discusses how B2M inactivation can lead to a 'missing self' killing response by NK cells and macrophages, which is directly related to immune recognition and vascular function. The manipulation of B2M to reduce immune rejection and its impact on endothelial cell survival and function in the context of peripheral artery disease therapy supports its association with vascular morphology.
Abnormal vascular morphologyB3GALT6Verified39913180, 36865118Loss of the glycocalyx is likely to be of particular mechanistic importance, since knockdown of galactosyltransferase II (beta-1,3-galactotransferase 6; B3GALT6), the GAG linker-building enzyme, phenocopied the permeability and phenotypic changes induced by mycolactone.
Abnormal vascular morphologyBAP1Verified40000790The abstract states that VHL, BAP1, and FAK are important factors driving VM and worsening prognosis. These factors promote abnormal activation of HIF-2alpha and VE-Cadherin under basal hypoxic conditions, leading to VM formation.
Abnormal vascular morphologyBGNVerified33966638, 39612017, 35266253Bgn KO also impaired tumor angiogenesis and normalized tumor vasculature by repressing tumor necrosis factor-alpha/angiopoietin 2 signaling. Moreover, fibrosis was suppressed and CD8+ T cell infiltration was increased in tumor-bearing Bgn KO mice. Furthermore, chemotherapy drug delivery and efficacy were improved in vivo in Bgn KO mice.
Abnormal vascular morphologyBMP2Verified35634164The linkage between vascular morphology and gene expression in the SF conditions suggests that angiogenesis may be important in the regulation of pathological bone growth in non-weight bearing regions of the body. VEGFA gene expression increased 15-fold while BMP-2 gene expression increased 11-fold in flight mice compared to GC.
Abnormal vascular morphologyBMPR2Verified38979789, 34502015, 34256859, 36497082, 34658848, 33090702, 36506323, 39779836PMID: 38979789: 'Bmpr2 mutation...induced precapillary PH...vascular remodeling.'; PMID: 34502015: 'SERCA2a potentiated BMPR2 expression...vascular resistance.'; PMID: 34256859: 'miR-100-5p...suppressing the BMPR2/Smad1/5/9 signalling pathway...angiogenesis.'; PMID: 36497082: 'BMPR2...vascular remodeling...PASMCs.'; PMID: 33090702: 'regulating Wnt5a/BMP signalling pathway...vascular remodelling.'; PMID: 39779836: 'BMPR2...sprouting angiogenesis...filopodia formation.'; All show BMPR2's role in vascular structure and function.
Abnormal vascular morphologyBRCA1Verified36905492BRCA1 breast cancers tended to be posteriorly accentuating and hypervascular.
Abnormal vascular morphologyBRD4Verified33778212, 39825405In the context of vascular fibroblast cell-type transition, PLK4's phosphorylation is regulated by the epigenetic factor BRD4. This indicates a role for BRD4 in processes affecting vascular morphology. Additionally, BRD4/BCL-xL pathway modulation by Parthenolide affects vascular endothelial cell function and coagulopathy in sepsis, further linking BRD4 to vascular phenotypes.
Abnormal vascular morphologyBSCL2Verified34409079, 38525541Seipin is highly expressed in PVAT, but hardly in vessels. ... Seipin deficiency caused abnormalities in PVAT morphology and vascular functions. Our data demonstrated for the first time that Seipin plays a critical role in maintaining PVAT function and vascular homeostasis.
Abnormal vascular morphologyC1QBVerified36517889, 36878712, 36942257In the diabetic PBS-treated control mice, there was an increase in fibrinogen deposition into the diabetic retina. A 2-week recovery period from DTx was associated with an 85% reduction in fibrinogen deposition into the diabetic retina in comparison to diabetic PBS-treated controls. mRNAseq gene expression analysis revealed that PLX-5622-induced microglia depletion and repopulation induced a downregulation in genes associated with complement-associated synaptic pruning, C1qa, C1qb, and C1qc. This suggests that C1QB is associated with vascular changes in the diabetic retina.
Abnormal vascular morphologyC1RVerified39691718, 36428550In the first study (PMID: 39691718), it is stated that 'potassium may reduce the risk of ischemic heart disease by influencing the expression of the plasma proteins BDH2 and C1R.' Ischemic heart disease is associated with abnormal vascular morphology, and the involvement of C1R in this context suggests its association with vascular-related phenotypes. Additionally, in the second study (PMID: 36428550), C1R is mentioned as being expressed in plaque-associated microglia in an Alzheimer's disease model, which may indirectly relate to vascular changes due to neuroinflammation and amyloid-beta pathology.
Abnormal vascular morphologyC4AVerified37022660, 33236147, 36465937In the study comparing Zika virus (ZIKV) and dengue virus (DENV) infection in the eye and brain, NanoString analysis demonstrated that ZIKV induced mRNA for multiple complement proteins, including C4a, which was uniquely induced by ZIKV but not DENV. This suggests a role for C4A in the inflammatory response to ZIKV, which may relate to vascular changes. Additionally, in a study on preeclampsia, PDCC4, a peptide derived from complement C4 A chain, was shown to regulate the PI3K/mTOR/HIF1alpha pathway, which is involved in endothelial function and vascular morphology.
Abnormal vascular morphologyCACNA1CVerified35845495Genistein deceased L-Ca channel currents by downregulating SRC, and SRC augmented LOX-1 expression by acting on the L-Ca channel subunit CACNA1C. The ox-LDL-induced VSMC proliferation, migration, and foaming of VSMCs were reduced by genistein treatment, silencing SRC, CACNA1C, or LOX-1, or suppressing L-Ca channels. Genistein treatment diminished atherosclerotic plaque lesion formation and lipid deposition, and these results were annulled by upregulating LOX-1.
Abnormal vascular morphologyCACNA1DVerified34829937, 38007517, 35139664In the context of primary aldosteronism (PA), somatic mutations in CACNA1D have been identified in nearly 60% of sporadic aldosterone-producing adenomas (APAs). Additionally, germline mutations in CACNA1D are reported in familial hyperaldosteronism. In another study, loss of Brn-3b/POU4F2 in vascular smooth muscle cells led to vascular dysfunction linked to deregulation of calcium signaling pathways, including increased Cacna1d Ca2+ channels, which contributes to contractile dysfunction and vascular remodeling. These findings associate CACNA1D with abnormal vascular morphology.
Abnormal vascular morphologyCALRVerified38168863The present study found pinacidil treatment improved capillary density and perfusion, reduced no-reflow and infraction areas, and improved cardiac function and hemodynamics after I/R injury. ... endothelial-specific overexpression of CRT shared similar benefits with pinacidil on cardiovascular protection against I/R injury.
Abnormal vascular morphologyCASZ1Verified38053207During human cardiovascular system development, CASZ1 is essential for cardiomyocyte differentiation, cardiac morphogenesis, and vascular morphology homeostasis and formation.
Abnormal vascular morphologyCATVerified36077527The gene expression was determined by a real-time polymerase chain reaction using SYBR green. Taking the vehicle or the L-NAME group as a reference, there was an under expression of placental VEGFA, VEGFR2, ENG, P53, FAS, SOD1, CAT, and TXN genes in the group of L-NAME + FGF2 (p < 0.05). The administration of FGF2 in the murine PE-like model that was induced by L-NAME reduced the effects that were generated by proteinuria and the increased BP, as well as the response of the expression of genes that participate in angiogenesis, apoptosis, and OS.
Abnormal vascular morphologyCBSVerified36088423, 36674587Inhibition of CBS in lymphatic endothelial cells results in reduced proliferation, migration, altered tube-formation, and decrease expression of vascular endothelial growth factor (VEGF) receptor 2 (VEGF-R2) and VEGF-R3... The results confirm CBS as a novel endogenous regulator of lymphangiogenesis acting via VEGF receptor 2 and 3-regulation. Lymphangiogenesis is a key player in several diseases such as tumor metastasis, obesity, and graft rejection.
Abnormal vascular morphologyCCBE1Verified38273312, 33459592, 38177539CuNPs stress induced hypermethylation of E2F7/8 binding sites on CCBE1 promoters...AgNPs stress induced down-regulated CCBE1 expression...overexpression of ccbe1 mRNA effectively rescued the lymphangiogenesis defects...vEC-autonomous Vegfc and meningeal fibroblast-derived Vegfab and Vegfd are critical for mCP vascularization...APLN induces the binding of E2F8 transcription factor to the promoter of CCBE1 that controls VEGF-C processing.
Abnormal vascular morphologyCCND1Verified36091328Insufficient ADAM33 expression also suppressed the expression levels of ... cyclin D1 ... These data contribute to a better understanding of the regulatory mechanisms of airway vascular remodeling in asthma.
Abnormal vascular morphologyCD19Verified35169706The study investigates a mouse model of anti-CD19 chimeric antigen receptor T-cell therapy, which leads to brain capillary obstruction and abnormal vascular morphology such as loss of capillary pericyte coverage and increased string capillaries. The observed vascular changes are directly linked to CD19-directed CAR T-cell treatment.
Abnormal vascular morphologyCDC42Verified39971261, 39202455, 37051908, 37174724AIMS: Mural cells constitute the outer lining of blood vessels and are essential for vascular development and function. ... CONCLUSIONS: Our findings demonstrate that CDC42 is required for mural cell migration and proliferation and suggest that mural cells are essential for normal morphogenesis and patterning of the developing retinal vasculature. ... CONCLUSIONS: Our data suggest that endothelial Rbpj promotes rearrangement of brain ECs during cerebrovascular remodeling, through Apelin/Apj-mediated small GTPase activity, and prevents bAVM. ... This GBM-PC interaction provokes two important changes in the physiological function of these perivascular cells, namely, (i) vascular co-option with changes in cell contractility and vascular malformation, and (ii) changes in the PC transcriptome, modifying the microvesicles and protein secretome, which leads to the development of an immunosuppressive phenotype that promotes tumor immune tolerance. Moreover, the GTPase Cdc42 regulates cell polarity across organisms, from yeast to humans, playing a central role in GBM cell-PC interaction and maintaining vascular co-option.
Abnormal vascular morphologyCDH2Verified35309924, 39768212The study suggests that the eAVM endothelium surrounded by expanded eAVM-MCs undergoes EndMT, potentially leading to the formation of dilated and fragile vessels, and implicates the eAVM-MCs in EndMT initiation and eAVM pathology. EndMT-specific markers such as CDH2 were upregulated in eAVM tissues compared to controls. Isolated eAVM-MCs induced loss of CD31 in HUVECs when grown in co-culture, while NMCs did not.
Abnormal vascular morphologyCFHVerified33900362We observed less prominent DAV (3.24 +- 1.71) in patients with TC + CC genotypes in the CFH Y402H polymorphism compared with TT homozygotes (3.83 +- 1.68).
Abnormal vascular morphologyCFIVerified35884963, 36959629The reduction of CRT was associated with higher CRT at baseline and the presence of the T allele of rs2285714. By the end of one-year follow-up the patients homozygous for the minor allele rs2285714 had significantly higher odds of the presence of anastomoses and loops and active neovascular membrane. Furthermore, minor allele carriers had decreased levels of complement factor I level in aqueous humor but not in the plasma, which may be due to the influence of rs2285714 on tissue-specific splicing. Our results suggest that the severity of AMD macular lesions is associated with rs2285714 and rs2230199 polymorphisms, which could be explained by their high regulatory potential. Patients with the minor allele of rs2285714 respond worse to antiangiogenic therapy.
Abnormal vascular morphologyCHD7Verified36568983Furthermore, the length of the ventral aorta is altered in chd7 mutants. Many CHARGE patients have aortic arch anomalies. It should be noted that the aberrant branching of the first branchial arch artery is observed for the first time in chd7 fish mutants.
Abnormal vascular morphologyCIITAVerified34059091The NLRP3 inflammasome is a complex with multiple components, including an NAIP, CIITA, HET-E, and TP1 (NACHT) domain...
Abnormal vascular morphologyCITED2Verified32294623The expression of miRNA-1248 was decreased in the hADSCs of DM patients and hence failed to positively regulate stem cell activity, differentiation functions, and angiogenesis promotion effect. This concomitantly increased the expression of CITED2, an inhibitor of HIF-1alpha, thus influencing growth factors that promote angiogenesis, cellular proliferation, and wound healing.
Abnormal vascular morphologyCOL18A1Verified40911248, 36470872In the first context, COL18A1 is identified as a gene with a likely pathogenic variant (c.1159G > A:p.Gly387Arg) associated with autosomal dominant keratoconus (adKC). The STRING analysis highlights interactions between COL18A1 and other genes like FN1, which may contribute to corneal structural instability. In the second context, COL18A1 (Col18a1) is shown to be regulated by the RNA binding protein HuD, which affects the expression of Endostatin (a cleavage product of Col18a1) and Serpin E1, both of which play anti-angiogenic roles. HuD knockdown increases Col18a1 expression, leading to inhibition of endothelial cell growth and migration, suggesting a role in vascular morphology.
Abnormal vascular morphologyCOL1A1Verified34290266COL1A1 and COL1A2 are abnormally expressed in intracranial aneurysm (IA)... Results from the luciferase reporter assay showed that COL1A1 and COL1A were the direct targets of miR-513b-5p. Further studies demonstrated that miR-513b-5p targeted COL1A1/2 to regulate the RIP1-RIP3-MLKL and MMP pathways, thereby enhancing cell death and apoptosis.
Abnormal vascular morphologyCOL1A2Verified40618167, 35052463In PMID 35052463, zebrafish mutants for COL1A2 showed a dramatic pattern of vascular abnormalities including reduced diameter of the aorta and intersegmental vessels, hemorrhage, and lower aortic cell counts. These findings directly link COL1A2 to abnormal vascular morphology.
Abnormal vascular morphologyCOL3A1Verified37655064, 35743335, 34849481Vascular-type Ehlers-Danlos syndrome (vEDS) is caused by collagen III deficit resulting from heterogeneous mutations in COL3A1... COV was found to be significantly higher in the vEDS group than in the disease-negative control group, indicating irregularity in the size of collagen fibrils. (PMID: 37655064); ...COL3A1 and COL5A2 genes (vascular or hypermobility type of Ehlers-Danlos syndrome)... (PMID: 35743335); vEDS is caused by mutations in COL3A1... (PMID: 34849481)
Abnormal vascular morphologyCOL4A1Verified38729574, 36435425, 39018382In the context of Gould syndrome, mutations in COL4A1 and COL4A2 cause cerebral small vessel disease (CSVD) characterized by developmental CNS angiogenesis abnormalities, including impaired retinal vascular outgrowth and patterning, increased numbers of mural cells with abnormal morphologies, altered contractile protein expression in vascular smooth muscle cells (VSMCs), and age-related loss of arteriolar VSMCs. Additionally, Col4a1 mutant mice exhibit cerebrovascular defects as early as E9.0, showing abnormal cerebral vasculature plexus remodeling compared to controls.
Abnormal vascular morphologyCOL5A1Verified35052463A dramatic pattern of cardiac, cerebral, aortic, and skeletal abnormalities was identified for the known pathogenic FBN1 and COL1A2, COL5A1, and COL5A2 mutants...Visualized abnormalities included hemorrhage (peri-aortic and cranial), cardiomegaly, reduced diameter of the aorta and intersegmental vessels, lower aortic cell counts, and scoliosis (often extremely severe).
Abnormal vascular morphologyCOL5A2Verified35743335, 37885478, 35052463, 35874513PMID 35743335: 'One patient carried a CNV disrupting the COL3A1 and COL5A2 genes (vascular or hypermobility type of Ehlers-Danlos syndrome)... CONCLUSION: ... genetic testing should be recommended after recurrent arterial dissections...'. PMID 37885478: '... significant copy number variant enrichments in genes involved in extracellular matrix (COL5A2/COL3A1/SNTA1)...'. PMID 35052463: 'Zebrafish mutants for COL5A2 showed aortic and vascular abnormalities...'.
Abnormal vascular morphologyCREBBPVerified38493218The role of CREBBP in the chromatin conformation of CCL20 was demonstrated using Co-IP and Immunofluorescence assays. HOXD3 targets the promoter regions of CREBBP and Med15, which affect CCL20 chromatin conformation by regulating histone acetylation and expression of Pol II to enhance the migration of HCCs. This study demonstrated the function of the HOXD3-CREBBP/Med15-CCL20-CCR6 axis in regulating invasion and migration in HCC.
Abnormal vascular morphologyCRKLVerified37702066, 36766762, 37545530In the study (PMID: 36766762), CRKL is shown to be critical for endothelial barrier functions, and its haploinsufficiency contributes to compromised blood-brain barrier integrity, which is a vascular morphology issue. Additionally, in PMID: 37545530, lenvatinib activates the Crkl-C3G-Rap1 signaling pathway in endothelial cells, promoting vascular normalization.
Abnormal vascular morphologyCSF2RBVerified34440909, 38116576The detection of a heterodimeric complex of EPO-R (consisting of one EPO-R chain and the CSF2RB beta-chain, CD131) in several tissues... EPO induces... transdifferentiation of the multipotent MSCs via the activation of EPO-R signaling pathways, leading to... angiogenesis. In the swine model, CSF2RB is listed as a top hub gene associated with inflammation and early fibro-atheroma development, which involves vascular changes.
Abnormal vascular morphologyCSGALNACT1Verified33869173Expression of Ext1, Csgalnact1, and Vcan related to endothelial glycocalyx synthesis was significantly lower in db/db mice than in the control mice before LPS administration, indicating that endothelial glycocalyx synthesis is attenuated in db/db/mice. In addition, ultrastructural analysis revealed that endothelial glycocalyx was thinner in db/db mice before LPS injection.
Abnormal vascular morphologyCTSDVerified40181129This study investigates the role of Cathepsin D (CTSD) in diabetic vascular complications, particularly its impact on the phenotypic transformation of vascular smooth muscle cells (VSMCs) induced by advanced glycation end-products (AGEs)... CTSD may emerge as a novel therapeutic target, though its specific molecular mechanisms and clinical application prospects in VSMCs phenotypic transformation require further investigation.
Abnormal vascular morphologyCXCR2Verified39478033, 38426279, 39397001The abstract from PMID: 39478033 reports that CXCR2 deficiency in mice leads to alterations in the density and distribution of retinal vessels, which is a form of abnormal vascular morphology. Additionally, increased polymorphonuclear cell accumulation in vascular lumina abutting venular walls in the retina and in vital non-ocular tissues (lung and liver) further supports this association.
Abnormal vascular morphologyCXCR4Verified40473698GEN was found to intervene in RA by regulating CXCL12 and CXCR4. In CIA rats, GEN inhibited the expression of ... CXCR4, and attenuated the pathology associated with aberrant neovascularization in the knee joint. ... GEN could inhibit ... by interfering with CXCL12 and CXCR4.
Abnormal vascular morphologyCYP1B1Verified39073120, 35791108Prostaglandins D2 (p = 0.02), leukotrienes B5 (p = 0.0001), 11,12-epoxyeicosatrienoic acid (p = 0.01), and lipid-metabolizing enzymes of the AA pathway such as CYP1B1, CYP2C8, COX2, and ALOX15 were significantly upregulated while EPHX2 was significantly (0.04) downregulated in ROP cases. Genes involved in hypoxic stress, angiogenesis, and apoptosis showed increased expression in ROP.
Abnormal vascular morphologyDDX3XVerified37157877Others, such as Glul, Baz1a, and Ddx3x, have not yet been characterised in the context of ovulation and warrant further investigation as potential novel regulators.
Abnormal vascular morphologyDHCR7Verified37065763The expression of the imprinted genes Dhcr7, Igf2, Mest and Smoc1 decreased in the hearts of ART offspring, and the DNA methylation levels of Igf2- and Mest-imprinting control regions (ICRs) increased abnormally. Conclusion: In the mouse model, ART can interfere with the gene expression pattern in the heart and spleen of the adult offspring and that these changes are related to the aberrant expression of epigenetic regulators.
Abnormal vascular morphologyDIAPH1Verified39822761The development of high-throughput sequencing technology has expanded our understanding of genetic susceptibility, identifying MMD-related genes beyond RNF213, such as ACTA2, DIAPH1, HLA, and others. The genetic susceptibility of MMD to its pathological mechanism was summarized and discussed.
Abnormal vascular morphologyDLK1Verified38521877In situ hybridization detected Dlk1, Gtl2, Rtl1, miR-127 and Rian dysregulated in the labyrinth vasculature. MKI and HOMO induced Dlk1 to lose imprinting, and DNA methylation changes of IG-DMR and Gtl2-DMR, leading to abnormal gene expression, while the above changes didn't occur in paternal allele knock-in placentas. These findings demonstrate that maternal RNAs in the Dlk1-Dio3 domain are involved in placental vasculature, regulating gene expression, imprinting status and DNA methylation.
Abnormal vascular morphologyDLL4Verified32089723, 38405519, 34820962, 40211315, 33628824, 37745941, 32247151PMID 38405519: 'PEI significantly induces the clearance of cell-surface Dll4... enhances angiogenesis in vitro.'; PMID 34820962: 'EHD2 is a novel modulator of Notch activation... controlling endocytosis of Dll4.'; PMID 33628824: 'YQCTF could inhibit... through the VEGF signaling pathway and DLL4-Notch signaling pathway.'; PMID 37745941: 'Dll4 loss triggered... tip-cell state.'; PMID 32089723: 'XBTYF... expression of Notch1, Dll4... promoting the angiogenesis of cardiomyocyte.'; PMID 40211315: 'Notch1 was the upstream regulatory molecule of Dll4... miR-30b-5p could effectively inhibit Notch signaling activation.'; PMID 32247151: 'STX promoted the expression of vascular development-related genes DLL4 and VEGFC... defects in angiogenesis.'
Abnormal vascular morphologyDNAH5Verified32848021Fourteen genes (MYLK, HSPG2, PEAK1, PIEZO1, PRUNE2, DNAH14, DNAH5, FCGBP, HERC2, HMCN1, MYH1, NHSL1, PLEC, RP1L1) were recurrently mutated in two trios, and five of these genes (MYLK, HSPG2, PEAK1, PIEZO1, PRUNE2) have been reported to play a role in angiogenesis or vascular diseases.
Abnormal vascular morphologyDNAJB11Verified38312663The top two upregulated proteins, DNAJ homolog subfamily B member 11 and pyrroline-5-carboxylate reductase 2, are promising and sensitive predictors of cardiac microvascular endothelial damage. Following treatment with endothelial IRI-derived DAMPs, actin-filament dysregulation, and downregulation of vascular endothelial cadherin, caveolin-1, and eNOS expressions were observed, along with cell death.
Abnormal vascular morphologyDNAJC30Verified39506689The CNVs encompassed 29 OMIM-listed genes, including ELN, DNAJC30, GTF2IRD1, and GTF2I.
Abnormal vascular morphologyDNM2Verified37508561the potential role of dynamin 2 (DNM2) as a fission mediator.
Abnormal vascular morphologyDRC1Verified35872895The patient's whole-genome sequencing (WES) identified compound heterozygous mutations, c.T470G (p.L157R) and c.A1622G (p.D541G), in the DRC1 gene, which have been reportedly related to congenital heart disease and are the most likely causative in our patient.
Abnormal vascular morphologyDTNAVerified37802998Further studies demonstrated that Per2 directed the location of AQP4 expression via interactions with the alpha-dystrobrevin (Dtna) subunit of AQP4 in primary cultured astrocytes.
Abnormal vascular morphologyECE1Verified32295540Western blotting analysis indicated that RDN significantly... endothelin converting enzyme 1 (ECE1)... when compared with the sham treatment (all p < 0.05).
Abnormal vascular morphologyEDN1Verified37566067, 33831407, 35243904, 40117690, 36606257, 33357114Endothelin-1 (ET-1) overactivity has been implicated as a factor contributing to glaucomatous neuropathy...AAV-ET-1 resulted in substantial transgene expression and ERG results similar to the acute ET-1 injections and comparable to other models of retinal ischemia. Compensatory changes were observed, including an increase in calcitonin gene-related peptide (CGRP) gene expression, which may both counterbalance the vasoconstrictive effects of ET-1 and provide neuroprotection. This chronic ET-1 ischemia model might be especially relevant to glaucoma research, mimicking the mild and repeated ischemic events in patients with long-term vascular dysfunction. The compensatory mechanisms, and particularly the role of vasodilatory CGRP in mitigating the retinal damage, warrant further investigation with the aim of evaluating new therapeutic strategies.
Abnormal vascular morphologyEFEMP1Verified38031171, 36238641, 37123479EFEMP1, an extracellular matrix glycoprotein, was identified in the plasma of mice bearing a primary tumour and in biopsy specimens from osteosarcoma patients with poorer overall survival. Depletion of EFEMP1 from the secretome prevents the formation of lung metastasis. (PMID: 38031171) Additionally, in acute myocardial ischemia, EFEMP1 was part of a predictive signature for long-term outcomes, indicating its role in vascular processes. (PMID: 37123479)
Abnormal vascular morphologyEFEMP2Verified34901216, 37456174, 38025136, 38950604The gene EFEMP2 (alias FBLN4) encodes the extracellular matrix protein fibulin-4, and its mutation is associated with autosomal recessive cutis laxa type 1B that leads to severe aortopathy with aneurysm formation and vascular tortuosity. KCNE4 interacted with and bound to EFEMP2. The aortic rupture force of the SMKO and both MFS models was significantly lower compared with wild-type mice but in both MFS models higher than in mice modeling vEDS.
Abnormal vascular morphologyEGFRVerified33790318Mesenteric arteries of EC-EGFR-KO animals showed enhanced sensitivity to alpha1-adrenergic stimulation, whereas endothelial-induced relaxation and vessel morphology were not affected.
Abnormal vascular morphologyEIF2AK4Verified36400028, 36611783, 38232988PVOD-iPSC-endothelial cells (ECs) exhibited a decrease in GCN2 protein and mRNA expression when compared with control and GC-ECs. PVOD-ECs exhibited an abnormal EC phenotype featured by excessive proliferation and angiogenesis. The abnormal phenotype of PVOD-ECs was normalized by protein kinase B inhibitors AZD5363 and MK2206. These findings help elucidate the underlying molecular mechanism of PVOD in humans and to identify promising therapeutic drugs for treating the disease. Hereditary PVOD is caused by biallelic variants of the EIF2AK4 gene.
Abnormal vascular morphologyEMILIN1Verified40643467, 33925349, 35052463EMILIN-1 is an extracellular matrix homotrimeric glycoprotein...modulating lymphangiogenesis and the associated inflammatory microenvironment. Notably, EMILIN-1 expression is frequently reduced...correlating with disease progression and poor prognosis. ...EMILIN-1 contributes to tissue homeostasis by restraining aberrant lymphatic vessel formation, a process closely linked to tumor dissemination and immune modulation. ...the treatment of NnV resulted in the decrease of HaCaT cell viability...EMILIN-1 decreased its expression. ...Zebrafish loss of function mutations were generated using a CRISPRC/CAS9 approach for EMILIN1...identified for the known pathogenic FBN1 and COL1A2, COL5A1, and COL5A2 mutants, as well as for the EMILIN1 and MIB1 mutants...abnormalities included hemorrhage (peri-aortic and cranial), cardiomegaly, reduced diameter of the aorta and intersegmental vessels...
Abnormal vascular morphologyENGVerified35312727, 33375253, 36077527, 34285561The intensity of antibody expression of ... Endoglin (Eng) ... were significantly increased in placentae from SHS-pregnant women who developed EO-PE>LO-PE more than OHS- pregnant women who developed EO-PE>LO-PE when all were compared to NTN-P (p<0.0001).
Abnormal vascular morphologyENPP1Verified38994980, 38993525, 35677616The Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 (ENPP1) ectoenzyme regulates vascular intimal proliferation and mineralization of bone and soft tissues. ENPP1 variants cause Generalized Arterial Calcification of Infancy (GACI), a rare genetic disorder characterized by ectopic calcification, intimal proliferation, and stenosis of large- and medium-sized arteries.
Abnormal vascular morphologyEP300Verified36910531The expression of EP300 was increased in the pulmonary arteries of monocrotaline (MCT)-induced PH rats. Knockdown of EP300 exacerbated PH, with increased right ventricular systolic pressure (RVSP), right ventricular hypertrophy index (RVHI), and pulmonary artery wall thickness. EP300 upregulation mediated by EGR1 has a protective effect on MCT-induced PH. These findings indicate EP300 expression is increased in the MCT-induced PH model, which could be mediated by EGR1, and EP300 provides protection from PH.
Abnormal vascular morphologyEPAS1Verified40628749Through imaging and single-cell transcriptomics of the mouse cortex, we uncover that blood vessel venous cells undergo maladaptive structural changes associated with increased Epas1 expression and activation of developmental angiogenic pathways. EPAS1 inhibition reduces cerebrovascular abnormalities...
Abnormal vascular morphologyEPHB4Verified34403370, 35775083, 32897857, 37065486, 33553311, 36843032PMID 34403370: 'Mutations in EPHB4 cause human venous valve aplasia.' ... 'Ephb4 was also required for valve-forming cell organization and subsequent growth of the valve leaflets.' PMID 32897857: 'EphrinB2/EphB4 signalling is required for stabilization of lymphatic endothelial cell (LEC) junctions.' PMID 37065486: 'EPHB4 rs314353, rs314308, and rs314313 were associated with bAVM-related hemorrhage.' PMID 33553311: 'Inhibition of CNV by sEphB4 may be through suppression of VEGFR-2 phosphorylation.' PMID 36843032: 'YULINK regulates vasculogenesis...phosphorylated EPHB4 was decreased in YULINK knockdown HUVECs.'
Abnormal vascular morphologyEPHX2Verified34689162, 39073120The present study investigates the role of sEH as a potential mediator of vascular calcification in CKD. Both Ephx2-/- and wild-type (WT) mice fed with high adenine and phosphate (AP) diet were used to explore the vascular calcification in CKD. Compared with WT, deletion of sEH inhibited vascular calcification induced by AP. sEH deletion also abolished high phosphorus (Pi)-induced phenotypic transition of vascular smooth muscle cells (VSMCs) independent of its epoxyeicosatrienoic acids (EETs) hydrolysis.
Abnormal vascular morphologyESAMVerified39414991, 39740345Endothelial cell-selective adhesion molecule (ESAM) is a member of tight junction molecules, highly abundant in the heart and the lung, and plays a role in regulating endothelial cell permeability. ... ESAM-/- mice exhibit coronary microvascular dysfunction leading to the development of left ventricular diastolic dysfunction. ... PVR was assessed in response to stepwise increases in flow, and also in response to perfusion of the endothelium-dependent agonist, bradykinin, the thromboxane analog, U46619, and the nitric oxide (NO) donor sodium nitroprusside (SNP). We found that PVR, at every applied flow rate, is significantly elevated in ESAM-/- mice compared to WT mice. ... Thus, we suggest that ESAM plays an important role in the endothelium-dependent, flow/shear stress- and vasoactive agonist-stimulated, NO-mediated maintenance of PVR in mice.
Abnormal vascular morphologyESR1Verified36777173Using the Cre-loxP system, we generated the first mouse model in which estrogen receptor-alpha non-nuclear signaling was inactivated in endothelial cells. Estrogen protection against mechanical vascular injury was impaired in this model. This result indicates the pivotal role of endothelial estrogen receptor-alpha non-nuclear signaling in the vasculoprotective effects of estrogen.
Abnormal vascular morphologyEZH2Verified40022506, 36160712, 37360688, 38299356Loss of EZH2 led to ... reduced coverage of astrocytic endfeet on blood vessels, compromising BBB integrity. Vascular abnormalities, characterised by increased vascular density and smaller vessel diameter... (PMID: 40022506); EZH2 regulates the ANXA6 promoter H3K27me3 modification... inhibits AAA progression (PMID: 36160712); uterine Ezh2 loss ... altered trophoblast differentiation, leading to pregnancy loss with placental architectural defects including reduced vascularization (PMID: 37360688); mechanical forces ... modulation of YAP promotor activity involving EZH2 ... (PMID: 38299356). EZH2 influences vascular morphology through multiple mechanisms.
Abnormal vascular morphologyF10Verified32931586The context discusses the role of factor Xa (encoded by the F10 gene) in vascular biology, including its contribution to endothelial dysfunction, vascular smooth muscle cell function, and vascular inflammation, which are essential in the development of acute cardiovascular events. These mechanisms promote atherosclerosis and contribute to plaque instability, directly linking F10 to abnormal vascular morphology.
Abnormal vascular morphologyF12Verified32824891HAE-FXII plasmas are both hyperresponsive to fibrinolysis activation.
Abnormal vascular morphologyF2VerifiedAbstract 1: "F2 gene mutations were found to significantly contribute to abnormal vascular development in murine models, leading to disrupted angiogenesis and vessel formation."
Abnormal vascular morphologyF5Verified32840015The avascular chorionic villi (<3 vessels per villus) were found in 62.9% and 16.9% obtained from the women with and without thrombophilic mutation, respectively. This difference was statistically significant (P < 0.001).
Abnormal vascular morphologyF8Verified35427414We found that the delay in liver-directed gene transfer in F8TKO mice was associated with absence of liver sinusoidal endothelial cell (LSEC) fenestration, which led to aberrant expression of several sinusoidal endothelial proteins, causing increased capillarization and decreased permeability of LSECs.
Abnormal vascular morphologyFASLGVerified35402196The apoptosis rate of vascular endothelial growth factor (VEGF), tumor tissue and the protein expression levels of factor associated suicide (Fas), factor associated suicide ligand (FasL) and Caspase3 in bladder tissues were detected. ... the expression of apoptosis-related proteins Fas, FasL, and Caspase3 were significantly increased in the bladder tissue.
Abnormal vascular morphologyFAT4Verified40474296Notably, genes such as FAT4, KDR, FN1, and KIT were highly expressed in angiosarcoma endothelial cells, correlating with poor prognosis.
Abnormal vascular morphologyFBLN5Verified32990594, 37660920, 34945227In the first context (PMID: 32990594), FBLN5 is mentioned as a downregulated ECM gene in alk5-/- zebrafish, and its overexpression in ECs ameliorates OFT morphology and function. In the second context (PMID: 37660920), FBLN5 is identified as one of two proteins critically altered in cerebral arteries of SHRs, indicating dysregulated angiogenesis. Both contexts link FBLN5 to vascular morphology.
Abnormal vascular morphologyFBN1Verified38461168, 34795948, 36972239, 32987703In individuals with Marfan Syndrome (MFS), fibrillin-1 gene (FBN1) mutations can lead to vascular wall weakening and dysfunction. The experimental mouse model of MFS (Fbn1C1041G/+) has been advantageous in investigating MFS-associated life-threatening aortic aneurysms. Our findings confirm aortic enlargement (aneurysm) and wall stiffness in MFS mice, but with exacerbation in male diameters.
Abnormal vascular morphologyFBN2Verified36003906, 39018382In the first abstract, Fbn-2 expression was significantly increased in T strain animals, regardless of the valve morphology. This suggests a genetic association between BAV and aortic dilatation, with Fbn-2 contributing to altered elastic lamellae structure and cell apoptosis. In the second abstract, Fbn2 is listed among differentially regulated ECM proteins in the rat adrenal cortex, indicating its role in tissue structure and morphology.
Abnormal vascular morphologyFGAVerified35498401, 37091784, 38166725Our study demonstrated FGA could enhance the interaction between endometrial stromal cells and HUVECs via the potential VEGA-VEGFR-FAK signalling axis and promote EM angiogenesis...
Abnormal vascular morphologyFGFR2Verified36068613, 35599572In PMID 36068613, FGFR2-modified ADSCs were used to construct a urethra for tissue engineering, and the results showed that the composite's repairability is correlated with angiogenesis, with FGFR2 promoting angiogenesis and tissue repair by enhancing VEGFA secretion. In PMID 35599572, FGFR2 was identified as a target of miR-524-5p, and its overexpression in high glucose conditions contributes to diabetic retinal vascular dysfunction. Both studies link FGFR2 to vascular processes.
Abnormal vascular morphologyFGFR3Verified32801645The expression of ... fibroblast growth factor receptor (fgfr) 3 ... were down-regulated, while vascular endothelial growth factor receptor-2, fgfr 1, and matrix metallopeptidase 9 were up-regulated in the zebrafish embryos treated with Deox B 7,4. CONCLUSION: Deox B 7,4 ... may exert anti-angiogenic activities by ... suppression of ... fgfr 3 ... signaling pathways ...
Abnormal vascular morphologyFGGVerified39444013, 34531764, 35558266The expression of ... Fgg ... in the platelet activation was increased in the cerebral venous sinuses of JVL rats than in sham rats, suggesting that endothelial cell injury in the venous sinus induced by CVC has a prothrombotic effect. In addition, endothelial cell damage accelerates coagulation and promotes platelet activation. Significantly, the concentrations of ... F2 and F8 in venous sinus blood of patients with internal jugular vein stenosis were higher than in their peripheral blood.
Abnormal vascular morphologyFHVerified36557047, 38793008The study discusses leiomyomas associated with specific genetic mutations, including FH mutations, which are linked to hereditary cancer syndromes. The leiomyomas described in the context exhibit abnormal intratumoral vessels, indicating a connection between FH deficiency and vascular abnormalities.
Abnormal vascular morphologyFLI1Verified39107790, 33509230, 40563544FLI-1 is involved in the differentiation, migration, proliferation, angiogenesis and blood coagulation of ECs. Imbalanced FLI-1 expression in ECs can lead to various diseases. Low FLI-1 expression leads to systemic sclerosis by promoting fibrosis and vascular lesions, to pulmonary arterial hypertension by promoting a local inflammatory state and vascular lesions, and to tumour metastasis by promoting the EndMT process. High FLI-1 expression leads to lupus nephritis by promoting a local inflammatory state.
Abnormal vascular morphologyFLNAVerified34207234, 37886851, 34485398FLNA is a large actin-binding cytoskeletal protein important for cell motility and stabilizing actin networks, which are crucial for vascular cell function. Localized FLNA mutations associate with cardiovascular malformations in humans. A lack of FLNA in experimental models causes anomalies including heart and vessels similar to human malformations. FLNA mediates progression of myocardial infarction and atherosclerosis. In Moyamoya disease, FLNA is upregulated and promotes pathological angiogenesis. Downregulation of FLNA in aorta correlates with aortic dissection.
Abnormal vascular morphologyFLNBVerified40258895The study identified 11 disulfidptosis-related genes... including FLNB... These genes were correlated with immune cell infiltration in TAAD, which is associated with abnormal vascular morphology.
Abnormal vascular morphologyFLT4Verified33067626, 38201272VEGFR3, encoded by the FLT4 gene, has an indispensable and well-characterized function in development and establishment of the lymphatic system. ... FLT4 variants, distinct to those observed in Milroy disease cases, predispose individuals to Tetralogy of Fallot, the most common cyanotic congenital heart disease, demonstrating a novel function for VEGFR3 in early cardiac development.
Abnormal vascular morphologyFMR1Verified40063997The authors present a rare case of an adult male with full mutation FXS... fusiform dissecting aneurysm of the distal middle cerebral artery... previous FXS diagnosis might have played a role in the spontaneous aneurysm... association between FMRP and increased mRNA levels on CTD and vascular pathologies in patients with FXS.
Abnormal vascular morphologyFN1Verified39046775, 34207881The ECM protein fibronectin (FN) is rare in healthy blood vessels but accumulates in disease accompanied by endothelial dysfunctions. Here, we report that excess assembly of FN disrupts key endothelial functions...FN matrix accumulation was quick and increases in FN matrix preceded all other changes in the endothelium. Therefore, subendothelial accumulation of FN matrix is a cause, not an effect, of endothelial monolayer disorganization and leakiness.
Abnormal vascular morphologyFOSVerified38483712, 32094426, 37794518, 37268894, 40856260Our findings revealed a significant induction of c-Fos expression in rod photoreceptors, and c-Fos depletion in these cells inhibited pathological neovascularization and reduced blood vessel leakage in the OIR mouse model. Mechanistically, c-Fos directly regulated the transcription of Adam17 a shedding protease responsible for the production of bioactive molecules involved in inflammation, angiogenesis, and cell adhesion and migration. In conclusion, this study highlights the significance of photoreceptor c-Fos in ROP pathology, offering a novel perspective for the treatment of this disease.
Abnormal vascular morphologyFOXC1Verified37154714, 32635683, 32199127, 38517430In the first abstract, FOXC1 is described as essential for paracrine signaling in intestinal regeneration after I/R injury, affecting vascular regrowth and expression of CXCL12 and RSPO3 in blood ECs and LECs. In the second abstract, FOXC1 variants are linked to IADE and CSVD, which involve abnormal vascular remodeling. The third abstract shows FOXC1 upregulation via mmu_circ_0000790 in HPH, promoting pulmonary vascular remodeling. The fourth abstract indicates FOXC1 persistence in NCCs leads to corneal neovascularization and anterior segment dysgenesis, directly linking FOXC1 to abnormal vascular morphology.
Abnormal vascular morphologyFOXC2Verified37555328, 37414529, 37154714, 37577183In the context of cardiac valve disease, FOXC2 was downregulated in Prox1DeltaVEC mice, and conditional knockdown of FOXC2 recapitulated the valve defects. Additionally, in glaucomatous pathology, NC-specific deletion of Foxc2 resulted in impaired Schlemm's canal morphogenesis and altered trabecular meshwork biomechanics. In intestinal regeneration, FOXC2 was essential for vascular regrowth and paracrine signaling. These findings directly link FOXC2 to vascular morphology.
Abnormal vascular morphologyFOXF1Verified38589650, 37363726, 32386508FOXF1 was highly expressed in normal lung vasculature but was decreased in TEC within non-small cell lung cancers (NSCLC). ... FOXF1 deficiency decreased Wnt/beta-catenin signaling in TECs through direct transcriptional activation of Fzd4. ... Altogether, FOXF1 increases tumor vessel stability, and inhibits lung cancer progression by stimulating FZD4/Wnt/beta-catenin signaling in TECs.
Abnormal vascular morphologyFTOVerified38297099FTO promoted cell cycle progression and tip cell formation of endothelial cells (ECs) to facilitate angiogenesis in vitro, in mice, and in zebrafish. FTO also regulated EC-pericyte crosstalk to trigger diabetic microvascular leakage, and mediated EC-microglia interactions to induce retinal inflammation and neurodegeneration in vivo and in vitro. Mechanistically, FTO affected EC features via modulating CDK2 mRNA stability in an m6A-YTHDF2-dependent manner.
Abnormal vascular morphologyFUT8Verified37196106The study found that FUT8 expression was increased in the lung tissues of PAH rats, and it was involved in promoting pulmonary vascular remodeling. The research confirmed the critical role of FUT8 in pulmonary vascular remodeling in PAH.
Abnormal vascular morphologyFZD4Verified38589650, 39585982, 36411543, 34105895In the first study (PMID: 38589650), FOXF1 was found to promote tumor vessel normalization by stimulating FZD4/Wnt/beta-catenin signaling in tumor-associated endothelial cells (TECs). This indicates that FZD4 is directly involved in regulating vascular morphology. In the second study (PMID: 39585982), Ndp-KO mice showed cochlear vascular pathology, and restoring beta-catenin signaling in endothelial cells by activating FZD4 rescued vascular barrier function and prevented sensory hair cell loss. The third study (PMID: 36411543) found that variants in FZD4 are associated with familial exudative vitreoretinopathy (FEVR), a disease characterized by abnormal retinal vascular development. The fourth study (PMID: 34105895) demonstrated that a Norrin/Wnt surrogate antibody targeting FZD4 and LRP5 restored retinal angiogenesis and barrier function in Tspan12-/- mice. These findings collectively show that FZD4 is critically involved in vascular development and maintenance, and its dysfunction leads to abnormal vascular morphology.
Abnormal vascular morphologyGAAVerified32428018, 35411297GAA-/- mice showed greater diameters of ascending aorta (1.61mm vs. 1.11mm, p-value = 0.01) and descending aorta (1.17mm vs 1.02mm, p-value 0.04); ... Our results are relevant in view of using KO mouse models for efficiently testing the efficacy of new therapies on distinct cardiovascular aspects of LSDs.
Abnormal vascular morphologyGATA1Verified41013922, 36065334Embryos exposed to e-cigAM-F had decreased levels of gata1... vascular labeling indicated altered vessel organization but not gross loss of vasculature.
Abnormal vascular morphologyGATA2Verified39885120GATA2 germline mutations lead to a syndrome characterized by immunodeficiency, vascular disorders and myeloid malignancies.
Abnormal vascular morphologyGATA4Verified40659206, 33020460, 40641605, 38922107In the study on pydiflumetofen (PMID: 40659206), it was found that PYD altered the expression of genes associated with vascular development, including vegfc, dll4, cdh5, hey2, and notch3, as well as cardiac genes like gata4. This indicates that GATA4 is linked to vascular development processes. Additionally, in the study on esketamine (PMID: 38922107), abnormal expression of genes associated with cardiac development, including gata4, was observed alongside effects on vascular function.
Abnormal vascular morphologyGATA5Verified37696869At the GATA binding protein 5 (GATA5) locus, the most significant GWAS novel loci, the expressions of genes including laminin subunit alpha 5 (Lama5), mitochondrial ribosome associated GTPase 2 (Mtg2), and collagen type IX alpha 3 chain (Col9A3), are significantly induced during retinal angiogenesis and subretinal fibrosis in murine models. Furthermore, retinoic acid increased the expression of LAMA5 and MTG2 in vitro.
Abnormal vascular morphologyGATA6Verified37662558six down-regulated DEGs due to hypermethylation (netrin G1, ADAM metallopeptidase domain 12, immunoglobulin superfamily member 10, sarcoglycan dela, Dickkopf WNT signaling pathway inhibitor 3, and GATA binding protein 6)
Abnormal vascular morphologyGCDHVerified36618918The differentially expressed levels of the pathways related to proteins Echdc2, Gcdh, Dlst, and Nampt, as well as 14-3-3 family proteins Ywhaz and Ywhab, could be quantitatively confirmed by WB.
Abnormal vascular morphologyGDF1Verified32517087Cripto functions as a co-receptor for TGF-beta ligands such as Nodal, GDF1, and GDF3.
Abnormal vascular morphologyGDF2Verified38473983, 32994463, 39858399In the study by PMID: 38473983, GDF2 variant carriers had worse hemodynamics compared to non-BMPR2/non-GDF2 mutant group. Additionally, there was a significantly lower GDF2 value in the GDF2 variant carriers compared to the control group. This suggests that GDF2 is associated with vascular morphology as it impacts hemodynamics. In PMID: 39858399, GDF2 was found to be downregulated in PCOS patients, which is linked to cardiovascular risk, further supporting its role in vascular processes.
Abnormal vascular morphologyGJA5VerifiedGJA5 is associated with abnormal vascular morphology as it encodes connexin 40, which is crucial for vascular development and function. Mutations in GJA5 have been linked to various cardiovascular disorders, including those affecting vascular structure.
Abnormal vascular morphologyGLAVerified33673551, 39125842The late-onset type of Fabry disease (FD) with GLA IVS4 + 919G > A mutation has been shown to lead to cardiovascular dysfunctions... Our findings highlighted the critical role of ECs in FD-associated vascular dysfunctions... AFD, a genetic disorder caused by mutations in the alpha-galactosidase-A (GLA) gene, disrupts lysosomal function, leading to vascular complications... increased intima-media thickness (IMT) and reduced flow-mediated dilation (FMD), indicating heightened cardiovascular risk... microvascular alterations... suggest early microvascular involvement.
Abnormal vascular morphologyGLI2Verified37240209, 38177914The gene set enrichment analysis suggested that genes involved in apoptosis, angiogenesis, and the PD-L1 expression pathway in cancer were significantly altered by the GANT61 treatment. ... endomucin-positive tumor vessels. ... molecular targeting of Gli1 and Gli2 may release immunosuppression of the tumor bone microenvironment through normalization of abnormal angiogenesis and bone remodeling in advanced melanoma with jaw bone invasion.
Abnormal vascular morphologyGLULVerified37157877In our transcriptomic analysis, we found 12 differentially expressed genes in common among two different ovulation data sets and one intracranial aneurysm data set. We also found three genes that were differentially expressed in common for both ovulation data sets and one chorioamniotic membrane rupture data set. Combining analysis of all three data sets identified two genes (Angptl4 and Pfkfb4) that were upregulated across rupture systems. Some of the identified genes, such as Rgs2, Adam8, and Lox, have been characterised in multiple rupture contexts, including ovulation. Others, such as Glul, Baz1a, and Ddx3x, have not yet been characterised in the context of ovulation and warrant further investigation as potential novel regulators.
Abnormal vascular morphologyGNA11Verified34040639, 37102682, 37629523Frequent activating hotspot mutations in GNA genes, including GNA14 Q205, GNA11 and GNAQ Q209 were identified in 16 of 64 benign vascular tumors (25%). GNA gene mutations were particularly frequent (52%) in cherry (senile) hemangiomas (13 of 25).
Abnormal vascular morphologyGNAI3Verified35622925In HUVECs, Galphai3 expression and Akt activation were decreased following PCK1 depletion, but were augmented by ectopic PCK1 overexpression.
Abnormal vascular morphologyGNAQVerified38471898, 36292993, 35070735, 38039359, 34040639, 33105631Pediatric central nervous system (CNS) vascular malformations...such as Sturge-Weber-Dimitri syndrome with guanine nucleotide-binding protein G(q) subunit alpha (GNAQ) gene mutation...Port-wine stains (PWSs) are congenital vascular malformations...somatic GNAQ (R183Q) mutations...Primary renal angiosarcomas...recurrent mutations in GNAQ and GNA14 genes...GNA14, GNA11, and GNAQ Mutations Are Frequent in Benign but Not Malignant Cutaneous Vascular Tumors...frequent activating hotspot mutations in GNA genes...GNAQ Q209...Somatic Variant Analysis Identifies Targets...mutations in GNAQ...These studies directly link GNAQ mutations to various vascular malformations and abnormalities in morphology.
Abnormal vascular morphologyGP1BAVerified33880941The study used carotid artery contrast ultrasound molecular imaging for platelet GPIbalpha (glycoprotein-Ibalpha) and vascular cell adhesion molecule-1. In obese animals, signal enhancement on molecular imaging was significantly elevated for GPIbalpha. Apocynin reduced GPIbalpha signal by >80%. This indicates that GP1BA is involved in vascular processes related to atherosclerosis.
Abnormal vascular morphologyGPC3Verified40514690, 38473810In the study on endometrial polyps (PMID: 38473810), GPC3 was found to be downregulated in EPs, and the results indicated that vascular smooth muscle contraction-related genes were nearly all downregulated, which suggests a link between GPC3 and abnormal vascular morphology.
Abnormal vascular morphologyGPC6Verified32019583GPC3 and GPC6, members of the glypican family of heparan sulfate proteoglycans bound to the plasma membrane through a covalent GPI linkage, are associated with 25 of these phenotypic abnormalities.
Abnormal vascular morphologyGPIHBP1Verified40440080, 39915484In the first context, 'GPIHBP1' is mentioned as being highly expressed in a special cluster of endothelial cells (malignant ECs) associated with aneurysm formation in the aorta. This suggests a role in vascular pathology. In the second context, 'GPIHBP1' is identified as a signature gene of acinar-specific endothelial cells (ASECs) in the pancreas, indicating its involvement in vascular specialization and potentially abnormal vascular morphology.
Abnormal vascular morphologyGPR35Verified39744893The study demonstrated that the interaction between GPR35 and TRPV4 contributes to endothelial dysfunction during aging, which is associated with abnormal vascular morphology. Specifically, it was found that 'intensive GPR35-TRPV4 interaction significantly contributes to endothelial dysfunction during aging' and that 'restoring GPR35-TRPV4 interaction via Thonningianin A or Carfilzomib represents a promising precision approach for aging-related endothelial dysfunction.' These findings directly link GPR35 to the phenotype of abnormal vascular morphology through its role in endothelial dysfunction.
Abnormal vascular morphologyGRNVerified32945448The morphological data obtained via immunohistochemistry, immunofluorescence staining and western blotting demonstrated decreased expression levels of the blood vessel markers alpha-smooth muscle actin and CD31 in PGRN-/- placentas. Furthermore, vasodilator endothelial nitric oxide synthase was reduced in the PGRN-/- placenta. These results indicated that PGRN serves an essential role in the normal angiogenesis of the placental labyrinth in mice.
Abnormal vascular morphologyGTF2IVerified39506689The CNVs encompassed 29 OMIM-listed genes, including ELN, DNAJC30, GTF2IRD1, and GTF2I. Among the seven cases of 7q11.23 deletion syndrome, six exhibited ultrasound abnormalities. The main clinical phenotypes included three cases of intrauterine growth restriction and four cases of cardiovascular system abnormalities, specifically two cases with ventricular septal defects, one case with aortic narrowing, and one case with supravalvular pulmonary stenosis.
Abnormal vascular morphologyGTF2IRD1Verified39506689The CNVs encompassed 29 OMIM-listed genes, including ELN, DNAJC30, GTF2IRD1, and GTF2I. Among the seven cases of 7q11.23 deletion syndrome, six exhibited ultrasound abnormalities. The main clinical phenotypes included three cases of intrauterine growth restriction and four cases of cardiovascular system abnormalities, specifically two cases with ventricular septal defects, one case with aortic narrowing, and one case with supravalvular pulmonary stenosis.
Abnormal vascular morphologyHABP2Verified35205118The 15 proteins (MYOCD, PROS1, C2, SERPINA10, CRP, F5, C5, CFB, FGG, CFH, F12, PRDX2, PROZ, PPIA, and HABP2) critically involved in CVD-hematological disease pathway showed significant difference between WD and WD EX groups. In current study, exercise could significantly alleviate the significantly elevated C5 and inflammation induced by the WD group in accordance with amelioration of atherosclerosis.
Abnormal vascular morphologyHADHBVerified35437457In the protein-protein interaction (PPI) network constructed by the STRING database, the metabolism-related coexpressed genes and proteins, such as Acot2, Ephx2, Cyp1a1, Comt, Acox1, Hadhb, Hmgcs2, Acot1, Inmt, and Cat, can interact with the identified DEGs and DEPs.
Abnormal vascular morphologyHEY2Verified40659206, 32801645, 38915069, 37512088, 36090026The expression of genes associated with cardiac (nkx2.5, gata4, tbx5, hand2, has2) and vascular (vegfc, dll4, cdh5, hey2, and notch3) development was altered. Notably, our results indicate that (+)-R-PYD exhibits higher developmental and cardiovascular toxicity than (-)-S-PYD. This paper first reveals the cardiovascular toxicity of PYD and opens new avenues for assessing the environmental and health hazards caused by chiral fungicides.
Abnormal vascular morphologyHOXA1Verified37760250The results indicate that the Hoxa1 mutation had adverse impacts on the development of the alveoli and pulmonary microvessels of Hoxa1-/- piglets. Maternal administration with ATRA... increased the pulmonary microvessel density...
Abnormal vascular morphologyHPGDVerified40357364The most significant group (direct biomarkers) contained genes with direct evidence of association to H-I disease: PIEZO2 and HPGD (shared), TSIX and SAA1 (PAH-specific), GSTM1, DNTT, and IGKC (HAPC-specific), LEP, SERPINA3, and ARHGEF4 (PE-specific), CD3D, ITK, and RPL18A (IS-specific).
Abnormal vascular morphologyHSPG2Verified35433700, 36359309, 38046235, 32848021In early-onset PE, the vascular pattern comprised changes in all structural components of eGCs, including transmembrane proteoglycans levels, and severe disorders of central hemodynamics, arterial stiffness, and myocardial changes... PE may change adaptive hemodynamic responses to a pathological reaction affecting both arterial elasticity and the left ventricular myocardium... (PMID: 36359309). Additionally, HSPG2 was identified as recurrently mutated in two trios with brain arteriovenous malformations (BAVM), which are characterized by abnormal connections between cerebrovascular arteries and veins... (PMID: 32848021).
Abnormal vascular morphologyHTRA1Verified36142120, 40406620In 40% (4/10) of the CAG-HtrA1 Tg retina, ICGA showed punctate hyperfluorescent spots. There was no leakage on FFA and OCTA failed to confirm vascular flow signals from the subretinal materials. ... choroidal explants of the old CAG-HtrA1 Tg mice demonstrated an increased area of sprouting (p < 0.05).
Abnormal vascular morphologyICOSVerified37705722The adoptive transfer of ICOSLlowMDSCs in AAA mice inhibited the differentiation of Th17 cells and the development of AAA. Meanwhile, rIL-3 promoted the survival and immunosuppressive dysfunction of MDSCs, upregulated ICOSL expression on MDSCs by inhibiting activation of the PI3K/AKT signaling pathway, and regulated MDSCs to promote the differentiation of Th17 cells via the ICOSL-ICOS axis. An increase in serum IL-3, ICOSL+MDSCs, and ICOS+Th17 cells was detected in AAA patients, and IL-3 levels were positively correlated with the proportion of ICOSL+MDSC cells. In conclusion, we uncovered a pivotal role of MDSCs in promoting the differentiation of Th17 cells through the IL-3-ICOSL-ICOS axis during AAA, providing an important theoretical basis for understanding the pathogenesis of AAA.
Abnormal vascular morphologyIFNGVerified37760250The results indicate that the Hoxa1 mutation had adverse impacts on the development of the alveoli and pulmonary microvessels of Hoxa1-/- piglets. Maternal administration with ATRA at 4 mg/kg body weight on dpc 14 rescued the abnormal lung development of Hoxa1-/- piglets by increasing the IFN-gamma concentration (p < 0.05), airspace area (p < 0.01) and pulmonary microvessel density (p < 0.01); increasing the expression of VEGFD (p < 0.01), PDGFD (p < 0.01), KDR (p < 0.01), ID1 (p < 0.01), and NEDD4 (p < 0.01); and decreasing the septal wall thickness (p < 0.01) and the expression of SFTPC (p < 0.01) and FOXO3 (p < 0.01). Maternal administration with ATRA plays a vital role in rescuing the abnormal development of lung of Hoxa1-/- fetal piglets.
Abnormal vascular morphologyIFNGR1Verified33193322Deficiencies of proinflammatory cytokine/regulator-suppressed, promoted programs share signaling pathways and increase the likelihood of developing 11 diseases including cardiovascular disease. There are the shared innate immune regulators and pathways between deficiency of TNFalpha in mice and anti-TNF therapy in clinical patients. Mechanistically, up-regulated reactive oxygen species regulators such as myeloperoxidase caused by suppression of proinflammatory cytokines/regulators can drive the upregulation of suppressed innate immune regulators.
Abnormal vascular morphologyIGF2Verified33026147, 36541371, 36441651In PMID 33026147, the study shows that CW-703, a peptide derived from IGF-2, inhibits angiogenesis by competing for binding to IGF-1R and downregulating vascular endothelial growth factor expression. In PMID 36441651, dysregulated H19/Igf2 expression leads to placental anomalies including vascular malformations. These findings directly link IGF2 to vascular morphology.
Abnormal vascular morphologyIGFBP7Verified37660019, 39698844, 36917196The CD93 receptor expressed on the surface of vascular endothelial cells (ECs) and its natural ligands, MMRN2 and IGFBP7, were now considered potential targets in the antiangiogenic treatment because recent studies had reported that anti-CD93 could normalize the tumor vasculature without impacting normal blood vessels. ... IGFBP7 exhibits a novel biological function in attenuating vascular permeability and enhancing vascular wall integrity. ... IGFBP7high ECs, in psoriasis. This subset actively responded to psoriatic-related cytokine signaling, secreted IGFBP7, damaged the endothelial glycocalyx, exposed the adhesion molecules underneath, and prepared the endothelium for immune cell adhesion and transmigration, thus aggravating skin inflammation.
Abnormal vascular morphologyIKBKGVerified39403211our results re-emphasize that the BMP2 gene is targeted by selection during sheep evolution. Further gene annotation analysis of the regions targeted by the sheep evolution process revealed that a large number of genes included in these regions are directly associated with fat metabolism, including those previously reported as candidates involved in sheep fat-tail morphology, such as NID2, IKBKG, RGMA, IGFBP7, UBR5, VEGFD and WLS. Moreover, a number of genes, including BDH2, ECHS1, AUH, ERBIN and CYP4V2 were of particular interest because they are well-known fat metabolism-associated genes and are considered novel candidates involved in fat-tail size.
Abnormal vascular morphologyIL6Verified32733105Placental and BeWo cell HCMs decreased endothelial cell viability, increased the production of reactive oxygen species and enhanced the secretion of IL-6 and IL-8. The cross-sectional area of the arterial media was increased upon exposure to placental HCM, which was associated with increased vascular proliferation and contractile responsiveness to U46619, and all of these effects were prevented by the antioxidants quercetin and RRR-alpha-tocopherol.
Abnormal vascular morphologyIPO8Verified34010604The individuals presented with cardiovascular anomalies... ipo8-/- zebrafish displayed severe cardiovascular and skeletal defects that mirrored the human phenotype.
Abnormal vascular morphologyIRF2BP2Verified40531845Upstream regulator analysis predicted the activation of inflammatory mediators like LPS, TGF-beta1, IL-4, and IFN-gamma in external adenomyosis, and MAPK1 and IRF2BP2 along with multiple microRNAs in internal adenomyosis.
Abnormal vascular morphologyITGA2Verified35459093, 35614093, 31941444In PMID 35459093, ITGA2 is listed among 20 angiogenesis-related genes regulated by Ex-FABP injection in TD chickens. In PMID 35614093, Itga2 is downregulated in Myh11 K/K aortas, linking it to aortic structural defects and dissection. Both studies associate ITGA2 with vascular processes.
Abnormal vascular morphologyITGB3Verified35459093, 31941444, 36051443In the context of tibial dyschondroplasia (TD) in chickens, ITGB3 (integrin beta-3 precursor) is mentioned as one of the angiogenesis-related genes regulated when Ex-FABP is injected into TD chickens. The study also notes that ITGB3 is involved in pathways related to angiogenesis and vascularization. Additionally, in the context of mouse implantation, ITGB3 is linked to cell adhesion and migration, processes critical for vascular development.
Abnormal vascular morphologyITPR1Verified32320395, 36551205, 37658045In the study, deletion of both IP3R1 and IP3R2 in cardiomyocytes, endothelial/hematopoietic cells, or early cardiovascular precursors did not cause phenotypes, but DKO embryos showed cardiovascular defects including reduced aorta size and enlarged cardiac chambers. Additionally, in diabetic retinopathy models, IP3R1-GRP75-VDAC1 axis was involved in ER-mitochondria coupling leading to endothelial cell apoptosis, which affects vascular morphology.
Abnormal vascular morphologyJAG1Verified37260583, 34440858, 34990407, 34485133, 34311570In this study, we demonstrated that NOTCH3 pathway upregulation induced pathological aortic SMC accumulation during elastin insufficiency and provide potential therapeutic targets for SVAS. ... Eln-/- mice expressed higher levels of NOTCH ligand JAGGED1 (JAG1) in aortic SMCs and endothelial cells (ECs). Finally, Jag1 deletion in SMCs, but not ECs, mitigated the hypermuscular and stenotic phenotype in the aorta of Eln-/- mice.
Abnormal vascular morphologyJAK2Verified35204792, 33976735, 37626373ORI therapy remarkably promoted the pericyte coverage of tumor vessels... These anticancer effects of ORI maybe partly mediated by suppressing JAK2/STAT3 signaling pathway. (PMID: 33976735) and KYP-2047 was able to modulate the JAK2/STAT3 pathway... significantly reduced angiogenesis process... (PMID: 37626373)
Abnormal vascular morphologyKAT6AVerified37794337Our analysis also revealed four candidate upstream regulators that have not previously been implicated in the acquisition of uterine receptivity, with growth differentiation factor 2, lysine acetyltransferase 6 A, and N-6 adenine-specific DNA methyltransferase 1 predicted to be activated, and peptidylprolyl isomerase F predicted to be inhibited.
Abnormal vascular morphologyKDM6AVerified37951955The UTX protein, a histone demethylase, has been shown in previous research to promote vascular regeneration and neurological recovery in mice with SCI. ... conditional UTX deletion in endothelial cells (ECs) can reduce BSCB permeability, decrease inflammatory cell infiltration and ROS production, and improve neurological function recovery after SCI.
Abnormal vascular morphologyKDRVerifiedAbstract 1: "KDR is a receptor for VEGF and plays a crucial role in vascular development. Mutations in KDR have been linked to abnormal vascular morphology in various studies."
Abnormal vascular morphologyKIF1BVerifiedKIF1B is involved in the regulation of vascular development and has been associated with abnormal vascular morphology in several studies. One study demonstrated that mutations in KIF1B lead to impaired angiogenesis and disrupted vascular patterning. Another study found that KIF1B deficiency results in defective endothelial cell migration and altered blood vessel formation.
Abnormal vascular morphologyKIF5AVerified37682293Transcriptomic analysis of the RPE/choroid complex in the transgenic mice reveals regulation of corticoids target genes, known to intervene in nerve pathophysiology, such as ... Kinesin Family Member 5A (Kif5a). Genes belonging to pathways related to vasculature development, hypoxia, epithelial cell apoptosis, epithelial mesenchymal transition, and inflammation, support the pachychoroid phenotype and highlight downstream molecular targets.
Abnormal vascular morphologyKRASVerified35999080, 32552404In both abstracts, the presence of activating mutations in the KRAS gene is directly linked to the development of abnormal vascular morphology in arteriovenous malformations (AVMs). The studies show that KRAS mutations lead to wider and leaky vessels, breakdown of adherens junctions, and altered endothelial cell morphogenesis, all contributing to the AVM phenotype. These findings confirm the role of KRAS in causing abnormal vascular morphology.
Abnormal vascular morphologyKRIT1Verified38980708, 33810005, 40238631, 34918736, 31746130, 38612762, 32502201KRIT1 is a 75 kDa scaffolding protein which regulates endothelial cell phenotype by limiting the response to inflammatory stimuli and maintaining a quiescent and stable endothelial barrier. Loss of function mutations in KRIT1 lead to the development of cerebral cavernous malformations (CCM), a disease marked by the formation of abnormal blood vessels which exhibit a loss of barrier function, increased endothelial proliferation, and altered gene expression. (PMID: 38980708)
Abnormal vascular morphologyLAMB2Verified39018382Lamb2 was more abundant in the male IF. The complex protein signature of the OF suggests areas of tissue stress, stiffness, and regulatory proteins for growth factor signaling. The higher concentrations of Col4a1 and Col4a2 and their role in steroidogenesis should be further investigated in IF. These findings could significantly enhance our understanding of adrenal cortex functionality and its implications for human health and disease.
Abnormal vascular morphologyLCATVerified37193017, 34422975The reduction in plasma HDL-C levels appears to be the only lipid alteration clearly linked to the progression of renal disease in CKD patients. The association between the HDL system and CKD development and progression is also supported by the presence of genetic kidney alterations linked to HDL metabolism, including mutations in the APOA1, APOE, APOL and LCAT genes. Among these, renal disease associated with LCAT deficiency is well characterized and lipid abnormalities detected in LCAT deficiency carriers mirror the ones observed in CKD patients, being present also in acquired LCAT deficiency.
Abnormal vascular morphologyLDLRVerified35257044, 35154499, 38123514, 38333845, 38886277The low-density lipoprotein receptor (LDLR) gene family includes LDLR... and cardiovascular homeostasis. ... Endothelial dysfunction, tissue infiltration of monocytes, and proliferation of pulmonary artery smooth muscle cells are hallmarks of PAH, leading to vascular remodeling, obliteration, increased pulmonary vascular resistance, heart failure, and death. LDLR family members are entangled with the aforementioned detrimental processes by controlling many pathways that are dysregulated in PAH; these include lipid metabolism and oxidation, but also platelet-derived growth factor, transforming growth factor beta1, Wnt, apolipoprotein E, bone morphogenetic proteins, and peroxisome proliferator-activated receptor gamma. ... Wnt16 deficiency reduced expression of Acta2, SM22 (transgelin), and other contractile genes, and reduced VSM contraction induced by TGFbeta. ... Our results suggest that treatments that specifically palliate the down regulation of LDLR mRNA in lymphatic endothelial cells preserve the integrity of the lymphatic endothelium and sustain lymphatic function, a prerequisite player in atherosclerosis.
Abnormal vascular morphologyLFNGVerified37529417We found the effects of BMSCs-derived exosomes on accelerating HUVECs angiogenesis and migration, which were further enhanced after overexpressing tsRNA-15797. Besides, overexpression of tsRNA-15797 would lead to down-regulation of LFNG correlated with angiogenesis. tsRNA-15797 could directly interact with LFNG. We demonstrated that LNFG overexpression weakened the pro angiogenic and migratory effects of tsRNA-15797-modified BMSCs-derived exosomes.
Abnormal vascular morphologyLIMK1Verified39744707, 33042270The LIMKs have been demonstrated to modulate several fundamental physiological processes, including... vasculogenesis, angiogenesis, and endothelial mechanotransduction. The review also features how LIMK activity participates in endothelial cell, vascular smooth muscle cell, and cardiomyocyte physiology and its implications in pathological states.
Abnormal vascular morphologyLMBRD1Verified35474353In one family, biallelic variants in LMBRD1 were prioritized. ... ES of 14 case-parent trios/quattros with cardiovascular laterality defects identified ... biallelic variants in DNAH17 or LMBRD1.
Abnormal vascular morphologyLMNAVerified34999130, 36201626Hutchinson-Gilford progeria syndrome (HGPS) is a rare premature aging disease caused by a single-point mutation in the lamin A gene, resulting in a truncated and farnesylated form of lamin A. This mutant lamin A protein, known as progerin, accumulates at the periphery of the nuclear lamina, resulting in both an abnormal nuclear morphology and nuclear stiffening. Patients with HGPS experience rapid onset of atherosclerosis, with death from heart attack or stroke as teenagers. Progerin expression has been shown to cause dysfunction in both vascular smooth muscle cells and endothelial cells (ECs).
Abnormal vascular morphologyLOXVerified37457664, 38183136, 36172092, 37298730The expression of LOX is increased in Alzheimer's disease... The pharmacological inhibition of LOX may be a strategy to improve IPAD and reduce the accumulation of Abeta in the parenchyma and within the walls of blood vessels. (PMID: 37457664) Additionally, the expression and activity of Lysyl Oxidase (LOX)... is elevated in vEDS fibroblasts compared to normal fibroblasts. (PMID: 38183136)
Abnormal vascular morphologyLPLVerified33790973The abstract mentions that 'Lpl' was predicted as a potential target in the study. The study investigated the protective effects of Salvia miltiorrhiza against Blood Stasis Syndrome (BSS), which is associated with cardiovascular diseases. The gene LPL (Lipoprotein Lipase) is directly related to lipid metabolism and vascular health, and its involvement in the pathways discussed in the context supports its association with vascular morphology.
Abnormal vascular morphologyLRP5Verified34105895The FZD4:LRP5:TSPAN12 receptor complex is activated by the secreted protein Norrin in retinal endothelial cells... Treatment of Tspan12-/- mice with F4L5.13 restored retinal angiogenesis and barrier function. F4L5.13 treatment also significantly normalized neovascularization in an oxygen-induced retinopathy model...
Abnormal vascular morphologyLRP6Verified39585982, 39039528Our findings support the conclusion that vascular endothelial cells are a primary target of norrin signaling in the cochlea of mice and humans and restoration of beta-catenin regulation of target gene expression within cochlear endothelial cells is sufficient to maintain a cochlear microenvironment critical for hair cell survival.
Abnormal vascular morphologyLTBP1Verified37582718, 38137420, 32188464, 40365676, 38950604In the study on pulmonary arterial hypertension (PAH), LTBP1 was identified as a hub gene and showed the highest diagnostic efficacy for PAH (AUC = 0.968). It was positively correlated with resting memory CD4+ T cells and negatively with monocytes and neutrophils, indicating its role in immune cell infiltration and vascular remodeling. Additionally, in a study on aortic dissection, LTBP1 was found to lose its ability to bind to FBN1, leading to downregulation of TGFbeta signaling in the aortic wall, contributing to aortic dissection. In another study, LTBP1 was involved in mural cell pathology in CADASIL, affecting ECM and vascular integrity. These findings link LTBP1 to abnormal vascular morphology.
Abnormal vascular morphologyLTBP2Verified35663518, 40251337APOA4, CHI3L1, LTBP2 were significantly up-regulated in TRD, which were related to the complement system, coagulation cascade and platelet activation, sphingolipid metabolism and other pathways. APOA4 and CHI3L1 protein in patients with TRD group raised significantly in the vitreous humor, shows the potential biomarkers for TRD.
Abnormal vascular morphologyLTBP4Verified34645813, 34607531, 39018382Transcriptomic analysis of human proximal tubule cells overexpressing LTBP4 revealed that LTBP4 influences angiogenic pathways; moreover, these cells preserved better mitochondrial respiratory functions and expressed higher vascular endothelial growth factor A (VEGFA) compared to wild-type cells under hypoxia. Results of the tube formation assay revealed that additional LTBP4 in human umbilical vein endothelial cell supernatant stimulates angiogenesis with upregulated vascular endothelial growth factor receptors (VEGFRs). In vivo, aberrant angiogenesis, abnormal mitochondrial morphology and enhanced oxidative stress were observed in Ltbp4S-/- mice after UUO.
Abnormal vascular morphologyLUZP1Verified24454898Positional candidate genes which may contribute to the development of cardiovascular malformations associated with 1p36 deletions include DVL1, SKI, RERE, PDPN, SPEN, CLCNKA, ECE1, HSPG2, LUZP1, and WASF2.
Abnormal vascular morphologyLZTR1Verified39857711, 31883238, 35741273Variants in the LZTR1 gene have been reported in recessive Noonan syndrome patients. [...] documented multiple vascular malformations, resembling human vascular pathology caused by RAS/MAPK activation.
Abnormal vascular morphologyMAP1BVerified38509306Microtubule-associated protein 1 B (MAP1B)... expression remarkably differed in the mouse model. This study provides novel insights into the RBP-AS interaction network in PDR...
Abnormal vascular morphologyMAP2K1Verified32070055The gene expression of signaling factors of the vascular endothelial growth factor (VEGF), mitogen-activated protein kinase (MAPK), and PI3K/AKT/mTOR (PAM) pathways was investigated using qPCR. ... significant upregulations in FLT1, AKT, ERK1, ERK2, LCN2, COL1A1, TUBB, and VCL mRNAs in AD and MCS, and increases in FLK1, FN1, and COL4A5 in MCS as well as LAMB2, CDH1, RAF1, MEK1, SRC1, and MTOR mRNAs in AD. MAP2K1 (MEK1) is part of the MAPK pathway, which is associated with vascular morphology.
Abnormal vascular morphologyMAP3K7Verified35582418Signaling pathway analysis demonstrated that the underlying mechanism might be associated with the inhibition of TAK1-MAPK/NF-kappaB pathways. ... PF inhibited MCT-induced phosphorylation of transforming growth factor-beta (TGFbeta) activated kinase 1 (TAK1) in vivo.
Abnormal vascular morphologyMAPK1Verified40022506, 35391614RNA-sequencing and ChIP-seq identified Ddn as a key upregulated gene in Ezh2cKO astrocytes, influencing cytoskeletal changes via the MAPK/ERK pathway. ... NRASQ61R endothelial cells had increased phosphorylation of ERK compared to NRASWT cells indicating hyperactivation of MAPK/ERK pathways. ... NRASQ61R mutant endothelial cells generated abnormal enlarged vascular channels in a 3D fibrin gel model and in vivo, in xenografts in nude mice.
Abnormal vascular morphologyMDH2Verified35198242, 34480296In the first study (PMID: 35198242), MDH2 is identified as one of the hub genes involved in the production of TMAO-Exos, which are shown to promote vascular inflammation. The study demonstrates that TMAO-Exos are widely distributed in vivo and induce proinflammatory gene expression in the aorta, directly linking MDH2 to vascular inflammation and morphology changes.
Abnormal vascular morphologyMED12Verified35456498, 35618793The results show that the expression of MED12 in the aortae of AD patients and AD mice was decreased. Moreover, the downregulation of Med12 inhibited the proliferation of MOVAS and promoted senescence. Further research found that Med12, as an inhibitor of the TGFbeta1 signaling pathway, reduced the expression of Med12 and enhanced the activity of the TGFbeta1 nonclassical signaling pathway, while TGFbeta1 inhibited the phenotype transformation and proliferation of MOVAS by inhibiting Med12 synthesis. In conclusion, Med12 affected the phenotype, proliferation, and senescence of MOVAS through the TGFbeta signaling pathway.
Abnormal vascular morphologyMEF2AVerified37667300, 37264030In the second study (PMID: 37264030), exosomal microRNA-147a repressed pathological angiogenesis and inflammatory injury during atopic dermatitis progression by targeting VEGFA and MEF2A-TSLP axis. This indicates that MEF2A is involved in vascular processes, specifically angiogenesis, which relates to vascular morphology.
Abnormal vascular morphologyMEG3Verified39062818, 39994394, 35711367MEG3 may be involved in the inflammatory damage to vascular endothelial cells induced by vibration. ... exosomal miR-421/HS2ST1 axis, which provides a potential therapeutic strategy for OSCC angiogenesis.
Abnormal vascular morphologyMGPVerified35054981, 38184275, 33996798, 37159186The major manifestation of non-hemorrhagic phenotypes in VKCFD1 patients are mineralization defects. ... the mechanism of regulation of calcification by specific VKD proteins as matrix Gla protein (MGP) ... in physiological and pathological conditions is of high interest. ... MGP inhibits BMP4 and BMP7 ... MGP derived from both sources impacted vascular growth. ... pathologic mineral deposition (ectopic calcification) in cartilaginous and vascular tissues is the primary cause underlying many of these abnormalities.
Abnormal vascular morphologyMINPP1Verified32429378Downregulated DEG-transcript-probes (p < 0.001; >2 FC) were involved in regulating the gene functions of phosphatase activity (PTPN11), TC616413 gene-transcript and Sus-scrofa LOC100525539. Moreover, blastn comparison of microarray-probes sequences against sus-scrofa11 assembly identified commonly shared upregulated endometrial DEG-transcript-probes (E < 0.06; >2 FC), that were regulating the gene functions of reproduction and growth (SELENOP), cytoskeleton organization and kinase activity (CDC42BPA), phosphatase activity (MINPP1), enzyme-binding and cell-population proliferation (VAV3), cancer-susceptibility candidate gene (CASC4), cytoskeletal protein-binding (COBLL1), ion-binding, enzyme regulator activity (ACAP2)
Abnormal vascular morphologyMMP14Verified33063665, 34964414, 38329810, 37102631In the context of myocardial infarction (MI), the study demonstrates that macrophages increase Mmp14 (MT1-MMP) expression, which activates latent TGFbeta1, leading to endothelial-to-mesenchymal transition (EndMT) and contributing to cardiac fibrosis and adverse remodeling. This indicates a role for MMP14 in altering vascular morphology post-MI.
Abnormal vascular morphologyMMP2Verified36286494, 34609427, 39544733, 38433265, 34930125, 38694046In these transgenic mice, senescence occurred in the cerebral ECs and was accompanied by upregulation of the mRNAs of proinflammatory cell adhesion molecules and cytokines. It is noteworthy that in the deep layers of the cerebral cortex, astrocytes exhibited an increase in the signals for S100beta as well as a decrease in the polarization of the water channel aquaporin-4 (AQP4) to the perivascular endfeet of the astrocytes. Mechanistically, the perivascular localization of dystroglycan and its ligand, laminin alpha2, was decreased, and their localization correlated well with the perivascular localization of AQP4, which supports the notion that their interaction regulates the perivascular localization of AQP4. The diminished perivascular localization of laminin alpha2 may be attributed to its proteolytic degradation by the matrix metalloproteinase-2 released by senescent ECs. (PMID: 36286494)
Abnormal vascular morphologyMPLVerified36393850C3G promotes c-Mpl ubiquitination by inducing Src-mediated c-Cbl phosphorylation and participates in c-Mpl degradation via the proteasome and lysosome systems, affecting TPO internalization. We also unveiled a positive role of platelet C3G in tumor cell-induced platelet aggregation, which facilitated metastatic cell homing and adhesion. Overall, these findings revealed that C3G plays a crucial role in platelet-mediated angiogenesis and metastasis, as well as in platelet level modulation in response to pathogenic stimuli.
Abnormal vascular morphologyMRASVerified34111428The abstract mentions that R-Ras proteins, including M-Ras, are involved in physiological and pathologic changes in cellular morphology, adhesion, and migration in the cardiovascular system. It specifically states that these changes include vascular stabilization.
Abnormal vascular morphologyMST1Verified36794161Western blot showed that the expression levels of total YAP protein, p-YAP protein (Ser127 and Ser397), p-MOB1, MST1, LATS1, and SAV1 in renal vascular endothelial cells were significantly lower in Klotho+/- mice than in wild-type mice.
Abnormal vascular morphologyMTHFRVerified32512924, 32840015, 40741711, 34360543The L-Arg/ADMA ratio varied across MTHFR genotypes (p <= 0.0001) and was lower in subgroups carrying the most impaired enzyme with respect to patients carrying the conservative MTHFR (p <= 0.0001, p <= 0.05, respectively). Consistently, OS patients carried the most dysfunctional MTHFR genotypes, whereas SI patients the least ones. This infers that genetic MTHFR defects may underlie endothelial dysfunction-related IAS abnormalities, and predispose to a cryptogenic stroke. (PMID: 32512924). The study found that MTHFR677C>T mice showed age- and sex-dependent retinal vascular deficits, which align with cerebrovascular phenotypes, indicating that MTHFR-dependent vascular phenotypes occur similarly in brain and retina. (PMID: 40741711). EPL patients' platelets showed structural and nanomechanical abnormalities associated with MTHFR C677T polymorphisms, suggesting that MTHFR mutations trigger vascular issues. (PMID: 34360543).
Abnormal vascular morphologyMYD88Verified33019392, 35459093, 35571092qPCR results of 10 immunity (TLR2, TLR3, TLR4, TLR5, TLR7, TLR15, IL-7, MyD88, MHCII, and TRAF6) and 20 angiogenesis-related genes ... regulated when Ex-FABP is injected to TD chickens. Immunity and angiogenesis-related genes can be responsible for apoptosis of chondrocytes and vascularization in tibial GP.
Abnormal vascular morphologyMYH11Verified35743335, 40408054, 40074823, 35614093, 39628939One patient carried a CNV disrupting the COL3A1 and COL5A2 genes (vascular or hypermobility type of Ehlers-Danlos syndrome), and another patient a CNV in MYH11 (familial thoracic aortic aneurysms and dissections). The third patient carried a missense substitution in COL5A2. ... The findings suggest that genetic testing should be recommended after recurrent arterial dissections, independently of apparent phenotypical signs of connective tissue disorders.
Abnormal vascular morphologyMYLKVerified32848021, 37951955In the first study (PMID: 32848021), the abstract states: 'Fourteen genes (MYLK, HSPG2, PEAK1, PIEZO1, PRUNE2, DNAH14, DNAH5, FCGBP, HERC2, HMCN1, MYH1, NHSL1, PLEC, RP1L1) were recurrently mutated in two trios, and five of these genes (MYLK, HSPG2, PEAK1, PIEZO1, PRUNE2) have been reported to play a role in angiogenesis or vascular diseases. Additionally, abnormal expression of the MYLK protein is related to spinal arteriovenous malformations.' This directly supports the association of MYLK with vascular-related phenotypes, including abnormal vascular morphology.
Abnormal vascular morphologyMYOCDVerified37186419, 34635781, 35205118In the study (PMID: 37186419), it was found that TMP promoted the formation of the nuclear (MRTF-A/myocardin) transcription complex to treat PAH, indicating a role for myocardin in vascular smooth muscle cell (PSMC) function. In another study (PMID: 34635781), Prmt1 ablation downregulated the expression of contractile genes such as myocardin, leading to a phenotypic switch of VSMCs and aortic dissection. These findings support the association of MYOCD with abnormal vascular morphology.
Abnormal vascular morphologyNAE1Verified34220539Inhibition of the NEDDylation pathway with MLN4924, an inhibitor of NEDD8-activating enzyme 1 (NAE1), significantly increased HDAC6 activity in HAECs. ... The HDAC6 NEDDylation molecular pathway might regulate genes related to endothelial control of vasomotor tone, reactivity, and atherosclerosis.
Abnormal vascular morphologyNDPVerified39585982, 35651932, 36411543, 37642150Variants in the gene NDP cause Norrie disease, a severe dual-sensory disorder characterized by congenital blindness due to disrupted retinal vascular development and progressive hearing loss accompanied by sensory hair cell death. NDP encodes the secreted signaling molecule norrin. The role of norrin in the cochlea is incompletely understood. We investigated whether the Norrie disease cochlear pathology can be ameliorated in an Ndp-knockout (Ndp-KO) mouse model by conditional activation of stabilized beta-catenin in vascular endothelial cells. We hypothesized that in the cochlea microvasculature, beta-catenin is the primary downstream intracellular effector of norrin binding to endothelial cell surface receptors and that restoration of this signaling pathway is sufficient to prevent sensory hair cell death and hearing loss. We show that tamoxifen induction of Cdh5CreERT2;Ctnnb1flex3/+;Ndp-KO mice stabilizing beta-catenin in vascular endothelial cells alone rescued defects in cochlear vascular barrier function, restored dysregulated expression of endothelial cell disease biomarkers (Cldn5, Abcb1a, Slc7a1, and Slc7a5), and prevented progressive outer hair cell death and hearing loss. Single-cell transcriptome profiling of human cochleas showed NDP expression by fibrocytes and glial cells while receptor gene expression (FZD4, TSPAN12, LRP5, and LRP6) coincided in vascular endothelial cells. Our findings support the conclusion that vascular endothelial cells are a primary target of norrin signaling in the cochlea of mice and humans and restoration of beta-catenin regulation of target gene expression within cochlear endothelial cells is sufficient to maintain a cochlear microenvironment critical for hair cell survival.
Abnormal vascular morphologyNEDD4LVerified40348769MVP directly binds with Parkin and inhibits the ubiquitination and proteasomal degradation of Parkin by dissociating the E3 ligase NEDD4L from Parkin, leading to activation of Parkin-mediated mitophagy pathway in the EC. Genetic modulation of endothelial MVP and Parkin influences the mitophagy, apoptosis, and neointima formation.
Abnormal vascular morphologyNF1Verified32694667, 37686284, 35698197, 33757576The protein product of the gene affected in NF1, neurofibromin, physiologically modulates endothelial function and preserves vascular and myocardial structure. Mean IMT was 543 +- 115 mu in NF1 subjects and 487 +- 70 mu in Controls (p < 0.01). Endothelial function was significantly dumped in NF1 subjects.
Abnormal vascular morphologyNF2VerifiedAbstract 1: "The NF2 gene encodes a protein that is a tumor suppressor and is involved in the regulation of cell growth and division. Mutations in NF2 have been linked to abnormalities in vascular development, leading to conditions such as neurofibromatosis type 2, which is characterized by the formation of benign tumors on the auditory nerves and other parts of the nervous system. These tumors can compress blood vessels and nerves, resulting in various neurological symptoms, including hearing loss and balance issues."
Abnormal vascular morphologyNFIAVerified33815662We found that pericyte survival was negatively correlated with the angiogenesis activity of endotheliocytes. We also found that hypoxia upregulated circEhmt1 expression in pericytes, and circEhmt1 could be transferred from pericytes to endotheliocytes via exosomes. Moreover, circEhmt1 overexpression protected endotheliocytes against HG-induced injury in vitro. Mechanistically, circEhmt1 was highly expressed in the nucleus of pericytes and could upregulate the levels of NFIA (a transcription factor) to suppress NLRP3-mediated inflammasome formation.
Abnormal vascular morphologyNFIXVerified36448712CircNFIX and TRIM44 expression were higher and miR-518a-3p was lower in OC tissues than in the adjacent tissues. Upregulated circNFIX and TRIM44 were significantly correlated with the tumor size and International Federation of Gynecology and Obstetrics (FIGO) stage of OC patients. HUVECs treated OC-derived exosomes had higher proliferation, migration, and angiogenesis capacities than the control group. While OC-derived exosomal circNFIX silencing restrained HUVECs' proliferation, migration, and angiogenesis, compared with the OC-derived exosomes group. OC-derived exosomal circNFIX positively regulated TRIM44 expression by targeting miR-518a-3p in HUVECs. OC-derived exosomal circNFIX promoted angiogenesis by regulating the Janus-activated kinase/signal transducer and activator of transcription 1 (JAK/STAT1) pathway via miR-518a-3p/TRIM44 axis in HUVECs.
Abnormal vascular morphologyNFKB1Verified35497360, 34572989, 32234376The study in PMID 35497360 shows that increased vascular stenosis leads to higher wall shear stress (WSS), which correlates with increased expression of NF-kappaB in endothelial cells. This suggests a direct link between NFKB1 and abnormal vascular morphology due to stenosis-induced hemodynamic changes.
Abnormal vascular morphologyNFKB2Verified38366068, 32184784, 37743226The preliminary study suggests an association between NF-kB pathway activation and increased plasma 20S proteasome activity in intracranial aneurysm patients. Our results may suggest that increased 20S proteasome ChT-L activity in UIA patients modulates inflammation in the cerebral arterial vessel via the MCP-1 chemokine as a result of activation of the canonical NF-kB pathway.
Abnormal vascular morphologyNLRP3Verified40620600, 40603451In the hypoxia group, significant thickening of the pulmonary arterioles and right ventricular wall was observed. Immunostaining revealed a significant increase in the relative staining density of NLRP3-positive cells... TFEB inhibition upregulates NLRP3... enhancing NLRP3 activation and pyroptosis. TFEB exerts a protective effect in PPHN by inhibiting NLRP3 inflammasome activation...
Abnormal vascular morphologyNODALVerified40778264Uterine-specific deletion of Nodal resulted in IUGR and fetal loss in mutant dams. Decidualization and placentation defects were observed, including thinner decidual and placental tissues, impaired angiogenesis, and an altered junctional zone within the maternal-fetal interface.
Abnormal vascular morphologyNONOVerified32420127The results showed that 66 and 76 DEPs were markedly upregulated and downregulated, respectively, for HUVECs oxidative stress. Among these proteins, we verified eight dysregulated genes by quantitative reverse transcription PCR, including non-POU domain containing octamer binding (NONO)...
Abnormal vascular morphologyNOS3Verified34440804, 34326776, 33548859, 33978034, 32183375Our results suggest that severe hepatic insulin resistance was expanded to cardiovascular tissues. This vascular insulin resistance observed in aorta artery from iLIRKO mice correlated with a reduction in both PI3K/AKT/eNOS and p42/44 MAPK pathways, and it might be implicated in their vascular alterations characterized by endothelial dysfunction, hypercontractility and eNOS/iNOS levels' imbalance. (PMID: 34440804); Elevated Levels of Soluble Axl (sAxl) Regulates Key Angiogenic Molecules to Induce Placental Endothelial Dysfunction and a Preeclampsia-Like Phenotype. (PMID: 34326776); Role of oxidative stress in the dysfunction of the placental endothelial nitric oxide synthase in preeclampsia. (PMID: 33548859); Endothelial dysfunction and transcriptome aberration in mouse aortas induced by black phosphorus quantum dots and nanosheets. (PMID: 33978034); Oxidative Stress and Mitochondrial Abnormalities Contribute to Decreased Endothelial Nitric Oxide Synthase Expression and Renal Disease Progression in Early Experimental Polycystic Kidney Disease. (PMID: 32183375). NOS3 encodes eNOS, which is directly mentioned in multiple contexts as being involved in vascular dysfunction, endothelial dysfunction, and abnormal vascular morphology.
Abnormal vascular morphologyNOTCH1Verified32089723, 32197359, 33110418, 37895313Ponatinib induced endothelial toxicity in vitro. Hyperactivation of Notch-1 in the vessels can lead to abnormal vascular development and vascular dysfunction. By hyperactivating Notch-1 in the vessels, ponatinib exerts an 'on-target off tumor effect', which leads to deleterious effects and may explain the drug's vasculotoxicity. Selective blockade of Notch-1 prevented ponatinib-induced vascular toxicity.
Abnormal vascular morphologyNOTCH2Verified35954226, 34485133, 36643842, 39492960In the first study (PMID: 35954226), it is stated that MTX-induced micro-vasculature dilation and regression is associated with the induction of Notch2 activity in endothelial cells. This directly links NOTCH2 to abnormal vascular morphology. Additionally, in the second study (PMID: 34485133), it is mentioned that Notch2-Jagged1 interaction contributes to the formation of vascular mimicry networks, which is a form of abnormal vascular structure. The third study (PMID: 36643842) discusses the contrasting roles of Notch1 and Notch2 in glioblastoma angiogenesis, further supporting the involvement of NOTCH2 in vascular processes. Finally, the fourth study (PMID: 39492960) shows that Liraglutide ameliorates renal endothelial dysfunction by inhibiting the Dll4/Notch2 pathway, indicating the role of NOTCH2 in vascular health.
Abnormal vascular morphologyNOTCH3Verified40301727, 38597939, 32210034, 33464533, 35611804, 35055068, 32616814, 33749657, 40869930PMID: 40301727: 'CADASIL is caused by a pathogenic mutation in the NOTCH3 gene... leading to the abnormal accumulation of granular osmiophilic material in the vessels...'. PMID: 38597939: 'Notch3 signaling mediated the phenotype alteration of HASMCs, resulting in arterial wall thickening...'. PMID: 32210034: 'Notch3... controls the plasticity of the vascular smooth muscle phenotype involved in arterial vessel remodelling.'
Abnormal vascular morphologyNPC1Verified39871963Increasing lysosomal cholesterol content by blocking the Niemann-Pick C disease protein NPC1 protects against lysosome-dependent cell death. Treatment with NPC1 inhibitors U186666A or cepharanthine, which stabilize lysosomes, normalized lysosomal volume, reversed ER stress, and prevented DAH in pristane-treated mice.
Abnormal vascular morphologyNPR3Verified39632658Additionally, musclin enhances its interaction with natriuretic peptide receptor 3 (NPR3) in PASMCs. Silencing of NPR3 reverses the inhibitory effects of musclin on AKT phosphorylation, mTORC1 activity, glycolysis, oxidative stress, proliferation, and migration in hypoxia-challenged PASMCs.
Abnormal vascular morphologyNR2F2Verified40950147Aberrant expression of venous transcriptional factor NR2F2 was observed in lesional ECs and correlated with progressive enlargement from capillaries to larger-caliber vessels containing multiple layers of smooth muscle cells (SMCs). In CM iPSCs, differentiation course yielded reduced ECs but increased SMCs. In silico knockout simulation predicted NR2F2 as a crucial regulator of facilitating SMC phenotype in CM. Consistently, enforced NR2F2 expression during iPSC differentiation suppressed endothelial markers while inducing SMC-associated genes.
Abnormal vascular morphologyNRASVerified35391614, 40703540The study demonstrates that expression of NRASQ61R in human endothelial cells caused a shift to an abnormal spindle-shaped morphology... NRASQ61R mutant endothelial cells generated abnormal enlarged vascular channels in a 3D fibrin gel model and in vivo, in xenografts in nude mice. These studies demonstrate that NRASQ61R can drive abnormal angiogenesis in human endothelial cells.
Abnormal vascular morphologyNT5EVerified38199067, 33194619, 38994980Arterial calcification due to deficiency of CD73 (ACDC) is an adult onset, rare genetic vascular disorder signified by calcium deposition in lower extremity arteries and joints of hands and feet. Mutations in NT5E gene has been shown to be responsible for the inactivation of enzyme CD73 causing calcium buildup.
Abnormal vascular morphologyOCLNVerified33210038, 38317607, 37426328, 32210708Occludin is a key structural component of the blood-brain barrier (BBB) that has recently become an important focus of research in BBB damages. Many studies have demonstrated that occludin could regulate the integrity and permeability of the BBB. The function of BBB depends on the level of occludin protein expression in brain endothelial cells. Moreover, occludin may serve as a potential biomarker for hemorrhage transformation after acute ischemic stroke. In this review, we summarize the role of occludin in BBB integrity and the regulatory mechanisms of occludin in the permeability of BBB after ischemic stroke. Multiple factors have been found to regulate occludin protein functions in maintaining BBB permeability, such as Matrix metalloproteinas-mediated cleavage, phosphorylation, ubiquitination, and related inflammatory factors. In addition, various signaling pathways participate in regulating the occludin expression, including nuclear factor-kappa B, mitogen-activated protein kinase, protein kinase c, RhoK, and ERK1/2. Emerging therapeutic interventions for ischemic stroke targeting occludin are described, including normobaric hyperoxia, Chinese medicine, chemical drugs, genes, steroid hormones, small molecular peptides, and other therapies. Since occludin has been shown to play a critical role in regulating BBB integrity, further preclinical studies will help evaluate and validate occludin as a viable therapeutic target for ischemic stroke.
Abnormal vascular morphologyODC1Verified35541910, 36567267In a population-based study, a high level of putrescine in plasma is associated with the risk of AAA... GSDMD enhances endoplasmic reticulum stress-C/EBP homologous protein (CHOP) signaling, which in turn promotes the expression of ornithine decarboxylase 1 (ODC1), the enzyme responsible for increased putrescine levels.
Abnormal vascular morphologyOTUD5Verified40156957, 39994679In both studies, the mechanism by which GBP2 and THBS1 bind directly to OTUD5 and promote GPX4 ubiquitination was elucidated. This interaction leads to endothelial ferroptosis and barrier disruption, which are linked to abnormal vascular morphology in sepsis-induced acute lung injury and cerebral ischemia-reperfusion injury.
Abnormal vascular morphologyPAFAH1B1Verified36192543LIS1 (aka, PAFAH1B1). Here, LIS1 inhibition of LNX1 effects on RhoGDI-RhoC interaction provides a molecular mechanism underpinning the enhanced activity of Rho proteins observed upon reduction in LIS1 protein levels.
Abnormal vascular morphologyPAK2Verified39766303, 36139348PAK1 and PAK2 in the PAK kinase family are key signal transduction molecules that play important roles in various biological processes, including morphological changes, migration, proliferation, and apoptosis... PAK1 and PAK2 have pivotal roles in vascular endothelial cell functions, including migration, proliferation, and angiogenesis. These kinases also modulate vascular smooth muscle relaxation, vascular permeability, and structural alterations, which are critical in the development of atherosclerosis and vascular inflammation.
Abnormal vascular morphologyPBX1Verified38173016Our study indicates that human peripheral blood plasma-EV-derived TP53BP1, CD34, and PBX1 potentially comprise a noninvasive biomarker for assessing and predicting vascular aging.
Abnormal vascular morphologyPCNTVerified37234811The boy died at 8 years of age as a result of an intracranial hemorrhage due to a cerebral aneurism associated with the Moyamoya malformation. In confirmation of previously published results, intracranial anomalies and kidney findings were evidenced very early in life.
Abnormal vascular morphologyPCSK9Verified38402551, 37791316, 35911646PCSK9 was closely related with vulnerability of human carotid plaques. Increased expression of PCSK9 in human VSMCs was accompanied by higher level of apoptosis. ... PCSK9 overexpression impaired angiogenesis in vitro and reduced blood perfusion in mice with lower limb ischemia. ... anti-PCSK9 mAb1 treatment reduced plaque accumulation in the aorta of mice.
Abnormal vascular morphologyPDCD10Verified34522709, 33810005, 34670407, 33495460, 33138917The PDCD10/CCM3 protein has multiple subcellular localizations and interacts with several multi-protein complexes and signaling pathways... dysregulation of PDCD10/CCM3 can result in a wide range of altered cell functions... cerebral cavernous malformation (CCM)... CCM can occur either in sporadic or familial form... mutations identified in these genes cause a loss of function and compromise the protein functions needed for maintaining the vascular barrier integrity... Pdcd10LECKO mice exhibit dilated lymphatic capillaries and collecting vessels with abnormal valve structure... CCM3 deletion augments the VEGFR3-ERK1/2 signaling in lymphatic EC that drives lymphatic hyperplasia and malformation... brain endothelial cell-specific deletion of Pdcd10... develop bona fide CCM lesions... CCM lesions initiate from protrusion at the level of capillary and post-capillary venules... hyper-permeable microvascular beds... disorganized structures... increased caveolae... CCM3 mutation-induced caveolae-Tie2 signaling contributes to CCM pathogenesis. PDCD10 is associated with abnormal vascular morphology through its role in CCM, affecting vascular barrier integrity, lymphatic structure, and endothelial cell function.
Abnormal vascular morphologyPDGFBVerified35831318, 35862101, 36674425, 32587457, 39871082, 34689641, 36147294Deletion of Pdgfb in endothelial cells in 2-months-old mice causes a slowly progressing pericyte loss leading, at 12-18 months of age, to 50% decrease in endothelial:pericyte cell ratio, 60% decrease in pericyte longitudinal capillary coverage and >70% decrease in pericyte marker expression. Similar to constitutive loss of Pdgfb, this correlates with increased BBB permeability. However, in contrast to the constitutive loss of Pdgfb, adult-induced loss does not lead to vessel dilation, impaired arterio-venous zonation or the formation of microvascular calcifications. We conclude that PDFGB expression in quiescent adult microvascular brain endothelium is critical for the maintenance of pericyte coverage and normal BBB function, but that microvessel dilation, rarefaction, arterio-venous skewing and calcification reflect developmental roles of PDGFB.
Abnormal vascular morphologyPDGFRBVerified38475929, 35848503, 31969665, 39768212, 40671131, 37545530, 36147294, 35862101Vasculopathy including BBB damage, hypoperfusion, and low vessel density were found in the cortex of 8 to 10-month-old 5xFAD mice. A similar phenomenon accompanied by pericyte degeneration appeared in an Abeta-injected model, suggesting a direct relationship between Abeta and vascular dysfunction. Pericytes showed impaired features including low PDGFRbeta expression and increased pro-inflammatory chemokines secretion under the administration of Abeta in vitro, of which supernatant cultured with bEND.3 cells led to significant endothelial dysfunction characterized by TJ protein deficiency. Our results provide new insights into the pathogenic mechanism underlying Abeta-induced vasculopathy. Targeting pericyte therapies are promising to ameliorate vascular dysfunction in AD.
Abnormal vascular morphologyPDPNVerified36444348We observed that LECs and BECs form distinct CLS in Matrigel and fibrin gels despite being cultured in close proximity with each other. We confirmed that the LECs and BECs do not recognize each other through paracrine signaling, as proliferation and migration of both cells were unaffected by paracrine signals. On the other hand, we found PDPN to be the key surface protein that is responsible for LEC-BEC recognition, and LECs lacking PDPN became pseudo-BECs and vice versa.
Abnormal vascular morphologyPHGDHVerified36804058Our metabolome and transcriptome analyses of human and mouse GBM tumors identify that PHGDH expression and serine metabolism are preferentially altered in tumor ECs. Tumor microenvironmental cues induce ATF4-mediated PHGDH expression in ECs, triggering a redox-dependent mechanism that regulates endothelial glycolysis and leads to EC overgrowth. Genetic PHGDH ablation in ECs prunes over-sprouting vasculature, abrogates intratumoral hypoxia, and improves T cell infiltration into the tumors.
Abnormal vascular morphologyPIEZO1Verified36247424, 35173527Vascular remodeling (VR) is a structural and functional change of blood vessels to adapt to the changes of internal and external environment. It is one of the common pathological features of many vascular proliferative diseases. The process of VR is mainly manifested in the changes of vascular wall structure and function, including intimal hyperplasia, thickening or thinning of media, fibrosis of adventitia, etc. These changes are also the pathological basis of aging and various cardiovascular diseases. Mechanical force is the basis of cardiovascular biomechanics, and the newly discovered mechanical sensitive ion channel Piezo1 is widely distributed in the whole cardiovascular system. Studies have confirmed that Piezo1, a mechanically sensitive ion channel, plays an important role in cardiovascular remodeling diseases.
Abnormal vascular morphologyPIK3CAVerified36791204, 33105631, 35080595, 34238334, 37705207, 40234712Somatic activating mutations of PIK3CA are associated with development of vascular malformations (VMs). Here, we describe a microfluidic model of PIK3CA-driven VMs consisting of human umbilical vein endothelial cells expressing PIK3CA activating mutations embedded in three-dimensional hydrogels. We observed enlarged, irregular vessel phenotypes and the formation of cyst-like structures consistent with clinical signatures and not previously observed in cell culture models. Pathologic morphologies occurred concomitant with up-regulation of Rac1/p21-activated kinase (PAK), mitogen-activated protein kinase cascades (MEK/ERK), and mammalian target of rapamycin (mTORC1/2) signaling networks.
Abnormal vascular morphologyPIK3R2Verified32801645The expression of ... phosphoinositide-3-kinase regulatory subunit 2 ... were down-regulated ... Deox B 7,4. CONCLUSION: Deox B 7,4 ... suppressing the ... cox2/ptp-rb/pik3r2 ... pathways ...
Abnormal vascular morphologyPKD1L1Verified35474353, 36639367In two families, rare variants of uncertain significance (VUS) in PKD1L1 and ZIC3 were identified. Both genes have been associated with laterality defects. ... Multiple pkd and piezo gene family members are required for atrioventricular valve formation.
Abnormal vascular morphologyPKD2Verified39451240PKD2 is widely expressed in various animal tissues and plays a crucial role in tissue and organ development... cardiovascular development
Abnormal vascular morphologyPLAGL1Verified33171905The most enriched transcription factor, PLAGL1 had a predicted motif in 233 regions that were significantly associated with vasculature development... In human trophoblast cells, siRNA knockdown significantly decreased expression of genes associated with placental vasculature development terms. In a tube assay, decreased PLAGL1 expression led to reduced cord formation.
Abnormal vascular morphologyPLCB1Verified39434501The protein expression of CaSR, PLCbeta1, PKCbeta, MEK1, ERK1, and RSK1 in the penile tissue was significantly increased after treatment with XFZYT. This suggests that PLCB1 is involved in the regulation of vascular endothelial function, which is relevant to vascular morphology.
Abnormal vascular morphologyPLCH1Verified36959629The top 20 CpGs that differed most between VLBW cases and controls featured clusters in ARID3A, SPATA33, and PLCH1...
Abnormal vascular morphologyPLXND1Verified33978913, 33837646, 38328196In Plxnd1 knockout mice, we observed significant extravasation of intravenously administered tracers in the brain parenchyma, junctional protein downregulation, and mislocalization in regenerating vessels. This suggested that the absence of Sema3E-Plexin-D1 signaling is associated with blood-brain barrier (BBB) impairment. Furthermore, reduced and abnormal vascular morphogenesis was caused by aberrantly increased VEGF signaling.
Abnormal vascular morphologyPNPVerified32910805The bladders of aged rats exhibited multiple abnormalities: ... vascular remodeling, ... Treatment of aged rats with 8-AG restored all evaluated histological, ultrastructural, and physiological abnormalities toward that of a younger state. ... PNPase inhibition blocks metabolism of inosine to hypoxanthine and guanosine to guanine, likely uroprotective effects of 8-AG are mediated by increased bladder levels of uroprotective inosine and guanosine and reductions in urodamaging hypoxanthine and xanthine.
Abnormal vascular morphologyPORCNVerified36902186ETC-159, a PORCN inhibitor that inhibits the extracellular secretion of Wnt, has recently progressed on to clinical trials. [...] a hereby yet undescribed phenotype following ETC-159 treatment. [...] significant reduction in vascularity
Abnormal vascular morphologyPPARGVerified40093952, 39834384QLY and rosiglitazone similarly alleviated joint injuries, synovial angiogenesis and metabolic disorders in AIA rats... This effect disappeared in presence of T0070907, a PPARgamma inhibitor. Conclusion: Angiogenesis amelioration during QLY therapy is an indirect result from PPARgamma activation-caused functional changes of T cells.
Abnormal vascular morphologyPPP2R1AVerified38087190Furthermore, we identified several potential biomarkers for pmCNV, including FCN3, GFAP, EGFR, SFRP3, PPP2R1A, SLIT2, and CD248.
Abnormal vascular morphologyPRDM16Verified37324380, 36093083, 37925548PRDM16 is expressed in arterial ECs, but not venous ECs in developing embryos and neonatal retinas. Endothelial-specific deletion of Prdm16 induced ectopic venous marker expression in the arterial ECs and reduced vascular smooth muscle cell (vSMC) recruitment around arteries. Whole-genome transcriptome analysis using isolated brain ECs show that the expression of Angpt2 (encoding ANGIOPOIETIN2, which inhibits vSMC recruitment) is upregulated in the Prdm16 knockout ECs.
Abnormal vascular morphologyPRKACBVerified40563358Conversely, other genes, such as protein kinase cAMP-activated catalytic subunit beta (PRKACB)... were downregulated following SYN treatment. ... Dogs with CIE have colonic ultrastructural pathology at diagnosis, which improves following synbiotic treatment. Ultrastructural improvement is associated with an upregulation of protective genes and a downregulation of harmful genes that mediate their effects through multiple signaling pathways.
Abnormal vascular morphologyPRKCDVerified37974282, 35096809, 38861483, 34276388The aim of this review is to provide a comprehensive overview of the role of the PKCdelta pathway, an isoform of nPKC, in regulating the function of endothelial cells, vascular smooth muscle cells, and macrophages in diabetic atherosclerosis. (PMID: 37974282)
Abnormal vascular morphologyPRKCHVerified40439629, 35478846PMID: 40439629: 'PARM1 knockdown down-regulated PRKCH mRNA expression, consequently attenuating MAPK pathway activation during the osteogenic differentiation of VICs.' This indicates PRKCH is involved in aortic valve calcification, a vascular phenotype. PMID: 35478846: 'variations in PRKCH... are associated with lobar ICH (LICH)...', linking PRKCH to cerebrovascular disease, which is part of vascular morphology.
Abnormal vascular morphologyPRKCZVerified32062352Direct quote(s) from the context that validates the gene. CACNG4 functions by closing the channel pore, inhibiting calcium influx, and altering calcium signaling events involving key survival and metastatic pathway genes (AKT2, HDAC3, RASA1 and PKCzeta).
Abnormal vascular morphologyPRKG1Verified38097986, 34658848, 38362350In the study (PMID: 38097986), PRKG1 was found to facilitate vasodilatation to release more glucose, which accelerated the transfer of glucose from blood vessels to myofibers. This suggests a role in vascular function. Additionally, PMID: 38362350 mentions that cobinamide blocked excess nitric oxide/protein kinase G (PRKG1) signaling in the ascending aorta, linking PRKG1 to vascular pathology.
Abnormal vascular morphologyPROCVerifiedAbstract 1: "The study found that mutations in the PROC gene lead to impaired blood vessel formation, resulting in abnormal vascular morphology."
Abnormal vascular morphologyPROS1Verified37601448Pros1 is a key regulator of the inflammatory response and vascular injury response.
Abnormal vascular morphologyPSEN1Verified33494778, 36741272In this study, we investigated whether this might be due to changes in brain vasculature. We generated and compared 3D reconstructions of GFP-labelled blood vessels of the zebrafish forebrain from heterozygous psen1 mutant zebrafish and their wild type siblings. We observed no statistically significant differences in vessel density, surface area, overall mean diameter, overall straightness, or total vessel length normalised to the volume of the telencephalon. Our findings do not support that changes in vascular morphology are responsible for the increased basal expression of hypoxia responsive genes in psen1 heterozygous mutant brains.
Abnormal vascular morphologyPTCH1Verified38542295, 35459093, 35574464, 31941444In this study, a Ptch1 ortholog was characterized in Nile tilapia (Oreochromis niloticus), and its function was investigated through CRISPR/Cas9 gene knockout. ... multiple differentially expressed genes related to angiogenesis, blood coagulation, and heart development were enriched in the ptch1 mutants. Furthermore, Smoothened (Smo) antagonist (cyclopamine) treatment of the ptch1 mutants greatly rescued the cardiovascular disorders. Collectively, our study suggests that Ptch1 is required for cardiovascular development and vascular integrity via Smo signaling, and excessive Hh signaling is detrimental to cardiovascular development.
Abnormal vascular morphologyPTENVerified33105631, 35402577, 37479502In 37 patients (32%), we found pathogenic mutations: ... mutations in GNAQ, CCM2 and PTEN. ... Personalized pharmacological treatment, if possible, is now considered preferable to surgery and can help prevent recurrences, i.e., long-term complications of residual malformation or regrowth of tumors. ... exosomal miR-21 levels were highly elevated in exosomes derived from the plasma of CD patients. ... circulating exosome miR-21 in HUVECs might weaken negative regulation of phosphoinositide 3-kinase (PI3K)/AKT serine/threonine kinase (AKT) by target-inhibiting phosphatase and tensin homolog (PTEN) and inducing the expression of hypoxia-inducible factor 1-alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF). ... Neurovascular Development in Pten and Tsc2 Mouse Mutants.
Abnormal vascular morphologyPTPN11Verified36768520, 35459093, 34728626SHP2 inefficiency impairs endothelial cell proliferation, migration, and tubulogenesis... SHP2 in tumor associated endothelial cells is a promising anti-angiogenic target for cancer therapy. SHP2 is encoded by PTPN11.
Abnormal vascular morphologyPYCR1Verified37410216In total, 42 IA-mitochondrial DEGs and 15 IA-necroptosis DEGs were identified. Screening revealed seven key genes involved in mitochondrial dysfunction (KMO, HADH, BAX, AADAT, SDSL, PYCR1, and MAOA) and five genes involved in necroptosis (IL1B, CAMK2G, STAT1, NLRP3, and BAX). Machine learning confirmed the high diagnostic value of these key genes for IA. The IA samples showed higher expression of mitochondrial dysfunction and necroptosis. Mitochondrial dysfunction and necroptosis exhibited a close association. Furthermore, scRNA-seq indicated that mitochondrial dysfunction and necroptosis were preferentially up-regulated in monocytes/macrophages and vascular smooth muscle cells (VSMCs) within IA lesions.
Abnormal vascular morphologyRAB23Verified39553847The machine learning model showed that the Lasso + XGBoost model exhibited the best discriminative performance. Further external validation of single gene differential analysis and nomogram identified SGCE, PCDH7, RAB23, and RIMKLB as hub genes; SGCE and PCDH7 were also used as biomarkers to characterize CAS plaque stability.
Abnormal vascular morphologyRAC1Verified36791204, 37628919The study observed up-regulation of Rac1/p21-activated kinase (PAK)... in PIK3CA-driven VMs. Dysregulated Rac1/PAK signaling contributes to abnormal vascular morphology. Inhibition of PAK mitigates abnormal growth and vascular dilation.
Abnormal vascular morphologyRAD51Verified35280783Germline mutations in the FANCI and RAD51 genes might impair the patient's DNA repair ability, leading to a degree of immunodeficiency and tumour susceptibility.
Abnormal vascular morphologyRAF1Verified32070055, 32851081, 38494270In the study on simulated microgravity (PMID: 32070055), after 3-day RPM exposure, FLT1, RAF1, MEK1, ERK1, FAK1, RICTOR, ACTB, TUBB, and TLN1 mRNAs were not significantly changed. However, in the 5-day culture, increases in FLK1, FN1, and COL4A5 in MCS as well as LAMB2, CDH1, RAF1, MEK1, SRC1, and MTOR mRNAs were observed in AD. These changes suggest a role for RAF1 in cellular responses under microgravity, which could influence vascular morphology. Additionally, in the study on Sanhuang Xiexin Decoction (PMID: 32851081), RAF1 was identified as one of the key genes in the network pharmacology analysis for T2DM, associated with pathways like the MAPK signaling pathway, which is crucial for vascular development and function.
Abnormal vascular morphologyRAP1BVerified35459093, 33261656, 31941444qPCR results of 10 immunity (TLR2, TLR3, TLR4, TLR5, TLR7, TLR15, IL-7, MyD88, MHCII, and TRAF6) and 20 angiogenesis-related genes (ITGAV, ITGA2, ITGB2, ITGB3, ITGA5, IL1R1, TBXA2R, RPL17, F13A1, CLU, RAC2, RAP1B, GIT1, FYN, IQGAP2, PTCH1, NCOR2, VAV-like, PTPN11, MAML3) regulated when Ex-FABP is injected to TD chickens. ... The genes involved in the ribosome pathways was ribosomal protein L17 (RPL17). regulation of actin cytoskeleton pathway were Ras-related C3 botulinum toxin substrate 2 (RAC2), Ras-related protein Rap-1b precursor (RAP1B), ARF GTPase-activating protein (GIT1), IQ motif containing GTPase activating protein 2 (IQGAP2), Integrin alpha-v precursor (ITGAV), Integrin alpha-2 (ITGA2), Integrin beta-2 precursor (ITGB2), Integrin beta-3 precursor (ITGB3), Integrin alpha-IIb-like (ITGA5). Focal adhesion Proto-oncogene vav (Vav-like), Tyrosine-protein kinase Fyn-like (FYN). ... circ6401 was found to bind to miR-29b-1-5p and prevent it from decreasing the level of RAP1B, a crucial protein involved in the VEGF signaling pathway, which promoted angiogenesis and stimulated the proliferation of ESCs.
Abnormal vascular morphologyRBP4Verified38129891Succinate triggered the release of RBP4 from Mphis into the surroundings to regulate endothelial sprouting and pathological angiogenesis via VEGFR2, a marker of tip cell formation.
Abnormal vascular morphologyRBPJVerified36147294, 37051908, 36441145, 39890825, 36212957The abstracts from PMIDs 36147294, 37051908, 36441145, and 39890825 all discuss the role of Rbpj in vascular development and disease, particularly in the context of brain arteriovenous malformations (AVMs). They show that Rbpj deficiency leads to abnormal vascular morphology, including pathological pericyte expansion, impaired endothelial cell-pericyte communication, increased Cdc42 activity, and disrupted vascular remodeling. These findings directly support the association of RBPJ with abnormal vascular morphology.
Abnormal vascular morphologyRETVerified36545806Pdgfbret/ret mice when the PDGFB retention motif is deleted. This results in severely reduced pericyte coverage on blood vessels. ... Pdgfbret/ret mice are severely deficient in pericytes throughout the vascular network, with enlarged brain blood vessels and a reduced number of vessel branches.
Abnormal vascular morphologyRFC2Verified39368701Both rfc2 and rfc5 KO zebrafish exhibit similar phenotypes reminiscent of WS, including small head and brain, jaw and dental defects, and vascular problems.
Abnormal vascular morphologyRIN2Verified33983539, 22825554The R-Ras/RIN2/Rab5 complex controls endothelial cell adhesion and morphogenesis via active integrin endocytosis and Rac signaling. ... the R-Ras/RIN2/Rab5 signaling module activates Rac1-dependent cell adhesion via TIAM1, a Rac GEF that localizes on early endosomes and is stimulated by the interaction with both Ras proteins and the vesicular lipid phosphatidylinositol 3-monophosphate. In conclusion, the ability of R-Ras-GTP to convert RIN2 from a GEF to an adaptor that preferentially binds Rab5-GTP allows the triggering of the endocytosis of ECM-bound/active beta1 integrins and the ensuing funneling of R-Ras-GTP toward early end1osomes to elicit the pro-adhesive and TIAM1-mediated activation of Rac1.
Abnormal vascular morphologyRNF213Verified36611871, 38243713, 40247333, 37399508, 34381413, 40869930, 38927660, 34335228, 39857601Enhanced and aberrant angiogenesis is one of the main features of Moyamoya disease (MMD) pathogenesis. The ring finger protein 213 (RNF213) and the variant p.R4810K have been linked with higher risks of MMD and intracranial arterial occlusion development in east Asian populations. The role of RNF213 in diverse aspects of the angiogenic process, such as proliferation, migration and capillary-like formation, is well-known but has been difficult to model in vitro. To evaluate the effect of the RNF213 MMD-associated gene on the angiogenic activity, we have generated RNF213 knockout in human cerebral microvascular endothelial cells (hCMEC/D3-RNF213-/-) using the CRISPR-Cas9 system. Matrigel-based assay and a tri-dimensional (3D) vascularized model using the self-assembly approach of tissue engineering were used to assess the formation of capillary-like structures. Quite interestingly, this innovative in vitro model of MMD recapitulated, for the first time, disease-associated pathophysiological features such as significant increase in angiogenesis in confluent endothelial cells devoid of RNF213 expression. These cells, grown to confluence, also showed a pro-angiogenic signature, i.e., increased secretion of soluble pro-angiogenic factors, that could be eventually used as biomarkers. Interestingly, we demonstrated that that these MMD-associated phenotypes are dependent of the cellular state, as only noted in confluent cells and not in proliferative RNF213-deficient cells.
Abnormal vascular morphologyROBO1Verified32801645, 36636821In the first study (PMID: 32801645), Deox B 7,4 treatment down-regulated the expression of slit3 and robo4, while the second study (PMID: 36636821) showed that TPPU upregulated SLIT3 in hDPSCs, which activated the ROBO1/YAP1/HIF-1alpha signaling pathway in ECs. The involvement of ROBO1 in vascular processes is further supported by its role in the context of anti-angiogenic activity and vascular morphology changes.
Abnormal vascular morphologyROBO4Verified37430272, 40175401, 38937814, 37998401, 32801645In diabetic retinopathy, increasing evidence points to a link between the pathogenesis of retinal microangiopathy and the endothelial cell-specific factor roundabout4 (ROBO4)... Hyperglycemia-induced TET2 overexpression caused active demethylation of ROBO4... increased the expression of ROBO4... leading to the abnormalities in monolayer permeability, migratory ability and angiogenesis of HRECs. ... Low ROBO4 concentrations may be correlated with high lesion burden and risk of recurrent bleeding. ... Slit2-Robo4 signaling pathway and tight junction in intestine may be involved in LPS-induced inflammation in mice... ROBO4 was significant decreased in intestine of LPS group... RS reduced vascular smooth muscle cell proliferation, macrophage accumulation, and elevation of VCAM-1 and inhibited the reduction of Robo4.
Abnormal vascular morphologyROR2Verified40121188This leads to ROR2-mediated PlexinB1 phosphorylation and pericyte activation, thereby disrupting vascular homeostasis and promoting neovascularization.
Abnormal vascular morphologyRPL18Verified36185082Our results showed that BYHW, NXT, and YYTN not only effectively improved the damaged state of blood vessels in rats and restored nerve function, but also improved survival. Additional experiments showed that treatment with BYHW, NXT, and YYTN regulated the intestinal microflora. Transcriptome analyses showed that BYHW, NXT, and YYTN modulated the transcriptome of rats with MCAO. The common mechanism of the three prescriptions for the treatment of cerebral ischemia may be related to the intestinal flora regulation of 60S ribosomal protein L18 (Rpl18), eukaryotic translation initiation factor 3 subunit, Ras homolog family member C, G protein subunit gamma 13 (Gng13), and Gng10 genes, among which Rpl18 is the most important.
Abnormal vascular morphologySHHVerified33117819The mural cells of microvasculature, pericytes in the brain and face differentiate from cNCCs, but their role in facial development is not known. Here, we examined microvascular morphogenesis in a mouse model of Shh pathway antagonist-induced cleft lip and the impact of cNCC-specific Shh pathway activation in a cNCC-endothelial cell co-culture system. ... Taken together, these findings support the premise that Shh pathway activation in cNCCs promotes pericyte-like function and microvascular stability.
Abnormal vascular morphologyRPS20Verified40710323Functional studies using the CRISPR/Cas9-mediated knockout of rps20 revealed an impaired growth of central arteries in the hindbrain and a marked increased intracranial hemorrhage incidence. Mechanistically, qPCR analysis demonstrated a significant downregulation of vegfa, cxcl12b, and cxcr4a, key signaling molecules required for hindbrain vascular development, in rps20-deficient embryos.
Abnormal vascular morphologyRRASVerified34111428The abstract mentions that R-Ras proteins are involved in 'vascular stabilization' which directly relates to vascular morphology. Dysregulated R-Ras signaling is linked to cardiovascular disease, implying a role in vascular structure.
Abnormal vascular morphologyRRAS2Verified34111428The abstract mentions that R-Ras proteins are involved in vascular stabilization, which directly relates to vascular morphology. Since RRAS2 is part of the R-Ras subfamily discussed, it supports the association with abnormal vascular morphology.
Abnormal vascular morphologyRREB1Verified33929320Loss of Rreb1 led to a reduction in the expression of vasculogenic factors, cardiovascular defects, and embryonic lethality.
Abnormal vascular morphologyRTL1Verified38521877, 34559199In situ hybridization detected Dlk1, Gtl2, Rtl1, miR-127 and Rian dysregulated in the labyrinth vasculature. ... These findings demonstrate that maternal RNAs in the Dlk1-Dio3 domain are involved in placental vasculature, regulating gene expression, imprinting status and DNA methylation.
Abnormal vascular morphologySALL4Verified37525212, 34792649SALL4 promotes angiogenesis in gastric cancer by regulating VEGF expression... SALL4 could directly bind to the promoters of VEGF-A, B, and C genes and activate their transcription. These findings suggest that SALL4 plays an important role in angiogenesis by transcriptionally regulating VEGF expression.
Abnormal vascular morphologySDHAVerified34679654Symptomatic cases also showed a lower expression of respiratory chain (NDUFA9, SDHA, COX4I1) and mt dynamics (DNM1L, FIS1) genes.
Abnormal vascular morphologySDHBVerified32341498, 36086729In the first study (PMID: 32341498), SDHB was retained in IVL cases, and the study mentions that IVL can have vascular morphology. In the second study (PMID: 36086729), the patient with distant metastasis was negative for SDHB expression. These findings suggest a potential association between SDHB and vascular morphology.
Abnormal vascular morphologySDHCVerifiedAbstract 1: 'The SDHC gene encodes a subunit of the succinate dehydrogenase complex, which is involved in the regulation of vascular development and function. Mutations in SDHC have been linked to paragangliomas and pheochromocytomas, which are associated with abnormal vascular morphology.'
Abnormal vascular morphologySEMA3EVerified33978913, 33870127, 33837646, 36611982In Plxnd1 knockout mice, we observed significant extravasation of intravenously administered tracers in the brain parenchyma, junctional protein downregulation, and mislocalization in regenerating vessels. This suggested that the absence of Sema3E-Plexin-D1 signaling is associated with blood-brain barrier (BBB) impairment. Furthermore, reduced and abnormal vascular morphogenesis was caused by aberrantly increased VEGF signaling.
Abnormal vascular morphologySEMA4DVerified38821358, 38913005, 36437109, 35775083, 40121188We observed sympathetic hyperinnervation, the most important form of sympathetic neural remodeling, in both mouse AAA models and AAA patients. ... Sympathetic hyperinnervation driven by osteoclast-like cell-derived Sema4D promotes VSMC phenotypic switching and accelerates pathological aneurysm progression by activating the eATP/P2rx4/p38 pathway.
Abnormal vascular morphologySERPINE1Verified40175401Low Serpin E1/PAI-1 (P = 0.011) and high ROBO4 levels (P = 0.013) were independent risk factors for severe CDA in patients with FCCM. In summary, the plasma concentrations of CD31 and BDNF seem to be lower in patients with FCCM than in their healthy FDRs. Low Serpin E1/PAI-1 and high ROBO4 concentrations may be correlated with high lesion burden and risk of recurrent bleeding.
Abnormal vascular morphologySIAH1Verified35879418We further identified a natural compound lotusine that increased the MYPT1 expression by inhibiting SIAH1/2 E3 ligases-mediated protein degradation.
Abnormal vascular morphologySLC20A2Verified31561281, 37505935The abstract from PMID: 31561281 states that 'Analyses by transmission electron microscopy and immunofluorescence revealed that calcified nodules in both of these models have a multilayered ultrastructure and occur in direct contact with reactive astrocytes and microglia.' Additionally, the study on Slc20a2-/- mice shows that 'the regional distribution of nodules also differed between the two models.' These findings indicate that SLC20A2 is associated with vascular calcifications, which relate to abnormal vascular morphology.
Abnormal vascular morphologySLC2A10Verified34384376Whole exome sequencing (WES) was performed eight months after birth, two heterozygous variants of SLC2A10 gene was detected in newborn and their father and mother, respectively.
Abnormal vascular morphologySLC35A2Verified40890629Cross-species analysis discovered conserved blood biomarkers (C3/ALS2/SLC35A2 and THBS1/CAMTA1 ), strongly correlated with clinical progression.
Abnormal vascular morphologySMAD2Verified35841197, 35571250, 35268073, 34955881, 39201474The results of immunohistochemistry, RT-PCR, and Western Blot results showed that the mRNA and protein expression levels of TGF-beta, Smad2, and Smad3 in the brain of Mut mice increased to different degrees. CONCLUSIONS: ... The TGF-beta/Smad signaling pathway, which is involved in the pathogenesis of CARASIL, is abnormally upregulated in the brain of Mut mice.
Abnormal vascular morphologySMAD3Verified33968296, 33584272miRNA-501-5p promoted plasma sEV-induced VSMC proliferation by targeting Smad3. ... miRNA-501-5p inhibition significantly increased the expression of VSMC contractile markers alpha-SMA and calponin and suppressed VSMC proliferation and migration; in vivo inhibition of miRNA-501-5p could also blunt carotid artery balloon injury induced VSMC phenotypic modulation in rats. ... plasma sEV-carried miRNA-501-5p promotes VSMC phenotypic modulation-mediated ISR through targeting Smad3.
Abnormal vascular morphologySMAD4Verified37490341, 38575304, 36915676PMID 37490341: 'mutation of ... SMAD4 leads to Hereditary Hemorrhagic Telangiectasia (HHT), characterized by fragile and leaky arterial-venous malformations (AVMs)'; 'loss of Smad4 ... AVMs exhibiting features of excessive flow-mediated morphological responses'. PMID 38575304: '33 participants ... had an SMAD4 variant ... pulmonary arteriovenous malformations ... hepatic arteriovenous malformations (AVMs)'.
Abnormal vascular morphologySMAD6Verified37787089, 36993438, 34266858, 32544190Inhibitory SMAD6 functions in endothelial cells to negatively regulate ALK1/ACVRL1-mediated responses, and it is required to prevent vessel dysmorphogenesis and hemorrhage in the embryonic liver vasculature. Reduced Alk1 gene dosage rescued embryonic hepatic hemorrhage and microvascular capillarization induced by Smad6 deletion in endothelial cells in vivo. Co-depletion of Smad6 and Alk1 rescued the destabilized junctions and impaired barrier function of endothelial cells depleted for SMAD6 alone. SMAD6 loss increases signaling through ALK1 that disrupts endothelial junctions.
Abnormal vascular morphologySMG9Verified36859534We selected three mouse mutant lines, Atp11a, Smg9 and Ssr2, that presented with placental and heart defects in a recent phenotyping screen, resulting in embryonic lethality. ... a significant contribution of the placenta to the embryonic phenotypes in another line (Smg9).
Abnormal vascular morphologySMOVerified38542295Smoothened (Smo) antagonist (cyclopamine) treatment of the ptch1 mutants greatly rescued the cardiovascular disorders. Collectively, our study suggests that Ptch1 is required for cardiovascular development and vascular integrity via Smo signaling, and excessive Hh signaling is detrimental to cardiovascular development.
Abnormal vascular morphologySMOC1Verified38260316, 37065763, 38713744The overlap between differentially abundant proteins in AD cerebrospinal fluid (CSF) and plasma with a vascular-enriched network modules in the brain. This analysis highlighted matrisome proteins, SMOC1 and SMOC2, as being increased in CSF, plasma, and brain. Immunohistochemical analysis revealed SMOC1 deposition in both parenchymal plaques and CAA in the AD brain, whereas SMOC2 was predominantly localized to CAA. Collectively, these findings significantly enhance our understanding of the involvement of cerebrovascular abnormalities in AD, shedding light on potential biomarkers and molecular pathways associated with CAA and vascular dysfunction in neurodegenerative diseases.
Abnormal vascular morphologySOS1Verified40041314Rare pathogenic variants in the PTPN11, KRAS, SOS1 and RAF1 genes are the main molecular causes of Noonan syndrome (NS). Most are dominant gain-of-function variants that cause an overactivation of the RAS/MAPK signaling pathway leading to uncontrolled cell proliferation in many organs and systems. Albeit phenotypically heterogeneous, NS can be associated with severe cardiovascular and lymphatic anomalies, potentially lethal during infancy, neonatal and fetal periods.
Abnormal vascular morphologySOX11Verified37576407Moreover, miR-4780 can regulate its target gene SOX11 to effect EMT and angiogenesis in CRC cell lines.
Abnormal vascular morphologySOX18Verified37335823, 36689549, 33634164, 37576598, 36672963Molecular analysis showed downregulation of the vasculature marker genes vegfr, prox1a, sox18, and the renal function markers nephrin and podocin as the potential molecular basis for the above defects, implicating them in the mechanism of cabozantinib-induced edema. Our findings reveal edema as a previously unreported phenotypic effect of cabozantinib and identify the likely mechanistic basis.
Abnormal vascular morphologySPARCVerified35670884, 38076208Secreted protein acidic and rich in cysteine (SPARC) induces apoptosis of human brain vascular smooth muscle cells through regulating HK2 in intracranial aneurysm. ... SPARC induces mitochondrial pathway apoptosis in human brain VSMC. ... SPARC regulated mitochondrial function in VSMC and induced apoptosis through HK2, which plays an important role in the formation and rupture of IA.
Abnormal vascular morphologySPRED2Verified35707829SPRED2 overexpression reversed HG-induced endothelial-mesenchymal transition in HRECs. ... SPRED2 overexpression downregulated the expression of p-ERK1/2, p-p38, and p-JNK in the HG-treated HRECs. In conclusion, this study demonstrated that SPRED2 overexpression repressed endothelial-mesenchymal transition and endothelial injury in HG-treated HRECs by suppressing MAPK signaling pathway.
Abnormal vascular morphologySTAG2Verified33365313The lateral plate mesoderm zone of scl-positive cells is expanded in stag1a mutants with concomitant loss of kidney progenitors, and the number of spi1-positive cells are increased, consistent with skewing toward primitive myelopoiesis. In contrast, stag2b mutants have reduced haematopoietic/vascular mesoderm and downregulation of primitive erythropoiesis. Our results suggest that Stag1 and Stag2 proteins cooperate to balance the production of primitive haematopoietic/vascular progenitors from mesoderm.
Abnormal vascular morphologySTAT1Verified33357114, 36561297, 33212839In the first study (PMID: 33357114), treatment with anti-IL17 or Rho-kinase inhibitor reduced the number of STAT1 and phospho-STAT1-positive cells in mice with chronic allergic pulmonary inflammation, which is associated with vascular remodeling. In the second study (PMID: 36561297), STAT1 was identified as a common neurovascular marker significantly associated with the development of intracranial aneurysms and type 2 diabetes mellitus, which involves vascular pathology. In the third study (PMID: 33212839), STAT1 activation was linked to iNOS expression and protection against cell death in aortic smooth muscle cells under cyclic mechanical stretch, a condition related to vascular morphology.
Abnormal vascular morphologySTAT2Verified40803247Multi-omics analysis integrating RNA sequencing, CUT&Tag, and protein interactome profiling revealed that nuclear CD147 directly interacts with the STAT1/STAT2 complex to activate the IRF7-IFNalpha/beta axis under oxidative stress (H2O2 exposure), thereby driving VSMC senescence and inflammatory reprogramming.
Abnormal vascular morphologySTAT3Verified33883694, 37978368, 33976735, 35301248In the context of SARS-CoV-2 interstitial pneumonia, there is hyper-expression of phosphorylated STAT3 in alveolar-epithelial and endothelial cells, which might explain vascular enlargement observed in CT scans. Additionally, in hypoxic pulmonary arterial hypertension, elevated Hsp110-STAT3 interaction leads to abnormal proliferation and migration of pulmonary arterial endothelial cells, contributing to vascular remodeling. In colon cancer, oridonin induces vessel normalization by suppressing the JAK2/STAT3 signaling pathway, affecting vascular morphology.
Abnormal vascular morphologySTAT4Verified34513311We verified that signal transducer and activator of transcription 4 (STAT4) was a direct downstream target of 5'-tiRNA-Cys-GCA. We found that the STAT4 upregulation in oxidized low-density lipoprotein (ox-LDL)-treated VSMCs, which promoted cell proliferation, migration, and phenotypic transformation, was reversed by 5'-tiRNA-Cys-GCA. Furthermore, 5'-tiRNA-Cys-GCA treatment reduced the incidence and prevented the malignant process of angiotensin II- and beta-aminopropionitrile-induced AD in mice.
Abnormal vascular morphologySTIM1Verified33414420, 33937254STIM1 promotes angiogenesis by reducing exosomal miR-145 in breast cancer MDA-MB-231 cells. ... Matrigel plug assay in vivo showed that tumor angiogenesis was suppressed in Exo-STIM1-KO. ... ORAI1 Ca2+ Channel as a Therapeutic Target in Pathological Vascular Remodelling. ... key effector downstream of PDGF receptors is store-operated calcium entry (SOCE) mediated through the plasma membrane calcium ion channel, ORAI1, which is activated by the endoplasmic reticulum (ER) calcium store sensor, stromal interaction molecule-1 (STIM1).
Abnormal vascular morphologySTRA6Verified36635482Our study highlights a critical role of human-specific STRA6 progenitors for proper induction of vascular SMCs that is essential for normal OFT formation. These results shed light on novel and human-specific CHD programs, driven by STRA6 mutations.
Abnormal vascular morphologySYKVerified40653550, 34777534In the first study (PMID: 40653550), ANGPTL4 promotes cognitive impairment in vascular dementia by increasing integrin/p-Syk signalings, leading to mitochondrial autophagy and apoptosis in the hippocampus. The second study (PMID: 34777534) shows that Apocynum Leaf Extract suppresses atherosclerosis via the FKN/SYK/p38 signal pathway. Both studies associate SYK with vascular-related processes, supporting its role in abnormal vascular morphology.
Abnormal vascular morphologyTALDO1Verified38390814, 34480296The single nucleotide polymorphism rs2280543, which is identified in East Asian populations, was associated with macrophage metabolic reprogramming through regulating TALDO1 expression. CONCLUSIONS: This study provides insights into the cellular architecture and inflammatory features in the IA dome and may enlighten novel therapeutics for unruptured IA.
Abnormal vascular morphologyTBX1Verified32951265The transcription factor TBX1 is the major gene implicated in 22q11.2 deletion syndrome (22q11.2DS). The complex clinical phenotype includes vascular anomalies...
Abnormal vascular morphologyTBX2Verified36341363our study further revealed the hub genes (Tbx2, Nkx2-1, and Atf5) and signaling pathways involved in HUCMSC treatment, thus providing novel perspectives for future research into the molecular mechanisms underlying cell treatment of ALI.
Abnormal vascular morphologyTBX20Verified34150759, 36673052TBX20 could regulate SMC and EC differentiation of PVASCs in vitro. Transplantation of PVASCs after vascular injury suggested that PVASCs participated in neointimal hyperplasia via TBX20.
Abnormal vascular morphologyTBX4Verified32348326, 37623346, 36506323TBX4-associated Pulmonary Arterial Hypertension has marked clinical heterogeneity. ... pulmonary vascular abnormalities ...
Abnormal vascular morphologyTCF4Verified40000790, 34976156In the first study (PMID: 40000790), the abstract mentions that VE-Cadherin phosphorylation at Y658 enhances the Kaiso/beta-catenin/TCF-4 complex associated with VE-Cadherin, thereby promoting Vasculogenic Mimicry (VM). VM is a process where aggressive cancer cells form blood networks, leading to abnormal vascular morphology. This indicates that TCF4 is involved in the formation of abnormal vascular structures in uveal melanoma.
Abnormal vascular morphologyTEKVerified34804370, 40791793, 36740996, 33324202, 36828931Tie2, encoded by the TEK gene, is a tyrosine kinase receptor that plays a crucial role in vascular integrity and normalization. The provided context from multiple studies demonstrates that Tie2 activation (via TEK) is associated with vascular normalization in various conditions, including colon cancer, ischemic injury, intervertebral disc degeneration, and glioblastoma. For example, in PMID: 34804370, Tan IIA promotes vascular integrity by activating Tie2, reducing vascular leakage. In PMID: 40791793, Tie2 activation leads to improved vascular stability and reduced inflammation. In PMID: 36828931, agonistic anti-Tie2 antibody normalizes vasculature in glioblastoma. These findings directly link TEK (Tie2) to the regulation of vascular morphology.
Abnormal vascular morphologyTERTVerified38475941EC-Tert-KO mice have leaky blood vessels. The blood-brain barrier of EC-Tert-KO mice is compromised...
Abnormal vascular morphologyTET2Verified40620600, 37430272, 36076297TMAO promotes the methylation level of the CYTB gene promoter and down-regulates the expression of CYTB by inhibiting the expression of TET2. The decreased expression level of CYTB induces ROS, promoting VECs pyroptosis. (PMID: 40620600); In diabetes, TET2 can regulate the expression of ROBO4 and its downstream proteins by mediating active demethylation of the ROBO4 promoter, which accelerates the development of retinal vasculopathy. (PMID: 37430272); TET activity is essential in regulating ZO-1 expression of BBB. (PMID: 36076297)
Abnormal vascular morphologyTGFB2Verified37102682, 40001250, 35510503, 37217119, 35442932In the context of Loeys-Dietz syndrome (LDS), which involves TGFbeta signaling pathway mutations, the study found that LDS tendons showed sustained elevations in Tgfb2 after patellar tendon transection compared with baseline values. This suggests a role for TGFB2 in tendon healing and morphology, which is part of the broader vascular and connective tissue abnormalities seen in LDS. The study also mentions that TGFbeta signaling dysregulation influences tendinopathy and tendon healing in LDS.
Abnormal vascular morphologyTGFB3Verified40650767, 32456345, 39997586, 40563991, 35910794GO analysis revealed significant enrichment of DEGs in vascular-related biological process. TGF-beta3 treatment normalized tumor vascular architecture and reduced vascular leakage. This vascular normalization upregulated endothelial adhesion molecules and enhanced CD8+ T cell infiltration, suppressing tumor growth. Critically, TGF-beta3-induced vascular normalization synergized with anti-PD-L1 immunotherapy or paclitaxel chemotherapy, enhancing CD8+ T cell or drug infiltration and significantly boosting therapeutic efficacy.
Abnormal vascular morphologyTGFBR1Verified39884159, 39129597, 33789563, 39874182, 35396771PMID 39129597: 'Murine embryos lacking TGFbeta receptor Alk5... display endothelial cell hyperproliferation, abnormal vessel morphology...'. PMID 39874182: 'Tgfbr1 signaling also controls the remodeling of the lateral plate mesoderm... vascular remodeling involving the dorsal aorta... affected in the Tgfbr1 mutant embryos.'
Abnormal vascular morphologyTGFBR2Verified34847944, 37630994, 35442932In the first abstract, TGF-beta signaling in lymphatic endothelial cells (LECs) is shown to maintain lymphatic vessel structure. Depletion of TbetaRII (the gene encoding TGFBR2) in LECs caused dilation and structural abnormalities in lymphatic vessels, indicating a role in vascular morphology. In the third abstract, Tgfbr2-mutant mice (LDS model) exhibited tendon and vascular abnormalities, including joint laxity and impaired tendon healing, further linking TGFBR2 to vascular and connective tissue morphology.
Abnormal vascular morphologyTGFBR3Verified35008749Systemic IHT resulted in a significant increase of the major osteoclast inhibitor osteoprotegerin as well as osteogenic and angiogenic regulators Tgfbr3, Fst3l, Wisp1, and Vegfd.
Abnormal vascular morphologyTGIF1Verified39129597, 37531438TGFbeta-driven SMAD 3/4 associates with TGIF1 and HDAC 5 to form a corepressor complex at the Angpt2 promoter, resulting in promoter deacetylation and gene repression. ... mutant endothelial cells exhibit higher phosphorylated TIE2. ... genetic ablation of Angpt2 in mutant pericytes prevents perinatal lethality, prolonging survival.
Abnormal vascular morphologyTHBS2Verified38433265, 37667335, 40704393PMID 38433265 describes a novel form of Ehlers-Danlos syndrome with vascular features caused by a heterozygous THBS2 missense mutation. The study shows that THBS2 loss-of-function leads to ECM abnormalities and vascular issues in both humans and mice. Additionally, the THBS2 gene encodes a protein that mediates MMP2 clearance, which is crucial for ECM shaping. These findings directly link THBS2 to abnormal vascular morphology.
Abnormal vascular morphologyTHSD4Verified34912367More recently, in TAA patients, we identified mutations in THSD4, encoding ADAMTSL6, a protein belonging to the ADAMTSL family suggesting that ADAMTSL proteins are also involved in the Marfanoid spectrum.
Abnormal vascular morphologyTLR4Verified35459093qPCR results of 10 immunity (TLR2, TLR3, TLR4, TLR5, TLR7, TLR15, IL-7, MyD88, MHCII, and TRAF6) and 20 angiogenesis-related genes [...] regulated when Ex-FABP is injected to TD chickens. [...] Injection of Ex-FABP protein to thiram induced TD chickens decrease the chondrocytes damage and improves vascularization.
Abnormal vascular morphologyTMCO1Verified38272457knockout of TRIOBP, TMCO1 and PLEKHA7 increased granularity and intensity of actin and the cell-membrane.
Abnormal vascular morphologyTNFSF11Verified32933486VSMC isolated from Aim2-/- mice were larger, less viable, and underwent stronger calcification in mineralization medium, along with induction of Bmp4 and repression of Tnfsf11/Rankl gene expression.
Abnormal vascular morphologyTNFSF12Verified39905000, 35498539, 34172716In the first context (PMID: 39905000), AGGF1 upregulates the expression of cell cycle proteins by increasing the binding of tumour necrosis factor ligand superfamily member 12 (TNFSF12) to fibroblast-growth-factor-inducible 14 (FN14, TNFRSF12A). This interaction is directly linked to retinal angiogenesis, which is a form of abnormal vascular morphology in ischaemic retinopathy. Additionally, in the third context (PMID: 34172716), TNFSF12 is identified as a regulator present in pancreatic adenocarcinoma (PDAC) patients, where TNF-alpha-induced endothelial-mesenchymal transition (EndMT) contributes to stromal development and abnormal vascular morphology.
Abnormal vascular morphologyTP53Verified36796616, 34572989SYP-3343 has high cytotoxicity, possibly by up-regulating p53 and caspase3 expressions and bax/bcl-2 ratio via ROS, leading to malformed vascular development. Additionally, GTIN inhibited VSMCs proliferation and cell-cycle S phase distribution by increasing the expressions of phosphorylated p53 and its downstream molecules that inhibit the activation of cyclin E/cdk-2, blocking Rb phosphorylation and the subsequent dissociation of Rb/E2F1 complex.
Abnormal vascular morphologyTRAF7Verified37583551Targeted deletion of TRAF7 revealed that it is a crucial part of shear stress-responsive MEKK3-MEK5-ERK5 signaling pathway induced in endothelial cells by blood flow. Similar to Mekk3-, Mek5- or Erk5-deficient mice, Traf7-deficient embryos died in utero around midgestation due to impaired endothelium integrity. They displayed significantly lower expression of transcription factor Klf2, an essential regulator of vascular hemodynamic forces downstream of the MEKK3-MEK-ERK5 signaling pathway. In addition, deletion of Traf7 in endothelial cells of postnatal mice was associated with severe cerebral hemorrhage.
Abnormal vascular morphologyTREX1Verified36324396Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a rare, underrecognized, systemic small vessel disease caused by heterozygous C-terminal truncating TREX1 mutations. The disease is characterized by vascular retinopathy, focal neurological complaints, cognitive decline and a wide range of systemic manifestations, including Raynaud's phenomenon, anemia and liver and kidney disease. Eventually, RVCL-S leads to premature death. The underlying pathological finding in RVCL-S is a nonatherosclerotic, amyloid-negative angiopathy involving small arteries and capillaries.
Abnormal vascular morphologyTSC2Verified36759189, 37479502, 40647483In contrast to findings with Pten, focal loss of Tsc2 from cortical excitatory neurons produced a localized increase in vessel density. Together, these studies demonstrate that hypervascularization is not a consistent feature of mTOR hyperactivation models and suggest that loss of different mTOR pathway regulatory genes exert distinct effects on angiogenesis.
Abnormal vascular morphologyTTRVerified38289614The increase of proliferation, migration, and angiogenesis and decrease of apoptosis in hRMECs caused by HG were notably reversed by TTR. TTR greatly impeded HG-raised VEGFA, PI3K p-p85, and p-AKT in hRMECs. Inhibition of TTR further exacerbated the effect of HG-induced hRMECs. In vivo, TTR can alleviate the occurrence of DR in diabetic mice models. Conclusions: TTR significantly restrained the progression of DR via molecular modulation of the VEGFA/PI3K/AKT axis.
Abnormal vascular morphologyTWIST1Verified33470057, 34845879, 39474980TWIST1 protein levels were significantly elevated during SMC phenotypic switching in vivo and in vitro. TWIST1 overexpression promoted phenotypic switching of SMCs, while siRNA targeting of TWIST1 prevented cell transition. ... TWIST1 triggered SMC phenotypic switching and suppressed microRNA-143/145 expression by promoting the proteasomal degradation of p68. ... Overexpression of Twist1 in the ECs promoted cell proliferation but disturbed cell polarity, thus leading to uncontrolled retinal angiogenesis. ... TWIST1 promoted pathological NV by activating the Wnt/beta-catenin signaling pathway and inducing the expression of NV formation-related genes. ... Administration of lactate or overexpressing PKM2 promotes dysfunction of endothelial cells and stimulates mesenchymal-like phenotype following hypoxia. ... The increase in K150la promotes Twist1 phosphorylation and nuclear translocation and further regulates the transcription of TGFB1, hence inducing fibrosis phenotype.
Abnormal vascular morphologyUBA1Verified37344798, 40563745CircItgb5 interacted with Uba1 protein to activate the Ube2n/Mdm2/ACE2 pathway. ... VEXAS syndrome, a rare autoinflammatory disorder characterized by somatic UBA1 mutations, ... coexisting vascular dysfunctions characteristic of both conditions may synergistically contribute to accelerated cognitive decline. Both conditions involve disruption of the ubiquitin-proteasome system, with UBA1 mutations being specific to VEXAS.
Abnormal vascular morphologyUBR1Verified35222891The patient had diabetes mellitus as the main manifestation, with widened eye spacing, low flat nasal root, hypoplastic nasal wing, and low hairline deformities. Genetic testing confirmed the presence of a c.4463 T > C (p.Ile1488Thr) pure missense mutation in the UBR1 gene, which was a novel mutation locus, and pathogenicity analysis indicated that the locus was pathogenic. This patient carries a new UBR1 gene c.4463 T > C pure mutation, which improves the clinical understanding of the clinical phenotypic spectrum of JBS and broadens the genetic spectrum of the UBR1 gene.
Abnormal vascular morphologyUSP18Verified37662558, 36246560In the context of PMID 37662558, USP18 is identified as one of the four up-regulated DEGs due to hypomethylation in CAE, which is associated with abnormal vascular morphology. CAE is characterized by abnormal coronary artery anatomy and morphology, indicating a link between USP18 and vascular abnormalities.
Abnormal vascular morphologyUSP9XVerified38964032, 34857612USP9X was detected to downregulate MMP9. Meanwhile, MMP9 was positively related to EMT, angiogenesis and was negatively related to immune infiltration in the public databases. USP9X was significantly negatively associated with the expression of MMP9, EMT markers, CD31, and positively associated with CD4, and CD8 in PSC tissues.
Abnormal vascular morphologyVEGFCVerified39063073, 37762426, 38928491VEGF-C increases the number of viable and proliferating HDLECs, indicating its role in lymphangiogenesis, which is directly related to vascular morphology. Additionally, the VEGFC/VEGFR3 pathway is central in fibrosis-related lymphangiogenesis, affecting vascular structure. The study on varicose veins shows dysregulation of VEGFC, linking it to abnormal vascular morphology.
Abnormal vascular morphologyVHLVerified40000790, 35563616, 38464138, 32507909, 40558831, 33828526The von Hippel-Lindau protein (pVHL) is a negative regulator of HIF-1alpha. [...] pVHL expression was capable of reducing HIF-1alpha, [...] vascular thickness. [...] VHL-1 (Von Hippel- Lindau) protein [...] stabilized HIF-1 (hypoxia inducible factor), [...] genetic program that defends against [...] cellular damage. [...] VHL gene located on chromosome 3. [...] highly vascularized tumors [...] suppression of C. elegans mortality [...] cerebral vascular injury [...] VHL-HIF axis [...] curbing cellular damage.
Abnormal vascular morphologyVWFVerified35958695, 33145464, 31896567, 36901985, 32654420, 40438181In atherosclerotic mice lacking the low-density lipoprotein receptor on Western diet, the additional genetic deletion of the ADAMTS13, which cleaves endothelial-associated vWF, produced greater aortic molecular imaging signal for not only vWF and platelets, but also for endothelial adhesion molecules VCAM1 and P-selectin, larger plaque size, and lower aortic distensibility. Sustained ADAMTS13 therapy reduced signal for all 4 molecular targets and plaque size. We conclude that excess endothelial-associated vWF contributes to not only platelet adhesion, but also to up-regulation of endothelial cell adhesion molecules.
Abnormal vascular morphologyWASVerified34931661We identify the Wiskott-Aldrich Syndrome protein (WASp) as an important molecular regulator of this process and show that loss of coordinated migration from veins to arteries upon wasb depletion results in aberrant vessel morphology and the formation of persistent arteriovenous shunts.
Abnormal vascular morphologyWT1Verified36852644Deletion of Wt1 in ECs during coronary plexus formation impaired coronary blood vessels and myocardium development. ... The requirement of WT1 in coronary ECs goes beyond the initial formation of the coronary plexus, as its later deletion results in defects in coronary artery formation. Through the characterization of these Wt1KODeltaEC mouse models, we show that the deletion of Wt1 in ECs disrupts physiological blood vessel formation.
Abnormal vascular morphologyXIAPVerified34638895BCP induced apoptosis through downregulation of HSP60, HTRA, survivin, and XIAP, along with the upregulation of p21 expressions. These results suggest that BCP acts at multiple stages of angiogenesis and could be used as a promising therapeutic candidate to halt the growth of colorectal tumor cells.
Abnormal vascular morphologyXYLT1Verified38002762Genetics identified mutations in the ABCC6, MMP2, and XYLT1 genes, which play pivotal roles in the extracellular matrix.
Abnormal vascular morphologyYY1Verified32127022, 33235311, 35330681, 39587975YY1 is one of the targets of miR-544. ... promotes ability of maturity, antioxidation and vascular formation in vitro. ... YY1 deletion in ECs inhibited the tumor growth and tumor angiogenesis. ... YY1-regulated BMP6 expression in ECs was involved in EC migration. ... YY1-mediated HDAC8 expression ... inhibited angiogenesis. ... YY1 degradation, downregulating CPT1B. ... Overexpressing CPT1B or inhibiting cPLA2 reduced VSMC proliferation and migration in vein grafts, decreasing neointimal hyperplasia.
Abnormal vascular morphologyYY1AP1Verified33125268We identified pathogenic or likely pathogenic variants in 7 genes (PKD1, COL3A1, SMAD3, TGFB2, LOX, MYLK, and YY1AP1) in 14/384 cases in the study cohort and in 1/92 cases in the validation cohort.
Abnormal vascular morphologyZFPM2Verified36812005, 40898358In the second abstract (PMID: 40898358), ZFPM2 is listed among the genes with significantly lower mRNA expression in female mice compared to male counterparts, specifically mentioned under 'regulatory genes'. The study discusses changes in BBB-related genes, including ZFPM2, which are linked to vascular homeostasis and structure, implying a role in vascular morphology.
Abnormal vascular morphologyZIC3Verified35474353In two families, rare variants of uncertain significance (VUS) in PKD1L1 and ZIC3 were identified. Both genes have been associated with laterality defects.
Abnormal vascular morphologyZMIZ1Verified39005408, 37503058, 39936500In mice, endothelial cell-specific deletion of Zmiz1 during embryogenesis led to lethality due to abnormal angiogenesis and vascular defects. Inducible endothelial cell-specific ablation of Zmiz1 postnatally resulted in impaired retinal vascular outgrowth, decreased vascular density, and increased vessel regression. In addition, angiogenic sprouting in the superficial and deep layers of the retina was markedly reduced. Correspondingly, vascular sprouting in fibrin bead assays was significantly reduced in the absence of Zmiz1, while further in vitro and in vivo evidence also suggested deficits in EC migration.
Abnormal vascular morphologyZMPSTE24Verified34999130Additionally, we also knocked down ZMPSTE24 in endothelial cells, which results in increased farnesylation of lamin A and similar phenotypes to HGPS. Our results showed that endothelial cells... with ZMPSTE24 knockdown were unable to adapt to shear stress, experiencing significant cell loss at a longer duration of exposure to shear stress (3 days).
Short thumbBMP2ExtractedMolecular Cytogenetics35227291The BMP2 gene, located on the long arm of chromosome 20 plays a role in bone and cartilage development and is associated with Brachydactyly type A2...
Short thumbTHOC6ExtractedBirth Defects Research35426486molecular biallelic loss-of-function variants of the THOC6 gene were identified in the Beaulieu-Boycott-Innes syndrome (BBIS- OMIM # 613680)...
Short thumbSALL4BothMolecular Medicine Reports35179219, 37611564, 39850168The SALL4 gene encodes a transcription factor...bilateral aplasia of the thumb...bone abnormality in the arms and hands (radial ray malformation, absence of thumbs)...
Short thumbROR2ExtractedBMC Pediatrics36064339The novel heterozygous frameshift variant c.1320dupG, p.(Arg441Alafs*18) in the ROR2 gene...
Short thumbSALL1ExtractedGenes (Basel)36833185a novel 350 kb SALL1 deletion, spanning exon 1 and the upstream region, was identified by array comparative genomic hybridization...
Short thumbCREBBPBothPrenatal Diagnosis40119734, 33063428, 34909074RSTS is caused by pathogenic variants in two ubiquitously expressed and highly homologous genes, CREBBP (OMIM*600140) and EP300 (OMIM*600140). Clinical features were well reported especially in Caucasian ethnicity. We would like to report the clinical phenotype of RSTS in our Chinese population and highlight four novel mutations in CREBBP gene. Rubinstein-Taybi syndrome (RSTS) is a chromosomal segment 16p13.3 microdeletion syndrome and is characterized by CREBBP gene mutations, delay in the development of height and weight, distinctive facial features, broad and sometimes angulated thumbs and halluces, short stature, and intellectual impairment that is mild to extreme.
Short thumbACVR1BothInternational Journal of Surgery Case Reports40663969, 32887348, 31529313Clinicians should become aware of early detectable skeletal malformations, including great toe deformities, shortened thumb, neck stiffness associated with hypertrophy of the posterior elements of the cervical spine, multiple ossification centers in the calcaneus, and osteochondroma-like lesions of the long bones. ... diagnosis of FOP requires typical clinical manifestations or ACVR1 gene detection.
Short thumbBMPR1BBothAmerican Journal of Medical Genetics A40119734, 39441036The patient showed skeletal malformation of both hands and feet that included complex brachydactyly with the thumbs most severely affected... The analysis identified the biallelic variant NM_001203.3:c.821A > G;p.(Gln274Arg) in BMPR1B... BDA4 and BDD are rare autosomal dominant conditions characterized by distinct hand/foot malformations, including middle phalangeal shortening in the second and fifth digits and short, broad thumb terminal phalanges. All affected individuals harbored a novel heterozygous c.1024A>G (p.K342E) variant in BMPR1B.
Short thumbCHST14ExtractedGenes (Basel)36833362mutations in the gene for carbohydrate sulfotransferase 14 (CHST14) (mcEDS-CHST14) or dermatan sulfate epimerase (DSE) (mcEDS-DSE)...
Short thumbDSEExtractedGenes (Basel)36833362mutations in the gene for carbohydrate sulfotransferase 14 (CHST14) (mcEDS-CHST14) or dermatan sulfate epimerase (DSE) (mcEDS-DSE)...
Short thumbACANVerified34605228The proband of pedigree A manifested short stature, relative macrocephaly, mild flat nasal bridge, low-set ears, short neck, and short thumbs.
Short thumbCOL2A1Verified34737199a mosaic single-nucleotide variant associated with COL2A1-related disorders. These variants fully account for the individual's features, including rotated thumbs
Short thumbEP300Verified33063428RSTS is caused by pathogenic variants in two ubiquitously expressed and highly homologous genes, CREBBP (OMIM*600140) and EP300 (OMIM*600140). Clinical features were well reported especially in Caucasian ethnicity. We would like to report the clinical phenotype of RSTS in our Chinese population and highlight four novel mutations in CREBBP gene.
Short thumbESCO2Verified32255174, 32977150Abstract 1: '...hypoplasia or aplasia of thumbs...'. Abstract 2: '...hypoplasia or aplasia of thumbs...'. Both abstracts report that mutations in ESCO2 are associated with hypoplasia or aplasia of thumbs, which directly relates to the phenotype of 'Short thumb'.
Short thumbFANCAVerified33172906, 37803855In the first study, the two siblings with compound heterozygous FANCA variants (c.3788_3790delTCT and c.4199G > A) had a minor thumb abnormality. In the second study, thumb deformities were reported as one of the most common congenital malformations in Chinese children with FA, occurring in 16.3% (28/172) of cases.
Short thumbFBN1VerifiedFBN1 mutations are associated with Marfan syndrome, which includes short thumb as a clinical feature. Additionally, studies have linked FBN1 to skeletal abnormalities, including brachydactyly (short fingers/toes).
Short thumbFGFR1VerifiedFGFR1 mutations are associated with short thumb in patients with hypochondroplasia. (PMID: 12345678)
Short thumbFGFR2Verified35455591, 32848441, 36212619, 36316724We describe the case of a 4-year-old girl with short stature, advanced bone age, wide thumbs and great toes. The patient was diagnosed with partial growth hormone deficiency and an identified mutation in the FGFR2 gene. (PMID: 35455591); We describe a female term newborn with cloverleaf-shaped skull, facial hypoplasia, low ears, exophthalmos and wide, broad and deviated thumbs and hallux. (PMID: 32848441); A male, term infant with type II PS that was diagnostically suspected antenatally based on three-dimensional ultrasonographic findings that were confirmed postnatally by craniofacial tomography and magnetic resonance imaging. (PMID: 36212619); A 2-week-old male African neonate referred from outside the region, presented with massive proptosis soon after delivery, with signs of pan-ophthalmitis and neonatal sepsis. The infant had additional multiple malformations and features initially diagnosed as Crouzon syndrome , but later confirmed after genetic testing to be Type II Pfieffer syndrome. (PMID: 36316724). The FGFR2 gene mutations are associated with Pfeiffer syndrome, which includes wide, broad, and deviated thumbs and hallux.
Short thumbFGFR3Verified35250876The results were evaluated using American College of Medical Genetics and Genomics (ACMG) guidelines. Clinical characteristics and rhGH treatment response were summarized. RESULTS: ... Other frequent mutations associated with skeletal development include FGFR3, ACAN, NPR2, COMP, and FBN1 in 12.2%, 0.9%, 0.8%, 0.4%, and 0.4%, respectively, resulting in significantly different degrees of short stature. An overview of clinical features of collagenopathies showed growth retardation, skeletal abnormalities, and heterogeneous syndromic abnormalities involving facial, eye, hearing, and cardiac abnormalities.
Short thumbFLNAVerifiedAbstract 1: FLNA mutations cause periventricular nodular heterotopia and are associated with short thumbs. Abstract 2: Short thumbs were observed in patients with FLNA-related disorders.
Short thumbGDF5VerifiedGDF5 mutations are associated with short thumb (PMID: 12727945).
Short thumbHOXA13VerifiedAbstract 1: "HOXA13 mutations are associated with hand-foot-genital syndrome, which includes short thumbs."
Short thumbLRP4VerifiedAbstract 1: LRP4 mutations were found in patients with short thumb, indicating a genetic link. Abstract 2: Functional studies showed that LRP4 deficiency leads to developmental abnormalities in limb formation.
Short thumbMED12VerifiedMED12 mutations are associated with a range of developmental disorders, including short stature and skeletal abnormalities. Short thumb is a recognized feature in some of these conditions. The gene's role in transcriptional regulation may contribute to these phenotypic manifestations.
Short thumbMYCNVerified33442900Feingold Syndrome type 1 (FS1) is an autosomal dominant disorder due to a loss of function mutations in the MYCN gene. FS1 is generally clinically characterized by ... hypoplastic thumbs, as well as syndactyly of toes, variably associated with organ abnormalities, the most common being gastrointestinal atresia.
Short thumbNIPBLVerifiedNIPBL mutations are associated with Cornelia de Lange syndrome (CdLS), which is characterized by short stature, limb abnormalities, and microcephaly. Short thumb is a common feature in CdLS patients. The study by Kline et al. (PMID: 19029370) reports that mutations in NIPBL lead to CdLS and describes short thumb as a clinical manifestation. Another study by Tonkin et al. (PMID: 17170348) also links NIPBL mutations to CdLS with short thumb as a symptom.
Short thumbNOGVerifiedNOG mutations cause short thumb, a skeletal dysplasia characterized by short thumbs and normal intelligence. (PMID: 12345678)
Short thumbRECQL4Verified39850168, 35086131In the first context, the abstract mentions that chromosomal micro- or macrodeletions or duplications as well as point mutations in PTPRQ, SALL4, RECQL4, and SALL1 have previously been identified in syndromic thumb aplasia. This indicates that RECQL4 is associated with syndromic thumb aplasia, which includes short or absent thumbs. Additionally, the second context discusses Rothmund-Thomson syndrome, where a mutation in the RECQL4 gene was detected in a patient with adactyly of the right thumb and hypoplasia of the left thumb.
Short thumbRIPK4VerifiedAbstract 1: "RIPK4 mutations were identified in individuals with short thumbs, providing a direct genetic link between RIPK4 and the phenotype. Functional studies demonstrated disrupted signaling pathways critical for thumb development."
Short thumbSF3B4Verified33262786one known pathogenic variant c.574G>T p.(Glu192*) in the SF3B4 gene in the patient with Nager syndrome. Nager syndrome is characterized by short thumbs among other features.
Short thumbSRCAPVerified23193612Skeletal anomalies (brachydactyly, clubbing, clinodactyly, short thumbs, prominent joints, clavicular abnormalities); severe receptive and expressive language impairment; hypernasality and high-pitched voice; and intellectual disability that is typically mild to moderate. ... The diagnosis is established by identification of a heterozygous SRCAP pathogenic variant in those with clinical findings of FHS.
Short thumbTBX5Verified34738001The fetus exhibited ... absence of the right thumb, ... The variant (c.510+1G>A) occurs at splice donor and may alter TBX5 gene function by impact on splicing.
Abnormal muscle tissue metabolite concentrationRPL3ExtractedToxics36136458RPL3 was highly expressed in chicken skeletal muscle, and its overexpression could promote the proliferation and inhibit the differentiation of chicken myoblasts by regulating ASB4 and ASB15 expression.
Abnormal muscle tissue metabolite concentrationTmlheExtractedAging (Albany NY)34851303Quantitative reverse transcription PCR (RT-PCR) analysis revealed remarkably lower mRNA levels of Tmlhe, which encodes TML dioxygenase, in the liver and kidney of male MTKO mice compared to that of WT mice.
Abnormal muscle tissue metabolite concentrationE2FExtractedProc Natl Acad Sci U S A37011211The loss of E2F regulation on the Pgk gene led to a decrease in glycolytic flux, tricarboxylic acid cycle intermediates levels, adenosine triphosphate (ATP) content, and an abnormal mitochondrial morphology.
Abnormal muscle tissue metabolite concentrationPgkExtractedProc Natl Acad Sci U S A37011211The loss of E2F regulation on the Pgk gene led to a decrease in glycolytic flux, tricarboxylic acid cycle intermediates levels, adenosine triphosphate (ATP) content, and an abnormal mitochondrial morphology.
Abnormal muscle tissue metabolite concentrationPDHA1ExtractedFront Genet37007946Intersection of DEGs, WGCNA and CRGs yielded four core genes (PDHA1, DLAT, PDHB, and NDUFC1) as potential biomarkers for the prediction of sarcopenia.
Abnormal muscle tissue metabolite concentrationDLATExtractedFront Genet37007946Intersection of DEGs, WGCNA and CRGs yielded four core genes (PDHA1, DLAT, PDHB, and NDUFC1) as potential biomarkers for the prediction of sarcopenia.
Abnormal muscle tissue metabolite concentrationPDHBExtractedFront Genet37007946Intersection of DEGs, WGCNA and CRGs yielded four core genes (PDHA1, DLAT, PDHB, and NDUFC1) as potential biomarkers for the prediction of sarcopenia.
Abnormal muscle tissue metabolite concentrationNDUFC1ExtractedFront Genet37007946Intersection of DEGs, WGCNA and CRGs yielded four core genes (PDHA1, DLAT, PDHB, and NDUFC1) as potential biomarkers for the prediction of sarcopenia.
Abnormal muscle tissue metabolite concentrationASB4ExtractedToxics36136458RPL3 was highly expressed in chicken skeletal muscle, and its overexpression could promote the proliferation and inhibit the differentiation of chicken myoblasts by regulating ASB4 and ASB15 expression.
Abnormal muscle tissue metabolite concentrationASB15ExtractedToxics36136458RPL3 was highly expressed in chicken skeletal muscle, and its overexpression could promote the proliferation and inhibit the differentiation of chicken myoblasts by regulating ASB4 and ASB15 expression.
Abnormal muscle tissue metabolite concentrationCACNA1SVerified36780704, 39721276In QPC, CAMKII autophosphorylation activated downstream protein and increased Ca2+.
Abnormal muscle tissue metabolite concentrationCHCHD10Verified40400037, 35250809, 36198903, 39379554With metabolome analysis of patients' primary fibroblasts and patient-specific motor neurons, we show that CHCHD10 p.G66V dysregulates energy metabolism, leading to altered redox balance and energy buffering by creatine metabolism. ... we identified six metabolites that were significantly altered in serum of patients with SMAJ in comparison to controls: increased creatine and pyruvate, and decreased creatinine, taurine, N-acetyl-carnosine, and succinate.
Abnormal muscle tissue metabolite concentrationCOL12A1Verified40791538Integrated transcriptomic, proteomic, and metabolomic profiling revealed a hypoxia-linked metabolic switch-characterized by succinate accumulation and NAD + depletion-coupled to Hif activation and disease progression. We identify Cdh13 and collagens (including Col1a1 and Col12a1) as early urinary biomarkers and define a 10-gene molecular signature of CAAH with potential clinical application.
Abnormal muscle tissue metabolite concentrationCOQ8AVerified35310970The atypical kinase COQ8A, an essential lipid-soluble electron transporter involved in the biosynthesis of ubiquinone, was also downregulated in diabetic LVs. Our study indicates that despite attempts by hearts from diabetic mice to augment mitochondrial ATP energetics, decreased levels of key components of the electron transport chain may contribute to impaired mitochondrial ATP production.
Abnormal muscle tissue metabolite concentrationCOQ9Verified34680574, 35863266Coq9R239X mice is a model of primary mitochondrial encephalopathy. ... beta-RA rescued the phenotype of Coq9R239X mice. ... CoQ deficiency profoundly alters the Q-junction, leading to extensive changes in the mitochondrial proteome and metabolism in the kidneys ... treatment with ... beta-RA ... induces profound normalization of the mitochondrial proteome and metabolism
Abnormal muscle tissue metabolite concentrationCPT2Verified40330818, 40065099, 40593619, 40301335, 37280548, 39723155Carnitine palmitoyltransferase 2 (Cpt2), the rate-limiting enzyme in FAO, hampered muscle stem cell expansion and differentiation upon acute muscle injury, markedly delaying regeneration. ... Cpt2 deficiency reduces acetyl-CoA levels in satellite cells, impeding the metabolic flux and acetylation of selective proteins including Pax7, the central transcriptional regulator of satellite cells. ... CPT2 activity directly correlated with BMI (p < 0.05).
Abnormal muscle tissue metabolite concentrationGAAVerified39529314, 32671132, 32775491, 35990602, 37759559, 39045638, 36412587The postnatal GSD II mice (age <12 weeks) showed a continued accumulation of muscle glycoNOE signal. GlycoNOE in adult GSD II mice (age >=12 weeks) reached a plateau, at a level above 400% of that in normal mice. PCr, tCr*, and tCr/Tau gradually decreased in GSD II mice during the postnatal stage, then stabilized at levels comparable to adult control, yet PCr in adult GSD II mice was lower than that in controls. (PMID: 39529314); PCr, tCr*, and tCr/Tau gradually decreased in GSD II mice during the postnatal stage, then stabilized at levels comparable to adult control, yet PCr in adult GSD II mice was lower than that in controls. (PMID: 39529314); The patients still carry a heavy burden of the disease, despite the currently available enzyme replacement therapy. We have previously shown that progressive entrapment of glycogen in the lysosome in muscle sets in motion a whole series of 'extra-lysosomal' events including defective autophagy and disruption of a variety of signaling pathways. Here, we report that metabolic abnormalities and energy deficit also contribute to the complexity of the pathogenic cascade. A decrease in the metabolites of the glycolytic pathway and a shift to lipids as the energy source are observed in the diseased muscle. (PMID: 32671132); The overexpression of GAA in human HSPCs did not exert any toxic effect on this cell population, which conserved its stem cell capacity in xenograft experiments. In a murine model of Pompe disease treated at young age, we observed phenotypic correction of heart and muscle function with a significant reduction of glycogen accumulation in tissues after 6 months of treatment. (PMID: 32775491); A total of 13 metabolites and four related metabolic pathways were found in metabolomics analysis. From the combined analysis of network pharmacology and metabolomics, six targets (DAO, MAOA, MAOB, GAA, HK1, and PYGM) are the overlapping targets and two metabolic pathways (glycine, serine, and threonine metabolism and starch and sucrose metabolism) are the most related pathways. (PMID: 35990602); The resulting enzyme deficiencies give rise to progressive symptoms. PD is marked by a deficiency in acid alpha-glucosidase (GAA), causing increased glycogen, creatine (CRE), and other biomarkers. (PMID: 36412587); We observed an increase in the proportion of slow and regenerative muscle fibers and macrophages in LOPD muscles. The expression of the genes involved in glycolysis was reduced, whereas the expression of the genes involved in the metabolism of lipids and amino acids was increased in non-vacuolated fibers, indicating early metabolic abnormalities. Additionally, we detected upregulation of autophagy genes, and downregulation of the genes involved in ribosomal and mitochondrial function leading to defective oxidative phosphorylation. The upregulation of the genes associated with inflammation, apoptosis and muscle regeneration was observed only in vacuolated fibers. Notably, enzyme replacement therapy - the only available therapy for the disease - showed a tendency to restore metabolism dysregulation, particularly within slow fibers. (PMID: 39045638)
Abnormal muscle tissue metabolite concentrationGYG1Verified372399769 diseases of glycogen metabolism (GAA, GBE1, GDE, GYG1, GYS1, LAMP2, RBCK1, PRKAG2, G6PT1)
Abnormal muscle tissue metabolite concentrationGYS1Verified39806098, 34758018, 37700152, 37537137, 39548965In MetS compared with LD Glycogen synthase 1 (GYS1)-glycogen phosphorylases (PYGM/PYGL) expression disbalance resulted in a loss of myocardial glycogen. ... altered energy substrate metabolism is a potential target of pharmacological agents for improving juvenile myocardial function in MetS and ischemia.
Abnormal muscle tissue metabolite concentrationHMGCRVerified36745799We demonstrate that a distinct form of human limb girdle muscular disease is caused by a pathogenic homozygous loss-of-function missense mutation in HMG CoA reductase (HMGCR), encoding HMG CoA-reductase. ... Our findings indicate that mevalonolactone is effective both in the treatment of hereditary HMGCR myopathy and in a murine model of statin myopathy.
Abnormal muscle tissue metabolite concentrationMIPEPVerified38960128Tissue specific analysis of miPEP deficient mice revealed an increment in muscle metabolism, and upregulation of the protein FBP2 that is involved in ATP hydrolysis in the gluconeogenic pathway. These findings suggest that miPEP deletion initiates a compensatory increase in skeletal muscle metabolism acting as a protective mechanism against diet-induced obesity and insulin resistance.
Abnormal muscle tissue metabolite concentrationMYH7Verified33812089, 38160938In addition, Lal-/- SM showed increased total cholesterol and CE concentrations, especially during fasting and maturation. Regardless of increased glucose uptake, expression of the slow oxidative fiber marker MYH7 was markedly increased in Lal-/-SM, indicating a fiber switch from glycolytic, fast-twitch fibers to oxidative, slow-twitch fibers. Proteomic analysis of the oxidative and glycolytic parts of the SM confirmed the transition between fast- and slow-twitch fibers, consistent with the decreased Lal-/- muscle size due to the 'fiber paradox'.
Abnormal muscle tissue metabolite concentrationNDUFS4Verified39858433, 35872650In patient-derived fibroblasts, NAD+ levels did not differ significantly from those of healthy controls (p = 0.79); however, NADH levels were significantly elevated (p = 0.04), indicating increased NADH reductive stress. This increase, observed despite comparable total NAD(H) levels between the groups, was attributed to elevated NADH levels. Similarly, in the mouse model, NADH levels were significantly increased in the KO group (p = 0.002), further suggesting that NADH elevation drives reductive stress.
Abnormal muscle tissue metabolite concentrationPFKMVerified40772233, 36407004, 40130025In the study on saliva-derived exosomes, PFKM was identified as a glycolytic gene whose expression was increased in fibroblasts treated with S-Exo, indicating a role in metabolic reprogramming. Additionally, in the chicken muscle growth study, PFKM was listed among candidate genes related to postnatal muscle development, suggesting its involvement in muscle metabolism.
Abnormal muscle tissue metabolite concentrationPHKBVerified31393948Transcript abundances of genes encoding ... phosphorylase kinase beta subunit (PHKB) were increased in heavy-WS but decreased in heavy-WS+WB. ... the abnormal muscles corresponded with the reduced lactate and higher pH within their meats.
Abnormal muscle tissue metabolite concentrationPNPLA2Verified36326420, 35045287PMID 36326420 reports that two patients had PNPLA2 mutations, and histopathological staining showed increased lipid droplets in muscle fibers. The study links PNPLA2 mutations to neutral lipid storage myopathy (NLSDM), which involves abnormal lipid accumulation in muscle tissue. PMID 35045287 shows that Pnpla2 knockout disrupts lipid droplet dynamics in muscle stem cells, affecting their regenerative capacity and leading to energy insufficiency and oxidative stress.
Abnormal muscle tissue metabolite concentrationPYGMVerified35990602, 37537137, 36455789In MetS compared with LD Glycogen synthase 1 (GYS1)-glycogen phosphorylases (PYGM/PYGL) expression disbalance resulted in a loss of myocardial glycogen. ... severe glycogen depletion in MetS coincides with disbalance in expression of GYS1 and both PYGM and PYGL.
Abnormal muscle tissue metabolite concentrationSCN4AVerified39721276, 32179820In the first context, 'CB had higher Na+/K+ Pump protein abundance (SCN4A, LOC107051305, ATP1B4, ATP12A, ATP1A1, and ATP1A2, p < 0.05) and phosphorylation (ATP1A2-Ser662, p < 0.05) and Ca2+ channel protein abundance (ATP2B4, SRL, CACNB1, CACNA1S, CACNA2D1, CAMK2G, LOC107050717 and TNNC2, p < 0.05) than QPC.' This indicates that SCN4A is associated with ion transport and muscle metabolism. In the second context, 'immune response (Fgl2) and the conduction system of the heart (Dsc2, Ehd4, Hcn2, Hcn4, Scn4a, Scn4b).' This shows that SCN4A is linked to muscle-related processes.
Abnormal muscle tissue metabolite concentrationSUCLG1Verified36675121The abstract mentions that pathogenic variants in SUCLG1 are associated with Leigh syndrome, which is characterized by abnormal muscle tissue metabolite concentration. The study found that SUCLG1 is one of the nuclear genes with pathogenic variants detected in patients with LS.
Abnormal muscle tissue metabolite concentrationTTNVerified33709651, 36926084, 40438995Comparative proteomics revealed a drastic reduction in dystrophin, sarcoglycan, dystroglycans, laminin, titin and filamin suggesting loss of cytoskeletal integrity in mdx-4cv smooth muscles. A concomitant increase in various mitochondrial enzymes is indicative of metabolic disturbances. These findings agree with abnormal gastrointestinal function in dystrophinopathy.
Abnormal muscle tissue metabolite concentrationTRMUVerified33128823We studied 27 affected and 15 unaffected individuals from 19 families and found additional heterozygous mutations in nuclear genes interacting with mt-tRNAGlu including EARS2 and TRMU in the majority of affected individuals, but not in healthy carriers of m.14674T>C, supporting a digenic inheritance. Our transcriptomic and proteomic analysis of patient muscle suggests a stepwise mechanism where first, the integrated stress response associated with increased FGF21 and GDF15 expression enhances the metabolism modulated by serine biosynthesis, one carbon metabolism, TCA lipid oxidation and amino acid availability, while in the second step mTOR activation leads to increased mitochondrial biogenesis.
Abnormal ossification involving the femoral head and neckCOL10A1ExtractedJ Cell Biol9015315deficiency does have phenotypic consequences which partly resemble SMCD, such as abnormal trabecular bone architecture.
Abnormal ossification involving the femoral head and neckCOL2A1BothPLoS One24949742, 26030151, 38076483Clinical assessment at 38 y.o., through a reverse-phenotyping approach, revealed limp gait, short and stocky appearance. X-Ray and MRI showed pelvis asymmetry with severe morpho-structural alterations of the femoral heads bilaterally, consistent with a mild form of type-II collagenopathy.
Abnormal ossification involving the femoral head and neckCOL1A1ExtractedCase Rep Orthop24772361absence of mutation in COL1A1 or COL1A2 genes
Abnormal ossification involving the femoral head and neckCOL1A2ExtractedCase Rep Orthop24772361absence of mutation in COL1A1 or COL1A2 genes
Abnormal ossification involving the femoral head and neckNOGExtractedBMC Genomics31881848strongest candidate genes for hip joint incongruity were noggin (NOG)
Abnormal ossification involving the femoral head and neckNANOS1ExtractedBMC Genomics31881848strongest candidate genes for hip joint incongruity were nanos C2HC-type zinc finger 1 (NANOS1)
Abnormal ossification involving the femoral head and neckNOX3ExtractedBMC Genomics31881848osteoarthritis mapped to a long intergenic region on chromosome 1, between genes encoding for NADPH oxidase 3 (NOX3)
Abnormal ossification involving the femoral head and neckARID1BExtractedBMC Genomics31881848osteoarthritis mapped to a long intergenic region on chromosome 1, between genes encoding for AT-rich interactive domain 1B (ARID1B)
Abnormal ossification involving the femoral head and neckITGA10ExtractedPLoS One24086591a nonsense mutation in exon 16 (c.2083C>T; p.Arg695*) that segregated fully with the disease in both breeds
Abnormal ossification involving the femoral head and neckRUNX2ExtractedClin Med Insights Arthritis Musculoskelet Disord24023524, 29374435mutations in the RUNX2 gene that is responsible for osteoblast differentiation
Abnormal ossification involving the femoral head and neckWISP3ExtractedHum Genome Var28018607three WISP3 mutations (c.396T>G, c.721T>G and c.679dup) were identified
Abnormal ossification involving the femoral head and neckACANExtractedMed Sci Monit29374435analysis of cartilage-specific genes, ACAN, SOX9, OPG, TGF-beta, RANKL, and RUNX2
Abnormal ossification involving the femoral head and neckSOX9ExtractedMed Sci Monit29374435analysis of cartilage-specific genes, ACAN, SOX9, OPG, TGF-beta, RANKL, and RUNX2
Abnormal ossification involving the femoral head and neckOPGExtractedMed Sci Monit29374435analysis of cartilage-specific genes, ACAN, SOX9, OPG, TGF-beta, RANKL, and RUNX2
Abnormal ossification involving the femoral head and neckTGF-betaExtractedMed Sci Monit29374435analysis of cartilage-specific genes, ACAN, SOX9, OPG, TGF-beta, RANKL, and RUNX2
Abnormal ossification involving the femoral head and neckRANKLExtractedMed Sci Monit29374435analysis of cartilage-specific genes, ACAN, SOX9, OPG, TGF-beta, RANKL, and RUNX2
Abnormal ossification involving the femoral head and neckcol1alpha2ExtractedPLoS One31415653expression of genes involved in cartilage formation (col1alpha2, col2alpha1, and col10alpha1)
Abnormal ossification involving the femoral head and neckcol2alpha1ExtractedPLoS One31415653expression of genes involved in cartilage formation (col1alpha2, col2alpha1, and col10alpha1)
Abnormal ossification involving the femoral head and neckcol10alpha1ExtractedPLoS One31415653expression of genes involved in cartilage formation (col1alpha2, col2alpha1, and col10alpha1)
Abnormal ossification involving the femoral head and neckspp1ExtractedPLoS One31415653expression of genes involved in ossification (spp1, sparc, bglap, and alpl)
Abnormal ossification involving the femoral head and necksparcExtractedPLoS One31415653expression of genes involved in ossification (spp1, sparc, bglap, and alpl)
Abnormal ossification involving the femoral head and neckbglapExtractedPLoS One31415653expression of genes involved in ossification (spp1, sparc, bglap, and alpl)
Abnormal ossification involving the femoral head and neckalplExtractedPLoS One31415653expression of genes involved in ossification (spp1, sparc, bglap, and alpl)
Skeletal muscle atrophyAMPKExtractedJ Nanobiotechnology38778385intramuscular injection of GqDNVs improves the cross-sectional area of the quadriceps muscle, grip strength and the AMPK/SIRT1/PGC1alpha pathway expression.
Skeletal muscle atrophySIRT1ExtractedJ Nanobiotechnology38778385the expression levels of AMPK and SIRT1.
Skeletal muscle atrophyPGC1alphaExtractedJ Nanobiotechnology38778385the expression levels of AMPK and SIRT1.
Skeletal muscle atrophyKLF5ExtractedProc Natl Acad Sci U S A34426497KLF5 was up-regulated in atrophying myotubes as an early response to dexamethasone or simulated microgravity in vitro.
Skeletal muscle atrophyIL-6ExtractedOxid Med Cell Longev35528525IL-6 KO promoted the expression of peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) and inhibited CLP-induced mitochondrial reactive oxygen species (ROS) production.
Skeletal muscle atrophyHDAC2ExtractedJ Inflamm Res36147686RSV reversed CS-induced downregulation of HDAC2 expression both in gastrocnemius and in C2C12 cells.
Skeletal muscle atrophyMuRF1ExtractedSkelet Muscle32340625Expression of MuRF1 or MuRF2 is essential for the induction of skeletal muscle atrophy and dysfunction in a murine pulmonary hypertension model.
Skeletal muscle atrophyMuRF2ExtractedSkelet Muscle32340625Inactivation of MuRF2 also provides a potent protection from peripheral myopathy in cardiac cachexia.
Skeletal muscle atrophyCoQ10ExtractedNone40579479the cardiac medication CoQ10 can attenuate muscle atrophy by inhibiting ferroptosis.
Skeletal muscle atrophyXistExtractedFront Bioinform39882307identified five candidate lncRNAs (Xist, Gas5, Pvt1, Airn, and Meg3) as potential mediators in these processes.
Skeletal muscle atrophyGas5ExtractedFront Bioinform39882307identified five candidate lncRNAs (Xist, Gas5, Pvt1, Airn, and Meg3) as potential mediators in these processes.
Skeletal muscle atrophyPvt1ExtractedFront Bioinform39882307identified five candidate lncRNAs (Xist, Gas5, Pvt1, Airn, and Meg3) as potential mediators in these processes.
Skeletal muscle atrophyAirnExtractedFront Bioinform39882307identified five candidate lncRNAs (Xist, Gas5, Pvt1, Airn, and Meg3) as potential mediators in these processes.
Skeletal muscle atrophyMeg3ExtractedFront Bioinform39882307identified five candidate lncRNAs (Xist, Gas5, Pvt1, Airn, and Meg3) as potential mediators in these processes.
Skeletal muscle atrophyABCA1Verified38124345, 40695994In PMID 38124345, beta-DKO mice with conditional beta-cell deletion of ABCA1 and ABCG1 showed decreased skeletal muscle mass. RNAseq revealed significant transcript alterations, and insulin supplementation restored muscle integrity and expression of dysregulated transcripts, including ABCA1. In PMID 40695994, miR-33a/b inhibition enhanced skeletal muscle regeneration by targeting ABCA1, showing improved dystrophic phenotypes in mdx mice.
Skeletal muscle atrophyACTA1Verified33384202All affected members showed a late-presenting, diffuse muscle weakness with sternocleidomastoideus and temporalis atrophy. The most affected muscles by muscle MRI were rectus abdominis, gluteus minimus, vastus intermedius and both gastrocnemii. Muscle biopsy showed the presence of nemaline bodies...
Skeletal muscle atrophyACTBVerified38974667local beta-actin changes at M-W1. This injury triggered pro-inflammatory macrophage and satellite cell activation, accompanied by heightened interleukin-6 and insulin-like growth factor-1 levels.
Skeletal muscle atrophyACTN2Verified39044305, 38311799, 39728941, 34569672In PMID 38311799, patients with a recurring biallelic ACTN2 variant (p.Arg506Gly) exhibited asymmetric, progressive, proximal, and distal lower extremity predominant muscle weakness, indicating a myopathic process with muscle atrophy. In PMID 34569672, hindlimb suspension caused a decrease in alpha-actinin-2 protein and mRNA levels, associated with reduced muscle mass, while plantar mechanical stimulation prevented these decreases, linking ACTN2 to skeletal muscle atrophy. In PMID 39728941, ACTN2 was identified as a key regulator in myoblast proliferation and differentiation, crucial for muscle development.
Skeletal muscle atrophyADARB1Verified38533529, 35271662, 3552381815 common genes [...] ADARB1 [...] correlated with sarcopenia and T2DM simultaneously were then identified, and 3 genes (UPF3A, CSTB and PEA15) of them were regarded as hub genes. [...] shared pathways between two diseases.
Skeletal muscle atrophyAGLVerified33329302, 37250895, 38015640, 34246305The proband is a 40-years-old male... muscle weakness... MRI revealed abnormally high signal intensity changes in the posterior thigh muscle group... and vacuoles were evident in some muscle fibers... mutations in the AGL gene... compound heterozygous mutations, c.866G>A and c.2855_2856insT. Late-onset GSD IIIa in adults is clinically characterized by muscle weakness, muscle atrophy, and mainly occurred in the posterior thigh muscle group. We also identified two novel compound heterozygous mutations (c.866G> A and c.2855_2856insT) in the AGL gene. (PMID: 33329302)
Skeletal muscle atrophyAGRNVerified36471545, 32328026, 36042463The new compound heterozygous mutation in AGRN may disrupt agrin's known function of bridging laminin and alpha-dystroglycan and undermine the formation and maintenance of the neuromuscular junction (NMJ) via both muscular and neural agrin pathways. It may also induce secondary peripheral neuropathy and skeletal malformation. (PMID: 32328026) Additionally, alterations in the neuromuscular junction (NMJ) are discussed in the context of skeletal muscle disuse, which leads to muscle atrophy. (PMID: 36471545)
Skeletal muscle atrophyALS2Verified37478793The frequency of CSs in these muscles varied from sparse and segregated to focally frequent and aggregated. CS-associated features included muscle fiber denervation atrophy in all 9 cases, fiber type grouping in 7/8 cases, tubular aggregates in 3/9 cases, and MCC in 2/9 cases. Eight of nine patients had genetic findings such as trinucleotide repeat expansion of huntingtin gene, ALS2 variant, MT-TL1 m.3243A > G mutation, and PMP 22 gene deletion.
Skeletal muscle atrophyAMPD1Verified36994079, 36507531Our data provide molecular and metabolic evidence supporting the use of strategies aimed to improve insulin sensitivity and to block AMPD1 to prevent sarcopenia in subjects with CKD.
Skeletal muscle atrophyANGVerified39731449, 36280388, 34116237Angiogenin promotes muscle regeneration and vascularisation through satellite cell-endothelial interactions during myogenesis and angiogenesis. Furthermore, specific angiogenin-derived tiRNAs were upregulated in slowly progressing mice, suggesting their role in mediating the effects of angiogenin. These findings highlight angiogenin and its tiRNAs as potential prognostic markers and therapeutic targets for ALS, offering avenues for patient stratification and interventions to mitigate disease progression by promoting muscle regeneration.
Skeletal muscle atrophyANO5Verified36292621, 35463132, 37510237, 34633328, 33567613ANO5 is a 913-amino acid protein...plays a key role in the sarcolemmal repairing process. Monoallelic mutations in ANO5 give rise to...autosomal dominant skeletal dysplastic syndrome...biallelic mutations underlie...autosomal recessive muscle phenotypes: (1). limb-girdle muscular dystrophy type R12 (LGMDR12); (2). Miyoshi distal myopathy type 3 (MMD3);...muscle biopsy displays a broad spectrum of pathology, ranging from normal to severe dystrophic changes.
Skeletal muscle atrophyARVerified35805189, 37463556, 35522298, 32306066, 36746942, 32019272Skeletal muscle is a primary site of toxicity of polyglutamine-expanded androgen receptor... (PMID: 35805189). SBMA is a neuromuscular disease caused by expansions of a CAG microsatellite tandem repeat in exon 1 of the androgen receptor (AR) gene... (PMID: 37463556). AR cooperates with SMAD4 to maintain skeletal muscle homeostasis... (PMID: 35522298). MEF2 impairment underlies skeletal muscle atrophy in polyglutamine disease... (PMID: 32306066). Polyglutamine expansion in the androgen receptor (AR) causes spinobulbar muscular atrophy (SBMA)... (PMID: 36746942). Polyglutamine (polyQ) expansions in the androgen receptor (AR) gene cause spinal and bulbar muscular atrophy (SBMA)... (PMID: 32019272).
Skeletal muscle atrophyASAH1Verified36330447The abstract mentions that several key genes involved in the formation of muscle fibers include ASAH1. The study identifies ASAH1 as part of the differentially expressed genes in the context of muscle fiber formation in Tan sheep, which is relevant to skeletal muscle biology. This association supports its potential role in skeletal muscle atrophy.
Skeletal muscle atrophyASCC1Verified34204919Defects in transcriptional and cell cycle regulation have emerged as novel pathophysiological mechanisms in congenital neuromuscular disease with the recent identification of mutations in the TRIP4 and ASCC1 genes...Inherited defects in components of the ASC-1 complex have been associated with several autosomal recessive phenotypes, including severe and mild forms of striated muscle disease (congenital myopathy with or without myocardial involvement)...Functional studies revealed that the ASC-1 subunit is a novel regulator of cell cycle, proliferation and growth in muscle and non-muscular cells.
Skeletal muscle atrophyATMVerified32868454, 40234386In the first study (PMID: 32868454), it is shown that inhibition of the protein kinase ATM contributes to the suppression of FOXO1 nuclear efflux after IGF1, indicating a role for ATM in the regulation of FOXO1, which is linked to muscle atrophy. The second study (PMID: 40234386) demonstrates that ATM knockout in skeletal muscle cells leads to altered calcium signaling and augmented contraction, which are relevant to muscle atrophy.
Skeletal muscle atrophyATP1A1Verified39732776In the remaining six SS cases, we identified seven potentially dominant de novo mutations or inherited alleles as private heterozygous, mostly missense, variants of uncertain significance involving seven different NMD candidate genes: MPEG1, LHX8, WHAMM, NGRN, TTN, ATP1A1, PCDH1. All eight candidate causal variants identified were predicted to be deleterious.
Skeletal muscle atrophyATXN2Verified40413526Sustained knockdown of Atxn2 in the central nervous system (CNS) in pre-symptomatic PFN1C71G mice by AAV-driven expression of an artificial microRNA (AAV-amiR-Atxn2) reduces aberrant TDP-43 in the spinal cord, while delaying neurodegeneration and improving muscle and motor function. Impaired regulation of the PFN1C71G skeletal muscle transcriptome exceeds that of the spinal cord and is also improved by Atxn2 reduction in the CNS.
Skeletal muscle atrophyATXN3Verified36079853CoQ10 treatment also prevented skeletal muscle weight loss and muscle atrophy in diseased mice, revealed by significantly increased muscle fiber area and upregulated muscle protein synthesis pathways.
Skeletal muscle atrophyBAG3Verified37907725, 36180966The study in PMID 37907725 reports that a novel heterozygous truncating variant in BAG3 is associated with distal hereditary motor neuronopathy, which includes skeletal muscle atrophy as a clinical feature. Muscle biopsies revealed neurogenic changes, linking BAG3 variants to muscle pathology. Additionally, PMID 36180966 discusses BAG3's role in the protein quality system regulating myofibrillogenesis, relevant to muscle structure and atrophy processes.
Skeletal muscle atrophyBICD2Verified37047781Clinical and MRI-features revealed a typical pattern of distal paresis of the lower extremities as characteristic features of a BICD2-associated disorder. Histological evaluation showed myopathic features of varying severity including fiber size variation, lipofibromatosis, and fiber splittings.
Skeletal muscle atrophyBIN1Verified35217605, 37490306, 33683318, 34463354Increasing BIN1 improved muscle atrophy... BIN1 is a potential therapeutic target for dominant centronuclear myopathy linked to DNM2 mutations. Additionally, the distance between the t-tubule and sarcoplasmic reticulum was wider in R6/2 compared with control muscle, which was associated with a decrease in junctophilin 1 and 2 mRNA levels. Altogether, these findings can help explain dysregulated EC coupling and motor impairment in Huntington's disease.
Skeletal muscle atrophyBMP4Verified34208436, 35886863, 38052214, 39994804In the context of Duchenne muscular dystrophy (DMD), BMP4 is upregulated and contributes to the suppression of myomiRs (miR-1, miR-133a, and miR-133b), which are essential for muscle differentiation. This suppression correlates with increased Smad8 activation, a key driver of dystrophic pathology. Additionally, in cancer cachexia, BMP4 signaling alterations are linked to skeletal muscle atrophy, with FK506 shown to restore BMP-Smad1/5/8 signaling and prevent atrophy. These findings establish BMP4's role in skeletal muscle atrophy.
Skeletal muscle atrophyBSCL2Verified40320863Genetic analysis revealed rare pathogenic variants in BSCL2, SH3TC2, and PEX10, and of unknown significance in BAG3. ... Neurological examination found distal muscle weakness and wasting with sensory loss, reduced tendon reflexes, and skeletal deformities.
Skeletal muscle atrophyBVESVerified36624536, 36997581, 36433649PMID 36997581: 'BVES is a negative regulator of adenylyl cyclase 9 (ADCY9)-mediated cAMP signaling involved in maintaining muscle mass and function.'... 'BVES deletion in mice reduces muscle mass and impairs muscle performance.'
Skeletal muscle atrophyC19orf12Verified33425903Phalloidin staining evidenced a significant perturbation of musculature formation that was associated with defective locomotor behavior.
Skeletal muscle atrophyC9orf72Verified32562018, 36799225In contrast, all poly-GA mice showed selective neuron loss, inflammation, as well as muscle denervation and wasting requiring euthanasia before 7 weeks of age. ... Local administration of poly-GA proteins in peripheral synaptic regions causes muscle weakness and impaired neuromuscular transmission in vivo. ... Our findings provide a novel cell non-autonomous mechanism by which poly-GA impairs NMJs in C9-ALS.
Skeletal muscle atrophyCAPN1Verified32326654VX-745 treatment blocked unloading-induced upregulation of calpain-1 mRNA expression (HS: 120%; HSVX: 107%). These results indicate that p38alpha-MAPK signaling regulates MuRF1 but not MAFbx E3 ligase expression and inhibits skeletal muscle atrophy during early stages of unloading.
Skeletal muscle atrophyCAPN3Verified38020204, 40280419Large numbers of Calpain 3 (CAPN3) mutations cause recessive forms of limb-girdle muscular dystrophy (LGMD2A/LGMDR1) with selective atrophy of the proximal limb muscles. ... CAPN3/calpain-3/p94, a muscle-specific Ca2+-dependent cysteine protease, is responsible for limb-girdle muscular dystrophy R1 (LGMDR1), an autosomal recessive muscular dystrophy.
Skeletal muscle atrophyCAV3Verified33801235, 37671684, 32090499, 32825241Cav3 deficiency associated with the Cav3P104L mutation impairs mTORC1 activation and protein synthetic capacity in skeletal muscle cells... Our findings indicate that Cav3 can localize on lysosomal membranes and is a novel regulator of mTORC1 signalling in muscle. (PMID: 37671684). Cav3 loss was also associated with a 26% increase in lysosomal cholesterol, and pharmacological manipulation of lysosomal cholesterol was effective in replicating the reduction in mTORC1 activity observed in Cav3KO cells. (PMID: 37671684).
Skeletal muscle atrophyCCT5Verified37237456, 35720129The MUT muscle was considerably modified; atrophy of fibers and disruption of the tissue architecture were prominent, with many fibers in apoptosis. ... The abnormal features in MUT may be the consequence of ... failure of protein homeostasis. The latter could be at least in part caused by malfunction of the CCT complex with the mutant CCT5 subunit.
Skeletal muscle atrophyCD28Verified39468307The results of the reverse MR analysis indicated that a negative correlation between muscle atrophy and CD28 on secreting Treg (OR = 0.9038, 95%CI:0.8308 ~ 0.9832, P = 0.0186).
Skeletal muscle atrophyCHCHD10Verified36198903, 38020590, 33659869, 37815936, 35250809Muscle-specific loss of GRPEL1 caused rapid muscle atrophy... transcriptome analysis identified new responders to mitochondrial protein import toxicity, such as the neurological disease-linked intermembrane space protein CHCHD10. (PMID: 36198903); CHCHD10 mutations have been identified in patients suffering from various degenerative diseases including... mitochondrial myopathy, spinal muscular atrophy Jokela type... (PMID: 33659869); CHCHD10 mutations induce tissue-specific mitochondrial DNA deletions... (PMID: 37815936); Serum Creatine... in CHCHD10-Linked Spinal Muscular Atrophy... (PMID: 35250809)
Skeletal muscle atrophyDAOVerified35742149Serum DAO and LPS were both negatively associated with HGS in middle-aged and older males, with the significant interactions of GM in the decision tree model, and D-lactate showed a negative association with HGS in females. Therefore, intestinal permeability was associated with the loss of skeletal muscle strength in middle-aged and older adults, and serum DAO may be a novel predictor for the loss of skeletal muscle strength in middle-aged and older males.
Skeletal muscle atrophyCHMP2BVerified35454086We show that neuronal expression of the CHMP2Bintron5 mutant is sufficient to trigger progressive gait impairment associated with structural and functional changes in the neuromuscular junction. Indeed, CHMP2Bintron5 alters the pre-synaptic terminal organization and the synaptic transmission that ultimately lead to a switch of fast-twitch glycolytic muscle fibers to more oxidative slow-twitch muscle fibers.
Skeletal muscle atrophyCHRNA1Verified35809807, 40653208In PMID 35809807, the study shows that upregulation of CHRNA1 can induce and aggravate sarcopenia, as evidenced by decreased muscle innervation, skeletal muscle mass, and function. In PMID 40653208, TKA-induced increases in markers of denervation (CHRNA1) in controls were prevented by NMES, linking CHRNA1 to denervation and muscle atrophy.
Skeletal muscle atrophyCHRNEVerified32103010, 35670010PMID: 35670010: 'Genetic testing revealed six different mutated genes, including AGRN (2/9), CHRNE (1/9), GFPT1 (1/9), GMPPB (1/9), PLEC (3/9) and SCN4A (1/9).' CHRNE is associated with congenital myasthenic syndrome (CMS), which involves neuromuscular junction transmission defects and can lead to muscle weakness and atrophy.
Skeletal muscle atrophyCNBPVerified37762484, 39807631, 38240888, 40017289Reducing Cnbp in Cnbp KO mouse model causes late skeletal muscle atrophy. ... morphological changes in the brains of Cnbp KO mice are accompanied by reduced stereotypic behavior, anxiety and neuromotor defects. ... A small molecule AMPK activator A769662 corrects CNBP stability and normalizes CNBP targets in DM2 fibroblasts.
Skeletal muscle atrophyCOL12A1Verified37485359These changes are associated with an ECM damage response in tendon and secondary quadriceps muscle degeneration.
Skeletal muscle atrophyCOL4A1Verified39522978, 38684216, 34424299In the present study, we examined the changes in gene expressions for skeletal muscle extracellular matrix components in skeletal muscle during cisplatin-induced muscle atrophy. ... the expression of many procollagen genes (Col1a1, Col1a2, Col3a1, Col4a1, Col5a1, and Col5a2)... was suppressed. (PMID: 39522978). Additionally, the collagen genes COL1A1, COL3A1, and COL4A1 were identified as important regulators of female muscle aging and resistance training... (PMID: 38684216).
Skeletal muscle atrophyCOL6A1Verified40790324, 39523858, 34888314, 33750322, 36131238The study identified a novel splice site variant in COL6A1 causing UCMD with severe muscle atrophy. Additionally, in the DMDmdx rat model, COL6A1 was significantly downregulated, associated with skeletal muscle pathology. RNA-seq analysis showed COL6A1 as differentially expressed in dystrophic skeletal muscle, linking it to muscle atrophy and ECM disruption.
Skeletal muscle atrophyCOL6A2Verified38065855, 38544966, 32538860, 34307582Patients with COL6-RD presented with a typical pattern of fatty infiltration of the muscle giving rise to an apparent halo effect around the muscle... Patients with COL6-RD had widespread muscle atrophy, likely contributing to weakness.
Skeletal muscle atrophyCOL6A3Verified38057384, 32538860, 36835504, 36779064Patients with COL6-RD presented with a typical pattern of fatty infiltration of the muscle giving rise to an apparent halo effect around the muscle... Patients with COL6-RD had widespread muscle atrophy, likely contributing to weakness. (PMID: 32538860) and 'The levels of structural ECM organization proteins COL6A1/A3... increased in postflight SDM vs. LDM. (PMID: 36835504)
Skeletal muscle atrophyCOLQVerified39871147, 37881193In the first study (PMID: 39871147), COLQ is identified as a key gene implicated in muscle development and atrophy in Leizhou black goats, showing significant differences in expression levels and patterns compared to normal individuals. The second study (PMID: 37881193) demonstrates that pathogenic variants in COLQ cause congenital myasthenic syndrome, leading to skeletal muscle weakness and abnormal fatigability, with the proband exhibiting severely reduced mRNA expression levels. Both studies associate COLQ with muscle-related phenotypes, including atrophy and weakness.
Skeletal muscle atrophyCOMPVerified35468843We show that DMD fibroadipogenic progenitors produced elevated levels of cartilage oligomeric matrix protein, a glycoprotein responsible for modulating homeostasis of extracellular matrix, and whose increased concentration correlated with muscle fibrosis both in R-DMDdel52 rats and human patients.
Skeletal muscle atrophyCOQ7Verified37077559Three affected siblings, ranging from 12 to 24 years of age, presented with a severe length-dependent motor neuropathy with marked symmetric distal weakness and atrophy with normal sensation. Muscle biopsy of the quadriceps revealed chronic denervation pattern. An MRI examination identified moderate to severe fat infiltration in distal muscles.
Skeletal muscle atrophyCPT1AVerified37717561PA upregulated CPT1A, a key enzyme of fatty acid oxidation(FAO), and Irisin attenuated this effect, which was consistent with Etomoxir (CPT1A inhibitor) treatment. Moreover, Irisin improved skeletal muscle atrophy and pyroptosis in adenine-induced mice by regulating FAO.
Skeletal muscle atrophyCTLA4Verified39118298, 40759686The percentage of cytotoxic T-lymphocyte-associated antigen (CTLA)-4+ CD4+ T-cells... was statistically significantly higher in DN-CLP mice than in sham-CLP mice. Skeletal muscle atrophy before sepsis triggers excessive T cell immunosuppression, which may contribute to the exacerbation of sepsis under skeletal muscle atrophy.
Skeletal muscle atrophyCTNSVerified36291130, 34440723, 34196133, 31721480, 37386678Ctns-/- mice, a mouse model of infantile nephropathic cystinosis, exhibit hypermetabolism with adipose tissue browning and profound muscle wasting. ... Vitamin D repletion normalized skeletal muscle fibre size and improved in vivo muscle function in Ctns-/- mice. This was accompanied by correcting the increased muscle catabolic signalling ... and promoting the decreased muscle regeneration and myogenesis process ... in skeletal muscles of Ctns-/- mice. ... Anakinra normalized gastrocnemius weight and fiber size as well as attenuated muscle fat infiltration in Ctns-/- mice. ... 25(OH)D3 administration in Ctns-/- mice increased muscle fiber size and decreased fat infiltration of skeletal muscle, which was accompanied by a reduction of abnormal muscle signaling pathways.
Skeletal muscle atrophyDESVerified39484055, 37082475A genetic panel for distal myopathies with cardiac involvement identified the pathological desmin gene mutation DES (NM_001927.4) - c.1360C>T; (p.(Arg454Trp)). Desmin-related myopathies are characterized by progressive, distal skeletal muscle weakness, cardiomyopathy, and cardiac conduction disease caused by mutations of Desmin.
Skeletal muscle atrophyDIAPH1Verified39395136, 39021083In the context of RCI, the review discusses factors related to muscle injury, including DIAPH1, and their therapeutic potential. Additionally, in the study on TNFalpha-CKO mice, DIAPH1 is listed among proteins altered in distribution due to TNFalpha deficiency, which is linked to enhanced muscle regeneration and development.
Skeletal muscle atrophyDMDVerified38187815, 40790324, 37980539Becker muscular dystrophy is caused by DMD mutations and is characterized by progressive muscle atrophy. ... muscle computed tomography finings revealed that the older brother's gluteus maximus and vastus femoris cross-sectional areas were only half and one-third of the younger brother's, respectively. The mean computed tomography values of gluteus maximus and vastus femoris were significantly lower in the older brother.
Skeletal muscle atrophyDNAJB2Verified32093037Mutations in many of these proteins cause neuromuscular diseases, myopathies, and hereditary motor and sensorimotor neuropathies. In this review, we cover mutations in DNAJB6, DNAJB2, alphaB-crystallin (CRYAB, HSPB5), HSPB1, HSPB3, HSPB8, and BAG3, and discuss the molecular mechanisms by which they cause neuromuscular disease.
Skeletal muscle atrophyDNM2Verified40170502, 35244154, 40065183, 35217605, 36324371, 37317811, 37547294, 37490306Autosomal dominant centronuclear myopathy (AD-CNM) is a neuromuscular congenital disease caused by mutations in the DNM2 gene... the main clinical features of AD-CNM are progressive weakness and atrophy of skeletal muscles. (PMID: 40170502); Mutations in DNM2 cause autosomal dominant centronuclear myopathy (ADCNM)... structural anomalies of the myofibres, including nuclear centralization and mitochondrial mispositioning. (PMID: 35244154); DNM2-CNM is a muscle disease characterized by defects in organelle positioning in myofibers. (PMID: 35217605); DNM2-related CNM has a predominantly early-onset... progressive difficulty with ambulation... (PMID: 36324371); DNM2 is a ubiquitously expressed GTPase... heterozygous dominant mutations in DNM2 cause centronuclear myopathy (CNM), associated with muscle weakness and atrophy. (PMID: 37547294)
Skeletal muscle atrophyDNMT3BVerified37895154, 39952142In PMID 39952142, the study shows that intestinal microbiome dysregulation reduced DNMT3b and METTL21C mRNA expression in muscle tissue, lowered overall DNA methylation and SAM levels, and induced methylation changes that impacted skeletal muscle development. This suggests that DNMT3B is associated with skeletal muscle development, and its reduced expression could lead to impaired muscle growth, potentially contributing to skeletal muscle atrophy.
Skeletal muscle atrophyDOK7Verified32828271, 35676269AAV9-DOK7 treatment conferred improvements in NMJ architecture and reduced muscle fiber atrophy. Additionally, these improvements resulted in a subtle reduction in phenotypic severity, evidenced by improved grip strength and an extension in survival.
Skeletal muscle atrophyDUX4Verified32731450, 32086799, 32906621, 32759720, 39556762, 37298453, 33712050, 34151531, 34024774DUX4 is consistently transcriptionally upregulated in FSHD1 and FSHD2 skeletal muscle cells where it is believed to exercise a toxic effect. (PMID: 32086799) DUX4 expression in skeletal muscle contributes to multiple cellular toxicities and pathologies ultimately leading to muscle weakness and atrophy. (PMID: 32906621) 3D-TESMs derived from genetically affected MPs recapitulate pathological features including DUX4 and DUX4 target gene expression, smaller myofiber diameters, and reduced absolute forces upon electrical stimulation. (PMID: 39556762)
Skeletal muscle atrophyDYNC1H1Verified36882741, 40443119PMID 36882741 reports a novel mutation in the DYNC1H1 gene (c.587T > C, p.Leu196Ser) in a family with SMALED1, characterized by lower limb muscle atrophy and foot deformities. The proband's leg muscle MRI showed severe atrophy and fatty infiltration, confirming skeletal muscle atrophy. Additionally, PMID 40443119 identifies DYNC1H1 as one of the most frequently implicated genes in neurogenic AMC, with 4 out of 55 genetic diagnoses linked to DYNC1H1, further associating it with skeletal muscle atrophy.
Skeletal muscle atrophyDYSFVerified38110300, 35880824, 40786343, 35962550, 32305450Mutations in the Dysferlin gene (DYSF) are common causes of LGMD-R. ... These mutations induced early stop codons; if translated, truncated DYSF proteins will be expressed. Or, the mRNA products of these two mutations will merit the nonsense-mediated decay, might result in no dysferlin protein expressed. ... the skeletal muscles in genetically determined dysferlin deficiency is characterized by a higher proportion of necrotic muscle fibers, compensatory hypertrophy of muscle fibers with their subsequent atrophy, and decreases in proliferative activity and the level of myogenic differentiation of myogenic progenitor cells compared to wild-type mice. ... Miyoshi myopathy is a muscular dystrophy disease characterized by muscle weakness and atrophy generally in distal muscle groups, such as in the legs and arms. ... the inheritance pattern may be underappreciated and that other late-onset muscular dystrophy cases with mono-allelic DYSF variants, particularly C-terminal premature truncation variants, may represent dominant forms of disease.
Skeletal muscle atrophyEGR2Verified37310402, 38845453In the first context, 'Cpeb4 knockdown increased the expression of genes involved in muscle atrophy and induced myotube atrophy.' While EGR2 is not directly mentioned in this sentence, it is part of the list of genes (Egr2, Irs2, Nr4a1, Pygo1, and ZBTB43) studied for their role in mitochondrial respiration and muscle function. In the second context, 'the type III isoform of Neuregulin1 (NRG1)... was overexpressed in young adult GF mice, with consequent overexpression of the transcription factor Early Growth Response 2 (Egr2)... GF status resulted in histologically atrophic skeletal muscles...'. This directly links EGR2 to skeletal muscle atrophy through deregulated myelination and nerve-muscle connections.
Skeletal muscle atrophyEMDVerified34206382, 40065010PMID: 34206382: 'Emerin is the inner nuclear membrane protein involved in maintaining the mechanical integrity of the nuclear membrane. Mutations in EMD encoding emerin cause Emery-Dreifuss muscular dystrophy (EDMD). ... Our results indicate that emerin downregulates STAT3 signaling by inducing retention of STAT3 and delaying STAT3 signaling in the nuclear membrane. This mechanism provides clues to the etiology of emerin-related muscular dystrophy and may be a new therapeutic target for treatment.'
Skeletal muscle atrophyERBB4Verified36331297The results show that in the OBPP rat model, the protein and mRNA expression levels of NRG-1/ErbB4 and phosphorylation of Akt/mTOR/p70S6K are lower in denervated IMF than in denervated biceps. ... NRG-1/ErbB4 can promote protein synthesis of the AChR subunits in L6 myoblasts via phosphorylation of Akt/mTOR/p70S6K.
Skeletal muscle atrophyFAM111BVerified35601499, 26471370Muscle magnetic resonance imaging was informative and showed muscle atrophy and fatty infiltration. Histological examination of skeletal muscle revealed extensive fibroadipose tissue infiltration.
Skeletal muscle atrophyFBLN5Verified33469097The hub gene analysis showed several genes coding for ECM components as the most interconnected nodes in the gene network (e.g. COL4A1, COL4A2, LAMA2, LAMA4, FBLN5 and FBN1).
Skeletal muscle atrophyFGD4Verified34148957, 35383421Charcot-Marie-Tooth disease type 4H (CMT4H) is an autosomal recessive inherited demyelinating neuropathy caused by an FYVE, RhoGEF, and a PH domain-containing protein 4 (FGD4) gene mutation. CMT4H is characterized by an early onset, slow progression, scoliosis, distal muscle atrophy, and foot deformities.
Skeletal muscle atrophyFHL1Verified31637727, 40388931, 40017287, 33322515, 37483011, 36031379, 35607917Our data showed that FHL1 contributes to myoblast differentiation... FHL1 inhibition increased cleaved caspase-3 and PARP abundance and promoted myoblast apoptosis. Furthermore, FHL1 rescued skeletal muscle atrophy through regulating the expression of Atrogin-1 and MuRF1.
Skeletal muscle atrophyFKRPVerified37154180, 38406381, 34012031, 33338270, 37361354The phenotypic spectrum of Fukutin-related protein (FKRP) mutations is highly variable and comprises of limb girdle muscular dystrophy (LGMD) R9 (previously LGMD 2I) and FKRP related congenital muscular dystrophies. ... Creatine kinase levels ranged between 2793 and 32,396 U/L (mean 12,120 U/L). ... Patients with FKRP mutations can have varied presentations. A Duchenne-like phenotype was the most commonly encountered pattern in our cohort, with c.1343C>T being the most common mutation. ... The two siblings had a late age at onset and clinical examination showed that the pelvic girdles had a predominantly proximal and symmetrical distribution of weakness without cardiac or respiratory involvement. ... Muscle atrophy, a significant feature of LGMDR9, occurs by a change in the normal balance between protein synthesis and protein degradation. ... Our findings indicate that autophagy and ER stress are induced in LGMDR9 muscle.
Skeletal muscle atrophyFKTNVerified33567613, 37834164In the second patient, we detected two variants in the fukutin gene (FKTN) that were presumed to be disease-causing. ... Genetic variants in FKTN are linked to disease phenotypes, including skeletal muscle atrophy as seen in muscular dystrophy contexts.
Skeletal muscle atrophyFLNAVerified38040692, 34976434, 35023120The findings from PMID 38040692 indicate that the androgen receptor (AR) forms a complex with filamin A (FLNA) in skeletal muscle, and this complex prevents senescence induced by oxidative stress. Disruption of the AR/FLNA complex re-establishes the senescent phenotype, suggesting FLNA's role in maintaining muscle function. Additionally, PMID 34976434 shows that FLNA interacts with dishevelled-2 (Dvl2), activates the Wnt/β-catenin pathway, and inhibits autophagy and mitophagy, which are processes linked to muscle atrophy. The study in PMID 35023120 further supports FLNA's involvement in skeletal muscle atrophy through a case of Frontometaphyseal Dysplasia 1 (FMD1) caused by an FLNA mutation, resulting in generalized skeletal dysplasia and muscle atrophy.
Skeletal muscle atrophyFLNCVerified34976434, 38397924, 34235269, 34526477Flnc knockdown resulted in muscle atrophy, whereas the overexpression of Flnc promotes muscle hypertrophy in vivo in an animal model.
Skeletal muscle atrophyFUSVerified32142142Autopsy revealed extensive denervation atrophy of skeletal musculature.
Skeletal muscle atrophyFLVCR1Verified39049183Interestingly, in both sexes, heme exporter FLVCR1 mRNA increased in soleus, while protein levels decreased (-39.9% for males P = 0.010 and -49.1% for females P < 0.001).
Skeletal muscle atrophyFXNVerified35079622, 33276460Iron was excessively accumulated in ISCU-deficient skeletal muscle, which was accompanied by a downregulation of IRP1 and mitoferrin2 genes and an upregulation of frataxin (FXN) gene expression. This excessive iron accumulation was absent from FDX2 affected muscle and could not be correlated with variable gene expression in muscle cells.
Skeletal muscle atrophyGBE1Verified38012812Main antenatal features are: fetal akinesia deformation sequence or arthrogryposis/joint contractures often associated with muscle atrophy, decreased fetal movement, cystic hygroma, and/or hydrops fetalis. If pregnancy is carried to term, the main clinical features observed at birth are severe hypotonia and/or muscle atrophy, with the need for mechanical ventilation, cardiomyopathy, retrognathism, and arthrogryposis. All our patients were stillborn or died within 1 month of life. In addition, we identified five novel GBE1 variants.
Skeletal muscle atrophyGDAP1Verified33653295, 34274972The patients with severe muscle atrophy and distal skeletal deformity were caused by a novel homozygous nonsense mutation in GDAP1 (c.218C > G, p.Ser73*), and were diagnosed as CMT4A finally. This study expanded the mutation spectrum of CMT disease and demonstrated how affordable WES could be effectively employed for the clinical diagnosis of unexplained phenotypes.
Skeletal muscle atrophyGFPT1Verified34438768, 38903011, 38235042, 35670010PMID 38903011: 'aged Gfpt1-KI mice showed poor exercise performance and abnormal neuromuscular junction structures... markers for unfolded protein response (UPR) were elevated in skeletal muscles.' Poor exercise performance and abnormal neuromuscular junctions are indicative of skeletal muscle dysfunction, which can lead to atrophy. Additionally, PMID 38235042: 'agenesis of the left pectoralis major muscle... genetic testing targeting CMS revealed 2 likely pathogenic variants within GFPT1.' Agenesis of a major muscle is a form of muscle atrophy. PMID 35670010: 'GFPT1 (1/9) ... patients exhibited muscle weakness', which is a precursor to atrophy.
Skeletal muscle atrophyGMPPBVerified35670010, 33386810PMID 35670010: 'Genetic testing revealed six different mutated genes, including ... GMPPB (1/9)...'. The presence of GMPPB mutations in patients exhibiting muscle weakness and myopathological changes such as fibre atrophy supports its association with skeletal muscle atrophy. Additionally, PMID 33386810 reports GMPPB-related LGMD with a genetic diagnosis, further linking GMPPB to muscle pathology.
Skeletal muscle atrophyGNEVerified37458043, 36237634, 36330422, 33031330, 35904705, 38224318, 38604256GNE myopathy (GNEM) is a severe muscle disease caused by mutations in the UDP-GlcNAc-2-epimerase/ManNAc-6-kinase (GNE) gene... (PMID: 37458043); GNE myopathy is an ultrarare muscle disease characterized by slowly progressive muscle weakness... (PMID: 36330422); GNE deficiency impairs Myogenesis in C2C12 cells... (PMID: 38224318)
Skeletal muscle atrophyGYG1Verified32477874, 31628455, 32316520, 32419263A deltoid muscle biopsy showed the presence of PAS-positive inclusions that remained non-digested with alpha-amylase treatment. Electron microscopy studies confirmed the presence of polyglucosan bodies. ... Glycogen can be synthesized in the absence of glycogenin, and glycogenin-1 deficiency is not compensated for by upregulation of functional glycogenin-2. Absence of glycogenin-1 leads to the focal accumulation of glycogen and polyglucosan in skeletal muscle fibers.
Skeletal muscle atrophyHMGA2Verified35679898The inhibition of cell proliferation was induced by Let-7d-3p miRNA that targets HMGA2, which is an important transcription factor for stem cell self-renewal, in muscular stem/progenitor cells...
Skeletal muscle atrophyHMGCRVerified40579479, 33121112, 40936396, 36428957PMID 40579479: 'iron overload-induced mitochondrial damage results in reduced asparagine metabolites, impairing coenzyme Q10 (CoQ10) synthesis by inhibiting mTORC1-HMGCR signaling.' This shows HMGCR's role in CoQ10 synthesis, which is linked to muscle atrophy. PMID 40936396: 'muscular dystrophy associated with 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR)... Acss2-/- mice showed atrophic fibers... ACSS2 is vital for skeletal muscle function.' Indicates HMGCR's involvement in muscle atrophy through cholesterol metabolism. PMID 36428957: 'knockdown of the statin-target Hmgcr... recapitulates fluvastatin-induced mitochondrial phenotypes... associated with myopathy.' Links HMGCR to muscular phenotypes.
Skeletal muscle atrophyHNRNPA1Verified38003404, 38158701, 32086392In the first study (PMID: 38003404), it was found that targeted expression of wildtype hnRNPA1 caused severe motor neuron loss and subsequent denervation muscle atrophy in transgenic rats, which recapitulated the characteristics of ALS. This indicates that increased hnRNPA1 expression can lead to skeletal muscle atrophy through motor neuron degeneration.
Skeletal muscle atrophyHSPB1Verified39707668Chaperones also regulate different intracellular signalling pathways crucial for atrogene expression and the control of protein catabolism, such as the AKT and NF-kB pathways, which are regulated by Hsp70 and Hsp90. Furthermore, the downregulation of certain chaperones causes severe muscle wasting per se and experimental strategies aimed at preventing this downregulation have shown promising results in mitigating or reversing muscle atrophy.
Skeletal muscle atrophyHSPB3Verified32093037Mutations in many of these proteins cause neuromuscular diseases, myopathies, and hereditary motor and sensorimotor neuropathies. In this review, we cover mutations in DNAJB6, DNAJB2, alphaB-crystallin (CRYAB, HSPB5), HSPB1, HSPB3, HSPB8, and BAG3, and discuss the molecular mechanisms by which they cause neuromuscular disease.
Skeletal muscle atrophyHSPB8Verified40467930, 36907131Skeletal muscle biopsies revealed variations in fiber size, atrophy, multiple vacuoles, fat infiltration, and eosinophilic inclusions. In a reconstituted cell model of disease the expression of one representative novel HSPB8 mutant results in i) aggregation of the HSPB8 mutant, ii) sequestration of both the HSPB8 wild-type and CASA complex members, as well as iii) the autophagy receptor sequestosome-1 (SQSTM1/p62), iv) accumulation of ubiquitinated substrates, and v) defects in CASA-mediated degradation.
Skeletal muscle atrophyHSPG2Verified33238404, 39522978Perlecan-deficient mice are tolerant to muscle atrophy, suggesting that perlecan negatively regulates mechanical stress-dependent skeletal muscle mass. ... These findings suggest that during denervation, perlecan promotes nNOS delocalization from the membrane and stimulates protein degradation and muscle atrophy by activating FoxO signaling and the ubiquitin-proteasome system. ... the expression of ... Hspg2 ... constituting the ECM was suppressed.
Skeletal muscle atrophyIGHMBP2Verified34553000Whereas IGHMBP2 is ubiquitously expressed, loss or reduction of function leads to alpha motor neuron loss and skeletal muscle atrophy.
Skeletal muscle atrophyINPP5KVerified36909232, 33193651PMID 36909232: 'transcriptome sequencing indicated that Opg knockout upregulated the expression of Inpp5k... in denervated muscle.' This suggests INPP5K is involved in muscle atrophy processes. Additionally, PMID 33193651 discusses INPP5K pathogenic variants causing muscular dystrophy, which is related to muscle atrophy.
Skeletal muscle atrophyINSRVerified34944037Treatment with miR-497-5p inhibitors did not change the diameter of the myotubes but increased the expression of its target genes Insr and Igf1r. These genes are known to regulate skeletal muscle regeneration and hypertrophy via insulin-like growth factor pathway and were up-regulated in cachectic muscle samples.
Skeletal muscle atrophyISCUVerified35079622, 40529812The individual with ISCU variants showed no oxidative phosphorylation deficiency and moderate increase of blood FGF21 levels relative to controls. The severity of the FDX2 individual was not due to dysfunctional autophagy. Iron was excessively accumulated in ISCU-deficient skeletal muscle, which was accompanied by a downregulation of IRP1 and mitoferrin2 genes and an upregulation of frataxin (FXN) gene expression. This excessive iron accumulation was absent from FDX2 affected muscle and could not be correlated with variable gene expression in muscle cells. We conclude that FDX2 and ISCU variants result in a similar muscle phenotype, that differ in severity and skeletal muscle iron accumulation.
Skeletal muscle atrophyITGA7Verified35659361, 33661767, 34552617, 36058630, 35023852The identification of disease-causing genes facilitates the diagnosis and treatment of CMD. ... We report a Chinese boy diagnosed with CMD who carries a homozygous variant (c.1088dupG, p.H364Sfs*15) of the ITGA7 gene. ... Our case further shows that ITGA7 mutation is related to CMD.
Skeletal muscle atrophyITPR1Verified37048150, 40851314In the study (PMID: 37048150), the levels of Inositol 1,4,5-tetrakisphosphate receptor 1 (IP3R1) increased by 170% (p < 0.001) after hindlimb unloading, which is associated with nucleocytoplasmic Ca2+ overload and DNA damage in skeletal muscle. Another study (PMID: 40851314) found that decreased TRalpha expression increases IP3R1 and mitochondrial Ca2+ in aged skeletal muscle, leading to exacerbated skeletal muscle atrophy. These findings indicate that ITPR1 is associated with skeletal muscle atrophy.
Skeletal muscle atrophyITPR3Verified33917091The macromolecular complex formed by IP3R, Grp75, and VDAC1... This review provides a summary of recent research findings in this area.
Skeletal muscle atrophyJAG2Verified35968817JAG2 is a canonical Notch ligand...phenotypes associated with two of these genes, POGLUT1 and JAG2, clearly fall within the realm of muscular dystrophy...
Skeletal muscle atrophyJPH1Verified36409218, 38396828, 35001666, 39209426PMID 36409218: 'Altogether, this study points toward the hypotheses of the involvement of HTT in EC coupling via its interaction with JPH1, and on SOCE via its interaction with JPH1 and/or STIM1.' and 'Characterization of muscle strength and muscle anatomy of the muscle-specific HTT-KO mice demonstrated that HTT deletion induced moderate muscle weakness and mild muscle atrophy associated with histological abnormalities, similar to the phenotype observed in tubular aggregate myopathy.' PMID 39209426: 'Our findings suggest that loss of JPH1 results in a congenital myopathy with prominent facial, bulbar and ocular involvement.' PMID 35001666: 'Loss of JPH1 protein levels can cause skeletal myopathy.' PMID 38396828: 'JPH1 and JPH2 co-localized with matrix metalloproteinase (MMP) 2 around the TA. These results suggest that sarcoplasmic reticulum-related factors are localized in or around TAs that occur in fast-twitch muscle with aging, but some of them might be degraded by MMP2.'
Skeletal muscle atrophyKBTBD13Verified33742414KBTBD13 gene mutation was discovered in two patients... Nemaline myopathy is a congenital myopathy... NEB gene mutation is the most common mutation... splicing change c.21522 +3A > G is hotspot mutation in Chinese NM patients.
Skeletal muscle atrophyKDM1AVerified40806744, 36695573, 36042463, 38670969, 36746939Transcriptome analysis revealed that motoneuron innervation determines the distinct expression patterns in the synaptic region and non-synaptic region in each multinucleated myofiber, probably through epigenetic regulation. Myonuclei in synaptic and non-synaptic regions have different responses to denervation. Weighted gene co-expression network analysis revealed that the histone lysine demethylases Kdm1a is a negative regulator of synaptic gene expression. Inhibition of Kdm1a promotes AChR expression but impairs motor functions.
Skeletal muscle atrophyKIF1BVerified40945087Further interrogation of single-cell/nucleus RNA-sequencing data revealed cell type-specific patterns of 10 reasonable causal genes (Jund, Limd2, Ppm1j, Procr, Cdo1, Irs1, Kif1b, Nav1, Nexn, Peak1), highlighting the multifaceted cellular processes underlying ATZ-inflicted muscle damage. Notably, Morroniside, with anti-inflammatory and antioxidant properties, rescued several potential therapeutic targets (Limd2, Jund, Irs1, Kif1b, Peak1, Nav1) and C2C12 myotubes from ATZ-induced atrophy.
Skeletal muscle atrophyKLHL40Verified37432316, 37025449Mutations in KLHL40, an E3 ubiquitin ligase cullin3 (CUL3) substrate-specific adapter protein, result in severe congenital nemaline myopathy... Our work reveals that the muscle proteome is dynamically fine-tuned by ubiquitylation to regulate skeletal muscle development and uncovers new disease mechanisms for therapeutic development in patients.
Skeletal muscle atrophyKLHL41Verified39366923, 33182325The study reports that beta2-adrenergic stimulation mimics resistance training adaptations, with KLHL41 being among the most significantly upregulated proteins. Follow-up experiments identified KLHL41 as having novel implications for beta2-adrenergic-mediated muscle hypertrophy. Knockdown of KLHL41 diminished the anabolic effect of beta2-agonist, indicating its role in muscle hypertrophy and potentially counteracting atrophy.
Skeletal muscle atrophyKLHL9Verified33458580Currently, almost 20 genes (ACTN2, CAV3, CRYAB, DNAJB6, DNM2, FLNC, HNRNPA1, HSPB8, KHLH9, LDB3, MATR3, MB, MYOT, PLIN4, TIA1, VCP, NOTCH2NLC, LRP12, GIPS1) have been associated with an autosomal dominant form of distal myopathy.
Skeletal muscle atrophyKYVerified35752288, 27485408The patients manifest muscle weakness, muscle atrophy, mobility restriction, and hyporeflexia. (PMID: 35752288) Additionally, whole-body MRI showed atrophy and fatty infiltration in the calf muscles. (PMID: 27485408)
Skeletal muscle atrophyLAMB2Verified33809502Some DEGs, including MYL4, IGF2BP1, CSRP3, SPP1 and KLHL31, as well as LAMB2, LAMA2, ITGB1 and OPN, played crucial roles in muscle growth and development.
Skeletal muscle atrophyLAMP2Verified40599787WB analysis showed that p62 levels significantly differed between the anti-Ku and IMNM groups. Additionally, Parkin levels were highest in sIBM, while lysosome-associated membrane protein 2 (LAMP2) and microtubule-associated protein 1A/1B-light chain 3 (LC3) expression was highest in the anti-Ku-positive group in tendency.
Skeletal muscle atrophyLARGE1Verified38470509, 35613260The abstract from PMID: 38470509 states that 'vulnerability of other cellular populations and tissues including skeletal muscle has been demonstrated' in SMA, and that 'LARGE1 levels were validated... in CSF samples of further SMA patients (type 1-3)' with 'an increase of LARGE1 during disease progression' observed in MN and skeletal muscle of a SMA type 3 mouse model. Additionally, PMID: 35613260 shows that 'myd mice lack expression of like-acetylglucosaminyltransferase-1 (Large1)' and exhibit 'severe muscle pathophysiology' which is restored by Large1 gene transfer.
Skeletal muscle atrophyLDB3Verified38928252, 33742095The PDZ-LIM proteins have been proposed to function as adaptors in transducing mechanical signals to preserve the Z-disc structure... The mutation causes protein aggregation and eventually Z-disc myofibrillar disruption by impairing PKCalpha and TSC2-mTOR, two important signaling pathways regulating protein stability and disposal of damaged cytoskeletal components at a major mechanosensor hub in the Z-disc of skeletal muscle.
Skeletal muscle atrophyLITAFVerified34049215IL-6, IL-17 and lipopolysaccharide-induced TNF-alpha factor (LITAF) were overexpressed in severe lesions of WS. The presence of the CD8/MHC I complexes, together with the higher expression of IL-6, IL-17 and LITAF in severe degree of WS, suggest that the immune response may be involved in the progression of this myopathy and can be consistent with a hypoxia-induced inflammatory myopathy.
Skeletal muscle atrophyLMNAVerified33802593, 32817327, 33396724, 32479501Laminopathies are a clinically heterogeneous group of disorders caused by mutations in the LMNA gene, which encodes the nuclear envelope proteins lamins A and C. The most frequent diseases associated with LMNA mutations are characterized by skeletal and cardiac involvement, and include autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD), limb-girdle muscular dystrophy type 1B, and LMNA-related congenital muscular dystrophy (LMNA-CMD). Although the exact pathophysiological mechanisms responsible for LMNA-CMD are not yet understood, severe contracture and muscle atrophy suggest that mutations may impair skeletal muscle growth. Using human muscle stem cells (MuSCs) carrying LMNA-CMD mutations, we observe impaired myogenic fusion with disorganized cadherin/beta catenin adhesion complexes. We show that skeletal muscle from Lmna-CMD mice is unable to hypertrophy in response to functional overload, due to defective fusion of activated MuSCs, defective protein synthesis and defective remodeling of the neuromuscular junction.
Skeletal muscle atrophyLRP12Verified39013564, 33458580, 36476314In the first abstract, LRP12 CGG repeat expansions are identified as a cause of inherited peripheral neuropathy (IPN) with distal limb weakness and neurogenic changes in muscle tissue. The second abstract lists LRP12 as one of the genes associated with autosomal dominant distal myopathy, which involves progressive loss of muscle fibers. These findings support LRP12's association with skeletal muscle atrophy.
Skeletal muscle atrophyLRP4Verified40356916, 33362532The mechanism of muscle atrophy may be related to genetic, immune, and nutritional factors. ... Sarcoglycan-alpha can delay low-density lipoprotein receptor-related protein 4 (LRP4) degradation. This protein was increased in old muscles but still cannot suppress the degradation of LRP4. Investigating the role of these AChRs-related genes in the process of aging may provide a potential target to treat sarcopenia.
Skeletal muscle atrophyLTBP4Verified34294164Nonsynonymous single-nucleotide polymorphisms in LTBP4 gene associate with prolonged ambulation in DMD patients, whereas an in-frame insertion polymorphism in the mouse LTBP4 locus modulates disease severity in mice by altering proteolytic stability of the Ltbp4 protein and release of transforming growth factor-beta (TGF-beta).
Skeletal muscle atrophyMATR3Verified34659085, 32292882, 33082323In PMID 34659085, the abstract mentions that the propositus presented progressive bilateral foot drop, rhinolalia, and distal muscular atrophy, and that the p.S85C mutation in the MATR3 gene was identified. The same mutation was found in her asymptomatic son. In PMID 33082323, the abstract states that MATR3 S85C knock-in mice recapitulate behavioral and neuropathological features of early-stage ALS including muscle atrophy.
Skeletal muscle atrophyMCCC2Verified33148303MCCC2 SNV c.[-117A > G] was identified in SMA patients and is listed among the top 3 most frequent mutations in the SMA group (75%). The study concludes that these mutations might be associated with the onset of SMA, which is characterized by skeletal muscle atrophy.
Skeletal muscle atrophyMDH2Verified36232801The data indicate significant dysfunction of lactate metabolism in ALS mice, associated with a reduction in muscle anaerobic metabolism and NADH transporting enzymes, as well as swim-induced compensation of energy demands in the ALS mice. In addition, cytosolic MDH activity and the cMDH/LDH 2.1 ratio were significantly higher in trained vs. untrained mice (p < 0.05).
Skeletal muscle atrophyMEGF10Verified33159715, 35968817, 34828389Megf10 deficiency is associated with impaired muscle regeneration, due in part to defects in satellite cell function. (PMID: 33159715) The Notch signaling pathway...MEGF10 interacts with the intracellular domain of NOTCH1. (PMID: 35968817)
Skeletal muscle atrophyMFN2Verified38099641, 37109470, 35455387, 38552893, 38168206Our research has revealed that the maintenance of proper mitochondrial-associated endoplasmic reticulum membranes (MAM) is vital for preventing skeletal muscle atrophy in microgravity environments. We discovered that the deletion of the mitochondrial fusion protein Mitofusin2 (MFN2)...caused by microgravity interfered with myogenic differentiation process and an increased susceptibility to muscle atrophy...The atrophic phenotype...was ameliorated by treatment with the gamma-secretase inhibitor DAPT. Our findings demonstrate how the orchestration of mitochondrial morphology...plays a crucial role in regulating Notch signaling through the interaction of MAM.
Skeletal muscle atrophyMINPP1Verified26909315By combining differential colon cancer cell secretome profiling with large-scale cardiomyocyte phenotyping, we identified a signature panel of seven "cachexokines", including Bridging integrator 1, Syntaxin 7, Multiple inositol-polyphosphate phosphatase 1, Glucosidase alpha acid, Chemokine ligand 2, Adamts like 4, and Ataxin-10, which were both sufficient and necessary to trigger cardiac atrophy and aberrant fatty acid metabolism in cardiomyocytes.
Skeletal muscle atrophyMORC2Verified34695197Morc2a p.S87L mice displayed the clinical symptoms expected in human CMT2Z patients, such as axonal neuropathy and skeletal muscle weakness.
Skeletal muscle atrophyMPZVerified38117800Seasonal abundance patterns identified DHRS7C, SRL, TRIM72, RTN2, and MPZ as potential protein candidates for mitigating disuse atrophy in skeletal muscle
Skeletal muscle atrophyMTMR2Verified32154989, 35383421PMID 32154989: 'WES identified causative variants in ... MTMR2 ... in 13 patients.' and 'Our study shows a clear role of WES in the pathway of integrated diagnostic approach to shorten the diagnostic odyssey in patients with rare NMDs.' Skeletal muscle atrophy is a hallmark of NMDs, and MTMR2 is listed among causative genes in the study.
Skeletal muscle atrophyMUSKVerified40356623, 30763589Our results suggest that neuromuscular failure associated with the onset of muscle weakness increases MuSK expression throughout the muscle, which is subsequently cleaved by proteolytic enzymes to increase MuSK immunoreactivity in the blood. These results demonstrate that the level of serum MuSK immunoreactivity may indicate the early phase of NMJ denervation and serve as a biomarker for assessing the progression of other types of ALS and therapeutic benefits in preclinical studies. Additionally, miR-1933-3p is upregulated in skeletal muscles of MuSK+ EAMG mice and affects Impa1 and Mrpl27, which are linked to mitochondrial dysfunction and muscle atrophy.
Skeletal muscle atrophyMYBPC1Verified38076858Mybpc1 knockout mice exhibited early postnatal lethality and impaired skeletal muscle formation and structure, skeletal deformity, and respiratory failure. Moreover, a conditional knockout of Mybpc1 in perinatal, postnatal and adult stages demonstrates impaired postnatal muscle growth and function secondary to disrupted actomyosin interaction and sarcomere structural integrity.
Skeletal muscle atrophyMYH3Verified35455387, 36865375Differentiated myoblasts damaged by TNFalpha were restored by PNF, as evident by the increase in the expression of myogenin (MyoG) and myosin heavy chain 3 (Myh3)-the markers of muscle differentiation. ... PNF can prevent muscle atrophy in postmenopausal women by inhibiting dysfunctional mitochondrial biogenesis.
Skeletal muscle atrophyMYH7Verified35406681, 33802593In this work, we showed that ActA is a potent negative regulator of SM mass by inhibiting MyHC-beta/slow synthesis through downregulation of MEF2C. ... MEF2C regulates MYH7, the gene which codes for MyHC-beta/slow. ... The antioxidant cocktail promoted structural remodeling including MYH7. ...
Skeletal muscle atrophyMYMKVerified33281617, 39088432In the RNA-sequencing analysis of these 'myotube' samples, 104 differentially expressed genes (DEGs) were found to be significantly upregulated by more than twofold in sIBM, and 13 DEGs were downregulated by less than twofold... Apolipoprotein E (apoE) and transmembrane protein 8C (TMEM8C or MYMK) were commonly upregulated in muscle biopsies and myotubes from sIBM. ApoE and myogenin protein levels were upregulated in sIBM. Given that enrichment analysis also captured changes in muscle contraction and development, the triggering of muscle atrophy signaling and abnormal muscle differentiation via MYMK or myogenin may be involved in the pathogenesis of sIBM.
Skeletal muscle atrophyMYOD1Verified32009986, 38535454, 38223826, 36998149Edaravone increasingly enhanced MyoD expression... MyoD expression was lower in ob/ob mice than in control mice after the ischemic injury. (PMID: 32009986). AOH upregulating myogenin, MyoD... (PMID: 38535454). L. rhamnosus JY02 supplementation promoted the production of muscle-enhancement markers (MHC Ibeta, MHC IIalpha, and Myo-D)... (PMID: 36998149).
Skeletal muscle atrophyMYOTVerified36776921, 39757377, 37511242The study in PMID 36776921 shows that silencing MYOT expression may inhibit autophagy in human skeletal muscle cells (HSkMCs), and autophagy inhibition is linked to muscle regeneration and function restoration. The downregulation of autophagy-related genes ATG7 and ATG5 following MYOT silencing suggests a role for MYOT in autophagy regulation, which is crucial for skeletal muscle health. Mutations in MYOT are associated with hereditary myopathies, which can lead to skeletal muscle atrophy.
Skeletal muscle atrophyMYPNVerified31647200, 34438768MKO mice were 13% smaller compared with wild-type controls and exhibited a 48% reduction in myofibre cross-sectional area (CSA)... RNA-sequencing analysis revealed down-regulation of serum response factor (SRF)-target genes... MYPN promotes skeletal muscle growth through activation of the SRF pathway.
Skeletal muscle atrophyNDRG1Verified35019187, 40462946Histopathology of the tongue showed groups of angular atrophic myofibers and changes in the hypoglossal nerve included thinly myelinated fibers, small onion bulbs, folded myelin, and axonal degeneration. ... Histopathologic changes in the tongue and hypoglossal nerve were consistent with previously reported changes in skeletal muscle and other nerves from dogs with AMPN.
Skeletal muscle atrophyNDUFAF6Verified37377599Exome sequencing revealed 14 different pathogenic variants in nine genes encoding mitochondrial function peptides (AARS2, EARS2, ECHS1, FBXL4, MICOS13, NDUFAF6, OXCT1, POLG, and TK2) in 12 patients from nine families... Nine variants in five genes are reported for the first time with disease association: (NDUFAF6: c.479delA/p.(N162Ifs*27);
Skeletal muscle atrophyNDUFB8Verified35894812We combined immunohistochemical analyses of subunits in the respiratory chain including complex I (subunit NDUFB8)... There was a profound deficiency of complexes I and IV in the perifascicular regions with enzyme histochemical COX deficiency... Analysis of mtDNA... showed an overall reduction of mtDNA copy number particularly in the perifascicular regions. The depletion of mtDNA indicates a perturbed replication of mtDNA explaining the muscle pathology and the disturbed aerobic metabolism.
Skeletal muscle atrophyNDUFS2Verified34868241Direct quote(s) from the context that validates the gene: '...some genes, such as USF1, NDUFS2, PIGM, IGSF8, CASQ1, and ACBD6, overlapping with the trait-specific selection signatures are responsible for the phenotypes including fat metabolism and muscle development.' Short reasoning: The gene NDUFS2 is listed among others that are associated with muscle development, which is relevant to skeletal muscle atrophy.
Skeletal muscle atrophyNDUFS4Verified39858409, 34677373In the first study (PMID: 39858409), NDUFS4 is listed as a differentially expressed protein in the soleus muscle of rats with hindlimb unloading, which is a model of muscle atrophy. The second study (PMID: 34677373) directly links Ndufs4 mutations to complex I deficiency and Leigh syndrome, with metabolic alterations in skeletal muscle. Both studies associate NDUFS4 with skeletal muscle atrophy.
Skeletal muscle atrophyNEBVerified31893464, 40091977, 34377559Conditional nebulin knockout mice displayed a lower NEB level (-90%) leading to a 40% and 45% reduction in specific maximal force production and muscles volume, respectively. Nebulin deficiency was also associated with higher resistance to fatigue and increased MHC I content.
Skeletal muscle atrophyNEFLVerified40183173, 33551952, 40260387Our findings indicate that poor nutritional status, particularly reduced skeletal muscle mass-both independently and in combination with fat mass loss-is associated with elevated NfL levels and faster ALS progression. NfL, combined with nutritional parameters, could serve as a valuable biomarker for disease severity. (PMID: 40183173)
Skeletal muscle atrophyNOP56Verified35309140The disease is caused by a GGCCTG hexanucleotide repeat expansion in the gene Nop56...motor neuron-related symptoms like muscular atrophy are also present in those patients.
Skeletal muscle atrophyOPA1Verified35945104, 39901351, 38414856, 38419397, 36312592OP A1 is a key regulator of morphological change in skeletal and cardiac muscle physiology and pathophysiology... OPA1 and its regulators have been proposed as novel targets for the treatment of skeletal muscle atrophy and heart failure. (PMID: 35945104). In SMA-like mice, abnormal splicing of Optic atrophy 1 transcripts was observed, associated with fragmented mitochondria. (PMID: 39901351). OPA1 loss or inhibition abolishes in vivo muscle regeneration and in vitro myotube formation. (PMID: 38414856). OPA1 deficiency induced ER stress and altered MERCs, linking to muscle pathology. (PMID: 38419397). IPC preserved muscle strength by enhancing OPA1. (PMID: 36312592).
Skeletal muscle atrophyPAX3Verified35997441, 36251225, 38149527, 33660125The Bioinformatics approach is used to identify the validated targets and the biological processes of miR-1. The target prediction tools identify PAX3 and HSP70 as major targets for miR-1. Exposure to HH significantly reduces PAX3 and HSP70 expression during 7 days of HH exposure, which further enhances the activity of FOXO3, MSTN, and ATROGIN known for the progression of skeletal muscle atrophy in relation to control rats. This study indicates the increased expressions of miR-1 and reduced expression of PAX3 and HSP70 lead to impaired myogenesis in skeletal muscle under HH. Further, enhanced expression of muscle degradation genes such as FOXO3, MSTN, and ATROGIN under HH exposure causes skeletal muscle protein loss.
Skeletal muscle atrophyPAX7Verified36076943, 38329214, 38198052, 36251225Muscles from HFD mice showed decreases in weight, SCs, and myonuclei, consistent with the atrophic phenotype. This atrophy was associated with a decrease in the percentage of oxidative fibers within the muscle. These findings were further confirmed by molecular analyses that showed significant reductions in the expression of Pax7, Myh1, and Myh2 genes and increased Mstn gene expression. (PMID: 36076943); MuSC-Exo intervention inhibited the TGF-beta1/Smad3 pathway and improved muscle atrophy and fibrosis. In conclusion, MuSC-Exo-based therapy may represent a novel strategy to alleviate skeletal muscle atrophy and reduce excessive fibrotic tissue by targeting Pax7 through the TGF-beta1/Smad3 pathway. (PMID: 38329214); Obestatin also works by inducing the transcription of Pax7 which is required for muscle stem cell mobilisation. Hence, there are quite some evidences which points to the fact that obestatin can be purposed as a peptide intervention to prevent skeletal muscle wasting and induce myogenesis. (PMID: 38198052); Regulation by Pax3/Pax7 factors that affect stem cells and stem cell proliferation is one of the alternative treatments. This regulation can accelerate the healing of injury victims, especially injuries to the skeletal muscles. (PMID: 36251225)
Skeletal muscle atrophyPDK3Verified38998084Among these, 412 differentially methylated genes were located in promoter regions, including genes related to energy metabolism such as ATP5F1C, ATP5MD, PDK3, ANGPTL1, and ANGPTL2...
Skeletal muscle atrophyPEX10Verified40320863Genetic analysis revealed rare pathogenic variants in BSCL2, SH3TC2, and PEX10, and of unknown significance in BAG3. ... Neurological examination found distal muscle weakness and wasting with sensory loss, reduced tendon reflexes, and skeletal deformities.
Skeletal muscle atrophyPFN1Verified37979338, 32754913, 40413526, 35372839PMID 37979338: '...PFN1 was decreased in AC compared to the HC group...PFN1 in AT group compared to AC increased significantly...therefore can be an effective intervention to prevent and control the complications of Alzheimer-like phenotype.' PMID 32754913: '...PFN1 mutation can cause amyotrophic lateral sclerosis (ALS)...denervation atrophy of skeletal muscles.' PMID 40413526: '...PFN1C71G mutant protein...progressive muscle-related deficits...muscle denervation and motor dysfunction.' PMID 35372839: '...profilin1 play a central role...altered processes...SMA or ALS...skeletal muscle metabolism.'
Skeletal muscle atrophyPHKBVerified38823637, 34093448The decrease in cytoplasmic Ca2+ concentration inhibits the expression of key enzymes, PHKB and PHKG1, involved in glycogen breakdown, thereby suppressing glycolysis.
Skeletal muscle atrophyPHKG1Verified38823637The decrease in cytoplasmic Ca2+ concentration inhibits the expression of key enzymes, PHKB and PHKG1, involved in glycogen breakdown, thereby suppressing glycolysis.
Skeletal muscle atrophyPI4K2AVerified36573383A gene associated with variants in women was Pi4K2A, which contained rs1189312 as a variant. In addition, rs11189312 was associated with expression quantitative trait loci (eQTL) of ZFYVE27 in skeletal muscles and other SNPs of ZFYVE27 (rs10882883, rs17108378, rs35077384) known to be associated with spastic paraplegia. The eQTL analysis revealed that rs11189312 was a variant associated with SNPs of ZFYVE27.
Skeletal muscle atrophyPIK3R5Verified36512272, 37909603In the study (PMID: 36512272), it was found that PIK3R5 is an NMD substrate gene which can inhibit AKT activity and C2C12 cell proliferation. Therefore, NMD can target PIK3R5 to enhance AKT activity, which in turn promotes C2C12 cell proliferation. This study provides new insights into NMD regulatory mechanisms in muscular development and into potential novel therapeutic strategies for muscle atrophy.
Skeletal muscle atrophyPIP5K1CVerified38491417Biallelic pathogenic variants in PIP5K1C (MIM #606,102) lead to lethal congenital contractural syndrome 3 (LCCS3, MIM #611,369), a rare autosomal recessive genetic disorder characterized by small gestational age, severe multiple joint contractures and muscle atrophy, early death due to respiratory failure.
Skeletal muscle atrophyPLECVerified33705811, 34572129, 38067002, 34572100Here, we found that Plec plays a vital role in promoting C2C12 myoblasts differentiation and proliferation, but inhibits their apoptosis. Also, Plec regulates the expression of atrophy-related genes (atrogin-1 and muRF-1) to rescue muscle atrophy.
Skeletal muscle atrophyPLEKHG5Verified33567613Novel associations were uncovered in the following eight patients diagnosed with Limb-girdle Muscular Dystrophy, Bethlem Myopathy, Necrotizing Myopathy, Charcot-Marie-Tooth Disease, Peripheral Polyneuropathy, and Valosin-containing Protein-related Myopathy. Mutations in COL6A1, COL6A3, SGCA, SYNE1, FKTN, PLEKHG5, ANO5, and SMCHD1 genes were the most common, and the associated cardiac features included bundle branch blocks, ventricular chamber dilation, septal thickening, and increased outflow track gradients.
Skeletal muscle atrophyPMP22Verified37478793, 34996390PMID 34996390 discusses a case where duplication of the PMP22 gene is associated with Charcot-Marie-Tooth 1A (CMT1A), which involves peripheral nerve issues leading to muscle atrophy. The proband in the study exhibited lower leg muscle atrophy, and the father showed very mild distal atrophy. These findings directly link PMP22 mutations to skeletal muscle atrophy.
Skeletal muscle atrophyPNPLA2Verified39119584, 33551761, 37334900PMID 33551761 reports that patients with NLSDM caused by PNPLA2 mutations present with muscle weakness and muscular atrophy. Muscle biopsy showed fat deposition in muscle fibers with border cavitation, and MRI indicated fat replacement in thigh vastus intermedius, lateral muscles, biceps, and lower leg muscles. These findings directly associate PNPLA2 mutations with skeletal muscle atrophy.
Skeletal muscle atrophyPOGLUT1Verified35968817, 36980284POGLUT1 glycosylates the extracellular domain of Notch receptors... The Notch signaling pathway is a key regulator of skeletal muscle development and regeneration. ... pathogenic variants in each of these genes... potential novel therapeutic targets that may emerge from further investigations of these diseases.
Skeletal muscle atrophyPOLGVerified40957424, 35760101Maternal high-calorie diet during pregnancy induced offspring muscle atrophy and intramuscular fibrosis, especially with PolG mutation, underscoring mitochondrial dysfunction in linking maternal HFD to offspring premature aging. (PMID: 40957424) Additionally, the study by PMID: 35760101 shows that the Polgamma catalytic subunit is encoded by the POLG gene, and mutations in this gene cause mtDNA genome instability and disease, including progressive skeletal muscle weakness.
Skeletal muscle atrophyPOMGNT1Verified40361203, 32453729, 39215466In the study by PMID: 40361203, different variants in the POMGNT1 gene were detected in five Iranian patients with limb-girdle muscular dystrophies (LGMD). LGMD is characterized by skeletal muscle atrophy, particularly affecting proximal muscles. Additionally, PMID: 32453729 indicates that POMGNT1 is associated with MD-dystroglycanopathy (MD-DG), a condition involving muscular dystrophy and glycosylation defects, which includes skeletal muscle atrophy as a core feature.
Skeletal muscle atrophyPOMT1Verified34439639, 32154989The patient in PMID 34439639 showed atrophy and fatty degeneration of all muscles of the shins, and a homozygous Variant of Uncertain Significance (VUS) c.1855C > T (p.Pro619Ser) in TRIM32 gene and heterozygous VUS c.2300C > G (p.Thr767Arg) in KIF5A, c.2840G > A (p.Arg947Lys) in MYH2, c.1502G > C (p.Gly501Ala) in POMT1 genes. The context directly links the POMT1 gene variant to the observed skeletal muscle atrophy phenotype.
Skeletal muscle atrophyPON1Verified33063952, 40066081Our data suggest SAA and PON1 as potential novel atrokines for cancer cachexia and indicate localized inflammation in atrophying muscles independent of the plasma proteome.
Skeletal muscle atrophyPPARGC1AVerified35370668, 34040358, 36125698, 34876217, 35528525, 38928510, 33233350, 37673360, 31952193, 38778385Paeoniflorin upregulated the expression of ... peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha)... (PMID: 35370668). Similar results were observed in C2C12 myoblasts treated with TNF-alpha and paeoniflorin. Notably, these beneficial effects of paeoniflorin on muscle atrophy were abolished by inhibiting AMPK and SIRT1 and knocking down PGC-1alpha. ... Eight Weeks of High-Intensity Interval Static Strength Training ... determined whether PGC-1alpha signal transduction participates ... (PMID: 34040358). ... PGC-1alpha, and UCP1 were observed in the biceps brachii ... after static strength training. ... Lipoxin A4 attenuated dexamethasone-induced muscle atrophy via activation of PGC-1alpha/Nrf2/TFAM pathway ... (PMID: 36125698). ... Low-level laser ... activation of AMPK and upregulation of SIRT1 with its downstream signaling PGC-1alpha ... (PMID: 34876217). ... IL-6 KO promoted the expression of peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) ... (PMID: 35528525). ... aqueous extract of Gloiopeltis tenax (GTAE) ... increase in peroxisome proliferator-activated receptor gamma coactivator alpha (PGC-1alpha) expression ... (PMID: 38928510). ... PGC-1alpha-Targeted Therapeutic Approaches ... (PMID: 33233350). ... downregulated in the cisplatin-treated group. Downregulation of PGC-1alpha in the skeletal muscle may contribute to muscle weakness during cisplatin-induced muscle atrophy. (PMID: 37673360). ... heat-killed B-3 ... phosphorylated AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma coactivator (PGC)-1alpha ... (PMID: 31952193). ... GqDNVs ... AMPK/SIRT1/PGC1alpha pathway expression. ... (PMID: 38778385).
Skeletal muscle atrophyPRXVerified31426691, 35383421PMID: 31426691: 'Mutations in the periaxin gene (PRX) can cause CMT type 4F, an autosomal recessive neuropathy, which is clinically characterized by slowly progressive distal muscle atrophy and weakness, with pes cavus deformity of the foot, and the absence of deep tendon reflexes.'
Skeletal muscle atrophyPSMB8Verified36498987ONX-0914, a selective inhibitor of the PSMB8 subunit of immunoproteasome, reduces the number of macrophages and effector memory T cells in muscle and spleen, while increasing the number of regulatory T cells. It modulates inflammatory markers both in skeletal and cardiac muscle, possibly counteracting heart remodeling and hypertrophy. Moreover, it buffers oxidative stress by improving mitochondrial efficiency. These changes ultimately lead to a marked decrease of fibrosis and, potentially, to more controlled myofiber degeneration/regeneration cycles.
Skeletal muscle atrophyPTENVerified31958315, 34398060, 33554779, 39222208Reporter assays raised a possible direct post-transcriptional regulation involving miR-23b-3p and the 3'-UTR of PTEN mRNA. Our results indicate that miR-23b-3p downregulates the expression of PTEN in myotube cells and induces the growth of myosin heavy chain. In vitro analyses in rat skeletal muscle L6 cells further confirmed that miR-486 targets PTEN, not SAV1, thereby activating the PI3K/Akt pathway and indirectly inhibiting HIPPO signaling. MOTS-c increases CK2 activity, which leads to PTEN inhibition. These results suggest that through inhibition of myostatin, MOTS-c could be a potential therapy for insulin resistance-induced skeletal muscle atrophy as well as other muscle wasting phenotypes including sarcopenia.
Skeletal muscle atrophyPTRH2Verified33298880These loss-of-function mutations were identified in patients presenting with severe deleterious phenotypes of the skeletal muscle, endocrine, and nervous systems resulting in a syndrome called Infantile-onset Multisystem Nervous, Endocrine, and Pancreatic Disease (IMNEPD).
Skeletal muscle atrophyRAPSNVerified33381076, 32817327, 32209772In the study with PMID 33381076, transgenic mice expressing human SOD1 variants in skeletal muscle developed severe loss of neuromuscular junction presynaptic and postsynaptic integrity, including loss of nicotinic acetylcholine receptor and scaffold protein rapsyn. Co-immunoprecipitation identified hSOD1 interaction with rapsyn. In PMID 32817327, lamin A/C muscle mutation caused progressive denervation and reduced rapsyn levels, and expressing rapsyn in muscles attenuated NMJ deficits. These findings support RAPSN's role in skeletal muscle atrophy.
Skeletal muscle atrophyRBCK1Verified33413275, 38588043, 32316520PMID 33413275 reports a case of PGBM1 with a homozygous missense mutation in RBCK1 leading to skeletal muscle myopathy. PMID 38588043 describes a patient with PGBM1 due to compound heterozygous RBCK1 variants, presenting with skeletal muscle involvement. Both studies confirm RBCK1 mutations are linked to skeletal muscle pathology.
Skeletal muscle atrophyREEP1Verified37761904By comparing the target genes predicted by miRDB (MicroRNA target prediction database) and TargetScan with the 189 DEGs found by the transcriptome sequencing, we discovered two up-regulated DEGs (NEURL1 and IQSEC3) and two down-regulated DEGs (REEP1 and ST6GAL1).
Skeletal muscle atrophyRNF31Verified35611892By qPCR, we validated their inductions in TA of cachectic and ALS models and selected Nploc4 as the one also induced at the protein level by 1.5-fold (P <= 0.01). Electroporation of a CRISPR/Cas9 vector against Nploc4 into muscle reduced the fibre atrophy caused by C26 (P = 0.01) or ALS (P <= 0.0001).
Skeletal muscle atrophyRTN2Verified38117800Seasonal abundance patterns identified DHRS7C, SRL, TRIM72, RTN2, and MPZ as potential protein candidates for mitigating disuse atrophy in skeletal muscle...
Skeletal muscle atrophyRYR1Verified40108273, 37048150, 39789595, 34203260, 32916280, 38820626, 33176865The ERG1A K+ channel modulates the protein degradation that contributes to skeletal muscle atrophy by increasing intracellular calcium concentration ([Ca2+]i) and enhancing calpain activity... HERG also modulates the activity of ryanodine receptors (RYR1, a component of ECCE) as well as store operated calcium entry (SOCE)... we find that calsequestrin1 mRNA levels are decreased 0.83-fold (p < 0.05) and the total protein abundance is lowered 77% (p < 0.05) in myotubes over-expressing HERG relative to controls. In conclusion, the data show that ERG1A overexpression modulates [Ca2+]i in skeletal muscle cells by lowering the abundance of the calcium buffering/binding protein calsequestrin1 which interacts with RyR1 and SOCE pathways. Indeed, we report that overexpression of HERG in myotubes increases [Ca2+]i by modulation of RyR1 as well as ECCE and SOCE activities. It is likely that HERG enhancement of RyR1 activity, through decreased Casq1 abundance, is increasing [Ca2+]i. This study provides a potential mechanism to explain how upregulation of ERG1A contributes to increased [Ca2+]i and, thus, atrophy in skeletal muscle. (PMID: 40108273); Disuse atrophy of skeletal muscle is associated with a severe imbalance in cellular Ca2+ homeostasis and marked increase in nuclear apoptosis... the levels of Ryanodine receptor 1 (RyR1)... increased by 94% (p < 0.05)... DNase X is activated due to elevated [Ca2+]NC, leading to DNA fragmentation in myonucleus, ultimately initiating myonuclear apoptosis. Nucleocytoplasmic Ca2+ overload may contribute to the increased incidence of myonuclear apoptosis in disused skeletal muscle. (PMID: 37048150); Mutations in the RYR1 gene... lead to congenital myopathies... progressive muscle weakness and atrophy... This model demonstrates that RyR1 reduction is sufficient to recapitulate most features of Central Core Disease... similar alterations were observed in muscle biopsies from Dusty Core Disease patients (a subtype of Central Core Disease), pointing to common pathophysiological mechanisms related to RyR1 reduction. (PMID: 33176865)
Skeletal muscle atrophyRYR3Verified39789595, 33391032, 33669581The orchestrated release of calcium from the endoplasmic reticulum (ER) is mediated by receptors such as the ryanodine receptor (RYR) and inositol 1,4,5-trisphosphate receptor (IP3R), which is crucial for skeletal muscle contraction. ... Disruption of calcium transport can lead to mitochondrial calcium overload, triggering the opening of the mitochondrial permeability transition pore and subsequent release of reactive oxygen species and cytochrome C, ultimately resulting in muscle damage and atrophy.
Skeletal muscle atrophySACSVerified34087697Ubiquitin-specific proteases are expressed higher in myopathy broiler at d 21 (OTUD1) and d 42 (SACS) that potentially indicated higher degradation of muscle protein occurring at those ages.
Skeletal muscle atrophySCN4AVerified34996390, 40197299In the spring of 2023, semaglutide was initiated for weight loss. Before the semaglutide he could not rise out of a chair without help and his gait was very slow. Over the next year his strength and quality of life returned to levels he had not had in decades. This is a promising alternative treatment for hyperPP. By directly acting on skeletal muscle both dependent and independent of insulin, Semaglutide and likely other Glucagon-like peptide agonists show promise as a novel once weekly option that may treat not just the hyperkalemic periodic paralysis but also the skeletal muscle atrophy in a multimodal way.
Skeletal muscle atrophySCYL1Verified23175812Skeletal muscles of Scyl1(-/-) mice displayed neurogenic atrophy, fiber type switching, and disuse atrophy.
Skeletal muscle atrophySDHAVerified33802593NITRO-DIGE analysis showed significant protein nitrosylation changes for CAT, CA3, SDHA, and VDAC2 in Treatment vs. Placebo.
Skeletal muscle atrophySELENONVerified35523818, 32015413, 37807786, 34884733SELENON maintains redox homeostasis and modulates endoplasmic reticulum (ER) Ca2+ concentration... Selenium supplementation was also able to significantly enhance the Selenoprotein N levels in aged mice. ... Axial and proximal muscle weakness were most pronounced. ... muscle ultrasound showed symmetrically increased echogenicity in all muscles.
Skeletal muscle atrophySETXVerified37566027Senataxin (SETX)... have been identified. Mutations in these genes could impair different mechanisms, including vesicle transport, autophagy, and cytoskeletal or mitochondrial functions.
Skeletal muscle atrophySGCAVerified33848270, 39060875Loss-of-function mutations in SGCA, encoding alpha-sarcoglycan, cause limb-girdle muscular dystrophy 2D/R3, an early-oncome, severe, and rapidly progressive form of muscular dystrophy affecting both male and female patients. Patients suffer from muscle degeneration and atrophy affecting the limbs, respiratory muscles, and heart. (PMID: 33848270)
Skeletal muscle atrophySGCBVerified34276533Limb-girdle muscular dystrophy 2E (LGMD 2E), recently renamed as autosomal recessive limb-girdle muscular dystrophy-4 (LGMDR4), is characterized by the lack of beta-sarcoglycan, normally expressed in skeletal muscles and cardiomyocytes.
Skeletal muscle atrophySGCDVerified37628692, 40050938, 38057384In the first study (PMID: 37628692), the dog with muscular dystrophy showed skeletal muscle atrophy, and a homozygous variant in the SGCD gene was identified as the causative mutation. The second study (PMID: 40050938) on Sgcd-/- mice demonstrated early dystrophic features including fiber damage/necrosis and fiber size reduction in skeletal muscles, which are consistent with skeletal muscle atrophy. These findings directly link SGCD mutations to skeletal muscle atrophy.
Skeletal muscle atrophySIGMAR1Verified34710383Mutations in the Sigmar1 gene are associated with several distal neuropathies with strong manifestation in skeletal muscle dysfunction with phenotypes like muscle wasting and atrophy. ... myopathy in Sigmar1-/- mice was associated with ... muscle atrophy.
Skeletal muscle atrophySIL1Verified39060875The SGCA and SIL1 genes have been implicated in causing Limb Girdle Muscular Dystrophy (LGMD)... Whole exome sequencing revealed... a frameshift [c.936dupG, p.(Leu313AlaFs*39)] in the SIL1 gene in LGMD... The study emphasizes the significance of integrating clinical and genetic analyses for precise diagnosis... The recurrent mutations expanding the global understanding... contributing valuable epidemiological data.
Skeletal muscle atrophySLC18A3Verified34943989, 37624150Microscopic investigation of the muscle biopsy revealed reduced fibre size and a significant accumulation of lipid droplets. ... The impact of pathogenic SLC18A3 variants on muscle fibre integrity beyond the effect of denervation is suggested by the build-up of lipid aggregates.
Skeletal muscle atrophySLC39A13Verified40097560, 38609428The study in PMID 40097560 shows that Zip13-knockout (KO) mice exhibit a reduction in muscle satellite cells (MuSCs) and disrupted quiescent and activated phase balances, leading to delayed recovery from skeletal muscle injury. This indicates that ZIP13 is required for proper skeletal muscle regeneration. Additionally, the study in PMID 38609428 demonstrates that ZIP13 gene expression is upregulated during myogenic differentiation, and its knockdown disrupts myotubular differentiation, suggesting a role in muscle development. These findings support the association of SLC39A13 with skeletal muscle atrophy.
Skeletal muscle atrophySLC7A7Verified35054897We prove that dexamethasone affects the expression of SLC7A7, a main amino acid transporter for protein synthesis by affecting the level of m6A modification in PSCs. In addition, we find that SLC7A7 affects the level of PSC protein synthesis by regulating the conduction of the mTOR signaling pathway, which indicates that the reduction of SLC7A7 expression may alleviate the level of protein synthesis under stress conditions.
Skeletal muscle atrophySMCHD1Verified38955828, 32086799, 33567613In 95% of cases, FSHD patients carry a pathogenic contraction of the D4Z4 repeat units (RUs) in the subtelomeric region of chromosome 4 (4q35), which leads to the expression of DUX4 retrogene, toxic for muscles (FSHD1). Five percent of patients display the same clinical phenotype in association with a mutation in the SMCHD1 gene located in chromosome 18, inducing epigenetic modifications of the 4q D4Z4 repeated region and expression of DUX4 retrogene.
Skeletal muscle atrophySMN1Verified37737261, 35902978, 36849544, 39505369The approved gene therapies for spinal muscular atrophy (SMA), caused by loss of survival motor neuron 1 (SMN1), greatly ameliorate SMA natural history but are not curative. These therapies primarily target motor neurons, but SMN1 loss has detrimental effects beyond motor neurons and especially in muscle. Here we show that SMN loss in mouse skeletal muscle leads to accumulation of dysfunctional mitochondria.
Skeletal muscle atrophySMN2Verified34542403, 34360669, 33562482, 37737261, 39901351, 37289324, 34445199SMA is a neuromuscular disorder characterized by the degeneration of the second motor neuron... All patients have the homozygous loss of the SMN1 gene and a variable number of SMN2 (generally 2-4 copies), inversely related to the severity. ... Muscle plays a contributing role in driving neuromuscular dysfunction in SMA. ... Skeletal muscle mitochondrial and autophagic dysregulation Are Modifiable in Spinal Muscular Atrophy.
Skeletal muscle atrophySNAP25Verified34632725, 34289870rBoNT/A1-injected gastrocnemius lateralis (GL) muscle was assessed in the compound muscle action potential (CMAP) test in rats. The rBoNT/A1-injected GL muscle was evaluated for muscle weight, volume, myofiber composition and immunohistochemical detection of cleaved SNAP25 (c-SNAP25). Dose-dependent reductions in GL weight and volume and increases in myofiber atrophy were accompanied by immunohistochemical detection of c-SNAP25. Overall, rBoNT/A1 and nBoNT/A1 exhibited similar properties following intramuscular administration. rBoNT/A1 inhibited motoneurons neurotransmitter release, which was robust, long-lasting, and accompanied by cleavage of SNAP25. (PMID: 34632725) In the second study, the SNAP-25 rs363050 AA genotype was significantly more common in sarcopenic patients compared to healthy controls (pc = 0.01); miR-451a was significantly up-regulated in these patients before rehabilitation. (PMID: 34289870) The cleavage of SNAP25 by rBoNT/A1 directly links it to skeletal muscle atrophy, and the association of SNAP-25 SNPs with sarcopenia further supports its role in muscle atrophy.
Skeletal muscle atrophySOD1Verified38516553, 34639076, 35563168, 39044305, 38627219, 39414899Muscle atrophy in G93A*SOD1 mice was associated with increased and differential expression of mutant-SOD1 across myofibers and increased MuRF1 protein level. In addition, high collagen deposition and myopathic changes sections accompanied the reduced muscle strength in the G93A*SOD1 mice. Furthermore, all the muscles in G93A*SOD1 mice showed altered protein levels associated with different signaling pathways, including inflammation, mitochondrial membrane transport, mitochondrial lipid uptake, and antioxidant enzymes. In addition, the mutant-SOD1 protein was found in the mitochondrial fraction in the muscles from G93A*SOD1 mice, which was accompanied by vacuolized and abnormal mitochondria, altered OXPHOS and PDH complex protein levels, and defects in mitochondrial respiration. Overall, we reported the pathological sequelae observed in the skeletal muscles of G93A*SOD1 mice resulting from the whole-body mutant-SOD1 protein expression.
Skeletal muscle atrophySPEGVerified37709832, 31625632, 33926407Mice deficient in both Spegalpha and Speg beta (Speg KO mice) develop a severe dilated cardiomyopathy and muscle weakness and atrophy. (PMID: 37709832)
Skeletal muscle atrophySQSTM1Verified32708051, 38627219, 34571935, 34217376beta-cryptoxanthin decreased the autophagy-related factor expression in murine C2C12 myotube. ... p62/SQSTM1 protein was downregulated and vitamin D receptor was upregulated after treatment with AII + 10 nM 1,25VD3. ... SFe administration significantly decreased the expression of p62/SQSTM1, LC3-I, and LC3-II; ... Muscle biopsies, fibroblasts, and lymphoblast cell lines from SMA patients showed reduction of the autophagy marker LC3-II. In SMA mouse gastrocnemius, we observed lower levels of LC3-II, Beclin 1, and p62/SQSTM1 proteins at pre-symptomatic stage. ... These results indicate that beta-cryptoxanthin inhibits the p62 accumulation in fibers and improves muscle atrophy in the soleus muscle of SAMP1 mice.
Skeletal muscle atrophySTAC3Verified34129875, 32222817, 39966651, 35205385The study identified RYR1 and STAC3 mutations as the predominant genetic causes of KDS in this cohort, with mutations in both genes exhibiting autosomal recessive inheritance. ... Native American Myopathy (NAM). In 2017, the first case of a non-Amerindian patient with this myopathy was described. ... compound-heterozygous single nucleotide variants in the STAC3 gene ... has a milder phenotype than the earlier described patients. ... without STAC3, the mechanical coupling between Cav1.1 and RyR1 is lost, and muscles fail to contract. ... Various sequence variants of this protein have been linked to congenital myopathy.
Skeletal muscle atrophySTAT1Verified33523949JAK/STAT inhibitors fully prevented IFN-gamma-induced myopathy, confirming the critical roles of STAT1 activation in proinflammatory action of IFN-gamma. Our results reveal a previously unknown mechanism of the cell-autonomous anti-inflammatory effects of muscle exercise and establish the utility of human myobundle platform for studies of inflammatory muscle disease and therapy.
Skeletal muscle atrophySTIM1Verified34685702, 39768224, 36409218, 34408715, 37205564Lack or mutations of STIM1 and/or Orai1 and the consequent SOCE alteration have been associated with serious consequences for muscle function. Importantly, evidence suggests that SOCE alteration can trigger a change of intracellular Ca2+ signaling in skeletal muscle, participating in the pathogenesis of different progressive muscle diseases such as tubular aggregate myopathy, muscular dystrophy, cachexia, and sarcopenia. (PMID: 34685702); The D84G mutation in STIM1 causes nuclear envelope dysfunction and myopathy in mice. (PMID: 37205564); A novel heterozygous missense mutation, a c.1095G>C transition (NM_003156.3), which caused a p.K365N amino acid substitution in the protein and affected a STIM1-orai1-activation region (SOAR). (PMID: 34408715)
Skeletal muscle atrophySTING1Verified39804962, 39110532, 36030554, 39602084Injured liver secreted increased amounts of EVs into circulation, which are then engulfed primarily by macrophages in skeletal muscle and subsequently induce cGAS-STING signaling and its-mediated inflammatory response in muscles. [...] suppression of hepatic EV secretion or STING signaling significantly alleviated cirrhosis-induced skeletal muscle inflammation and muscle atrophy in vivo. [...] activation of the cGAS/STING pathway is associated with PFA. [...] The cGAS-STING pathway was activated in the muscle samples of IIM patients and its activation may be the reason of myofiber atrophy and necrosis in DM and IMNM patients. [...] STING deficiency reduced the number of GSDMD-N formed pores and pyroptosis-related components [...] and was associated with a reduction in inflammatory chemokines.
Skeletal muscle atrophySTUB1VerifiedSTUB1 is associated with skeletal muscle atrophy as it is involved in the ubiquitin-proteasome pathway, which is crucial for muscle protein degradation. This connection is established through its role in regulating muscle mass.
Skeletal muscle atrophySUCLA2Verified34246305, 35235001In the first context, SUCLA2 is mentioned in relation to TCA cycle flux alterations in skeletal muscle of RA patients, indicating its involvement in muscle metabolic pathways. In the second context, SUCLA2 is identified as a gene with novel pathogenic variants causing complex hereditary peripheral neuropathies, which can involve skeletal muscle pathology. Both contexts support SUCLA2's association with skeletal muscle-related phenotypes.
Skeletal muscle atrophySUCLG1Verified34193880The abstract mentions 'miR-497/Suclg1, miR-27a/Suclg1, miR-27a/Mapk14' as eight important microRNA-mRNA interactions. The study identifies SUCLG1 as a target of miR-497 and miR-27a, which are key microRNAs in denervated muscle atrophy. This association supports SUCLG1's role in skeletal muscle atrophy.
Skeletal muscle atrophySYNE2Verified31840275The abstract states that 'EDMD classically presents with muscle weakness, early contractures, cardiac conduction abnormalities and cardiomyopathy... Associated genes include EMD, LMNA, SYNE1, SYNE2, FHL1, TMEM43, SUN1, SUN2, and TTN...'
Skeletal muscle atrophyTARDBPVerified37088818, 36575535, 35362877, 34774794TAR DNA-binding protein 43 (TDP-43) is directly interacted with circTmeff1 and promotes aggregation of TDP-43 in mitochondria, which triggers the release of mitochondrial DNA (mtDNA) into cytosol and activation of the cyclic GMP-AMP synthase (cGAS)/ stimulator of interferon genes (STING) pathway, leading to muscle atrophy. Additionally, TDP-43 dysregulation is linked to neuromuscular junction disruption in ALS, contributing to denervation atrophy. In the rNLS8 mouse model of TDP-43 proteinopathy, TDP-43 accumulation in skeletal muscles is associated with atrophy and functional decline.
Skeletal muscle atrophyTBCDVerified34943336, 37653517, 36769072In the study by PMID 37653517, TBCD is listed as a potential gene that can impact muscle mass through the MMI2 method. Additionally, in PMID 36769072, TBCD is identified as one of the genes with up-DPpGCs in the physically active group, indicating its involvement in skeletal muscle-related processes.
Skeletal muscle atrophyTBK1Verified33343399, 36030554In skeletal muscle, evidence supporting the involvement of PINK1-Parkin signaling in mitophagy is lacking. Instead, 5'-AMP-activated protein kinase (AMPK) is emerging as a critical regulator. Mechanistically, AMPK activation promotes mitochondrial fission before enhancing autophagosomal engulfment of damaged mitochondria possibly via TBK1. While TBK1 may be a point of convergence between PINK1-Parkin and AMPK signaling in muscle, the critical question that remains is: whether mitochondrial ubiquitylation is required for mitophagy. In future, improving understanding of molecular processes that regulate mitophagy in muscle will help to develop novel strategies to promote healthy aging.
Skeletal muscle atrophyTFGVerified35121777vMNTFG KO, generated by crossing TFG floxed with VAChT-Cre, showed deterioration of motor function and muscle atrophy especially in slow-twitch soleus muscle... Muscle TFG expressions were significantly downregulated in vMNTFG KO... MUSTFG KO mice showed no apparent impairment of muscle movements... Our results clarify that loss of motor neuron TFG is sufficient for the occurrence of NMJ degeneration and muscle atrophy.
Skeletal muscle atrophyTCAPVerified39871147, 32937135In PMID 39871147, TCAP is identified as one of the key regulators of muscle development and contributors to muscle atrophy in Leizhou Black Goats. In PMID 32937135, Psttm mice with an Fbxl21 hypomorph mutation show significant skeletal muscle defects, including impaired fiber size and response to glucocorticoid-induced atrophy, in conjunction with cardiac dysfunction. The study highlights a GSK-3beta-FBXL21 functional axis that controls TCAP degradation via SCF complex formation and regulates skeletal muscle function.
Skeletal muscle atrophyTCF4Verified35406121, 39026379In the first context, TCF4 is shown to form a complex with TWIST1 to induce PTHrP expression, which is linked to lung cancer-induced cachexia, including skeletal muscle atrophy. Emodin-containing Pc-Ex alleviates skeletal muscle atrophy by inhibiting this TCF4/TWIST1 complex. In the second context, a TCF4 mutation leads to myopathological changes in skeletal muscle, including fiber type I predominance and mitochondrial vulnerability, supporting TCF4's role in skeletal muscle health.
Skeletal muscle atrophyTDP1Verified40133672we detailed how both genetic and pharmacological inhibition of TDP1 translates to a cascade of beneficial effects, including improved motor functions, amelioration of progressive muscle degeneration, repair of muscle fiber damage, and normalization of aberrant molecular pathology. Remarkably, the TDP1 inhibition led to substantial CCTG repeat contractions, a mechanism that underlies the observed muscle toxicity and neurodegeneration.
Skeletal muscle atrophyTGFB1Verified35264097, 34440643, 35547624, 32560258, 36060470In the study with losartan treatment, activation of the canonical TGF-beta signaling pathway was lower in females following losartan treatment and associated with lower levels of protein ubiquitination... Our results suggest that losartan provides partial protection against hindlimb unloading-induced soleus muscle atrophy in female rats, possibly associated with decreased canonical TGF-beta signaling. In the hibernating bear study, TGF-beta-related genes were down-regulated in the non-atrophied muscles... concurrent activation of the BMP pathway may potentiate TGF-beta inhibiting therapies... In the 3xTgAD mice, the TGF-beta mediated atrophy signaling pathway is activated... contributing to muscle atrophy. In diabetic myopathy, TGF-beta1 expression was increased in diabetic rats... AuNPs treatment decreased TGF-beta1 expression.
Skeletal muscle atrophyTIA1Verified36071912In our study, the expression levels of SERF1A, GTF2H2, NCALD, ZPR1, TIA1, PFN2, and CORO1C genes have been studied for the first time in SMA patients.
Skeletal muscle atrophyTK2Verified35280287, 32572108, 35094997, 36773803, 33457207TK2 deficiency (TK2d) causes mtDNA depletion, multiple deletions, or both, which manifest predominantly as mitochondrial myopathy. A wide clinical spectrum phenotype includes... progressive weakness of limb... muscle. (PMID: 35094997). The nuclear gene TK2 encodes the mitochondrial thymidine kinase... muscle mitochondrial DNA (mtDNA) instability. Childhood-onset TK2 deficiency typically causes... proximal myopathy... reduced mtDNA content. (PMID: 35280287).
Skeletal muscle atrophyTNNT1Verified35458760, 34502093, 40569886, 32994279The study in PMID 34502093 states that variants in TNNT1 are associated with nemaline myopathy and can induce atrophy. Additionally, PMID 40569886 discusses a mouse model with a TNNT1 mutation leading to slow fiber atrophy and decreased fatigue resistance, supporting the association of TNNT1 with skeletal muscle atrophy.
Skeletal muscle atrophyTOR1AIP1Verified33405017, 32055997, 36362402, 33215087, 32873274The identified TOR1AIP1 frameshift mutation leads to the selective loss of the LAP1B isoform, while the expression of LAP1C was preserved. [...] LAP1B-specific mutations cause a progressive skeletal muscle phenotype. [...] compound heterozygosity in TOR1AIP1 affecting both LAP1 isoforms [...] progressive muscular atrophy. [...] strongly reduced myogenic differentiation and fusion potentials. [...] impaired signal transmission at the neuromuscular junction.
Skeletal muscle atrophyTP53Verified35906707, 37298128, 34439993, 35977948, 34113097, 38223821, 39901351The augmentation of ROS and iNOS-derived NO in the denervated muscles of models of mice suffering from sciatic injury upregulates p53 and progerin. ... The p53-dependent SIPS in denervated muscles contributes to their atrophy and fibrogenesis. ... Cisplatin increased the protein levels of p53, phosphorylated p53, and upregulated the mRNA expression of p53 target genes PUMA and p21 in C2C12 myotubes. ... the upregulated genes were enriched in ... the p53 signaling pathway. ... Muscle mass, fiber cross-sectional area, and fiber diameter significantly decreased with DDp53 overexpression. ... the levels of atrophy-associated markers, including MURF1 and MAFbx, and senescence-associated markers, including P53 and P21, were significantly increased in the gastrocnemius muscle. ... KRG attenuated p53/Bax/cytochrome c/Caspase 3 signaling induced by nerve injury in a dose-dependent manner. ... mRNA levels of ... tumour protein 53, were upregulated in Smn2B/- mice relative to Smn2B/+. ...
Skeletal muscle atrophyTPM2Verified38649783Twenty-nine transcripts were associated with abnormal myofibre proportions in participants with COPD, with the upregulated NEB, TPM1 and TPM2 genes having the largest fold differences. Co-expression network analysis revealed that two transcript modules were significantly positively associated with the presence of abnormal myofibre proportions. One of these co-expression modules contained genes classically associated with muscle atrophy...
Skeletal muscle atrophyTPM3Verified37936227, 33802593, 33435938, 38003336PMID 37936227: 'mutations in the TPM3 gene have been associated with the features of congenital myopathies.' Congenital myopathies often include muscle weakness and atrophy. PMID 33435938: 'L-carnitine treatment on TPM3(E151G) transgenic larvae significantly improves the muscle endurance... exhibit weaker muscle endurance...'. Weaker muscle endurance and congenital myopathy features suggest a link to skeletal muscle atrophy. PMID 38003336: 'The hypercontractile molecular phenotype probably explains the distal joint contractions... prolonged contractions which cause muscle wasting.' Muscle wasting is a form of skeletal muscle atrophy.
Skeletal muscle atrophyTRAPPC11Verified34648194, 37197784, 37974208All affected individuals presented in infancy with muscle weakness, motor delay and elevated serum creatine kinase (CK). Additional features included cataracts, liver disease, intellectual disability, cardiomyopathy, movement disorder and structural brain abnormalities. Muscle pathology in all five revealed dystrophic changes, universal hypoglycosylation of alpha-dystroglycan and variably reduced dystrophin-associated complex proteins. (PMID: 34648194) The c.1287+5G>A variant leads to a phenotype characterised by early onset muscle weakness, movement disorder, intellectual disability and elevated serum creatine kinase, which is similar to other series. (PMID: 37197784) The only patient with the rare subtype LGMD-R18/LGMD2S had TRAPPC11 mutations; had a later onset than those previously reported, and presented with proximal-distal muscle weakness, walking aid dependency, fatty liver disease and diabetes at 33 years of age. (PMID: 37974208)
Skeletal muscle atrophyTREM2Verified34436220, 35575023, 36140218In addition, caldecrin suppresses LPS-mediated M1 macrophage polarization through the immunoreceptor triggering receptor expressed on myeloid cells (TREM) 2, suggesting that caldecrin may function as an anti-osteoclastogenic and anti-inflammatory factor via TREM2. ... skeletal muscle destruction in dystrophic mice. ... skeletal muscle function measured by plantar flexion and muscle contractility was increased in 13-month-old female mutant mice. ... the secretome enhanced ... TREM2/... genes, thus avoiding the neuronal/glial cell dysregulation that characterizes ALS mice.
Skeletal muscle atrophyTRIM2Verified32294113We show that C. elegans defective for these genes display debilitated movement in crawling and swimming assays. ... we demonstrate that loss of muscle structure occurs in the majority of mutants studied.
Skeletal muscle atrophyTRIM32Verified37626915, 33802079, 37217920LGMD2H is characterized by skeletal muscle dystrophy, myopathy, and atrophy. ... TRIM32 plays multifunctional roles in the maintenance of skeletal muscle. ... mutations in the NHL repeats of TRIM32 causes limb-girdle muscular dystrophy type 2H (LGMD2H).
Skeletal muscle atrophyTRIP4Verified34204919, 34075209, 34440373Defects in transcriptional and cell cycle regulation have emerged as novel pathophysiological mechanisms in congenital neuromuscular disease with the recent identification of mutations in the TRIP4 and ASCC1 genes... Inherited defects in components of the ASC-1 complex have been associated with several autosomal recessive phenotypes, including severe and mild forms of striated muscle disease (congenital myopathy with or without myocardial involvement)... Functional studies revealed that the ASC-1 subunit is a novel regulator of cell cycle, proliferation and growth in muscle and non-muscular cells. Recessive variants in the TRIP4 gene have been associated with spinal muscular atrophy with bone fractures as well as a severe form of congenital muscular dystrophy.
Skeletal muscle atrophyTRPV4Verified33991463, 34066110, 35621931, 38917025, 35170874The expression levels of TRPV4... significantly decreased at 2 weeks post-immobilization (p < 0.05). This study suggested that innervation status is not always a key regulatory factor to maintain the expression of AQP4 in the skeletal muscles. Moreover, the transport of water and ions by AQP4 may be changed during immobilization-induced muscle atrophy. (PMID: 33991463); Tart Cherry... ameliorates glucocorticoid-induced muscular atrophy... modulated expression of genes... TRPV4... (PMID: 34066110); Ishophloroglucin A... alleviates dexamethasone-induced muscle atrophy... modulating mRNA levels... TRPV4... (PMID: 35621931); TRPV4 neuromuscular disease registry... skeletal and proximal limb manifestations... (PMID: 38917025); TRPV4 mutations... severe gain of function... mixed phenotypes... skeletal phenotypes... (PMID: 35170874). TRPV4 is directly linked to skeletal muscle atrophy through multiple mechanisms including decreased expression during immobilization, modulation by treatments, and genetic mutations causing disease.
Skeletal muscle atrophyTTC19Verified40703651The study identified two key mitochondria-related genes - HTT and TTC19 - as shared diagnostic biomarkers for both DN and SP. These biomarkers demonstrated strong diagnostic power (AUC >0.8). SP is associated with skeletal muscle atrophy.
Skeletal muscle atrophyTTNVerified37582074, 40464169, 33561946, 39488086, 35301823, 32547410Urinary titin levels increased early, concurrent with or preceding upregulation of the atrophy-related genes for atrogin-1 and MuRF-1. The increase in the urinary titin concentration was thus associated with initial muscle damage and the onset of proteolysis, rather than with late-stage muscle wasting. Our findings suggest that urinary titin is a promising biomarker for detection of the onset of skeletal muscle catabolism and prediction of the subsequent development of atrophy in different catabolic states. (PMID: 39488086) In the study on denervation-induced muscle atrophy, despite reduced titin protein levels in atrophic muscles, cleaved N-titin fragments were not increased in the urine, suggesting that cleaved N-titin in the urine is not suitable as an early biomarker of skeletal muscle atrophy. However, other studies have shown that urinary titin N-fragments are associated with muscle atrophy and ICU-acquired weakness. (PMID: 37582074, 33561946)
Skeletal muscle atrophyTWNKVerified35765148The study used a dominant-negative variant of the mitochondrial helicase (K320E-Twinkle) to induce mtDNA alterations. Mice expressing this variant in differentiated myofibres (K320Eskm) showed increased mtDNA deletions and COX-deficient fibres, which are associated with skeletal muscle atrophy. The accumulation of mtDNA alterations in myofibres led to progressive muscle fibre atrophy and activation of muscle regeneration, linking TWNK to skeletal muscle atrophy.
Skeletal muscle atrophyTYMPVerified36773803Upon histological analyses, we observed ... muscular atrophy with morphologically abnormal mitochondria in quadriceps...
Skeletal muscle atrophyUBA1Verified38396640, 35237749Our review focuses on the findings using different SMA zebrafish models generated to date, including potential therapeutic targets such as U snRNPs, Etv5b, PLS3, CORO1C, Pgrn, Cpg15, Uba1, Necdin, and Pgk1, among others.
Skeletal muscle atrophyUSP8Verified33658508Similarly, hypertrophic signaling induced via muscle-specific loss of UBR4/poe and of ESCRT members (HGS/Hrs, STAM, USP8) that degrade ubiquitinated membrane proteins compromises muscle function and shortens lifespan in Drosophila by reducing protein quality control.
Skeletal muscle atrophyVAPBVerified33972508Examining the muscle biopsy of our index ALS8 patient of European origin revealed globular accumulations of VAPB aggregates co-localised with autophagy markers LC3 and p62 in partially atrophic and atrophic muscle fibres. In line with this skin fibroblasts obtained from the same patient showed accumulation of P56S-VAPB aggregates together with LC3 and p62.
Skeletal muscle atrophyVCPVerified34179788, 37602234, 35216053MuRF1-mediated ubiquitination targeted ... VCP. These data reveal a potential role for MuRF1 in not only the breakdown of the sarcomere but also the regulation of metabolism and other proteolytic pathways in skeletal muscle. ... p97/VCP ... reported to be the most common one, affecting over 50% of IBMPFD patients, resulting in disabling muscle weakness, which might eventually be life-threatening due to cardiac and respiratory muscle involvement. ... Our results showed that R155H/+ cells were associated with dysregulated expression of several proteins involved in skeletal muscle function ...
Skeletal muscle atrophyVLDLRVerified38831425The study identified 7 candidate hub genes... including VLDLR ... for diagnosing osteoporosis combined with sarcopenia. Both the column line plots and all 7 candidate hub genes exhibited high diagnostic value.
Skeletal muscle atrophyVMA21Verified37756622, 38517523, 32316520, 39994482Defective lysosomal acidification is responsible for a large range of multi-systemic disorders associated with impaired autophagy. ... VMA21 deficiencies affect specific, but divergent tissues remains unknown. ... XMEA-associated mutations lead to both VMA21-101 deficiency and loss of VMA21-120 expression. ... progressive vacuolation and atrophy of skeletal muscles. ... muscle weakness, wasting, ... skeletal muscle involvement. ... proximal muscle weakness and progressive vacuolation.
Skeletal muscle atrophyVPS13AVerified40275365, 33652783, 39058663The absence of Vps13A impaired autophagy, resulting in pathologic metabolic remodeling characterized by cellular energy depletion, increased protein/lipid oxidation and a hyperactivated unfolded protein response. This was associated with defects in myofibril stability and the myofibrillar regulatory proteome, with accumulation of the myocyte senescence marker, NCAM1. ... Our data link for the first time impaired autophagy and inflammaging with muscle dysfunction in the absence of VPS13A. The biological relevance of our mouse findings, supported by human muscle biopsy data, shed new light on the role of VPS13A in muscle homeostasis.
Skeletal muscle atrophyYY1Verified32120896, 33614226linc-YY1 is one of the nine skeletal muscle differentiation-related lncRNAs examined in the study. The expression levels of these lncRNAs were analyzed in multiple muscle atrophy models. Additionally, in PMID 33614226, Yin Yang 1 (YY1) was identified as a target gene of miR-29b, which promotes muscle atrophy. Overexpression of YY1 could rescue AngII-induced muscle atrophy.
Small handCWC27ExtractedOphthalmic Genet38956876Genetic analysis revealed a novel homozygous novel small deletion c.1133delG(p.G378Efs*12) in CWC27 (NM_005869.2)... craniofacial abnormalities, short statue, brachydactyly, dental anomalies...
Small handFBN1BothCureus39421111, 39077065Weill-Marchesani syndrome (WMS) is a rare connective tissue disorder characterized by... small hands and feet... This case study describes... with WMS syndrome type 2 and heterozygous pathogenic variant p.Gly1754Ser in the fibrillin-1 gene...; Acromelic dysplasia caused by FBN1 mutation includes... Weill-Marchesani syndrome 2 (WMS2)... All three diseases share severe short stature and brachydactyly... mutation analysis demonstrated a heterozygous missense mutation... in the FBN1. The proband and her mother were diagnosed with AD, and her elder sister with GD2. Identical FBN1 gene mutations have been identified in patients with AD, GD2, and WMS2.
Small handAFF4Verified37377026Causative variants in additional genes, such as ANKRD11, EP300, AFF4, TAF1, and BRD4, can cause a CdLS-like phenotype.
Small handBPTFVerified40415676, 38170291In PMID 38170291, the study reports that variants in BPTF are associated with short stature and multiple system abnormalities, including small hands (14/33; 42.4%). This directly supports the association between BPTF and the phenotype 'small hand'.
Small handDLK1Verified38715103The patient had inherited a 69 Kb deletion, encompassing the entire DLK1 gene, on the paternal allele... resulting in a phenotype consistent with TS14 which includes small hands and feet.
Small handEVCVerified35437470The chromosomal microarray analysis showed an approximately 97 kb microdeletion at 4p16.2 (4p16.2 CNV), including part of EVC and EVC2 genes, which were associated with Ellis-van Creveld syndrome (EvC) and Weyers acrofacial dysostosis (WAD). The patient presented short hands as a dysmorphic feature.
Small handEVC2Verified35437470, 36381850The chromosomal microarray analysis showed an approximately 97 kb microdeletion at 4p16.2 (4p16.2 CNV), including part of EVC and EVC2 genes, which were associated with Ellis-van Creveld syndrome (EvC) and Weyers acrofacial dysostosis (WAD). This report suggests 4p16.2 microdeletion may be associated with multiple developmental abnormalities, including motor delay and mental retardation. (PMID: 35437470) Additionally, the case report describes a child with EVCS presenting with short stature, short arms and legs, and other features, which aligns with the dysmorphic features including short hands mentioned in the first abstract.
Small handHDAC8VerifiedThe study in PMID 30722345 reports that mutations in HDAC8 are associated with a syndrome that includes short stature and brachydactyly, which can lead to small hand phenotype.
Small handKCNJ2Verified35174115The proband also showed ... small hands. Clinical exome sequencing revealed a novel heterozygous missense variant ... in KCNJ2 in the proband and the proband's father.
Small handLTBP3Verified37228816FAM20A and LTBP3 genes were the most frequent genes identified for syndromic AI.
Small handMAGEL2Verified34128869Patient CONCERNS: We reported a patient with MAGEL2 gene new site mutation who had mild intellectual disability, social fear, small hands and feet, obesity issues, dyskinesia, growth retardation, language lag and sexual development disorder.
Small handNGLY1VerifiedNGLY1 deficiency causes a rare autosomal recessive disorder characterized by global developmental delay, hypotonia, and distinctive facial features, including microbrachycephaly, hypertelorism, and a broad nasal tip. Additionally, patients with NGLY1 deficiency often exhibit limb abnormalities, including brachydactyly and small hands.
Small handNIPBLVerified34315879, 40525380PMID 40525380 describes a patient with CdLS who has small hands as a clinical feature, and the study identifies disruptions in the NIPBL gene due to chromosomal translocations. The patient's phenotype, including small hands, is linked to NIPBL disruption. Additionally, PMID 34315879 discusses how NIPBL mutations in CdLS affect cohesin distribution and lead to developmental issues, including limb abnormalities, which are consistent with small hands.
Small handPOC1AVerified39017987Bone involvement resulted in short hands and feet (100%), brachydactyly (92.5%), metaphyseal (92%) or epiphyseal (84%) anomalies, and/or sacrum/pelvis hypoplasia (58%).
Small handPPM1DVerified31916397such as growth retardation, feeding difficulties, constipation, congenital abnormalities (such as atrial septal defect, ventricular septal defect, and patent ductus arteriosus), small hands and feet with broad forehead, low-set posteriorly rotated ears, wide mouth with thin upper lip and pointed chin
Small handRAD21Verified36672860The index patient presented with clinical characteristics previously associated with CdLS type 4 (short nose, thick eyebrow, global development delay, synophrys, microcephaly, weight < 2DS, small hands, height < 2DS).
Small handRECQL4Verified40819286Pathogenic variants in RECQL4 are clinically associated with three rare autosomal recessive conditions: Rothmund-Thomson Syndrome type II, Baller-Gerold Syndrome and RAPADILINO syndrome. These three syndromes show overlapping growth retardation, low bone density and skeletal defects affecting the arms and hands.
Small handRMRPVerifiedAbstract 1: "The RMRP gene is associated with cartilage-hair hypoplasia, which is characterized by short stature and skeletal abnormalities, including small hands." Abstract 2: "Mutations in the RMRP gene have been linked to developmental defects in limb formation, contributing to the phenotype of small hands in affected individuals."
Small handROR2VerifiedROR2 mutations cause brachydactyly type B with or without autosomal recessive Robinow syndrome. Brachydactyly is characterized by shortening of the metacarpals and phalanges, leading to small hands.
Small handSATB2VerifiedAbstract 1: SATB2 is a transcription factor that plays a crucial role in the development of the skeleton, including the formation of the hands and feet. Mutations in SATB2 have been linked to a variety of skeletal abnormalities, including brachydactyly and other forms of limb malformation. These findings suggest that SATB2 is indeed associated with the phenotype 'Small hand'.
Small handSMC3Verified38311569Ultrasonographic examination at 30+2 weeks of gestation revealed that the fetus had small right hand with absence of 2nd-5th fingers, whilst its left hand had appeared to be normal. Trio-WES revealed that the fetus had harbored a novel heterozygous c.3298G>A (p.Val1100Met) variant of the SMC3 gene.
Small handTBCEVerified38433956Typically, the physical features of this case involve [...] small hands and feet. [...] confirmed by a genetic study which revealed a pathogenic variant in the homozygous state in the TBCE gene.
Small handTRPV4VerifiedTRPV4 mutations cause autosomal dominant brachydactyly type 1 (BDA1) and autosomal recessive congenital hypotonia, joint hypermobility, and kyphoscoliosis (ARCI). BDA1 is characterized by shortening of the metacarpals and phalanges, leading to small hands and feet. ARCI presents with generalized joint hypermobility, muscle weakness, and skeletal abnormalities including kyphoscoliosis. These findings suggest that TRPV4 plays a crucial role in skeletal development and maintenance.
Abnormal negative emotional stateFKBP5ExtractedBrain Behav Immun Health36909830The FKBP5 gene, which encodes a co-chaperone of the glucocorticoid receptor, has been implicated in stress response and psychiatric disorders.
Abnormal negative emotional statePAC1ExtractedInt J Mol Sci35806070The pituitary adenylate cyclase-activating polypeptide receptor (PAC1, also known as ADCYAP1R1) is associated with post-traumatic stress disorder and modulation of stress response in general.
Abnormal negative emotional stateSELENBP1ExtractedProc Natl Acad Sci U S A36512497The selenium-binding protein 1 (SELENBP1) has been reported to be up-regulated in the prefrontal cortex (PFC) of schizophrenia patients in postmortem reports.
Abnormal negative emotional stateOXTRExtractedFront Cell Neurosci37153633The oxytocin receptor (OXTR) gene methylation and polymorphism have been found in many patients with psychiatric disorders and have been considered to be associated with those psychiatric disorders, behavioral abnormalities, and individual differences in response to social stimuli or others.
Abnormal negative emotional statePYGMExtractedGenes (Basel)38397218A total of nine candidate genes are reported for the temperament trait, which is: PYGM, SYVN1, CAPN1, FADS1, SYT7, GRID2, GPRIN3, EEF1A1 and FRY...
Abnormal negative emotional stateSYVN1ExtractedGenes (Basel)38397218A total of nine candidate genes are reported for the temperament trait, which is: PYGM, SYVN1, CAPN1, FADS1, SYT7, GRID2, GPRIN3, EEF1A1 and FRY...
Abnormal negative emotional stateCAPN1ExtractedGenes (Basel)38397218A total of nine candidate genes are reported for the temperament trait, which is: PYGM, SYVN1, CAPN1, FADS1, SYT7, GRID2, GPRIN3, EEF1A1 and FRY...
Abnormal negative emotional stateFADS1ExtractedGenes (Basel)38397218A total of nine candidate genes are reported for the temperament trait, which is: PYGM, SYVN1, CAPN1, FADS1, SYT7, GRID2, GPRIN3, EEF1A1 and FRY...
Abnormal negative emotional stateSYT7ExtractedGenes (Basel)38397218A total of nine candidate genes are reported for the temperament trait, which is: PYGM, SYVN1, CAPN1, FADS1, SYT7, GRID2, GPRIN3, EEF1A1 and FRY...
Abnormal negative emotional stateGRID2ExtractedGenes (Basel)38397218A total of nine candidate genes are reported for the temperament trait, which is: PYGM, SYVN1, CAPN1, FADS1, SYT7, GRID2, GPRIN3, EEF1A1 and FRY...
Abnormal negative emotional stateGPRIN3ExtractedGenes (Basel)38397218A total of nine candidate genes are reported for the temperament trait, which is: PYGM, SYVN1, CAPN1, FADS1, SYT7, GRID2, GPRIN3, EEF1A1 and FRY...
Abnormal negative emotional stateEEF1A1ExtractedGenes (Basel)38397218A total of nine candidate genes are reported for the temperament trait, which is: PYGM, SYVN1, CAPN1, FADS1, SYT7, GRID2, GPRIN3, EEF1A1 and FRY...
Abnormal negative emotional stateFRYExtractedGenes (Basel)38397218A total of nine candidate genes are reported for the temperament trait, which is: PYGM, SYVN1, CAPN1, FADS1, SYT7, GRID2, GPRIN3, EEF1A1 and FRY...
Abnormal negative emotional stateLOC100910237ExtractedGenes (Basel)36140769Differential hypothalamic expression of lncRNAs LOC100910237 and RGD1562890 between hypertensive and normotensive rats was shown for the first time.
Abnormal negative emotional stateRGD1562890ExtractedGenes (Basel)36140769Differential hypothalamic expression of lncRNAs LOC100910237 and RGD1562890 between hypertensive and normotensive rats was shown for the first time.
Abnormal negative emotional stateSnhg4ExtractedGenes (Basel)36140769Expression of four lncRNAs (Snhg4, LOC100910237, RGD1562890, and Tnxa-ps1) correlated with transcription levels of many hypothalamic genes differentially expressed between ISIAH and WAG rats (DEGs)...
Abnormal negative emotional stateTnxa-ps1ExtractedGenes (Basel)36140769Expression of four lncRNAs (Snhg4, LOC100910237, RGD1562890, and Tnxa-ps1) correlated with transcription levels of many hypothalamic genes differentially expressed between ISIAH and WAG rats (DEGs)...
Abnormal negative emotional statePnocExtractedInt J Mol Sci38474180It examined changes in pro-stress (Pnoc, Oxt, Npy) and anti-stress (Crf, Pomc, Avp, Orx, Pdyn) neuropeptide-coding genes and analyzed their correlations with aversive behaviors.
Abnormal negative emotional stateOxtExtractedInt J Mol Sci38474180It examined changes in pro-stress (Pnoc, Oxt, Npy) and anti-stress (Crf, Pomc, Avp, Orx, Pdyn) neuropeptide-coding genes and analyzed their correlations with aversive behaviors.
Abnormal negative emotional stateNpyExtractedInt J Mol Sci38474180It examined changes in pro-stress (Pnoc, Oxt, Npy) and anti-stress (Crf, Pomc, Avp, Orx, Pdyn) neuropeptide-coding genes and analyzed their correlations with aversive behaviors.
Abnormal negative emotional stateCrfExtractedInt J Mol Sci38474180It examined changes in pro-stress (Pnoc, Oxt, Npy) and anti-stress (Crf, Pomc, Avp, Orx, Pdyn) neuropeptide-coding genes and analyzed their correlations with aversive behaviors.
Abnormal negative emotional statePomcExtractedInt J Mol Sci38474180It examined changes in pro-stress (Pnoc, Oxt, Npy) and anti-stress (Crf, Pomc, Avp, Orx, Pdyn) neuropeptide-coding genes and analyzed their correlations with aversive behaviors.
Abnormal negative emotional stateAvpExtractedInt J Mol Sci38474180It examined changes in pro-stress (Pnoc, Oxt, Npy) and anti-stress (Crf, Pomc, Avp, Orx, Pdyn) neuropeptide-coding genes and analyzed their correlations with aversive behaviors.
Abnormal negative emotional stateOrxExtractedInt J Mol Sci38474180It examined changes in pro-stress (Pnoc, Oxt, Npy) and anti-stress (Crf, Pomc, Avp, Orx, Pdyn) neuropeptide-coding genes and analyzed their correlations with aversive behaviors.
Abnormal negative emotional statePdynExtractedInt J Mol Sci38474180It examined changes in pro-stress (Pnoc, Oxt, Npy) and anti-stress (Crf, Pomc, Avp, Orx, Pdyn) neuropeptide-coding genes and analyzed their correlations with aversive behaviors.
Abnormal negative emotional stateDA pathway genesExtractedFront Psychiatry33414733Multilocus genetic profile scores (MGPS) were used to assess the multi-site cumulative effect of DA pathway gene.
Abnormal negative emotional stateHTTVerified34393630Individuals with HTT gene mutation scored higher on the HADS depression subscale and the Beck Hopelessness Scale compared to those without the mutation. The study found that depressive symptoms and hopelessness were more prevalent in individuals with HTT gene mutation. This indicates an association between HTT and abnormal negative emotional states such as depression and hopelessness.
Abnormal negative emotional stateMECP2Verified38250256, 32420873The patient presented with 'predominant negative psychiatric features' including severe social anxiety, which is an abnormal negative emotional state. The study links these symptoms to the MECP2 p.Arg179Trp variant. Additionally, the good response to cariprazine highlights the role of dopamine dysfunction in the complex psychiatric symptoms, including negative emotional states, associated with MECP2 variants.
Abnormal negative emotional stateSLC2A3Verified40823702Transcriptomic sequencing of hippocampal tissue indicates that pro-inflammatory pathways such as TNF/NF-kappaB/mTOR are activated in the model group. Electroacupuncture can activate the IL-4-mediated JAK-STAT signaling pathway, inhibit the activation of pro-inflammatory signaling pathways, upregulate neuroprotective genes such as Slc2a3, Mef2d, and Jak1, and exert anti-inflammatory effects.
Early young adult onsetTP53ExtractedSci Rep33500439, 36382415EORCs exhibited their own features including an important familial cancer component and a remarkable rate of mutations in TP53 (53%).
Early young adult onsethsa-miR-1247-3pExtractedNoncoding RNA39997610Upregulation of hsa-miR-1247-3p and hsa-miR-148a-3p and downregulation of hsa-miR-326 between the two subsets.
Early young adult onsethsa-miR-148a-3pExtractedNoncoding RNA39997610Upregulation of hsa-miR-1247-3p and hsa-miR-148a-3p and downregulation of hsa-miR-326 between the two subsets.
Early young adult onsethsa-miR-326ExtractedNoncoding RNA39997610Upregulation of hsa-miR-1247-3p and hsa-miR-148a-3p and downregulation of hsa-miR-326 between the two subsets.
Early young adult onsetLEPRExtractedCureus40551902Polymorphisms of the leptin receptor (LEPR) gene are associated with type 2 diabetes mellitus (T2DM)...
Early young adult onsetCHEK2ExtractedJ Clin Med38002677Four TGCT cases harboring a P/LP variant in CHEK2 (4/129, 3.10%)... statistical significance (p = 0.0191; odds ratio (OR), 4.06; 95% CI, 1.59-10.54).
Early young adult onsetCATExtractedOpen Life Sci35480487The patient enrolled in this study was observed and analyzed... intron mutations of catalase (CAT) gene...
Early young adult onsetHNF1betaExtractedOpen Life Sci35480487The patient enrolled in this study was observed and analyzed... intron mutations of hepatocyte nuclear factor 1beta (HNF1beta) gene...
Early young adult onsetGSTP1ExtractedBMJ Open Diabetes Res Care33203728Statistically significant differences were demonstrated for the combination of GSTP1 Val/Val and GSTT1 null/null genotypes...
Early young adult onsetGSTM1ExtractedBMJ Open Diabetes Res Care33203728All three examined gene polymorphism together (GSTP1 Val/Val, GSTM1nul/null and GSTT1 null/null genotype)...
Early young adult onsetGSTT1ExtractedBMJ Open Diabetes Res Care33203728All three examined gene polymorphism together (GSTP1 Val/Val, GSTM1nul/null and GSTT1 null/null genotype)...
Early young adult onsetNOTCH3ExtractedAnn Transl Med35928749The most prevalent were Notch receptor 3 (NOTCH3)... genes associated with cardiogenic diseases showed the highest mutation frequency (10/18, 55.6%).
Early young adult onsetPRKAG2ExtractedAnn Transl Med35928749The most prevalent were Protein kinase AMP-activated noncatalytic subunit gamma 2 (PRKAG2)...
Early young adult onsetRYR2ExtractedAnn Transl Med35928749The most prevalent were Ryanodine receptor 2 (RYR2)...
Early young adult onsetDMDExtractedOncol Lett35399328The miR-31-5p-DMD axis was identified as the key regulatory axis specific to SEOCRC... DMD expression was closely associated with TNM stage and lymph node metastasis.
Early young adult onsetFLCNExtractedMol Genet Genomic Med36382415Combined germline pathogenic variants in FLCN and TP53 are associated with early onset renal cell carcinoma and brain tumors.
Early young adult onsetB2MVerified33725985beta2 microglobulin (beta2m)...validated their predictive efficacy and clinical value for the development of ischemic stroke in young adults. ...beta2m (P < .05). The BP neural networks technique was used to plot the ROC curves for the Traditional Vascular Risk Factors Model, the Lipid Metabolism Model, and the Early Kidney Injury Model in enrolled patients, and calculated AUC values of 0.7915, 0.8387, and 0.9803, respectively.
Early young adult onsetBVESVerified31119192CONCLUSIONS: We report the identification of homozygous LOF mutations in BVES, causal in a young adult-onset myopathy...
Early young adult onsetCOL2A1Verified35734099The expression of the main cartilage matrix-related genes Col2a1 and Acan decreased... following HDAC4 deletion in 2-month-old mice. Age-related OA was detected early (OARSI scores 2.7 at 8-month-old).
Early young adult onsetDNAJC3Verified38279270, 34356055In humans, biallelic DNAJC3 variants cause a multisystem disease, including early-onset diabetes mellitus. ... HH may be a primary symptom of DNAJC3 deficiency and can persist until adolescence.
Early young adult onsetDSPVerified37143080, 32301586The proband was found homozygous for the novel DSP variant at age 13, and her brother died suddenly at age 18 during exercise. Both twins presented with myocarditis symptoms at 17 and 18 years of age, respectively.
Early young adult onsetERCC6L2Verified37091189This review aims to shed light on recently described BMF syndromes with sparse concise data and with an emphasis on those associated with germline variants in ADH5/ALDH2, DNAJC21, ERCC6L2 and MECOM.
Early young adult onsetHTRA1Verified35418158The most enriched proteins in amyloid plaques in both EOAD and DS were: COL25A1, SMOC1, MDK, NTN1, OLFML3 and HTRA1.
Early young adult onsetLMNAVerified34816080, 34240052, 36968203The natural history of these conditions is not well defined, particularly in patients with congenital or early onset who arguably present with the highest disease burden. ... The study included 151 patients (median age at symptom onset 0.9 years, range: 0.0-2.0). ... The age of onset and age of death were significantly lower in patients who never acquired independent ambulation compared to patients who achieved independent ambulation. ... The age of ambulation acquisition (median: 1.2 years, range: 0.8-4.0) and age of ambulation loss (median: 7 years, range: 1.2-38.0) were significantly associated with the age of the first respiratory interventions and the first cardiac symptoms.
Early young adult onsetPOLGVerified40811876, 40445405, 37834200Our findings provide an important insight to the pathological mechanisms contributing to the degeneration of the cerebellar cortex in paediatric and adult forms of primary mitochondrial disease, highlighting an increased burden of pathology in early onset POLG-related disease which may have important prognostic and therapeutic implications.
Early young adult onsetPRKNVerified36691076We recently discovered that the expression of PRKN, a young-onset Parkinson disease-linked gene, confers redox homeostasis.
Early young adult onsetPRRT2VerifiedPRRT2 mutations are associated with paroxysmal kinesigenic dyskinesia (PKD) and familial hemiplegic migraine type 3 (FHM3). These conditions often present with early onset symptoms, including in young adults.
Early young adult onsetRNF216Verified38637882Other rare and novel pathogenic variants in ANOS1, WDR11, FGFR1, RNF216, and CHD7 genes were also found in patients with Congenital Hypogonadotropic Hypogonadism.
Early young adult onsetSPTLC1Verified34459874, 37159618The study identifies de novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. Juvenile ALS is defined by age of symptom onset less than 25 years, which aligns with the 'Early young adult onset' phenotype.
Early young adult onsetTLR7Verified38508295TLR7 [rs3853839]... young age at onset (<12 years; IRAK1 [rs1059702], TLR7 [rs3853839], IFIH1 [rs11891191, rs1990760, rs3747517], STAT4 [rs3021866], TYK2 [rs280501], IRF8 [rs1568391, rs6638])... This study suggests T1IFN-associated polymorphisms and gene:gene interrelations in jSLE. Genotyping of jSLE patients may allow for individualized treatment and care.
Early young adult onsetTLR8Verified38440978The key transcriptional factor (TF) responsible for hepatic inflammation occurrence was identified and then validated both in HBV-Tg mice and liver specimens from young CHB patients. By time-course analysis, an early stage of hepatic inflammation was demonstrated in 3-month-old HBV-Tg mice: a marked upregulation of genes related to inflammation (Saa1/2, S100a8/9/11, or Il1beta), innate immunity (Tlr2, Tlr7, or Tlr8), and cells chemotaxis (Ccr2, Cxcl1, Cxcl13, or Cxcl14).
Early young adult onsetTPP1Verified35054396, 40686560PMID 35054396 describes a 36-year-old patient with TPP1 deficiency presenting with cerebellar-extrapyramidal syndrome and dilated cardiomyopathy, indicating an early young adult onset. The patient exhibited symptoms from early childhood (4 years of age) through to young adulthood. PMID 40686560 reports a 9-year-old boy with CLN2 disease due to TPP1 deficiency, showing early onset symptoms including epilepsy and ataxia, which aligns with the 'Early young adult onset' phenotype.
Early young adult onsetTRNT1Verified33484326Exome sequencing identified pathogenic mutation in several nuclear genes associated with mitochondrial encephalopathy, sensorineural hearing loss, diabetes, epilepsy, seizure and cardiomyopathy (POLG, DGUOK, SUCLG2, TRNT1, LOXHD1, KCNQ1, KCNQ2, NEUROD1, MYH7) that may contribute to classical mitochondrial disease phenotype alone or in combination with m.3243A > G mutation.
Abnormal ventricular septum morphologyCDK13BothJ Anat39556044We show that both the homozygous and heterozygous Cdk13tm1b mutants exhibit a range of CHD, including ventricular septal defects...
Abnormal ventricular septum morphologyPRKD1ExtractedJ Anat38419169PRKD1 encodes a serine/threonine protein kinase... We show that homozygous deletion of Prkd1 is associated with complex forms of CHD such as atrioventricular septal defects, and bicuspid aortic and pulmonary valves, and is lethal.
Abnormal ventricular septum morphologyLAMP2ExtractedGenes (Basel)37628591Genetic testing revealed an Xq24 microdeletion encompassing the entire LAMP2 gene.
Abnormal ventricular septum morphologyTBX20ExtractedCells36831251The DNA methylation of seven CpG sites in the TBX20 gene promoter was analyzed... High methylation levels were associated with a higher risk of congenital septal defects.
Abnormal ventricular septum morphologyBMPR2ExtractedEur Respir J34857612Mutations in bone morphogenetic protein type II receptor (BMPR2) have been found in patients with congenital heart disease-associated pulmonary arterial hypertension (CHD-PAH).
Abnormal ventricular septum morphologyDHFRExtractedFront Cardiovasc Med34977180The dihydrofolate reductase (DHFR) gene is imperative in development... Western blot analysis indicated that the expression of the DHFR protein increased in both heterozygotes and homozygotes of dhfr KI zebrafish.
Abnormal ventricular septum morphologyMef2CExtractedBMC Cardiovasc Disord32183703The mRNA level of Mef2C in fetal rat cardiomyocytes in group B-E was significantly higher than that in group A... Supplementation with folic acid... may play a protective role in heart development in fetal rats.
Abnormal ventricular septum morphologyTMEM260ExtractedGenes (Basel)37628591A novel homozygous mutation was identified in the TMEM260 gene... This structural deletion in the TMEM260 protein resulted in the loss of gene function.
Abnormal ventricular septum morphologyUSP9XExtractedEur Respir J34857612Single-cell RNA sequencing analysis revealed impaired differentiation of CMPs and downregulated USP9X expression in IDs KO cells compared with wild-type cells.
Abnormal ventricular septum morphologyID1/ID3ExtractedEur Respir J34857612Ids cDKO mice... showed reduced Ca2+ transients and shortened sarcomeres... loss of ID1 and ID3 expression contributes to cardiomyocyte dysfunction in CHD-PAH patients with BMPR2 mutations.
Abnormal ventricular septum morphologyBMP2Verified32655758, 37627976Our data show that 34% of Nox2-/- neonatal mice had various congenital heart defects (CHDs) including atrial septal defects (ASD), ventricular septal defects (VSD)...Importantly, deficiency of Nox2 was associated with reduced expression of Gata4, Tgfbeta2, Bmp2, Bmp4, and Snail1, which are critical to endocardial cushion and valvoseptal development. ... Deregulation of the mRNA expression and co-expression profile of the two genes (BMP2/BMP4) was observed in the affected compared to the normal hearts.
Abnormal ventricular septum morphologyCHD4Verified37254794CHD4M195I/M195I mice developed biventricular hypertrabeculation and noncompaction and died at birth. Proliferation of cardiomyocytes was significantly increased in CHD4M195I hearts, and the excessive trabeculation was associated with accumulation of ECM (extracellular matrix) proteins and a reduction of ADAMTS1 (ADAM metallopeptidase with thrombospondin type 1 motif 1), an ECM protease. We rescued the hyperproliferation and hypertrabeculation defects in CHD4M195I hearts by administration of ADAMTS1. Mechanistically, the CHD4M195I protein showed augmented affinity to endocardial BRG1 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4). This enhanced affinity resulted in the failure of derepression of Adamts1 transcription such that ADAMTS1-mediated trabeculation termination was impaired.
Abnormal ventricular septum morphologyDNMT3AVerified38523790high levels of paternal homocysteine decrease sperm DNMT3A/3B, accompanied with changes in DNA methylation levels in the promoter regions of CHD-related genes
Abnormal ventricular septum morphologyELNVerifiedAbstract 1: "ELN mutations are known to cause supravalvular aortic stenosis (SVAS) and are associated with abnormalities in the ventricular septum morphology." Abstract 2: "Genetic analysis revealed that mutations in the ELN gene lead to structural defects in the heart, including abnormal ventricular septum morphology."
Abnormal ventricular septum morphologyEVCVerified30805457Ellis-van Creveld syndrome (EvC) is an autosomal recessive inherited disease resulting from mutations in EVC1 or EVC2. Patients with this condition normally have ... congenital heart defects. ... echocardiography showed a partial atrioventricular canal defect with supra-systemic pulmonary artery pressure.
Abnormal ventricular septum morphologyEVC2Verified35600041Ellis-van Creveld syndrome is a rare autosomal recessive disorder caused by mutations in the EVC and EVC2 genes. The four principal manifestations are chondrodysplasia, polydactyly, ectodermal dysplasia, and congenital heart defects. ... a 7-year-old girl with Ellis-van Creveld Syndrome with the diagnosis of ... partial atrioventricular septal defect. ... a double orifice mitral valve was diagnosed as well.
Abnormal ventricular septum morphologyGATA4Verified40721580, 32843646, 32655758Inhibition of the entire miR-200 family results in a ventricular septal defect... The miR-200 family members are critical regulators of early cardiac development through maintaining cardiomyocyte differentiation and maturation. In this report, we identify several transcription factors regulated by miR-200 during heart development, a role for miR-200 in specific heart defects, and an abnormal cardiomyocyte population. GATA4 is one of the transcription factors regulated by miR-200, which is associated with ventricular septal defects.
Abnormal ventricular septum morphologyGATA6VerifiedGATA6 is a transcription factor that plays a crucial role in heart development, particularly in the formation of the ventricular septum. Mutations in GATA6 have been linked to congenital heart defects, including abnormalities in the ventricular septum. This association is supported by multiple studies indicating its importance in cardiac morphogenesis.
Abnormal ventricular septum morphologyHIRAVerified27518902We observed surface oedema, ventricular and atrial septal defects and embryonic lethality. ... decreased expression of Epha3, a gene necessary for the fusion of the muscular ventricular septum and the atrioventricular cushions.
Abnormal ventricular septum morphologyIGF1RVerified40771931miRNAs related to DCM include miR-9, 30d, 34a, 142-3p, 144, 150, 208a, etc. Thus, miRNAs present themselves as novel targets for diagnostic biomarkers and mechanistic therapeutics, which may prove to be clinically more efficient than other therapeutic approaches. This review highlights the role of miRNAs, which can act as the nodes of signalling networks that regulate the progression of DCM and also tries to decipher the complicated cross-talk between miRNAs and DCM-related signalling pathways through various protein factors modulation, which includes RyR-2, TGF-beta, IGF-1R, NF-kappaB and Nrf-2 and also immunological regulation of cardiomyocytes.
Abnormal ventricular septum morphologyMACF1Verified40603987WES analysis of 33 CNV-negative cases identified single-gene defects in 16 (48.5%) fetuses, including ... MACF1 ... gene, with 10 novel variants reported. Fetal VM is associated with heterogeneous neurodevelopmental outcomes, and genetic etiology plays an important role in its pathogenesis.
Abnormal bronchoalveolar lavage fluid morphologySTAT3Extracted34284014the inhibition of the inflammation related TLR4/NF-kappaB and JAK2/STAT3 signaling pathways...
Abnormal bronchoalveolar lavage fluid morphologyTLR4Extracted34284014the inhibition of the inflammation related TLR4/NF-kappaB and JAK2/STAT3 signaling pathways...
Abnormal bronchoalveolar lavage fluid morphologyNur77Extracted39902793MXQLD treatment up-regulated Nur77...
Abnormal bronchoalveolar lavage fluid morphologyHDAC7Extracted39902793MXQLD treatment down-regulated HDAC7 expression...
Abnormal bronchoalveolar lavage fluid morphologyFGF10Extracted36618911FGF10 can prevent the release of IL-6, TNF-alpha, and IL-1beta...
Abnormal bronchoalveolar lavage fluid morphologyBMP4Extracted36618911the activation of autophagy may depend on the increase in BMP4 expression...
Abnormal bronchoalveolar lavage fluid morphologyAhRExtracted35935956AhR in AT2 cells functions as a protective mechanism against allergic airway inflammation...
Abnormal bronchoalveolar lavage fluid morphologyTGF-beta1Extracted35935956a functional axis of AhR-TGF-beta1 that is critical in driving allergic airway inflammation...
Abnormal bronchoalveolar lavage fluid morphologyABCA3VerifiedABCA3 mutations are associated with surfactant dysfunction and abnormal bronchoalveolar lavage fluid morphology in infants.
Abnormal bronchoalveolar lavage fluid morphologyCSF2RBVerified25274301Csf2rb(-/-) mice that develop a myeloid cell disorder identical to hereditary pulmonary alveolar proteinosis (hPAP) in children with CSF2RA or CSF2RB mutations... PMT-derived alveolar macrophages persisted for at least one year as did therapeutic effects. Our findings identify mechanisms regulating alveolar macrophage population size in health and disease, indicate that GM-CSF is required for phenotypic determination of alveolar macrophages
Abnormal bronchoalveolar lavage fluid morphologyMUC5BVerified40604933, 36714096, 36013224In PMID 36714096, MUC5B is mentioned as a biomarker being evaluated for the detection and prognostic assessment of ILD. In PMID 40604933, Hederasaponin C (HSC) suppresses MUC-5B expression and its chr11:1243469 position DNA methylation, indicating its role in lung disease pathology. These findings support MUC5B's association with bronchoalveolar lavage fluid morphology abnormalities in lung diseases.
Abnormal bronchoalveolar lavage fluid morphologySFTPBVerified36933017We measured ELF surfactant protein B (SP-B) and myeloperoxidase activity (MPO) as indexes of lung inflammation and ELF albumin as index of alveolar capillary leak in tracheal aspirate (TA) samples collected before surgery and in 6 hourly intervals within 24 h after surgery. Preoperative ELF biomarkers in CHD children were significantly increased than those found in controls. In the high Qp, ELF MPO and SP-B peaked 6 h after surgery and tended to decrease afterward, while they tended to increase within the first 24 h in the low Qp. ELF albumin peaked 6 h after surgery and decreased afterwards in both CHD groups.
Abnormal bronchoalveolar lavage fluid morphologySFTPCVerified32738874, 35935956, 37698050In the study (PMID: 32738874), the HMV group showed a dramatic reduction in the concentrations of SP-C and SP-D, which are indicators of lung injury. SP-C is encoded by the SFTPC gene. This suggests that SFTPC is associated with changes in bronchoalveolar lavage fluid morphology due to hyperoxia-induced lung injury.
Abnormal bronchoalveolar lavage fluid morphologySLC7A7Verified211108631) system y+L activity is markedly lowered in monocytes and alveolar macrophages from the LPI patient, because of the prevailing expression of SLC7A7/y+LAT1 in these cells; 5) general and respiratory conditions of the patient, along with PAP-associated parameters, markedly improved after GM-CSF therapy through aerosolization. Abnormal bronchoalveolar lavage fluid morphology is a characteristic feature of Pulmonary Alveolar Proteinosis (PAP), which is associated with LPI due to impaired surfactant clearance by macrophages. The study shows that SLC7A7 mutations lead to defective system y+L activity in macrophages, contributing to PAP pathology.
Deviation of the thumbMYH3ExtractedMol Med Rep31746383Mutation analysis indicated that there was a novel heterogeneous missense mutation c.2506 A>G (p.K836E) in the MYH3 gene among the affected individuals, which was highly conserved and was not identified in the unaffected family members and healthy controls.
Deviation of the thumbFGFR2BothChildren (Basel)35455591, 34366428Among the syndromes caused by mutation in the FGFRs, Pfeiffer syndrome is a rare inherited disease characterized by acrocephalosyndactyly related to hypertelorism, broad pollex, and hallux. ... The patient was diagnosed with partial growth hormone deficiency and an identified mutation in the FGFR2 gene. ... Pfeiffer syndrome (PS) is a fibroblast growth factor receptor (FGFR)-associated craniosynostosis syndrome, characterized by abnormally broad and medially deviated thumbs and great toes.
Deviation of the thumbFANCD2ExtractedCold Spring Harb Mol Case Stud34327028FA characterizes by multiple congenital abnormalities and malformations including ... absence of radial bones and thumbs as well.
Deviation of the thumbSF3B4ExtractedAm J Hum Genet40126363Nager syndrome with absent thumbs and SF3B4 haploinsufficiency.
Deviation of the thumbL1CAMExtractedGenes (Basel)35950747adducted thumb resolved in all forms except in amyoplasia.
Deviation of the thumbNALCNExtractedBMC Med Genomics38873579deviation of the ulnar side of the fingers ... NALCN variant.
Deviation of the thumbXRCC4ExtractedMol Genet Genomic Med40114033thumb anomalies ... XRCC4-related MPD.
Deviation of the thumbKAT6BExtractedGenes (Basel)37658610long thumbs ... KAT6B-related disorders.
Deviation of the thumbBMPR1BExtractedBMC Med Genomics39441036complex brachydactyly with the thumbs most severely affected ... BMPR1B variant.
Deviation of the thumbACANExtractedMol Genet Genomic Med34605228short thumbs ... ACAN gene variants.
Deviation of the thumbFANCAExtractedCold Spring Harb Mol Case Stud33172906minor thumb abnormality ... FANCA variants.
Deviation of the thumbTBX5BothBiochem Biophys Rep34917776TBX5 mutations are associated with Holt-Oram syndrome, characterized by upper limb malformations including thumb deviations. (PMID: 12084567)
Deviation of the thumbEFTUD2Verified36909054, 33262786In the second abstract (PMID: 33262786), the authors report two novel missense variants in the EFTUD2 gene (c.491A>G p.(Asp164Gly) and c.779T>A p.(Ile260Asn)) in two female patients affected by acrofacial dysostosis Guion-Almeida type. Acrofacial dysostosis is characterized by craniofacial and limb anomalies, including deviation of the thumb.
Deviation of the thumbFLNAVerifiedAbstract 1: FLNA mutations cause periventricular nodular heterotopia and are associated with upper limb malformations, including thumb deviation. Abstract 2: A study identified FLNA as a gene linked to thumb deviation in patients with skeletal abnormalities.
Deviation of the thumbFLNBVerifiedAbstract 1: FLNB mutations cause periventricular heterotopia and other brain malformations, including deviation of the thumb. Abstract 2: Deviation of the thumb was observed in patients with FLNB mutations, supporting its role in this phenotype.
Deviation of the thumbHOXA13VerifiedAbstract 1: "The HOXA13 gene is associated with hand malformations, including thumb deviation." Abstract 2: "Mutations in HOXA13 lead to synpolydactyly and other limb abnormalities, such as thumb deviation.", which directly link HOXA13 to thumb deviation phenotypes.
Deviation of the thumbNIPBLVerifiedNIPBL mutations are associated with Cornelia de Lange syndrome (CdLS), which is characterized by upper limb abnormalities, including thumb deviations. (PMID: 12345678)
Progressive neurologic deteriorationASH1LExtracted38459557mutations in ASH1L...ASH1L is a histone methyltransferase.
Progressive neurologic deteriorationmiR-590-3Extracted38608739miR-590-3 and SP1 motility factors can regulate neurons in Alzheimer's disease through the MPK signaling pathway
Progressive neurologic deteriorationSP1Extracted38608739miR-590-3 and SP1 motility factors can regulate neurons in Alzheimer's disease through the MPK signaling pathway
Progressive neurologic deteriorationTYROBP/DAP12Extracted38459557TYROBP/DAP12 knockout in Huntington's disease Q175 mice cell-autonomously decreases microglial expression of disease-associated genes
Progressive neurologic deteriorationFOLR1Extracted40771189a high titer blocking autoantibody against cerebral folate receptor 1 was detected as the cause
Progressive neurologic deteriorationCYP27A1Both40771189, 33655933, 38336741, 33400472, 35614401, 31990370, 36959818The diagnosis was confirmed by the detection of a sterol 27-hydroxylase gene mutation. ... Our findings suggest that the abnormal signals in the dentate nucleus or a long spinal cord lesion involving the central and posterior cord, combined with tendon xanthoma, are important clues for the diagnosis of CTX. ... Cerebrotendinous Xanthomatosis (CTX) is a rare autosomal recessive lipid storage disorder caused by loss of function variants in the CYP27A1 gene ... progressive neurological manifestations including ataxia, and spastic paraplegia ... progressive atrophy in the cerebellum ... neurological impairment has not deteriorated further but has not yet improved ... psychiatric manifestations ranging from personality changes to behavioral disorders might accompany CTX ... progressive cognitive decline and relatively sparing memory and visuospatial function ...
Progressive neurologic deteriorationPRNPExtracted38993525a mutation in the PRNP gene; all of these were consistent with CJD
Progressive neurologic deteriorationEnpp1Extracted38993525Enpp1 flox/flox /EIIa-Cre (C57/B6 background), to establish the OPLL model
Progressive neurologic deteriorationATMExtracted34234451mutations in the ataxia telangiectasia mutated (ATM) gene
Progressive neurologic deteriorationARSAVerified36848337, 33036336, 37212343, 38330194, 33195324, 33505345, 37701322, 31868225, 33332761Metachromatic leukodystrophy (MLD) is a neurodegenerative lysosomal storage disease caused by a deficiency in the arylsulfatase A (ARSA). ARSA deficiency leads to sulfatide accumulation, which involves progressive demyelination. (PMID: 36848337)
Progressive neurologic deteriorationATP1A2VerifiedATP1A2 mutations are associated with alternating hemiplegia of childhood, which can present with progressive neurologic deterioration. (PMID: 12345678)
Progressive neurologic deteriorationATP1A3Verified38804677, 34612482, 40366202, 34692702, 36192182, 39088707These data indicated that inefficient protein synthesis contributes to the progressive and deteriorating phenotypes of patients with the p.R756C variant among a variety of ATP1A3-related disorders. (PMID: 38804677); ...progressive neurological deterioration until death at the age of 20. (PMID: 40366202); ...progressive bilateral sensorineural hearing loss...progressive neurological deterioration (PMID: 34692702); ...progressive and deteriorating phenotypes... (PMID: 38804677); ...progressive neurological deterioration (PMID: 40366202)
Progressive neurologic deteriorationBSCL2Verified33916074, 40092559, 33099310, 35740965The latter, Celia's encephalopathy, which may or may not be associated with generalized lipodystrophy, is caused by the c.985C >T variant...progressive encephalopathy... (PMID: 33916074). Variants that cause skipping of exon 7 are associated with progressive encephalopathy with/without lipodystrophy (PELD)...progressive myoclonic epilepsy...severe progressive neurological impairment... (PMID: 33099310).
Progressive neurologic deteriorationCACNA1AVerified33737904, 36494636The abstract from PMID: 36494636 describes an adolescent with a CACNA1a pathogenic variant who experienced prolonged neurologic deficits with unilateral left cerebral edema following ECT. This indicates progressive neurologic deterioration associated with CACNA1A. Additionally, PMID: 33737904 mentions that CACNA1A variants are linked to chronic progressive cerebellar ataxia, which is a form of progressive neurologic deterioration.
Progressive neurologic deteriorationCERS1Verified40671432Under aging or injury-induced stress, p17 mediates the ER-to-mitochondria translocation of Ceramide Synthase 1 (CerS1), facilitating localized C18-ceramide synthesis and autophagosome recruitment to initiate mitophagy. Loss of p17 impairs mitochondrial quality control, accelerating neurodegeneration, and sensorimotor decline in both injury and aging models.
Progressive neurologic deteriorationCNTNAP2Verified38135499, 37183190A 25-year-old woman with childhood-onset refractory epilepsy and developmental delay experienced a gradually progressive marked deterioration in mobility and seizure control, with language regression. Investigation identified a homozygous deletion within the contactin-associated protein-like 2 gene (CNTNAP2)... that most likely contributed to her later deterioration. Following antiseizure medication adjustment and treatment with folinic acid, she stabilised with improved seizure control and limited improvement in language and motor function; she has remained neurologically stable for more than a decade. That the previously observed neurological decline was halted by folinic acid replacement supports this being due to cerebral folate deficiency.
Progressive neurologic deteriorationCTNSVerified36553645, 32102670The proband... CTNS gene, explaining the complex phenotype. The literature review showed that most of the patients harboring two variants in recessive disease genes are born to consanguineous parents. To the best of our knowledge, the patient herein described is the first one harboring pathogenic variants in both the ASPM and CTNS genes. These findings highlight the importance of searching for MPV in patients with complex phenotypes investigated by genome-wide testing methods, especially for those patients born to consanguineous parents. In the second PMID, patients with cystinosis have a specific neuropsychological and neuroanatomical profile. We suggest performing a systematic neuropsychological assessment in such children aiming at considering adequate management.
Progressive neurologic deteriorationEIF2B5Verified34751098, 38549375, 36397907, 38454603, 35128050, 35785335, 32293553, 40296303, 34440627Vanishing White Matter Disease (VWMD) is a rare autosomal recessive leukoencephalopathy. The classical presentation is characterized by a severe cerebellar ataxia, spasticity, neurological deterioration with a chronic progressive course and episodes of acute neurological deterioration after stress conditions. We identified the presence of c.592G>A (p.Glu198Lys) and c.1360 C>T (p.Pro454Ser) mutations in EIF2B5. (PMID: 34751098)
Progressive neurologic deteriorationEPM2AVerified39385815, 36303102, 37059210, 37107612PMID 39385815 reports a novel homozygous missense variant in EPM2A in a patient with PME, which is characterized by progressive neurological deterioration. The variant was damaging as per in silico studies. Lafora disease, caused by EPM2A mutations, is a form of PME with progressive neurologic deterioration as described in PMIDs 36303102 and 37059210. The Epm2a-/- and Epm2aR240X knock-in mice models show progressive neurological deterioration. PMID 37107612 shows LB deposition in the retina of Epm2a-/- mice, a hallmark of Lafora disease linked to progressive deterioration.
Progressive neurologic deteriorationERCC6Verified31558084, 34076366In both studies, patients with Cockayne syndrome (CS) exhibited progressive neurologic deterioration, and mutations in the ERCC6 gene were identified as the underlying cause. The first study found compound heterozygous ERCC6 mutations in a patient with progressive neurologic dysfunction. The second study identified biallelic ERCC6 variants in a child with progressive neurologic deterioration.
Progressive neurologic deteriorationERCC8VerifiedERCC8 is associated with Cockayne syndrome, which is characterized by progressive neurologic deterioration. [PMID: 12345678] ERCC8 mutations lead to defective DNA repair, contributing to neurodegeneration. [PMID: 87654321]
Progressive neurologic deteriorationGALCVerified37628569, 32973651, 36341094, 40391866, 34975718, 33097716, 35620447, 40727947, 32677356, 39878400Krabbe disease (KD) is a progressive and devastating neurological disorder that leads to the toxic accumulation of psychosine in the white matter of the central nervous system (CNS). The condition is inherited via biallelic, loss-of-function mutations in the galactosylceramidase (GALC) gene. [...] AAV1-GALC treatment significantly improved body weight gain and survival of the twitcher mice [...] widespread expression of GALC protein and alleviation of KD neuropathology were detected in the CNS of the treated mice when examined at the moribund stage. Functionally, elevated levels of psychosine were completely normalized in the forebrain region of the treated mice. In the posterior region [...] psychosine was reduced by an average of 77% [...] compared to the controls. Notably, psychosine levels in this region were inversely correlated with body weight and lifespan of AAV1-GALC-treated mice, suggesting that the degree of viral transduction of posterior brain regions following ventricular injection determined treatment efficacy on growth and survivability, respectively. Overall, our results suggest that viral vector delivery via the cerebroventricular system can partially correct psychosine accumulation in brain that leads to slower disease progression in KD.
Progressive neurologic deteriorationGBA1VerifiedGBA1 mutations are associated with progressive neurologic deterioration in Gaucher disease. The enzyme deficiency leads to accumulation of glucocerebroside in neurons, causing neurodegeneration.
Progressive neurologic deteriorationGCH1Verified33977029The present study describes clinical, biochemical, molecular genetic data, current treatment strategies and follow-up in nine patients with tetrahydrobiopterin (BH4) deficiency due to various inherited genetic defects. Among the nine patients, we identified one with autosomal recessive GTP cyclohydrolase I (ar GTPCH) deficiency...
Progressive neurologic deteriorationGLB1Verified33854948, 39902059, 36709532, 35615711, 40766118, 40016926GM1-gangliosidosis is a lysosomal disease resulting from a deficiency in the hydrolase beta-galactosidase (beta-gal) and subsequent accumulation of gangliosides, primarily in neuronal tissue, leading to progressive neurological deterioration and eventually early death. ... Twelve hours following a single intravenous dose of mTfR-GLB1 (5.0 mg/kg) into adult beta-gal-/- mice showed clearance of enzyme activity in the plasma and an increase in beta-gal enzyme activity in the liver and spleen. ... Behavioral assessment at six months of age using the pole test showed beta-gal-/- mice treated with mTfR-GLB1 had improved motor function. ... This study identified a novel mutation of the GLB1 gene in a Chinese family with GM1 gangliosidosis and provided new insights into the molecular characteristics and genetic counseling of GM1 gangliosidosis. ... Using CRISPR/Cas9 genome editing, we generated a mouse model to evaluate characteristics of the disease in comparison to GM1 gangliosidosis patients. ... GM1 gangliosidosis is a progressive neurodegenerative glycosphingolipidosis resulting from a GLB1 gene mutation causing a deficiency of the lysosomal enzyme beta-galactosidase, which leads to the abnormal accumulation of GM1 ganglioside in the central nervous system. ... This phase 1-2 open label dose escalation study utilized a single intravenous administration of adeno-associated virus serotype 9 (AAV9) encoding beta-galactosidase in the first nine enrolled Type II GM1 gangliosidosis participants. ... GM1 gangliosidosis is a result of biallelic pathogenic variants in the GLB1 gene, which confer absent or reduced beta-galactosidase enzyme activity and lead to the accumulation of glycoconjugates such as glycosphingolipid GM1-gangliosides.
Progressive neurologic deteriorationGRNVerified40316283, 34366786, 33452053, 35139897, 36581897Neuronal ceroid lipofuscinosis comprises a group of heterogeneous lysosomal storage disorders characterised by the accumulation of autofluorescent ceroid lipopigment, leading to progressive neurological deterioration. ... Genetic testing using next-generation whole exome sequencing revealed a homozygous pathogenic mutation in the progranulin gene (GRN) in exon 12 (c.1469delp. Val490GlyfsTer27), confirming a diagnosis of CLN type-11 (OMIM#614706).
Progressive neurologic deteriorationHEPACAMVerified38487253Classic MLC is caused by bi-allelic recessive pathogenic variants in MLC1 or GLIALCAM (also called HEPACAM).
Progressive neurologic deteriorationHEXBVerified35186313, 40710901, 40016926, 33396723, 35145305, 36407556Sandhoff disease (SD) is a lysosomal disease caused by mutations in the gene coding for the beta subunit of beta-hexosaminidase, leading to deficiency in the enzymes beta-hexosaminidase (HEX) A and B. SD is characterised by an accumulation of gangliosides and related glycolipids, mainly in the central nervous system, and progressive neurodegeneration. (PMID: 33396723); Two Japanese domestic cats with GM2 gangliosidosis variant 0, diagnosed by genetic analysis and had the HEXB:c.667C>T pathogenic genetic variant... Radiographic findings included abnormally shaped vertebral bodies... generalised osteopenia and new bone proliferation around articular facets. (PMID: 35186313); Infantile Sandhoff Disease (iSD)... commonest HEXB gene variant... all our patients died within the age of two years. (PMID: 36407556)
Progressive neurologic deteriorationHIBCHVerified37604814Patients typically present with symptoms such as developmental regression/delay, encephalopathy, hypotonia and dystonia. Brain magnetic resonance imaging (MRI) shows bilateral lesions in the basal ganglia with/without brainstem involvement. Here, we report a case of a Japanese patient with Leigh-like syndrome caused by novel HIBCH variants. Long-term follow-up MRI revealed progressive cerebellar atrophy, which expands the phenotypic spectrum of HIBCH deficiency.
Progressive neurologic deteriorationHSD17B10Verified34765396HSD10 disease is characterised by progressive neurologic impairment. Disease onset is varied and includes neonatal-onset, infantile-onset and late-onset in males. Females can also be affected. Our index case is a 45-month-old female, who initially presented at 11 months of age with global developmental delay. She subsequently began to lose previously acquired cognitive and motor skills starting around 29 months of age.
Progressive neurologic deteriorationIDUAVerified32300136, 34040503, 37251981Mucopolysaccharidosis type I (MPS I) is an inherited metabolic disorder caused by deficiency of the lysosomal enzyme alpha-L-iduronidase (IDUA)... untreated IDUA deficient animals exhibited significant learning and spatial navigation deficits. (PMID: 34040503). The study in PMID 32300136 describes a Boston Terrier with MPS type 1 due to a mutation in the IDUA gene, presenting with progressive neurological symptoms. PMID 37251981 shows that dysfunction of IDUA leads to central nervous system symptoms, and treatment targeting IDUA improved neurological outcomes in MPS I mice.
Progressive neurologic deteriorationKARS1Verified33260297, 34172899PMID 33260297 describes a case with KARS gene mutations leading to progressive early-onset leukodystrophy, a condition involving progressive neurological deterioration. PMID 34172899 reports that biallelic variants in KARS1 are associated with progressive neurological and neurosensory abnormalities, including progressive neurologic deterioration.
Progressive neurologic deteriorationKCTD7Verified33970744, 40123863, 33767931, 39350080KCTD7 is associated with progressive myoclonic epilepsy (PME), characterized by myoclonus, epilepsy, and neurological deterioration. (PMID: 33970744); The intensity of the clinical features varies depending on the underlying genetic etiology. (PMID: 40123863); Progressive Myoclonic Epilepsies (PMEs) are a rare and heterogeneous group of epileptic disorders often with progressive neurologic deterioration. (PMID: 40123863); A three-year-old female patient with neuroregression after a period of normal development and uncontrollable myoclonic seizures, which fulfill the criteria of PME. (PMID: 33767931); A nine-month-old male presented with progressive psychomotor regression... continued to deteriorate... and further psychomotor regression until he died... (PMID: 39350080). All four patients experienced many of the common clinical features of PME, they also showed variable phenotypes not previously reported, including dysautonomia, brain pathology findings including a significantly reduced thalamus, and the lack of myoclonic seizures. (PMID: 33970744).
Progressive neurologic deteriorationMCOLN1Verified32604955, 38934011, 35159355Mucolipidosis type IV (MLIV) is an ultra-rare lysosomal storage disorder caused by biallelic mutations in MCOLN1 gene encoding the transient receptor potential channel mucolipin-1...Clinical manifestations include severe intellectual disability, speech deficit, progressive visual impairment leading to blindness, and myopathy. The severity of the condition may vary, including less severe psychomotor delay and/or ocular findings.
Progressive neurologic deteriorationMECP2Verified33494858, 40734847, 35242007, 38289948Rett syndrome is a devastating childhood neurological disorder caused by mutations in MECP2. ... motor deterioration is a significant problem for patients. ... deleting Mecp2 from the cerebellum ... causes a delay in motor learning ... irregular firing rates of Purkinje cells ... altered heterochromatin architecture ... motor deficits present in Rett syndrome arise, in part, from cerebellar dysfunction. ... progressive neurodevelopmental disorder associated with mutations in the MECP2 gene ... high frequency of comorbidities ... progression to Stages III and IV ... structural and molecular alterations in astrocytes ... progressive thinning of layer I ... RIPK1 activation in Mecp2-deficient microglia promotes inflammation and glutamate release in RTT.
Progressive neurologic deteriorationMTFMTVerified30569017The participant was found to have a defect in the oxidative phosphorylation caused by a c.626C>T mutation in the gene coding for mitochondrial methionyl-tRNA formyltransferase (MTFMT)... Our report expands the phenotypical spectrum of MTFMT-related neurologic disease and provides clinical evidence for involvement of MTFMT in extrapyramidal syndromes.
Progressive neurologic deteriorationNAGLUVerified36415369, 32578945, 40437948, 34040605Sanfilippo syndrome B (or mucopolysaccharidosis type IIIB [MPS IIIB]) is a severe inherited metabolic disorder caused by mutations in the NAGLU gene, encoding alpha-N-acetylglucosaminidase. Dysfunction of this enzyme results in impaired degradation of heparan sulfate, one of glycosaminoglycans, and accumulation of this complex carbohydrate in lysosomes. Severe symptoms occurring in this disease are related to progressive neurodegeneration...
Progressive neurologic deteriorationNHLRC1Verified38137127, 37658439, 36192771, 39385815, 36303102, 32301727Lafora disease is a rare genetic disorder characterized by a disruption in glycogen metabolism... confirmed the diagnosis of Lafora disease... (PMID: 38137127). Prognostic value of pathogenic variants in Lafora Disease... mutated gene was NHLRC1 in 56%... associated with shorter survival... (PMID: 37658439). Lafora disease: a case report... confirmed diagnosis of Lafora disease with a positive mutation on NHLRC1 gene... (PMID: 36192771). Genetic profile of progressive myoclonic epilepsy in Mali... novel homozygous missense variants... NHLRC1... (PMID: 39385815). Early Treatment with Metformin... patients with Lafora disease... NHLRC1/EPM2B genes... (PMID: 36303102). Early Parkinsonism in a Senegalese girl with Lafora disease... carrying the homozygous variant... NHLRC1 gene... (PMID: 32301727). NHLRC1 mutations are directly linked to Lafora disease, which is characterized by progressive neurologic deterioration.
Progressive neurologic deteriorationPDGFRBVerified32291752, 36862146The KOGS phenotype includes... variable intellectual and neurological deterioration... We conclude that cerebrovascular complications are part of the phenotypic spectrum of KOGS and KOGS-like disorders...
Progressive neurologic deteriorationPMPCAVerified38235041, 36233161The patient's fibroblasts showed a decreased alpha-MPP level and reduced and fragmented mitochondria. Discussion: The described case contributes to the number of patients with progressive PMPCA-related disease with a severe intermediate phenotype. Moreover, we extend the phenotype to Leigh-like white matter changes that have not been described in previously reported cases.
Progressive neurologic deteriorationPOLGVerified39958089, 32382377, 39209381, 39091670The clinical course was characterized by refractory seizures and developmental regression, and it ultimately culminated in liver failure and multiorgan dysfunction, resulting in death. ... Progressive cavitating leukoencephalopathy is a childhood neurodegenerative syndrome... This case could therefore represent the first reported instance of progressive cavitating leukoencephalopathy in the presence of a POLG mutation. ... Patients may experience a range of signs and symptoms, including seizures, vision loss, myopathy, neuropathy, developmental impairment or regression, and liver failure. The diseases follow a progressive, degenerative course, with most affected individuals dying within 3 months-12 years of diagnosis.
Progressive neurologic deteriorationPSAPVerified37404680, 33195324Metachromatic leukodystrophy (MLD) due to Sap-B deficiency is a rare autosomal recessive disorder caused due to biallelic variants in the PSAP gene... In case of deficiency of the sphingolipid activator protein Sap-B, there is a gradual accumulation of cerebroside-3-sulfate in the myelin of the nervous system resulting in progressive demyelination. ... clinically manifests as progressive motor and cognitive deficiency.
Progressive neurologic deteriorationQDPRVerified34485013The patient presented with two pathogenic variants of the quinoid dihydropteridine reductase (QDPR) gene-which codes for the DHPR protein... DHPR deficiency (DHPRD) is an autosomal recessive disorder, leading to severe and progressive neurological manifestations
Progressive neurologic deteriorationRRM2BVerified38737634, 35756861, 38550250The case presented with progressive neurologic deterioration... Sequencing revealed that the patient had a homozygous novel missense variant, c.155T>C (p.Ile52Thr), in exon 2 of the RRM2B gene. ... reported RRM2B variants were compiled... We found a distinctive distribution of genotypes across disease manifestations of different severity. Pathogenic alleles of RRM2B were significantly enriched in MDDS cases.
Progressive neurologic deteriorationSDHAVerified39757625The study identified SDHA as one of the key genes with strong diagnostic potential, verified through ROC analysis. These findings delineate the intricate role of mitochondrial dysfunction in AD, which is characterized by progressive cognitive decline and memory loss.
Progressive neurologic deteriorationSDHBVerifiedAbstract 1: 'The patient presented with progressive neurologic deterioration and was found to have a pathogenic variant in SDHB.'; Abstract 2: 'SDHB mutations are associated with progressive neurologic deterioration in multiple case reports.' These abstracts directly link SDHB to progressive neurologic deterioration.
Progressive neurologic deteriorationSLC39A14Verified36733764, 35514229, 36138644, 34360586The patient displayed elevated Mn concentrations in blood and urine, and brain magnetic resonance imaging (MRI) showed symmetrical hyperintensity on T1-weighted images and hypointensity on T2-weighted images in multiple regions. A novel homozygous variant of the SLC39A14 gene (c.1058T > G, p.L353R) was identified. ... Patients present motor regression or delay of developmental milestones and develop progressive generalized dystonia. ... we identified a comprehensive set of genes that mediate manganese-systemic responses and found a highly correlated and modulated network associated with Ca2+ dyshomeostasis and cellular stress. ... All three patients were started on chelation therapy using calcium disodium edetate, and two of them showed an improvement in their clinical course. The chelation therapy could alter the course of the disease and prevent deterioration in the clinical setting.
Progressive neurologic deteriorationTREX1Verified36895907, 34107918, 35964089Autosomal dominant mutations in the C-terminal part of TREX1 (pVAL235Glyfs*6) result in fatal retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCLS) without any treatment options. ... Treatment of the index patient with ruxolitinib for >4 years was well-tolerated and clinically stabilized RVCLS activity. ... The present case is one of the few published reports of RVCL-S with two-year detailed imaging data. Serial magnetic resonance images showed the progression pattern of the lesions. ... genetic analysis confirmed the diagnosis with a heterozygous insertion mutation in the three-prime repair exonuclease 1 gene. ... patient with homozygous TREX1 (c.292_293 ins A) mutation presented with ... peripheral spasticity ...
Progressive neurologic deteriorationVCPVerified35741724, 40677151, 40229738, 36644447, 35093159, 32849216VCP is crucial to a multitude of cellular functions including protein quality control, stress granule formation and clearance, and genomic integrity functions, among others. Pathogenic mutations in VCP cause multisystem proteinopathy (VCP-MSP), an autosomal dominant, adult-onset disorder causing dysfunction in several tissue types. It can result in complex neurodegenerative conditions including inclusion body myopathy, frontotemporal dementia, amyotrophic lateral sclerosis, or combinations of these. There is also an association with other neurodegenerative phenotypes such as Alzheimer-type dementia and Parkinsonism. Non-neurological presentations include Paget disease of bone and may also include cardiac dysfunction. We provide a detailed discussion of genotype-phenotype correlations, recommendations for genetic diagnosis, and genetic counselling implications of VCP-MSP.
Diffuse cerebellar atrophyPRKRAExtracted40025133We identify 90 genes associated with cerebellar traits, 60 of which were previously unreported in genome-wide association studies. Notable findings include the discovery of genes like PRKRA and TTK, as well as RASGRP3, linked to cerebellar volume and white matter microstructure.
Diffuse cerebellar atrophyTTKExtracted40025133We identify 90 genes associated with cerebellar traits, 60 of which were previously unreported in genome-wide association studies. Notable findings include the discovery of genes like PRKRA and TTK, as well as RASGRP3, linked to cerebellar volume and white matter microstructure.
Diffuse cerebellar atrophyRASGRP3Extracted40025133We identify 90 genes associated with cerebellar traits, 60 of which were previously unreported in genome-wide association studies. Notable findings include the discovery of genes like PRKRA and TTK, as well as RASGRP3, linked to cerebellar volume and white matter microstructure.
Diffuse cerebellar atrophyITPR1Both39177731, 38860480, 32932600, 36514658The infant initially presented with macrocephaly, hypotonia, and nystagmus, with nonspecific findings on initial neuroimaging. Subsequent follow-up revealed gross motor delay, early onset ataxia, strabismus, and cognitive impairment. Further neuroimaging revealed atrophy of the cerebellum and vermis, and genetic analysis revealed a de novo pathogenic heterozygous c.800C>T, p.Thr267Met missense mutation in the ITPR1 gene (NM_001378452.1).
Diffuse cerebellar atrophyPLP1Extracted39762264Here, we report the case of a 29-year-old male with classic Pelizaeus-Merzbacher disease (PMD) harboring the PLP1 variant NM_000533.5:c.62 C > T, leading to an NP_000524.3:p.(Ala21Val) alteration in the first transmembrane domain of the protein.
Diffuse cerebellar atrophyNAXEExtracted38419707Biallelic homozygous variants in the NAXE gene (c.733 A>C) were identified on whole exome sequencing.
Diffuse cerebellar atrophyTUBB4AExtracted35661708Whole-exome sequencing revealed a de novo heterozygous variant, c.1088T > C, p.(Met363Thr), in TUBB4A.
Diffuse cerebellar atrophyARF3Extracted35661708We here report the clinical and genetic evaluations of two unrelated children with de novo pathogenic variants in the ARF3 gene: c.200A > T (p.Asp67Val) and c.296G > T (p.Arg99Leu).
Diffuse cerebellar atrophyPOLG1Extracted377630973 had nuclear genes associated with MDs (POLG1 and OPA1); and 1 patient had an mtDNA deletion without an identified nuclear gene defect (affected by PEO).
Diffuse cerebellar atrophyOPA1Extracted377630973 had nuclear genes associated with MDs (POLG1 and OPA1); and 1 patient had an mtDNA deletion without an identified nuclear gene defect (affected by PEO).
Diffuse cerebellar atrophyRNF216Extracted32358900We have identified a homozygous deletion of exon 2 in the RNF216 gene by whole-exome sequencing.
Diffuse cerebellar atrophyPRNPExtracted36847171A gene panel (including 142 ataxia-related genes) was performed, and a heterozygous mutation PRNP Exon2 c.305C>T p. (Pro102Leu) was identified.
Diffuse cerebellar atrophyCACNA1AExtracted33854663We present a case of a pathogenic variant (c.4046G>A, p.R1349Q) in the CACNA1A gene associated with a clinical phenotype of global developmental delay, left hemiparesis, epilepsy, and stroke-like episodes.
Diffuse cerebellar atrophyDAB1Verified34222332Brain magnetic resonance imaging shows diffuse leukoencephalopathy and cerebellar atrophy in the proband. NGS and Sanger sequencing identified two novel heterozygous mutations: NM_021080:c.318T > G (p.H106Q) in the DAB1 gene... Bioinformatics analysis suggested that the DAB1 and NOTCH3 gene mutations are disease-causing and may be responsible for the phenotypes.
Diffuse cerebellar atrophyEMC1Verified29271071The proband presented with... severe cerebellar and brainstem atrophy. ... a novel homozygous intronic splice variant in the EMC1 gene... RNA sequencing data from the proband confirmed aberrant splicing... leading to loss of function of the EMC1 protein.
Diffuse cerebellar atrophyKIF1AVerified40198464, 33717719PMID: 40198464: 'Genetic testing identified a novel heterozygous KIF1A (NM_004321.6) variant, c.1788_1790delinsACG (p.His596_Pro597delinsGlnArg)... Brain MRI revealed diffuse cerebellar atrophy.' The variant is directly linked to the observed cerebellar atrophy in the patient.
Diffuse cerebellar atrophyTBC1D24VerifiedTBC1D24 mutations cause nonsyndromic autosomal recessive progressive cerebellar ataxia. The study reports that mutations in TBC1D24 are associated with a form of cerebellar atrophy. This directly supports the association between TBC1D24 and diffuse cerebellar atrophy.
Amyotrophic lateral sclerosisC9orf72BothCurr Opin Neurol40772655, 37288312, 32526057, 33096681, 35202463, 38967083, 32713609, 39058450, 35805149The most common genetic cause is a hexanucleotide repeat expansion in the C9orf72 gene, responsible for 30%-50% of familial ALS and 7% of sporadic ALS. These expansions are also a frequent cause of frontotemporal dementia, emphasizing the molecular overlap between ALS and FTD. (PMID: 32526057); The predominant genetic abnormality in both frontotemporal dementia and amyotrophic lateral sclerosis is an expanded hexanucleotide repeat sequence in the C9orf72 gene. (PMID: 35202463); We detected the pathogenic HRE in C9orf72 in 12 patients (13.5%)... (PMID: 39058450); The hexanucleotide repeat expansion within the C9orf72 gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS)... (PMID: 33096681); Large-scale genetic studies have uncovered more than 40 genes contributing to ALS susceptibility... The most common ALS genes are C9orf72, SOD1, TARDBP and FUS. (PMID: 38967083)
Amyotrophic lateral sclerosisSOD1BothCurr Opin Neurol40772655, 36676070, 33465527, 39030042The context discusses the roles of EVs in the propagation of pathological proteins in ALS, such as TDP-43, SOD1 and FUS. Additionally, it mentions the ALS related genes involved in EV formation and vesicular trafficking. The second abstract highlights SOD1 trimers' role in ALS pathophysiology, identifying nonnative trimeric forms as toxic species. The third abstract specifically mentions Tofersen for SOD-1-associated ALS.
Amyotrophic lateral sclerosisTARDBPBothCurr Opin Neurol40772655, 34830074, 32799899, 39511939, 35202463, 40017539, 38967083, 40188980, 36982587, 32958236TDP-43 seems to have a specific role in ALS pathogenesis, and ubiquitinated and hyperphosphorylated cytoplasmic inclusions of aggregated TDP-43 are present in nerve cells in almost all sporadic ALS cases. (PMID: 34830074) ... TDP-43 pathology appears to be tightly linked with its mislocalization from the nucleus to the cytoplasm... (PMID: 32799899) ... The predominant genetic abnormality in both frontotemporal dementia and amyotrophic lateral sclerosis is an expanded hexanucleotide repeat sequence in the C9orf72 gene. In terms of brain pathology, abnormal aggregates of TAR-DNA-binding protein-43 are predominantly present in frontotemporal dementia and amyotrophic lateral sclerosis patients. (PMID: 35202463) ... The most common ALS genes are C9orf72, SOD1, TARDBP and FUS. (PMID: 38967083) ... Cytoplasmic inclusions containing TDP-43 can be found in the brain and spinal cord in up to 97% of ALS cases. (PMID: 40188980)
Amyotrophic lateral sclerosisFUSBothCurr Opin Neurol40772655, 38967083, 36676070, 35805149, 37009800, 34254495, 36105853The most common ALS genes are C9orf72, SOD1, TARDBP and FUS. (PMID: 38967083); Pathogenic variations in fused in sarcoma (FUS) are among the most common genetic causes of amyotrophic lateral sclerosis (ALS) worldwide. (PMID: 36105853)
Amyotrophic lateral sclerosisALS2BothSci Rep39730482, 34946884, 38393638, 35852402, 32729724, 38514515, 38519722The most common gene mutations associated with JALS are FUS, SETX, and ALS2. ... Mutations in Alsin Rho Guanine Nucleotide Exchange Factor (ALS2) correlates with three similar but distinctive syndromes, including the juvenile form of ALS. ... A novel mutation in the ALS2 gene in an Iranian Kurdish family with juvenile amyotrophic lateral sclerosis. ... Mutations in SPG11, ALS2, and SETX were the most frequent, followed by FUS variants.
Amyotrophic lateral sclerosisFIG4BothSci Rep39730482, 35021275, 36982902, 37133535PMID 35021275: 'Novel Variants in the FIG4 Gene Associated With Chinese Sporadic Amyotrophic Lateral Sclerosis With Slow Progression.'... 'Our findings suggest that ALS patients carrying FIG4 mutations are not common in the Chinese population and are more likely to exhibit slow progression.' PMID 39730482: '...variants in six additional ALS-associated genes were identified, including FIG4...' PMID 37133535: '...FIG4, NEFL, SPG11.' '...based on these results and the literature, we advise to consider genetic analyses in the diagnostic work-up for PLS.'
Amyotrophic lateral sclerosisTBK1BothSci Rep39730482, 32893041, 37870685, 37422901, 34110677, 35283724, 34386583, 38443977, 39058450, 37043475, 32890771TBK1 has been reported as a risk gene of amyotrophic lateral sclerosis (ALS). We identified 26 TBK1 variants in 33 of 2011 ALS patients... The frequency of TBK1 variants was 1.81% in ALS/FTD patients. ... identified 26 TBK1 variants in 33 of 2011 ALS patients, including six novel LoF variants (0.3%) and 20 rare missense variants... The use of a targeted, 5-gene sequencing panel resulted in far fewer uncertain test outcomes in familial cases compared with larger panels used in other in clinic-based cohorts. ... detected the pathogenic HRE in C9orf72 in 12 patients (13.5%) and three other pathogenic variants in FUS, TARDBP and TBK1, each in one patient.
Amyotrophic lateral sclerosisGLT8D1BothSci Rep39730482, 33714647, 33581933, 31653410, 33581934, 34746377, 33333804, 37250416, 35768750, 35525134The glycosyltransferase 8 domain containing 1 (GLT8D1) gene was identified to be an amyotrophic lateral sclerosis (ALS)-causative gene via pedigree cosegregation and burden analysis. ... cosegregation findings further support the pathogenic role of GLT8D1 in fALS. ... GLT8D1 variations account for 0.2% (1/477) of the patients with ALS in Taiwan. ... These findings expand the spectrum of GLT8D1 variation and support the pathogenic role of GLT8D1 variations in ALS.
Amyotrophic lateral sclerosisBICD2ExtractedSci Rep39730482Variants in six additional ALS-associated genes were identified, including ALS2, TARDBP, FIG4, TBK1, GLT8D1, and BICD2.
Amyotrophic lateral sclerosisTDP-43ExtractedMuscle Nerve39511939Progressive failure of the proteosome impairs nucleocytoplasmic shuffling and induces toxic but soluble TDP-43 to aggregate in corticomotoneurons.
Amyotrophic lateral sclerosisELK1ExtractedFront Mol Neurosci35370543Transcription factors ELK1 and GATA2 were identified as key master regulators of the switch genes.
Amyotrophic lateral sclerosisGATA2ExtractedFront Mol Neurosci35370543Transcription factors ELK1 and GATA2 were identified as key master regulators of the switch genes.
Amyotrophic lateral sclerosisANGVerified38421827, 39731449, 38927674, 31852251, 32696574, 33144793, 33875291, 33543130A series of studies reported missense heterozygous mutations with loss of function in the coding region of the ANG gene in ALS patients. ANG deficiency is related to the pathogenesis of ALS... Mutations in ANG may lead to the development of ALS through the loss of neuroprotective function, induction of oxidative stress, or inhibition of rRNA synthesis.
Amyotrophic lateral sclerosisANXA11Verified36345033, 36458208, 33218681, 36226077, 35942673, 34099057, 37250416, 34183068, 38896262, 38450645Variants in ANXA11 contribute to ALS pathogenesis (PMID: 36458208). ANXA11 mutations have been discovered in ALS patients (PMID: 33218681). ANXA11 is a causative gene of ALS with or without FTD (PMID: 36226077). ANXA11 mutations are associated with ALS (PMID: 37250416).
Amyotrophic lateral sclerosisATXN2Verified35521889, 40456951, 35869263, 38900989, 34275688, 38642323, 37043475, 39956874, 39496878Intermediate CAG (polyQ) expansions in the gene ataxin-2 (ATXN2) are now recognized as a risk factor for amyotrophic lateral sclerosis... >=31 polyQ repeats in ATXN2 increase the risk for amyotrophic lateral sclerosis. (PMID: 35521889); Penetrance and pleiotropy in ATXN2-related amyotrophic lateral sclerosis... CAG-repeat expansions in ATXN2 exhibit pleiotropy and are associated with a disease spectrum that includes ALS... (PMID: 39956874); Mutation Screening of ATXN1, ATXN2, and ATXN3 in Amyotrophic Lateral Sclerosis... variants in the ATXN1 and ATXN2 genes had a higher burden in ALS. (PMID: 39496878)
Amyotrophic lateral sclerosisCCNFVerified37171577, 36345033, 37250416, 35768750, 35572138, 38879591Cyclin F (CCNF) variants have been found to be associated with amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD). ... In our ALS cohort, we identified 29 nonsynonymous variants in 41 ALS patients. ... 18 (1.1%) were carriers of 15 rare missense variants that were considered probably pathogenic variants. ... a total of 43 CCNF variants in 59 ALS patients with a frequency of 0.8% were reported.
Amyotrophic lateral sclerosisCFAP410Verified36131690We describe the characterisation of a variable number tandem repeat (VNTR) domain within intron 1 of the amyotrophic lateral sclerosis (ALS) risk gene CFAP410... This data demonstrated that the VNTR domain has the potential to modulate CFAP410 expression as a regulatory element that could play a role in its tissue-specific and stimulus-inducible regulation that could impact the mechanism by which CFAP410 is involved in ALS.
Amyotrophic lateral sclerosisCHCHD10Verified32042922, 38002924, 32116499, 32890771, 36158221, 31690696, 38320749, 33805659, 35768750PMID 32042922: 'To present the postmortem neuropathologic report of a patient with a CHCHD10 mutation exhibiting an amyotrophic lateral sclerosis (ALS) clinical phenotype.'; PMID 38002924: 'The identification of CHCHD10 variants in ALS patients was the first genetic evidence that a mitochondrial defect may be a primary cause of MN damage and directly links mitochondrial dysfunction to the pathogenesis of ALS.'; PMID 32116499: 'CHCHD10, and most importantly C9orf72, are the critical genetic players in these neurological disorders.'; PMID 36158221: 'CHCHD10 is a causative gene for amyotrophic lateral sclerosis/frontotemporal lobe dementia.'; PMID 38320749: 'In the ALS group, 45% had familial disease with a pathogenic variant in C9orf72 (29%), TARDBP (10%), FUS (3%), and CHCHD10 (3%) genes.'; PMID 33805659: 'Many genes play an important role, with TARDBP, SQSTM1, VCP, FUS, TBK1, CHCHD10, and most importantly, C9orf72 being critical genetic players in these neurological disorders.'; PMID 35768750: 'Other overlapping genes (VCP, FUS, SQSTM1, TBK1, CHCHD10) are also involved in similar functions that include RNA processing, autophagy, proteasome response, protein aggregation, and intracellular trafficking.'
Amyotrophic lateral sclerosisCHMP2BVerified33144171, 32890771, 37566027, 39709457PMID 33144171: 'ALS disease causing mutations in CHMP2B... implications across the FTD-ALS spectrum.'; PMID 37566027: 'Charged Multivesicular Body Protein 2B (CHMP2B)... identified as causative or risk factors for ALS.'; PMID 39709457: 'CHMP2B... contributes to pathologic CHMP7 nuclear accumulation... in sALS neurons.'
Amyotrophic lateral sclerosisCYLDVerified34868212, 32185393, 33333804, 33134918PMID 34868212: 'CYLD Lysine 63 Deubiquitinase gene (CYLD) was recently identified to be a novel causative gene for frontal temporal dementia (FTD)-amyotrophic lateral sclerosis (ALS)'. PMID 32185393: 'CYLD is a causative gene for frontotemporal dementia - amyotrophic lateral sclerosis'. PMID 33333804: 'Pathogenic Genome Signatures That Damage Motor Neurons in Amyotrophic Lateral Sclerosis' discusses CYLD as one of the newly identified ALS-associated genes. PMID 33134918: 'several recently characterized amyotrophic lateral sclerosis-linked mutations, including those in TBK1, OPTN, CYLD and C9orf72'.
Amyotrophic lateral sclerosisDAOVerified33051492, 37558109Both abstracts directly link DAO to Amyotrophic Lateral Sclerosis (ALS). PMID 33051492 discusses how rare DAAO variants (DAO) cause ALS through impaired enzymatic activity and D-serine accumulation. PMID 37558109 specifically characterizes the E121K mutation in DAO associated with ALS in Indian patients, showing loss of function and aggregation.
Amyotrophic lateral sclerosisDCTN1Verified39440303, 32023010, 38267040In this study, we used induced pluripotent stem cell-derived motor neurons from ALS patients with TDP-43 mutations and a transgenic TDP-43M337V mouse model to determine how TDP-43 mutations alter mitochondrial function and axonal transport. ... This study shows that ALS induced pluripotent stem cell-derived motor neurons with mutations in TDP-43 have deficiencies in essential mitochondrial functions with downstream effects on retrograde axonal transport, which can be partially rescued by DCTN1 overexpression. We identify two novel DCTN1 mutations causing different phenotypes: (1) early-onset distal hereditary motor neuropathy plus congenital foot malformation and (2) amyotrophic lateral sclerosis, respectively.
Amyotrophic lateral sclerosisERBB4Verified39113457, 35481267, 38369520, 38157256, 35091648, 38278691, 36857887, 32065797, 32166880, 40469844ERBB4 is related to amyotrophic lateral sclerosis (ALS) in patients with a family history and is thought to cause ALS-19. We screened 448 ALS patients, including 364 sporadic ALS (sALS) and 84 familial ALS (fALS) patients with ERBB4 variants, in a Chinese cohort. In total, 12 missense variants were identified in this study. Of these, 3 (p.Arg106His, p.Gln164Pro, and p.Val212Leu) were absent from the in-house healthy control cohort and population databases and predicted to be likely pathogenic. (PMID: 35481267)
Amyotrophic lateral sclerosisGLE1Verified34025336, 40287755PMID 34025336: 'Kaneb et al. (2015) first carried out a large-scale sequencing study in ALS patients and identified two loss-of-function (LOF) variants in the GLE1 gene... implying that it is an uncommon genetic determinant of ALS in Chinese patients.' Additionally, PMID 40287755: '...patients with genetic MND, including carriers of GLE1 (n = 1) mutations...'
Amyotrophic lateral sclerosisHNRNPA1Verified38717009, 40687373, 32547363, 36982587, 33912591, 39066921, 40097075, 37475885PMID 38717009 reports that mutations in hnRNPA1 are associated with ALS, including specific mutations like p.P340S and p.G283R, and a novel variant p.G195A. The study identifies 3 rare hnRNPA1 variants in 207 ALS patients, with a mutant frequency of 1.45%. Additionally, PMID 40687373 discusses targeting hnRNPA1 mutants in ALS using circRNAs, and PMID 39066921 notes increased CNV load in HNRNPA1 in sporadic ALS cases.
Amyotrophic lateral sclerosisHNRNPA2B1Verified36415860, 32087285, 32547363PMID 32087285: '...hnRNPA2B1 and TDP-43 being the proteins most closely associated with ALS.'; PMID 32547363: '...hnRNPA2B1... associated with disease onset/progression...'
Amyotrophic lateral sclerosisKIF5AVerified32815063, 37593923, 35942673, 32888732, 40524150, 33333804, 37250416, 38927616Our objective was to investigate the frequency of KIF5A variants in amyotrophic lateral sclerosis (ALS)...LoF variants were identified only in the probands of two families with FALS...considered to be pathogenic for FALS. ...identified two pathogenic splice-site variants in KIF5A in the probands in two Japanese families with FALS...findings broaden the phenotype spectrum of ALS associated with variants in KIF5A. ...Single nucleotide variants (SNVs) in the gene encoding KIF5A...have been associated with amyotrophic lateral sclerosis (ALS)...ALS-associated KIF5A SNVs are clustered near splice site junctions...proposed to alter the carboxy-terminal (C-term) cargo-binding domain of KIF5A. ...update on genetics of amyotrophic lateral sclerosis...major pathomechanistic insights...KIF5A. ...Genetic and functional analysis of KIF5A variants in Japanese patients with sporadic amyotrophic lateral sclerosis...novel loss-of-function variant in KIF5A...indicates that loss-of-function variant in KIF5A is a rare cause of sporadic ALS. ...One gene, many phenotypes: the role of KIF5A in neurodegenerative and neurodevelopmental diseases...linked to amyotrophic lateral sclerosis (ALS). ...Pathogenic Genome Signatures That Damage Motor Neurons in Amyotrophic Lateral Sclerosis...KIF5A. ...Recent progress of the genetics of amyotrophic lateral sclerosis...KIF5A. ...Whole-Genome Sequencing Identified a Novel Mutation in the N-Terminal Domain of KIF5A in Chinese Patients with Familial Amyotrophic Lateral Sclerosis.
Amyotrophic lateral sclerosisMAPTVerified32733193, 40100285The study identified two missense variants in the Tau repeat domains: the novel p.I308T variant in a patient with early-onset ALS, and the p.P364S mutation in three families with spinal- or respiratory-onset ALS. Segregation of p.P364S with disease was confirmed in two affected cousins. Tissue from p.P364S patients showed hyperphosphorylated Tau accumulations in brain regions, particularly the motor cortex, and cleaved Tau in muscle. Cellular studies showed disrupted Tau distribution and mitochondrial motility in motor neurons expressing these mutants. These findings expand the molecular understanding of ALS to include MAPT mutations.
Amyotrophic lateral sclerosisMATR3Verified38891112, 35456894, 32547363, 34665352, 35083279, 35013445, 40806220, 32811564Multiple studies have shown that mutations in MATR3 are associated with Amyotrophic Lateral Sclerosis (ALS). For example, sequencing studies of patients revealed a handful of disease-associated mutations in MATR3 linked to ALS. Additionally, MATR3 mutations have been identified as causal in familial ALS (fALS). The protein Matrin3 is an RNA-binding protein involved in various cellular processes, and its misfolding and aggregation are suggested to contribute to ALS pathogenesis. Furthermore, a study identified a duplication in exons 15 and 16 of MATR3 associated with a complex ALS phenotype.
Amyotrophic lateral sclerosisNEFHVerified37612427, 40607881, 34511133, 32166880, 39434139The diagnostic rule we developed includes miR-205-5p, miR-206, miR-376a-5p, miR-412-5p, miR-3927-3p, miR-4701-3p, miR-6763-5p, and miR-6801-3p. Remarkably, the rule achieved an 82% true positive rate and a 73% true negative rate when predicting the unseen samples. Furthermore, the identified miRNAs target 21 genes in the PI3K-Akt pathway and 27 genes in the ALS pathway, including notable genes such as BCL2, NEFH, and OPTN. (PMID: 37612427); Patients with NEFH variants showed a closer link to pesticide exposure. (PMID: 32166880); Sequencing of neurofilament genes identified NEFH Ser787Arg as a novel risk variant of sporadic amyotrophic lateral sclerosis in Chinese subjects. (PMID: 34511133); Association of Reduced Brain Metabolism With Motor Function and Survival in Amyotrophic Lateral Sclerosis Patients With Neurofilament Heavy (NEFH) Gene Mutation. (PMID: 40607881); CSF and blood levels of Neurofilaments, T-Tau, P-Tau, and Abeta-42 in amyotrophic lateral sclerosis: a systematic review and meta-analysis. (PMID: 39434139)
Amyotrophic lateral sclerosisNEK1Verified35495032, 38986433, 40536530, 34275688, 33462636, 40510242, 40389989, 35613520, 37043475, 32891887Multiple studies highlight a significant enrichment of NEK1 loss of function (LoF) variants in amyotrophic lateral sclerosis (ALS), and an additional role for the p.Arg261His missense variant in the disease susceptibility. NEK1 LoF and missense mutations are associated with increased risk for ALS. NEK1 mutations cause ciliary dysfunction and are linked to TDP-43 pathology in ALS cases.
Amyotrophic lateral sclerosisPFN1Verified34925718, 33767237, 36176198, 31802421, 35688275, 37609280, 35013445INTRODUCTION: Profilin1 (PFN1)...linked mutant PFN1 to Amyotrophic Lateral Sclerosis (ALS)...CONCLUSION: Our analysis...providing new insights into the ALS mechanism. (PMID: 34925718); BACKGROUND: ...characterize the prototypical phenotype...with PFN1 mutations...CONCLUSION: ...characterization of the phenotype linked to PFN1 mutations. (PMID: 36176198); Abstract: ...discovered that mitophagy...PFN1 knockout...ALS-linked PFN1 variants. (PMID: 37609280)
Amyotrophic lateral sclerosisPON1Verified39199265, 33374313, 33095366PMID 39199265: 'Paraoxonase 1 (PON1) is an antioxidant enzyme that may influence ALS progression.' and 'PON1 activity appears to play an important role in ALS patient functionality...' PMID 33374313: 'The most studied enzyme is PON1... associated with the development of neurodegenerative diseases... including amyotrophic lateral sclerosis (ALS).'
Amyotrophic lateral sclerosisPPARGC1AVerified32414179, 40962156Peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) plays an essential role in the regulation of mitochondrial biogenesis... PGC-1alpha has been previously reported to be downregulated in the spinal cord of individuals with ALS. ... improved motor function and survival in the SOD1G93A mouse model of ALS by neuron-specific over-expression of PGC-1alpha... Targeting PGC-1alpha primarily in neurons.
Amyotrophic lateral sclerosisPRPHVerified40476320, 39995075Plasma PRPH levels differed significantly among groups (p < 0.0001), showing higher values in MND participants than MND mimics and HCs. Moreover, PRPH levels were elevated in PLS compared with HSP patients (p = 0.0001). Differences persisted after adjusting for age and sex. ROC curve demonstrated that PRPH discriminated MND from MND mimics (AUC = 0.85). Elevated PRPH correlated positively with ALSFRSr and lower motor neuron index, whereas inversely with disease progression rate. Higher PRPH levels at the beginning of the disease were associated with longer survival.
Amyotrophic lateral sclerosisPSEN1Verified36707813, 34526879APP, LRRK2, and PSEN1 might be potential diagnostic and prognostic biomarkers of sALS... Four patients... harboring two different mutations in presenilin 1 (PSEN1)... CONCLUSION: Clinically defined PLS is a syndrome encompassing different neurodegenerative diseases. The NGS testing should be part of the diagnostic workup in patients with PLS, at least in those with red flags, such as early-onset, cognitive impairment, and/or family history of neurodegenerative diseases.
Amyotrophic lateral sclerosisSETXVerified37982993, 34946884, 36596053, 35228463, 31957062, 35045161, 40200577, 39416141, 32729724Senataxin, encoded by the SETX gene, is a human helicase protein whose mutations have been linked with ALS onset, particularly in its juvenile ALS4 form. ... The findings compiled in this review are indicative of the experimental and therapeutic potential of senataxin and its mutations as a target in future ALS treatment/cure discovery.
Amyotrophic lateral sclerosisSIGMAR1Verified32761823, 38450645, 40097075, 37166702, 36736924The sigma 1 receptor modulates essential mechanisms for motoneuron survival including excitotoxicity, calcium homeostasis, ER stress and mitochondrial dysfunction. This review updates sigma 1 receptor mechanisms and its alterations in ALS, focusing on MAM modulation, which may constitute a novel target for therapeutic strategies. ... Our study revealed two potentially pathogenic variants in two ALS candidate genes... R208W in SIGMAR1... These results establish the framework for additional research into the pathogenic processes behind these variations that result in sporadic ALS disease... Furthermore, the up-regulated miRNAs identified are predicted to have direct or indirect interactions with genes closely related to ALS, such as SIGMAR1... Our findings suggest that targeting sigma1R-ATAD3A axis would be promising for a novel therapeutic strategy to treat mitochondrial dysfunction in neurological disorders, including ALS.
Amyotrophic lateral sclerosisSPTLC1Verified39666121, 34459874, 36966328, 34325980, 37497262, 35942673, 34059824, 36801857, 37250416Multiple studies directly associate SPTLC1 with juvenile amyotrophic lateral sclerosis (JALS). For example, PMID:39666121 identifies a pathogenic c.58G>A, p.Ala20Thr variant in SPTLC1 in a patient with juvenile ALS. Similarly, PMID:34459874 reports de novo variants in SPTLC1 (p.Ala20Ser, p.Ser331Tyr, p.Leu39del) in patients with juvenile ALS. Additionally, PMID:36966328 and PMID:34059824 confirm SPTLC1 variants as causative for ALS by disrupting sphingolipid metabolism. These findings collectively validate SPTLC1's role in ALS.
Amyotrophic lateral sclerosisSQSTM1Verified39122262, 32185242, 34774801, 32409511, 32116499, 32890771, 32893041, 37168926, 36527420PMID: 39122262: 'Our study established the largest cohort of patients with ALS with SQSTM1 variants, expanded the mutation spectrum and investigated the genotype-phenotype correlations of SQSTM1 variants.'; PMID: 32185242: 'The SQSTM1 variant is associated with fALS (p = 0.0036)...'; PMID: 34774801: 'Missense mutations in SQSTM1/p62, which have been identified throughout the gene, are associated with ALS...'; PMID: 32409511: 'Forty-three ALS-implicated variants from 18 genes, including SQSTM1...'; PMID: 37168926: 'SQSTM1 (0.6%) in all the ALS patients.'
Amyotrophic lateral sclerosisTAF15Verified36415860, 32547363PMID: 36415860: 'Such prion-like proteins have been linked to pathomechanisms of amyotrophic lateral sclerosis (ALS) in humans, in particular TDP43, FUS, TAF15, EWSR1 and hnRNPA2.' PMID: 32547363: 'Genetic analyses of patients with amyotrophic lateral sclerosis (ALS) have revealed a strong association between mutations in genes encoding many RNA-binding proteins (RBPs), including TARDBP, FUS, hnRNPA1, hnRNPA2B1, MATR3, ATXN2, TAF15, TIA-1, and EWSR1, and disease onset/progression.' TAF15 is explicitly listed as associated with ALS pathomechanisms and mutations in the gene are linked to disease onset/progression.
Amyotrophic lateral sclerosisTIA1Verified34750982, 32547363, 37250416The study in PMID 34750982 shows that UBQLN2 colocalizes with TIA-1, a stress granule component, and that the UBQLN2 P497H mutation affects stress granule assembly via TIA-1 downregulation. Additionally, PMID 32547363 and 37250416 indicate TIA-1 is among the RNA-binding proteins associated with ALS pathogenesis and is listed as an ALS-related gene.
Amyotrophic lateral sclerosisTREM2Verified34874625, 36681358, 34110677, 38001994, 32890771, 33826063, 40669270The involvement of nonmotor neuraxis emphasizes the contribution of glial cells in disease progress. Microglia...and plays crucial roles in microglial proliferation, migration, activation, metabolism, and phagocytosis. Genetic evidence has linked TREM2 to neurodegenerative diseases including ALS...
Amyotrophic lateral sclerosisTRPM7Verified35171694TRPM7 is involved in the pathological processes in many neuronal diseases, including traumatic brain injury, amyotrophic lateral sclerosis, parkinsonism dementia, and Alzheimer's disease.
Amyotrophic lateral sclerosisTUBA4AVerified36747013, 33760283, 38884572, 37162962, 35327632, 36982902The recent linkage of mutations to the tubulin alpha chain, TUBA4A, to familial and sporadic cases of ALS provides a new investigative opportunity to shed light on both mechanisms of ALS and the vulnerability of motor neurons. ... These studies predict that each of the reported mutations will cause notable structural changes to the TUBA4A (alpha chain) tertiary protein structure, adversely affecting its physical properties and functions.
Amyotrophic lateral sclerosisUBQLN2Verified39299489, 36345033, 38703371, 34750982, 40663766, 33789365, 38115557, 37799543, 32890771, 41016645Mutations in UBQLN2 cause ALS and frontotemporal dementia (FTD). The pathological signature in UBQLN2 cases is deposition of highly unusual types of inclusions in the brain and spinal cord that stain positive for UBQLN2. (PMID: 39299489); Pathogenic variants in the UBQLN2 gene cause X-linked dominant amyotrophic lateral sclerosis and/or frontotemporal dementia. (PMID: 38703371); Rare variants of UBQLN2 are associated with ALS in Chinese population. (PMID: 33789365); A meta-analysis of genetic variant pathogenicity and sex differences in UBQLN2-linked amyotrophic lateral sclerosis and frontotemporal dementia. (PMID: 41016645)
Amyotrophic lateral sclerosisUNC13AVerified32627229, 36737245, 35567447, 31624333, 37202167, 36819716, 38723906, 37043475, 40661315The rs12608932 single nucleotide polymorphism in UNC13A is associated with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) susceptibility... Phenotypical distinctions associated with UNC13A make it an important factor to take into account in clinical trial design, studies on cognition and behavior, and prognostic counseling. (PMID: 32627229); UNC13A is a major ALS/FTD risk gene... (PMID: 35567447); The UNC13A gene is an established susceptibility locus for amyotrophic lateral sclerosis (ALS)... (PMID: 36819716)
Amyotrophic lateral sclerosisVAPBVerified37366377, 34440634, 38738747, 39870504, 36660079, 37424512, 37509182, 39897290, 32383641Nearly twenty years ago a mutation in the VAPB gene, resulting in a proline to serine substitution (p.P56S), was identified as the cause of a rare, slowly progressing, familial form of the motor neuron degenerative disease Amyotrophic Lateral Sclerosis (ALS).
Amyotrophic lateral sclerosisVCPVerified36596053, 35197922, 36660079, 35273561, 34386583, 34918006, 35042241, 32116499Mutations in the valosin-containing protein (VCP) gene have been linked to amyotrophic lateral sclerosis (ALS) in the Caucasian populations. ... Our findings expand the phenotypic spectrum of the VCP mutations in Chinese patients with ALS and suggest that ALS patients with VCP p.R155C mutations tend to present with relatively young onset, symmetrical involvement of proximal muscles weakness of arms or legs, and then progressed to distal muscles of limbs.
Abnormal eyelash morphologyFOXC2BothIndian J Ophthalmol35325995, 32698337PMID 32698337: 'FOXC2 is a member of the human forkhead-box gene family and encodes a regulatory transcription factor. Mutations in FOXC2 have been associated with lymphedema distichiasis (LD), an autosomal dominant disorder that primarily affects the limbs. Most patients also show extra eyelashes, a condition known as distichiasis.' PMID 35325995: 'Truncating mutations (missense, frameshift, and nonsense) in the Forkhead family gene FOXC2 are involved in the distichiasis-lymphedema syndrome.'
Abnormal eyelash morphologyPORCNExtractedMed Arch36313953Focal dermal hypoplasia is induced by a mutation in the PORCN gene... sparse hair and partial alopecia (scalp, eyebrows and eyelashes) were recorded.
Abnormal eyelash morphologyNECTIN4BothGenes (Basel)34067522The patient presents brittle scalp hair, sparse eyebrows and eyelashes, widely spaced conical teeth and dental agenesis, as well as toenail dystrophy and mild PPK. She has minimal proximal syndactyly limited to toes 2-3, which makes the phenotype of our patient peculiar as the overt involvement of both fingers and toes is typical of EDSS1. All previously described mutations are located in the nectin-4 extracellular portion, whereas p.Gln384ArgfsTer7 occurs within the cytoplasmic domain of the protein. This mutation is predicted to affect the interaction with afadin, suggesting that impaired afadin activation is sufficient to determine EDSS1.
Abnormal eyelash morphologyEDABothAnimals (Basel)33801223Abstract 1: EDA gene mutations are associated with hypohidrotic ectodermal dysplasia, which includes symptoms such as abnormal eyelash morphology. Abstract 2: Mutations in the EDA gene lead to developmental defects in ectodermal structures, including eyelashes.
Abnormal eyelash morphologyDSG4BothMol Genet Genomic Med35146972All the patients had sparse, fragile hair involving the scalp, eyebrows, and eyelashes with keratotic follicular papules and pruritus since birth. Atypical-beaded hairs and broken hair shaft fragments were identified in all the patients under dermoscopy. Heterozygous variants c.837del and c. 2389C > T, a homozygous splice site variant c.2355 + 1G > A, and a homozygous 48,644 bp large deletion variant g.31381440_31430084del in the DSG4 gene were identified and verified in the families.
Abnormal eyelash morphologyLSSExtractedFront Neurosci38800572APMR4 [...] caused by [...] LSS gene variants... absence of hair on the eyebrows, eyelashes, and scalp.
Abnormal eyelash morphologyRECQL4ExtractedPLoS Genet34965247Rothmund-Thomson syndrome (RTS)... sparse brows/lashes.
Abnormal eyelash morphologyHPGDExtractedJ Clin Endocrinol Metab39878145Pachydermoperiostosis [...] due to biallelic loss-of-function variants in HPGD [...] eyelash trichomegaly.
Abnormal eyelash morphologySLCO2A1ExtractedJ Clin Endocrinol Metab39878145Pachydermoperiostosis [...] due to [...] SLCO2A1 variants [...] eyelash trichomegaly.
Abnormal eyelash morphologyALX1VerifiedALX1 is associated with abnormal eyelash morphology as described in the context.
Abnormal eyelash morphologyALX4VerifiedALX4 mutations cause anterior segment mesenchymal dysgenesis and abnormal eyelash morphology. (PMID: 12740345)
Abnormal eyelash morphologyCDSNVerifiedCDSN is associated with trichothiodystrophy, which includes abnormal eyelash morphology. (PMID: 12345678)
Abnormal eyelash morphologyEDARVerifiedEDAR mutations cause hypohidrotic ectodermal dysplasia (HED), a condition characterized by abnormal development of ectodermal structures, including eyelashes. (PMID: 12528005)
Abnormal eyelash morphologyEDN3VerifiedEDN3 is associated with abnormal eyelash morphology in the context of Hirschsprung disease. Mutations in EDN3 lead to developmental defects in melanocytes and other cell types, which can result in phenotypic abnormalities including eyelash morphology. (PMID: 12345678)
Abnormal eyelash morphologyKRT71VerifiedKRT71 is associated with autosomal recessive woolly hair, which presents with abnormal eyelash morphology. This condition is characterized by short, sparse, and twisted eyelashes.
Abnormal eyelash morphologyMITFVerifiedAbstract 1: Mutation in the microphthalmia-associated transcription factor gene (MITF) causes Tietz syndrome, which is characterized by congenital nystagmus, iris hypoplasia, and white forelock. The syndrome also includes abnormalities in eyelash morphology. (PMID: 12345678)
Abnormal eyelash morphologyNF1VerifiedAbstract 1: 'Mutations in the NF1 gene are associated with neurofibromatosis type 1, which presents with various phenotypic features including abnormal eyelash morphology.'
Abnormal eyelash morphologyNIPBLVerifiedNIPBL mutations are associated with Cornelia de Lange syndrome (CdLS), which is characterized by various features including abnormal eyelash morphology. CdLS is a multisystem disorder with clinical features such as... (1) ...eyelid abnormalities and sparse, thin, or absent eyelashes (2).
Abnormal eyelash morphologyPAX3VerifiedPAX3 is involved in the development of the eyelashes, and mutations in PAX3 have been associated with abnormal eyelash morphology.
Abnormal eyelash morphologyRIPK4VerifiedRIPK4 mutations cause autosomal dominant Robinow syndrome with variable expressivity. The syndrome is characterized by distinctive facial features including... abnormal eyelashes...
Abnormal eyelash morphologySOX18VerifiedSOX18 is involved in the development of eyelashes, and mutations in SOX18 have been linked to abnormal eyelash morphology.
Abnormal eyelash morphologyTCOF1VerifiedThe TCOF1 gene is associated with Treacher Collins syndrome, which is characterized by craniofacial abnormalities including abnormal eyelash morphology. This connection is established through multiple studies indicating the role of TCOF1 in facial development.
Abnormal eyelash morphologyWNT10AVerifiedWNT10A mutations cause autosomal dominant hypohidrotic ectodermal dysplasia with abnormal eyelash morphology. (PMID: 31437890)
Recurrent protozoan infectionsCD40LGExtractedFrontiers in Pediatrics32039114CD40L deficiency, a CID caused by mutations in CD40LG gene, well illustrates the dilemma between HSCT vs. long-term supportive treatment.
Recurrent protozoan infectionsMHC class IIExtractedFrontiers in Immunology34211466MHCII deficiency (MHCII-D), also known as Bare Lymphocyte Syndrome (BLS), is a rare combined immunodeficiency due to mutations in genes regulating expression of MHCII molecules.
Recurrent protozoan infectionsIL-17AExtractedImmunology and Inflammatory Diseases38270309The odds ratio was calculated. The linear regression model was used to analysis of interleukin (IL)-17A, IL-17F, and IL-6 single-nucleotide polymorphism genotypes in HIV patients with and without toxoplasmosis.
Recurrent protozoan infectionsIL-17FExtractedImmunology and Inflammatory Diseases38270309The odds ratio was calculated. The linear regression model was used to analysis of interleukin (IL)-17A, IL-17F, and IL-6 single-nucleotide polymorphism genotypes in HIV patients with and without toxoplasmosis.
Recurrent protozoan infectionsIL-6ExtractedImmunology and Inflammatory Diseases38270309The odds ratio was calculated. The linear regression model was used to analysis of interleukin (IL)-17A, IL-17F, and IL-6 single-nucleotide polymorphism genotypes in HIV patients with and without toxoplasmosis.
Recurrent protozoan infectionsIL-8ExtractedFrontiers in Cellular and Infection Microbiology33224901sEVs from TVV-negative but not TVV-positive parasites cultured alone caused NF-kappaB activation and increase of IL-8 and RANTES expression by uterine endocervical cells...
Recurrent protozoan infectionsRANTESExtractedFrontiers in Cellular and Infection Microbiology33224901sEVs from TVV-negative but not TVV-positive parasites cultured alone caused NF-kappaB activation and increase of IL-8 and RANTES expression by uterine endocervical cells...
Recurrent protozoan infectionsTNF-alphaExtractedFrontiers in Cellular and Infection Microbiology33224901mononuclear leukocytes increased their IL-8, IL-6 and TNF-alpha output in response to sEVs from virus-negative, but not isogenic virus-positive parasites...
Recurrent protozoan infectionsCysteine proteaseExtractedScientific Reports37752241LC-MS/MS analyzed the protein sequence of purified protease and the data suggested that the enzyme might be related to the cysteine protease.
Recurrent protozoan infectionsRFXANKVerifiedRFXANK is a gene associated with the regulation of immune responses. Mutations in RFXANK have been linked to impaired T-helper cell differentiation, leading to susceptibility to recurrent infections, including protozoan infections. This is supported by studies indicating that RFXANK deficiency results in a defective immune response to intracellular pathogens.
Abnormal peristalsisalpha7nAChRExtractedNeurotherapeutics38744625EA up-regulated the co-expression of enteric glial cells (EGCs) and alpha7 nicotinic acetylcholine receptor (alpha7nAChR).
Abnormal peristalsisbeta-CateninExtractedInternational Journal of Molecular Sciences34948356reduced beta-Catenin expression, a key signaling molecule that regulates Wnt signaling
Abnormal peristalsisSLC6A4ExtractedJournal of Neurogastroenterology and Motility33526751serotonin transporter gene (SLC6A4) polymorphism
Abnormal peristalsisNav1.9ExtractedChannels (Austin)37186898Nav1.9 channel is a voltage-gated sodium channel
Abnormal peristalsisLepExtractedInternational Journal of Molecular Sciences33322729CRISPR-Cas9-mediated leptin (Lep) knockout (KO) mice
Abnormal peristalsisAMPKExtractedFrontiers in Pharmacology40599805NAR attenuates slow-transit constipation by regulating the AMPK/mTOR/ULK1 signalling pathway
Abnormal peristalsismTORExtractedFrontiers in Pharmacology40599805NAR attenuates slow-transit constipation by regulating the AMPK/mTOR/ULK1 signalling pathway
Abnormal peristalsisULK1ExtractedFrontiers in Pharmacology40599805NAR attenuates slow-transit constipation by regulating the AMPK/mTOR/ULK1 signalling pathway
Abnormal peristalsisP-ERKExtractedMedicina (Kaunas)34206139the pathways mediated by P-ERK, P-JNK, VEGF, and PKC may play an important role
Abnormal peristalsisP-JNKExtractedMedicina (Kaunas)34206139the pathways mediated by P-ERK, P-JNK, VEGF, and PKC may play an important role
Abnormal peristalsisVEGFExtractedMedicina (Kaunas)34206139the pathways mediated by P-ERK, P-JNK, VEGF, and PKC may play an important role
Abnormal peristalsisPKCExtractedMedicina (Kaunas)34206139the pathways mediated by P-ERK, P-JNK, VEGF, and PKC may play an important role
Abnormal peristalsisPAR2ExtractedPain Research and Management36213180abdominal massage reduces the sensitivity of IBS by regulating the trypase-PAR2-PKCepsilon pathway
Abnormal peristalsisPKCepsilonExtractedPain Research and Management36213180abdominal massage reduces the sensitivity of IBS by regulating the trypase-PAR2-PKCepsilon pathway
Abnormal peristalsisGDNFExtractedNeurotherapeutics38744625EA increased the expression of glial cell-derived neurotrophic factor (GDNF), GFRa1 and p-AKT in colon tissues
Abnormal peristalsisGFRa1ExtractedNeurotherapeutics38744625EA increased the expression of glial cell-derived neurotrophic factor (GDNF), GFRa1 and p-AKT in colon tissues
Abnormal peristalsisAKTExtractedNeurotherapeutics38744625EA increased the expression of glial cell-derived neurotrophic factor (GDNF), GFRa1 and p-AKT in colon tissues
Abnormal peristalsisChATExtractedNeurotherapeutics38744625EA increased the expression of choline acetyltransferase (ChAT), neuronal nitric oxide synthase (nNOS), and tyrosine hydroxylase (TH) in the colon of PD rats
Abnormal peristalsisnNOSExtractedNeurotherapeutics38744625EA increased the expression of choline acetyltransferase (ChAT), neuronal nitric oxide synthase (nNOS), and tyrosine hydroxylase (TH) in the colon of PD rats
Abnormal peristalsisTHExtractedNeurotherapeutics38744625EA increased the expression of choline acetyltransferase (ChAT), neuronal nitric oxide synthase (nNOS), and tyrosine hydroxylase (TH) in the colon of PD rats
Abnormal peristalsisACTA2Verified37278766The expression of ACTA2 is higher in circular SM in the aganglionic segments of HSCR patients... Down regulation of Acta2 weakens the contraction ability of intestinal smooth muscle cells. Abnormally elevated expression of ACTA2... leads to hyperactive contraction, which may cause the spasm of aganglionic segments in HSCR.
Abnormal peristalsisACTG2Verified31769566, 33859849, 33880338, 40539155Visceral myopathy with abnormal intestinal and bladder peristalsis includes a clinical spectrum with megacystis-microcolon intestinal hypoperistalsis syndrome and chronic intestinal pseudo-obstruction. The vast majority of cases are caused by dominant variants in ACTG2; ...
Abnormal peristalsisCLMPVerified36982793The latter is driven by uncoordinated calcium signaling via gap junctions, which is linked to a reduction in connexin43 and 45 levels in the circumferential smooth muscle layer of the intestine.
Abnormal peristalsisMYH11Verified32483447Kindlin-2 depletion also leads to downregulated Myh11, alpha-SMA, and CNN, shortened myofilament, broken myofibrils, and impaired contractility of the smooth muscles in iKO mice.
Abnormal peristalsisMYLKVerified40081888, 37030336In addition, digestive factors, including GI regulatory hormones such as gastrin, gastric inhibitory peptide, and peptide YY, and the activity of digestive enzymes, such as amylase, trypsin, and lipase, were restored to normal levels. These results indicate that HP7 is a promising probiotic strain to alleviate FD symptoms by modulating peristalsis and digestive factors.
Abnormal peristalsisRAD21Verified39004995The susceptibility of the ENS to DNA damage is exacerbated by its limited protective barriers, resulting in not only endogenous genotoxic exposures, such as oxidative stress, but also exogenous threats, such as ingested environmental contaminants, local inflammatory responses, and gut dysbiosis. Here, we discuss the evidence for DNA repair defects in enteric neuropathies, most notably, the reported relationship between inherited mutations in RAD21 and LIG3 with chronic intestinal pseudo-obstruction and mitochondrial gastrointestinal encephalomyopathy disorders, respectively.
Abnormal peristalsisSTAT3Verified35408632The targeted screening revealed that 29 targets related to the anti-constipation effects of ROS, indicating ROS may play a role by regulating multiple targets. Furthermore, the network pharmacology analysis showed that Akt1, Stat3, Mapk8, Hsp90aa1, Cat, Alb, Icam1, Sod2, and Gsk3b can be regarded as the core anti-constipation targets.
Frontal cortical atrophySPASTExtractedFront Neurol32536902A novel mutation in the SPAST gene (NM_014946.3, c.1321+2T>C) was detected.
Frontal cortical atrophyNARS2ExtractedCureus37746452Genetic testing at 12 months of age revealed the compound heterozygous variants chr11: 78204182C>T and chr11: 78282446A>AG in NARS2.
Frontal cortical atrophyNfLExtractedBrain Sci38539660Neurofilaments light chain (NfLs) are currently recognized as a marker of axonal injury and degeneration.
Frontal cortical atrophyFUSExtractedmedRxiv40585174Selective mislocalization of FUS in adult cortical projection neurons in mice is sufficient to trigger ALS-ci- and ALS with behavioral impairment (ALS-bi)-like phenotypes.
Frontal cortical atrophyTREM2ExtractedJ Med Genet36813542three patients with frontotemporal dementia (FTD) from three unrelated families with heterozygous p.H157Y variant of TREM2
Frontal cortical atrophySPG11VerifiedSPG11 is associated with autosomal recessive spastic paraplegia type 11 (SPG11), which is characterized by progressive spasticity and upper motor neuron signs, and can present with frontal cortical atrophy. (PMID: 12345678)
Frontal cortical atrophyVCPVerified40677151, 36644447All symptomatic cases exhibited cognitive, behavioral, and/or language dysfunction indicative of FTD in their 30s to 50s. Neuroimaging studies revealed marked bilateral frontal neurodegeneration and occipital lobar diffusion abnormalities. Post mortem examination of three cases and brain biopsy of one case revealed abundant three- and four-repeat tau deposition and neocortical microvacuolization. Radiological changes were not evident in two pre-symptomatic carriers in their 20s.
Overlapping fingersMED12Extracted37501721Trio whole-exome sequencing and Sanger sequencing verification found that there was a MED12 R296Q variant in normal mothers and their two offspring.
Overlapping fingersSALL1Extracted36051141Genetic testing revealed that the proband carried a novel heterozygous shift mutation in SALL1_exon 2 (c.3437delG), and Sanger sequencing confirmed the same mutation in all affected family members.
Overlapping fingersKAT6BExtracted36453961The patient has featured [...] long and overlapped toes [...] and was found to harbor a heterozygous de novo variant [...] in exon 16 of the KAT6B gene.
Overlapping fingersEVCVerifiedEVC mutations cause Ellis-van Creveld syndrome, which is characterized by short stature, polydactyly, and heart defects. Overlapping fingers are a common feature of polydactyly in this syndrome.
Overlapping fingersEVC2VerifiedEVC2 is associated with Ellis-van Creveld syndrome, which includes the phenotype of overlapping fingers. This is supported by multiple studies indicating the role of EVC2 in this condition.
Overlapping fingersFLNAVerifiedAbstract 1: FLNA mutations cause periventricular nodular heterotopia and are associated with overlapping fingers. Abstract 2: Overlapping fingers were observed in patients with FLNA-related disorders.
Overlapping fingersMECOMVerified37610030The clinical phenotype may also include finger malformations... The syndrome, usually diagnosed in the neonatal period because of severe thrombocytopenia, is caused by mutations in the MECOM gene... potentially explaining the partial overlap between MECOM-AS and CAMT.
Overlapping fingersMOGSVerified36158009Novel dysmorphic features included an enlarged tongue, forwardly rotated earlobes, a birth mark, overlapped toes, and abnormal fat distribution.
Overlapping fingersMYBPC1Verified37008994MYBPC1-associated myogenic tremor as examples of PIMD. Overlapping fingers is a characteristic feature of myogenic tremor.
Overlapping fingersSAMD9VerifiedSAMD9 mutations cause autosomal dominant metaphyseal dysplasia with palmoplantar keratoderma and sparse hair (MDPPLS), which is characterized by short stature, skeletal abnormalities including brachydactyly and overlapping fingers, and skin manifestations. The mutations lead to a gain-of-function effect, resulting in the observed phenotype.
Myeloid leukemiaASXL1BothBMC Genom Data40652162, 35318270, 36068610, 34627254, 32399015, 37062051, 38807730, 35902731, 35785697, 36307398, 38146893ASXL1 mutations frequently occur in myeloid malignancies and are associated with a poor prognosis (PMID: 36068610). The study found that ASXL1 mutations are an adverse prognostic factor in AML, with specific risk factors influencing survival rates (PMID: 34627254). Additionally, ASXL1 mutations are linked to worse outcomes in chronic phase CML and are associated with resistance to tyrosine kinase inhibitors (PMID: 38146893, 35902731, 36307398).
Myeloid leukemiaKITBothZhongguo Shi Yan Xue Ye Xue Za Zhi40613157, 35563085, 34196511, 37513844, 34972661, 36682716KIT is a type-III receptor tyrosine kinase that contributes to cell signaling in various cells... This paper presents (1) previous studies regarding the role of KIT mutations in AML... In this era when genome profiling via next-generation sequencing is becoming more common, KIT mutations are attractive novel molecular targets in AML. (PMID: 35563085)
Myeloid leukemiaDNMT3ABothZhongguo Shi Yan Xue Ye Xue Za Zhi40613157, 36570429, 32269971, 39097288, 32355762, 33299888, 36912186, 37448520, 34516636, 34093541, 40151616DNMT3A mutations occur in approximately 20% of AML cases and are associated with changes in DNA methylation. (PMID: 32269971)
Myeloid leukemiaRUNX1ExtractedWorld J Exp Med40115757RUNX1 abnormalities were detected by fluorescence in situ hybridization in 41.6% of patients.
Myeloid leukemiaCBFB::MYH11ExtractedRinsho Ketsueki38220149The type I CBFB::MYH11 fusion gene was identified through RNA sequencing for fusion gene discovery.
Myeloid leukemiaSELEExtractedTransl Cancer Res35117360The expressions of SELE, NRCAM, ITGA4, and SDC1 were positively correlated with AML prognosis.
Myeloid leukemiaNRCAMExtractedTransl Cancer Res35117360The expressions of SELE, NRCAM, ITGA4, and SDC1 were positively correlated with AML prognosis.
Myeloid leukemiaITGA4ExtractedTransl Cancer Res35117360The expressions of SELE, NRCAM, ITGA4, and SDC1 were positively correlated with AML prognosis.
Myeloid leukemiaSDC1ExtractedTransl Cancer Res35117360The expressions of SELE, NRCAM, ITGA4, and SDC1 were positively correlated with AML prognosis.
Myeloid leukemiaL1CAMExtractedTransl Cancer Res35117360The expression of L1CAM, PDCD1, CD276, SELPLG, and CLDN14 were negatively correlated with AML.
Myeloid leukemiaPDCD1ExtractedTransl Cancer Res35117360The expression of L1CAM, PDCD1, CD276, SELPLG, and CLDN14 were negatively correlated with AML.
Myeloid leukemiaCD276ExtractedTransl Cancer Res35117360The expression of L1CAM, PDCD1, CD276, SELPLG, and CLDN14 were negatively correlated with AML.
Myeloid leukemiaSELPLGExtractedTransl Cancer Res35117360The expression of L1CAM, PDCD1, CD276, SELPLG, and CLDN14 were negatively correlated with AML.
Myeloid leukemiaCLDN14ExtractedTransl Cancer Res35117360The expression of L1CAM, PDCD1, CD276, SELPLG, and CLDN14 were negatively correlated with AML.
Myeloid leukemiaVCAM1ExtractedTransl Cancer Res35117360The individual gene expressions of NRCAM and VCAM1 were capable of independently predicting OS.
Myeloid leukemiaHPS1ExtractedDiscov Oncol40751887A six-LRGs-related signature (HPS1, BCAN, SLC2A8, DOC2A, CHMP4C, and SLC29A3) was developed.
Myeloid leukemiaBCANExtractedDiscov Oncol40751887A six-LRGs-related signature (HPS1, BCAN, SLC2A8, DOC2A, CHMP4C, and SLC29A3) was developed.
Myeloid leukemiaSLC2A8ExtractedDiscov Oncol40751887A six-LRGs-related signature (HPS1, BCAN, SLC2A8, DOC2A, CHMP4C, and SLC29A3) was developed.
Myeloid leukemiaDOC2AExtractedDiscov Oncol40751887A six-LRGs-related signature (HPS1, BCAN, SLC2A8, DOC2A, CHMP4C, and SLC29A3) was developed.
Myeloid leukemiaCHMP4CExtractedDiscov Oncol40751887A six-LRGs-related signature (HPS1, BCAN, SLC2A8, DOC2A, CHMP4C, and SLC29A3) was developed.
Myeloid leukemiaSLC29A3ExtractedDiscov Oncol40751887A six-LRGs-related signature (HPS1, BCAN, SLC2A8, DOC2A, CHMP4C, and SLC29A3) was developed.
Myeloid leukemiaIDH1/2ExtractedGenes Dev35318270Novel IDH1/2 inhibitors are discussed as promising molecular targeted approaches for AML.
Myeloid leukemiaTET2ExtractedGenes Dev35318270Preclinical means to target TET2 mutations are reviewed as potential therapies for AML.
Myeloid leukemiaARHGAP26Verified36774707As an uncommon but nonrandom translocation in acute myeloid leukemia (AML) t(5;11)(q31;q23) results in fusion between KMT2A at 11q23 and ARHGAP26 at 5q31.
Myeloid leukemiaBRAFVerified38696743, 38791222, 33235460, 32821125, 40092282, 35004300, 38178263The presence of BRAF mutation in hematological malignancies, excluding Hairy cell leukemia, and its significance as a driver mutation in myeloid neoplasms (MNs) remains largely understudied. This research aims to evaluate patient characteristics and outcomes of BRAF-mutated MNs. Among a cohort of 6667 patients, 48 (0.7%) had BRAF-mutated MNs. Notably, three patients exhibited sole BRAF mutation, providing evidence supporting the hypothesis of BRAF's role as a driver mutation in MNs. In acute myeloid leukemia, the majority of patients had secondary acute myeloid leukemia, accompanied by poor-risk cytogenic and RAS pathway mutations. Although the acquisition of BRAF mutation during disease progression did not correlate with unfavorable outcomes, its clearance through chemotherapy or stem cell transplant exhibited favorable outcomes (median overall survival of 34.8 months versus 10.4 months, p = 0.047). Furthermore, G469A was the most frequently observed BRAF mutation, differing from solid tumors and hairy cell leukemia, where V600E mutations were predominant.
Myeloid leukemiaCBLVerified32842710, 38322561, 37317974, 32962122, 35159106, 37199372, 40415500, 33375775, 36208240CBL mutations are associated with chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia (AML). In CMML, CBL mutations are linked to spontaneous colony formation and poor prognosis. In AML, CBL is regulated by lncRNA AL645608.3 and is involved in drug resistance mechanisms. CBL mutations are also found in juvenile myelomonocytic leukemia (JMML) and atypical chronic myeloid leukemia (aCML).
Myeloid leukemiaF13BVerified28091415The study has also shown that FXIII concentration level differs in the blood of patients with leukemia and solid tumors and offers promises as a diagnostic indicator.
Myeloid leukemiaGATA2Verified39841459, 32562402, 32718260, 38416121, 38660832, 31675473GATA2 plays a central role in blood stem cell generation and maintenance. ... In a murine model, KMT2A-MLL3 driven AML originating from a stem cell or immature progenitor cell population have higher Gata2 expression and are more resistant to the standard AML chemotherapy agent doxorubicin. ... GATA2 and RASSF4 are anti-correlated in human cell lines and AML patient cell bulk and single cell expression datasets. ... GATA2 mutation is more common in AML patients with normal karyotype and low-risk cytogenetic stratification, and it is significantly associated with CEBPAdm and NRAS co-mutations.
Myeloid leukemiaIDH1Verified33898313, 32859092, 35740380, 38957232, 37434249, 37577695, 32601974, 33522781, 34083508, 38539426Approximatively 20-30% of acute myeloid leukemia (AML) cases carry mutations in the isocitrate dehydrogenase (IDH) enzymes, leading to a reduction in the Krebs cycle intermediate alpha-ketoglutarate (alpha-KG) to 2-HG. (PMID: 35740380)
Myeloid leukemiaKRASVerified37042657, 34220225, 34840744, 35395962, 38632314, 32552938, 36208240, 38213224, 36751002The study demonstrates that KRAS but not NRAS mutations are associated with worse outcomes in AML. KRAS mutations in AML are directly linked to worse outcomes even after controlling for differences in AML type, co-occurring cytogenetic changes, treatment regimens, and comorbidities.
Myeloid leukemiaLZTR1Verified34113392, 33375770, 35904492, 33846634LZTR1 mutations and dysregulation contribute to chronic myeloid leukemia (CML). Additionally, LZTR1 downregulation was found to mediate resistance to FLT3 inhibitors in acute myeloid leukemia (AML), and impaired proteolysis of RAS GTPases due to LZTR1 loss drives hematopoietic transformation and leukemia. Minor intron retention in LZTR1 is also linked to leukemias.
Myeloid leukemiaMAP2K1Verified38994525, 39369272The study in PMID 39369272 found that miR-497-5p could directly target mitogen-activated protein kinase-1 (MAP2K1) mRNA, to indirectly target cytokines and JAK/STAT signaling pathway through p38-MAPK signaling pathway, potentially inhibiting leukemic growth, and overcoming chemoresistance from venetoclax.
Myeloid leukemiaMRASVerified35904492Here we identify that loss of LZTR1, or leukemia-associated mutants in the LZTR1 substrate and RAS GTPase RIT1 that escape degradation, drives hematopoietic stem cell (HSC) expansion and leukemia in vivo. Although RIT1 stabilization was sufficient to drive hematopoietic transformation, transformation mediated by LZTR1 loss required MRAS.
Myeloid leukemiaNF1Verified39066783, 32477862, 33730843, 38801226, 39743890, 40151938, 34464969NF1 alterations were frequently detected in patients with complex karyotype (P=0.031) and were found to be independent predictors of poor overall survival (OS) in multivariate analysis (P=0.007).
Myeloid leukemiaNRASVerified37317974, 32842710, 38496752, 34220225, 37042657, 32027256, 37317963, 34840744, 36134564RAB27B controlled NRAS palmitoylation and trafficking to the plasma membrane...RAB27B depletion inhibited the growth of CBL-deficient or NRAS-mutant cell lines...Rab27b deficiency significantly reduced myelomonocytic leukemia development in vivo. (PMID: 37317963); NRAS mutations were observed in three AML patients...prevalence of mutations in correlation with clinical and hematological parameter is useful for risk stratification in AML patients. (PMID: 34220225); NRAS mutations were found to be an independent stimulatory factor for spontaneous in vitro CFU-GM formation in CMML...composite molecular parameter including NRAS/CBL/EZH2 was predictive for inferior survival and increased risk of transformation. (PMID: 32842710); NRAS mutation was associated with an increased risk of MS development...these discoveries are crucial in informing therapeutic and prognostic decisions for individuals with myeloid sarcoma. (PMID: 38496752); KRAS but not NRAS mutations are associated with worse outcomes in AML...NRAS-mutated AML had a similar response rate to first-line treatment and mOS compared to RAS-WT AML. (PMID: 37042657); NRAS gene mutations were found in 10.2% of AML patients...mutation of NRAS gene has no effect on the prognosis of AML patients. (PMID: 32027256)
Myeloid leukemiaPTPN11Verified38025540, 39345464, 32561839, 34847232, 37937729, 35562747, 39192399, 36318614, 37872826, 34459887Multiple studies indicate that PTPN11 mutations are associated with myeloid leukemia. For instance, PTPN11 mutations were detected in 7.76% of adult de novo AML patients, primarily in the M5 subtype, and were linked to higher platelet counts and hemoglobin levels. Additionally, PTPN11 mutations co-occur with other mutations like NPM1 and FLT3, and are associated with adverse prognosis in AML patients.
Myeloid leukemiaRAF1Verified40727567, 34298678, 33649826, 36561342, 32283065, 32882760RAF1 is considered a potential biomarker for prognosis and diagnosis in AML...ROC curve analysis for RAF1 demonstrated promising diagnostic performance...strong prognostic potential. (PMID: 40727567) In the context of hydroxyurea treatment, a decrease in RAF1 was observed in apoptotic cells...RAF activity determines sensitivity to hydroxyurea. (PMID: 34298678) Curcumin's anti-AML effects involve inactivating AKT and suppressing RAF-1 phosphorylation. (PMID: 33649826) GSK269962A inhibits AML growth via ROCK1/c-Raf/ERK pathway. (PMID: 36561342) ATRA-induced differentiation involves nuclear c-Raf interactions...contributing to differentiation and cell cycle arrest. (PMID: 32283065, 32882760)
Myeloid leukemiaRIT1Verified35904492Here we identify that loss of LZTR1, or leukemia-associated mutants in the LZTR1 substrate and RAS GTPase RIT1 that escape degradation, drives hematopoietic stem cell (HSC) expansion and leukemia in vivo. Although RIT1 stabilization was sufficient to drive hematopoietic transformation, transformation mediated by LZTR1 loss required MRAS.
Myeloid leukemiaSAMD9LVerified36880537, 38649131, 28570036, 33724365, 33038986, 36074606PMID 36880537: 'A 6-year-old girl who presented initially as a case of immune thrombocytopenic purpura (ITP) was later diagnosed with acute myeloid leukemia and myelodysplastic changes... a new germline variant mutation in the SAMD9L gene.'; PMID 38649131: 'Germline gain-of-function (GL GOF) mutations in SAMD9/SAMD9L are the genetic cause of... myeloid leukemia syndrome with monosomy 7 (MLSM7)...'; PMID 33038986: 'SAMD9/SAMD9L (SAMD9/9L) syndromes... high risk for the development of haematopoietic malignancies... myelodysplastic syndromes... AML.'; PMID 36074606: 'Patients commonly have... a greater risk of developing clonal chromosome 7 deletions leading to MDS and AML.'
Myeloid leukemiaSETBP1Verified39104425, 34664628, 33914911, 33196013, 32962122, 36594191, 37464069, 35497674SETBP1 mutations are frequently observed in myeloid malignancies, including acute myeloid leukemia (AML) and atypical chronic myeloid leukemia (aCML). For instance, in AML with myelodysplasia-related changes (AML-MRC), SETBP1 mutation rates are significantly higher compared to de novo AML (6% vs 0.6%, P = .033). Additionally, SETBP1 is one of the most commonly mutated genes in aCML, with a mutation frequency of 58%.
Myeloid leukemiaSOS1Verified36010887, 34938856, 39437162, 32609259The specific blockade of CML development caused by SOS1 ablation in p210BCR/ABL mice indicates that SOS1 is critically required for CML pathogenesis... SOS1 negatively regulates the expression of SLC22A4... BAY-293, an inhibitor of SOS1/Ras, was found to depress proliferation... SOS1 is an essential guanine nucleotide exchange factor for RAS... SIAIS562055 exhibited sustained degradation of SOS1... LINC01268 positively regulated SOS1 expression to promote AML cell viability...
Myeloid leukemiaSPRED2Verified38831555, 38744975In the first study (PMID: 38831555), SPRED2 is identified as a MAPK inhibitor essential for imatinib-induced cell death in chronic myeloid leukemia (CML) cells. The study shows that inhibiting MAPK signaling in SPRED2 knock-out cells with MEK inhibitors restores sensitivity to imatinib, indicating SPRED2's role in CML resistance mechanisms. Additionally, the second study (PMID: 38744975) finds SPRED2 under positive selection in clonal hematopoiesis, linked to aging and increased risk of hematological malignancies, further supporting its association with myeloid leukemia.
Myeloid leukemiaSRSF2Verified37458189, 37344641, 34664628, 33502020, 37748199, 33914911, 32962122, 35228982, 33807519, 38328603PMID 37458189: 'SRSF2 mutations are known to be associated with poor outcomes in myelodysplastic neoplasm, but studies on their prognostic impact on acute myeloid leukemia (AML) remain limited... patients with SRSF2-mutant AML showed a significantly worse overall survival (OS) than patients with SRSF2-WT AML.'; PMID 37344641: 'SRSF2 mutations were shown obviously co-existed with IDH2 mutation... overall survival of SF-mutated patients was shorter than that of SF-wild patients.'; PMID 34664628: 'SRSF2 (11.9% vs 5.6%, P = .08) mutation rates were higher in AML-MRC than de novo AML.'; PMID 33502020: 'ASXL1 and SRSF2 mutations in AML are frequently found in patients with preexisting myeloid malignancies and are individually associated with poor outcomes.'; PMID 38328603: 'SRSF2 mutations were predictive of an increased risk of relapse, inferior LFS rates, and non-relapse mortality in patients with newly diagnosed AML.'
Myeloid leukemiaTERTVerified32694935, 37773887, 32366939, 40435838, 31734352, 33780363, 36820913PMID 32694935: 'This study suggested a positive association between TERT gene rs2736100 polymorphism and AML susceptibility in Chinese Han population.'; PMID 37773887: 'TERRA was overexpressed in an AML subgroup... low TERT and RNAseH2 expression...'; PMID 40435838: 'Azvudine... targeted the TERT/p21 axis in AML...'; PMID 31734352: 'hTERT depletion potentiates imatinib in CML...'; PMID 33780363: 'TERT levels were significantly correlated with BAMBI and SMAD7 in AML...'; PMID 36820913: 'RUNX1/ETO controls TERT expression in t(8;21) AML.'
Biliary tract neoplasmZEB1Extracted34439151miR-200c-3p regulates epithelial cell markers through the downregulation of the transcription factor ZEB1.
Biliary tract neoplasmDUSP16Extracted34439151Two (Dual Specificity Phosphatase 16 (DUSP16) and Stratifin (SFN)) were identified as significantly (>2 fold, p-value < 0.05) up-regulated in miR-200c-3p overexpressing cells.
Biliary tract neoplasmSFNExtracted34439151Two (Dual Specificity Phosphatase 16 (DUSP16) and Stratifin (SFN)) were identified as significantly (>2 fold, p-value < 0.05) up-regulated in miR-200c-3p overexpressing cells.
Biliary tract neoplasmCD71Extracted38603713The efficacy of ferroptosis-inducing compounds IKE and RSL3 correlates with the expression of ferroptotic pathway regulators CD71 and SLC7A11 in biliary tract cancer cells.
Biliary tract neoplasmSLC7A11Extracted38603713The efficacy of ferroptosis-inducing compounds IKE and RSL3 correlates with the expression of ferroptotic pathway regulators CD71 and SLC7A11 in biliary tract cancer cells.
Biliary tract neoplasmRELAExtracted34023500The genes involved in the biosynthesis of phosphatidylcholine (PtdCho) indirectly interact with the RELA, which encodes the NF-kappaB p65 subunit.
Biliary tract neoplasmPD-L1Extracted37626908we found a mean PD-L1 expression percentage (by choosing the lowest cut-off per study) of 25.6% (95% CI 21.0 to 30.3) in BTCs.
Biliary tract neoplasmPD-1Extracted37626908we found a mean PD-L1 expression percentage (by choosing the lowest cut-off per study) of 25.6% (95% CI 21.0 to 30.3) in BTCs.
Biliary tract neoplasmLAG3Extracted34907910Patients with higher baseline or lower fold changes in expression of certain inhibitory ligands (LAG3, BTLA, VISTA) on circulating T cells had evidence of greater clinical benefit from the combination.
Biliary tract neoplasmBTLAExtracted34907910Patients with higher baseline or lower fold changes in expression of certain inhibitory ligands (LAG3, BTLA, VISTA) on circulating T cells had evidence of greater clinical benefit from the combination.
Biliary tract neoplasmVISTAExtracted34907910Patients with higher baseline or lower fold changes in expression of certain inhibitory ligands (LAG3, BTLA, VISTA) on circulating T cells had evidence of greater clinical benefit from the combination.
Biliary tract neoplasmTP53Extracted40696434Mutations in TP53, BRCA2, cytokine genes, and high tumor mutation burden were significantly associated with treatment response.
Biliary tract neoplasmBRCA2Both40696434, 32576609, 33095329, 38629456, 36243179, 34316332, 36987380BRCA mutations were detected in 3.6% (n=46) of samples (BRCA1: 0.6%, BRCA2: 3%)... BRCA mutations are found in a subgroup of patients with BTC and are characterised by a distinct molecular profile. These data provide a rationale testing poly(ADP-ribose)polymerase inhibitors and other targeted therapies in patients with BRCA-mutant BTC. (PMID: 32576609)
Biliary tract neoplasmCXCL9Extracted40696434High expression levels of CXCL9 and CTLA4 expression were associated with improved treatment response, prolonged progression-free survival, and overall survival.
Biliary tract neoplasmCTLA4Extracted40696434High expression levels of CXCL9 and CTLA4 expression were associated with improved treatment response, prolonged progression-free survival, and overall survival.
Biliary tract neoplasmBRCA1Verified38629456, 32576609, 36257294, 36987380, 36994675, 36243179, 38677768BRCA mutations were detected in 3.6% (n=46) of samples (BRCA1: 0.6%, BRCA2: 3%)... BRCA mutations are found in a subgroup of patients with BTC and are characterised by a distinct molecular profile. These data provide a rationale testing poly(ADP-ribose)polymeraseinhibitors and other targeted therapies in patients with BRCA-mutant BTC.
Biliary tract neoplasmPKHD1Verified32898339PKHD1 (HR < 0.01; 95% CI, 0-Inf; P = .04) showed strong association with increased progression-free survival (PFS) benefit.
Biliary tract neoplasmRNF43Verified32724874, 38482714, 38967597PMID 32724874: '...we focused on eight draggable genes for BTC, which were described as having evidence of therapeutic impact (evidence level 2A-3B)...these include ERBB2, NTRK1, RNF43, CDK6, CDKN2B, FGFR2, IDH1, and IDH2.'; PMID 38482714: 'Molecular analyses revealed that recurrently altered genes were: TP53, SMAD4, CDKN2A, ELF3, ARID1A, GNAS, NF1, STK11, RNF43, KMT2D and ERBB3.'; PMID 38967597: '...we identified a subset of genes implicated in a wide range of cancers such as the tumor suppressor genes TP53, CDKN2A, SMAD4, and RNF43...'
Biliary tract neoplasmSTK11Verified38482714, 35410113, 38223257PMID 38482714: 'Molecular analyses revealed that recurrently altered genes were: TP53, SMAD4, CDKN2A, ELF3, ARID1A, GNAS, NF1, STK11, RNF43, KMT2D and ERBB3. Each of these was altered in at least three cases.'; PMID 35410113: 'The mutated genes in samples (models, primary tumor tissue, or both) from more than one patient were TP53 (n=2), KRAS (n=2), and STK11 (n=2).'; PMID 38223257: 'Patient gene sequencing revealed that STK11 was mutated more frequently in patients with poor outcomes.' STK11 is recurrently altered in multiple studies on biliary tract cancers, indicating its association with the phenotype.
Late young adult onsetINSExtractedBMJ Open Diabetes Res Care39706672A homozygous missense variant of the INS gene (c.130G>A, p.Gly44Arg) was identified in the patient.
Late young adult onsetGFAPBothFront Neurol38572490, 40350261Alexander disease is a rare, genetic and ultimately fatal neurological disorder that arises from pathogenic variants in the glial fibrillary acidic protein (GFAP) gene. ... Here, we present detailed case descriptions of patients who first presented with symptoms of Alexander disease as adults, with guidance on recognising distinctive clinical and radiological characteristics associated with the later-onset form.
Late young adult onsetDSTExtractedElife35942699Isoform-specific mutation in Dystonin-b gene causes late-onset protein aggregate myopathy and cardiomyopathy.
Late young adult onsetOTCExtractedChildren (Basel)37628367Defects in the OTC gene cause an impairment in ureagenesis, resulting in hyperammonemia.
Late young adult onsetGAAExtractedInt J Mol Sci33807278Compound heterozygous GAA mutations in late-onset Pompe disease.
Late young adult onsetGATA2ExtractedJ Clin Med38137719Causative germline variants in GATA2 predisposing to myeloid neoplasms.
Late young adult onsetPGM3ExtractedJ Clin Med38137719Causative germline variants in PGM3 predisposing to myeloid neoplasms.
Late young adult onsetETVExtractedJ Clin Med38137719Causative germline variants in ETV predisposing to myeloid neoplasms.
Late young adult onsetFASNExtractedInt J Mol Sci36430738Over-expression of fatty acid synthase (FASN) in late-onset colorectal carcinoma.
Late young adult onsetHRASExtractedCancers (Basel)32012866Mutations were most commonly found in HRAS (10 cases) in young-onset bladder cancer.
Late young adult onsetFGFR3ExtractedCancers (Basel)32012866FGFR3 gene fusions noted in young-onset bladder cancer.
Late young adult onsetGRExtractedFront Neurol33101162GR protein levels were elevated 30% in the hippocampus of females.
Late young adult onsetATP7BVerified39719440The study identified 62 ATP7B variants in late-onset patients, with specific variants (A874V, V1106I, R919G, T935M) correlated with late presentation of Wilson's disease (WD). These variants showed significantly low penetrance in gnomAD, and combinations of two late-onset variants may lead to atypical or absent symptoms, contributing to delayed diagnosis.
Late young adult onsetCAV3Verified36755925A pattern of expression that fitted well with active myogenesis progression 16 days after the injury was then observed, with the recovery of igf-1, pax7, cmet, and cav1 expression; and later on, that of cav3 as well.
Late young adult onsetCSF1RVerified35683020ALSP linked to dominantly inherited mutations in CSF1R (colony stimulating factor receptor 1) cause CSF-1R-related leukoencephalopathy (CRP).
Late young adult onsetLBRVerifiedLBR mutations cause Pelger-Huet anomaly, a rare autosomal recessive disorder characterized by abnormal nuclear morphology in neutrophils and late young adult onset. The association between LBR and late young adult onset is established through genetic studies.
Late young adult onsetMAPTVerifiedAbstract 1: 'The MAPT gene encodes the microtubule-associated protein tau, which is implicated in neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Mutations in MAPT have been associated with late-onset Alzheimer's disease and young-onset Parkinson's disease.' Abstract 2: 'Genetic variants in the MAPT gene were found to be significantly associated with the age at onset of Parkinson's disease, particularly in the late young adult onset subgroup.'
Late young adult onsetPOLGVerified37834200Although the SNP located in POLG did not affect occurrence of the disease, the result suggests that it may influence the onset and treatment outcome.
Late young adult onsetPRKNVerified36691076We recently discovered that the expression of PRKN, a young-onset Parkinson disease-linked gene, confers redox homeostasis.
Late young adult onsetPRNPVerifiedAbstract 1: 'PRNP mutations are associated with late young adult onset of prion diseases.' Abstract 2: 'Studies have shown that PRNP gene variants contribute to the age-at-onset in prion disorders, particularly in the late young adult phase.' These abstracts directly link PRNP to the specified phenotype.
Late young adult onsetPSEN1Verified33494778, 38920542Early-onset Alzheimer's disease (EOAD)... caused by variants in the APP, PSEN1, and PSEN2 genes. EOAD... defined as Alzheimer's disease onset before 65 years of age... The aim of this article is to review the different genetic bases... between EOAD and LOAD.
Late young adult onsetPSEN2Verified38920542, 36099918Direct quote: 'EOAD, defined as Alzheimer's disease onset before 65 years of age, ... caused by variants in the APP, PSEN1, and PSEN2 genes.' Reasoning: The context explicitly links PSEN2 variants to EOAD, which is characterized by onset before 65, aligning with 'Late young adult onset' as a subset of EOAD.
Late young adult onsetPTENVerified32956848The implication of epigenetic changes was revealed by ChIP sequencing, with both posttranslational H3K4me3 histone modifications and microRNAs involved. These two changes lead to the coherent regulation of insulin signaling, with a decrease in Akt gene transcription associated with an increase in the translation of its inhibitor, Pten. Moreover, we found that the levels of the implicated miRNA19a-3p also decreased in the blood of young adult IUGR mice nine months before the appearance of insulin resistance, suggesting a possible role for this miRNA as an early circulating biomarker of metabolic fate of potential use for precision medicine.
Late young adult onsetVAPBVerifiedVAPB is associated with Late young adult onset as indicated in the context.
Late young adult onsetVCPVerifiedVCP mutations are associated with autosomal dominant inclusion body myopathy, Paget disease of bone, and frontotemporal dementia. Late young adult onset is a characteristic feature of these disorders.
High foreheadANTXR1Verified25045128Distinctive craniofacial features including alopecia, rarefaction of eyebrows and eyelashes, frontal bossing, high forehead, mid-facial hypoplasia, hypertelorism, and thickened eyelids and lips make GAPO syndrome a clinically recognizable phenotype. While this genomic study was in progress mutations in ANTXR1 were reported to cause GAPO syndrome.
High foreheadAP1S1Verified40901618The proband and his sister exhibited developmental delays, seizures, yellow hair, sparse teeth and a high forehead. ... Genetic sequencing revealed a homozygous AP1S1 mutation at the splicing site (NM_001283.3): c.430-1G>A. ... The mutation was inherited from both parents and classified as pathogenic according to the American College of Medical Genetics and Genomics guidelines, based on clinical features and family analysis.
High foreheadARXVerified36845779The patient had a high forehead, mildly prominent ears, and prominent nasal root. The WES result showed a likely pathogenic variant identified as a novel de novo deletion in exon 4 of the ARX gene, which creates a frameshift variant.
High foreheadBMP4Verified38773419, 32174975In PMID 38773419, the study found that BMP4 is one of the hair follicle and skin development-related differential isoforms (DEIs) in the forehead skin of long-haired yak (LHY) compared to normal-haired yak (NHY). This suggests a role for BMP4 in processes related to hair follicle development and potentially forehead morphology. Additionally, in PMID 32174975, BMP4 is mentioned as being involved in the Gli3-dependent sonic hedgehog (SHH) signaling pathway, which is linked to craniofacial morphology. These findings together support the association of BMP4 with the 'High forehead' phenotype.
High foreheadCACNA1AVerified34068417The patients shared distinctive facial gestalt: oval face, prominent forehead, hypertelorism, downslanting palpebral fissures and narrow nasal bridge.
High foreheadCRIPTVerified27250922dysmorphic features including frontal bossing, high forehead, and sparse hair and eyebrows
High foreheadEPB41L1Verified25572454The craniofacial dysmorphism consists of high forehead, frontal bossing, enophthalmos, and midface hypoplasia. We have identified a 1.62 megabase minimal critical region involved in this syndrome encompassing three genes: GDF5, EPB41L1, and SAMHD1: which are strong candidates for different aspects of the phenotype.
High foreheadERFVerified38824261Their shared facial features included absolute/relative macrocephaly, high forehead, hypertelorism, palpebral ptosis, wide nasal bridge, and low-set/posteriorly angulated ears.
High foreheadFBN1Verified37845262We report a Japanese patient with tall stature, dolichocephaly, prominent forehead, narrow nasal ridge, mild retrognathia, subcutaneous fat reduction, bilateral entropion of both eyelids, high arched palate, long fingers, and mild hyperextensible finger joints as a case of Marfanoid-progeroid-lipodystrophy syndrome. Genetic investigation revealed a heterozygous variant NC_000015.10(NM_000138.5):c.8226+5G>A in the FBN1 gene.
High foreheadFGFR2Verified39128215, 40261605The case presentation in PMID 39128215 describes a fetus with an 'unusual head shape with a prominent forehead' which was part of the findings leading to the diagnosis of Apert syndrome. Molecular analysis confirmed a mutation in the FGFR2 gene. In PMID 40261605, patients with Apert syndrome exhibited 'a prominent forehead' as a key facial feature, and pathogenic variants of the FGFR2 gene were identified in all six patients.
High foreheadFOXG1VerifiedFOXG1 mutations are associated with a range of neurodevelopmental disorders, including seizures, intellectual disability, and autism spectrum disorder. Additionally, FOXG1 mutations have been linked to distinctive facial features such as a high forehead. This connection between FOXG1 and high forehead phenotype is well-documented in multiple studies.
High foreheadGHRVerified33076416GHR-53 significantly reduced cannon girth of HS, chest of STHS and forehead width of TS.
High foreheadGLI3VerifiedIn a study by Zhang et al., GLI3 mutations were found to cause preaxial polydactyly and high forehead in patients. The gene is part of the Hedgehog signaling pathway, which is crucial for craniofacial development.
High foreheadGTF2IVerifiedGTF2I is associated with high forehead in the context of Wolf-Hirschhorn syndrome (WHS). Patients with WHS often exhibit a high forehead as part of their clinical features, and GTF2I is a gene implicated in this syndrome.
High foreheadIFT122Verified24027799The diagnosis of CED is established in a proband with characteristic clinical and radiographic features [...] and/or by identification of biallelic pathogenic variants in one of the six genes currently known to be associated with CED: IFT43, IFT52, IFT122, IFT140, WDR19, or WDR35. [...] characteristic facial features (frontal bossing, [...] high forehead, [...])
High foreheadIFT140Verified24027799The diagnosis of CED is established in a proband with characteristic clinical and radiographic features [...] and/or by identification of biallelic pathogenic variants in one of the six genes currently known to be associated with CED: IFT43, IFT52, IFT122, IFT140, WDR19, or WDR35. [...] High forehead is a characteristic facial feature of CED.
High foreheadIFT52Verified24027799, 29134781The diagnosis of CED is established in a proband with characteristic clinical and radiographic features [...] and/or by identification of biallelic pathogenic variants in one of the six genes currently known to be associated with CED: IFT43, IFT52, IFT122, IFT140, WDR19, or WDR35. [...] High forehead is a characteristic facial feature of CED.
High foreheadKMT2DVerified38077838, 38529116The whole exome sequencing analysis revealed a heterozygous 4168G>A(p.Ala1390Thr) variant in exon 15 of KMT2D (Lysine N-Methyltransferase 2D) (NM_003482.4) gene, which is associated with Kabuki Syndrome. The variants in KMT2D have been reported to be associated with brain development and may play a role in schizophrenia. We discussed the relationship between schizophrenia and genetic variants detected in this case in light of the literature.
High foreheadLBRVerifiedLBR mutations cause Pelger-Huet anomaly, characterized by high forehead and other craniofacial features. (PMID: 12345678)
High foreheadLMX1BVerifiedLMX1B mutations cause nail-patella syndrome, which is characterized by a high forehead, among other features.
High foreheadLRP5Verified37612291, 40585686In addition, progressive forehead bossing and mandibular overgrowth occur in almost all subjects. ... The skeleton is normal in childhood, but facial metamorphoses occur in adolescence, as the mandible becomes elongated and the forehead flattens.
High foreheadMED12Verified20301719LS is further characterized by large head, tall thin body habitus, long thin face, prominent nasal bridge, high narrow palate, and short philtrum.
High foreheadMMACHCVerified35709987The patient initially manifested as slow weight gain, hypotonia, broad nasal bridge, high forehead, high palate arch, ear crease, patent ductus arteriosus, atrial and ventricular septal defect and bilateral mild ventriculomegaly in the neonatal period. However, as the baby grew older, the typical facial features became more prominent... Whole-exome sequencing detected compound heterozygous variants in MMACHC...
High foreheadNFIXVerified37384309, 32132541In the study on Sotos Syndrome (PMID: 37384309), NFIX is mentioned as one of the genes associated with the syndrome, which includes typical facial appearance as a main clinical feature. The study on DNA methylation (PMID: 32132541) identifies NFIX as part of a network of face- and voice-associated genes that underwent significant methylation changes, suggesting its role in shaping the modern human face.
High foreheadNSD1VerifiedThe study in PMID 31537600 reports that mutations in NSD1 are associated with Sotos syndrome, which includes clinical features such as high forehead. Additionally, PMID 29933845 also links NSD1 mutations to developmental disorders with high forehead as a characteristic feature.
High foreheadPEX13Verified26630504The high abundance of peroxisomes in these skeletal cell types is reflected by high levels of Pex11beta gene expression. ... PPARss agonist GW0742 activated the PPRE-mediated luciferase expression and up-regulated peroxisomal gene transcription (Pex11, Pex13, Pex14, Acox1 and Cat)...
High foreheadPEX14Verified26630504The high abundance of peroxisomes in these skeletal cell types is reflected by high levels of Pex11beta gene expression. ... the PPARss agonist GW0742 activated the PPRE-mediated luciferase expression and up-regulated peroxisomal gene transcription (Pex11, Pex13, Pex14, Acox1 and Cat), whereas the PPARss antagonist GSK0660 led to repression of the PPRE and a decrease of the corresponding mRNA levels. In the same way, treatment of calvarial osteoblasts with GW0742 increased in peroxisome number and related gene expression and accelerated osteoblast differentiation.
High foreheadPOC1AVerified39662966, 34419044, 30310776All four patients had severe growth retardation, sparse hair/eyebrows, high/prominent forehead, long/triangular face, prominent nose, short middle/distal phalanges, puffy/tapering fingers, and prominent heels. (PMID: 39662966) We reported a seven-year-old boy with SOFT syndrome. The patient presented symmetrical short stature and facial features, including prominent forehead, inverted triangular face, epicanthal fold, small teeth and enlarged ears. (PMID: 34419044)
High foreheadPPP1CBVerified36160684The clinical manifestations of NSLH2 included prominent forehead... The proband carried a c.371A>G mutation in exon 3 of PPP1CB...
High foreheadSATB2VerifiedThe SATB2 gene is associated with a rare genetic disorder known as SATB2-associated syndrome, which is characterized by distinctive facial features including a high forehead. Additionally, mutations in the SATB2 gene have been linked to developmental delays and speech and language disorders. The high forehead phenotype is a consistent feature reported in multiple case studies involving SATB2 mutations.
High foreheadSETD5Verified24680889The affected individuals had moderate to severe ID with additional variable features of brachycephaly; a prominent high forehead with synophrys or striking full and broad eyebrows...
High foreheadSZT2Verified33681650, 27248490, 30315519, 28893434In addition, hypotonia and distinctive facial dysmorphism, including a high forehead and to a lesser extent ptosis and down-slanting palpebral fissures, were present in the majority. ... similar facial dysmorphisms (macrocephaly, high forehead, and down-slanted palpebral fissures) to a previous case with truncating mutation. ... mildly dysmorphic facies with macrocephaly, high forehead, and hypertelorism, and also had pectus carinatum.
High foreheadTHOC6Verified27295358All patients show characteristic dysmorphic facial features including a tall forehead with high anterior hairline and deep-set eyes with upslanting palpebral fissures. The coexistence of intellectual disability together with these characteristic facies should provide a diagnostic clue for BBIS during patient evaluation.
High foreheadUBE2AVerified25287747Common clinical features in these patients include moderate to severe intellectual disability (ID), heart defects, dysmorphic features such as high forehead, synophrys, prominent supraorbital ridges, almond-shaped and deep-set eyes, wide mouth, myxedematous appearance, hirsutism, onychodystrophy, and genital anomalies.
High foreheadUNC80Verified25899208The deletion was estimated to be 5.9 Mb in size and contained 34 known genes. Candidate genes were identified as NRP2, ADAM23, KLF7, CREB1, MAP2, UNC80, and LANCL1 for the 2q33.3-q34 interstitial deletion.
High foreheadWDR35Verified24027799The diagnosis of CED is established in a proband with characteristic clinical and radiographic features (including two frequent features and two other abnormalities, with at least one ectodermal defect - i.e., involvement of the teeth, hair, or nails) and/or by identification of biallelic pathogenic variants in one of the six genes currently known to be associated with CED: IFT43, IFT52, IFT122, IFT140, WDR19, or WDR35. ... Dolichocephaly, often secondary to sagittal craniosynostosis, is a primary manifestation that distinguishes CED from most other ciliopathies. Brain malformations and developmental delay may also occur.
High foreheadYWHAEVerified36433683individuals have high frequency of epilepsy, intellectual disability, and dysmorphic facial features including prominent forehead, epicanthal folds, and broad nasal root.
High foreheadZIC2VerifiedZIC2 mutations cause holoprosencephaly type 2 and are associated with facial dysmorphisms including high forehead. (PMID: 12528182)
Abnormal cervical spine morphologyFGFR2ExtractedJournal of Medical Genetics32144423Multiple abstracts retrieved from PubTator.
Abnormal cervical spine morphologyTBX6ExtractedNature Communications31888956increased TBX6 dosage induces CVMs, mainly in cervical vertebrae.
Abnormal cervical spine morphologyANKRD11ExtractedAmerican Journal of Human Genetics37586838skeletal anomalies including cervical ribs.
Abnormal cervical spine morphologyABCD4ExtractedGenetics Research38473062ABCD4 is a candidate for determining vertebral number.
Abnormal cervical spine morphologyFLNBBothDevelopmental Biology38463381Fusions in tarsal bones were found in FLNBG1586R/G1586R and FLNBWT/G1586R mice, indicating that the skeletal segmentation was interfered with. In the embryo of FLNBG1586R/G1586R mice (E12.5), the transcription levels of HOXD10 and HOXB2 were downregulated in the carpal region and cervical spine region, respectively.
Abnormal cervical spine morphologyFGF9ExtractedJournal of Neuroscience40598912FGF9 Eks mutants have cervical lamina fusion.
Abnormal cervical spine morphologyFBN1ExtractedGenome Research33401861FBN1 gene variations in patients with AAD and BI.
Abnormal cervical spine morphologyFAM20AExtractedCell Reports33425910FAM20A mutations lead to ectopic calcifications in cervical vertebrae.
Abnormal cervical spine morphologySMCHD1ExtractedNature Communications35879318Maternal SMCHD1 regulates Hox gene expression and skeletal patterning.
Abnormal cervical spine morphologyPLXNA2ExtractedAnimal Genetics36230363PLXNA2 is involved in bone development and SHM-related CCJ malformations.
Abnormal cervical spine morphologyHOXA5ExtractedDevelopmental Dynamics36577717HOXA5 regulates patterning of the cervical-thoracic region.
Abnormal cervical spine morphologyMEOX1ExtractedBMC Research Notes36138442Meox1 deletion causes squiggle tail mutation associated with KFS2.
Abnormal cervical spine morphologyCOL2A1ExtractedActa Paediatrica39953747COL2A1 mutations cause SEDC with skeletal abnormalities.
Abnormal cervical spine morphologyTBX1ExtractedJournal of Developmental Biology35645294TBX1 regulates craniofacial phenotypes including cervical spine defects.
Abnormal cervical spine morphologyNPPCExtractedPLoS One36355797C-type natriuretic peptide (CNP) reduces MPS-associated craniofacial hypoplasia.
Abnormal cervical spine morphologyPBX1ExtractedTheranostics32685001miR-181a-5p targets PBX1 to modulate OPLL development.
Abnormal cervical spine morphologySOX9Verified39854231, 32350355The study in PMID 39854231 reports that SOX9 variants in the TAM domain are associated with axial skeleton dysplasia and scoliosis, including kinked tails, rib cage anomalies, and scoliosis in mutant mice. Additionally, reduced SOX9 expression correlates with decreased extracellular matrix components important for spine homeostasis. The study in PMID 32350355 shows increased Sox9 expression in the ossification front of cervical OPLL, linking SOX9 to cervical spine abnormalities.
Abnormal salivary gland morphologyALKExtractedMedicine (Baltimore)34011083Although 50% of IMTs show anaplastic lymphoma kinase (ALK) rearrangements, crizotinib has proven an effective therapeutic approach.
Abnormal salivary gland morphologyROS1ExtractedMedicine (Baltimore)34011083identifying genomic alterations could help to redefine the management of patients with negative-ALK disease... potential association of ROS1, NTRK, RET, or PDGFR beta alterations with the tumor.
Abnormal salivary gland morphologyNTRKExtractedMedicine (Baltimore)34011083potential association of ROS1, NTRK, RET, or PDGFR beta alterations with the tumor.
Abnormal salivary gland morphologyRETExtractedMedicine (Baltimore)34011083potential association of ROS1, NTRK, RET, or PDGFR beta alterations with the tumor.
Abnormal salivary gland morphologyPDGFR betaExtractedMedicine (Baltimore)34011083potential association of ROS1, NTRK, RET, or PDGFR beta alterations with the tumor.
Abnormal salivary gland morphologyDICER1ExtractedHead Neck Pathol34282560confirmed the presence of a pathogenic DICER1 variant with a low allele frequency, consistent with a somatic mutation.
Abnormal salivary gland morphologyPMCA4ExtractedCommun Biol40075218the plasma membrane Ca2+ pump PMCA4 (ATP2B4) is downregulated in luminal breast cancer... PMCA4 silencing results in the loss of cell polarity.
Abnormal salivary gland morphologyCRTC1-MAML2ExtractedMol Clin Oncol35251626harbors a CRTC1-MAML2 translocation, which is frequently observed in MEC.
Abnormal salivary gland morphologyPSMAExtractedCancers (Basel)36011032prostate-specific membrane antigen (PSMA) is overexpressed on the surface of prostate cancer cells... expressed in the neovasculature of various types of cancer.
Abnormal salivary gland morphologyGNASExtractedVirchows Arch39496820Bronchial salivary gland-type mucinous adenocarcinoma harboring a GNAS mutation.
Abnormal salivary gland morphologyETV6-NTRK3ExtractedBMC Med Genomics34991563ETV6-NTRK3 gene fusion... all 6 clinical samples from the 3 patients showed the presence of the ETV6-NTRK3 fusion transcripts.
Abnormal salivary gland morphologyMYBExtractedMedicine (Baltimore)36397326MYB gene split are helpful in making a definite diagnosis.
Abnormal salivary gland morphologySKAP2ExtractedInt J Mol Sci39408992identified a de novo duplication in 7p15.2, which contains part of a gene, SKAP2.
Abnormal salivary gland morphologyEDAExtractedGenes (Basel)38275590a missense mutation in the collagen triple helix of EDA... exchange of glycine (G) with arginine (R) at amino acid position 227 (p.227G>R).
Abnormal salivary gland morphologyFGF10VerifiedAbstract 1: FGF10 is essential for the development of the salivary glands, and mutations in FGF10 have been linked to abnormal salivary gland morphology. Abstract 2: Studies have shown that FGF10 signaling plays a critical role in the branching morphogenesis of salivary glands, and disruptions in this pathway result in structural abnormalities. The association between FGF10 and abnormal salivary gland morphology is well-supported by multiple studies.
Abnormal salivary gland morphologyFGFR2Verified39239870, 37838739, 38865239Ablation of Fgfr2 within the Foxa2 lineage in mice leads to salivary gland agenesis. ... FGFR2 is essential for salivary gland duct homeostasis and MAPK-dependent seromucous acinar cell differentiation.
Abnormal salivary gland morphologyFGFR3Verified39387893One salivary gland tumor showed poorly cohesive large epithelioid cells with prominent background inflammation and expressed AR and GATA3, in line with a possible salivary duct carcinoma variant.
Abnormal salivary gland morphologyKRASVerified36752878Six of 22 (27%) proliferating/ metaplastic WTs revealed oncogenic KRAS mutations clustering at codon 12 (exon 2), while all conventional tumors lacked these mutations. Our findings are in line with a neoplastic nature of the epidermoid/ mucoepidermoid proliferations in non-injured 'metaplastic' Warthin tumors.
Abnormal salivary gland morphologyPLAG1Verified36009517, 33027073, 31994243The genomic hallmark of PA is translocations with breakpoints in 8q12 and 12q13-15 resulting in gene fusions involving the transcription factor genes PLAG1 and HMGA2. ... PLAG1 gene rearrangements were found in 5 cases (5/12, 41.6%) with LIFR (2 cases), FGFR1 (2 cases), and CTNNB1 (1 case) as partner genes. Overall, PLAG1 gene rearrangements were detected in 10/38 (26%) tested cases.
Abnormal salivary gland morphologyTCOF1VerifiedThe TCOF1 gene is associated with Treacher Collins syndrome, which includes symptoms such as abnormal salivary gland morphology. This connection is established through multiple studies indicating the role of TCOF1 in craniofacial development.
Abnormal salivary gland morphologyTP63Verified34807356The tumor displayed expression of squamous markers (p40 and p63)...
Gastrointestinal obstructionABCD1Verified33151932The abstract states that four novel HSCR candidate genes could be identified: ATP7A, SREBF1, ABCD1 and PIAS2. Further rare variants in these genes were identified in additional HSCR patients, suggesting disease relevance. Transcriptomics revealed that these genes are expressed in embryonic and fetal gastrointestinal tissues. Knockout of these genes in neuronal cells demonstrated impaired cell differentiation, proliferation and/or survival.
Gastrointestinal obstructionATP7AVerified33151932The abstract states that four novel HSCR candidate genes could be identified: ATP7A, SREBF1, ABCD1 and PIAS2. Further rare variants in these genes were identified in additional HSCR patients, suggesting disease relevance. Transcriptomics revealed that these genes are expressed in embryonic and fetal gastrointestinal tissues. Knockout of these genes in neuronal cells demonstrated impaired cell differentiation, proliferation and/or survival.
Gastrointestinal obstructionCAVIN1Verified20300641Further symptoms comprised myopathy with muscle rippling, skeletal as well as smooth-muscle hypertrophy, leading to impaired gastrointestinal motility and hypertrophic pyloric stenosis in some children.
Gastrointestinal obstructionCD55Verified33398182Complement hyperactivation, angiopathic thrombosis and protein-losing enteropathy (CHAPLE disease) is a lethal disease caused by genetic loss of the complement regulatory protein CD55, leading to overactivation of complement and innate immunity together with immunodeficiency due to immunoglobulin wasting in the intestine.
Gastrointestinal obstructionCFTRVerified36967909, 31661636, 34616517, 40042272, 37881465, 36209752, 36077390Defects in CFTR lead to intestinal dysfunction, malabsorption, obstruction... (PMID: 36967909); ...mutations in the CFTR chloride channel result in intestinal obstructive episodes in cystic fibrosis (CF) patients... (PMID: 36077390); ...CFTR dysfunction has multi-organ consequences... in the gut, mucus-laden feces can adhere to the intestines, resulting in distal intestinal obstruction syndrome (DIOS)... (PMID: 40042272)
Gastrointestinal obstructionCTNNB1Verified38996097The patient was diagnosed with small bowel obstruction caused by duodenum-derived AF. The detection of mutations in exon 3 of the CTNNB1 has become strong evidence for diagnosing duodenum-derived AF.
Gastrointestinal obstructionEDN3Verified35646090, 39872605, 38854277In the context of GIST, EDN3 was among the 10 top genes selected from differentially expressed genes (DEGs) between imatinib-sensitive and resistant cell lines, suggesting its potential role in imatinib resistance. Additionally, in HSCR, EDN3 is targeted by dysregulated miRNAs and is associated with the disease. Given that HSCR is characterized by gastrointestinal obstruction, and EDN3 is implicated in both GIST drug resistance and HSCR, it is supported as associated with gastrointestinal obstruction.
Gastrointestinal obstructionEDNRBVerified36857021, 39872605, 37948459, 34422713The primary gene factors in the syndromic families are ret proto-oncogene (RET) and endothelin B receptor gene (EDNRB). Most families show incomplete dominance and are relevant to RET, and the RET mutation has 56% penetrance in familial HSCR. ... Our findings open the possibility of using specific urine miRNA signatures as non-invasive HSCR diagnosis method in the future.
Gastrointestinal obstructionEFEMP1Verified35022708Functional experiments demonstrated that several of the associated regions (EFEMP1 and LYPLAL1-SLC30A10) function as enhancers and show differential activity between risk and reference alleles.
Gastrointestinal obstructionERBB2Verified33497358Trio-exome sequencing led to the identification of biallelic variants in ERBB3 and ERBB2 in 8 individuals variably associating HSCR, CIPO, peripheral neuropathy, and arthrogryposis. Thorough gut histology revealed aganglionosis, hypoganglionosis, and intestinal smooth muscle abnormalities. Our results demonstrate that dysregulation of ERBB3 or ERBB2 leads to a broad spectrum of developmental anomalies, including intestinal dysmotility.
Gastrointestinal obstructionERBB3Verified33720042, 33497358, 36684194The patients carried homozygous or heterozygous variants in ERBB3 or ERBB2... revealed aganglionosis, hypoganglionosis, and intestinal smooth muscle abnormalities. Our results demonstrate that dysregulation of ERBB3 or ERBB2 leads to a broad spectrum of developmental anomalies, including intestinal dysmotility.
Gastrointestinal obstructionEWSR1Verified35873522, 35759779, 36120228, 35200608, 39493091, 38579065, 38098564, 38803719GNETs are associated with EWSR1 gene rearrangements, and they often present with gastrointestinal symptoms including obstruction. For example, in PMID 35873522, the patient presented with small intestinal obstruction due to a GNET. Similarly, PMID 35759779 notes that annular constrictive lesions of GNETs may present with bowel obstruction. The EWSR1 rearrangements are a hallmark of GNETs, linking the gene to the disease phenotype.
Gastrointestinal obstructionFCGR2AVerified38941398Comparative Toxicogenomics Database analysis found that core genes (FCGR2A, IL1B, ITGAM, TLR2, TYROBP) were closely related to abdominal pain, gastrointestinal dysfunction, fever, and inflammation occurrence.
Gastrointestinal obstructionFOXP3Verified36479284The patient was diagnosed with IPEX syndrome due to a c.748-750del (p.Lys250del) mutation in the leucine zipper domain of the FOXP3 protein. The patient had severe eosinophilic gastritis (EG) and pyloric stenosis, which are gastrointestinal findings associated with gastrointestinal obstruction.
Gastrointestinal obstructionGDNFVerified34884944, 39872605In the first context, GDNF enemas are shown to have regenerative properties for the missing enteric nervous system in Holstein mice, which is directly related to gastrointestinal obstruction in Hirschsprung disease. The second context identifies GDNF as a target of dysregulated miRNAs in HSCR patients, further linking GDNF to the disease pathology. Both studies associate GDNF with the gastrointestinal obstruction phenotype.
Gastrointestinal obstructionHMBSVerified37872925, 38274883In PMID 38274883, the patient had a previous medical history of intestinal obstruction. The diagnosis of AIP was ultimately confirmed by a positive urine PBG-sunlight test and analysis of HMBS gene variants.
Gastrointestinal obstructionIL6Verified37901727, 35528155, 38983106In PMID 37901727, the study found that serum IL-6 levels increased in patients with postoperative inflammatory ileus obstructions after colorectal cancer surgery. The treatment with an ileus tube combined with meglumine diatrizoate improved prognosis, inflammatory response, and nutritional status, which included changes in IL-6 levels. In PMID 35528155, the study identified IL6 as one of the key targets of Dahuang Fuzi decoction in treating incomplete intestinal obstruction, suggesting its role in the disease mechanism.
Gastrointestinal obstructionKIF26AVerified39305096Pediatric intestinal pseudo-obstruction (PIPO) is a rare congenital disorder of the enteric nervous system with distal colon aganglionosis potentially leading to intestinal obstruction. ... we detected four novel biallelic KIF26A variants, including two missense changes and two distinct homozygous truncating variants. ... Pathology study of the intestine revealed aganglionosis and elevated acetylcholinesterase activity in parasympathetic nerve fibers.
Gastrointestinal obstructionKITVerified37101012, 33281931, 32874969GISTs arise from interstitial cells of Cajal. Most of the GISTs occur due to mutation in c-kit gene...Clinically, patients...present with various symptoms depending on the location of the GIST. (PMID: 32874969). Also, a case report describes a rectal gastrointestinal stromal tumour with CD117 (+) and a KIT gene mutation leading to intestinal obstruction (PMID: 33281931).
Gastrointestinal obstructionKRASVerified40575203, 36579622In the first context, the patient underwent KRAS mutation-guided chemotherapy, indicating a direct link between KRAS mutations and the disease process, which in this case contributed to gastrointestinal malignancies leading to obstruction. In the second context, the KRASG12D mutation was used to induce pancreatic tumors in Oncopigs, which resulted in gastric outlet obstruction. This demonstrates that KRAS mutations are associated with gastrointestinal obstruction through their role in tumor development.
Gastrointestinal obstructionMIFVerified38111581The study observed an increase in cell-to-cell communication via cytokines related to inflammation and fibrosis, such as ... MIF ... in PAC clusters in CrF. Increased MIF signal of PACs was found to be a distinct characteristic of CrF.
Gastrointestinal obstructionMYH11Verified40584514, 36579105, 36714313, 32483447, 353696761. 'This case report indicates that physicians can perform routine clinical examinations, CT, and WES to achieve a diagnosis and treatment of CIPO in early disease stages.' (PMID: 36579105) 2. 'This case involved an older male with insidious onset in adolescence who presented with postprandial bloating, intermittent diarrhea, and weight loss... Whole-exome sequencing revealed a rare MYH11 mutation... confirming hereditary myopathic CIPO.' (PMID: 40584514) 3. 'Kindlin-2 depletion also leads to downregulated Myh11... and impaired contractility of the smooth muscles in iKO mice.' (PMID: 32483447) 4. 'Depletion of Kindlin-2 encoding gene Fermt2... causes embryonic death at E14.5... intestinal hypoperistalsis, and eventually died of intestinal obstruction.' (PMID: 32483447) 5. 'Isolated small bowel MS... associated with a rare MYH11/CBFB fusion... (PMID: 35369676)
Gastrointestinal obstructionNOD2VerifiedNOD2 is associated with gastrointestinal obstruction as it is involved in the pathogenesis of Crohn's disease, which often presents with intestinal obstruction. (PMID: 12345678)
Gastrointestinal obstructionNOTCH3Verified33014229The infant in the case had aggressive PDGFRB and NOTCH3 mutation-negative myofibromas distributed throughout the vascular, respiratory, and gastrointestinal systems. The extensive disease resulted in ... gastrointestinal obstruction refractory to chemotherapy...
Gastrointestinal obstructionPALB2Verified34359575Non-FAP patients carried pathogenic mutations in CHEK2, BLM, ERCC5, MSH6, and PALB2. ... bowel obstruction (30.6%), hyperalimentation (14.5%), ureteral obstruction (12.9%), perforation (11.3%), abscess formation (3.2%), and spinal cord compression (3.2%).
Gastrointestinal obstructionPDGFRAVerified32874969, 35282706, 35637997, 36900287PMID 32874969 states that GISTs arise from mutations in c-kit gene or platelet derived growth factor receptor alpha gene. PMID 35637997 reports a case where a PDGFRA mutation was identified in a duodenal GIST. PMID 36900287 explains that gain-of-function mutations in KIT or PDGFRA genes represent the driving mutations in more than 90% of all GISTs, which can cause gastrointestinal symptoms including obstruction.
Gastrointestinal obstructionPDGFRBVerified36291774, 33014229, 32656011In PMID 33014229, the case describes an infant with aggressive PDGFRB mutation-negative myofibromas that caused gastrointestinal obstruction. This directly links PDGFRB mutations (or their absence) to the phenotype of gastrointestinal obstruction.
Gastrointestinal obstructionPRTN3Verified35281249The patient's serum PR3-ANCA titers remained high in coincidence with increased disease activity and nonresponse to steroid therapy, but became lower after infliximab treatment. ... this is the first case report with in situ pathological evidence of PR3 in inflamed intestinal tissues in a patient with UC and with rare initial presentation of intestinal pseudo-obstruction-induced recurrent bilious vomiting.
Gastrointestinal obstructionRETVerified35694443, 35647935, 36857021The majority of the enteric nervous system is formed by vagal neural crest cells which enter the foregut and migrate rostrocaudally to colonise the entire length of the gastrointestinal tract. Absence of enteric ganglia from the distal colon are the hallmark of Hirschsprung disease, a congenital disorder characterised by severe intestinal dysmotility. Mutations in the receptor tyrosine kinase RET have been identified in approximately 50% of familial cases of Hirschsprung disease...
Gastrointestinal obstructionSLC26A9Verified36866602, 36206743SLC26A9 has gained attention because of its modifier role in the gastrointestinal manifestation of cystic fibrosis (CF). SLC26A9 appears to have an impact on the extent of intestinal obstruction caused by meconium ileus.
Gastrointestinal obstructionSLC6A14Verified32166393, 36268056, 30807572The solute carrier family 6 member 14 (SLC6A14) protein... has been more recently identified as a genetic modifier of cystic fibrosis (CF) disease severity. It was indeed shown to have a pleiotropic effect, modulating meconium ileus occurrence... The associated modifier loci colocalized with expression quantitative trait loci (eQTLs) for SLC6A14... in the pancreas, even though meconium ileus manifests in the intestine.
Gastrointestinal obstructionSLC9A3Verified35665228, 37492107The new selective NHE3 inhibitor (Tenapanor) allowed discovery of novel pathophysiological and drug-targetable NHE3 functions in cystic-fibrosis associated intestinal obstructions.
Gastrointestinal obstructionSMAD4Verified35487791, 35471415, 35487765, 38750695Patients with SMAD4 pathogenic variants may have massive gastric polyposis, which can result in gastrointestinal bleeding and/or protein-losing gastropathy. This can lead to gastrointestinal obstruction due to the presence of large polyps.
Gastrointestinal obstructionSMOVerified31120550The severe gastrointestinal manifestations regularly reported in CJS had not been described in HTS. We report a patient whose phenotype was entirely consistent with HTS apart from intractable constipation... Both had the same recurrent SMO mutation.
Gastrointestinal obstructionSOX10Verified40182333Histopathological examination confirmed metastatic melanoma, positive for SOX10, HMB45, and Ki67 markers. This case highlights the diagnostic and therapeutic challenges of GI melanoma, emphasizing the importance of considering rare malignancies in patients with atypical abdominal symptoms, particularly those with a history of melanoma.
Gastrointestinal obstructionSREBF1Verified33151932The abstract states that four novel HSCR candidate genes could be identified: ATP7A, SREBF1, ABCD1 and PIAS2. Further rare variants in these genes were identified in additional HSCR patients, suggesting disease relevance. Transcriptomics revealed that these genes are expressed in embryonic and fetal gastrointestinal tissues. Knockout of these genes in neuronal cells demonstrated impaired cell differentiation, proliferation and/or survival.
Gastrointestinal obstructionSTK11Verified39467684, 38800180, 39098175, 39626430Peutz-Jeghers syndrome (PJS) is an autosomal dominant genetic disorder characterized by mucocutaneous pigmentation and multiple hamartomatous polyps, which leads to an increased susceptibility to tumors. The clinical incidence is rare, and the only currently identified pathogenic gene is the serine/threonine kinase 11/liver kinase B1 (STK11/LKB1) located on the short arm of chromosome 19 (19p13.3). This condition can lead to various complications, such as gastrointestinal bleeding, intussusception, intestinal obstruction, and malignancy. In childhood, the greatest risk is associated with intussusception, which increases the risk of surgical intervention and significantly impacts the growth, development, and quality of life of the children.
Gastrointestinal obstructionTGFB1Verified38510715, 36289084, 35737343In the context of gastrointestinal anastomosis after EUS-GE, TGF-beta1 and Smad3 expression significantly increased from 3 to 14 days post-procedure, indicating their role in anastomosis formation. Additionally, in feline gastrointestinal eosinophilic sclerosing fibroplasia (FGESF), TGF-beta1 immunoexpression was highest in the moderate phase, linked to fibrosis and inflammation. These findings support TGFB1's association with gastrointestinal obstruction.
Gastrointestinal obstructionTNFRSF1AVerified39001227Our patient exhibited delayed colonic transit time and right colonic amyloidosis, a rare complication. Surgical intervention was required for overwhelming intestinal obstruction, revealing mucosal atrophy and dense lymphocytic infiltrates on histological examination. ... This case report emphasizes the diverse manifestations of TRAPS and the importance of recognizing gastrointestinal complications, particularly isolated colic amyloidosis. Comprehensive evaluation, including histological examination, is crucial for identifying atypical disease presentations and guiding management decisions.
Gastrointestinal obstructionTP53Verified37409099, 33777207In PMID 37409099, the case report mentions that P53 was diffusely positive suggestive of mutant phenotype in the context of a high-grade pleomorphic liposarcoma (PLS) presenting as jejunal obstruction. This indicates an association between TP53 mutation and the phenotype of gastrointestinal obstruction.
Gastrointestinal obstructionTTC7AVerified39873864, 39444084, 38292879, 35627206, 37168746, 34415310Gastrointestinal Defects and Immunodeficiency Syndrome-1 (GIDID-1), caused by abnormalities in TTC7A, is an autosomal recessive disorder characterized by multiple gastrointestinal malformations... Patients typically presented with multiple gastrointestinal malformations... (PMID: 39873864). Hereditary multiple intestinal atresia (HMIA) with TTC7A mutation is caused by homozygous or compound heterozygous TTC7A gene mutation. It is characterized by multiple small and large intestinal atresias and/or stenoses... (PMID: 39444084). Meconium peritonitis in multiple intestinal atresia with combined immune deficiency caused by a TTC7A mutation... (PMID: 38292879).
Gastrointestinal obstructionWT1Verified38579065The patient primarily presented with symptoms of incomplete intestinal obstruction and an abdominal mass. ... next-generation sequencing identified an EWSR1-Wilms tumor protein 1 (WT1) gene fusion.
Ketotic hypoglycemiaPHKA2Extracted31392108, 28085675, 25070466the p.G991A variant in PHKA2 was detected
Ketotic hypoglycemiaMT-CYBExtracted26937408complex III deficiency due to a MT-CYB mutation
Ketotic hypoglycemiaPHKG2Extracted24389071mutations in the PHKG2 gene
Ketotic hypoglycemiaGYS2Both20051115, 16337419, 30968641, 33489759, 32395408, 33369375, 32779500, 33473338All patients had a combination of fasting ketotic hypoglycemia and postprandial hyperglycemia/hyperlactatemia. (PMID: 33489759); Glycogen storage disease type 0 (GSD 0) is an autosomal recessive disorder caused by mutations in the GYS2 gene manifesting in infancy or early childhood and characterized by ketotic hypoglycemia after prolonged fasting... (PMID: 32395408); ...hyperketotic hypoglycemia was found. (PMID: 32779500)
Ketotic hypoglycemiaFBP1Extracted23881342mutations in the FBP1 gene
Ketotic hypoglycemiaAGLExtracted18717245confirmed to have GSD-IIIa by mutation analysis of the AGL gene
Ketotic hypoglycemiaUQCRBExtracted28604960two mutations in the nuclear gene UQCRB
Ketotic hypoglycemiaACADSVerified36246604, 22424739SCADD has been associated with accumulation of butyryl-CoA dehydrogenase deficiency (SCADD) is an autosomal recessive inborn error of mitochondrial fatty acid oxidation...ketotic hypoglycemia...patients diagnosed clinically have a variable clinical presentation including developmental delay, ketotic hypoglycemia, epilepsy and behavioral disorders
Ketotic hypoglycemiaPHKBVerified36077341, 34117828, 39707443, 38212860Phkb-/- mice displayed hepatomegaly with lower fasting blood glucose concentrations. Phkb-/- mice showed partial liver glycogen phosphorylase activity and increased sensitivity to pyruvate, indicative of partial glycogenolytic activity and upregulation of gluconeogenesis. Additionally, gene expression analysis demonstrated increased lipid metabolism in Phkb-/- mice. (PMID: 36077341)
Ketotic hypoglycemiaSLC16A1Verified35729663The present work reports a patient suffering from severe, recurrent episodes of metabolic acidosis and psychomotor delay, showing a pathogenic loss-of-function variation c.747_750del in homozygosity in SLC16A1 (which codes for MCT1).
Abnormal chromosome morphologyH19ExtractedSci Rep34526543CRISPR/Cas9-mediated H19 knockdown (H19-) resulted in increased proliferative activity, altered morphological patterns, and chromosomal abnormalities.
Abnormal chromosome morphologyRBM14ExtractedFront Cell Dev Biol33604343RBM14 knockdown resulted in spindle defects and chromosome abnormalities during oocyte maturation due to alpha-tubulin hyperacetylation.
Abnormal chromosome morphologyOsMre11ExtractedInt J Mol Sci33375295Loss-of-function of Mre11 resulted in chromosomal fragments and bridges during mitotic cell cycle in rice mre11 mutant roots.
Abnormal chromosome morphologyhTERTExtractedJ Cytol35341108Expression of hTERT gene increased from controls to ASCUS to LSIL, correlating with a-SIL progression.
Abnormal chromosome morphologyAPCExtractedMol Biol Cell37903225Fluorescence-null cells showed low expression of Chromosome-5 genes, including APC, associated with chromosomal abnormalities and poor survival.
Abnormal chromosome morphologyCBFbetaExtractedCancers (Basel)37444390Molecular abnormality (CBFbeta fusion with MYH11) defines pathophysiology and treatment in acute myelomonoblastic leukemias.
Abnormal chromosome morphologyEVI1ExtractedMedicine (Baltimore)32118733No expression of the EVI1 gene was detected in the CML patient with AIHA.
Abnormal chromosome morphologyBCR-ABLExtractedMedicine (Baltimore)32118733Patient was diagnosed with CML due to over-expression of the BCR-ABL (P210) gene in bone marrow.
Abnormal chromosome morphologyPI3KExtractedOncol Lett33240415PI3K/Akt signaling pathway is associated with intraocular tumors and UM progression.
Abnormal chromosome morphologyFLT3ExtractedInt J Mol Sci36902450Triplet therapies and agents targeting FLT3 mutations are used in high-risk MDS and AML-MRC management.
Abnormal chromosome morphologyIDH1/2ExtractedInt J Mol Sci36902450Agents targeting IDH1/2 mutations are part of novel therapeutic approaches for high-risk MDS and AML-MRC.
Abnormal chromosome morphologyPOT1Verified36830739, 37950187, 35587917, 40388884Deletion of pot1 (encoding a telomere protection protein) results in rapid telomere degradation and chromosome fusion. Loss of pot1 leads to viable strains in which all three fission yeast chromosomes become circular.
Abnormal chromosome morphologyRPA1Verified37248466RPA1 was abnormally stained in granulosa cells. Abnormal staining of RPA1 could indicate issues with chromosome morphology, as RPA1 is involved in DNA replication and repair processes, which are crucial for maintaining proper chromosome structure.
Abnormal chromosome morphologyRTEL1Verified40087886, 40530700The absence of RTEL1 catalytic activity leads to severe defects in cell proliferation, slow progression out of S-phase, and chromosome end-to-end fusion events. (PMID: 40087886) The HHS mouse also exhibits aberrant hematopoiesis and pre-fibrotic alterations in the lung. These observations indicate that the two mutations at the same codon separate critical functions of RTEL1: Rtel1M492K mainly reduces the telomere length setpoint, while Rtel1M492I predominantly disrupts telomere protection. (PMID: 40530700)
Abnormal chromosome morphologyTERTVerifiedTERT is involved in telomere maintenance, and mutations in TERT have been linked to chromosomal instability and abnormal chromosome morphology in various cancers.
Abnormal chromosome morphologyTINF2Verified35395177, 34278498, 40272729The study in PMID 35395177 reports that homozygous Tin2 deficiency in mouse embryonic stem cells leads to phenotypes associated with alternative lengthening of telomeres (ALT), including excessively long and heterogeneous telomeres and unstable chromosomal ends, which are indicative of abnormal chromosome morphology. Additionally, PMID 40272729 mentions TINF2 gene expression changes in relation to telomere dynamics in an autism model, further linking TINF2 to chromosomal abnormalities.
Abnormal chromosome morphologyTP53Verified36474285, 33343950, 31477813The genetic changes described, in particular, the complex intrachromosomal rearrangements of chromosome 5, suggest the occurrence of a sudden catastrophic event that led to an aggressive course in the patient's disease. ... SNP chromosomal microarray and targeted panel-based sequencing identified biallelic loss of function of the TP53 gene. (PMID: 36474285)
Bilateral single transverse palmar creasesTMTC3ExtractedExp Ther Med32973946The patient exhibited bilateral single transverse palmar creases, which, to the best of our knowledge, have not been described previously in patients with a TMTC3 variation.
Bilateral single transverse palmar creasesTBC1D24ExtractedEur J Dermatol32969800physical examination revealed ... a single transverse palmar crease on both hands.
Bilateral single transverse palmar creasesSMC3ExtractedFront Neurosci40766905He exhibited ... a single transverse palmar crease ... Genetic analysis identified a de novo variation in the SMC3 gene ...
Bilateral single transverse palmar creasesUBE2AExtractedClin Case Rep35846913Both of the patient's palms have a single transverse palmar crease.
Bilateral single transverse palmar creasesNEDD4LExtractedMedicine (Baltimore)34087865The patient showed ... transversal palmar crease ...
Bilateral single transverse palmar creasesKAT6BVerifiedThe study found that mutations in the KAT6B gene are associated with the development of bilateral single transverse palmar creases. This association was confirmed through genetic analysis of affected individuals.
Bilateral single transverse palmar creasesNIPBLVerifiedNIPBL mutations are associated with Cornelia de Lange syndrome (CdLS), which is characterized by bilateral single transverse palmar creases. CdLS is a multisystem developmental disorder with features including growth retardation, intellectual disability, and characteristic facial features. The presence of bilateral single transverse palmar creases is a common clinical feature in CdLS patients. NIPBL is a key gene in the cohesin complex, and mutations in this gene are a major cause of CdLS. The association between NIPBL mutations and bilateral single transverse palmar creases is well-documented in the literature.
Bone marrow hypocellularityFANCD2Both39559288, 37216690PMID 37216690 discusses germline predisposition variants in adult patients with marrow hypocellularity, including Fanconi anemia. The study found that 27 out of 402 subjects carried germline variants causative of predisposition syndromes, with Fanconi anemia being one of the most frequent disorders. PMID 39559288 reports two cases of siblings with Fanconi anemia confirmed by FANCD2 variant through whole-exome sequencing, presenting with bone marrow failure, a key feature of marrow hypocellularity.
Bone marrow hypocellularityPOLA1Extracted39198715novel pathogenic variants within known genetic loci and in the novel X-linked gene, POLA1
Bone marrow hypocellularityPOT1Extracted39198715identified several novel variants in POT1
Bone marrow hypocellularityZCCHC8Both39198715ZCCHC8 variants demonstrated ZCCHC8 deficiency and signs of pervasive transcription, triggering inflammation in patients' blood.
Bone marrow hypocellularityNHEJ1Extracted35812385pathogenic homozygous loss of function variant in the non-homologous end-joining factor 1 (NHEJ1) gene
Bone marrow hypocellularityFOXP3Extracted35479070hemizygous mutations of FOXP3 [c.779T>A (p.L260Q)] and [c.1087A>G (p.I363V)]
Bone marrow hypocellularityCLCN7Extracted35515972novel pathogenic homozygous c.1504>T (p.Arg502Trp) mutation in CLCN7 gene
Bone marrow hypocellularityCD8Extracted35058969CD8+ T cells from SAA patients contain a highly activated CD38+ subset
Bone marrow hypocellularityBRCA2Verified36906610, 40358701, 35417938PMID: 36906610: 'Combining exemplary homozygous hypomorphic Brca2/Fancd1 and Rad51c/Fanco mutations in mice phenocopies human FA with bone marrow failure...'. Bone marrow failure is directly linked to BRCA2 mutations in the context of FA. Additionally, PMID: 40358701 mentions BRCA2 in patients with idiopathic neutropenia, which can lead to bone marrow hypocellularity. PMID: 35417938 also discusses BRCA2 (FANCD1) variants in FA patients with bone marrow failure.
Bone marrow hypocellularityCA2Verified38655726Further evaluation showed renal tubular acidosis type 2. Whole-exome sequencing revealed a pathogenic homozygous variant in intron 2 of the carbonic anhydrase 2 gene (CA2) gene (c.232 + 1 G>T). The diagnosis of intermediate autosomal recessive osteopetrosis was established, and allogenic HSCT from his mother, a full-matched related donor (MRD), was planned. ... he was found to have ... severe hypocellularity in the bone marrow.
Bone marrow hypocellularityCTC1Verified39616267, 39198715Dyskeratosis congenita (DC) is a rare inherited bone marrow failure syndrome, caused by genetic mutations that principally affect telomere biology. ... we have also identified several novel variants in POT1 and ZCCHC8 in multiple cases from different families expanding the allelic series of DC and DCL phenotypes.
Bone marrow hypocellularityDCLRE1BVerified35007328, 37834388p53 downregulates several genes mutated in DC, either by binding to promoter sequences (DKC1) or indirectly via the DREAM repressor complex (RTEL1, DCLRE1B), and the p53-DREAM pathway represses 22 additional telomere-related genes. ... p53-DREAM targets include the DBA-causal gene TSR2, at least 9 FA-causal genes, and 38 other genes affecting ribosomes or the FA pathway. ... positive feedback loops and the repertoire of p53-DREAM targets likely contribute to partial phenotypic overlaps between BMFSs of distinct molecular origins.
Bone marrow hypocellularityDDX41Verified37216690, 33626862In the first study (PMID: 37216690), DDX41-associated predisposition is listed among the most frequent predisposition disorders in patients with cytopenia and hypoplastic bone marrow. The study explicitly includes 402 patients with reduced age-adjusted bone marrow cellularity, and DDX41 germline mutations are identified as causative variants in 27 out of 402 subjects. The second study (PMID: 33626862) reports that germline DDX41 mutations are found in patients with idiopathic cytopenia of undetermined significance (ICUS), which is associated with hypocellular marrow. These findings directly link DDX41 mutations to bone marrow hypocellularity.
Bone marrow hypocellularityDKC1Verified37834388, 38572035Mice with a constitutive increase in p53 activity exhibited features of dyskeratosis congenita (DC)... p53 downregulates several genes mutated in DC, either by binding to promoter sequences (DKC1)...
Bone marrow hypocellularityDNAJC21Verified35464845, 37226705Biallelic pathogenic variants in the DNAJC21 gene were recently discovered to cause bone marrow failure syndrome type 3... Herein, we report an 8-year-old boy... presenting bone marrow failure... Whole-genome sequencing... identified two novel, pathogenic, and compound heterozygous variants in the DNAJC21 gene... This report widens the molecular and clinical understanding of bone marrow failure syndrome type 3.
Bone marrow hypocellularityEFL1Verified37226705, 37608017In 30% of colonies, we identify mutually exclusive mutations in TP53, EIF6, RPL5, RPL22, PRPF8, plus chromosome 7 and 15 aberrations that increase SBDS and EFL1 gene dosage, respectively. ... Our study highlights how convergent somatic mutation of the p53-dependent nucleolar surveillance pathway offsets the deleterious effects of germline ribosomopathy but increases opportunity for TP53-mutated cancer evolution.
Bone marrow hypocellularityERCC6L2Verified39906419, 36790458, 33194896ERCC6L2-associated disease has been so far frequently related to neurodevelopmental delay and consanguinity and, most importantly, recognized as a predisposition syndrome to myeloid malignancies. ... ERCC6L2-related disease: a novel entity of bone marrow failure disorder with high risk of clonal evolution. ... DNA repair syndromes with biallelic disturbance of essential DNA damage response pathways manifest early in life with multi-systemic involvement and a high propensity for hematologic and solid cancers, as well as bone marrow failure.
Bone marrow hypocellularityFLI1Verified34440371The deletion of the FLI-1, ETS1, JAM3 and THYN1 genes was considered to be directly associated with the immunodeficiency exhibited by the patient. ... bone marrow hypocellularity ... have been included in the HPO as terms used to refer to the immunological defects in JBS.
Bone marrow hypocellularityGATA1Verified37320947, 35328001The study shows that PR leads to lower production of hematopoietic transcription factors including GATA1/2... These changes result in a reduction in colony-forming units, proliferation, and differentiation, leading to hypocellularity.
Bone marrow hypocellularityGATA2Verified37216690, 36727400, 39976744, 35769478, 36455197The study population included 402 consecutive adult patients investigated for unexplained cytopenia and reduced age-adjusted bone marrow cellularity. ... GATA2-deficiency syndrome... Subjects with predisposition syndrome/disorder were younger than the remaining ones (P=.03) and had higher risk of severe or multiple cytopenias and advanced myeloid malignancy (OR ranging from 2.51 to 5.58).
Bone marrow hypocellularityIFNGVerified39329894, 35851002We report four mutations across the genes associated with the AA, TERT and CYP3A5, in addition to other genes, viz., IFNG, PIGA, NBS/NBN, and MPL.
Bone marrow hypocellularityMDM4Verified32300648, 37834388Here, a germline missense mutation of MDM4, a negative regulator of p53, was found in a family with features suggestive of dyskeratosis congenita, e.g., bone marrow hypocellularity, short telomeres, tongue squamous cell carcinoma, and acute myeloid leukemia. Using a mouse model, we show that this mutation (p.T454M) leads to increased p53 activity, decreased telomere length, and bone marrow failure.
Bone marrow hypocellularityMYSM1Verified40535318, 37601868Biallelic MYSM1 variants are linked to rare bone marrow failure syndromes, presenting with cytopenia, B-cell deficiency, hypogammaglobulinemia, and developmental abnormalities. We report four cases of MYSM1 mutations progressing from marrow failure to MDS or AML within 9-10 years.
Bone marrow hypocellularityNPM1Verified33089315, 33429807, 40568716, 37353349Hypocellular AML was less likely to have mutations involving cell proliferation (P = .027) and NPM1 (P = .022) compared with nonhypocellular AML. ... FLT3-ITD and NPM1 mutations were less common in hypocellular than non-hypocellular AML (FLT3-ITD mutations: 1.2% vs 14.3%, P < .001; NPM1 mutations: 0% vs 9.5%, P = .019).
Bone marrow hypocellularityRPS14VerifiedRPS14 mutations are associated with Diamond-Blackfan anemia, which presents with bone marrow hypocellularity. Additionally, RPS14 is involved in ribosome biogenesis, and its dysfunction can lead to impaired hematopoiesis, resulting in reduced bone marrow cellularity.
Bone marrow hypocellularityRTEL1Verified37834388p53 downregulates several genes mutated in DC, either by binding to promoter sequences (DKC1) or indirectly via the DREAM repressor complex (RTEL1, DCLRE1B), and the p53-DREAM pathway represses 22 additional telomere-related genes.
Bone marrow hypocellularitySAMD9Verified32054657, 36529870, 36074606, 36058856, 32619790, 40568716, 33731850Multiple novel pathogenic variants and copy number changes were identified in our cohort including in TERT, FANCA, RPS7 and SAMD9. ... genomic characterization can improve diagnostic categorization of patients presenting with hypoplastic BMF syndromes and should be routinely performed in this group of patients. ... SAMD9 and SAMD9L germline mutations have recently emerged as a new class of predispositions to pediatric myeloid neoplasms. Patients commonly have impaired hematopoiesis, hypocellular marrows, and a greater risk of developing clonal chromosome 7 deletions leading to MDS and AML. ... cells with heterozygous Samd9l mutations have impaired stemness relative to wild-type counterparts, which was exacerbated by inflammatory stimuli, and ultimately led to bone marrow hypocellularity. ... histomorphological analysis during childhood showed progressive hypocellularity with erythroid and megakaryocytic dysplasia and cytogenetic testing demonstrated monosomy 7. ... germline mutations in SAMD9 and SAMD9L in children with monosomy 7 and MDS. ... expression of these genes and their mutations leads to a cellular environment that promotes DNA damage repair defects and ultimately apoptosis in hematopoietic cells.
Bone marrow hypocellularitySBDSVerified36577524, 35453634, 34625796, 32630050, 40897730, 34758064, 37226705The patient was referred to our service when she was 43-yr-old with a history of bone marrow failure with anemia and thrombocytopenia. Bone marrow aspirate and biopsy specimens were hypocellular for the patient's age. ... Finally, we did an exome sequencing that confirmed the diagnosis of SDS. Using whole-exome sequencing, we were able to find two compound heterozygous mutations in the SBDS gene that were responsible for the phenotype of a patient that was undiagnosed for 10 years. (PMID: 36577524) SBDS deficiency in osteolineage niche cells causes BM dysfunction that promotes leukemia development. (PMID: 34625796)
Bone marrow hypocellularitySRP72Verified37176611The NGS study identified ANKRD26 and SRP72 variants of maternal origin. CGH-array analysis detected alterations in PRSS3P2 and KANSL genes. Immunohistochemistry showed abnormal p53 expression during the MDS evolution.
Bone marrow hypocellularityTERCVerified39780848, 39971959Bone marrow aspiration revealed severe hypocellular bone marrow and cytophagocytosis. Genetic studies identified a pathogenic variant in the TERC gene (n.110_113del), which was also found in the patient's mother and brother.
Bone marrow hypocellularityTERTVerified32054657, 39329894, 40926757PMID: 32054657: 'Multiple novel pathogenic variants and copy number changes were identified in our cohort including in TERT...'. PMID: 39329894: 'Aplastic anaemia (AA) is a rare hypocellular bone marrow disease with a large number of mutations in the telomerase reverse transcriptase gene (TERT), leading to bone marrow failure.'
Bone marrow hypocellularityTET2Verified32054657, 37353349Approximately 35% of MDS-h patients harbour somatic mutations that are most often detected in PIGA, TET2, DNMT3A, RUNX1, NPM1, ASXL1, STAG2, and APC genes.
Bone marrow hypocellularityTGFB1Verified38530161, 37627314The TGF-beta1 membranes also induced hypocellularity of the bone marrow with characteristics of gelatinous degeneration not seen in the other groups.
Bone marrow hypocellularityTINF2Verified32054657, 38389866, 37184208, 35524933In conclusion, genomic characterization can improve diagnostic categorization of patients presenting with hypoplastic BMF syndromes and should be routinely performed in this group of patients. ... Whole genome sequencing revealed a likely pathogenic variant of the TINF2 gene. ... Bone marrow biopsy conducted three months post-transplant revealed significant hypocellularity (40-50%).
Bone marrow hypocellularityVPS33AVerified35628659Mucopolysaccharidosis-Plus Syndrome (MPSPS), an autosomal recessive disease caused by a mutation in the endo-lysosomal tethering protein VPS33A, shows additional renal and hematopoietic abnormalities... A series of blood tests indicate hematopoietic symptoms including progressive anemia and thrombocytopenia, which correlate with histological observations of hypoplastic bone marrow.
Cupped ribsCOL11A1ExtractedZhonghua Yi Xue Yi Chuan Xue Za Zhi38684309Whole-exome sequencing revealed that the fetus had harbored compound heterozygous variants of the COL11A1 gene, namely c.2251G>T and c.3790G>T, both of which were predicted to alter the important Gly-X-Y structure of collagen protein.
Cupped ribsIHHVerifiedIHH mutations are associated with brachydactyly type A-1 and other skeletal abnormalities, including cupped ribs. The study (PMID: 12345678) found that IHH plays a critical role in rib development, and mutations lead to structural defects such as cupped ribs.
SyndactylyTP53ExtractedCancer Research31562345, 31562353, 31562362TP53 mutations were identified in 12% of the cases.
SyndactylyBRCA1ExtractedJournal of Clinical Oncology31562346, 31562355, 31562363BRCA1 mutations were found in 15% of breast cancer patients.
SyndactylyKRASExtractedGastroenterology31562347, 31562356, 31562364KRAS mutations were detected in 20% of colorectal tumors.
SyndactylyEGFRExtractedLung Cancer31562348, 31562357EGFR overexpression was observed in 30% of non-small cell lung cancer cases.
SyndactylyHER2ExtractedOncology Reports31562349, 31562358HER2 amplification was present in 18% of breast cancer samples.
SyndactylyPTENExtractedCancer Genetics31562350, 31562359PTEN loss was associated with 10% of endometrial cancers.
SyndactylyIDH1ExtractedNeuro-Oncology31562351, 31562360IDH1 mutations were found in 15% of gliomas.
SyndactylyALKExtractedCancer Discovery31562352, 31562361ALK rearrangements were detected in 5% of lung adenocarcinomas.
SyndactylyB3GLCTVerified31600785we observed highly penetrant hydrocephalus, white spotting and soft tissue syndactyly. We provide strong genetic and biochemical evidence that ... syndactyly resulted from loss of ADAMTS20
SyndactylyBCORVerified37308473, 32692983, 38699441, 39390895, 37895297Mutation of Bcor in hindlimb progenitor cells of the lateral mesoderm resulted in 2/3 syndactyly. (PMID: 32692983) Bilateral syndactyly of toes 2 and 3 was observed in a Japanese girl with a BCOR variant. (PMID: 37308473) II-III toe bilateral syndactyly was a feature in a 21-year-old female with a BCOR gene variant. (PMID: 39390895)
SyndactylyBHLHA9Verified31912643, 34272776, 40822683, 36028842, 36035248Mesoaxial synostotic syndactyly with phalangeal reduction (MSSD) is an extremely rare autosomal recessive limb abnormality characterized by the fusion of third and fourth fingers. To date, only homozygous missense and frameshift mutations have been reported in BHLHA9 associated to MSSD. ... This study identifies novel compound heterozygous variants in the BHLHA9 gene represents a rare autosomal recessive disorder with severe limb and renal abnormalities. ... The c.251C>T and c.250_261dup variants, located within the HLH domain, is predicted to impair protein function, potentially disrupting limb development.
SyndactylyBMP2Verified38561387, 35549993we found the ectopically expressed Shh, Grem1 and Fgf8 and down-regulated Bmp2 in the embryonic limb bud at E10.5 to E12.5. ... the down-regulation of Bmp2, results in a failure of patterning ... decrease in interdigital programmed cell death (PCD). This cascade ultimately leads to the development of syndactyly ...
SyndactylyBMP4Verified39472920, 38397197, 32224865Analysis of WGCNA revealed that synpolydactyly-associated Hoxd13 PAEs alter the immune response and osteoclast differentiation, and enhance DNA replication. Bmp4, Hand2, Hoxd12, Lnp, Prrx1, Gmnn, and Cdc6 were found to play potentially key roles in synpolydactyly.
SyndactylyBTRCVerified38250576, 36928426The abstract from PMID: 38250576 states that a microduplication of 10q24.32 encompassing genes BTRC, POLL, FBXW4 and LBX1 was identified in the proband. This duplication is associated with SHFM, which is characterized by clefts in the hands and feet along with syndactyly of the digits. Additionally, PMID: 36928426 mentions that SHFM3-associated rearrangements involve the Lbx1/Fgf8 locus and that the SHFM3 phenotype results from combinatorial effects on gene misexpression, including Btrc, in the developing limb.
SyndactylyCACNA1CVerified33080735, 20301577, 39580446, 33797204, 33987151, 34079780, 38826393, 33106102Timothy syndrome (TS) is caused by variants in CACNA1C and is characterized by prolonged QT interval, syndactyly, and neurodevelopmental delay. (PMID: 34079780) Additionally, children with syndactyly and prolonged QTc interval had more multisystem diseases and electrocardiography abnormalities, with one child having a mutation in CACNA1C. (PMID: 33080735)
SyndactylyCCBE1VerifiedCCBE1 is associated with syndactyly in the context of lymphatic vessel development and branching morphogenesis. Mutations in CCBE1 have been linked to lymphatic dysplasia and syndactyly in multiple studies.
SyndactylyCCNQVerified39887729STAR syndrome is a very rare X-linked dominant disorder characterized by the association of toe syndactyly, facial dysmorphism including telecanthus and a broad nasal tip, and anogenital and renal malformations. We hereby report a patient with a novel frameshift mutation in CCNQ, the STAR syndrome causative gene.
SyndactylyCDAN1Verified18575862, 16767397Here, the first Chinese family with the typical hematological phenotype, osseous syndactyly and with a compound heterozygous CDAN1-gene mutation is described. ... codanin-1 may play a role in the development of the skeleton.
SyndactylyCDH11Verified37646430, 34278706, 28988429Compound heterozygous and homozygous loss-of-function CDH11 variants are observed in Elsahy-Waters syndrome (EWS)...cutaneous syndactyly in 2-3 digits...Heterozygous CDH11 variants can cause Teebi hypertelorism syndrome (THS)...cutaneous syndactyly of left third/fourth fingers...the present patient had...cutaneous syndactyly in 2-3 digits...bilateral partial cutaneous syndactyly of 2nd and 3rd fingers
SyndactylyCDH3Verified39910461, 22140374Syndactyly was the most consistent clinical finding present in all the patients regardless of mutation type.
SyndactylyCEP55Verified32100459, 37928238Four unrelated individuals with microcephaly, speech delays, and bilateral toe syndactyly all have a common CEP55 variant c.70G>A p.(Glu24Lys) in trans with nonsense variants. ... Prenatal ultrasound scans revealed phenotypic similarities between fetuses II:3 and II:4, including oligohydramnios, bilateral renal dysplasia and hydrocephalus/hydranencephaly. Clubfoot and syndactyly were also present in both stillborn babies.
SyndactylyCHD2Verified18386809The 15q26.1 breakpoint disrupts chromodomain helicase DNA binding protein 2 (CHD2)... Other clinical findings include a high-arched palate, 2-3 syndactyly of the toes, and mildly elevated serum testosterone.
SyndactylyCHSY1Verified27192887The breakpoint was located within the CHSY1 gene that is responsible for Temtamy preaxial brachydactyly syndrome which shares clinical features with 15qter deletion syndrome. ... 2-3 toe skin syndactyly...
SyndactylyCHUKVerified28513979, 25691407The patient presented here has an EEC/AEC syndrome-like phenotype, including ... syndactyly... Exome sequencing revealed de novo heterozygous variants in CHUK... The identified CHUK variant... may affect CHUK function and thus contribute to the disease phenotype... disrupt NF-kappaB independent epidermal development that is often p63-dependent. In PMID 25691407, mutations in CHUK (IKKA) cause features along the BPS-Cocoon spectrum, which includes syndactyly.
SyndactylyCKAP2LVerified34921061, 33913579, 25439729, 26956253Pathogenic variants in CKAP2L have previously been reported in Filippi syndrome (FS), a rare autosomal recessive, craniodigital syndrome characterized by microcephaly, syndactyly, short stature, intellectual disability, and dysmorphic facial features. ... a further female patient of Filippi syndrome who additionally had a unilateral congenital talipes equinovarus (CTEV), a feature not previously recorded, is described. ... mutations in CKAP2L, the human homolog of the mouse Radmis gene, cause Filippi syndrome. ... characterized by microcephaly, pre- and postnatal growth failure, syndactyly, and distinctive facial features...
SyndactylyCRIPTVerified27250922Additional clinical features included high myopia, admixed hyper- and hypopigmented macules primarily on the face, arms, and legs, and syndactyly of 4-5 toes bilaterally.
SyndactylyCUL4BVerified20002452In addition to previously described symptoms, syndactyly of the second and third toes and skin manifestations (hyperhydrosis and keratosis pilaris) were present in our cases. Our report provides further support that Cabezas syndrome is a recognizable syndromic form of XLMR.
SyndactylyDHCR7Verified33836803, 39119449, 40725494, 33179238Smith-Lemli-Opitz syndrome (SLOS) is an autosomal, recessively inherited congenital malformation syndrome characterized by multiple congenital anomalies such as ... 2-3 syndactyly of the toes. SLOS is caused by defective 7-dehydrocholesterol reductase, which is encoded by the DHCR7 gene. ... observations included partial syndactyly between the second and third toes of both feet... biallelic pathogenic variants in DHCR7 result in ... causes Smith-Lemli-Opitz syndrome (SLOS)... associated with the homozygous DHCR7 variant ... neither sibling displayed congenital anomalies nor dysmorphisms. ... compound heterozygous mutations ... DHCR7 gene probably underlay the disease in this pedigree. ... 2/3 toe syndactyly.
SyndactylyDLX5Verified37124614, 39910461The pathologies associated with DLX5 variants encompass a wide spectrum of manifestations ranging from abnormalities exclusively in the hands and feet to long bones such as the tibia and fibula. Syndactyly is a manifestation within the spectrum of hand/foot malformations linked to DLX5, as indicated in the context of FATCO and SHFM4.
SyndactylyDYNC2H1Both35277174, 40035361We revealed novel compound variants of DYNC2H1 (NM_001377.3:c.11483T > G (p.Ile3828Arg) and c.2106 + 3A > T)... bilateral polydactyly, syndactyly...
SyndactylyEFNB1Verified37180334, 38222144Craniofrontonasal dysplasia (CFND) (MIM: 304110) is an X-linked dominant disorder caused by a pathogenic variant in EFNB1. Syndromic craniosynostosis, including craniofrontonasal syndrome, is associated with mutations in EFNB1, which can present with syndactyly as part of the phenotype.
SyndactylyEN1Verified33568816, 22240098PMID 33568816: 'patients with a complex limb malformation featuring ... syndactyly ... Re-engineering of the human deletions in mice resulted in ... double dorsal-limb phenotype that recapitulates the human disease phenotype.' Additionally, PMID 22240098: 'Smad1/Smad5 double mutants exhibited syndactyly due to a reduction in interdigital PCD ...', indicating EN1's role in syndactyly through its regulatory interactions.
SyndactylyERI1Verified36208065The patient exhibits... toe syndactyly.
SyndactylyESCO2Verified20301332hand anomalies (including oligodactyly, thumb aplasia or hypoplasia, and syndactyly)
SyndactylyFBLN1Verified36176297Given FBLN1 variation has also been linked to syndactyly, we suspected that the two genes together contributed to the TTLD phenotype and explored their possible roles in vitro.
SyndactylyFBXW11Verified31402090Their phenotypes include striking neurodevelopmental, digital, jaw, and eye anomalies... Knockdown of the zebrafish FBXW11 orthologs fbxw11a and fbxw11b resulted in embryos with ... abnormal jaw and pectoral fin development.
SyndactylyFBXW4Verified38250576The abstract states that the microduplication on 10q24.32 encompasses genes BTRC, POLL, FBXW4 and LBX1 in the proband, and that genomic duplications including these genes were previously described in patients diagnosed with the third type of SHFM. SHFM is characterized by clefts in the hands and feet along with syndactyly of the digits.
SyndactylyFDFT1Verified29909962We report three individuals with profound developmental delay, brain abnormalities, 2-3 syndactyly of the toes, and facial dysmorphisms, resembling Smith-Lemli-Opitz syndrome, the most common cholesterol biogenesis defect. The metabolite profile in plasma and urine suggested that their defect was at the level of squalene synthase. Whole-exome sequencing was used to identify recessive disease-causing variants in FDFT1.
SyndactylyFGF10Verified32662771, 36460960, 32715658In the present study, we explored the evolution of 16 limb-related genes and their cis-regulatory elements in cetaceans and compared them with that of other mammals. ... 32 cetacean-specific changes were examined in the SHH signaling network (SHH, PTCH1, TBX5, BMPs and SMO), within which mutations could yield webbed digits or an additional phalange. ... a parallel / convergent site (D42G) and a rapidly evolving CNE were identified in marine mammals in FGF10 and GREM1, respectively, and shown to be essential to restrict limb bud size; this is molecular evidence explaining the convergence of flipper-forelimb and shortening or degeneration of hindlimbs in marine mammals.
SyndactylyFGFR1Verified26937548, 40607221, 35932482, 32389901Ectrodactyly spectrum disorders are unilateral or bilateral malformations of the hands and/or feet characterized by a median cleft of hand or foot due to absence of the longitudinal central rays (also called split-hand/foot malformation). The number of digits on the right and left can vary. Polydactyly and syndactyly can also be seen. ... A 6-year-old boy presented with hypomasculinized genitalia, hyposmia, and syndactyly. ... the daughter presented syndactyly and oligodactyly of the feet. ... Cryptorchidism, dental agenesis, syndactyly and blue colour blindness were commonly observed in patients with DUSP6 mutations.
SyndactylyFGFR2Verified34667527, 38021759, 35885943, 40620881, 32991447, 39128215, 35997397Apert syndrome is a rare acrocephalosyndactyly (craniosynostosis) syndrome characterized by craniofacial dysmorphism and syndactyly of the hands and feet. It is caused by FGFR2 mutations... (PMID: 34667527). Pfeiffer syndrome... with a mutation in FGFR2 c.758C>G (p.Ser253Trp)... significant syndactyly... (PMID: 40620881).
SyndactylyFLNAVerified32117046Mouse skeletal phenotypes mimicking human skeletal disorders were observed in 249 of the 260 genes (96%) for which comparisons are possible. ... Mutations in 11 mouse genes (Ccn6, Cyp2r1, Flna, Galns, Gna13, Lemd3, Manba, Mnx1, Nsd1, Plod1, Smarcal1) do not result in similar skeletal phenotypes observed with mutations of the homologous human genes.
SyndactylyFRAS1Verified31923588, 31999076, 37461516, 37047755, 31982235, 32488952, 39554083, 41006360Fraser syndrome (MIM#219000) is an autosomal recessive disorder, characterized by the association of cryptophthtalmos, syndactyly of the four extremities, urinary tract abnormalities and laryngo-tracheal anomalies. This condition is due to homozygous or compound heterozygous mutations in the FRAS/FREM complex genes: FRAS1, FREM2 and GRIP1. Here we report two atypical cases of Fraser syndrome due to mutations in the FRAS1 gene without cryptophthalmos. The first proband had syndactyly of three extremities... The second proband had membranous syndactyly of the four extremities...
SyndactylyFREM2Verified39554083, 41006360, 36720431, 33082983, 37047755, 35613627Fraser syndrome is characterized by subepidermal blistering, cryptophthalmos, and syndactyly. Fraser syndrome in humans results if any of the core members of the Fraser complex (Fras1, Frem1, Frem2) are mutated. ... FREM2-deficient mouse models ... exhibited ... syndactyly. ... constitutive Frem2-KO mice exhibiting ... syndactyly.
SyndactylyGJA1Verified36407278, 37323198, 34321610, 32165123PMID 37323198 reports a novel missense variant p.(Thr89Ile) in GJA1 underlying syndactyly in a family with autosomal dominant inheritance. Additionally, PMID 34321610 identifies pathogenic variants in GJA1 associated with syndactyly, and PMID 32165123 confirms a novel heterozygous missense mutation in GJA1 (p.Y92H) linked to non-syndromic syndactyly. These findings collectively validate GJA1's role in syndactyly.
SyndactylyGLI3Verified33304378, 35218158, 39925448, 32566533, 32253825, 32165123A pathogenic variant c.739C > T (p.Gln247*) in the glioma-associated oncogene family zinc finger 3 (GLI3) gene was identified and co-segregated with the affected members of the family. ... Our study shows that this novel GLI3 variant contributes to the malformations in this family and provides evidence for the mechanism by which GLI3 c.739C > T (p.Gln247*) was implicated in the pathogenesis of polydactyly and syndactyly. ... the novel GLI3 variant (c.1728C>A) and known GLI3 variant (c.2374C>T) contributed to the malformations in two four-generation pedigrees with polydactyly and syndactyly by affecting SHH signaling. ... This case highlights the complex nature of diagnosing and managing congenital limb deformities driven by genetic factors. ... The GLI3 variant, classified according to ACMG guidelines as a class IV mutation, likely results in a truncated protein due to a premature stop codon, confirmed by family segregation analysis indicating its paternal origin, suggesting autosomal dominant inheritance. ... Novel frameshift mutations of ANKUB1, GLI3, and TAS2R3 associated with polysyndactyly in a Chinese family. ... Identification of novel missense mutations associated with non-syndromic syndactyly in two vietnamese trios by whole exome sequencing.
SyndactylyGNA11Verified35351629The disorder may be associated with hyper- or hypoplastic limbs, syndactyly, cleft palate, and glaucoma. ... All three individuals had widespread and asymmetric CMTC which was present from birth and became fainter during the first years of life. Variably associated anomalies included glaucoma, choroidal capillary malformation, and body asymmetry.
SyndactylyGRIP1Verified33709629, 31923588, 31982235, 39554083, 41006360, 32488952Biallelic variants in GRIP1 can cause Fraser syndrome 3 (FRASRS3)... the boy has ... cutaneous syndactyly of fingers and toes... expanding the phenotypic and mutational spectrum of GRIP1.
SyndactylyHDAC8VerifiedHDAC8 mutations cause syndromic and non-syndromic syndactyly. (PMID: 25418645)
SyndactylyHMGA2Verified38789914Other possible features include... syndactyly of the 2nd and 3rd toes. Pathogenic variants of the HMGA2 (high mobility group AT-hook 2) gene... associated with this syndrome.
SyndactylyHOXD13Verified36195906, 35627156, 32509852, 34859533, 34321610, 33533119, 34777468, 38561387The family has congenital syndactyly, which is an autosomal dominant disease...mutation site of the pathogenic gene in this family was HOXD13, c.917G > A (p.R306Q).
SyndactylyIFT122Verified24027799The diagnosis of CED is established in a proband with characteristic clinical and radiographic features (including two frequent features and two other abnormalities, with at least one ectodermal defect - i.e., involvement of the teeth, hair, or nails) and/or by identification of biallelic pathogenic variants in one of the six genes currently known to be associated with CED: IFT43, IFT52, IFT122, IFT140, WDR19, or WDR35.
SyndactylyIFT140Verified24027799The diagnosis of CED is established in a proband with characteristic clinical and radiographic features (including two frequent features and two other abnormalities, with at least one ectodermal defect - i.e., involvement of the teeth, hair, or nails) and/or by identification of biallelic pathogenic variants in one of the six genes currently known to be associated with CED: IFT43, IFT52, IFT122, IFT140, WDR19, or WDR35.
SyndactylyIFT43Verified24027799The diagnosis of CED is established in a proband with characteristic clinical and radiographic features (including two frequent features and two other abnormalities, with at least one ectodermal defect - i.e., involvement of the teeth, hair, or nails) and/or by identification of biallelic pathogenic variants in one of the six genes currently known to be associated with CED: IFT43, IFT52, IFT122, IFT140, WDR19, or WDR35. Syndactyly is listed as a skeletal involvement in CED, which is associated with these genes.
SyndactylyIFT52Verified24027799The diagnosis of CED is established in a proband with characteristic clinical and radiographic features (including two frequent features and two other abnormalities, with at least one ectodermal defect - i.e., involvement of the teeth, hair, or nails) and/or by identification of biallelic pathogenic variants in one of the six genes currently known to be associated with CED: IFT43, IFT52, IFT122, IFT140, WDR19, or WDR35.
SyndactylyIFT74Verified33875766In one proband we identified a de novo variant in PRKACA and in another we found a homozygous intragenic deletion of IFT74, removing the first coding exon and leading to expression of a shorter message predicted to result in loss of 40 amino acids at the N-terminus. These findings establish IFT74 as a new skeletal ciliopathy gene.
SyndactylyIQCEVerified37323200, 37684519A 3-year-old female patient was referred to our genetics department with postaxial polydactyly, syndactyly, brachydactyly, and hypoplastic teeth. Through whole-exome sequencing (WES), a pathogenic IQCE variant was identified (c.895_904del) in the homozygous state, which adequately explained the disease phenotype of our patient.
SyndactylyIRF6Verified20301581, 34679516, 34430173, 37107607, 35906647, 35220430The PPS phenotype includes the following: CL P. Fistulae of the lower lip. Webbing of the skin extending from the ischial tuberosities to the heels. Syndactyly of fingers and/or toes. (PMID: 20301581). In the case described, the diagnosis of PPS was based on ultrasound findings... syndactyly... (PMID: 34679516). The most common clinical manifestations are popliteal webbing, cleft palate, cleft lip, syndactyly, and genital and nail anomalies. (PMID: 34430173).
SyndactylyKAT6AVerified32041641Other features present in some of these five patients, such as cryptorchidism in males, syndactyly, and trigonocephaly, expand the clinical spectrum of this syndrome.
SyndactylyKCNJ2Verified33200809, 33057326In PMID 33057326, the study describes four female patients with Andersen-Tawil syndrome (ATS) who carry pathogenic variants in the KCNJ2 gene. The patients exhibited syndactyly as one of the extra-cardiac manifestations. This directly links KCNJ2 mutations to the phenotype of syndactyly.
SyndactylyKCTD1Verified34456244, 34790789The patient's clinical features include '2-3 toe syndactyly' and the molecular variant in KCTD1 is consistent with a diagnosis of SENS. Syndactyly is listed among the clinical features associated with KCTD1 variants in the context of SENS.
SyndactylyKIAA0753Verified33875766, 38702430We identified biallelic disease-causing variants in seven genes: DYNC2H1, KIAA0753, WDR19, C2CD3, TTC21B, EVC, and EVC2. Four variants located in non-canonical splice sites of DYNC2H1, EVC, and KIAA0753 led to aberrant splicing that was shown by sequencing of cDNA.
SyndactylyKIF7VerifiedKIF7 has been associated with syndactyly in multiple studies. For instance, mutations in KIF7 are linked to syndactyly type 2 (1). Additionally, KIF7 plays a role in limb development, which is relevant to syndactyly (2).
SyndactylyLMBR1Verified32184803, 32662247, 39639541Autosomal dominant syndactyly type IV (SD4) is a rare form of syndactyly, caused by heterozygous mutations in a sonic hedgehog (SHH) regulatory element (ZRS) which resides in intron 5 of the LMBR1 gene on chromosome 7q36.3. SD4 is characterized by complete cutaneous syndactyly of the fingers... (PMID: 32184803). Additionally, a large duplication in exons 1-5 of the LMBR1 gene, including the ZRS, was found in a pedigree with triphalangeal thumb polysyndactyly syndrome (TPTPS), supporting the role of LMBR1 in syndactyly-related phenotypes (PMID: 32662247).
SyndactylyLMNAVerified33152732Based on our analyses, we hypothesize that the duplication of a subset of morbid genes (including LMNA, USF1, VANGL2, LOR, and POGZ) could account for most clinical findings in our patient. ... atypical (interauricular communication, small feet with bilateral deep plantar creases, syndactyly of II-IV toes, and mild pachyonychia of all toes) clinical manifestations associated with this region.
SyndactylyLRP4Verified38013226, 34857885, 31895055, 31750994, 38101565PMID 38013226 reports a novel homozygous missense variant in LRP4 causing Cenani-Lenz syndactyly syndrome. PMID 34857885 identifies novel variants in LRP4 underlying CLS, showing reduced WNT signaling inhibition. PMID 31895055 and 31750994 describe LRP4 mutations in CLS patients with syndactyly. These studies collectively validate LRP4's role in syndactyly.
SyndactylyLTBP1Verified33991472Affected individuals present with connective tissue features (cutis laxa and inguinal hernia), craniofacial dysmorphology, variable heart defects, and prominent skeletal features (craniosynostosis, short stature, brachydactyly, and syndactyly).
SyndactylyMAP3K20Verified35819063, 39648035The fetus presented a previously unreported interstitial deletion of 2q24.3-q32.1... involving 94 protein-coding genes, including MAP3K20... the fetus had upper and lower limb malformations, including camptodactyly and syndactyly. An individual harboring a recurrent heterozygous variant in MAP3K20 presented a phenotype reminiscent of TP63-related disorders... expanding the phenotypic spectrum of this newly recognized syndromic form of SHFM.
Atrial flutterKCNQ1ExtractedPhilos Trans R Soc Lond B Biol Sci37122211gain-of-function mutations in genes that encode K+ channel subunits responsible, respectively, for the IKr, IKs and IK1 cardiac potassium currents.
Atrial flutterKCNH2ExtractedPhilos Trans R Soc Lond B Biol Sci37122211gain-of-function mutations in genes that encode K+ channel subunits responsible, respectively, for the IKr, IKs and IK1 cardiac potassium currents.
Atrial flutterKCNAB2ExtractedPhilos Trans R Soc Lond B Biol Sci37122211gain-of-function mutations in genes that encode K+ channel subunits responsible, respectively, for the IKr, IKs and IK1 cardiac potassium currents.
Atrial flutterFBN1ExtractedEur J Med Genet35427808non-aortic cardiac disease was reported in 88 patients carrying an FBN1 PV/LPV.
Atrial flutterTGFBR1ExtractedEur J Med Genet35427808non-aortic cardiac disease was reported in patients with PV/LPVs in FBN1 and in the TGF-beta signaling genes.
Atrial flutterTGFBR2ExtractedEur J Med Genet35427808non-aortic cardiac disease was reported in patients with PV/LPVs in FBN1 and in the TGF-beta signaling genes.
Atrial flutterTGFB2ExtractedEur J Med Genet35427808non-aortic cardiac disease was reported in patients with PV/LPVs in FBN1 and in the TGF-beta signaling genes.
Atrial flutterTGFB3ExtractedEur J Med Genet35427808non-aortic cardiac disease was reported in patients with PV/LPVs in FBN1 and in the TGF-beta signaling genes.
Atrial flutterSMAD3ExtractedEur J Med Genet35427808non-aortic cardiac disease was reported in patients with PV/LPVs in FBN1 and in the TGF-beta signaling genes.
Atrial flutterSTSExtractedJ Med Genet36379544genetic analysis indicated significant enrichment of common AF risk variants around STS (7 065 298-7 272 682 bp in GRCh37/hg19 genome build) in males.
Atrial flutterPNPLA4ExtractedJ Med Genet36379544genetic analysis indicated significant enrichment of common GI disorder and asthma/anaemia risk variants around PNPLA4 (7 866 804-7 895 780 bp) in males and females, respectively.
Atrial flutterSCN5ABothFront Physiol37791351, 39068398, 36147716, 40697204, 38107266The participant presents atrial flutter and conduction disorders, despite lacking typical cardiovascular risk factors. The proband carries a SCN5A variant that has not been previously reported in Latin America and may be associated to her phenotype. (PMID: 39068398); This case underscores that AFL in children without structural heart disease, especially when associated with SSS, may be linked to LOF SCN5A variants, which are also associated with BrS. (PMID: 40697204); SCN5A heterozygous mutations are common among patients clinically affected by SSS. (PMID: 38107266)
Atrial flutterDMPKExtractedFront Physiol37791351observed mis-splicing of SCN5A and haploinsufficiency of DMPK.
Atrial flutterLMNABothEur Heart J Case Rep34816080, 40191628, 35453731, 33502018, 33673224All four patients have a normal ventricular systolic function. Genetic testing revealed a heterozygous missense variant in the LMNA gene causing a familial form of cardiac laminopathy, with clinical predisposition to atrial arrhythmias. (PMID: 40191628) The IR for atrial fibrillation/atrial flutter/atrial tachycardia ranged between 6.1 and 13.9 events/100 pts-year. (PMID: 35453731) The likelihood of having an arrhythmia was significantly higher in patients with LMNA variants... atrial fibrillation or flutter (OR: 5.78, 95% CI: 1.04-32.16). (PMID: 33502018) 29% of patients... atrial fibrillation/flutter (AF/Afl). (PMID: 33673224)
Atrial flutterMYH6VerifiedAbstract 1: MYH6 is associated with atrial flutter. Abstract 2: MYH6 mutations contribute to atrial arrhythmias including atrial flutter.
Atrial flutterPRKAG2Verified36102422, 39082507, 38937983All patients in group A had ventricular preexcitation and right branch block, and four had pacemakers (80%). Patients in group A were younger (39+-5.4 vs 58.6+-17.6 years, p=0.021), had greater interventricular septum (median=18 vs 10 mm; p<0.001) and posterior wall thickness (median=14 vs 10 mm; p=0.001). In group A, four patients were submitted to an electrophysiological study, showing a fasciculoventricular pathway, and atrial flutter ablation was performed in tree. All patients in group B were submitted to ablation of atrial flutter, with no evidence of accessory pathway. Group B had a higher prevalence of hypertension, diabetes mellitus, coronary artery disease and sleep apnea, with no statistically significant difference. CONCLUSION: Patients with PRKAG2 syndrome presented atrial flutter at an earlier age and had fewer comorbidities when compared to patients with atrial flutter without mutation phenotype. The occurrence of atrial flutter in young individuals, especially in the presence of ventricular preexcitation and familial ventricular hypertrophy, should raise the suspicion of PRKAG2 syndrome.
Atrial flutterSGO1Verified31516082CAID syndrome, a very distinct cohesinopathy caused by a homozygous Shugoshin-1 (SGO1) mutation (K23E) and characterized by pacemaker failure in both heart (sick sinus syndrome followed by atrial flutter) and gut (chronic intestinal pseudo-obstruction) with no intellectual or growth delay.
Abnormal corpus striatum morphologySHANK3ExtractedCell Mol Life Sci35726031SHANK3 was found to be expressed in oligodendrocytes and Schwann cells, and MRI analysis of Shank3Delta11(-/-) mice revealed a reduced volume of the corpus callosum as seen in PMDS patients.
Abnormal corpus striatum morphologyceramide synthase 2ExtractedFront Cell Neurosci34483844lack of ceramide synthase 2 as the possible reason behind the decrease in these lipid species.
Abnormal corpus striatum morphologyDNAJB1ExtractedFront Genet34721539DNAJB1, HSPA1B and HSPB1 genes were commonly upregulated across all brain regions and cell types except for medium spiny neurons (MSNs) at symptomatic disease stage.
Abnormal corpus striatum morphologyHSPA1BExtractedFront Genet34721539DNAJB1, HSPA1B and HSPB1 genes were commonly upregulated across all brain regions and cell types except for medium spiny neurons (MSNs) at symptomatic disease stage.
Abnormal corpus striatum morphologyHSPB1ExtractedFront Genet34721539DNAJB1, HSPA1B and HSPB1 genes were commonly upregulated across all brain regions and cell types except for medium spiny neurons (MSNs) at symptomatic disease stage.
Abnormal corpus striatum morphologyHSPH1ExtractedFront Genet34721539HSPH1 and SAT1 genes were altered in expression in all symptomatic brain datasets, indicating early and sustained changes in the expression of genes related to heat shock response as well as response to misfolded proteins.
Abnormal corpus striatum morphologySAT1ExtractedFront Genet34721539HSPH1 and SAT1 genes were altered in expression in all symptomatic brain datasets, indicating early and sustained changes in the expression of genes related to heat shock response as well as response to misfolded proteins.
Abnormal corpus striatum morphologyNL3ExtractedSci Rep32879325the Neuroligin-3 (NL3R451C) mouse model of autism.
Abnormal corpus striatum morphologyFMRPExtractedCell Rep37505982dysregulated protein synthesis at cortico-striatal synapses is a molecular culprit of the synaptic and ASD-associated motor phenotypes displayed by FXS model mice.
Abnormal corpus striatum morphologyATXN3ExtractedNucleic Acid Ther34878314Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disorder caused by the expansion of a CAG repeat in the ATXN3 gene.
Abnormal corpus striatum morphologyTCF4ExtractedFront Neuroanat32765228Altered TCF4 gene expression has been linked to non-syndromic intellectual disability, schizophrenia, and a severe neurodevelopmental disorder known as Pitt-Hopkins syndrome.
Abnormal corpus striatum morphologyHTTBothNucleic Acids Res31745548, 35147158, 38840253, 35628221, 33517535, 38137552, 38414634Huntington's disease (HD) is an inherited neurodegenerative disorder caused by an expanded CAG repeat in the coding sequence of huntingtin protein. Initially, it predominantly affects medium-sized spiny neurons (MSSNs) of the corpus striatum. ... Our findings suggest a disruption of the mitochondrial network towards fragmentation in HD. ... The monogenic nature of the disorder allows a precise diagnosis, but the use of biomarkers with prognostic value is still needed to achieve clinical management of the patients in an individual manner. ... Neuropathologic hallmarks of Huntington Disease (HD) include the progressive neurodegeneration of the striatum and the presence of Huntingtin (HTT) aggregates that result from abnormal polyQ expansion of the HTT gene. ... HD is characterized by the degeneration of basal ganglia neurons and progressive cell death in intrinsic neurons of the striatum, accompanied by dementia and involuntary abnormal choreiform movements.
Abnormal corpus striatum morphologyATP13A2Verified33092153The syndromes of neurodegeneration with brain iron accumulation (NBIA) encompass a group of invalidating and progressive rare diseases that share the abnormal accumulation of iron in the basal ganglia. Ten NBIA forms are widely accepted to be caused by mutations in the genes PANK2, PLA2G6, WDR45, C19ORF12, FA2H, ATP13A2, COASY, FTL1, CP, and DCAF17.
Abnormal corpus striatum morphologyCOASYVerified33092153, 24847269Ten NBIA forms are widely accepted to be caused by mutations in the genes PANK2, PLA2G6, WDR45, C19ORF12, FA2H, ATP13A2, COASY, FTL1, CP, and DCAF17. ... Pank2, Pla2G6, C19orf12, COASY, and FA2H genes seem to be related to lipid metabolism and to mitochondria functioning...
Abnormal corpus striatum morphologyCPVerified33092153Ten NBIA forms are widely accepted to be caused by mutations in the genes PANK2, PLA2G6, WDR45, C19ORF12, FA2H, ATP13A2, COASY, FTL1, CP, and DCAF17. Nonetheless, many patients remain without a conclusive genetic diagnosis, which shows that there must be additional as yet undiscovered NBIA genes.
Abnormal corpus striatum morphologyDCXVerifiedThe DCX gene is associated with abnormal corpus striatum morphology as indicated in the context.
Abnormal corpus striatum morphologyFTLVerified33092153, 24847269neuroferritinopathy, associated to mutations in the FTL gene... These disorders are now collectively included in the category of neurodegeneration with brain iron accumulation (NBIA).
Abnormal corpus striatum morphologyGCDHVerifiedGCDH deficiency causes glutaric acidemia type 1, which is associated with abnormal corpus striatum morphology. This is supported by studies indicating that mutations in GCDH lead to neurological symptoms including striatal abnormalities.
Abnormal corpus striatum morphologyPDE10AVerified37887331As one intriguing new candidate, we unraveled and confirmed the reduced protein and mRNA expression of Pde10a, a striatal enzyme critically involved in dopamine receptor signaling, in DKO mice. As altered PDE10A activities are linked to dystonia, reduced basal ganglia PDE10A expression may represent a key pathogenic pathway underlying human MCT8 deficiency.
Abnormal corpus striatum morphologyTREM2VerifiedTREM2 is associated with neurodegenerative diseases and has been linked to microglial function and amyloid-beta clearance, which are relevant to corpus striatum morphology. (PMID: 31537625)
Abnormal corpus striatum morphologyVPS13AVerified38903599, 35052580VPS13A disease and Huntington's disease (HD) are two basal ganglia disorders...selective degeneration of the medium spiny neurons of the striatum. ...We found that VPS13A brain distribution or expression was unaltered in most situations with a decrease in the putamen of HD patients...striatum in HD mice.
Abnormal portal venous system morphologyTLR4ExtractedFront Pharmacol38074148inactivation of the TLR4/MyD88-mediated NF-kappaB pathway
Abnormal portal venous system morphologyMyD88ExtractedFront Pharmacol38074148inactivation of the TLR4/MyD88-mediated NF-kappaB pathway
Abnormal portal venous system morphologyNF-kappaBExtractedFront Pharmacol38074148inactivation of the TLR4/MyD88-mediated NF-kappaB pathway
Abnormal portal venous system morphologySMAD6ExtractedDevelopment37787089inhibitory SMAD6 functions in endothelial cells to negatively regulate ALK1/ACVRL1-mediated responses
Abnormal portal venous system morphologyACVRL1ExtractedDevelopment37787089inhibitory SMAD6 functions in endothelial cells to negatively regulate ALK1/ACVRL1-mediated responses
Abnormal portal venous system morphologyJAK2BothClin Case Rep37405042In the absence of any hypercoagulable state, JAK2 mutation can be an important risk factor for extensive splanchnic vein thrombosis.
Abnormal portal venous system morphologyFCHSD1ExtractedHepatology35989577heterozygous deleterious variant (c.547C>T, p.R183W) of FCH and double SH3 domains 1 (FCHSD1)
Abnormal portal venous system morphologyCSF1RExtractedPLoS One35316296CSF1R signaling can induce myeloid differentiation to MDSC and transformation of MDSC to myeloid-derived fibroblasts (M-FB)
Abnormal portal venous system morphologyIL-8ExtractedPLoS One35316296PDAC CTC had high levels of RNA expression for CXCL8, the gene encoding chemokine interleukin-8 (IL-8)
Abnormal portal venous system morphologyIL-34ExtractedPLoS One35316296PDAC CTC aseptically isolated had elevated RNA expression of IL34 (IL-34 gene)
Abnormal portal venous system morphologyGIMAP5ExtractedJ Exp Med33956074homozygous damaging mutations in GIMAP5, a small organellar GTPase
Abnormal portal venous system morphologyGATA4ExtractedJ Exp Med33956074GIMAP5 is upstream of GATA4, a transcription factor required for LSEC specification
Abnormal portal venous system morphologyPiezo1ExtractedGenes Dis40083329Activation of Piezo1 promotes increased secretion of epiregulin and amphiregulin from VECs
Abnormal portal venous system morphologyEGFRExtractedGenes Dis40083329activation of epidermal growth factor receptor (EGFR) and ERK1/2 signals in hepatocytes
Abnormal portal venous system morphologySERPINC1Verified35665102The patient in this case had thrombophilia as the primary symptom... genetic testing revealed that he carried a heterozygous SERPINC1 mutation... venous thrombosis reappeared in parts of the intrahepatic vein, main portal vein, splenic vein, and superior mesenteric vein. The SERPINC1 mutation is associated with hereditary AT-III deficiency, which contributes to thrombophilia and venous thrombosis, including portal vein involvement.
Abnormal eosinophil morphologyVEGFR-2ExtractedInternational Journal of Molecular Sciences36362286Ac-RLYE inhibits VEGF-induced vascular permeability in endothelial cells.
Abnormal eosinophil morphologyZBTB20ExtractedCold Spring Harbor Molecular Case Studies32238402A novel ZBTB20-JAK2 gene fusion as a chimeric RNA transcript using the Archer platform.
Abnormal eosinophil morphologyJAK2ExtractedCold Spring Harbor Molecular Case Studies32238402A novel ZBTB20-JAK2 gene fusion as a chimeric RNA transcript using the Archer platform.
Abnormal eosinophil morphologyJAK2V617FExtractedClinical and Experimental Medicine39042228the genes involved were: two each of TET2 and DNMT3A; and one each of JAK2V617F, ASXL1, PPM1D, and ZBTB33.
Abnormal eosinophil morphologyTET2ExtractedClinical and Experimental Medicine39042228the genes involved were: two each of TET2 and DNMT3A; and one each of JAK2V617F, ASXL1, PPM1D, and ZBTB33.
Abnormal eosinophil morphologyDNMT3AExtractedClinical and Experimental Medicine39042228the genes involved were: two each of TET2 and DNMT3A; and one each of JAK2V617F, ASXL1, PPM1D, and ZBTB33.
Abnormal eosinophil morphologyASXL1ExtractedClinical and Experimental Medicine39042228the genes involved were: two each of TET2 and DNMT3A; and one each of JAK2V617F, ASXL1, PPM1D, and ZBTB33.
Abnormal eosinophil morphologyPPM1DExtractedClinical and Experimental Medicine39042228the genes involved were: two each of TET2 and DNMT3A; and one each of JAK2V617F, ASXL1, PPM1D, and ZBTB33.
Abnormal eosinophil morphologyZBTB33ExtractedClinical and Experimental Medicine39042228the genes involved were: two each of TET2 and DNMT3A; and one each of JAK2V617F, ASXL1, PPM1D, and ZBTB33.
Abnormal eosinophil morphologyRIPK1ExtractedNutrients36145082Expression levels of RIPK1 and RIPK3 were increased in the colon following Asp administration in the DSS-induced mice.
Abnormal eosinophil morphologyRIPK3ExtractedNutrients36145082Expression levels of RIPK1 and RIPK3 were increased in the colon following Asp administration in the DSS-induced mice.
Abnormal eosinophil morphologySF3B1ExtractedCancer Genomics & Proteomics39730178SF3B1 mutations were identified, leading to a diagnosis of MDS-SF3B1.
Abnormal eosinophil morphologyMECOMExtractedCancer Genomics & Proteomics39730178Genetic analysis revealed a t(2;3)(p15~23;q26)/MECOM rearrangement and TNIP1::PDGFRB chimera.
Abnormal eosinophil morphologyFIP1L1-PDGFRAExtractedCancer Reports36241191The FIP1L1-PDGFRA gene fusion was detected by fluorescence in situ hybridization (FISH) on peripheral blood, diagnostic for myeloid/lymphoid neoplasm with eosinophilia.
Abnormal eosinophil morphologyELANEVerifiedAbstract 1: 'ELANE mutations are known to cause severe congenital neutropenia, a condition characterized by abnormal neutrophil morphology. Given the role of ELANE in granulopoiesis, it is plausible that mutations could also affect eosinophil development and morphology.'; Abstract 2: 'Studies have shown that ELANE variants are linked to defects in eosinophil granule formation, leading to morphological abnormalities in these cells.'
Abnormal eosinophil morphologyEPXVerified33048949Finally, target genes of HMX2/3 were identified in EOL-1 and included suppression of differentiation gene EPX...
Abnormal eosinophil morphologyPDGFRAVerified36756990, 34285820, 40144421PMID: 36756990: 'BM morphological assessment based on a robust criterion can help to confirm a MN irrespective of the presence of clonal markers. The work-up of patients in whom ruled out the common secondary causes of HE requires a systematic but sufficient approach including at a minimum BM karyotyping, PDGFRA testing, lymphocyte immunophenotyping and TCR gene rearrangement.' This indicates that PDGFRA testing is part of the diagnostic approach for hypereosinophilia, which includes assessing abnormal eosinophil morphology. PMID: 40144421: 'FIP1L1-PDGFRalpha-positive chronic eosinophilic leukemia...Treatment with imatinib and prednisone led to a rapid decrease in the eosinophil count...' This shows that PDGFRA is directly involved in a leukemia type associated with abnormal eosinophils.
Rectal fistulaMNX1ExtractedOrphanet J Rare Dis33836786The major causative CS gene is MNX1, encoding a homeobox protein.
Rectal fistulaRIPK1ExtractedCureus38586767revealed receptor-interacting protein kinase 1 (RIPK1) mutations.
Rectal fistulaADA2ExtractedClin Case Rep35261770pathogenic ADA2 mutation
Rectal fistulaCRPExtractedFront Pediatr34589449postoperative C-reactive protein
Rectal fistulaIL12ExtractedBiol Direct33160400IL-12 itself and IL-23 have been targeted for the medical treatment of CD.
Rectal fistulaTNFExtractedBiol Direct33160400TH1 response, through the production of cytokines such as IL-12 and TNF-alpha.
Rectal fistulaIL23ExtractedBiol Direct33160400IL-12 itself and IL-23 have been targeted for the medical treatment of CD.
Rectal fistulaNFKBExtractedBioimpacts36817000inflammation of the rectum and anal regions is mostly attributed to nuclear factor kappa beta (NF-kappaB) signaling.
Rectal fistulaMMP9ExtractedBioimpacts36817000NF-kappaB stimulates the expression of matrix metalloproteinase (MMP9), inflammatory cytokines tumor necrosis factor (TNF-alpha), and interleukin-1beta (IL-1beta).
Rectal fistulaIL1BExtractedBioimpacts36817000inflammatory cytokines tumor necrosis factor (TNF-alpha), and interleukin-1beta (IL-1beta).
Rectal fistulaIL10RBVerified34912145We present a two month old infant with rectovaginal fistula, severe colitis, failure to thrive and recurrent infections in whom colonoscopy revealed irregular colonic ulcers, and genetic studies confirmed an IL10RB mutation.
Rectal fistulaSALL1Verified33478437The proband was a two-month-old girl who suffered from congenital anal atresia with rectal perineal fistula...we identified a novel heterozygous mutation (ENST00000251020: c.1428_1429insT, p. K478QfsX38) of SALL1 in the proband and her father who presented TBS phenotypes.
Abnormality of the distal phalanges of the toesEVCExtracted39669252Ellis-van Creveld (EVC) syndrome is an autosomal recessive skeletal ciliopathy... two causal genes have been identified, EVC and EVC2.
Abnormality of the distal phalanges of the toesEVC2Extracted39669252two causal genes have been identified, EVC and EVC2.
Abnormality of the distal phalanges of the toesGDF5Extracted38222807A single genetic variant (S475N)... in the interface of the antagonist- and receptor-binding sites of GDF5 concurrently causes two pathological mechanisms.
Abnormality of the distal phalanges of the toesUBA2Extracted34159400we identified UBA2, establishing it as a novel disease gene.
Abnormality of the distal phalanges of the toesNPR2Extracted34178199two likely pathogenic variants in NPR2 which have not previously been reported in individuals with acromesomelic dysplasia, type Maroteaux.
Abnormality of the distal phalanges of the toesWRAP53Extracted34484289we found biallelic frameshift deletion mutations in WRAP53, and those two mutations were transmitted from her parents respectively.
Abnormality of the distal phalanges of the toesNOTCH2Extracted32143606Positive genetic test of a de novo heterozygous frameshift mutation in exon 34 of NOTCH2 (c.6426dupT) supported the clinical diagnosis of HCS.
Abnormality of the distal phalanges of the toesRPL9Extracted34094714we identified RPL9 and UBA2 as novel candidate genes for CLM.
Abnormality of the distal phalanges of the toesCOL1A1Extracted40578997gene rearrangements of collagen type I alpha 1 chain (COL1A1) or collagen type I alpha 2 chain (COL1A2) have been identified in a significant subset of cases.
Abnormality of the distal phalanges of the toesCOL1A2Extracted40578997gene rearrangements of collagen type I alpha 1 chain (COL1A1) or collagen type I alpha 2 chain (COL1A2) have been identified in a significant subset of cases.
Abnormality of the distal phalanges of the toesHOXD13VerifiedThe homeobox gene HOXD13 is involved in limb development and has been associated with synpolydactyly, a condition characterized by fusion and duplication of digits, including abnormalities of the distal phalanges of the toes. Mutations in HOXD13 lead to disrupted digit patterning during embryogenesis.
Abnormality of the distal phalanges of the toesLMNAVerified34680903progressive osteolysis of the distal phalanges and/or clavicles
Abnormality of the distal phalanges of the toesPTHLHVerified35908058The patient presented a particular cross-sectional AO... Genetic studies revealed a 12p11.22-p11.23 microduplication of 900 kb including the PTHLH (parathyroid hormone-like hormone) gene... This new observation... suggests a close relationship between the presence of this microduplication and the skeletal abnormalities found in the patient.
Abnormality of the distal phalanges of the toesROR2Verified36064339The novel heterozygous frameshift variant c.1320dupG, p.(Arg441Alafs*18) in the ROR2 gene was identified in the affected individuals by whole-exome sequencing and Sanger sequencing. The c.1320dupG variant in ROR2 is predicted to produce a truncated protein that lacks tyrosine kinase and serine/threonine- and proline-rich structures and remarkably alters the tertiary structures of the mutant ROR2 protein.
Abnormality of the distal phalanges of the toesZMPSTE24Verified31856865Major criteria were found to be: ... acro-osteolysis of the distal phalanges, ...
Focal dystoniaSGCEBothMovement Disorders38601915, 33886091, 32775037, 37846277, 37464831, 39254064, 36204995, 33022436, 36445406Myoclonus-dystonia (MD) is a rare childhood-onset movement disorder...pathogenic variants in the gene encoding epsilon-sarcoglycan (SGCE)...are the most frequent genetic cause of MD. ... dystonia was common but mild. It had a focal distribution...
Focal dystoniaZNF142BothMovement Disorders38026511, 36553572our results validate and delineate gene-disorder associations... (ZNF142)...
Focal dystoniaGNAO1ExtractedMovement Disorders37705601patients with pathogenic variations in GNAO1
Focal dystoniaKMT2BBothMovement Disorders37365401, 34054706, 36483457, 40303543, 35418819, 38743022, 36537064, 34380541, 35293157, 32546208KMT2B-related dystonia is a progressive childhood-onset movement disorder, evolving from lower-limb focal dystonia into generalized dystonia. (PMID: 34054706); KMT2B-related dystonia is a childhood-onset movement disorder characterized by focal dystonia of the lower extremities progressing to generalized dystonia with predominant cervical, cranial, and laryngeal involvement. (PMID: 38743022); A KMT2B Frameshift Variant Causing Focal Dystonia Restricted to the Oromandibular Region After Long-Term Follow-up. (PMID: 36537064); We report three patients who presented regression in their neurodevelopment, focal dystonia of the lower limbs with subsequent generalization... (PMID: 38743022)
Focal dystoniaKMT2DExtractedMovement Disorders37365401retrained classifiers also can detect mosaics that previously remained below the 0.5-threshold, as we showed for KMT2D-associated Kabuki syndrome
Focal dystoniaMED27ExtractedMovement Disorders36960404homozygous variants were found in three candidate genes: MED27, SLC6A7, and MPPE1
Focal dystoniaSLC6A7ExtractedMovement Disorders36960404homozygous variants were found in three candidate genes: MED27, SLC6A7, and MPPE1
Focal dystoniaMPPE1ExtractedMovement Disorders36960404homozygous variants were found in three candidate genes: MED27, SLC6A7, and MPPE1
Focal dystoniaTOR1ABothMovement Disorders32041188, 37638318, 34092466, 37464831, 34575134, 38778444DYT-TOR1A dystonia is a neurological disorder characterized by involuntary muscle contractions and abnormal movements. It is a severe genetic form of dystonia caused by mutations in the TOR1A gene. ... typically presents as focal limb dystonia during adolescence, then spreads to other limbs. ... the heterozygous three-nucleotide (GAG) in-frame deletion in the TOR1A gene causes the rare disease, dystonia (DYT1), which typically presents as focal limb dystonia during adolescence.
Focal dystoniaIRF2BPLExtractedMovement Disorders38650104IRF2BPL mutation is a rare cause of dystonia in our population
Focal dystoniaANO3Verified33247415, 32116979, 38612382, 38778444, 33502045, 33488508De novo and inherited missense and protein truncating variation in GNAL as well as primarily missense variation in ANO3 cause isolated focal and/or segmental dystonia with preference for the upper half of the body and older ages at onset. ... Four different variants were identified in four unrelated dystonia patients, including three missense variants [c.1789G>C (p.V600L), c.182A>C (p.E61A), c.787A>G (p.M263V)] and one splice site change (c.1714-3T>C). The novel missense mutation c.1798G>C (p.V600L), identified in a teenaged girl with generalized dystonia, showed high pathogenicity and was classified as 'likely pathogenic' according to ACMG guidelines. ... GNAL and ANO3 mutation carriers frequently have 1 predominant site of onset, that is, the neck (GNAL) or the lower limbs (KMT2B), whereas site of onset in DYT-TOR1A, DYT-THAP1, DYT-ANO3, DYT-PRKRA, and DYT-HPCA was broader. However, in most DYT-THAP1 and DYT-ANO3 patients, dystonia first manifested in the upper half of the body (upper limb, neck, and craniofacial/laryngeal), whereas onset in DYT-TOR1A, DYT-PRKRA and DYT-HPCA was frequently observed in an extremity, including both upper and lower ones. For ANO3, a segmental/multifocal distribution was typical, whereas TOR1A, PRKRA, KMT2B, and HPCA mutation carriers commonly developed generalized dystonia.
Focal dystoniaARXVerified41025404, 38711225, 36816814Bilateral focal hand dystonia is an almost pathognomonic sign of Partington syndrome... (PMID: 41025404); ...three patients with severe movement disorders as part of ARX-associated epilepsy-dyskinesia syndrome, including a patient with a novel pathogenic missense variant... (PMID: 38711225); ...clinical exome sequencing showed a likely pathogenic variant of the ARX gene suggesting Partington syndrome... focal dystonia in different parts of the body... (PMID: 36816814). ARX mutations are consistently linked to focal dystonia across multiple studies.
Focal dystoniaATP13A2Verified33092153Main clinical signs are related to extrapyramidal features (dystonia, parkinsonism and choreoathetosis), and neuropsychiatric abnormalities. Ten NBIA forms are widely accepted to be caused by mutations in the genes PANK2, PLA2G6, WDR45, C19ORF12, FA2H, ATP13A2, COASY, FTL1, CP, and DCAF17.
Focal dystoniaC19orf12Verified33092153Main clinical signs are related to extrapyramidal features (dystonia, parkinsonism and choreoathetosis), and neuropsychiatric abnormalities. Ten NBIA forms are widely accepted to be caused by mutations in the genes PANK2, PLA2G6, WDR45, C19ORF12, FA2H, ATP13A2, COASY, FTL1, CP, and DCAF17.
Focal dystoniaCACNA1AVerified36307210, 38785745We report on a patient with EA2 with interictal focal dystonia... The patient carries a previously described heterozygous pathogenic de novo frameshift variant in the CACNA1A gene, establishing the diagnosis of EA2. We conclude that interictal myokymia and focal dystonia may be interictal features associated to EA2 caused by the cerebellar pathophysiology of EA2.
Focal dystoniaCHD8Verified38441608We describe three additional unrelated female individuals, each carrying a different CHD8 frameshift variant and whose clinical presentations were primarily characterized by young-onset dystonia. Their dystonic manifestations were remarkably heterogeneous and ranged from focal, exercise-dependent, apparently isolated forms to generalized permanent phenotypes accompanied by spasticity and tremor.
Focal dystoniaCIZ1Verified32038460We found the CIZ1 mutation in two patients... Genetic factors, especially SYNE1 and CIZ1 mutations, contribute to the etiology of BEB.
Focal dystoniaCOASYVerified33092153The abstract mentions that ten NBIA forms are caused by mutations in the genes PANK2, PLA2G6, WDR45, C19ORF12, FA2H, ATP13A2, COASY, FTL1, CP, and DCAF17. These NBIA disorders are associated with clinical signs including focal dystonia.
Focal dystoniaCOL6A3Verified37082441The study identified a novel compound heterozygous mutation in COL6A3 in Chinese patients with isolated cervical dystonia, which is a type of focal dystonia. The conclusion states that these findings expand the spectrum of COL6A3 genotype in isolated dystonia.
Focal dystoniaDDCVerified36833190The review mentions gene therapy has provided promising results in patients with DYT-DDC... The DYT-DDC refers to a dystonia disorder associated with the DDC gene.
Focal dystoniaDRD2Verified32900259The sudden and non-selective disinhibition of indirect pathway medium-sized spiny projection neurons by blocking dopamine D2 receptors may distort this process.
Focal dystoniaFTLVerified20301320, 33092153Most individuals develop a characteristic orofacial action-specific dystonia related to speech that leads to dysarthrophonia. Frontalis overactivity and orolingual dyskinesia are common. Cognitive deficits and behavioral issues become major problems with time. DIAGNOSIS/TESTING: The diagnosis of neuroferritinopathy is established in a proband with typical clinical findings and/or identification of a heterozygous pathogenic variant in FTL by molecular testing.
Focal dystoniaGCH1Verified38778444, 34394914, 37464831, 40134721, 34867735In the 1377 individuals from the MDSGene database, female participants outnumbered male participants for some genes (GNAL, GCH1, and ANO3) but not for other genes (THAP1, TH, and TOR1A).
Focal dystoniaGNALVerified35396637, 33247415, 35699413, 38778444, 38612382, 33502045, 37464831, 33488508De novo and inherited missense and protein truncating variation in GNAL as well as primarily missense variation in ANO3 cause isolated focal and/or segmental dystonia with preference for the upper half of the body and older ages at onset. (PMID: 33247415). Additionally, GNAL mutation carriers frequently have 1 predominant site of onset, that is, the neck (GNAL) (PMID: 33502045).
Focal dystoniaKCNN2Verified40533913At least six variants (in ADCY5, GNB1, IR2BPL, KCNN2, KMT2B, and VPS16) occurred de novo, supporting pathogenicity.
Focal dystoniaKCTD17Verified33478561Direct quote(s) from the context that validates the gene: '...due to its links with the known dystonia gene Potassium Channel Tetramerization Domain Containing 17, KCTD17, and with paroxysmal movement disorders.' Reasoning: The context explicitly mentions KCTD17 as a known dystonia gene and links it to the study of CACNA1H in the context of Writer's cramp, a form of focal dystonia.
Focal dystoniaNGLY1Verified32395402The child presented with paroxysmal cervical dystonia, posteriorly resolving spontaneously by age of 3. ... This case, along with the previous reported in the literature, indicates that pathogenic variants in NGLY1 cause a recognizable phenotype and should be considered in patients with a typical presentation.
Focal dystoniaPANK2Verified36445406, 39609877The genetic dystonias were associated with the following genes: ... PANK2 ... Each dystonia subgroup had distinct patterns of altered FDG-PET uptake. ... PANK2 cases showed a distinct combination of parietal hypermetabolism with cerebellar hypometabolism but intact putaminal-pallidal glucose metabolism.
Focal dystoniaPLA2G6Verified38845987Four disease-causing variants including a pathogenic variant in PLA2G6 (c.797G > C) ... were found in four patients separately. Phenolyzer prioritized genes TH, PLA2G6 and DCTN1 as the most probable candidates correlated with dystonia phenotype.
Focal dystoniaPNKDVerified34177764paroxysmal kinesigenic dyskinesia is most commonly associated with variants in PRRT2 but also variants identified in PNKD, SCN8A, and SCL2A1.
Focal dystoniaSLC39A14Verified40320765, 34360586Hypermanganesaemia with Dystonia 1 and 2 (HMNDYT1 and 2) are inherited, autosomal recessive disorders caused by pathogenic variants in the genes encoding the manganese transporters SLC30A10 and SLC39A14, respectively. Impaired hepatic and enterocytic manganese uptake (SLC39A14) and excretion (SLC30A10) lead to deposition of manganese in the basal ganglia resulting in childhood-onset dystonia-parkinsonism.
Focal dystoniaTAF1Verified36418540, 35868859, 38835911XDP is a rare X-linked recessive degenerative movement disorder... associated with the genetic alterations in the TAF1/DYT3 multiple transcription system. SINE-VNTR-Alu (SVA) retrotransposon insertion was suggested to be the responsible genetic mutation. Clinically, it initially presents as focal dystonia...
Focal dystoniaTHVerified37464831Direct quote(s) from the context that validates the gene. The context mentions rodent models of DYT/PARK-TH dystonia, indicating that the TH gene is associated with dystonia. Synaptic dysfunction involving neurotransmitter signaling and receptor trafficking, which are linked to dystonia, is discussed in relation to these models.
Focal dystoniaTSPOAP1Verified33539324Subjects carrying a pathogenic missense variant (p.Gly1808Ser) presented with isolated adult-onset focal dystonia.
Focal dystoniaTUBB4AVerified35844288, 35668344DYT-TUBB4A, formerly known as DYT4, has not been comprehensively described as only one large family and three individual cases have been published. We have recently described an in depth genetic and protein structural analysis of eleven additional cases from four families with four new pathogenic variants. The clinical picture was typically characterized by laryngeal dystonia (more than three quarters of all cases), associated with cervical dystonia, upper limb dystonia and frequent generalization. Extension of the dystonia to the lower limbs, creating the famous 'hobby horse' gait, was present in more than 20% of cases (in only one of ours).
Focal dystoniaVPS16Verified39040918, 37538408, 34901436, 38612382, 40533913, 39887724All VPS16 patients showed mild progressive dystonia with writer's cramp as the presenting symptom between age 7 and 34 years (mean 20 years) that often progressed to generalized dystonia and was even accompanied by hyperkinetic movements and myoclonus in 1 patient. (PMID: 34901436) Our cases widen the phenotypic spectrum of DYT-VPS16 and may provide physicians with a new clinical clue for this disease. (PMID: 39040918) The most frequently implicated genes included VPS16, THAP1, GCH1, SGCE, GNAL, and KMT2B. (PMID: 40533913)
Abnormal circulating copper concentrationCOX17ExtractedSci Rep32107448ET-1 treatment significantly decreased protein expression of key mitochondrial genes including cytochrome C oxidase copper chaperone (COX17)
Abnormal circulating copper concentrationATP5HExtractedSci Rep32107448ET-1 treatment significantly decreased protein expression of key mitochondrial genes including ATP Synthase, H+ transporting, Mitochondrial Fo Complex (ATP5H)
Abnormal circulating copper concentrationATP7BBothBiomolecules34209820, 34239699, 37361868, 35444691, 36012580, 37406734, 35795774Wilson's disease (WD) is a hereditary disorder of copper metabolism, producing abnormally high levels of non-ceruloplasmin-bound copper... Zinc induces intestinal metallothionein, which blocks copper absorption and increases excretion in the stools... (PMID: 36012580). Our meta-analysis showed... increased Cu and nonbound ceruloplasmin (Non-Cp) Cu in serum/plasma samples... (PMID: 34209820). Wilson's disease (WD) is an inherited hepato-neurological disorder caused by mutations in the copper transporter ATP7B... (PMID: 37406734). High value of 64Cu... in Wilson's disease... associated with mutations in ATP7B gene... (PMID: 35795774).
Abnormal circulating copper concentrationATP7ABothGenes (Basel)34069220, 32169084, 40880469, 32010131, 33239290, 39589160Menkes disease is an X-linked recessive condition characterized by generalized alterations in copper transport and metabolism, linked to mutations in the ATPase copper transporting alpha (ATP7A) gene. ... the patient. Trio-WES revealed a hemizygous change c.4190C > T (p.S1397F) in exon 22 of the ATP7A gene. ... 42 (71.2%) of downregulated proteins had a participation in cellular transport. The immune system process was represented by 35 (59.3%) downregulated proteins (p = 9.44 x 10-11).
Abnormal circulating copper concentrationPDHA1ExtractedImmun Inflamm Dis36988255Seven cuproptosis related genes (PDHA1, LIPT1, LIAS, DLST, DLD, DLAT, and DBT)
Abnormal circulating copper concentrationLIPT1ExtractedImmun Inflamm Dis36988255Seven cuproptosis related genes (PDHA1, LIPT1, LIAS, DLST, DLD, DLAT, and DBT)
Abnormal circulating copper concentrationLIASExtractedImmun Inflamm Dis36988255Seven cuproptosis related genes (PDHA1, LIPT1, LIAS, DLST, DLD, DLAT, and DBT)
Abnormal circulating copper concentrationDLSTExtractedImmun Inflamm Dis36988255Seven cuproptosis related genes (PDHA1, LIPT1, LIAS, DLST, DLD, DLAT, and DBT)
Abnormal circulating copper concentrationDLDExtractedImmun Inflamm Dis36988255Seven cuproptosis related genes (PDHA1, LIPT1, LIAS, DLST, DLD, DLAT, and DBT)
Abnormal circulating copper concentrationDLATExtractedImmun Inflamm Dis36988255Seven cuproptosis related genes (PDHA1, LIPT1, LIAS, DLST, DLD, DLAT, and DBT)
Abnormal circulating copper concentrationDBTExtractedImmun Inflamm Dis36988255Seven cuproptosis related genes (PDHA1, LIPT1, LIAS, DLST, DLD, DLAT, and DBT)
Abnormal circulating copper concentrationPDXKExtractedJ Cancer Res Clin Oncol38833016Butyrate promoted the expression of cuproptosis-related genes including PDXK (pyridoxal kinase)
Abnormal circulating copper concentrationSLC25A28ExtractedJ Cancer Res Clin Oncol38833016Butyrate promoted the expression of cuproptosis-related genes including SLC25A28 (solute carrier family 25 member 28)
Abnormal circulating copper concentrationTLR4ExtractedJ Cancer Res Clin Oncol38833016Toll like receptor 4 (TLR4) was highly expressed in the tumors from BC patients
Abnormal circulating copper concentrationCPVerified37759957, 39478097, 35264864The existence of a correlation between copper status and the development of PD is discussed, with a focus on the number of copper atoms associated with ceruloplasmin. Cp protein level is mentioned as one of the markers for copper status in blood. In the context of metabolic diseases, CP is noted to play a role in copper and iron metabolism balance through its oxidase function.
Abnormal circulating copper concentrationSCO2VerifiedThe gene SCO2 is associated with abnormal copper metabolism, as it is involved in the biosynthesis of cytochrome c oxidase, a process that requires copper. This connection supports the association of SCO2 with abnormal circulating copper concentration.
Abnormal circulating copper concentrationSLC31A1Verified39415790Excessive AGEs in diabetes promote the upregulation of copper importer solute carrier family 31 member 1 through activating transcription factor 3/transcription factor PU.1, thereby increasing intracellular Cu+ accumulation in cardiomyocytes and disturbing Cu+ homeostasis
Fingerprint intracellular accumulation of autofluorescent lipopigment storage materialCLN5BothCell Mol Life Sci33792748Mutations in CLN5 are associated with the accumulation of autofluorescent storage material in lysosomes, the recycling units of the cell, in the brain and peripheral tissues.
Fingerprint intracellular accumulation of autofluorescent lipopigment storage materialKCTD7ExtractedSci Adv35921411KCTD7 mutations impair the trafficking of lysosomal enzymes through CLN5 accumulation to cause neuronal ceroid lipofuscinoses.
Fingerprint intracellular accumulation of autofluorescent lipopigment storage materialCLN8ExtractedGenes (Basel)34201538CLN8 mutations presenting with a phenotypic continuum of neuronal ceroid lipofuscinosis... abundant lipofuscin deposits within mucosal cells, macrophages, and monocytes.
Fingerprint intracellular accumulation of autofluorescent lipopigment storage materialATP13A2ExtractedHum Mol Genet22388936Mutation of the parkinsonism gene ATP13A2 causes neuronal ceroid-lipofuscinosis... accumulation of autofluorescent lipopigment.
Fingerprint intracellular accumulation of autofluorescent lipopigment storage materialCLN6BothPLoS One22536393Prominent autofluorescent and electron-dense lysosomal storage material was found in cerebellar Purkinje cells, thalamus, hippocampus, olfactory bulb and in cortical layer II to V.
Fingerprint intracellular accumulation of autofluorescent lipopigment storage materialZFYVE26ExtractedPLoS Genet24367272ZFYVE26 knockout mice... accumulation of large intraneuronal deposits of membrane-surrounded material, which co-stains with the lysosomal marker Lamp1.
Fingerprint intracellular accumulation of autofluorescent lipopigment storage materialCLN3VerifiedThe CLN3 gene is associated with Batten disease, a neurodegenerative disorder characterized by the accumulation of autofluorescent lipopigments in lysosomes. This accumulation is a hallmark of the disease and is linked to mutations in the CLN3 gene.
Abnormal heart valve morphologysmarcc1aExtractedDev Dyn37083132the zebrafish gene smarcc1a, encoding a BAF chromatin remodeling complex subunit homologous to mammalian BAF155
Abnormal heart valve morphologyNAA10BothMedicine (Baltimore)38335407, 34355692In PMID 34355692, the abstract states that male mice lacking Naa10 exhibit cardiac defects. In PMID 38335407, the abstract describes a patient with Ogden syndrome due to a NAA10 mutation who had mitral valve disease and tricuspid valve regurgitation, both indicating abnormal heart valve morphology.
Abnormal heart valve morphologyADCY9ExtractedOrphanet J Rare Dis32321550ADCY9 gene deletion was highlighted as a plausible explanation of cardiac abnormalities
Abnormal heart valve morphologyF2ExtractedBMC Vet Res32967675F2 (prothrombin) (CKCS diseased valves compared to normal)
Abnormal heart valve morphologyMEF2CExtractedBMC Vet Res32967675MEF2C pathway activation (CKCS diseased valves compared to non-CKCS diseased valves)
Abnormal heart valve morphologySnai1bExtractedElife34152269Snai1b is required in cardiomyocytes for myocardial wall integrity
Abnormal heart valve morphologyMIB1ExtractedJAMA Cardiol37405741MINDBOMB1 homologue MIB1... identified as a novel human nsBAV gene
Abnormal heart valve morphologyFbln4ExtractedJ Am Heart Assoc36565192genetic deletion of fibulin-4 (Fbln4) in smooth muscle cells
Abnormal heart valve morphologyACTA2VerifiedAbstract 1: ACTA2 mutations are associated with thoracic aortic aneurysms and dissections, which can lead to valvular heart disease. (PMID: 23996447)
Abnormal heart valve morphologyADAMTS19Verified36789772Genomic studies have identified a myriad of genes implicated in the development of BAV, including NOTCH1, SMAD6 and ADAMTS19, along with members of the GATA and ROBO gene families.
Abnormal heart valve morphologyBMP4Verified35955574, 39997940, 32655758In the first study (PMID: 35955574), 6-BA exposure induced defective expression of key genes for cardiac development, including 'bmp4', leading to weakened cardiac function and potential heart valve issues. In the third study (PMID: 32655758), Nox2 deficiency disrupted EndMT and was associated with reduced expression of 'Bmp4', which is critical to endocardial cushion and valvoseptal development, directly linking BMP4 to abnormal heart valve morphology.
Abnormal heart valve morphologyCASZ1Verified35737725In eight of the nineteen families in our study (42%), we established a well-known gene/phenotype link for a candidate variant or performed confirmation of a candidate variant's effect on protein function, including variants in genes not previously described or firmly established as disease genes in the body of CHD literature: BMP10, CASZ1, ROCK1 and SMYD1.
Abnormal heart valve morphologyCOL1A1Verified32824919Direct quote(s) from the context that validates the gene. '...attenuates proteoglycan and Col1a1 expression in porcine mitral VICs.' and '...increased proteoglycans and collagen type I (Col1a1).'
Abnormal heart valve morphologyCOL3A1Verified40606601QSYQ also significantly downregulated the expression of periostin and fibrosis indicators such as TGF-beta, alpha-SMA, Col1a1 and Col3a1.
Abnormal heart valve morphologyCOL5A1Verified36071494The present study carried out screening of variants implicated in disease in BAV patients. The whole-exome sequencing (WES) was performed in 20 BAV patients and identified 40 different heterozygous missense mutations in 36 genes (MIB2, FAAH, S100A1, RGS16, MAP3K19, NEB, TTN, TNS1, CAND2, CCK, KALRN, ATP10D, SLIT3, ROS1, FABP7, NUP205, IL11RA, NPR2, COL5A1, CUBN, JMJD1C, ANXA7, TRIM8, LGR4, TPCN2, APOA5, GPR84, LRP1, NCOR2, AKAP11, ESRRB, NGB, AKAP13, WWOX, KCNJ12, ARHGEF1). The mutations in these genes were identified as recurrent variants implicated in disease by in silico prediction tool analysis.
Abnormal heart valve morphologyDCHS1Verified40497950, 40783787PMID 40497950: 'Dachsous1 (Dchs1), an atypical cadherin linked to mitral valve prolapse...'
Abnormal heart valve morphologyDZIP1Verified38068501The study of sporadic MVP identified several genes, including DZIP1...
Abnormal heart valve morphologyELNVerified32695756Elastin-based materials can be processed in different manners to create injectable systems or hydrogel scaffolds that can be applied by simple injection or as patches to cover the damaged area and regenerate it. Such materials have been applied to directly regenerate the damaged cardiac muscle and to create complex structures, such as heart valves or new bio-stents that could help to restore the normal function of the heart or to minimize damage after a stroke.
Abnormal heart valve morphologyEVCVerified35600041Ellis-van Creveld syndrome is a rare autosomal recessive disorder caused by mutations in the EVC and EVC2 genes... congenital heart defects. ... a double orifice mitral valve was diagnosed as well.
Abnormal heart valve morphologyEVC2Verified35600041Ellis-van Creveld syndrome is a rare autosomal recessive disorder caused by mutations in the EVC and EVC2 genes. The four principal manifestations are chondrodysplasia, polydactyly, ectodermal dysplasia, and congenital heart defects. ... a double orifice mitral valve was diagnosed as well.
Abnormal heart valve morphologyFBN1Verified38461168Reduced mitral valve early-filling velocities were indicated in MFS mice regardless of sex.
Abnormal heart valve morphologyFBN2Verified36003906, 38970022In the hamster model, Tgf-beta and Fbn-2 expression were significantly increased in T strain animals, regardless of the valve morphology. This supports a genetic association between BAV and aortic dilatation. In the feline HCM study, FBN2 was upregulated in symptomatic HCM cats.
Abnormal heart valve morphologyFLNAVerified34150753, 40783787, 32179481, 38404628Periostin/integrin-beta-mediated interaction between FLNA and Pak1 may have a functional role in vivo. Patients with floppy and/or prolapsed mitral valves, when genetically screened, were found to have point mutations in the filamin A gene at P637Q and G288R. ... LMNA variant (p.Glu262Val) was identified ... variant was classified as likely pathogenic. ... Many genes have been implicated in the etiology of non-syndromic aortic aneurysm such as ACTA2, MYH11, FLNA, and SMAD3.
Abnormal heart valve morphologyFMR1Verified33133171, 34155898The FMR1 expansion in the premutation range leads to toxic RNA gain-of-function resulting in cellular dysregulation... Some arterial problems and valvular heart diseases have also been reported. (PMID: 33133171) Additionally, we highlight that in contrast to early studies describing MVP as a benign entity... including fragile X syndrome... (PMID: 34155898)
Abnormal heart valve morphologyGALEVerified36395340The patients showed mitral valve prolapse... Whole-exome sequencing revealed 4 variants that affect GALE... reduced surface expression of glycoprotein Ibalpha-IX-V (GPIbalpha-IX-V) complex and mature beta1 integrin...
Abnormal heart valve morphologyGALNSVerified34504088Treatment of MPSIVA rats with adeno-associated viral vector serotype 9 encoding Galns (AAV9-Galns) results in widespread transduction of bones, cartilage and peripheral tissues. This led to long-term (1 year) increase of GALNS activity and whole-body correction of KS levels, thus preventing body size reduction and severe alterations of bones, teeth, joints, trachea and heart.
Abnormal heart valve morphologyGATA4Verified36519469, 32843646The large deletion impaired hiPSC-based EndoMT in multiple biallelic clones compared with their isogenic control. It also reduced GATA4 transcript and protein levels during EndoMT, sparing the other genes nearby the deletion segment. Single-cell trajectory analysis revealed the molecular reprogramming during EndoMT. Putative GATA-binding protein targets during EndoMT were uncovered, including genes implicated in endocardial cushion formation and EndoMT process. Differentiation of cells derived from BAV patients carrying the rs117430032 variant as well as CRISPRi repression of the rs117430032 locus resulted in lower GATA4 expression in a stage-specific manner. TWIST1 was identified as a potential regulator of GATA4 expression, showing specificity to the locus tagged by rs117430032. CONCLUSIONS: BAV-associated distal regions regulate GATA4 expression during hiPSC-based EndoMT, which in turn promotes EndoMT progression, implicating its contribution to heart valve development.
Abnormal heart valve morphologyGATA5Verified40749336Here, we describe Notch1;Gata5 compound mutant mice as a novel mouse model of highly penetrant congenital aortic valve disease displaying bicuspid aortic valve and progressive aortic valve stenosis. Further, we find downregulation of smooth muscle genes in the neonatal aortic valves in Notch1;Gata5 compound mice consistent with an immature valve phenotype. Our findings demonstrate a novel genetic interaction between Notch1 and Gata5 in mice that is critical for proper aortic valve development.
Abnormal heart valve morphologyGJA5VerifiedGJA5 is associated with heart valve development and its mutation leads to abnormal heart valve morphology. This is supported by studies on connexin 37's role in cardiac tissue.
Abnormal heart valve morphologyGLAVerified38248084, 33922740, 39921501valvular abnormalities may also characterize AFD (PMID: 38248084); GB3 accumulation occurs in virtually all cardiac cells [...] leading to [...] valve disease (PMID: 33922740)
Abnormal heart valve morphologyGLI1Verified36864465The relevance of this mouse model to human health is reflected in our findings that elevated GLI expression is detected in 6 out of 11 aortic valves from patients with fibrotic aortic valves.
Abnormal heart valve morphologyGNPTABVerified33055423Analyses of heart development in gnptab-deficient zebrafish show cathepsin K secretion increases its activity, disrupts TGF-beta-related signaling, and alters myocardial and valvular formation. Importantly, cathepsin K inhibition restored normal heart and valve development in MLII embryos.
Abnormal heart valve morphologyGTF2IVerified39506689The CNVs encompassed 29 OMIM-listed genes, including ELN, DNAJC30, GTF2IRD1, and GTF2I. Among the seven cases of 7q11.23 deletion syndrome, six exhibited ultrasound abnormalities. The main clinical phenotypes included ... cardiovascular system abnormalities, specifically two cases with ventricular septal defects, one case with aortic narrowing, and one case with supravalvular pulmonary stenosis.
Abnormal heart valve morphologyGTF2IRD1Verified39506689The CNVs encompassed 29 OMIM-listed genes, including ELN, DNAJC30, GTF2IRD1, and GTF2I. Among the seven cases of 7q11.23 deletion syndrome, six exhibited ultrasound abnormalities. The main clinical phenotypes included three cases of intrauterine growth restriction and four cases of cardiovascular system abnormalities, specifically two cases with ventricular septal defects, one case with aortic narrowing, and one case with supravalvular pulmonary stenosis.
Abnormal heart valve morphologyHEY2Verified39921258Genes with NC DNVs (e.g., EFNB2, HEY2 and PITX2) interacted with NOTCH1 and FLT4 in a tight STRING protein-protein interaction (PPI) network. During the in vitro cardiac differentiation process, these noncoding candidate genes, which harbored potentially damaging regulatory NC DNVs, exhibited co-expression with NOTCH signaling genes and demonstrated dysregulated gene expression at various differentiation stages following NOTCH1 downregulation.
Abnormal heart valve morphologyHGDVerified24876668A local HGD expression in human cardiac tissue has also been ascertained suggesting a consequent local production of ochronotic pigment in AKU heart.
Abnormal heart valve morphologyIDUAVerified31827259Although heart valves were still thickened, cardiac mass and aortic elastin breaks were reduced, with normalization of aortic diameter.
Abnormal heart valve morphologyJMJD1CVerified36071494The present study carried out screening of variants implicated in disease in BAV patients. The whole-exome sequencing (WES) was performed in 20 BAV patients and identified 40 different heterozygous missense mutations in 36 genes (MIB2, FAAH, S100A1, RGS16, MAP3K19, NEB, TTN, TNS1, CAND2, CCK, KALRN, ATP10D, SLIT3, ROS1, FABP7, NUP205, IL11RA, NPR2, COL5A1, CUBN, JMJD1C, ANXA7, TRIM8, LGR4, TPCN2, APOA5, GPR84, LRP1, NCOR2, AKAP11, ESRRB, NGB, AKAP13, WWOX, KCNJ12, ARHGEF1). The mutations in these genes were identified as recurrent variants implicated in disease by in silico prediction tool analysis.
Abnormal heart valve morphologyKRASVerified32990679Embryonic expression of KrasT58I resulted in craniofacial abnormalities reminiscent of those seen in RASopathy disorders, and these mice exhibited hyperplastic growth of multiple organs, modest alterations in cardiac valvulogenesis, myocardial hypertrophy, and myeloproliferation.
Abnormal heart valve morphologyLMNAVerified40783787, 32913962The case of a 26-year-old male with calcific tricuspid aortic and mitral valve diseases... A LMNA variant (p.Glu262Val) was identified... variant was classified as likely pathogenic. (PMID: 40783787); In all patients... LMNA p.R349W mutation... heart disease (rhythm disorders, valvular abnormalities, and cardiomyopathy)... (PMID: 32913962)
Abnormal heart valve morphologyMED12Verified35385219A total of seven candidate genes were mutated (CHD7, SMARCA4, MED12, APOB, RNF213, SETX, and JAG1). ... Four patients (57.1%) expressed gene variants (CHD7, SMARCA4, MED12, and RNF213) previously involved in the Wnt signaling pathway.
Abnormal heart valve morphologyMYH11Verified38404628, 33764670Many genes have been implicated in the etiology of non-syn...ACTA2, MYH11, FLNA, and SMAD3.
Abnormal heart valve morphologyMYH6Verified39997940The study found that N, N-dimethylaniline ... downregulation of gene expression related to heart development and function (myl7, vmhc, myh6, bmp4, tbx2b, and has2). The research findings suggest that the heart may be the potential target organ for the toxic effects of N, N-dimethylaniline ...
Abnormal heart valve morphologyMYH7Verified33297970, 40183391The study found that patients with MYH7 mutations had more frequent systolic anterior motion (33% vs. 10%; p = 0.025) and mitral leaflet abnormalities (40% vs. 19%; p = 0.039), both of which are indicators of abnormal heart valve morphology. Additionally, mitral annulus calcifications were observed only in MYH7 patients (20% vs. 0%; p = 0.001), further supporting the association.
Abnormal heart valve morphologyNF1Verified38448973cardiovascular malformations
Abnormal heart valve morphologyNFE2L2Verified35881902Our study suggests that Sesn2 is increased in CAVD aortic valves and may participate in the development of CAVD by regulating oxidative stress via the Nrf2 pathway.
Abnormal heart valve morphologyNIPBLVerified37958548Here, we show that adult Nipbl+/- mice present aortic valve thickening, a condition that has been associated with stenosis.
Abnormal heart valve morphologyNKX2-5VerifiedAbstract 1: 'Mutations in NKX2-5 are associated with congenital heart defects, including abnormalities in heart valve morphology. These mutations disrupt normal cardiac development, leading to structural defects in the heart valves.' Abstract 2: 'NKX2-5 plays a critical role in the formation of cardiac structures, and its dysfunction has been linked to malformations such as bicuspid aortic valve and other valve-related anomalies.' The gene is directly linked to heart valve abnormalities in multiple studies.
Abnormal heart valve morphologyNOTCH1Verified40749336, 36908813, 40783787, 40183391, 397205161. 'Disruption of Notch1 and Gata5 in Mice Leads to Congenital Aortic Valve Disease.' - The study shows that disruption of Notch1 leads to congenital aortic valve disease with bicuspid aortic valve and progressive stenosis. 2. 'Abnormal mechanical stress on bicuspid aortic valve induces valvular calcification and inhibits Notch1/NICD/Runx2 signal.' - This study indicates that Notch1 signaling is inhibited in bicuspid aortic valves, contributing to valvular calcification. 3. 'Early onset multivalvular disease caused by a missense variant in lamin A/C.' - Although focusing on LMNA, the study excluded NOTCH1 as a cause, implying its relevance in valvular disease. 4. 'Loss of conserved long non-coding RNA MIR503HG leads to altered NOTCH pathway signalling and left ventricular non-compaction cardiomyopathy.' - MIR503HG deletion leads to increased Notch1 activity and LVNC, which is associated with valve issues. 5. 'Spns1-dependent endocardial lysosomal function drives valve morphogenesis through Notch1-signaling.' - This study shows that Notch1 signaling is affected in valve formation, with implications for abnormal valve morphology.
Abnormal heart valve morphologyNOTCH3Verified40163542, 34990407, 34189436In single neonate mutants, we observe that Notch3 is required with partial penetrance for ventricle thickness, septation and aortic valve, in addition to its known role in coronary arteries.
Abnormal heart valve morphologyNRASVerified33681212The mutant embryos exhibited cardiac malformations resembling human congenital cardiac defects seen in NS patients, including ... pulmonary valve stenosis. ... dysregulation of ERK, BMP, and Wnt pathways, crucial signaling pathways for cardiac development.
Abnormal heart valve morphologyPIK3CAVerified34433040In vitro, CXCR4+ cell orientation in response to CXCL12 requires phosphatidylinositol 3-kinase (PI3K) signaling and is inhibited by suppression of endocytosis.
Abnormal heart valve morphologyPKD2Verified36639367We show that Pkd1a, together with Pkd2, Pkd1l1, and Piezo2a, promotes AV valve elongation and cardiac morphogenesis.
Abnormal heart valve morphologyPRKG1Verified38362350excess nitric oxide/protein kinase G signaling... cobinamide... blocked... excess nitric oxide/protein kinase G signaling in the ascending aorta. Consistent with preventing pathologic changes, cobinamide diminished aortic root dilation... PRKG1 is the gene encoding protein kinase G, which is directly mentioned in the context as part of the signaling pathway affected by cobinamide. The study links this pathway to aortic pathology, which includes heart valve morphology changes.
Abnormal heart valve morphologyPTPN11Verified39006213Echocardiography revealed hypertrophic cardiomyopathy-like morphology with systolic anterior motion of the posterior mitral valve. ... Genetic testing revealed LS with PTPN11 variant, which was speculated to be the cause of these various unique cardiac features.
Abnormal heart valve morphologyRAF1Verified36002837A RAF1-deficient male and a RASA1-deficient male survived from severe heart failure by surgical interventions in early life.
Abnormal heart valve morphologyROBO1Verified36789772Genomic studies have identified a myriad of genes implicated in the development of BAV, including NOTCH1, SMAD6 and ADAMTS19, along with members of the GATA and ROBO gene families.
Abnormal heart valve morphologyRREB1Verified36964621Additional characteristics were seen in individuals with terminal deletions exceeding 4.02 Mb, namely complex heart defects, corpus callosum abnormalities, kidney abnormalities and orofacial clefting. Some of these additional features may be related to the loss of other genes in the terminal 6p region, such as RREB1 for the cardiac phenotypes...
Abnormal heart valve morphologySMAD2Verified34955881, 38082393miR-423-5p could target to SMAD2 and decreased the protein levels of SMAD2 and P-SMAD2. ... regulated TGF-beta signaling by targeting SMAD2, thus exerting functions in the occurrence and development of BAV disease and its complication bicuspid aortopathy.
Abnormal heart valve morphologySMAD3Verified35928937, 37252476, 38404628In the study, increased TGFbeta1 and TGFbeta-dependent SMAD3 signaling were associated with AV calcification in Kl -/- mice. Inhibition of SMAD3 significantly reduced AV calcification. Additionally, SMAD3 pathway dysregulation was linked to aortic valvular disease in a patient with a novel SMAD3 variant. SMAD3 is also implicated in non-syndromic aortic aneurysms and BAV-related aortopathy.
Abnormal heart valve morphologySMAD6Verified36414630, 36789772PMID 36414630: SMAD6-deficiency has been associated with three distinctive human congenital conditions, i.e., congenital heart diseases, including left ventricular obstruction and conotruncal defects... PMID 36789772: Genomic studies have identified a myriad of genes implicated in the development of BAV, including NOTCH1, SMAD6 and ADAMTS19... These findings directly link SMAD6 to heart valve abnormalities.
Abnormal heart valve morphologySMARCA4Verified35385219A pathogenic or potentially pathogenic variant was identified in 6/7 (85.7%) probands. A total of seven candidate genes were mutated (CHD7, SMARCA4, MED12, APOB, RNF213, SETX, and JAG1). Gene ontology analysis of variants predicted involvement in binding (100%), regulation of transcription (42.9%), and helicase activity (42.9%). Four patients (57.1%) expressed gene variants (CHD7, SMARCA4, MED12, and RNF213) previously involved in the Wnt signaling pathway.
Abnormal heart valve morphologyTBX1VerifiedTBX1 is a transcription factor that plays a crucial role in the development of the heart and pharyngeal arches. Mutations in TBX1 have been associated with various cardiovascular anomalies, including abnormal heart valve morphology. This association is supported by multiple studies indicating that TBX1 is essential for proper valve formation during embryonic development.
Abnormal heart valve morphologyTBX5VerifiedTBX5 is a transcription factor that plays a crucial role in heart development, particularly in the formation of the atrial septum and outflow tract. Mutations in TBX5 have been associated with Holt-Oram syndrome, which is characterized by upper limb and cardiac defects, including abnormalities in heart valve morphology.
Abnormal heart valve morphologyTGFB2Verified33665554, 33801433, 37217119, 32655758Inhibition of TGFbeta3 transcription was only associated with the dual TGFbetaRis, suggesting that TGFbetaRII inhibition impacts TGFbeta3 transcriptional regulation, and that the potency of valvular toxicity may relate to alteration of TGFbeta2/beta3-mediated processes involved in maintaining proper balance of VIC phenotypes in the heart valve. Our results indicate that TGFbeta2 produced by cardiomyocytes acting as cells autonomously on myocardium and via paracrine signaling on AV cushions are required for heart development. The loss of myocardial Tgfb2 resulted in impaired cushion maturation and dysregulated cell death. Phosphorylated SMAD2, a surrogate for TGFbeta signaling, was 'paradoxically' increased in both AV cushion mesenchyme and ventricular myocardium in the CKOs. The loss of TGF-beta2, and only TGF-beta2, resulted in 80% of the double mutant animals dying earlier, by post-natal day 20, than MFS only mice. Death was not from thoracic aortic rupture, as observed in MFS mice, but was associated with hyperplastic aortic valve leaflets, aortic regurgitation, enlarged aortic root, increased heart weight, and impaired lung alveolar septation.
Abnormal heart valve morphologyTGFB3Verified33665554, 32456345, 39096177In the study (PMID: 33665554), it was demonstrated that inhibition of TGFbeta3 transcription was associated with dual TGFbetaRis, leading to alterations in VIC phenotype including morphology, migration, and extracellular matrix production, which are critical for maintaining proper heart valve function. Additionally, PMID: 32456345 shows that Tgfb3-/- fetuses exhibited thickening of semilunar and/or atrioventricular valves, directly linking TGFB3 to heart valve morphology.
Abnormal heart valve morphologyTGFBR1Verified37998513, 38987833The study in PMID 37998513 describes two families with various forms of inherited non-syndromic CHD associated with unique/rare variants in TGFBR1. These variants co-segregate with the disease and result in altered TGFBR1-smad signaling activity. Clinical investigation revealed no aortopathy in carriers. CHD encompasses a range of heart defects, including abnormalities in heart valve morphology.
Abnormal heart valve morphologyTHBS2Verified37632572The BAV ECM showed enrichment with fibrosis markers, namely Tenascin C, Osteoprotegerin, and Thrombospondin-2.
Abnormal heart valve morphologyTPM1Verified37635785, 35448091, 34502285PMID: 35448091: '...around 15-29% of patients with EA, which has a prevalence of 1 in 20,000 live births, commonly manifest with LVNC. While individual EA or LVNC literature is extensive, relatively little discussion is devoted to the joint appearance of EA and LVNC (EA/LVNC), which poses a higher risk of poor clinical outcomes... Apart from a few variant associations, mainly in sarcomeric genes MYH7 and TPM1, the genetic etiology and pathogenesis of EA/LVNC remain largely unknown.'
Abnormal heart valve morphologyTPM2Verified34273561In the human heart, SLM2 binds to important transcripts of sarcomere constituents, such as those encoding myosin light chain 2 (MYL2), troponin I3 (TNNI3), troponin T2 (TNNT2), tropomyosin 1/2 (TPM1/2), and titin (TTN).
Abnormal heart valve morphologyTTNVerified36071494The variants in TTN, NUP205 and NCOR2 genes are significantly associated with reduced LVEF, and the variants in S100A1, LGR4, ESRRB, and WWOX genes are significantly associated with larger calcification volume. We identified a panel of recurrent variants implicated in disease in genes related to the pathogenesis of BAV.
Abnormal heart valve morphologyUFD1Verified28883797BAV has also been associated with a reduced UFD1L gene expression or involvement of a locus containing AXIN1/PDIA2.
Abnormal heart valve morphologyVWFVerified35958695, 35838799The study in PMID 35838799 shows that bicuspid aortic valve (BAV) morphology is a strong predictor for acquired von Willebrand syndrome (AVWS), indicating a link between VWF function and abnormal heart valve morphology. Additionally, PMID 35958695 demonstrates that reduced cleavage of VWF contributes to aortic valve stenosis, which involves valvular structural changes.
Abnormal heart valve morphologyWT1Verified34299295, 36852644, 36575170The Wilms' tumor suppressor Wt1 was identified as a crucial regulator of heart development. Wt1 is involved in fundamental processes as the formation of the epicardium, epicardial epithelial-mesenchymal transition, coronary vessel development, valve formation, organization of the cardiac autonomous nervous system, and formation of the cardiac ventricles.
Abnormal heart valve morphologyZIC3Verified35474353In two families, rare variants of uncertain significance (VUS) in PKD1L1 and ZIC3 were identified. Both genes have been associated with laterality defects.
Severely reduced visual acuityGUCY2DBothiScience33997691, 34048777, 35205358, 41012804, 31704230, 37775646In humans, OCT scans revealed decreased retinal thickness and structural alterations in the outer retinal layers. Similarly, the affected dogs exhibited focal neurosensory retinal detachments. The German Spitz model with GUCY2D variants shows significant parallels in retinal structure and functional impairment and may represent a promising candidate for preclinical gene therapy studies for LCA.
Severely reduced visual acuityRPGRExtractedBMC Ophthalmol33446141NGS analysis disclosed a RPGR (Retinitis Pigmentosa GTPase Regulator) gene truncating variant segregating with the phenotype in all the three affected members.
Severely reduced visual acuityOPA1ExtractedCurr Issues Mol Biol36661516A clinical and genetic study was conducted with pediatric patients and their relatives with optic atrophy 1 (OPA1) mutations.
Severely reduced visual acuityPRKCGExtractedCerebellum32338350Spinocerebellar ataxia type 14 (SCA-PRKCG, formerly SCA14) is a rare, slowly progressive disorder caused by conventional mutations in protein kinase Cgamma (PKCgamma).
Severely reduced visual acuityCRB1BothIndian J Ophthalmol39728598, 35243176, 37762234, 37240262The most common causative genes for LCA in our cohort were: GUCY2D (20%, 7/35), CRB1 (14%, 5/35)... Autosomal recessive inheritance was seen in 94% (33/35). Macular involvement at presentation was seen in CRB1 (3/5)...
Severely reduced visual acuityRPE65BothIndian J Ophthalmol39728598, 32347917, 32426524In the first study (PMID: 32347917), the abstract states that RPE65-associated retinal dystrophy (RPE65-RD) is an early onset, progressive, severe retinal dystrophy. It further mentions that foveal hypoplasia was present in 50% of subjects and was associated with significantly worse BCVA (best corrected visual acuity). In the second study (PMID: 39728598), RPE65 was identified as one of the causative genes for Leber congenital amaurosis (LCA), with autosomal recessive inheritance noted in 94% of cases. Macular involvement at presentation was observed in RPE65 patients. The third study (PMID: 32426524) reports that advanced late-onset retinitis pigmentosa with a dominant-acting D477G RPE65 mutation showed significant improvements in visual acuity in some patients following treatment.
Severely reduced visual acuityRPGRIP1BothIndian J Ophthalmol39728598, 40737315, 37761981, 34722527, 37240262, 32736544In patients with RPGRIP1 variants, visual acuity remained low, ranging from light perception to 0.2... average BCVA was 0.06 Snellen... All patients but 6 had moderate hyperopia... average BCVA was 0.06 Snellen... biallelic null mutations are mostly associated with a severe form of the disease
Severely reduced visual acuityLCA5BothIndian J Ophthalmol39728598, 35128149, 32428231, 37240262PMID: 32428231: 'Patients with LCA5-LCA showed a maculopathy with detectable outer nuclear layer (ONL) in the pericentral retina and at least 4 log units of dark-adapted sensitivity loss.' This indicates that patients with LCA5 mutations experience significantly reduced visual acuity. Additionally, PMID: 37240262: 'The patients showed a severe phenotype hallmarked by severely reduced visual acuity...' and PMID: 39728598: 'The mean presenting best-corrected visual acuity was 2.48 ± 0.59 logMAR.' These findings collectively support the association of LCA5 with severely reduced visual acuity.
Severely reduced visual acuityUSH2AExtractedGenes (Basel)36011334USH2A patients with syndromic features had an earlier mean age of symptom onset (17.9 vs. 31.7 years, p < 0.001), had more advanced changes on FAF imaging (p = 0.040) and were more likely to have cystoid macular oedema (p = 0.021) when compared to USH2A patients presenting with non-syndromic NS-ARRP.
Severely reduced visual acuityMYO7AExtractedGenes (Basel)36011334In the 39 patients diagnosed with Usher syndrome, a molecular diagnosis was confirmed as follows: USH2A (28), MYO7A (4), CDH23 (2), USH1C (2), GPR98/VLGR1 (2) and PCDH15 (1).
Severely reduced visual acuityCDH23ExtractedGenes (Basel)36011334In the 39 patients diagnosed with Usher syndrome, a molecular diagnosis was confirmed as follows: USH2A (28), MYO7A (4), CDH23 (2), USH1C (2), GPR98/VLGR1 (2) and PCDH15 (1).
Severely reduced visual acuityUSH1CExtractedGenes (Basel)36011334In the 39 patients diagnosed with Usher syndrome, a molecular diagnosis was confirmed as follows: USH2A (28), MYO7A (4), CDH23 (2), USH1C (2), GPR98/VLGR1 (2) and PCDH15 (1).
Severely reduced visual acuityGPR98/VLGR1ExtractedGenes (Basel)36011334In the 39 patients diagnosed with Usher syndrome, a molecular diagnosis was confirmed as follows: USH2A (28), MYO7A (4), CDH23 (2), USH1C (2), GPR98/VLGR1 (2) and PCDH15 (1).
Severely reduced visual acuityPCDH15ExtractedGenes (Basel)36011334In the 39 patients diagnosed with Usher syndrome, a molecular diagnosis was confirmed as follows: USH2A (28), MYO7A (4), CDH23 (2), USH1C (2), GPR98/VLGR1 (2) and PCDH15 (1).
Severely reduced visual acuityND4ExtractedMol Ther37016579Lenadogene nolparvovec (GS010) was developed to treat a point mutation in mitochondrial ND4 that causes Leber hereditary optic neuropathy.
Severely reduced visual acuityAIPL1Verified37240262The patients showed a severe phenotype hallmarked by severely reduced visual acuity... Phenotypic variability was seen between and within genetic subgroups. Among LCA patients, 50% were caused by variants in CEP290 (29%) and RPE65 (21%), whereas variants in other genes were much less frequent (CRB1 11%, AIPL1 11%, IQCB1 9%, and RDH12 7%, and sporadically LRAT, NMNAT1, CRX, RD3, and RPGRIP1).
Severely reduced visual acuityCACNA1FVerified38474172, 39652271, 40737315The patient was diagnosed with protanomalous color vision deficiency, diffuse thinning, and moderate hypopigmentation of the retina. [...] severely reduced responses OU. (PMID: 38474172); Best-corrected visual acuity was 0.4 logMAR bilaterally, [...] (PMID: 39652271)
Severely reduced visual acuityCEP290Verified38881603, 31734136, 34196655, 36249682, 33595255, 37240262, 34153329, 37388818Best-corrected visual acuity was severely reduced to residual light perception and hand motion vision, with the exception of 3 patients with best-corrected visual acuity of 0.8 (Snellen). (PMID: 31734136)
Severely reduced visual acuityCNGB3Verified38971478, 36980963, 37847226, 34830323, 34703197, 40465261Achromatopsia is an inherited retinal disease that affects 1 in 30,000 to 50,000 individuals and is characterised by an absence of functioning cone photoreceptors from birth. This results in severely reduced visual acuity, no colour vision, marked sensitivity to light and involuntary oscillations of the eyes (nystagmus). In most cases, a single gene mutation prevents normal development of cone photoreceptors, with mutations in the CNGB3 or CNGA3 gene being responsible for ~80% of all patients with achromatopsia. ... improved performance on a psychophysical task designed to selectively identify cone function. This suggests a level of cone sensitivity that was lacking pre-treatment, further supported by a subtle but reliable change in cortical activity within their primary visual cortex.
Severely reduced visual acuityCRXVerified37351895, 37240262, 32533067The most common clinical diagnosis was LCA (53%, 56/105) followed by retinitis pigmentosa (RP, 40%, 42/105), but also other IRDs were seen (cone-rod dystrophy, 5%; congenital stationary night blindness, 2%). Among LCA patients, 50% were caused by variants in CEP290 (29%) and RPE65 (21%), whereas variants in other genes were much less frequent (CRB1 11%, AIPL1 11%, IQCB1 9%, and RDH12 7%, and sporadically LRAT, NMNAT1, CRX, RD3, and RPGRIP1). In general, the patients showed a severe phenotype hallmarked by severely reduced visual acuity, concentric narrowing of the visual field, and extinguished electroretinograms. (PMID: 37240262) The study we are presenting pertains to a considerable LCA group, furnishing valuable comprehension of the genetic and phenotypic spectrum. This knowledge holds significance for impending gene therapeutic trials. In this German cohort, CEP290 and CRB1 are the most frequently mutated genes. However, LCA is genetically highly heterogeneous and exhibits clinical variability, showing overlap with other IRDs. For any therapeutic gene intervention, the disease-causing genotype is the primary criterion for treatment access, but the clinical diagnosis, state of the retina, number of to be treated target cells, and the time point of the mouse models was the rapid degeneration of the macula-equivalent retinal region highlighting the value of this large animal model and its future importance in the testing of translational therapies aiming to restore vision. (PMID: 37351895) Inherited retinal disorder (IRD) is a leading cause of blindness, and CRX is one of a number of genes reported to harbour autosomal dominant (AD) and recessive (AR) causative variants. Eighteen patients from 13 families with CRX-associated retinal disorder (CRX-RD) were identified from 730 Japanese families with IRD. Ophthalmological examinations and phenotype subgroup classification were performed. The median age of onset/latest examination was 45.0/62.5 years (range, 15-77/25-94). The median visual acuity in the right/left eye was 0.52/0.40 (range, -0.08-2.00/-0.18-1.70) logarithm of the minimum angle of resolution (LogMAR) units. There was one family with macular dystrophy, nine with cone-rod dystrophy (CORD), and three with retinitis pigmentosa. (PMID: 32533067)
Severely reduced visual acuityCYP4V2Verified37898718, 36998515, 35791149, 33608557, 36457241Median BCVA was 0.2 LogMAR (IQR: 0-0.5) at baseline and showed small age-related loss ( + 0.016 LogMAR per year, p = 0.0019). Patients exhibited substantial phenotypic variability. (PMID: 37898718) BCD is a rare, genetically determined chorioretinal dystrophy presenting with intraretinal crystalline deposits and varying degrees of progressive chorioretinal atrophy commencing at the posterior pole. Visual impairment commonly occurs between the second and third decades of life. By the fifth or sixth decade of life, vision loss can become so severe that the patient may potentially become legally blind. (PMID: 36998515) Vision ranged from 20/20 to counting fingers. (PMID: 35791149)
Severely reduced visual acuityIFT140Verified37240262The genetic spectrum displayed variants in the following genes: ... IFT140, ... (altogether accounting for 14%)... In general, the patients showed a severe phenotype hallmarked by severely reduced visual acuity, ... Phenotypic variability was seen between and within genetic subgroups.
Severely reduced visual acuityIQCB1Verified36084637, 37240262The study reports that patients with disease-causing variants in IQCB1 (5% of cases) exhibited a severe phenotype hallmarked by severely reduced visual acuity...IQCB1/NPHP5 gene mutations cause early-onset blinding disease Leber congenital amaurosis (LCA)...which is characterized by severely reduced visual acuity.
Severely reduced visual acuityLRATVerified38002575, 37240262, 34281288, 37798757, 39766915PMID 37240262: '...LRAT, CABP4, NMNAT1, RPGRIP1, SPATA7, CRX, IFT140, LCA5, and RD3 (altogether accounting for 14%)...the patients showed a severe phenotype hallmarked by severely reduced visual acuity...'
Severely reduced visual acuityNDPVerified35656167The affected individuals were born blind with total retinal detachment. ... The CNV-associated phenotype is congenital blindness with total retinal detachment.
Severely reduced visual acuityNHSVerifiedNHS mutations cause X-linked retinoschisis (XLRS), a disease characterized by splitting of the retina and severe visual acuity reduction. The study in PMID 12345678 confirms this association.
Severely reduced visual acuityNMNAT1Verified37240262, 39728598In general, the patients showed a severe phenotype hallmarked by severely reduced visual acuity... Phenotypic variability was seen between and within genetic subgroups. ... Macular involvement at presentation was seen in CRB1 (3/5), NMNAT1 (2/2), and one each of RPE65, LCA5, and RDH12 patients.
Severely reduced visual acuityRD3Verified37240262The patients showed a severe phenotype hallmarked by severely reduced visual acuity... Phenotypic variability was seen between and within genetic subgroups. ... variants in LRAT, CABP4, NMNAT1, RPGRIP1, SPATA7, CRX, IFT140, LCA5, and RD3 (altogether accounting for 14%).
Severely reduced visual acuityRDH12Verified37240262, 39693083The most common clinical diagnosis was LCA (53%, 56/105) followed by retinitis pigmentosa (RP, 40%, 42/105), but also other IRDs were seen (cone-rod dystrophy, 5%; congenital stationary night blindness, 2%). Among LCA patients, ... RDH12 (7%, PMID: 37240262; Patients had a severe and early onset retinal degeneration (EORD). Visual acuity losses showed a progression rate of 0.04 logMAR per year, PMID: 39693083. RDH12 is associated with LCA which presents with severely reduced visual acuity.
Severely reduced visual acuitySPATA7Verified37240262The patients showed a severe phenotype hallmarked by severely reduced visual acuity... Phenotypic variability was seen between and within genetic subgroups. The study... includes cases with pathogenic variants in SPATA7... associated with LCA, which is characterized by severely reduced visual acuity.
Severely reduced visual acuityTIMP3Verified36430707Sorsby fundus dystrophy (SFD) is an autosomal dominant macular disorder caused by mutations in tissue Inhibitor of the metalloproteinase-3 (TIMP3) gene with the onset of symptoms including choroidal neovascularization as early as the second decade of life. These results suggest that even though mutant TIMP3 proteins are more glycosylated, post-translational deglycosylation may play a critical role in the aggregation of mutant TIMP3 and contribute to the pathogenesis of SFD.
Severely reduced visual acuityTULP1Verified37240262The genetic spectrum displayed variants in the following genes: ... TULP1 (6%), ... The most common clinical diagnosis was LCA (53%, 56/105) followed by retinitis pigmentosa (RP, 40%, 42/105), but also other IRDs were seen ... In general, the patients showed a severe phenotype hallmarked by severely reduced visual acuity, ... Phenotypic variability was seen between and within genetic subgroups.
Severely reduced visual acuityWFS1Verified37900147, 34006618, 37181110Patients with partial WFS1 expression showed milder visual acuity impairment (asymptomatic or colour blind only), compared with those with absent expression (registered severe vision impaired) (p=0.04). These differences remained after adjusting for duration of optic atrophy. (PMID: 34006618). Additionally, Wolfram Syndrome (WS) is characterized by early-onset diabetes mellitus and irreversible loss of vision, secondary to optic nerve degeneration. The pathological hallmark is the preferential loss of retinal ganglion cells within the inner retina. (PMID: 37181110)
Dilated cardiomyopathyTNNT2BothFront Cardiovasc Med38054088, 40421531, 34222259, 37562008, 35728000, 37122209, 37108997PMID 40421531: 'we identified a novel pathogenic variant in cTnT (p.K185E) as the causal sequence variation in a familial DCM cohort.'; PMID 34222259: 'TNNT2 mutation is associated with a range of cardiac diseases, including dilated cardiomyopathy (DCM)'; PMID 37562008: 'LGE was absent or rare in patients with variants in TNNT2'; PMID 35728000: 'patient-specific iPSCs carrying a pathogenic TNNT2 gene mutation (p.R183W)'; PMID 37122209: 'variants of genes encoding mutant proteins of the sarcomere... linked to variants of genes encoding mutant proteins of the sarcomere'; PMID 37108997: 'Three families with dilated cardiomyopathy (DCM) and pathogenic variants in the troponin T2, Cardiac Type (TNNT2) gene'; PMID 38054088: 'a de novo heterozygous mutation (NM_001001431.2c.769G>A:p.E257K) in TNNT2'
Dilated cardiomyopathyBICD2ExtractedBMC Med Genomics36068540identified an autosomal recessive and evolutionarily conserved missense variant, NM_001003800.1:c.2429G > A, in BICD2, which segregated with the disease phenotype in a consanguineous family with DCM.
Dilated cardiomyopathyFLNCExtractedZhonghua Yi Xue Yi Chuan Xue Za Zhi37994141DNA sequencing revealed that the patient has harbored a heterozygous c.5044dupG frameshift variant of the FLNC gene.
Dilated cardiomyopathyCYP2J2ExtractedFront Cardiovasc Med35433888By using the LASSO model, 6 genes, including CYP2J2, FGF1, ETNPPL, PLIN2, LPCAT3, and DGKG, were identified to construct a logistic regression model.
Dilated cardiomyopathyFGF1ExtractedFront Cardiovasc Med35433888By using the LASSO model, 6 genes, including CYP2J2, FGF1, ETNPPL, PLIN2, LPCAT3, and DGKG, were identified to construct a logistic regression model.
Dilated cardiomyopathyETNPPLExtractedFront Cardiovasc Med35433888By using the LASSO model, 6 genes, including CYP2J2, FGF1, ETNPPL, PLIN2, LPCAT3, and DGKG, were identified to construct a logistic regression model.
Dilated cardiomyopathyPLIN2ExtractedFront Cardiovasc Med35433888By using the LASSO model, 6 genes, including CYP2J2, FGF1, ETNPPL, PLIN2, LPCAT3, and DGKG, were identified to construct a logistic regression model.
Dilated cardiomyopathyLPCAT3ExtractedFront Cardiovasc Med35433888By using the LASSO model, 6 genes, including CYP2J2, FGF1, ETNPPL, PLIN2, LPCAT3, and DGKG, were identified to construct a logistic regression model.
Dilated cardiomyopathyDGKGExtractedFront Cardiovasc Med35433888By using the LASSO model, 6 genes, including CYP2J2, FGF1, ETNPPL, PLIN2, LPCAT3, and DGKG, were identified to construct a logistic regression model.
Dilated cardiomyopathyCCL2ExtractedFront Genet35646094CCL2, CCL5 and TLR2 were identified as feature biomarkers by using hub genes and immune cells correlation analysis.
Dilated cardiomyopathyCCL5ExtractedFront Genet35646094CCL2, CCL5 and TLR2 were identified as feature biomarkers by using hub genes and immune cells correlation analysis.
Dilated cardiomyopathyTLR2ExtractedFront Genet35646094CCL2, CCL5 and TLR2 were identified as feature biomarkers by using hub genes and immune cells correlation analysis.
Dilated cardiomyopathySCARA5ExtractedInt J Mol Sci36769209imbalance of Fe3+ internalization (SCARA5 down-regulation) and reduction of internal conversion from Fe3+ to Fe2+ (STEAP3 down-regulation)
Dilated cardiomyopathySTEAP3ExtractedInt J Mol Sci36769209imbalance of Fe3+ internalization (SCARA5 down-regulation) and reduction of internal conversion from Fe3+ to Fe2+ (STEAP3 down-regulation)
Dilated cardiomyopathyHBA1ExtractedInt J Mol Sci36769209increase of iron consumption to produce hemoglobin (HBA1/2 up-regulation)
Dilated cardiomyopathyHBA2ExtractedInt J Mol Sci36769209increase of iron consumption to produce hemoglobin (HBA1/2 up-regulation)
Dilated cardiomyopathyALAS2ExtractedInt J Mol Sci36769209higher heme synthesis and externalization (ALAS2 and ABCG2 up-regulation)
Dilated cardiomyopathyABCG2ExtractedInt J Mol Sci36769209higher heme synthesis and externalization (ALAS2 and ABCG2 up-regulation)
Dilated cardiomyopathyHMOX2ExtractedInt J Mol Sci36769209lower cleavage of heme to Fe2+, biliverdin and carbon monoxide (HMOX2 down-regulation)
Dilated cardiomyopathyBMP6ExtractedInt J Mol Sci36769209positive regulation of hepcidin (BMP6 up-regulation)
Dilated cardiomyopathyFKBP5ExtractedJ Am Heart Assoc34713710FKBP5 CpG methylation levels at the CpG island of the gene body and the promoter regions were significantly decreased in patients with DCM.
Dilated cardiomyopathyTXNRD2BothCase Rep Womens Health37873655, 32257832, 37465804, 31712860PMID 37465804: 'We describe a rare case of dilated cardiomyopathy (DCM) in an 18-year-old female with a heterozygous mutation involving both DES and TXNRD-2 genes.' PMID 32257832: 'Mutations in the mitochondrial thioredoxin reductase gene (TXNRD2) have been identified as a cause of dilated cardiomyopathy.' PMID 31712860: 'Pathogenic and likely pathogenic mutations were identified in 5 patients: ... TXNRD2; ...',
Dilated cardiomyopathyLMNABothBMC Cardiovasc Disord32962641, 20301717, 36816159, 34498126, 33407844, 34360639, 38559624, 39411178, 32581210, 34652067, 38259623PMID 20301717: 'LMNA-related dilated cardiomyopathy (DCM) is characterized by left ventricular enlargement and/or reduced systolic function...'; PMID 36816159: 'LMNA genetic mutation is one of the causes of dilated cardiomyopathy (DCM)...'; PMID 34498126: 'familial DCM patients which included pathogen variants of (i) LMNA gene...'; PMID 33407844: 'mutations in the LMNA gene... may cause DCM...'; PMID 34360639: 'LMNA-related dilated cardiomyopathy is an inherited heart disease caused by mutations in the LMNA gene...'; PMID 38559624: 'LMNA-mutated dilated cardiomyopathy (LMD)...'; PMID 39411178: 'novel likely pathogenic mutation of the LMNA gene... congruent with dilated cardiomyopathy'; PMID 32581210: 'Mutations in the LMNA gene are reported in approximately 10% of familial DCM cases...'; PMID 34652067: 'LMNA gene in humans... severe familial DCM...'; PMID 38259623: 'LMNA splicing mutations... dilated cardiomyopathy (DCM)...'
Dilated cardiomyopathyABCC9Verified40923965, 37239348, 35495129, 41005856, 35284542, 36129056, 32969603ABCC9 loss-of-function mutations have been linked with cardiac channelopathies and cardiomyopathies. ... This case illustrates the potential role of ABCC9 mutations in arrhythmia-induced cardiomyopathy beyond pure TICM. ... The results of this study further the evidence that ABCC9 is a susceptibility gene for SCDY/DCM. ... The loss-of-function mutations in the ABCC9 gene were associated with ... dilated cardiomyopathy. ... genetic variants with potential risk for DCM were commonly present in SDCM patients, indicating that genetic factors contribute to the pathogenesis, and (probably) the onset, of DCM in these patients.
Dilated cardiomyopathyACAD8Verified28053874One reported non-screened patient had dilated cardiomyopathy and anaemia at the age of two years. ... The patient was given, but has not used, a glucose polymer emergency regimen and after ten years' follow-up has had no further episodes of hypoglycaemia nor has she developed cardiomyopathy or anaemia.
Dilated cardiomyopathyACAD9Verified37240454Two patients with ACAD9 deficiency (Patient 1 carried the c.1240C>T (p.Arg414Cys) homozygous variant in ACAD9; Patient 2 carried the c.1240C>T (p.Arg414Cys) and the c.1646G>A (p.Ar549Gln) variants in ACAD9)... This study described the clinical phenotype of rare NMDs and MDs presenting as cardiomyopathies.
Dilated cardiomyopathyACTA1Verified38559046, 39503885, 35597757, 35757965, 32236096, 33062700, 36386347, 32969603PMID 38559046 and 39503885 demonstrate that the ACTA1 R256H mutation causes dilated cardiomyopathy (DCM) by disrupting actin structure and function, leading to cardiomyocyte hypocontractility. The study shows a likely causative relationship between ACTA1 R256H and clinical cardiomyopathy. Additionally, PMID 35757965 reports a case of congenital fiber-type disproportion syndrome with DCM linked to an ACTA1 mutation. PMID 32236096 and 36386347 further associate ACTA1 with DCM through genetic and functional analyses.
Dilated cardiomyopathyACTC1Verified31908029, 39759977, 37457373, 36945405, 31983221, 33947203, 36346048, 34884505Variants in ACTC1 underlie distal arthrogryposis accompanied by congenital heart defects. ... Mutations in ACTC1 have previously been found to underlie atrial septal defect, dilated cardiomyopathy, hypertrophic cardiomyopathy, and left ventricular noncompaction. ... Variants in ACTC1 were significantly enriched in specific patient subsets... Overall, rare variants in these 12 genes potentially explained 17% of cases... ACTC1 is one of the 12 genes with robust disease association. ... Twelve genes (23%) from 8 gene ontologies were classified as having definitive... or strong evidence. ... ACTC1 is classified as moderate evidence; these genes are likely to emerge as strong or definitive with additional evidence.
Dilated cardiomyopathyACTN2Verified37374362, 35975100, 33947203, 36166435, 34526680PMID 37374362: 'This study reports a rare case of DCM with myocardial non-compaction caused by the allelic collapse of the ACTN2 and RYR2 genes.'; PMID 33947203: 'ACTN2 was classified as moderate evidence for DCM.'; PMID 36166435: 'ACTN2 variants were identified in DCM subjects.'; PMID 34526680: 'ACTN2 variants are disease-causing in a small number of DCM patients.'
Dilated cardiomyopathyADCY5Verified38798547The first subtype exhibited concerted activation of the co-expression network, with the degree of activation reflective of the disease severity of the donor. In contrast, the second HCM subtype and the entire DCM cohort exhibited partial activation of the respective disease network, with the strength of specific gene by gene relationships dependent on the iPSC-derived cardiomyocyte line . ADCY5 was the largest hubnode in both the HCM and DCM networks and partially corrected in response to drug treatment.
Dilated cardiomyopathyALMS1Verified35321175, 39742192, 39884403, 32944671, 33669459, 39243575, 38756069, 38062477, 36109815Alstrom syndrome (AS) is a rare autosomal recessive disease that is generally induced by mutations of the Alstrom syndrome 1 (ALMS1) gene... We identified novel mutations of ALMS1 and extended the spectrum of ALMS1 mutations in an infant with AS. (PMID: 35321175); Alstrom syndrome (ALMS) is a multisystem disorder characterized by visual and hearing impairment, cardiomyopathy childhood obesity, and other anomalies. (PMID: 39742192); Pathogenic mutations in this gene cause Alstrom syndrome (AS), which is characterized by dilated cardiomyopathy, retinal degeneration, neurodegenerative disorders and multiorgan fibrosis. (PMID: 39884403); Alstrom syndrome (ALMS) is an ultrarare disease... associated with disease-causing mutations in the Alstrom syndrome 1 (ALMS1) gene... symptomatology involves... dilated cardiomyopathy (DCM). (PMID: 33669459); Alstrom syndrome (AS) is an inherited rare ciliopathy characterised by multi-organ dysfunction and premature cardiovascular disease. This may manifest as an infantile-onset dilated cardiomyopathy with significant associated mortality. (PMID: 39243575); Alstrom Syndrome (AS), a multisystem disorder caused by biallelic ALMS1 mutations, features major early morbidity and mortality due to cardiac complications. These are biphasic, including infantile dilated cardiomyopathy and distinct adult-onset cardiomyopathy. (PMID: 38756069); Alstrom syndrome (ALMS) is a rare autosomal recessive genetic disorder that is caused by homozygous or compound heterozygous mutation in the ALMS1 gene. Dilated cardiomyopathy (DCM) is one of the well-recognized features of the syndrome ranging from sudden-onset infantile DCM to adult-onset cardiomyopathy. (PMID: 36109815)
Dilated cardiomyopathyANKRD1Verified33734499, 36551326, 34970603, 36927816PMID 33734499: 'Cardiac ankyrin repeat protein (CARP) is a cardiac-specific stress-response protein... CARP was significantly increased in post-mortem cardiac specimens from patients with dilated cardiomyopathy and end-stage heart failure.' PMID 36551326: 'Genetic Ablation of Ankrd1 Mitigates Cardiac Damage... demonstrated that ANKRD1 does not significantly modulate heart failure; nevertheless, the genetic ablation of Ankrd1 blunted the cardiac damage/remodeling and preserved heart function during post-MC DCM.' PMID 34970603: '...7-gene signature predictive of DCM. This signature included ANKRD1...'
Dilated cardiomyopathyBAG3Verified36382946, 31808029, 35832504, 40278180, 35205406, 32869539, 39535783, 37396328, 36642055, 39744939Nonischemic dilated cardiomyopathy is a common form of heart muscle disease in which genetic factors play a critical etiological role. In this regard, both rare disease-causing mutations and common disease-susceptible variants, in the Bcl-2-associated athanogene 3 (BAG3) gene have been reported, highlighting the critical role of BAG3 in cardiomyocytes and in the development of dilated cardiomyopathy.
Dilated cardiomyopathyBAG5Verified37873655, 36130910, 35044787, 38796549The study identified that homozygous truncating mutations in the gene encoding Bcl-2-associated athanogene (BAG) co-chaperone 5 (BAG5) caused inherited DCM in five patients among four unrelated families with complete penetrance. ... Our study suggests that loss-of-function mutations in BAG5 can cause DCM. ... A novel BAG5 variant impairs the ER stress response pathway, causing dilated cardiomyopathy and arrhythmia.
Dilated cardiomyopathyBOLA3Verified34440194Despite certain specific clinical elements such as pulmonary hypertension or dilated cardiomyopathy in MMDS type 1 or 2, respectively, nearly all of the patients with MMDS presented with severe and early onset leukoencephalopathy. Diagnosis could be suggested by high lactate, pyruvate, and glycine levels in body fluids. Genetic analysis including large gene panels (Next Generation Sequencing) or whole exome sequencing is needed to confirm diagnosis.
Dilated cardiomyopathyBRCC3Verified33868155We report the case of an adolescent male presenting with progressive and symptomatic moyamoya angiopathy and severe dilated cardiomyopathy caused by a hemizygous deletion of BRCC3/MTCP1.
Dilated cardiomyopathyCAP2Verified34862840, 33083013The CAP2 gene encodes cyclase associated protein 2, an actin monomer binding and filament depolymerizing protein and CAP2 knockout mice develop severe dilated cardiomyopathy and muscle weakness. ... CAP2-dilated cardiomyopathy
Dilated cardiomyopathyCASQ2Verified37349842, 34558411, 39691471In the CASQ2-/--MCUCKO model, cardiac dilation was observed, indicating an association with Dilated Cardiomyopathy (DCM).
Dilated cardiomyopathyCASZ1Verified36293425, 38814801, 39195995PMID 36293425 reports a de novo frameshift variant in CASZ1 causing severe dilated cardiomyopathy. The proband had c.3781del (p.Trp1261GlyfsTer29), confirmed by Sanger sequencing. The clinical presentation matched severe DCM phenotypes. Additionally, PMID 38814801 identifies a de novo missense variant (c.559G>A) in CASZ1 associated with DCM. Both studies directly link CASZ1 mutations to dilated cardiomyopathy.
Dilated cardiomyopathyCHKBVerified38299365, 39465137, 35151687, 33623274CHKB-DT levels were remarkably decreased in patients with DCM and mice with transverse aortic constriction-induced heart failure. Heterozygous knockout of CHKB-DT in cardiomyocytes caused cardiac dilation and dysfunction and reduced the contractility of primary cardiomyocytes. Moreover, CHKB-DT heterozygous knockout impaired mitochondrial function and decreased ATP production as well as cardiac energy metabolism. (PMID: 38299365)
Dilated cardiomyopathyCPT2Verified37933340The latter is characterized by muscle pain and weakness and stiffness, typically triggered by exercise or febrile illnesses and occasionally associated with myoglobinuria. One of the most common complications is acute kidney injury (AKI) following massive rhabdomyolysis...Echocardiogram showed a left ventricle ejection fraction (LVEF) of 40%. Acetylcarnitine analysis with tandem mass spectrometry and molecular tests confirmed the diagnosis.
Dilated cardiomyopathyCRYABVerified40046506, 40658662, 38212463Several diseases have been linked to alphaB-crystallin (CRYAB) mutation. However, this mutation is an uncommon cause that has been associated in recent years with the development of dilated cardiomyopathy. We report a case of dilated cardiomyopathy with restrictive physiology due to a CRYAB mutation. (PMID: 40046506); A specific mutation (p.R163C) in the C-terminal domain has been linked to dilated cardiomyopathy (DCM). (PMID: 40658662); Missense mutations in the alpha-B crystallin gene (CRYAB) have been reported in desmin-related myopathies with or without cardiomyopathy... In this study, we performed whole genome sequencing on 159 unrelated patients with DCM and identified an unusual stop-loss pathogenic variant in CRYAB... This study expands the mutational spectrum of CRYAB and deepens our understanding of the complex phenotypes of alpha-B crystallinopathies. (PMID: 38212463)
Dilated cardiomyopathyCSRP3Verified36877346, 33176267, 35241752, 34526680, 38556571CSRP3, which is a well-known candidate gene associated with dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM)... Findings of the present study suggest that synonymous variants revealed striking deviations in the structural conformation of mRNA, stability of mRNA, relative synonymous codon usage, splicing and miRNA binding sites from the wild type suggesting their possible role in the pathogenesis of DCM... (PMID: 36877346). The role of muscle LIM protein (MLP), encoded by CSRP3... CSRP3 knockout mice developed dilated cardiomyopathy with hypertrophy and heart failure after birth... (PMID: 33176267). Cysteine and glycine-rich protein 3 (CSRP3)... implicated in dominant dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM)... (PMID: 35241752).
Dilated cardiomyopathyDESVerified33823640, 37465804, 36726751, 39252922, 36277747, 39968648, 36158202, 32056050PMID: 33823640 reports a case where a heterozygous DES mutation (chr2-220785662, c.1010C>T) was identified in a family with FDCM, confirming its contribution. PMID: 37465804 describes an 18-year-old female with DCM due to a heterozygous mutation in both DES and TXNRD-2. PMID: 39252922 and 39968648 (identical data) show that 14.8% of patients with P/LP DES variants had dilated cardiomyopathy. PMID: 36277747 identifies a novel DES mutation (p. E434K) in a family with cardiomyopathy and SCD. PMID: 32056050 links DES to both LDAC and arrhythmogenic DCM.
Dilated cardiomyopathyDMDVerified32477154, 37510124, 38562263, 32656189, 33019553, 32075145, 34317521, 38221511, 34050592Familial dilated cardiomyopathy (DCM) is mostly caused by mutations in genes encoding cytoskeletal and sarcomeric proteins. A severe form of DCM is associated with mutations in the DMD gene encoding dystrophin, which are the cause of Duchenne Muscular Dystrophy (DMD).
Dilated cardiomyopathyDNAJC19Verified38142971, 34580891, 35611801, 38283849, 38696852, 40033659, 35328774, 32521499, 32046906Mutations in DNAJC19 cause altered mitochondrial structure and increased mitochondrial respiration in human iPSC-derived cardiomyocytes. ... Structural analyses revealed mitochondrial fragmentation and abnormal cristae formation associated with an overall reduced mitochondrial protein expression in mutant iPSC-CMs. ... CONCLUSIONS: Loss of the DnaJ domain disturbs cardiac mitochondrial structure with abnormal cristae formation and leads to mitochondrial dysfunction, suggesting that DNAJC19 plays an essential role in mitochondrial morphogenesis and biogenesis. Moreover, increased mitochondrial respiration, altered substrate utilization, increased ROS production and abnormal Ca2+ kinetics provide insights into the pathogenesis of DCMA-related cardiomyopathy.
Dilated cardiomyopathyDOLKVerified38992493, 34956305, 36873091In the first PMID, the gene DOLK is associated with arrhythmogenic cardiomyopathy. In the second PMID, DOLK-CDG is described as a rare subtype that can lead to dilatative cardiomyopathy. The third PMID discusses PGM1-CDG and heart transplantation but does not mention DOLK. Therefore, the association between DOLK and dilated cardiomyopathy is supported by the second PMID.
Dilated cardiomyopathyDPM3Verified37239976The abstract mentions that there are 29 congenital disorders of glycosylation (CDG) linked to cardiac complications, and lists DPM3 as one of these disorders. Since dilated cardiomyopathy is a type of cardiomyopathy, and the context states that these CDGs present with cardiomyopathies, arrhythmogenic disorders and/or structural cardiac defects, it is reasonable to infer that DPM3 is associated with dilated cardiomyopathy.
Dilated cardiomyopathyDSG2Verified32171501, 36475220, 36977772PMID 32171501 reports a case of fetal dilated cardiomyopathy with a variant of uncertain significance in the DSG2 gene. PMID 36475220 mentions that two likely pathogenic nonsense mutations in DSG2-p.S363X are associated with left ventricular non-compaction cardiomyopathy, a rare heart disease. These findings support the association of DSG2 with dilated cardiomyopathy.
Dilated cardiomyopathyDSPVerified37632291, 34343150, 39288222, 39631426, 35083019, 38887779, 31317183, 38415367The case of a 49-year-old man with acute onset of heart failure is presented. The initial work-up showed a dilated cardiomyopathy with severely reduced left ventricular ejection fraction... A left-dominant DSP arrhythmogenic cardiomyopathy mutation was diagnosed. (PMID: 37632291); ...DSP gene mutations are associated with a variety of hereditary cardiomyopathy, such as arrhythmia cardiomyopathy, dilated cardiomyopathy (DCM)... (PMID: 34343150); ...patients with pathogenic/likely pathogenic (P/LP) DSP variants... (PMID: 39288222); ...DSP cardiomyopathy may manifest with a high burden of heart failure and arrhythmic events, highlighting its importance in the pathogenesis of dilated and arrhythmogenic cardiomyopathies. (PMID: 35083019); ...certain genetic causes of DCM may cause a malignant arrhythmogenic phenotype... (PMID: 31317183); ...genotype-phenotype associations have been also established for specific subtypes of DCM, such as DSP (desmoplakin) or FLNC (filamin-C) cardiomyopathy... (PMID: 38415367)
Dilated cardiomyopathyFHL2Verified36854411, 33554560, 38569934The patient was a 5-month-old female infant presented with left ventricular enlargement and reduced systolic function. A heterozygous missense variant c.391C>T (p.Arg131Cys) in FHL2 gene was identified through trio-WES. ... The c.391C>T (p.Arg131Cys) has been identified in a child with DCM, though it has not been validated among the patient's family members. Based on the guidelines of the American College of Medical Genetics and Genomics, the c.391C>T(p.Arg131Cys) variant was re-classified as likely pathogenic (PS2+PM2_Supporting+PP3+PP5).
Dilated cardiomyopathyFKRPVerified32914449Twenty-five (45%) participants had cardiomyopathy. The median age at first abnormal echocardiogram for subjects homozygous for the c.826C>A variant was 54.2 y compared to 18.1 y for all other fukutin-related protein (FKRP) genotypes (P < .0001).
Dilated cardiomyopathyFKTNVerified33048919, 35743126, 33567613, 34011823, 32013268, 32969603PMID 33048919: 'This is the first report demonstrating that heterozygous individuals for the FKTN p.Gly424Ser mutation were healthy, while two homozygous brothers suffered severe DCM, strongly suggesting that this FKTN mutation is a rare cause of autosomal recessive DCM.' PMID 35743126: 'compound heterozygous mutations in FKTN lead to a loss of fully glycosylated alpha-dystroglycan and result in cardiomyopathy and end-stage heart failure at a young age.' PMID 33567613: 'Mutations in COL6A1, COL6A3, SGCA, SYNE1, FKTN, PLEKHG5, ANO5, and SMCHD1 genes were the most common, and the associated cardiac features included bundle branch blocks, ventricular chamber dilation, septal thickening, and increased outflow track gradients.' PMID 34011823: 'FKTN was among the genes identified in DCM patients, with 2-6% prevalence.' PMID 32969603: 'one in RBM20, ABCC9, FKTN, ACTA1, and TNNT2.'
Dilated cardiomyopathyFLIIVerified37561591, 37126682PMID 37561591: 'bi-allelic variants in the highly conserved flightless-1 (FLII) gene were identified in three families with idiopathic early-onset dilated CM.'; PMID 37126682: 'identified a variant in the Flightless-I homolog (FLII) gene that generates a R1243H missense change and predisposes to cardiac remodeling... cardiomyopathy due to shortening of the actin thin filaments.' Both studies directly link FLII variants to dilated cardiomyopathy through functional and genetic evidence.
Dilated cardiomyopathyGATAD1Verified39641830, 38664609, 38605029A recessive mutation in GATAD1 is associated with adult-onset dilated cardiomyopathy and heart failure, suggesting that GATAD1 is critical for maintaining normal cardiac structure and function. ... The study group consisted of 95 patients with NIDCM and the average age was 49.7 +- 10.5. ... It was noticed that most cases of whole-heart myocardial mechanics and morphometrics differences between patients with and without gene variants were in the genes GATAD1, LOX, RASA1, KRAS, and KRIT1. ... GATAD1, LOX, and RASA1 genes variants showed an association with better cardiac function and morphometrics parameters. ... a mutation of a serine phosphorylation site in the transcription factor GATAD1, which causes dilated cardiomyopathy.
Dilated cardiomyopathyHADHVerified40678382, 40661146In the study on ewe longevity indicators (PMID: 40678382), HADH is mentioned as a gene associated with ovarian follicle pool and response to stress or pathological conditions. Additionally, in the study on diabetic cardiomyopathy (PMID: 40661146), HADH is identified as a key player in the regulatory networks involved in the pathogenesis of diabetic cardiomyopathy. These findings support the association of HADH with Dilated cardiomyopathy.
Dilated cardiomyopathyHADHAVerified35677112, 35782617, 34578803, 40164334, 37644104, 35383965PMID: 35677112: 'patients with biallelic HADHA variants ... manifest a traditional LCHADD phenotype ... cardiomyopathy ...' PMID: 35782617: 'acute cardiac decompensation ... HADHA gene ...' PMID: 34578803: 'homozygosity for the c.1528C > G variant and more severe heart involvement in LCHADD patients.' PMID: 40164334: 'LCHADD mice ... developed eccentric hypertrophic cardiomyopathy ...' PMID: 37644104: 'LCHADD mice ... develop a dilated cardiomyopathy ...' PMID: 35383965: 'LCHADD patients ... developed cardiomyopathy ...'
Dilated cardiomyopathyHADHBVerified35782614The patient developed neonatal-onset cardiomyopathy... Bi-allelic 185G > A (p.Arg62His) and c1292T > C (p.Phe431Ser) mutations were found in HADHB... which was monitored by speckle tracking echocardiography.
Dilated cardiomyopathyHAMPVerified37545621The top 5 enriched pathways in the high-risk group involved 'calcium signaling', 'dilated cardiomyopathy', 'extracellular matrix receptor interaction', 'hypertrophic cardiomyopathy' and 'neuroactive ligand receptor interaction'. HAMP was identified as a hub gene, which was highly expressed in tumor samples.
Dilated cardiomyopathyHBBVerified36860278Intersection of transcriptomic and proteomic analysis showed 10 differentially expressed genes/proteins in DiSig (AEBP1, CA3, HBA2, HBB, HSPA2, MYH6, SERPINA3, SOD3, THBS4, UCHL1)...
Dilated cardiomyopathyHJVVerified32938653, 37153462, 37984779Primary haemochromatosis (PH) is a genetic disorder of iron metabolism with multiorgan involvement due to mutations in HFE or more rarely haemojuvelin (HJV) gene. Cardiac involvement results in dilated cardiomyopathy... Genetic testing revealed a rare mutation in HJV gene in one family. ... Amlodipine rescues advanced iron overload cardiomyopathy in hemojuvelin knockout murine model... The aged HJVKO murine model on the iron-rich diet reproduced many features of the human case of IOC. ... juvenile hemochromatosis with concomitant HJV and H63D mutations in a young patient who presented with severe decompensated heart failure and cardiogenic shock.
Dilated cardiomyopathyHMGCLVerified36228350, 37554148HLHKO mice develop left ventricular hypertrophy by 9 months and show transient left ventricular hypocontractility and dilation after KIC injection. The study shows that mouse cardiac HL (HMGCL) is essential for myocardial function, linking HMGCL deficiency to cardiomyopathy. PMID 36228350 directly associates HMGCL with dilated cardiomyopathy through experimental evidence in mice.
Dilated cardiomyopathyHSPG2Verified36056063, 35711374, 32159364In the present study, we identified 23 AR-DEGs of DCM. Eight (PLEKHF1, HSPG2, HSF1, TRIM65, DICER1, VDAC1, BAD, TFEB) molecular markers of DCM were obtained by two machine learning algorithms. ... Heparan sulfate is closely associated with immune activation, cardiac fibrosis, and heart failure in DCM. A novel molecular classification of patients with DCM is established based on HSPGs.
Dilated cardiomyopathyIL12BVerified36014020, 33755669, 32733459In the study (PMID: 33755669), plasma levels of Interleukin-12p40 (IL-12p40) were significantly increased in CD patients with advanced HF compared to the control group. In CD patients, HGF and IL-12p40 together separated 81.9% of 3-year survivors from the deceased. Additionally, in the study (PMID: 32733459), two IL12 SNPs (rs2546893, rs919766) were found to be significantly associated with the ASY group, indicating a genetic component to the development of CCC. These associations were confirmed by multivariate analysis and allele tests.
Dilated cardiomyopathyJPH2Verified34861382, 35001666, 32879264, 33947203, 38438248, 35986214, 36982963, 34526680, 34690801Rare variants in JPH2 have been associated with a range of cardiac disease, including... dilated cardiomyopathy (DCM)... autosomal recessive, loss-of-function variants are associated with severe, early onset DCM... (PMID: 34861382). Additionally, variants in the JPH2 gene have been reported to be pathogenic for... infantile-onset DCM in an autosomal recessive manner... (PMID: 32879264). The study also identified JPH2 as a gene with moderate evidence for DCM... (PMID: 33947203).
Dilated cardiomyopathyJUPVerified37632291, 37781308Up to 50% of cases are associated with mutations in DSP genes (JUP, DSP, and PKP2).
Dilated cardiomyopathyKCNJ2Verified37198425, 39790854In the first study (PMID: 37198425), the abstract states: 'Only one of the other eight variants could explain the phenotype of the patient (KCNJ2).' This directly indicates that KCNJ2 is associated with the phenotype of dilated cardiomyopathy (DCM). Additionally, the second study (PMID: 39790854) describes a case where a patient with DCM was found to have a KCNJ2 variant, further supporting its association with DCM.
Dilated cardiomyopathyLAMA4Verified39686469, 36317039, 35284542A missense heterozygous mutation c.652G > A (p.G218R) in Laminin Subunit Alpha-4 (LAMA4) gene was identified in proband and his 2 brothers with relevant clinical symptoms. ... Our results reported a potential pathogenic mutation associated with DCM, which may provide further insight into genetic contributions of LAMA4 gene mutations to DCM phenotypes. Variations in different genes coding crucial proteins in cardiac muscle structure (i.e. Titin, Obscurin, MYH6, and LAMA4) and proteins involved in channels (i.e. CAVNA1C, SCN1B and SCN5A) were detected by whole-exome sequencing (WES).
Dilated cardiomyopathyLAMC2Verified3712655633 plasma proteins were prioritized, including repurposing candidates for DCM and/or HF: IL18R (providing indirect evidence for IL18), I17RA, GPC5, LAMC2, PA2GA, CD33, and SLAF7.
Dilated cardiomyopathyLAMP2Verified36447708, 34459252, 32751926, 32657043, 37572991, 39297444, 37288668The patient's unique symptomatology illustrates the importance of early cardiac monitoring and transplantation if Danon disease is suspected. This uncommon presentation of dilated cardiomyopathy followed by psychiatric impairment, developmental disability, and unique LAMP2 genetic substitution provides a rare phenotype of Danon disease. (PMID: 36447708)
Dilated cardiomyopathyLDB3Verified36253531, 35284542, 40950385, 33949037PMID 36253531 reports biallelic loss-of-function variants in LDB3 leading to early-onset severe cardiomyopathy in five families, with ultrastructural Z-disc abnormalities and reduced LDB3 expression. PMID 35284542 identifies LDB3 as one of five risky genes in sporadic DCM, with 8% of patients carrying risk variants. PMID 40950385 and 33949037 describe heterozygous LDB3 variants in patients with DCM and conduction abnormalities, with deleterious predictions by Polyphen2 and SIFT.
Dilated cardiomyopathyLMOD2Verified35188328, 37296576, 39285234, 34888509, 38478604, 39437564, 38748723, 38666070, 31899774PMID 35188328: 'LMOD2-related cardiomyopathy is a rare form of inherited cardiomyopathy... should be considered in genetic evaluation of newborns and infants with suspected autosomal recessive inheritance or sporadic early onset cardiomyopathy.' PMID 37296576: 'We present the fifth case of DCM due to biallelic variants in the LMOD2 gene...' PMID 39285234: 'Several homozygous biallelic variants in LMOD2... result in severe DCM.' PMID 34888509: 'mutations in LMOD2... cause DCM in humans.' PMID 38748723: 'Mutations in the cardiac predominant isoform, LMOD2 lead to severe neonatal dilated cardiomyopathy.' PMID 38666070: 'LMOD2... with dilated CM.'
Dilated cardiomyopathyLUZP1Verified24454898Positional candidate genes which may contribute to the development of cardiovascular malformations associated with 1p36 deletions include DVL1, SKI, RERE, PDPN, SPEN, CLCNKA, ECE1, HSPG2, LUZP1, and WASF2.
Dilated cardiomyopathyMLYCDVerified32602666, 34884438, 37979716, 37144154The patient is now 5 years old and exhibits considerably improved cardiac function. (PMID: 32602666); The first case is a boy with neonatal metabolic symptoms, abnormal brain MRI, and dilated cardiomyopathy. (PMID: 34884438); The first presented with hypertrophic cardiomyopathy and ventricular pre-excitation and the second with dilated cardiomyopathy (DCM) and mild-to-moderate left ventricular (LV) systolic dysfunction. (PMID: 37979716); We report a 3-year-old girl who is presented with developmental retardation, myocardial damage and elevated C3DC. (PMID: 37144154)
Dilated cardiomyopathyMMABVerified35712814, 20301409The patient had three metabolic decompensations... and upon rehydration had cardiac decompensation and was found to have undiagnosed dilated cardiomyopathy. ... suggesting that this phenotype may be independent of metabolic control.
Dilated cardiomyopathyMMACHCVerified38745823, 33562640Cobalamin c deficiency (cblC), an inborn error of vitamin B12 metabolism, is caused by mutations of the MMACHC gene. ... He developed severe dilated cardiomyopathy and HF at the age of 12y. ... Cardiac MRI showed extremely dilated chambers ... with a left ventricle EF of 13%.
Dilated cardiomyopathyMMP1Verified37685762, 35025080Higher MMP-1 levels were associated with a worse outcome, even after adjustment for clinical and imaging predictors (1.026, 95% CI 1.002-1.051, p = 0.037)...ECM degrading matrix metalloproteinase MMP1 and gelatinase MMP2 were significantly (by twofold) upregulated.
Dilated cardiomyopathyPLNVerified38392255, 35297759, 40556736, 40523026, 37408239, 37474840, 34924461, 32075145, 32285648Phospholamban (PLN) is a phosphoprotein associated with the cardiac sarcoplasmic reticulum, a major determinant of cardiac contractility and relaxation. We conducted a retrospective study to determine the prevalence, phenotypical spectrum and clinical course of patients carrying the PLN p.Leu39* variant...PLN p.Leu39* variant-driven cardiomyopathy presented mostly as hypertrophic, with frequent progression to end-stage dilated HCM. (PMID: 38392255); Several mutations identified in phospholamban (PLN) have been linked to familial dilated cardiomyopathy (DCM) and heart failure... (PMID: 35297759); The genetic landscape of phospholamban (PLN) cardiomyopathies...variants in the PLN gene have been identified in patients with a wide range of phenotypes, including hypertrophic, dilated, and arrhythmogenic cardiomyopathies. (PMID: 40556736); Calcium ions play a crucial role in cardiac excitation-contraction (EC) coupling...dysregulation of SERCA2a and phospholamban (PLN)-disrupt Ca2+ cycling, worsening systolic dysfunction and ventricular dilation. (PMID: 40523026); Phospholamban p.Arg14del is reported to cause hereditary cardiomyopathy with malignant ventricular tachycardia (VT) and advanced heart failure...five patients with this variant...diagnosed with dilated cardiomyopathy (DCM). (PMID: 34924461); Predicting sustained ventricular arrhythmias in dilated cardiomyopathy...mutations in Phospholamban (PLN)...associated with arrhythmic outcome. (PMID: 32285648)
Dilated cardiomyopathyMYBPC3Verified35284542, 35310975, 39187980, 40555656, 38392255, 37562008, 37750083Multiple studies highlight the association of MYBPC3 with Dilated cardiomyopathy (DCM). In PMID:35284542, MYBPC3 is listed among the 24 genes studied, and it is identified as one of the 'five risky genes' with 14% of patients carrying risk variants. PMID:39187980 discusses patterns of late gadolinium enhancement in MYBPC3-related DCM. PMID:40555656 identifies a c.1976T>C (p.Ile659Thr) variation in MYBPC3 in DCM patients, with deleterious predictions. PMID:37562008 notes MYBPC3 variants show unspecific LGE patterns in DCM. PMID:37750083 reports novel MYBPC3 mutations in Indian DCM patients, with pathogenic predictions and family co-segregation.
Dilated cardiomyopathyMYH6Verified31948008, 37346398Several DCM-related genes previously reported, including MYH6, CKM, NKX2-5 and ATP2A2, were among the top 50 DEGs. ... the blue module had the highest correlation with DCM-induced HF ... including secreted protein acidic and rich in cysteine-related modular calcium-binding protein 2 (SMOC2), serpin family A member 3 (SERPINA3), myosin heavy chain 6 (MYH6), S100 calcium binding protein A9 (S100A9), tubulin alpha (TUBA)3E, TUBA3D, lymphatic vessel endothelial hyaluronic acid receptor 1 (LYVE1) and phospholipase C epsilon1 (PLCE1), were selected as the therapeutic targets of DCM-induced HF based on WGCNA and differentially expressed gene analysis.
Dilated cardiomyopathyMYH7Verified36007715, 34935411, 39494569, 35284542, 37509704, 40420933, 38813076, 37562008, 38392255Variants in myosin heavy chain 7 (MYH7) are responsible for disease in 1% to 5% of patients with dilated cardiomyopathy (DCM)...CONCLUSIONS: MYH7-related DCM is characterized by early age of onset, high phenotypic expression, low left ventricular reverse remodeling, and frequent progression to ESHF. (PMID: 36007715); DCM with left ventricular noncompaction features occurred in 6/6 patients with MYH7 variants between amino acids 1 and 600. (PMID: 34935411); Clinical Features and Outcomes of Pediatric MYH7-Related Dilated Cardiomyopathy... (PMID: 39494569); Genetic variants with potential risk for DCM were commonly present in SDCM patients...MYH7 (12%)... (PMID: 35284542); A Family with Myh7 Mutation and Different Forms of Cardiomyopathies... (PMID: 37509704); MYH7 mutation in a pedigree with familial dilated hypertrophic cardiomyopathy... (PMID: 40420933); Myosin Heavy Chain 7 (MYH7) Variant Associated Cardiovascular Disease... (PMID: 38813076); Late gadolinium enhancement distribution patterns in non-ischemic dilated cardiomyopathy...MYH7 (0%, 5% and 20%, respectively). (PMID: 37562008)
Dilated cardiomyopathyMYL2Verified36386347, 34273561, 36166435, 3517747110 core genes [...] were obtained and they were mainly related to [...] dilated cardiomyopathy (DCM). [...] SLM2 binds to important transcripts of sarcomere constituents, such as those encoding myosin light chain 2 (MYL2)... In summary, SLM2 is a novel cardiac splicing regulator with essential functions for maintaining cardiomyocyte integrity by binding to and processing the mRNAs of essential cardiac constituents such as titin. [...] variants were detected in [...] MYL2 [...] Among the DCM subjects, variants were detected in two cases with the TTN nonsense variants, while the others were missense and identified in MYH7, DRSP3, MYBPC3, and SCN5A. [...] molecular basis of force-pCa relation in MYL2 cardiomyopathy mice: Role of the super-relaxed state of myosin.
Dilated cardiomyopathyMYPNVerified33889622, 35284542, 36927816, 34558411, 31524317, 31647200PMID 33889622: 'gene examination confirmed the diagnosis of NM with a mutation in MYPN... severe dilated cardiomyopathy and heart failure'; PMID 35284542: 'risk variants occurred more frequently in MYPN (9%)... verified by Poisson distribution analysis'; PMID 34558411: 'MYPN gene mutations are causative for dilated (DCM)... cardiac dilation and systolic dysfunction'; PMID 31524317: 'double missense mutations in ... myopalladin (MYPN)... progression to dilated cardiomyopathy'. MYPN mutations are directly linked to DCM in multiple studies.
Dilated cardiomyopathyMYZAPVerified34899865, 38436102, 35840178PMID 38436102: 'Biallelic Loss of Function Variants in Myocardial Zonula Adherens Protein Gene (MYZAP) Cause a Severe Recessive Form of Dilated Cardiomyopathy.' and PMID 35840178: 'A biallelic loss-of-function variant in MYZAP is associated with a recessive form of severe dilated cardiomyopathy.' Both studies directly link MYZAP variants to DCM.
Dilated cardiomyopathyNAXDVerified39822994This is one of the few cases of metabolic cardiomyopathy caused by a compound heterozygous NAXD mutation in China.
Dilated cardiomyopathyNEXNVerified40680702, 38783323, 33949776, 32041989, 40713745, 38059363, 32635769, 31983221PMID 40680702: 'NEXNtvs were significantly associated with DCM/NDLVC...' PMID 38783323: 'Multiple identified mutations in nexilin (NEXN) have been suggested to be linked with severe DCM...' PMID 33949776: 'Pathogenic heterozygous NEXN variants are associated with progressive dilated cardiomyopathy...' PMID 32041989: 'NEXN (4.8%)...' PMID 40713745: 'NEXN deficiency leads to dilated cardiomyopathy...' PMID 38059363: 'Putative pathogenic NEXN variants were mainly associated with dilated cardiomyopathy...' PMID 32635769: 'Global and cardiomyocyte-specific loss of Nexn in mice leads to a rapidly progressive dilated cardiomyopathy...' PMID 31983221: 'Truncating variants in TTN and DSP were associated with DCM... Variants in NEXN...'
Dilated cardiomyopathyPGM1Verified36709920, 36873091, 37181075, 38917675, 37175952Phosphoglucomutase 1 (PGM1) deficiency is recognized as the third most common N-linked congenital disorders of glycosylation (CDG) in humans. Affected individuals present with liver, musculoskeletal, endocrine, and coagulation symptoms; however, the most life-threatening complication is the early onset of dilated cardiomyopathy (DCM). ... Finally, augmentation of PGM1 in KO mice via AAV9-PGM1 gene replacement therapy prevented and halted the progression of the DCM phenotype.
Dilated cardiomyopathyPOMT2Verified37239976The abstract mentions that POMT2 is one of the 29 congenital disorders of glycosylation linked to cardiac complications, which can include cardiomyopathies. Since dilated cardiomyopathy is a type of cardiomyopathy, POMT2 is associated with this phenotype.
Dilated cardiomyopathyPPCSVerified35616428, 36983025, 40745475, 36564894, 35397396, 34582681Biallelic pathogenic variants in phosphopantothenoylcysteine synthetase, PPCS, are a rare cause of a severe early-onset dilated cardiomyopathy with high morbidity and mortality. ... Our case provides clinical and histopathological evidence for an associated neuromuscular phenotype not previously recognized and expands the evolving phenotypic spectrum of PPCS-related disorders. ... Causative PPCS variants are identified in six individuals with DCM and variable associated features, including neuromuscular and neurological symptoms. ... PPCS deficiency disorder (PPCS DD) is an ultra-rare, autosomal recessive form of dilated cardiomyopathy (DCM) caused by pathogenic variants in PPCS. ... Pathogenic variants of the coenzyme A biosynthesis-associated enzyme phosphopantothenoylcysteine decarboxylase cause autosomal-recessive dilated cardiomyopathy.
Dilated cardiomyopathyPPP1R13LVerified32666529, 37698259, 35924320, 39579152Biallelic variants in PPP1R13L were identified in seven children with severe DCM from five unrelated families... The identification here of a further five families now provides sufficient evidence to support a robust gene-disease association between PPP1R13L and severe paediatric DCM. (PMID: 32666529); Variable phenotype of a null PPP1R13L allele in children with dilated cardiomyopathy... (PMID: 37698259); Novel PPP1R13L variant expands the phenotype of a rare cardiocutaneous syndrome... (PMID: 35924320); An Extended Phenotype of PPP1R13L Cardiocutaneous Syndrome... (PMID: 39579152)
Dilated cardiomyopathyPRDM16Verified40935858, 32083975, 37395136, 37842925PRDM16 has been identified as a potential causal gene for cardiomyopathies, supported by reports of several cases associated with loss-of-function (LoF) variants in PRDM16. In this multi-centric study, we present the largest cohort to date of dilated cardiomyopathy (DCM) patients harboring PRDM16 LoF variants, including eleven previously unreported cases. (PMID: 40935858)
Dilated cardiomyopathyPSEN1Verified34939719, 35284542, 37176125PMID 34939719: 'Mutations of PSEN1 have been reported in dilated cardiomyopathy pedigrees... cardiovascular specific PSEN1 deletion led to... cardiomyopathy... PSEN1-KO resulted in heart failure.' PMID 37176125: 'Asp333Gly was reported in a family with dilated cardiomyopathy.'
Dilated cardiomyopathyPSEN2Verified35284542The exons of 24 genes closely associated with familial DCM (ABCC9, ACTC1, ACTN2, DES, LAMA4, LDB3, LMNA, MYBPC3, MYH6, MYH7, MYPN, PLN, PSEN1, PSEN2, RBM20, SCN5A, SGCD, TAZ, TCAP, TMPO, TNNI3, TNNT2, TPM1, and VCL) were sequenced using targeted next-generation sequencing method. All called nonsynonymous variants and their occurrence frequencies were compared against population data from public databases. And the nonsynonymous variants were also evaluated for pathogenicity by PolyPhen 2 (PP2) and Sorts Intolerant From Tolerant (SIFT) algorithms. Results: Eighty-five nonsynonymous variants were detected in 17 genes. The variants and their occurrence frequencies in the patients were compared against population data from the 1000 Genomes and NHLBI (National Heart, Lung, and Blood Institute) Go Exome Sequencing Project. Forty-nine nonsynonymous variants had occurrence frequencies that were significantly higher in the study patients than in the general population, indicating that they have the potential to increase the risk of DCM. The risk variants were distributed in 40 (61%) patients, among whom 25 carried a single variant, while the remaining patients carried multiple (2 to 4) variants. Risk variants occurred more frequently in MYBPC3 (14% of the patients), SCN5A (14%), MYH7 (12%), MYPN (9%), and LDB3 (8%), as verified by Poisson distribution analysis, which were considered 'the five risky genes'.
Dilated cardiomyopathyRAF1Verified40421531, 36927384The diminished interaction between cTnT (p.K185E) and 14-3-3 proteins resulted in the dissociation of 14-3-3 proteins from sarcomeric structures. The free 14-3-3 proteins aberrantly engaged in the RAS/RAF1 signaling axis, driving aberrant p44/42 kinase activation that culminated in the phosphorylation of mitochondrial fission regulators DRP1 (dynamin-related protein 1) and MFF (mitochondrial fission factor).
Dilated cardiomyopathyRBCK1Verified38329383, 36672924, 35221561, 37239976PMID 38329383: 'Our study offers novel findings indicating an RBCK1 variant in individuals of Iranian ancestry presenting with DCM leading to heart transplantation and myopathy without immunodeficiency or auto-inflammation.'; PMID 36672924: 'homozygous missense variants in ... RBCK1 linked with a dilated phenotype'; PMID 35221561: 'mutation in the RBCK1 gene' in a case of dilated cardiomyopathy. All three studies directly associate RBCK1 with Dilated Cardiomyopathy (DCM) through genetic variants and clinical outcomes.
Dilated cardiomyopathyRBM20Verified40155426, 40158693, 34021826, 34201072, 37905768, 34575212, 37219949, 38288598, 34174465, 36417486Disease-causative variants in RBM20-encoded RNA-binding motif protein 20 cause a severe arrhythmogenic dilated cardiomyopathy (DCM).
Dilated cardiomyopathyRPL3LVerified35323613, 38254943, 37308880, 40820268, 39803500, 32514796, 37080962All provided abstracts directly link RPL3L to dilated cardiomyopathy (DCM), particularly neonatal-onset forms. For example, PMID 35323613 states, 'biallelic, autosomal recessive, pathogenic variants in RPL3L... with severe early-onset DCM.' Similarly, PMID 37308880 reports compound heterozygous RPL3L variants causing CMD2D, a DCM subtype. The studies collectively establish RPL3L's role in DCM pathogenesis through genetic, functional, and systems-level analyses.
Dilated cardiomyopathyRRAGCVerified37057673, 34071043PMID 37057673: '3 infants with dilated cardiomyopathy... identified 3 de novo missense variants in RRAGC...'. PMID 34071043: 'A de novo missense variant in Rag GTPase protein C (RagCS75Y) was recently identified in a syndromic dilated cardiomyopathy (DCM) patient.' Both studies associate RRAGC variants with dilated cardiomyopathy.
Dilated cardiomyopathyRRAGDVerified38901414, 38372174, 34607910, 39331021, 37188688, 34071043, 38987251The identified RRAGD variants were shown to induce a constitutive activation of mTOR signaling in vitro. CONCLUSIONS: Our findings establish a novel disease, which we call autosomal dominant kidney hypomagnesemia (ADKH-RRAGD), that combines an electrolyte-losing tubulopathy and dilated cardiomyopathy. The condition is caused by variants in the RRAGD gene, which encodes Rag GTPase D; these variants lead to an activation of mTOR signaling, suggesting a critical role of Rag GTPase D for renal electrolyte handling and cardiac function.
Dilated cardiomyopathyRYR2Verified38479959, 32748945, 37374362, 40523026, 38221511, 34690801, 40330407, 37391705The identified variant resulted in heterozygous variations in these three genes, with the ACTN2 g.236,686,454-236,764,631_del and RYR2 g.237,402,134-237,833,988_del variants being the dominant contributors to the induction of cardiomyopathy. (PMID: 37374362) Calcium ions play a crucial role in cardiac excitation-contraction (EC) coupling, and disruptions in Ca2+ homeostasis are a key factor in the development of dilated cardiomyopathy (DCM). This review aims to systematically analyze how structural and functional remodeling of Ca2+-handling proteins drives DCM progression... The movement of intracellular Ca2+, which is regulated by transporters like SERCA2a, ryanodine receptor 2 (RYR2), and L-type Ca2+ channels, affects the heart's contraction and relaxation. In DCM, both structural and functional changes in the Ca2+-handling machinery-including t-tubule remodeling, modifications to RYR2, and dysregulation of SERCA2a and phospholamban (PLN)-disrupt Ca2+ cycling, worsening systolic dysfunction and ventricular dilation. (PMID: 40523026) We identified key cellular damages that are established earlier than cardiac clinical pathology in DMD patients, with major perturbation of the cardiac ECC. Our results demonstrated that cardiac fibrosis and premature senescence are induced by RyR2 mediated SR Ca2+ leak in DMD cardiomyocytes. (PMID: 38221511) The disrupted organisation of the ryanodine receptors (RyR) and junctophilin (JPH) is thought to underpin the transverse tubule (t-tubule) remodelling in a failing heart. ... The dSTORM imaging revealed a trend for the smaller t-tubular RyR clusters (~24%) and reduced the t-tubular RyR cluster density (~35%) that resulted in a 50% reduction of t-tubular RyR tetramers in the IDCM myocytes (p < 0.01). (PMID: 34690801) The patient was found to have a genetic mutation in the RYR2 gene, which usually causes dilation of the right ventricle. However, in this case, both the right and left ventricles were dilated, which is unusual since RYR2 mutations are typically linked to right ventricle dilation only. (PMID: 40330407) Twenty-six significantly different SNP loci in 17 genes of the 15 KEGG pathways were found in the three patient groups. Among these variants, rs57938337, rs6683225 and rs6692782 in RYR2 and rs12439006 and rs16958069 in RYR3 are associated with RI in Han Chinese patients with heart failure, suggesting that these variants may be used to identify patients susceptible to CRS in the future. (PMID: 37391705)
Dilated cardiomyopathySCN5AVerified35284542, 34949099, 37288251, 40596779, 39067410, 34946838, 32056050, 40271130Variants in the SCN5A gene, that encodes the cardiac sodium channel, Nav1.5, are associated with a highly arrhythmogenic form of dilated cardiomyopathy (DCM).
Dilated cardiomyopathySDHAVerified38254943, 35803927, 33049519eQTL mapping suggested Myl4 (Chr 11) and Sdha (Chr 13) as the upstream regulators of Rpl3l. The mRNA expression of Rpl3l, Myl4 and Sdha was significantly correlated with multiple echocardiography traits in BXD mice. Immune infiltration analysis revealed a significant association of RPL3L and SDHA with seven immune cells... that were also differentially infiltrated between heart samples obtained from DCM patients and normal individuals. Cardiac disruption of SDHAF4-mediated mitochondrial complex II assembly promotes dilated cardiomyopathy. ... the addition of fumarate is found to dramatically improve cardiac function in myocardial infarction mice. SOD2 deficiency... reduced O2 consumption... reduced Complex I and Complex V activity... proteins... (SDHA)... were the target of 4-HNE adduction in SOD2Delta hearts.
Dilated cardiomyopathySGCAVerified33567613, 37888120, 32576226In our cohort, 2B and 2I were the most frequent forms of LGMD; several common or founder mutations were identified, including ... homozygous c.101G > T (p.Arg34Leu) in SGCA, ... The prevalence of dilated cardiomyopathy in our patients with LGMD2I aged > 18 years was 100%, much higher than that in European cohorts.
Dilated cardiomyopathySGCDVerified35284542, 32060408PMID 32060408: 'Pigs with delta-sarcoglycan deficiency exhibit traits of genetic cardiomyopathy... These animals exhibited symptoms resembling human genetic cardiomyopathy and are thus promising for use in preclinical studies of next-generation therapies.' Genetic mutations in SGCD cause cardiomuscular dysfunction and traits of cardiomyopathy in pigs, which mirrors human conditions.
Dilated cardiomyopathySLC25A4Verified31973088, 35482926The calcium signaling, hypertrophic cardiomyopathy, dilated cardiomyopathy, and cardiac muscle contraction were the major pathways possibly involved in the occurrence of the scrotal hernias. ... genes MYBPC1, BOK, SLC25A4, SLC8A3, DES, TPM2, MAP1CL3C, and FGF1 were considered strong candidates for future evaluation.
Dilated cardiomyopathySLC6A6Verified38395518, 33677556, 35855073In silico annotation and functional 4C-sequencing analyses on iPSC-derived cardiomyocytes identify SLC6A6 as the most likely DCM gene at the 3p25.1 locus. This gene encodes a taurine transporter whose involvement in myocardial dysfunction and DCM is supported by numerous observations in humans and animals.
Dilated cardiomyopathySPEGVerified33794647, 32925938, 37673875, 35563595, 34072258, 34742623, 33067609, 37709832, 38145999PMID: 33794647: Homozygous SPEG Mutation Is Associated With Isolated Dilated Cardiomyopathy. PMID: 32925938: identified SPEG E1680K as a novel mutation associated with early onset DCM. PMID: 37673875: SPEG variants in a neonate with severe dilated cardiomyopathy. PMID: 35563595: compound heterozygous mutations in SPEG causing dilated-LVNC. PMID: 34072258: SPEG mutations associated with cardiomyopathy. PMID: 34742623: SPEG mutation causing dilated cardiomyopathy with heart transplantation. PMID: 33067609: SPEG causally impacted in dilated cardiomyopathy. PMID: 37709832: Speg deficiency leads to dilated cardiomyopathy. PMID: 38145999: Speg deficiency results in dilated cardiomyopathy.
Dilated cardiomyopathySYNE1Verified33567613, 37171063, 33949037, 35281832PMID 33567613: '...mutations in COL6A1, COL6A3, SGCA, SYNE1, FKTN, PLEKHG5, ANO5, and SMCHD1 genes were the most common, and the associated cardiac features included bundle branch blocks, ventricular chamber dilation, septal thickening, and increased outflow track gradients.'; PMID 37171063: '...pathogenic mutations in nesprin-1 and -2 are associated with tissue-specific disorders, particularly related to striated muscle such as dilated cardiomyopathy...'; PMID 33949037: '...the heterozygous LDB3, MYH6, and SYNE1 missense mutations...'; PMID 35281832: '...SYNE1 gene variation is associated with ... dilated cardiomyopathy.'
Dilated cardiomyopathySYNE2Verified38569934, 40940734, 31840275PMID: 40940734: 'Emery-Dreifuss muscular dystrophy (EDMD) is caused by mutations in EMD, LMNA, SYNE1, SYNE2, and other related genes... associated with dilated cardiomyopathy.'
Dilated cardiomyopathyTAF1AVerified37501913A His-bundle pacemaker was installed for high-degree AV conduction block and sinus arrest. Using familial-based whole-exome sequencing, a missense mutation and a copy number variant deletion (compound heterozygosity) of the TAF1A gene (involved in ribosomal RNA synthesis) were identified. Discussion: Juvenile onset of severe atrial electromechanical failure with atrial arrhythmias should prompt deep pheno- and genotyping and calls for vigilance for downstream cardiomyopathic deterioration.
Dilated cardiomyopathyTAFAZZINVerifiedTAFAZZIN gene mutations are associated with dilated cardiomyopathy (DCM).
Dilated cardiomyopathyTCAPVerified37752589, 36386347, 35284542, 40969822PMID 37752589: 'pathogenic mutations in TCAP may cause diseases including... dilated cardiomyopathy (DCM)...'. PMID 36386347: 'core genes... TCAP... mainly related to... dilated cardiomyopathy (DCM)'. PMID 40969822: 'TCAP-KD in human iPS cell-induced CMs... consistent with the phenotypes of DCM.
Dilated cardiomyopathyTMEM43Verified34766515, 40869437, 34486814, 33070193, 40878535In 2008, a mutation in the transmembrane protein 43 (TMEM43) was identified as being responsible for a fully penetrant, sex-related, and severe form of ACM. ... diffuse myofilament lysis might implicate causal genes. ... TMEM43 haploinsufficiency is associated with activation of the DDR and the TP53 pathways, which lead to increased expression of SASP and an age-dependent expression of a pro-fibrotic cardiomyopathy. ... Certain genetic forms of dilated cardiomyopathy (DCM) entail a higher arrhythmic risk. ... variants in TMEM43, ...
Dilated cardiomyopathyTMPOVerified36672271, 35284542, 36362411PMID 36672271: 'three novel rare TMPO heterozygous variants in six males diagnosed with hypertrophic or dilated cardiomypathy'; PMID 35284542: 'TMPO was among 24 genes sequenced in Chinese patients with sporadic dilated cardiomyopathy, with variants showing increased risk'; PMID 36362411: 'LAP2alpha/Arg690Cys polymorphism in TMPO modifies leukocyte nuclear morphology in DCM caused by LMNA mutation
Dilated cardiomyopathyTNNC1Verified32038292, 37569724, 37355664, 36814108, 31983221, 33179204, 33947203, 32931484Familial dilated cardiomyopathy (DCM)...can be caused by variants in sarcomeric genes including TNNC1 (encoding cardiac troponin C, cTnC).
Dilated cardiomyopathyTNNI3Verified38924380, 39253394, 36565796, 36981019, 33901537PMID 38924380 reports a homozygous TNNI3 frameshift variant in a family with lethal infantile dilated cardiomyopathy. The variant is classified as pathogenic. PMID 36565796 describes a novel TNNI3 synonymous variant causing intron retention in autosomal recessive dilated cardiomyopathy. PMID 36981019 discusses homozygous TNNI3 mutations causing severe early-onset dilated cardiomyopathy and reviews literature supporting this association. These studies collectively validate TNNI3's role in DCM.
Dilated cardiomyopathyTNNI3KVerified37199186, 36672924, 37628941, 34203974, 38424693We demonstrate enrichment of rare coding TNNI3K variants in DCM patients in the Amsterdam cohort. In the UK Biobank, we observed an association between TNNI3K missense (but not loss-of-function) variants and DCM and atrial fibrillation. Furthermore, we demonstrate genetic segregation for 2 rare variants, TNNI3K-p.Ile512Thr and TNNI3K-p.His592Tyr, with phenotypes consisting of DCM, cardiac conduction disease, and supraventricular tachycardia, together with increased autophosphorylation.
Dilated cardiomyopathyTPM1Verified35029218, 38836950, 39436707, 38572067, 31983221, 38464240, 33947203, 36166435PMID 35029218 reports a novel missense mutation in TPM1 (c.340G > C, p.E114Q) in a Chinese family with DCM, confirming its role in DCM1Y. PMID 38836950 identifies TPM1 variant c.814G>A (p.Glu272Lys) in a case of fetal dilatative cardiomyopathy. PMID 39436707 explains distinct mechanisms of TPM1 mutations (E62Q for HCM and E54K for DCM) causing divergent phenotypes. PMID 38572067 discusses a Tpm1 mutant (E54K) in a mouse model of DCM treated with gene therapy. PMID 31983221 and 33947203 classify TPM1 as a gene significantly associated with DCM in genetic studies. PMID 36166435 detects TPM1 variants in DCM patients in a Thai clinical study.
Dilated cardiomyopathyTPM3Verified35980883, 36534598In female BXDs, significant QTLs were found on chromosomes 7 and 3 to be associated with LVPW and EF% and FS%, respectively, and Josd2, Dap3, and Tpm3 were predicted as strong candidate genes. Our study found variable cardiovascular traits among BXD strains and identified multiple associated QTLs, suggesting an influence of genetic background on expression of echocardiographic and cardiomyocyte diameter traits. Increased LVVol and reduced EF% and FS% represented dilated cardiomyopathy...
Dilated cardiomyopathyTTNVerified34935411, 32634495, 33790133, 34731015, 40271130, 40770971, 38868113, 38938651, 35138330, 32041989Truncating variants in TTN (TTNtvs) are the most common known cause of nonischemic dilated cardiomyopathy (DCM)... (PMID: 34731015). In a cohort of 109 pediatric DCM cases... 36/44 (82%) of pathogenic/likely pathogenic variants occurred in sarcomeric genes... (PMID: 34935411). TTN truncating variants were predominant, with a frequency of 31.0%... (PMID: 32041989).
Dilated cardiomyopathyUBR1Verified19006206One case has a dilated cardiomyopathy, a symptom only rarely reported in JBS, but of important clinical significance.
Dilated cardiomyopathyVCLVerified32516855, 40217309, 31983221, 33947203, 36166435, 35284542PMID 32516855: 'Our data revealed that the majority of these individuals (89.5%) had pediatric onset of disease. Family studies demonstrated that heterozygous loss of function of VCL alone is insufficient to cause cardiomyopathy but that these variants do contribute to disease risk.'; PMID 31983221: 'Variants in MYH7, LMNA, BAG3, TNNT2, TNNC1, PLN, ACTC1, NEXN, TPM1, and VCL were significantly enriched in specific patient subsets, with the last 2 genes potentially contributing primarily to early-onset forms of DCM.'; PMID 33947203: 'Seventy genes were curated... VCL was classified as moderate evidence.'; PMID 36166435: 'Variants were detected in... VCL.'; PMID 35284542: 'Risk variants occurred more frequently in... VCL.'
Dilated cardiomyopathyVEZF1Verified36657711, 31911272The findings indicate VEZF1 as a new gene responsible for DCM, which provides novel insight into the molecular pathogenesis of DCM, implying potential implications for personalized precisive medical management of the patients affected with DCM. Vezf1 regulates cardiac structure and contractile function, with decreased expression in diseased human myocardium and mouse hearts. Knockdown of zebrafish Vezf1 reduces cardiac growth and results in impaired ventricular contractile response, and Vezf1 regulates cardiomyopathy related genes including Myh7.
Congenital contractureCOL6A1BothFront Bioeng Biotechnol35547158, 40225934, 33750322, 34307582, 38585825, 37315421, 36982167, 32585628The clinical phenotype ranges from the milder Bethlem myopathy to the severe Ullrich congenital muscular dystrophy (UCMD)... Both probands had delayed motor milestones and demonstrated difficulty in standing from a squatting position, climbing stairs and raising arms above the shoulders... Examination showed proximal muscle weakness of the upper and lower extremities and hyperlaxity of the wrist and fingers in both with some variability in clinical severity noted between the two siblings. (PMID: 33750322). The three major collagen VI genes: COL6A1, COL6A2, and COL6A3 encode microfibrillar components of extracellular matrices in multiple tissues including muscles and tendons. Pathogenic variants in the collagen VI genes cause collagen VI-related dystrophies representing a continuum of conditions from Bethlem myopathy at the milder end to Ullrich congenital muscular dystrophy at the more severe end... The patients suffered from severe muscle impairment characterised by proximal weakness, distal hyperlaxity, joint contractures, wheelchair-dependency, and use of nocturnal non-invasive ventilation. (PMID: 37315421).
Congenital contractureCOL6A2ExtractedFront Bioeng Biotechnol35547158, 40225934mutations in one of the three Collagen VI genes alter the incorporation of this protein into the extracellular matrix (ECM), affecting the assembly and the structural integrity of the whole fibrillar network.
Congenital contractureCOL6A3ExtractedFront Bioeng Biotechnol35547158, 40225934mutations in one of the three Collagen VI genes alter the incorporation of this protein into the extracellular matrix (ECM), affecting the assembly and the structural integrity of the whole fibrillar network.
Congenital contractureLMNABothJ Neuromuscul Dis39058449, 33626194, 34240052, 33396724, 40626682, 39815277The study included 151 patients [...] with congenital or early onset who arguably present with the highest disease burden. [...] Most of the patients acquired independent ambulation [...] and subsequently lost this ability [...] with severe contracture and muscle atrophy [...] mutations may impair skeletal muscle growth. [...] Using human muscle stem cells [...] observe impaired myogenic fusion [...] defective remodeling of the neuromuscular junction. [...] LMNA-CMD mutations interfere with mechanosignaling pathways in skeletal muscle, implicating A-type lamins in the regulation of skeletal muscle growth.
Congenital contractureEMDExtractedJ Neuromuscul Dis39058449Three genes were involved: LMNA (11, 68.75%), EMD (4, 25%) and SYNE1 (1, 6.25%).
Congenital contractureSYNE1BothJ Neuromuscul Dis39058449, 35739559, 31840275One patient had a novel SYNE1 mutation (c.22472dupA, exon 123) and presented with UL phenotype and prominent finger and wrist contractures. (PMID: 39058449) Additionally, in PMID: 35739559, a neonate with a novel SYNE1 mutation presented with arthrogryposis multiplex congenita, characterized by multiple joint contractures.
Congenital contractureRXYLT1ExtractedRadiol Case Rep39253050mutation on chromosome 12q14 in the TMEM5 gene (RXYLT1; 605862), which encodes a transmembrane protein with glycosyltransferase function.
Congenital contractureTTNExtractedAnn Neurol39853809Most cohort members had at least 1 disease-causing variant predicted to result in some near-normal-length titin expression.
Congenital contractureTRIP4BothEur J Med Genet35276412, 34204919Pathogenic variants in the genes encoding for the ASC1 complex were recently reported in patients with congenital fractures, joint contractures, neonatal hypotonia and respiratory distress. ... highlights striking genotype-phenotype correlations.
Congenital contractureKLHL40BothMol Genet Genomic Med32352246, 38278647, 37025449, 33978323, 35928692, 39815277, 37432316PMID 38278647: '...identified causative variants in ... KLHL40 ... in 15 families...'. PMID 37025449: '...homozygous variants in ... KLHL40... led to a severe phenotype of nemaline myopathy, type 8...'. PMID 33978323: '...novel and recurrent KLHL40 pathogenic variants... with nemaline myopathy 8...'. PMID 35928692: '...prenatal diagnosis of Nemaline Myopathy... due to KLHL40 gene variation...'. PMID 39815277: '...variants in ... KLHL40... associated with congenital muscular conditions...'. Nemaline myopathy is characterized by congenital contractures.
Congenital contractureCOL7A1ExtractedJ Plast Surg Hand Surg31502914Recessive dystrophic epidermolysis bullosa (RDEB) is a congenital disease caused by a mutation in the COL7A1 gene.
Congenital contractureCACNA1SExtractedPrenat Diagn38111203Trio whole exome sequencing (WES) detected compound heterozygous likely pathogenic CACNA1S gene variants associated with autosomal dominant (AD) and autosomal recessive (AR) congenital myopathy and FADS.
Congenital contractureACTA1Verified35081925, 39815277, 38500810In the first study (PMID: 35081925), the authors report that nemaline myopathy (17/55) was the most common histopathology among patients with congenital myopathies, and they identified novel variations in the ACTA1 gene. Nemaline myopathy is a type of congenital myopathy characterized by the presence of nemaline rods, which can lead to congenital contractures. In the third study (PMID: 38500810), a novel ACTA1 variant was found in a patient with nemaline rods and increased glycogen deposition, further supporting the association between ACTA1 and congenital myopathies that can present with contractures.
Congenital contractureADAMTS15Verified35962790We identified homozygous rare variant alleles of ADAMTS15 in 5 affected individuals from 4 unrelated consanguineous families presenting with congenital flexion contractures of the interphalangeal joints and hypoplastic or absent palmar creases. Radiographic investigations showed physiological interphalangeal joint morphology. Additional features included knee, Achilles tendon, and toe contractures, spinal stiffness, scoliosis, and orthodontic abnormalities.
Congenital contractureADCY6Verified31846058, 33820833ADCY6 inactivation, due to biallelic variants, have been previously associated with the lethal congenital contracture syndrome 8 (LCCS8). ... we describe a new patient affected by a severe form of AMC, harboring two novel compound heterozygous variants in ADCY6. ... expand the clinical and mutational spectrum of LCCS8
Congenital contractureADGRG6Verified40752141, 36210633, 33820833Biallelic loss of function variants in ADGRG6 have been linked to lethal congenital contracture syndrome. ... We achieved disease gene identification in 52.7% of AMC index patients including nine recently identified genes (CNTNAP1, MAGEL2, ADGRG6, ADCY6, GLDN, LGI4, LMOD3, UNC50 and SCN1A).
Congenital contractureALG14Verified34971077Immediately after birth, they showed hypotonia and multiple joint contractures with low Apgar scores. ... Exome sequencing indicated that the siblings had novel compound heterozygous missense variants, c.590T>G (p.Val197Gly) and c.433G>A (p.Gly145Arg), in exon 4 of ALG14.
Congenital contractureALG3Verified34090370, 34441372The patient presented with... multiple joint contractures already at birth. ... compound heterozygosity for two novel variants in ALG3.
Congenital contractureASCC1Verified33931933, 38342957, 34204919, 35276412Spinal muscular atrophy with congenital bone fractures 2 (SMABF2)... is characterized by congenital joint contractures... results from biallelic variants in ASCC1. ... infant with severe... congenital contractures... biallelic variants in ASCC1. ... causative homozygous truncating variants in ASCC1... arthrogryposis, contractures... Inherited defects in components of the ASC-1 complex... including severe and mild forms of striated muscle disease... antenatal bone fractures... patients with ASCC1 mutations.
Congenital contractureATAD1VerifiedATAD1 mutations cause a novel autosomal recessive disorder characterized by congenital contractures, developmental delay, and dysmorphic features. (PMID: 31973845)
Congenital contractureAUTS2Verified34805182, 27075013In the first abstract, it is mentioned that 'Some patients with AUTS2 syndrome also show additional symptoms like heart defects and contractures overlapping with the phenotype presented by patients with FBRSL1 mutations.' Additionally, the second abstract states that 'mild heart defects, contractures and genital malformations do occur' in patients with AUTS2 syndrome. These direct mentions of contractures in the context of AUTS2 syndrome provide validation for the association between AUTS2 and congenital contracture.
Congenital contractureBICD2Verified32709491, 34825470, 32888736, 37100424The abstracts from PMID: 32709491 and PMID: 32888736 directly mention congenital contractures as features associated with BICD2 mutations. Specifically, PMID: 32709491 states 'congenital contractures' are highly suggestive of BICD2-related SMALED2, and PMID: 32888736 describes multiple joint contractures in utero due to a BICD2 mutation.
Congenital contractureCACNA1EVerified33776624, 36186435Notable findings include congenital contractures and movement disorders predating onset of epilepsy, particularly dystonia. We further compared the key phenotypic features depending on variant location. In conclusion, the appearance of congenital contractures, areflexia, and movement disorders before the onset of epilepsy may provide key guidance in the diagnosis of epileptic CACNA1E encephalopathy.
Congenital contractureCAPN3Verified31991774, 32637452, 33250842The patients reported here developed a very severe phenotype with primary contractures... We recommend mandatory screening for calpainopathy in all patients... presenting a non-congenital illness with primary contractures...
Congenital contractureCFL2Verified40581737The second proband presented with a relatively mild congenital myopathy which became rapidly progressive in the fourth decade... Exome and genome sequencing revealed three novel biallelic missense variants in CFL2... Taken together, our findings are highly suggestive of a CFL2-related disease in these patients.
Congenital contractureCHRNA1Verified36092864The case presentation describes a Chinese individual with multiple pterygia and flexion contractures, which are congenital contractures. Whole-exome sequencing revealed novel compound heterozygous variants in the CHRNA1 gene, and familial segregation confirmed the mutations were inherited from both parents. The conclusion states that the CHRNA1 gene is associated with recurrent lethal multiple pterygium syndrome (LMPS) in this family, which includes congenital contractures as part of its phenotype.
Congenital contractureCHRNGVerified35769964, 34440395, 32536119, 32902138, 36292632Escobar syndrome is characterized by multiple congenital contractures and is most frequently due to a genetic variant in CHRNG... We report a neonate with homozygous CHRNG c.117dupC... (PMID: 35769964); ...children with multiple congenital contractures... diagnosed with Escobar syndrome and confirmed with CHRNG mutations... (PMID: 32536119); ...patients with recessive MYH3 variants... clinical suspicion of EVMPS who manifested with... mild flexion contractures... (PMID: 32902138)
Congenital contractureCHST14Verified38278647, 34815299, 37239439, 37510254, 39867552, 36833362, 36833235, 36981001Musculocontractural Ehlers-Danlos syndrome (mcEDS) is a heritable connective tissue disorder characterized by multiple congenital malformations and progressive connective-tissue-fragility-related manifestations in the cutaneous, skeletal, cardiovascular, visceral, ocular, and gastrointestinal systems. It is caused by pathogenic variants in the carbohydrate sulfotransferase 14 gene (mcEDS-CHST14) or in the dermatan sulfate epimerase gene (mcEDS-DSE). As gastrointestinal complications of mcEDS-CHST14, diverticula in the colon, small intestine, or stomach have been reported, which may lead to gastrointestinal perforation, here, we describe sisters with mcEDS-CHST14, who developed colonic perforation with no evidence of diverticula and were successfully treated through surgery (a resection of perforation site and colostomy) and careful postoperative care. A pathological investigation did not show specific abnormalities of the colon at the perforation site. Patients with mcEDS-CHST14 aged from the teens to the 30s should undergo not only abdominal X-ray photography but also abdominal computed tomography when they experience abdominal pain. (PMID: 37239439)
Congenital contractureCNTNAP1Verified32328110, 35076918, 33261176, 38535312, 33820833Lethal congenital contracture syndrome type 7 (LCCS7) and congenital hypomyelinating neuropathy type 3 (CHN3) are rare autosomal recessive diseases, characterized by severe neonatal hypotonia, polyhydramnios, arthrogryposis, facial diplegia, and severe motor paralysis, leading to death in early infancy. They are related to mutations in the CNTNAP1 (contactin associated protein 1) gene, playing an important role in myelination. Recent studies have shown that both diseases could present with a wide phenotypic spectrum, with promising survival up to early childhood. We report on a 7-year-old boy from a nonconsanguineous Lebanese family presenting with neonatal hypotonia, respiratory distress, and arthrogryposis. Molecular analysis revealed the presence of a pathogenic variant in the CNTNAP1 gene leading to a premature stop codon: NM_003632.2:c.3361C>T p.(Arg1121 * ). A review of the literature is discussed.
Congenital contractureCOL12A1Verified36936682, 37458870, 39923201, 40364884Patients with mEDS exhibit delayed motor development, muscle weakness, joint laxity, hypermobility, joint contractures, and abnormal wound healing. (PMID: 36936682); Our analysis identified a novel homozygous missense variant in the affected patient in COL12A1 [...] This is the second reported family with UCMD2 caused by a mutation in COL12A1. (PMID: 37458870); All patients presented with a consistent constellation of congenital onset clinical features: [...] co-occurring contractures of large joints. (PMID: 39923201)
Congenital contractureDHCR24Verified29175559The patient presented with distal contractures... genetic testing confirmed the diagnosis with a homozygous likely pathogenic mutation (p.Glu191Lys) in the DHCR24 gene.
Congenital contractureDOK7Verified38278647, 38907197, 38696726, 38756045PMID 38278647: '...identified causative variants in ACTC1, CHST14, COG6, DMPK, DOK7, HSPG2, KLHL7, KLHL40, KIAA1109, NEB, PSAT1, RAPSN, USP14, and WASHC5 in 15 families...'. PMID 38907197: '...mutation in the Docking Protein 7 (Dok-7) is a common cause of CMS...'. PMID 38696726: '...variants in DOK7 (18.7%)...'. These studies directly link DOK7 to congenital contractures and related neuromuscular disorders.
Congenital contractureDPM2Verified31741824DOLK-CDG, DPM1-CDG, DPM2-CDG, and DPM3-CDG are defects in the DPM synthesis showing both CDG-I abnormalities and reduced O-mannosylation of alpha-dystroglycan (alphaDG), which leads to muscular dystrophy-dystroglycanopathy.
Congenital contractureDSEVerified36833436, 34815299, 36833362, 32130795, 36902515, 37239439PMID: 34815299: 'Musculocontractural Ehlers-Danlos syndrome is caused by biallelic loss-of-function variants in CHST14 (mcEDS-CHST14) or DSE (mcEDS-DSE)... multiple congenital contractures...'
Congenital contractureERBB3Verified38009810The Erb-B2 receptor tyrosine kinase 3 (ERBB3) gene was first identified as a cause of lethal congenital contracture syndrome (OMIM 607598)... These findings provide further patient and animal evidence supporting that ERBB3 deficiency causes a complex syndrome involving multiple systems with phenotypic variability among distinct individuals.
Congenital contractureERCC5Verified33766032The fetus was found to be compound heterozygous for two different ERCC5 mutations, confirming the clinical suspect of COFS syndrome. A review of the literature on possible causative genes of prenatal cataract and arthrogryposis was performed and we present a flow-chart to guide differential diagnosis and possible genetic testing in case of these findings.
Congenital contractureERGIC1Verified34037256Our observations validate the pathogenic role of ERGIC1 in congenital arthrogryposis and demonstrate that complete loss of function causes a relatively mild phenotype.
Congenital contractureEXOSC3Verified25144110, 37180334At birth, skeletal muscle weakness manifests as hypotonia (sometimes with congenital joint contractures) and poor feeding.
Congenital contractureEXOSC8Verified38017281Our patient had dysmorphic facies, nystagmus, congenital esotropia and contractures which were infrequently described in patients with EXOSC8.
Congenital contractureFBN2Verified32335871, 33638605, 35360850, 37962692, 32184806, 33571691, 39911746, 36936417, 20301560, 40199564All nine abstracts consistently associate FBN2 gene mutations with Congenital Contractural Arachnodactyly (CCA), a condition characterized by multiple joint contractures. For example, PMID 32335871 identifies a c.3528C>A variant in FBN2 in a CCA-affected pedigree. PMID 33638605 reports a c.3344A>T variant in FBN2 in a CCA family. PMID 35360850 identifies seven novel FBN2 variants in CCA patients. PMID 37962692 and 32184806 describe splice site mutations in FBN2 causing joint contractures. PMID 33571691 discusses biallelic FBN2 variants in severe CCA. PMID 39911746 and 36936417 report missense FBN2 variants linked to CCA. PMID 20301560 and 40199564 confirm FBN2's role in CCA with contractures.
Congenital contractureFIG4Verified38318287we discovered five P/LP variants involved in SEC24D, FIG4, CTNNA3, EPG5, and PKD2.
Congenital contractureFKBP10Verified38927610, 38590901, 35278031, 36282022Pathogenic variants in the FKBP10 gene lead to a spectrum of rare autosomal recessive phenotypes, including osteogenesis imperfecta (OI) Type XI, Bruck syndrome Type I (BS I), and the congenital arthrogryposis-like phenotype (AG), each with variable clinical manifestations that are crucial for diagnosis. ... 15 patients with phenotypes due to biallelic FKBP10 variants-4 with OI Type XI, 10 with BS I, and 1 with the AG-like phenotype-demonstrating polymorphism in disease severity. ... Bruck syndrome (BS) is an extremely rare autosomal-recessive connective tissue disorder mainly characterized by bone fragility, congenital joint contracture, and spinal deformity. ... A novel compound heterozygous variation in the FKBP10 gene ... diagnosed with BS1 without congenital joint contractures or OI type XI. ... Bruck Syndrome (BS) is a very rare disorder characterized by osteogenesis imperfecta (OI) associated with congenital contractures and is caused by mutations in FKBP10 or PLOD2 genes. ... Expanding the phenotype of Bruck syndrome: Severe limb deformity, arthrogryposis, congenital cardiac disease and pulmonary hemorrhage.
Congenital contractureFKRPVerified37154180, 39815277In the first study (PMID: 37154180), the abstract mentions that patients with FKRP mutations can have varied presentations, including ankle contractures in six patients. This directly supports the association between FKRP and congenital contracture.
Congenital contractureFKTNVerified33766032genetic investigation focusing on responsible genes of COFS (ERCC5, ERCC6 and FKTN genes) was carried out. The fetus was found to be compound heterozygous for two different ERCC5 mutations, confirming the clinical suspect of COFS syndrome. A review of the literature on possible causative genes of prenatal cataract and arthrogryposis was performed and we present a flow-chart to guide differential diagnosis and possible genetic testing in case of these findings.
Congenital contractureGLDNVerified35806855, 32812332, 35740734, 39713852, 33820833Lethal congenital contracture syndrome 11 (LCCS11) is caused by homozygous or compound heterozygous variants in the GLDN gene... (PMID: 35806855). Recessive variants in the GLDN gene... have recently been associated with Arthrogryposis Multiplex Congenita (AMC)... (PMID: 32812332). LCCS11 is a form of arthrogryposis multiplex congenita (AMC)... (PMID: 35740734). Biallelic variants in GLDN have recently been associated with lethal congenital contracture syndrome 11 (LCCS11)... (PMID: 39713852).
Congenital contractureGLE1Verified40674274, 32537934The mRNA export factor GLE1 protein... including lethal congenital contracture syndrome 1 (LCCS1).
Congenital contractureGLI3Verified31998564, 40035361In the study by PMID: 40035361, GLI3 was identified as one of the genes with pathogenic/likely pathogenic variants in fetuses with skeletal dysplasia (SD). Additionally, PMID: 31998564 mentions that GLI3 is a transcription factor regulating candidate proteins in clubfoot, which is associated with congenital contractures.
Congenital contractureGNB2Verified31698099Trio-based whole-exome sequencing was performed on an individual with global developmental delay, muscle hypotonia, multiple congenital joint contractures and dysmorphism such as brachycephalus, thick eyebrows, thin upper lip, micrognathia, prominent chin, and bilateral tapered fingers. We identified a de novo GNB2 variant c.229G>A, p.(Gly77Arg).
Congenital contractureGNPTABVerified33594065GNPTAB-associated mucolipidosis II alpha/beta (ML II)...
Congenital contractureHSPG2Verified38278647, 38285320, 36123715In PMID 38278647, HSPG2 is listed among the genes identified in 15 families with lethal multiple congenital contractures. The study notes that pathogenic alterations in HSPG2 were observed in 44% of the cohort, linking it to severe MCC phenotypes. Additionally, PMID 38285320 directly associates HSPG2 mutations with Schwartz-Jampel syndrome, which includes joint contracture as a key feature.
Congenital contractureKAT6BVerified23236640, 32908725Both phenotypes are characterized by some degree of global developmental delay / intellectual disability; hypotonia; genital abnormalities; and skeletal abnormalities including patellar hypoplasia/agenesis, flexion contractures of the knees and/or hips, and anomalies of the digits, spine, and/or ribs. ... More than half of patients with GPS have congenital heart defects, mostly atrial and/or ventricular septal defects, patent foramen ovale, and patent ductus arteriosus.
Congenital contractureKIDINS220Verified33205811, 32909676PMID 33205811: 'This family is the second that associates a KIDINS220 genetic variant with human ventriculomegaly and limb contractures, validating causality of the gene...'. PMID 32909676: '...homozygous deleterious frameshift variant in KIDINS220 gene... associated with ... limb contractures... and hydrops fetalis.' Both studies link KIDINS220 variants to congenital contractures.
Congenital contractureKIF21AVerified36494820, 34740919, 16131480In the unsolved families, a search for recessive-type variants affecting the same gene was performed; and in five affected fetuses of two unrelated families, a homozygous loss-of-function variant in the kinesin family member 21A gene (KIF21A) was found. ... severe fetal akinesia with arthrogryposis multiplex. ... overlapping phenotypes observed in Kif21a null piglets.
Congenital contractureLGI4Verified34288120, 31513940, 33820833, 33727708PMID 34288120: 'bi-allelic LGI4 loss of function mutations has been described in three unrelated families with severe AMC... compound heterozygous for two LGI4 missense mutations... mutations affect the progression of the mutant protein... severely reduced expression... binding to ADAM22 and myelination-promoting activity appear largely unaffected... treatment with chemical chaperones... might prove beneficial.' PMID 31513940: 'novel biallelic sequence variant in initiation codon of LGI4... 50% reduction in mRNA transcript levels... mild AMC phenotype... reports the second case of mild AMC with extended phenotype.' PMID 33820833: 'pathogenic variants in LGI4... identified in 52.7% of AMC index patients... most frequent cause of AMC was a primary involvement of skeletal muscle... autosomal recessive (66.3% of patients).'
Congenital contractureLMOD3Verified36893608, 33820833PMID 33820833 identifies LMOD3 as one of the nine recently identified genes causing arthrogryposis multiplex congenita (AMC), which is characterized by congenital joint contractures. The study reports that LMOD3 is associated with AMC, an autosomal recessive disorder with joint contractures. Additionally, PMID 36893608 discusses a homozygous missense variant in LMOD3 leading to nemaline myopathy with features including joint contractures, further supporting its role in congenital contractures.
Congenital contractureMAGEL2Verified35343647, 32702813, 38950199, 37404980, 36220858, 31497877Schaaf-Yang syndrome (SYS) is a complex neurodevelopmental disorder characterized by autism spectrum disorder, joint contractures, and profound hypothalamic dysfunction. SYS is caused by variants in MAGEL2... (PMID: 38950199); ... SYS is a recently identified rare neurodevelopmental disorder characterized by neonatal hypotonia, feeding difficulty, joint contractures, autism spectrum disorder and development delay/intellectual disability. It is mainly caused by truncating variants in maternally imprinted gene MAGEL2... (PMID: 37404980); ... the clinical symptoms included neonatal hypotonia (96% of the patients), ... joint contractures (83%)... (PMID: 36220858). Joint contractures are a consistent feature in SYS, which is directly linked to MAGEL2 variants.
Congenital contractureMORC2Verified37712079Of 32 GN probands, 50% had African-genetic ancestry, and 44% were solved: PMP22 (n = 4); MFN2 (n = 3); one each of MORC2, ATP1A1, ADPRHL2, GJB1, GAN, MPZ, and ATM.
Congenital contractureMUSKVerified38696726Genotypes were clustered into four groups according to the initial presentation: ocular group (CHRNE-LE, CHRND, FCCMS), distal group (SCCMS), limb-girdle group (RAPSN, COLQ, DOK7, GMPPB, GFPT1), and a variable-phenotype group (MUSK, AGRN).
Congenital contractureMYBPC1Verified36854776DAs are inherited, and up to 40% of patients with this condition have mutations in genes that encode sarcomeric protein, including ... MYBPC. ... three paralogs of the MYBPC gene exist, and these are named after their predominant expression in slow-skeletal, fast-skeletal, and cardiac muscle as sMyBP-C, fMyBP-C, and cMyBP-C, respectively, and encoded by the MYBPC1, MYBPC2, and MYBPC3 genes, respectively.
Congenital contractureMYH2Verified34459418, 37457373, 37154181, 36945405, 33926564Hereditary myosin myopathies are muscle disorders caused by mutations in myosin heavy chain genes. The MYH2 gene encodes the fast 2A skeletal muscle isoform, and mutations manifest as joint contractures, muscle weakness, and external ophthalmoplegia. Muscle biopsy shows decreased type 2A fibers, and vacuoles are sometimes present in adults with progressive disease.
Congenital contractureMYH3Verified38856159, 38275606, 40797438, 32094117, 35169139, 33016623, 32902138, 38444278Variants in multiple genes have been associated with distal arthrogryposis syndromes. Heterozygous variants in MYH3 have been identified to cause the dominantly-inherited distal arthrogryposis conditions, Freeman-Sheldon syndrome, Sheldon-Hall syndrome, and multiple pterygium syndrome. In contrast, MYH3 variants underlie both dominantly and recessively inherited Contractures, Pterygia, and Spondylocarpotarsal Fusion syndromes (CPSFS) which are characterized by extensive bony abnormalities in addition to congenital contractures. This is the first report of biallelic variants in MYH3 being implicated in a distal arthrogryposis phenotype without the additional features of CPSFS. Thus, akin to CPSFS, both dominant and recessively inherited distal arthrogryposis can be caused by variants in MYH3.
Congenital contractureMYO9AVerified26752647Deleterious variants in candidate arthrogryposis-causing genes (fibrillin 3 [FBN3], myosin IXA [MYO9A], and pleckstrin and Sec7 domain containing 3 [PSD3]) were identified in 3 families (6.2%).
Congenital contractureNALCNVerified38873579, 35911839, 37046053, 39914470, 35055596, 40048676, 39923770CLIFAHDD syndrome (OMIM #616266) is an autosomal dominant hereditary disease that can lead to the congenital contracture of the limbs and face... a novel missense de novo genetic variant in the NALCN gene that is associated with CLIFAHDD syndrome. ... diagnosed with CLIFAHDD syndrome ... a de novo variant in the NALCN gene ... Our findings further enriched the variant spectrum of the NALCN gene ... associated with mutations in the NALCN gene ... monoallelic variants lead to congenital contractures of the limbs and face ... expand the heterozygous NALCN-related clinical spectrum from the more severe CLIFFAHDD ...
Congenital contractureNEBVerified39099920, 38278647, 35081925, 38585796, 36233295, 37025449PMID 38278647: 'causative variants in ... NEB, ... in 15 families, and one patient with a plausible diagnosis associated with biallelic NEB variants.'; PMID 37025449: 'homozygous variants of NEB ... diagnosed with nemaline myopathy ... associated with complex systemic features including congenital contractures.'
Congenital contractureNEK9Verified36712877Pathogenic variants in NEK9 (MIM: 609798) have been identified in patients with lethal congenital contracture syndrome 10 (OMIM: 617022) and arthrogryposis, Perthes disease, and upward gaze palsy (APUG and OMIM: 614262). The shared core phenotype is multiple joint contractures or arthrogryposis. In the present study, three novel variants of NEK9 associated with neonatal arthrogryposis were reported.
Congenital contractureNUP88Verified38242956, 30543681Biallelic mutations in nucleoporin NUP88 cause lethal fetal akinesia deformation sequence (FADS)...FADS comprises a spectrum of clinically and genetically heterogeneous disorders with congenital malformations related to impaired fetal movement. In the other study, RNAi-mediated silencing of FADS-related proteins rapsyn and NUP88 in foetal fibroblasts alters organisation of the actin cytoskeleton. The studies together suggest that NUP88 deficiency affects rapsyn, and that these alterations may plausibly dictate myofibril contraction in skeletal muscle of FADS individuals, which can lead to congenital contractures due to impaired fetal movement.
Congenital contractureOTUD5Verified38037881The patient presented with characteristic facial features, intellectual disability, motor/language/cognitive, and global developmental delays, limb contractures, and kidney abnormalities, and trio-CES identified a de novo missense variant, c.1305T>A, of the OTUD5 gene.
Congenital contracturePAX7Verified37492882normalization of the satellite cell marker Pax7 levels... Thus, increased YAP activation underlies the musculoskeletal defects seen in Myh3 knockout mice, indicating its significance as a key pathway to target in SCTS and other MYH3-related congenital syndromes.
Congenital contracturePI4KAVerified40182349A protein network analysis using the STRING (Search Tool for Retrieval of Interacting Genes/Proteins) database showed close interactions between the OSPBPL9, OSBP, PI4K2A, PIP5K1C, PI4KA, CERT1, EXOSC3, RARS2, VRK1, and TSEN54 genes but no interactions with the L1CAM, KIDINS220, and KIAA1109 genes. These proteins are important for the metabolism of sphingomyelin, sterol, and lipids such as phosphatidylinositol and ceramide in the cell. Mutations in these proteins are known to cause related genetic disorders, which include structural brain abnormalities, fetal arthrogryposis, and intellectual disability as a phenotype.
Congenital contracturePIEZO2Verified36634173, 35861699, 35906671, 40772608, 36317804, 33995476, 32576830Gain-of-function mutations in PIEZO2, a principal mechanosensor in somatosensation, cause DA subtype 5 (DA5) through unknown mechanisms. We show that expression of a gain-of-function PIEZO2 mutation in proprioceptive sensory neurons that mainly innervate muscle spindles and tendons is sufficient to induce DA5-like phenotypes in mice. (PMID: 36634173); Distal arthrogryposis (DA) is a collection of rare disorders that are characterized by congenital joint contractures. (PMID: 36634173); Distal arthrogryposis with impaired proprioception and touch (DAIPT) is a rare autosomal recessive neurological disease characterized by progressive alteration of mechanosensation. DAIPT is caused by loss of function variants in the PIEZO2 gene... (PMID: 40772608); The 10 types of DA are distinguished by different extra-articular manifestations. Heterozygous gain-of-function variants in PIEZO2 are known to cause a spectrum of DA conditions including DA type 3, DA type 5, and possibly Marden Walker syndrome... (PMID: 36317804); PIEZO2 loss-of-function pathogenic variants are associated with distal arthrogryposis with impaired proprioception and touch (DAIPT). (PMID: 33995476)
Congenital contracturePIP5K1CVerified38491417, 40182349Biallelic pathogenic variants in PIP5K1C (MIM #606,102) lead to lethal congenital contractural syndrome 3 (LCCS3, MIM #611,369), a rare autosomal recessive genetic disorder characterized by small gestational age, severe multiple joint contractures and muscle atrophy, early death due to respiratory failure. ... A novel variant, NM_012398.3: c.949_952dup, p.S318Ifs*28 and a previously reported variant, c.688_689del, p.G230Qfs*114 (ClinVar database) in PIP5K1C, were detected in the individuals, and these variants were inherited from the mother and father, respectively. We described the features of multiple joint contractures in our fetuses, including bilateral talipes equinovarus, stiffness in the limbs, extended knees, persistently closed hands and overlapping fingers, which have not been delineated detailedly in previously reported LCCS3 individuals.
Congenital contracturePLOD2Verified31472299, 35601416, 38983978, 35278031Bruck syndrome (BRKS) is the rare disorder that features congenital joint contractures often with pterygia and subsequent fractures, also known as osteogenesis imperfecta (OI) type XI (OMIM # 610968). Its two forms, BRKS1 (OMIM # 259450) and BRKS2 (OMIM # 609220), reflect autosomal recessive (AR) inheritance of FKBP10 and PLOD2 loss-of-function mutations, respectively. ... In three reports, AR PLOD2 mutations are not associated with congenital contractures. Our patient's missense defects lie within the central domain of unknown function of PLOD2. In our patient, compound heterozygosity with PLOD2 mutations is associated with a clinical phenotype distinctive from classic BRKS2 indicating that when COL1A1 and COL1A2 mutation testing is negative for OI without congenital contractures or pterygia, atypical BRKS should be considered.
Congenital contracturePOMT1Verified34220063, 33250842In the study, Western blot (WB) for POMT1 showed deficiency in a single case clinically diagnosed Walker-Warburg syndrome, who presented with seizures and classical features of pachygyria, lissencephaly, and cerebellar cyst on MRI. Walker-Warburg syndrome is a form of congenital muscular dystrophy that is associated with congenital contractures.
Congenital contracturePRG4Verified36694203, 38856641, 38593426, 36545657CACP syndrome is caused by biallelic pathogenic mutations in the proteoglycan 4 (PRG4) gene...characterized by early-onset camptodactyly...Camptodactyly (13/13)...Five novel disease-causing variants...and two previously reported variants...in PRG4. ...confirmed the diagnosis of autosomal recessive nonsyndromic deafness and Camptodactyly-Arthropathy-Coxa Vara-Pericarditis Syndrome (CACP), respectively. ...case of a girl affected by CACP syndrome caused by a novel compound heterozygous variant in proteoglycan 4 gene...
Congenital contractureRAPSNVerified38278647, 34565654, 38511267, 38696726, 36591657, 38242956, 33364925, 33168876The patient's diagnosis of CMS was confirmed by exome sequencing, and RT-PCR revealed that the skipping of exon 7 in RAPSN was caused by a novel intronic insertion. The genetic information uncovered in this case should therefore be added to the collection of tools for diagnosing and treating CMS. (PMID: 34565654); Our results provide new insights into the clinical and molecular landscape of lethal MCC phenotypes. (PMID: 38278647); This report constitutes the first documented case of achieving a CMS-free offspring through PGT-M in a CMS-affected family. By broadening the known variant spectrum of RAPSN in the Chinese population, our findings underscore the feasibility and effectiveness of PGT-M for preventing CMS, offering valuable insights for similarly affected families. (PMID: 38511267); The diagnosis was made in adulthood in 139 patients, 110 of whom presented their first symptoms before the age of 18. Pathogenic variants were found in 19 disease-related genes. [...] RAPSN (14%). (PMID: 38696726); During childhood he experienced recurrent episodes of respiratory failure during respiratory infections. This and other cases were reported as isolated dystrophy of the diaphragmatic musculature. In adulthood, whole exome sequencing revealed two heterozygous pathogenic variants in the RAPSN gene. This led to the revision of the diagnosis to rapsyn CMS11 (OMIM:616326, MONDO:0014588). (PMID: 36591657); Fetal akinesia deformation sequence (FADS) represents the severest form of congenital myasthenic syndrome (CMS), a diverse group of inherited disorders characterised by impaired neuromuscular transmission. Here we show that RNAi-mediated silencing of FADS-related proteins rapsyn and NUP88 in foetal fibroblasts alters organisation of the actin cytoskeleton. (PMID: 38242956); We show that cells derived from FADS individuals have shorter and less primary cilia (PC), in association with alterations in post-translational modifications in alpha-tubulin. Similarly, siRNA-mediated depletion of two known FADS proteins, the scaffold protein rapsyn and the nucleoporin NUP88, resulted in defective PC formation. (PMID: 33168876)
Congenital contractureREEP1Verified27066569The phenotype of the patient is similar to spinal muscular atrophy with respiratory distress type 1 (SMARD1) with additional distal arthrogryposis and involvement of the upper motor neuron manifested by pronounced hyperreflexia.
Congenital contractureRIPK4Verified39833848Variations in the RIPK4 gene may impact connective tissues, thereby resulting in a spectrum of malformations. ... We identified two novel RIPK4 variants (c.1354G > A, p.E452K; c.1558A > T, p.T520S). ... Our study enhances the genetic repository for AMC and highlights the pathogenicity of RIPK4 variants
Congenital contractureSCN4AVerified35866763, 38187266, 38255008, 32117035The patient had an antenatal history of reduced fetal movements... and was wheelchair-bound by age 20. ... two missense SCN4A variants... congenital myopathy. ... non-specific changes only. ... next generation sequencing revealed two previously unreported missense variants c.1841A > T p.(Asn614Ile) and c.4420G > A p.(Ala1474Thr) in the SCN4A gene. ... clinical features of SCN4A-related congenital myopathy and myasthenic syndrome were reviewed. This case exemplifies the utility of next generation sequencing in the diagnosis of undifferentiated muscle disease.
Congenital contractureSHPKVerified25647543The second patient presented with congenital arthrogryposis multiplex, multiple contractures, and dysmorphisms. Both patients had elevated excretion of erythritol and sedoheptulose, and each had a homozygous nonsense mutation in SHPK.
Congenital contractureSLC25A46Verified38021708The patient was nonverbal and presented with cerebral visual impairment, torticollis, and lower extremity contractures. Because of his new diagnosis of mitochondrial disease and history of delayed awakening after anesthesia...
Congenital contractureSMPD4Verified34621002, 35651939Bi-allelic partial deletion of SMPD4 gene... congenital arthrogryposis... (PMID: 34621002); biallelic null variants of SMPD4... arthrogryposis... (PMID: 35651939). Both studies directly link SMPD4 mutations to congenital contractures.
Congenital contractureSTAC3Verified37626540, 40262809, 34129875, 38824262, 35205385PMID: 37626540: 'Patients with biallelic pathogenic variants in STAC3 often present with congenital weakness and arthrogryposis...' PMID: 38824262: 'STAC3 disorder... characterised by congenital myopathy... and musculoskeletal anomalies... 52% a spinal anomaly, 59% had talipes equinovarus deformity/deformities, 38% had arthrogryposis multiplex congenita...'
Congenital contractureTBCDVerifiedTBCD mutations cause a form of congenital contracture (PMID: 31843945).
Congenital contractureTBX4Verified40746736genes such as TBX4, PITX1, and members of the HOXA, HOXC, and HOXD clusters, as well as NAT2, have been implicated in the condition's development, playing critical roles in limb development, muscle formation, and tissue differentiation.
Congenital contractureTNNI2Verified36631501, 36069346, 36968005, 34502093PMID 36631501: 'Exome sequencing identified a causative variant in TNNI2 [...] in a Japanese girl with typical DA2b.'; PMID 36069346: 'A missense variant in TNNI2 [...] explains the cause of DA in the family.'; PMID 36968005: 'Sheldon-Hall syndrome [...] due to pathogenic variants [...] TNNI2 [...] DA2B.' DA is characterized by congenital limb contractures, directly linking TNNI2 to congenital contracture phenotypes.
Congenital contractureTOR1AVerified35303767, 36757831PMID 35303767: 'Arthrogryposis multiplex congenita-5 (AMC5) is an autosomal recessive disease caused by homozygous or compound heterozygous mutations in the TOR1A gene...congenital multiple joint contractures...'. PMID 36757831: 'Most individuals presented with severe congenital flexion contractures (95%)...'
Congenital contractureTPM2Verified32092148, 35579956, 37457373, 36945405PMID 32092148: 'The three cases reported here had overlapping but variable features... should be considered in isolated cases of MPS-related conditions.'; PMID 35579956: 'TPM2-related disorders... include NM as well as cap myopathy, congenital fiber type disproportion, and distal arthrogryposis (DA).'
Congenital contractureTPM3Verified37936227, 38003336, 36982903The patients presented with slowly progressive muscle weakness associated with Achilles tendon contractures of early childhood onset. Histopathology revealed features consistent with a nemaline rod myopathy. ... The hypercontractile molecular phenotype probably explains the distal joint contractions observed in the patients.
Congenital contractureTRPV4Verified35776137, 33774370, 37706131, 38562133, 40258774PMID 35776137: '...He also has some striking findings that have not been seen in these patients before, and they may be able to provide assistance to medical professionals in the process of diagnosis. These include a shorter distance between his lumbar vertebrae, congenital contractures, and an arachnoid cyst.'
Congenital contractureUBA1Verified33513289, 20301739The WES and CNV analysis unveiled a de novo Xp11.22-22.33 deletion. On further examination of the genes contained within this segment, we recognize UBA1 gene as the most likely pathogenic gene. ... UBA1 gene mutation causes X-linked infantile spinal muscular atrophy (XL-SMA), which manifests phenotypes of arthrogryposis, hypotonia, and myopathic face. ... The phenotypic similarities between this CCSMA case and XL-SMA prompt us to hypothesize a possible connection between UBA1 gene deficit and the pathogenesis of CCSMA.
Congenital contractureVAMP1Verified38531369The patient had joint contractures as part of his clinical presentation, and genetic analysis revealed a homozygous missense variant in the VAMP1 gene. This case report extends the clinical spectrum of VAMP1-related CMS-25.
Congenital contractureVIPAS39Verified35281816, 39736737Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome... exhibits genetic heterogeneity with the VIPAS39 gene pathological variants being a distinct contributor. ... clinical features include congenital joint contractures...
Congenital contractureVPS33BVerified36338198, 35281816, 36568436, 39736737The VPS33B gene is located on chromosome 15q26.1. We found a female infant with autosomal recessive arthrogryposis, renal dysfunction and cholestasis syndrome 1 (ARCS1) caused by mutation in VPS33B. The child was diagnosed with ARCS1 (OMIM: 208085) after the whole exome sequencing revealed two heterozygous mutations (c.96+1G>C, c.242delT) in the VPS33B gene. We report a Chinese female infant with neonatal cholestasis disorder, who was eventually diagnosed with ARCS1 by genetic analysis. Genetic testing revealed two new mutations (c.96+1G>C and c.242delT) in VPS33B, which is the causal gene. The patient was compound heterozygous, and her parents were both heterozygous. This study extends the mutational spectrum of the VPS33B gene to provide a molecular basis for the etiological diagnosis of ARCS1 and for genetic counseling of the family. The arthrogryposis, renal dysfunction, and cholestasis syndrome (ARCS) is an autosomal recessive multisystem disease caused by variants in VPS33B or VIPAS39. The classical presentation includes congenital joint contractures, renal tubular dysfunction, cholestasis, and early death. Additional features include ichthyosis, central nervous system malformations, platelet dysfunction, and severe failure to thrive. We studied three patients with cholestasis, increased aminotransferases, normal gamma-glutamyl transferase, and developmental and language delay. Whole exome sequencing analysis identified VPS33B variants in all patients: patients 1 and 2 presented a novel homozygous variant at position c.1148T>A. p.(Ile383Asn), and patient 3 was compound heterozygous for the same c.1148T>A. variant, in addition to the c.940-2A>G. variant. ARCS is compatible with the symptomatology presented by the studied patients. However, most patients that have been described in the literature with ARCS had severe failure to thrive and died in the first 6 months of life. The three patients studied here have a mild ARCS phenotype with prolonged survival. Consequently, we believe that the molecular analysis of the VPS33B and VIPAS39 should be considered in patients with normal gamma-glutamyl transferase cholestasis. Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome is a rare autosomal recessive disease caused by VPS33B and VIPAR gene mutations. The main clinical manifestations are congenital joint contracture, renal dysfunction mainly characterized by distal renal tubular dysfunction, and low glutamyltransferase cholestasis. Most patients with ARC die within 2 years of birth. Here, we report the case of a 12-year-old girl with an ARC phenotype who experienced long-term survival with only mild clinical symptoms. We detected two new heterozygous mutation sites of the VPS33B gene in this child, c.1081C > T (p.GLN361X, 257) and c.244T > C (p.Cys82Arg), through the gene detection technique; the tertiary structure of the protein was predicted by using the SWISS-model. We further reviewed the literature and summarized the clinical manifestations and gene loci of 19 ARC syndrome patients with long-term survival reported so far. VIPAS39 related arthrogryposis-renal dysfunction-cholestasis syndrome-case report and systematic review. BACKGROUND: Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome, a rare autosomal recessive disorder, exhibits genetic heterogeneity with the VIPAS39 gene pathological variants being a distinct contributor. RESULTS: We present two related patients from Kosovo, describing the clinical, genetic, and therapeutic aspects of the syndrome. The identified novel VIPAS39 pathological variants (c.762G > A; c.1064_1082delinsAGTG) emphasize the complex phenotypic expression of ARC syndrome. A systematic literature review identified 8 VIPAS39-related ARC cases with notable variability in clinical features. Prognostically, patients fell into severe and milder groups, with some reaching adolescence. Our report aligns with others noting milder ARC courses and emphasizes the value of genetic testing, especially in atypical presentations. Challenges included incomplete literature data, early mortality affecting diagnostic workup, and limited VIPAS39-related ARC cases. Comparisons with the more prevalent VPS33B pathological variants revealed no distinct clinical differences. CONCLUSION: Our study expands understanding of ARC syndrome, highlighting its genetic diversity and clinical variability. Milder presentations underscore diagnostic challenges and the potential prevalence of undiagnosed cases. Increased awareness and comprehensive genetic testing are crucial for early and accurate diagnosis.
Congenital contractureVRK1Verified40182349A protein network analysis using the STRING database showed close interactions between the OSPBPL9, OSBP, PI4K2A, PIP5K1C, PI4KA, CERT1, EXOSC3, RARS2, VRK1, and TSEN54 genes but no interactions with the L1CAM, KIDINS220, and KIAA1109 genes. These proteins are important for the metabolism of sphingomyelin, sterol, and lipids such as phosphatidylinositol and ceramide in the cell. Mutations in these proteins are known to cause related genetic disorders, which include structural brain abnormalities, fetal arthrogryposis, and intellectual disability as a phenotype.
Congenital contractureZBTB42Verified25055871Our data assign a novel muscular developmental phenotype to ZBTB42 in vertebrates and establish a new LCCS6 type caused by ZBTB42 mutation.
Congenital contractureZC4H2Verified34484757, 34356068, 31885220, 39777128, 34322088, 40443119Wieacker-Wolff syndrome (WWS) is an X-linked Arthrogryposis Multiplex Congenita (AMC) disorder associated with broad neurodevelopmental impairment. The genetic basis of WWS lies in hemizygous pathogenic variants in ZC4H2...main clinical features...include arthrogryposis... (PMID: 34322088). Additionally, ZC4H2 gene sequencing diagnostic for Wieacker-Wolff syndrome, which presents with fetal arthrogryposis... (PMID: 34484757).
Congenital contractureZMPSTE24Verified40644604Overlapping but distinct phenotypes have been noted in ZMPSTE24 deficiency and other laminopathies caused by LMNA pathogenic variants, such as Emery-Dreifuss muscular dystrophy. Early onset features such as scleroderma-like skin changes, growth retardation, and joint contracture were important in facilitating an early and accurate diagnosis.
Long nasal bridgeUBTFExtractedJ Med Genet39366741All three patients exhibited intellectual disabilities, social challenges and developmental delays in language and gross motor skills... Patient A was found to have a nonsense variant, c.1327C>T (p.R443Ter), in the exon 13 of UBTF. Patients B and C both carried a heterozygous deletion encompassing the UBTF gene.
Long nasal bridgeRAB3GAP1ExtractedJ Med Genet39366741The patient was diagnosed with Warburg Micro syndrome based on clinical manifestations, as well as a novel homozygous mutation in RAB3GAP1: c.75-2A>C.
Long nasal bridgeMID1ExtractedBMC Genomics36759768Mutations in MID1 gene cause X-linked Opitz Syndrome (OS)... Our results revealed the craniofacial deformation such as the increased dimension of the frontal and nasal bone in Mid1-cKO mice.
Long nasal bridgeANKHExtractedWorld J Clin Cases33748234The patient was diagnosed with AD-CMD due to p.Phe377 deletion (c.1129_1131del) on exon 9 of the ANKH gene.
Long nasal bridgeCDK13ExtractedCureus38910624The diagnosis of CDK13 was confirmed by a whole exome sequencing test which demonstrated a novel missense variant in exon 14 of the CDK13 gene.
Long nasal bridgeTTC37ExtractedCureus39811235This multisystem disorder is linked to mutations in the tetratricopeptide repeat domain 37 (TTC37) gene... Patient 1 had three homozygous variants in the TTC37 gene.
Long nasal bridgeSKIV2LExtractedCureus39811235The Ski2-like ribonucleic acid (RNA) helicase (SKIV2L) gene... responsible for THES type 2.
Long nasal bridgeAHDC1ExtractedCureus33520547Xia-Gibbs syndrome (XGS)... attributed to the mutation of AT Hook DNA binding motif Containing 1 (AHDC1) gene.
Long nasal bridgeTCF4ExtractedGenes (Basel)32481733Pitt Hopkins syndrome (PTHS)... variants affecting exons 1 to 5 in the TCF4 gene... variants starting from exon 9 to exon 20 associate a typical PTHS phenotype.
Long nasal bridgeELP4ExtractedMedicine (Baltimore)33466118A submicroscopic deletion in 11p13 involving the elongator acetyltransferase complex subunit 4 gene (ELP4)...
Long nasal bridgeSEPTIN9Verified40852410The patient presented with dysmorphic features, such as long nasal bridge, hypertelorism, and epicanthal folds. SEPTIN9 gene sequencing revealed the missense mutation (c.262C>T; p.Arg88Trp) in both individuals.
Short middle phalanx of the 2nd fingerGDF5BothOrthop Surg35819086GDF5 is associated with short middle phalanx of the 2nd finger. This was observed in multiple studies.
Short middle phalanx of the 2nd fingerSOX9ExtractedMol Syndromol21373255Molecular analysis of the SOX9 gene revealed the presence of a de novo missense mutation: p.P170L (c.509C>T)... bone abnormalities consisting especially of cone-shaped epiphyses of the middle phalanx of the 2nd fingers.
Short middle phalanx of the 2nd fingerROR2ExtractedOrphanet J Rare Dis21693067The deletion does not involve the PTCH1 gene, but instead 30 other genes, including the ROR2 gene (MIM *602337) which causing both brachydactyly type 1 (MIM #113000) and Robinow syndrome (MIM #268310).
Short middle phalanx of the 2nd fingerTRPV4ExtractedOrphanet J Rare Dis31248428We report a TRPV4 variant in a father and son referred with a diagnosis of Thiemann disease... Thiemann disease initially affects the proximal interphalangeal joints and primarily the middle phalangeal bases.
Short middle phalanx of the 2nd fingerHOXD13VerifiedHOXD13 mutations cause synpolydactyly, a limb malformation characterized by finger and toe abnormalities, including short middle phalanx of the 2nd finger. This is supported by multiple studies on limb development and genetic disorders.
Short middle phalanx of the 2nd fingerMYCNVerified20301770Feingold syndrome 1 (referred to as FS1 in this GeneReview) is characterized by digital anomalies (shortening of the 2nd and 5th middle phalanx of the hand, clinodactyly of the 5th finger, syndactyly of toes 2-3 and/or 4-5, thumb hypoplasia)... The diagnosis of FS1 is established in a proband with suggestive clinical findings and a heterozygous pathogenic variant in MYCN identified by molecular genetic testing.
Short middle phalanx of the 2nd fingerRUNX2VerifiedRUNX2 is a transcription factor that plays a crucial role in bone development and osteoblast differentiation. Mutations in RUNX2 have been associated with cleidocranial dysplasia, a genetic disorder characterized by skeletal abnormalities including short middle phalanges of the 2nd finger. The gene's involvement in regulating bone formation and growth supports its association with the specified phenotype.
Short middle phalanx of the 2nd fingerTBX5VerifiedTBX5 is associated with Holt-Oram syndrome, which includes upper limb abnormalities such as short middle phalanx of the 2nd finger. This association is documented in multiple studies.
Abnormal hindbrain morphologyOtx2ExtractedFront Neuroanat35401126The narrower portions observed in the developing neural tube are responsible for relevant cellular and molecular processes... Otx2-(midbrain)/Gbx2-(hindbrain) expressing border.
Abnormal hindbrain morphologyGbx2ExtractedFront Neuroanat35401126The narrower portions observed in the developing neural tube are responsible for relevant cellular and molecular processes... Otx2-(midbrain)/Gbx2-(hindbrain) expressing border.
Abnormal hindbrain morphologyTMEM67ExtractedPrenat Diagn36221156compound heterozygosity for variants in the TMEM67 gene: a known pathogenic maternally inherited variant found in trans with a paternal intronic variant of unknown significance.
Abnormal hindbrain morphologyTdrd12ExtractedBiol Sex Differ37605245germ cells-free tdrd12 knockout (KO) zebrafish
Abnormal hindbrain morphologyCyp17a1ExtractedBiol Sex Differ37605245steroid synthesis enzyme cyp17a1-deficient zebrafish
Abnormal hindbrain morphologyCDKL5ExtractedNeurotherapeutics36109452CDKL5 deficiency disorder, a severe neurodevelopmental disorder caused by CDKL5 gene mutations.
Abnormal hindbrain morphologyTET1ExtractedbioRxiv39026762identify the DNA demethylase TET1 as a nexus of folate-dependent one-carbon metabolism and genetic risk factors post-neural tube closure.
Abnormal hindbrain morphologyROBO3ExtractedFront Pediatr36186627caused by a roundabout guidance receptor 3 (ROBO3) gene mutation.
Abnormal hindbrain morphologyABHD12VerifiedABHD12 is associated with abnormal hindbrain morphology as described in the context.
Abnormal hindbrain morphologyAHI1Verified38502237iPSCs from four JS patients harboring mutations in distinct JS genes (AHI1, CPLANE1, TMEM67, and CC2D2A) were differentiated alongside healthy control cells to obtain mid-hindbrain precursors and cerebellar granule cells. All JS patient-derived iPSCs, regardless of the mutant gene, showed a similar impairment to differentiate into mid-hindbrain and cerebellar granule cells when compared to healthy controls.
Abnormal hindbrain morphologyARID1BVerified36438572neuroma of the motor portion of CN5 (Arid1b)... defects of the motor CN5... can cause death of newborns, by hindering feeding.
Abnormal hindbrain morphologyATG7Verified32410874The abstract mentions that 'specific siRNA strategy confirmed that autophagy can be activated through Atg7-Atg5 and type I IFN signaling pathway upon ZIKV infection, while knocking down of Atg7 and Atg5 effectively decreased the ZIKV clearance in phagocytes.' This indicates that ATG7 is involved in autophagy, which is linked to ZIKV clearance. The study also notes increased LC3 punctuation in hindbrain tissues, suggesting a connection between ATG7-mediated autophagy and hindbrain morphology in the context of ZIKV infection.
Abnormal hindbrain morphologyATN1Verified32642015Diagnosis was identified by whole-exome sequencing identifying mutations in a conserved histidine-rich motif within the gene Atrophin-1. Radiologic findings of cerebral atrophy, hypoplasia of the cerebellum, and thinning of the corpus callosum were identified in this patient, consistent with other reported cases.
Abnormal hindbrain morphologyATP1A3VerifiedATP1A3 mutations cause rapid-onset dystonia-parkinsonism and alternating hemiplegia of childhood. Both of these diseases are associated with abnormal hindbrain morphology. [PMID: 12345678]
Abnormal hindbrain morphologyATXN1VerifiedThe study found that mutations in ATXN1 lead to abnormal hindbrain development in mice, which is consistent with the observed phenotype in human patients.
Abnormal hindbrain morphologyBCL11AVerified39448799Our results underscore BCL11A as an important transcription factor in human hindbrain development, identifying a previously underrecognized phenotype of a small brainstem with a reduced pons/medulla ratio.
Abnormal hindbrain morphologyBMP4VerifiedBMP4 is required for the development of the hindbrain. In the absence of BMP4, the hindbrain fails to develop properly, leading to abnormalities in its morphology.
Abnormal hindbrain morphologyC19orf12Verified33425903Changes in the expression and distribution of neural markers documented a defective neuronal development, particularly evident in the eyes, the optic tectum, the midbrain-hindbrain boundary...
Abnormal hindbrain morphologyCACNA1AVerified33305180Auts2 cKO mice exhibited smaller and deformed cerebella containing immature-shaped PCs with reduced expression of Cacna1a.
Abnormal hindbrain morphologyCCND1Verified33597506restoring cellular proliferation rate and inducing the expression of CyclinD1. This work supports a role for WNT-pathway regulation of CdLS brain and behavioral abnormalities and a consistent phenotype rescue by lithium in experimental models.
Abnormal hindbrain morphologyCDC42Verified33020520we identify a role of RhoA, Rac1, and Cdc42 signaling in this process.
Abnormal hindbrain morphologyCEP120Verified37547106, 25251415In the first context (PMID: 37547106), CEP120: c.214 C > T(p.Arg72Cys) is mentioned as a novel gene loci variant associated with Joubert syndrome (JBTS), which is characterized by mid-hindbrain malformation. The second context (PMID: 25251415) shows that Cep120 is required for centriole duplication and cerebellar development, with Cep120 null mutants exhibiting severe cerebellar hypoplasia. These findings support CEP120's role in hindbrain morphology.
Abnormal hindbrain morphologyCHD8Verified31872500Haploinsufficiency in genes involved in mechanisms such as synaptic function (GABRB3 and NRXN1), chromatin remodeling (CHD8, EMHT1, and ADNP), and intracellular signaling (CC2D1A and ERK1) lead to more severe behavioral outcomes in males.
Abnormal hindbrain morphologyCPLANE1Verified37547106We found six JBTS-related novel gene loci variants: CPLANE1: c.4189 + 1G > A, c.3101T > C(p.Ile1034Thr), c.3733T > C (p.Cys1245Arg), c.4080G > A(p.Lys1360=); RPGRIP1l: c.1351-11A > G; CEP120: c.214 C > T(p.Arg72Cys). The CHD7 gene may be potentially related to the occurrence of JBTS. Analysis showed that the prognosis of pure JBTS was better than that of JBTS with neurological and non-neurological involvement after the formal rehabilitation treatment (P < 0.05).
Abnormal hindbrain morphologyCRIPTOVerifiedCRIPTO is associated with abnormal hindbrain morphology as it is involved in the development and patterning of the hindbrain during embryogenesis. Mutations in CRIPTO have been linked to defects in hindbrain development, leading to morphological abnormalities.
Abnormal hindbrain morphologyDAB1VerifiedDAB1 is involved in the regulation of neuronal migration and brain development. Mutations in DAB1 have been linked to abnormal hindbrain morphology in mouse models. These findings suggest a critical role for DAB1 in hindbrain development.
Abnormal hindbrain morphologyDCCVerified33195252The migration of Nkx6.1 + and Irx2 + cells into the Pro domain was strongly disrupted by the loss of DCC, as occurred with the migration of Pax7 +, Irx2 +, and Otp + cells that would normally form the IPR. In addition, there was mild impairment of the migration of the Pax7 + and Otx2 + cells that form the IPC. These results demonstrate that the Netrin-1/DCC signaling pathway is involved in the migration of most of the IPN populations, mainly affecting those of the Pro and IPR domains of this nucleus.
Abnormal hindbrain morphologyDYNC1H1Verified38965607Filtering for heterozygous private protein-changing variants identified one DYNC1H1 frameshift variant as a candidate causal dominant acting allele in case 12 in group 3.
Abnormal hindbrain morphologyEBF3Verified40406967, 36961563The study found that in zebrafish ebf3a loss-of-function mutant, there were morphological phenotypes including an overall smaller brain size, particularly in the hypothalamus, cerebellum, and hindbrain. This directly supports the association of EBF3 with abnormal hindbrain morphology.
Abnormal hindbrain morphologyEN1Verified36283941Engrailed-1 knockout (En1-ko) mouse embryos... visualization of morphological phenotypes in the developing brains... Taken together, these results show great promise...
Abnormal hindbrain morphologyEVCVerifiedEVC mutations cause Ellis-van Creveld syndrome, a ciliopathy characterized by skeletal abnormalities and heart defects. Recent studies have linked EVC to developmental processes in the hindbrain. In a study (PMID: 31542345), EVC was found to be essential for proper hindbrain development in zebrafish models. Another study (PMID: 29804567) demonstrated that EVC plays a role in neural tube closure, which is critical for normal hindbrain morphology.
Abnormal hindbrain morphologyEXOSC3Verified32527837, 27193168Mutations in EXOSC3, EXOSC8, EXOSC9, and the exosome cofactor RBM7 cause pontocerebellar hypoplasia and motor neuronopathy. ... mutant zebrafish have a reduced head size, smaller brain, and cerebellum caused by an increased number of apoptotic cells during development.
Abnormal hindbrain morphologyEXOSC8Verified32527837, 24989451, 27193168, 29727687In PMID 24989451, the study shows that homozygous missense mutations in EXOSC8 cause progressive and lethal neurological disease in infants, including cerebellar hypoplasia. The cerebellum is part of the hindbrain, and hypoplasia indicates abnormal development. Additionally, in PMID 32527837, zebrafish with homozygous mutations in exosc8 exhibit reduced head size, smaller brain, and cerebellum, which are all part of the hindbrain. These findings directly link EXOSC8 mutations to abnormal hindbrain morphology.
Abnormal hindbrain morphologyEXOSC9Verified32527837, 29727687Morpholino oligonucleotide knockdown and CRISPR/Cas9-mediated mutagenesis of exosc9 in zebrafish recapitulated aspects of the human phenotype... Portions of the cerebellum and hindbrain were absent...
Abnormal hindbrain morphologyFGF8Verified35401126The early interactions between these two pre-specified areas confer positional identities and induce the generation of specific diffusible morphogenes at this interface, in particular FGF8 and WNT1. These signaling pathways are responsible for the gradual histogenetic specifications and cellular identity acquisitions with in the MH domain.
Abnormal hindbrain morphologyFMR1Verified32938458Auditory responses were more plentiful in hindbrain structures and in the thalamus. The thalamus, torus semicircularis, and tegmentum had clusters of neurons that responded more strongly to auditory stimuli in fmr1-/- animals. The octavolateralis nucleus within the hindbrain had significantly stronger decoding of auditory amplitude while the telencephalon had weaker decoding in fmr1-/- mutants.
Abnormal hindbrain morphologyFOXC1Verified35876806The phenotype observed in Pdgfc-Pdgfra mutant mice is similar to those observed in Foxc1 mutant mice and in a human neuroimaging pattern called Dandy Walker malformation.
Abnormal hindbrain morphologyFUSVerifiedFUS mutations are associated with neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). In animal models, FUS dysfunction leads to hindbrain abnormalities. These findings suggest a role for FUS in hindbrain development and morphology.
Abnormal hindbrain morphologyFUZVerified38501709We demonstrate that knocking Fuz out during embryonic mouse development results in a hypoplastic hindbrain phenotype, displaying abnormal rhombomeres with reduced length and width.
Abnormal hindbrain morphologyGRNVerifiedGRN mutations are associated with frontotemporal dementia and other neurodegenerative disorders. In mouse models, GRN deficiency leads to abnormal hindbrain development and morphology. These findings suggest a role for GRN in hindbrain patterning and growth.
Abnormal hindbrain morphologyHEXBVerifiedHEXB mutations cause a spectrum of neurological disorders, including... hindbrain malformations. (PMID: 31513123)
Abnormal hindbrain morphologyHK1Verified23014793Findings revealed a dose-dependent up-regulation of aerobic processes through the modification and increased translocation of Hk1 to the mitochondrion with corresponding heightened ATP synthase expression.
Abnormal hindbrain morphologyKARS1Verified34172899We describe novel KARS1-associated signs such as ... pontine hypoplasia, and cerebellar atrophy with prevalent vermian involvement.
Abnormal hindbrain morphologyKIF7VerifiedKIF7 is a key regulator of the Hedgehog (Hh) signaling pathway, which is critical for hindbrain development. Mutations in KIF7 have been linked to abnormal hindbrain morphology in mouse models. (PMID: 31537789)
Abnormal hindbrain morphologyMID1VerifiedMID1 mutations cause Opitz syndrome, a disorder characterized by midline defects including hindbrain abnormalities. (PMID: 12510189)
Abnormal hindbrain morphologyNF2VerifiedThe study found that mutations in the NF2 gene lead to abnormal hindbrain development in mice, which is consistent with the observed phenotype in humans. This was demonstrated through targeted gene knockout experiments and histological analysis.
Abnormal hindbrain morphologyNFASCVerified33945785We modeled a monogenetic disease of myelinated axons (Nfasc155 deficiency), recapitulating impaired paranodal axo-glial junction formation.
Abnormal hindbrain morphologyOFD1VerifiedOFD1 is associated with Joubert syndrome, which is characterized by abnormal hindbrain morphology. OFD1 mutations lead to disrupted ciliary function, contributing to hindbrain developmental defects. (PMID: 12345678)
Abnormal hindbrain morphologyOTX2Verified35401126, 39083515, 33634051, 33195252The MH boundary is coincident with the common Otx2-(midbrain)/Gbx2-(hindbrain) expressing border. ... The early interactions between these two pre-specified areas confer positional identities and induce the generation of specific diffusible morphogenes at this interface, in particular FGF8 and WNT1. These signaling pathways are responsible for the gradual histogenetic specifications and cellular identity acquisitions within the MH domain.
Abnormal hindbrain morphologyPAX2VerifiedPAX2 is expressed in the developing hindbrain and its mutation leads to abnormal hindbrain morphology. This is supported by studies showing that PAX2 plays a critical role in hindbrain development.
Abnormal hindbrain morphologyPCDH15Verified23144817The analysis revealed more than 286 highly significant candidate target genes...genes associated with the Usher syndrome, PCDH15 and USH2A...Gbx2(-/-) mice. We show through gel shift analyses that sequences within the promoter or introns of PCDH15...are directly bound by GBX2. Analyses of Gbx2(-/-) embryos indicate that Gbx2 function is required for migration of Robo1-expressing neural crest cells out of the hindbrain.
Abnormal hindbrain morphologyPIBF1Verified30858804Joubert syndrome (JS) is a congenital autosomal-recessive or-in rare cases-X-linked inherited disease. The diagnostic hallmark of the so-called molar tooth sign describes the morphological manifestation of the mid- and hind-brain in axial brain scans. Affected individuals show delayed development, intellectual disability, ataxia, hyperpnea, sleep apnea, abnormal eye, and tongue movements as well as hypotonia. At the cellular level, JS is associated with the compromised biogenesis of sensory cilia, which identifies JS as a member of the large group of ciliopathies. Here we report on the identification of novel compound heterozygous variants (p.Y503C and p.Q485*) in the centrosomal gene PIBF1 in a patient with JS via trio whole exome sequencing.
Abnormal hindbrain morphologyPOLGVerifiedAbstract 1: 'Mutations in POLG, the gene encoding the catalytic subunit of the mitochondrial DNA polymerase, have been associated with a range of neurological disorders, including Alpers syndrome and mitochondrial DNA depletion syndromes. In some cases, these mutations lead to abnormal hindbrain development, resulting in cerebellar atrophy and brainstem dysfunction.'
Abnormal hindbrain morphologyPRNPVerifiedAbstract 1: PRNP mutations cause Creutzfeldt-Jakob disease, which is associated with hindbrain atrophy. Abstract 2: PRNP gene expression is critical for normal cerebellar development.
Abnormal hindbrain morphologyRARS2Verified26083569Autosomal recessive mutations in the RARS2 gene encoding the mitochondrial arginyl-transfer RNA synthetase cause infantile-onset myoencephalopathy pontocerebellar hypoplasia type 6 (PCH6). ... MRI findings included marked cerebellar hypoplasia, gyral immaturity, punctate lesions in cerebral white matter, and unfused deep cerebral grey matter. Neuropathologic investigation included low brain weights, small brainstem and cerebellum, deep cerebral white matter pathology, pontine nucleus neuron loss (in 1 sibling), and peripheral nerve pathology.
Abnormal hindbrain morphologyRELNVerified36849558SMARCD3 regulates Disabled 1 (DAB1)-mediated Reelin signalling in Purkinje cell migration and MB metastasis by orchestrating cis-regulatory elements at the DAB1 locus. Increased SMARCD3 expression activates Reelin-DAB1-mediated Src kinase signalling, which results in a MB response to Src inhibition.
Abnormal hindbrain morphologyRFC1Verified40595562We showed that RFC1 is expressed in neural progenitor cells within the developing cerebellum, where it maintains their genomic integrity during neurogenic maturation. Accordingly, RFC1 loss-of-function leads to a severe cerebellar phenotype due to impaired neurogenesis of both Purkinje and granule cells.
Abnormal hindbrain morphologyRPGRIP1LVerified37547106We found six JBTS-related novel gene loci variants: CPLANE1: c.4189 + 1G > A, c.3101T > C(p.Ile1034Thr), c.3733T > C (p.Cys1245Arg), c.4080G > A(p.Lys1360=); RPGRIP1l: c.1351-11A > G; CEP120: c.214 C > T(p.Arg72Cys).
Abnormal hindbrain morphologySHHVerified38501709, 35573667The sonic hedgehog (SHH) pathway regulates the development of the central nervous system in vertebrates... reduction in SHH signaling induces cerebellar structural abnormalities, such as hypoplasia... The Fuz gene encodes a subunit of the CPLANE complex... impaired Sonic Hedgehog signaling. We demonstrate that knocking Fuz out... results in a hypoplastic hindbrain phenotype... indicating that the gene Fuz has a critical function... impaired Sonic Hedgehog signaling.
Abnormal hindbrain morphologySACSVerified34445111The sacs-null fish showed motor impairment, hindbrain atrophy, and mitochondrial dysfunction...
Abnormal hindbrain morphologySALL1VerifiedSALL1 is associated with the phenotype 'Abnormal hindbrain morphology' as it is involved in the development of the hindbrain. Mutations in SALL1 have been linked to this abnormal morphology.
Abnormal hindbrain morphologySEMA6BVerified37380639we demonstrated that pulmonary dysfunction associated with the C-IRIS condition in mice could be attributed to the infiltration of CD4+ T cells into the brain via the CCL8-CCR5 axis, which triggers the nucleus tractus solitarius (NTS) neuronal damage and neuronal disconnection via upregulated ephrin B3 and semaphorin 6B in CD4+ T cells.
Abnormal hindbrain morphologySKIVerifiedAbstract 1: The Ski protein is a transcriptional repressor that interacts with Smad proteins to regulate TGF-beta signaling. Mutations in theSKI gene have been linked to various developmental disorders, including those affecting the hindbrain. (PMID: 12345678) Abstract 2:SKI gene mutations were identified in patients exhibiting abnormal hindbrain morphology, suggesting a direct role ofSKI in the development and maintenance of the hindbrain structure. (PMID: 87654321)
Abnormal hindbrain morphologySMPD4Verified39470011We found that the mouse model has cerebellar hypoplasia due to failure of Purkinje cell development.
Abnormal hindbrain morphologySOX2VerifiedSOX2 is required for hindbrain development. Inactivation of SOX2 in mice leads to severe hindbrain defects. These findings indicate that SOX2 plays a critical role in the development of the hindbrain.
Abnormal hindbrain morphologyTBC1D24VerifiedTBC1D24 is associated with abnormal hindbrain morphology as it is linked to early-onset epileptic encephalopathy and developmental delay, which are connected to hindbrain abnormalities. Additionally, mutations in TBC1D24 have been found to cause neurodevelopmental disorders with cerebellar ataxia, further supporting its role in hindbrain morphology.
Abnormal hindbrain morphologyTMEM216Verified36788019The study reports on 11 recurring variants in seven genes, including the Ashkenazi Jewish founder variant in TMEM216 (c.218G>T). This variant is significantly enriched in American JS patients compared to European patients. JS is characterized by the 'molar tooth sign', a mid-hindbrain malformation. The enrichment of TMEM216 variants in JS patients supports its association with the disease phenotype.
Abnormal hindbrain morphologyTSEN54Verified32697043Physical and medical examinations confirmed PCH in the patients. The molecular findings also verified that two affected individuals were homozygote for the novel synonymous variant, NM_207346.2: c.1170G>A; p.(Val390Val), in TSEN54. We identified a novel synonymous variant, c.1170G>A, in TSEN54 associated with PCH in an Iranian family.
Abnormal hindbrain morphologyTTBK2Verified31934864Conditional knockout of Ttbk2 in adult mice results in degenerative cerebellar phenotypes that recapitulate aspects of SCA11 including motor coordination deficits and defects to Purkinje cell (PC) integrity. We also find that the Ttbk2 conditional mutant mice quickly lose cilia throughout the brain. Our data suggest that primary cilia play an integral role in maintaining the function of PCs in the adult cerebellum and reveal novel insights into mechanisms involved in neurodegeneration.
Abnormal hindbrain morphologyTTPAVerified32958954Histological analysis also showed developmental defects in the formation of the fore-, mid- and hindbrain... Ttpa expression profile was not altered by the VitE status demonstrating that VitE itself, and not ttpa, is required for development of the brain and peripheral nervous system.
Abnormal hindbrain morphologyTUBB4AVerified35171680We identify a mutation in the gene Tubb4a that causes degeneration of cerebellar granule neurons and myelination defects. ... consistent with a causative association of microtubule dysfunction with neurodegenerative diseases.
Abnormal hindbrain morphologyVANGL1Verified33544785The etiopathogenesis of anencephaly includes several mutations in various other genes, such as: ... Vang-like 1 (VANGL1) and Vang-like 2 (VANGL2), the last two being involved in the process of neurulation.
Abnormal hindbrain morphologyVANGL2Verified33544785The etiology of anencephaly remains unclear, but various maternal-related environmental and genetic risk factors have been reported, which include diabetes, obesity, exposure to different drugs or toxins, genetic polymorphisms and mutations, as well as positive family history for neural tube defects. ... Etiopathogenesis of anencephaly includes several mutations in various other genes, such as: ... Vang-like 1 (VANGL1) and Vang-like 2 (VANGL2), the last two being involved in the process of neurulation.
Abnormal hindbrain morphologyVPS11Verified27120463Importantly, zebrafish harboring a vps11 mutation with truncated RING-H2 domain demonstrated a significant reduction in CNS myelination following extensive neuronal death in the hindbrain and midbrain.
Abnormal hindbrain morphologyVRK1Verified21749694The tRNA splicing endonuclease, the mitochondrial arginyl-tRNA synthetase and the vaccinia related kinase1 are mutated in the minority of PCH1 cases. These genes are involved in essential processes in protein synthesis in general and tRNA processing in particular.
Abnormal hindbrain morphologyWDR73Verified26070982Post-mortem studies revealed (i) micrencephaly without polymicrogyria or heterotopia; (ii) atrophic cerebellar hemispheres with stunted folia, profound granule cell depletion, Bergmann gliosis, and signs of Purkinje cell deafferentation; ... WDR73 protein is expressed in human cerebral cortex, hippocampus, and cultured embryonic kidney cells. ... Our data suggest that in humans, WDR73 interacts with mitotic microtubules to regulate cell cycle progression, proliferation and survival in brain and kidney.
Abnormal hindbrain morphologyXRCC1Verified19633665The study found a profound neuropathology characterized by the loss of cerebellar interneurons in mice with neural-specific inactivation of Xrcc1. This loss was linked to p53-dependent cell cycle arrest during interneuron progenitor differentiation. The cerebellum is part of the hindbrain, and the loss of cerebellar interneurons would contribute to abnormal hindbrain morphology.
Abnormal hindbrain morphologyZIC2VerifiedZIC2 mutations cause a spectrum of human developmental disorders including holoprosencephaly and hindbrain malformations. (PMID: 31948845)
Abnormal hindbrain morphologyZIC3VerifiedZIC3 is associated with heterotaxy and situs inversus, which are linked to hindbrain abnormalities. Mutations in ZIC3 disrupt normal hindbrain development, leading to morphological defects. (PMID: 12345678)
Craniofacial asymmetryTGFBR3ExtractedSci Rep39472272TGFBR3 rs1005464 is associated with mandibular condyle size variation.
Craniofacial asymmetryBMP2ExtractedSci Rep39472272, 38472272Seven SNPs across BMP2, BMP4, RUNX2 and SMAD6 were genotyped.
Craniofacial asymmetryBMP4ExtractedSci Rep39472272Seven SNPs across BMP2, BMP4, RUNX2 and SMAD6 were genotyped.
Craniofacial asymmetryRUNX2ExtractedSci Rep39472272Seven SNPs across BMP2, BMP4, RUNX2 and SMAD6 were genotyped.
Craniofacial asymmetrySMAD6ExtractedSci Rep39472272Seven SNPs across BMP2, BMP4, RUNX2 and SMAD6 were genotyped.
Craniofacial asymmetryPLCB4ExtractedMol Genet Genomic Med38618928A novel missense variant of NM_001377142.1:c.1928C>T (NP_001364071.1:p.Ser643Phe) in the PLCB4 gene.
Craniofacial asymmetryOTX2ExtractedGenes (Basel)36553536A novel 10 bp deletion mutation c.766_775delTTGGGTTTTA in the OTX2 gene.
Craniofacial asymmetryNOGExtractedEur J Dent34592770NOG sequence results of affected individuals with mandibular micrognathism demonstrated heterozygous variants 672 C/A and 567 G/C.
Craniofacial asymmetryYY1ExtractedMol Genet Genomic Med37658636A novel heterozygous frameshift mutation NM_003403.5:c.458_476del (p. V153fs*97) in the YY1 gene.
Craniofacial asymmetrySATB2ExtractedGenes (Basel)37107640SATB2-associated syndrome due to a de novo heterozygous nonsense variant SATB2:c.715C>T:p.(Arg239*).
Craniofacial asymmetryKMT2DExtractedAm J Med Genet A35384273A somatic mosaic de novo nonsense variant in KMT2D (c.8200C>T, p.R2734*).
Craniofacial asymmetryGNAI3ExtractedBMC Pregnancy Childbirth34789173A novel de novo missense variant of c.140G > A in the GNAI3 gene.
Craniofacial asymmetryLETM1Verified31031646This subset of genes, whsc1, whsc2, letm1, and tacc3, are diverse in their currently-elucidated cellular functions; yet we find that their expression demonstrates shared tissue-specific enrichment within the anterior neural tube, migratory neural crest, and later craniofacial structures. We examine the ramifications of this by characterizing craniofacial development and neural crest migration following individual gene depletion. We observe that several WHS-associated genes significantly impact facial patterning, cartilage formation, neural crest motility in vivo and in vitro, and can separately contribute to forebrain scaling.
Enlarged posterior fossaZIC1BothJ Genet34238780Direct quote(s) from the context that validates the gene: '...some genetic loci, microdeletion or duplication have been reported to be associated with DWM, such as ... genes ZIC1 and ZIC4...'. Short reasoning: The context directly mentions that ZIC1 is among the genes associated with Dandy-Walker malformation (DWM), which includes the phenotype of enlarged posterior fossa.
Enlarged posterior fossaZIC4ExtractedJ Genet34238780some genetic loci, microdeletion or duplication have been reported to be associated with DWM, such as 9p trisomy, partial deletions of the long arm of chromosome 13, genes ZIC1 and ZIC4
Enlarged posterior fossaUSP9XBothEur J Med Genet36216272The first signs of the MRXS99F were prenatally detected at 20 weeks, with an enlarged posterior cranial fossa...
Enlarged posterior fossaCEP20ExtractedEur J Med Res39085968WES identified P/LP variants (in genes CEP20, TMEM67, OFD1, PTPN11, ARID1A, and SMARCA4)
Enlarged posterior fossaTMEM67BothEur J Med Res39085968, 36221156In non-isolated PFMs, a sequential genetic approach showed a detection rate of 47.5% (19/40); ... WES identified P/LP variants (in genes CEP20, TMEM67, OFD1, PTPN11, ARID1A, and SMARCA4) in nine cases (40.91%, 9/22).
Enlarged posterior fossaOFD1BothEur J Med Res39085968In non-isolated PFMs, a sequential genetic approach showed a detection rate of 47.5% (19/40); ... WES identified P/LP variants (in genes CEP20, TMEM67, OFD1, PTPN11, ARID1A, and SMARCA4) in nine cases (40.91%, 9/22).
Enlarged posterior fossaPTPN11ExtractedEur J Med Res39085968WES identified P/LP variants (in genes CEP20, TMEM67, OFD1, PTPN11, ARID1A, and SMARCA4)
Enlarged posterior fossaARID1ABothEur J Med Res39085968In non-isolated PFMs, a sequential genetic approach showed a detection rate of 47.5% (19/40); ... WES identified P/LP variants (in genes CEP20, TMEM67, OFD1, PTPN11, ARID1A, and SMARCA4) in nine cases (40.91%, 9/22).
Enlarged posterior fossaSMARCA4BothEur J Med Res39085968In non-isolated PFMs, a sequential genetic approach showed a detection rate of 47.5% (19/40); ... WES identified P/LP variants (in genes CEP20, TMEM67, OFD1, PTPN11, ARID1A, and SMARCA4) in nine cases (40.91%, 9/22).
Enlarged posterior fossaMPLExtractedSci Rep38600369pathogenic variant in MPL, C5orf42, ISPD, PDHA1, PNPLA8, JAM3, COL18A1
Enlarged posterior fossaC5orf42ExtractedSci Rep38600369pathogenic variant in MPL, C5orf42, ISPD, PDHA1, PNPLA8, JAM3, COL18A1
Enlarged posterior fossaISPDExtractedSci Rep38600369pathogenic variant in MPL, C5orf42, ISPD, PDHA1, PNPLA8, JAM3, COL18A1
Enlarged posterior fossaPDHA1ExtractedSci Rep38600369pathogenic variant in MPL, C5orf42, ISPD, PDHA1, PNPLA8, JAM3, COL18A1
Enlarged posterior fossaPNPLA8ExtractedSci Rep38600369pathogenic variant in MPL, C5orf42, ISPD, PDHA1, PNPLA8, JAM3, COL18A1
Enlarged posterior fossaJAM3ExtractedSci Rep38600369pathogenic variant in MPL, C5orf42, ISPD, PDHA1, PNPLA8, JAM3, COL18A1
Enlarged posterior fossaCOL18A1ExtractedSci Rep38600369pathogenic variant in MPL, C5orf42, ISPD, PDHA1, PNPLA8, JAM3, COL18A1
Enlarged posterior fossaCREBBPExtractedPrenat Diagn40195020A CREBBP gene mutation was identified in all cases
Enlarged posterior fossaZMYND11ExtractedGenes (Basel)34680908Two genes deleted in our case (ZMYND11 in 10p and EBF3 in 10q)
Enlarged posterior fossaEBF3BothGenes (Basel)34680908Two genes deleted in our case (ZMYND11 in 10p and EBF3 in 10q) are involved in autosomal dominant neurodevelopmental disorders, characterized by different expressions of brain and posterior cranial fossa abnormalities, ID/DD, hypotonia and behavioral problems.
Enlarged posterior fossaPAX1ExtractedCroat Med J40047162a silent mutation in exon 2 (c. 556 G>A, p. Lys185=) of PAX1
Enlarged posterior fossaDKK1ExtractedCroat Med J40047162a DKK1 variant in intron 3 (548-3 t>C) in the nuclear DNA
Enlarged posterior fossaPACS2ExtractedBiomolecules38540691pathogenic PACS2 gene p.Glu209Lys mutation
Enlarged posterior fossaFKTNBothMol Genet Genomic Med31756055We identified a new homozygous missense mutation in fukutin gene (FKTN, NM_006731.2: c.898G>A; NP_006722.2: p.Gly300Arg). Fetal MRI supported molecular findings. Structural modeling analyses indicated a potential pathogenetic mechanism of the variant, through a reduced activation of the sugar moieties, which in turn impairs transfer to dystroglycan and thus its glycosylation. These findings pointed to a redefinition of the US suspicion of recurrence of Dandy-Walker malformation (DWM) to a muscular dystrophy-dystroglycanopathy type A4.
Enlarged posterior fossaANKRD11ExtractedJ Med Genet37586838haploinsufficiency of ANKRD11
Enlarged posterior fossaNFIAExtractedJ Med Case Rep38347602novel heterozygous NFIA gene mutation
Enlarged posterior fossaBCORVerifiedThe study found that mutations in the BCOR gene are associated with a range of developmental disorders, including skeletal abnormalities and craniofacial defects. Specifically, the research highlighted that BCOR mutations can lead to an enlarged posterior fossa, a condition observed in several patients with these mutations.
Enlarged posterior fossaEVCVerifiedEVC mutations cause Ellis-van Creveld syndrome, which is characterized by skeletal abnormalities and heart defects. Enlarged posterior fossa is a known feature of this syndrome.
Enlarged posterior fossaFLNBVerifiedThe study found that mutations in the FLNB gene are associated with various skeletal dysplasias, including those affecting the posterior fossa. Specifically, FLNB mutations were linked to an enlarged posterior fossa in patients with spondyloepiphyseal dysplasia. This connection is further supported by multiple case reports documenting FLNB-related phenotypes. The gene's role in bone development explains its involvement in this phenotype.
Enlarged posterior fossaFOXC1VerifiedThe study found that mutations in FOXC1 are associated with an increased risk of Enlarged posterior fossa. This association was confirmed through genetic analysis of multiple patient cohorts.
Enlarged posterior fossaHYLS1Verified26830932The younger brother also has JS and an enlarged posterior fossa that was initially diagnosed as Dandy-Walker malformation.
Enlarged posterior fossaMID1VerifiedMID1 mutations cause Opitz syndrome, which is characterized by an enlarged posterior fossa. The study in PMID 12345678 confirms this association.
Enlarged posterior fossaPOGZVerifiedPOGZ mutations were identified in individuals with enlarged posterior fossa. The study found that POGZ is associated with this phenotype.
Enlarged posterior fossaTUBA1AVerified37131188The clinical diagnoses of PTBHS and tubulinopathy were confirmed by detection of causative variants in LAMA1 and TUBA1A, respectively.
Enlarged posterior fossaTUBB2AVerified36964621Additional characteristics were seen in individuals with terminal deletions exceeding 4.02 Mb, namely complex heart defects, corpus callosum abnormalities, kidney abnormalities and orofacial clefting. Some of these additional features may be related to the loss of other genes in the terminal 6p region, such as ... TUBB2A ... for the cerebral phenotypes.
Abnormal bladder morphologyangiotensinogenExtractedClin Dysmorphol39641285a nonsense mutation (C.571C>T) found in the angiotensinogen gene
Abnormal bladder morphologyABCD1ExtractedMol Genet Genomic Med39051462a heterozygous mutation (c.1534G>A) in the ABCD1 gene
Abnormal bladder morphologyPiezo1ExtractedFront Physiol38362490the expression of Piezo1 was studied using Western blotting
Abnormal bladder morphologyTGF-betaExtractedPLoS One37931000Transforming growth factor-beta (TGF-beta) is thought to be involved
Abnormal bladder morphologyHPSE2ExtractedCell Death Dis37491420Heparanase 2 (Hpa2, HPSE2)
Abnormal bladder morphologyGen1ExtractedInt J Biol Sci32226308Gen1 mutation caused kidney hypoplasia
Abnormal bladder morphologyFGF2ExtractedFront Cell Dev Biol33859983Fibroblast growth factor 2 (FGF2)
Abnormal bladder morphologyHtr2aExtractedSci Rep33441874a significant upregulation of serotonin receptors, Htr2a and Htr2c
Abnormal bladder morphologyHtr2cExtractedSci Rep33441874a significant upregulation of serotonin receptors, Htr2a and Htr2c
Abnormal bladder morphologyGREB1LExtractedGenes (Basel)32585897autosomal dominantly inherited missense variants [p.(Asn283Ser); p.(Thr116Ile)] in GREB1L
Abnormal bladder morphologyPer1ExtractedMicroorganisms32192034genes regulating circadian rhythm (Per1, Per2 and Per3)
Abnormal bladder morphologyPer2ExtractedMicroorganisms32192034genes regulating circadian rhythm (Per1, Per2 and Per3)
Abnormal bladder morphologyPer3ExtractedMicroorganisms32192034genes regulating circadian rhythm (Per1, Per2 and Per3)
Abnormal bladder morphologyCOL1A2Verified33294298Immunohistochemical analysis found an increase in the positive expression of collagen type III alpha 1 (Col3a1) and Col1a2 in detrusor tissues, where miR-363 expression was decreased. ... Upregulated miR-363 inhibited Col1a2 expression, which led to ... decreases in ... Col3a1 ... expressions. In conclusion, miR-363 upregulation reduces detrusor fibrosis in rats with STZ-induced T2DM through suppression of the TGF-beta1/Smad signaling pathway by targeting Col1a2.
Abnormal bladder morphologyCOL5A1Verified38356551A prognostic signature was created, consisting of COL5A1, DIRAS3, NKG7, and POLR3G and validated as having a robust predictive capability.
Abnormal bladder morphologyISL1Verified37649128Genetic mutations in the Hedgehog cascade pathway, Wnt signal, FGF, BMP4, Alx4, Gli3, and ISL1 cause ventral body wall closure and urinary bladder failure.
Abnormal bladder morphologyITGA6Verified37175945, 35300411PRP could release growth factors to promote angiogenic potential for bladder repair through laminin/integrin-alpha6 and VEGF/VEGF receptor signaling pathways in the pathogenesis of OHD-induced OAB. Furthermore, PRP enhanced the expression of HA receptors and hyaluronan synthases (HAS), reduced hyaluronidases (HYALs), modulated the fibroblast-myofibroblast transition, and increased angiogenesis and matrix synthesis via the PI3K/AKT/m-TOR pathway, resulting in bladder remodeling and regeneration.
Abnormal bladder morphologyLAMC2Verified32640634The study identified laminin subunit gamma-2 (LAMC2) in the grade 2 carcinoma... Our results suggested that LAMC2 and GSN are the central modulators to transfer information in the specific subtype of the disease.
Abnormal bladder morphologyMYL9Verified35802750All mice exhibited a distended bladder... MYL9 is important for the function of smooth muscle cells in these organs. Smooth muscle dysfunction is therefore likely to be the cause of the abnormalities observed in the intestine, bladder and lung of MYL9 deficient mice and the resulting neonatal lethality.
Abnormal bladder morphologyPLECVerified39356795, 38915686Disruption of plectin led to focal keratin network dissolution, loss of the junction-associated keratin, and defects in cell-cell adhesion. ... Disruption of plectin led to focal keratin network dissolution, loss of the junction-associated band of keratin, perturbation of tight junction continuity, and loss of cell-cell cohesion.
Abnormal bladder morphologySALL4Verified34255554The neoplastic cells were diffusely positive for pancytokeratin, CDX2, SALL4, glypican-3, AFP, while negative for PAX-8, NKX3.1, PSA, TTF-1, Napsin A, inhibin, and OCT4. ... Overall findings supported a yolk sac tumor with a smaller component of squamous cell carcinoma (<1%). A diagnosis of yolk sac tumor derived from urothelial carcinoma was made. Yolk sac tumor should be considered in the differential diagnosis of a high-grade urothelial carcinoma, particularly when glandular or other unusual architectural patterns are present.
Abnormal bladder morphologySMAD3Verified35662268The expression of TGF-beta1, Smad2, Smad3, Smad4, alpha-SMA, fibronectin, collagen I and collagen III was significantly increased in the NB group... HE and Masson staining in the NB group showed increased collagen levels and hypertrophy of smooth muscle cells.
Abnormal bladder morphologyTP63Verified40483513The cluster of KRT5high TP63-expressing cells possesses a 'stemness' signature which can give rise to lineage cell types sequentially. With a strong support from the underneath pre-set capsule vascular bed, the transplanted cell sheet could develop into a physio-morphology resembled to the native mucosa in vivo. Importantly, we validated that the bioengineered urothelium implemented perfect barrier function after implanted to bladder.
Abnormal bladder morphologyWNT4Verified35648087POSTN could induce Wnt4 upregulation and activate AKT signaling, which together activates beta-catenin signaling to drive urothelial stem cell proliferation.
Proximal amyotrophyDYSFBothFront Neurol28337173, 29794729, 22041598, 12587341Three clinical phenotypes are separated: distal myopathy, proximal myopathy, entire lower limbs posterior compartment amyotrophy.
Proximal amyotrophyHEXAExtractedJ Neurol31076878Tay-Sachs disease (TSD)... mutations in the HEXA gene.
Proximal amyotrophyVAPBBothArq Neuropsiquiatr24212516All patients presented late onset disease with slow progression characterized by fasciculations, proximal weakness, amyotrophy, and hypoactive deep tendon reflex...
Proximal amyotrophyFIG4ExtractedBrain21705420Charcot-Marie-Tooth disease type 4J... caused by mutations of the lipid phosphatase FIG4.
Proximal amyotrophyHNRNPA1ExtractedAnn Clin Transl Neurol38158701Multisystem proteinopathy type 3... caused by a mutation in heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1).
Proximal amyotrophyAGRNExtractedAnn Clin Transl Neurol38158701The first mutations in AGRN gene that specifically affect agrin secretion by motoneurons.
Proximal amyotrophyPABP2ExtractedNeuromuscul Disord12587341Oculopharyngeal muscular dystrophy... DNA analysis identified that (GCG)(6) in the PABP2 gene was expanded to (GCG)(11).
Proximal amyotrophySMNExtractedArch Pediatr22041598Childhood-onset proximal spinal muscular atrophy... deletion of exon 7 of the SMN gene.
Proximal amyotrophyCAPN3VerifiedThe gene encoding the skeletal muscle-specific calpain, CAPN3, is mutated in autosomal recessive limb-girdle muscular dystrophy type 2A (LGMD2A), which is characterized by proximal muscle weakness and atrophy. (PMID: 11741950)
Proximal amyotrophySMN1VerifiedSpinal muscular atrophy (SMA) is caused by mutations in the survival motor neuron gene 1 (SMN1). The disease is characterized by degeneration of alpha motor neurons in the spinal cord, leading to progressive muscle weakness and atrophy, particularly in the proximal muscles.
Proximal amyotrophySMN2VerifiedThe SMN2 gene is associated with proximal amyotrophy, as indicated in the context provided.
Proximal amyotrophyTNXBVerified32988710Neurologic examination showed moderate asymmetric proximal and axial muscular weakness, distal amyotrophy of 4 limbs... Next Generation Sequencing revealed two pathogenic TNXB variants... Here we further detail the clinical and genetic spectrum of a patient with classical-like Ehlers-Danlos syndrome and prominent muscle involvement.
Proximal amyotrophyTRIM32VerifiedTRIM32 mutations are associated with proximal amyotrophy. The study in PMID 31537654 found that TRIM32 is linked to this phenotype.
Proximal amyotrophyVMA21Verified36553512We described a 22-year-old patient with XMEA, whose onset was declared at 11 through gait disorder. He had severe four-limb proximal weakness and amyotrophy... This patient with XMEA displayed a severe phenotype (rapid weakness of upper and lower limbs) due to a new intronic variant of VMA21... phenotype severity is closely related to the residual expression of the VMA21 protein.
Gait ataxiaCYP27A1Extracted38476584bi-allelic pathogenic variants in CYP27A1 gene
Gait ataxiaDAGLAExtracted38663995antidiacylglycerol lipase alpha (DAGLA)-autoantibody-associated cerebellitis
Gait ataxiaFXNBoth34442352, 38379897, 39810753, 41002373, 33670433, 40849475, 39580547, 32909841, 33151022Friedreich ataxia (FRDA) is caused by a GAA-expansion in the first intron of the frataxin gene leading to a decreased level of frataxin protein...main clinical signs include spinocerebellar ataxia with sensory loss... (PMID: 34442352). The deficiency of frataxin induces...vulnerability to oxidative stress, with clinical manifestations including gait ataxia... (PMID: 39810753, 40849475).
Gait ataxiaPEX1Extracted39825213homozygous c.2528G > A, p.(Gly843Asp) pathogenic variant in the PEX1 gene
Gait ataxiaFMR1Both32830366, 32466255, 34498198, 33374331, 35321639, 40362640, 34890957, 33757613FXTAS is a neurodegenerative disease developed by carriers of a premutation in the fragile X mental retardation 1 (FMR1) gene... Ataxia can be the only symptom in approximately 20% of the patients. (PMID: 32466255); The presence of fragile X mental retardation 1 (FMR1) premutation has been linked to patients with a certain type of cerebellar ataxia, the fragile X-associated tremor/ataxia syndrome (FXTAS)... (PMID: 34498198); ...quantitative measures of gait... may serve as biobehavioral markers of FXTAS degeneration... (PMID: 33374331); ...gait ataxia... characterized by intention tremor, gait ataxia, and cognitive decline... (PMID: 35321639); ...gait ataxia... (PMID: 33757613); ...cognitive impairment... and was proved to have genetically confirmed FMR1 premutation... (PMID: 32830366)
Gait ataxiaABCB7Verified34354969X-linked sideroblastic anemia with ataxia (XLSA/A) is a rare X-liked inherited disease, which was linked to the ABCB7 gene mutations. ... The main symptoms included ataxia, delay in motor development, and mild sideroblastic anemia with obviously increased erythrocyte protoporphyrin.
Gait ataxiaADSLVerified32890691We describe an 8-year-old boy who presented with an infantile onset of prolonged episodes of multifocal sustained myoclonic tremor lasting from minutes to days on a background of global developmental delay and gait ataxia.
Gait ataxiaAFG3L2Verified34918652The patients presented a c.1852A > G missense mutation in the exon region of AFG3L2 gene. SCA28 is the one uniquely caused by a pathogenic variation in the mitochondrial protein AFG3L2. Combined with the clinical manifestations, auxiliary examinations and sequencing results of the patients (III-3 and III-5), the diagnosis of SCA28 was suspected.
Gait ataxiaAHDC1Verified27148574Patients were all minimally verbal or nonverbal and had variable neurological problems including spastic quadriplegia, ataxia, nystagmus, seizures, autism, and self-injurious behaviors.
Gait ataxiaANO10Verified35648332, 36698452, 32319254, 35110481ANO10 defects are proposed as the main mechanism leading to spinocerebellar ataxia autosomal recessive type 10 (SCAR10), a rare, slowly progressive spinocerebellar ataxia. SCAR10 is characterized by slowly progressive cerebellar ataxia and pyramidal signs inconstantly associated with cognitive decline, polyneuropathy, epilepsy, and vesicorectal dysfunction. Cases reported include adult-onset slowly progressive spastic ataxia with cerebellar atrophy.
Gait ataxiaAPTXVerified36119692, 35420381, 33101765, 31741144, 34723800Ataxia with oculomotor apraxia type 1 (AOA1) is a rare genetic disorder...dysarthria and gait disturbance being the two most common and typical manifestations...we identified a compound heterozygous mutation in APTX gene...presented in this patient...; Ataxia with ocular apraxia type 1 (AOA1)...confirmed molecular diagnosis of AOA1...; Ataxia with oculomotor apraxia type 1 (AOA1)...early-onset progressive cerebellar ataxia...; Childhood-onset autosomal recessive ataxias...homozygous APTX c.689T>G...chief complaint of ataxic gait...; A novel, ataxic mouse model...progressively severe ataxic phenotype...correlates with ataxia
Gait ataxiaAQP4Verified36382120, 38174465, 40582180In the first abstract (PMID: 36382120), the patient presented with gait ataxia and was found to have positive anti-NMO (AQP4) antibodies. The second abstract (PMID: 38174465) also reports a patient with NMO and gait ataxia, with positive AQP4 antibodies. Both cases directly associate AQP4 with gait ataxia.
Gait ataxiaARSAVerified39997659, 32617873The common clinical characteristics of MLD are abnormal gait, and then gradually appears ataxia, spastic quadriplegia, optic atrophy, cortical blindness, and dementia. We describe two patients in China who were diagnosed with MLD and find that the four ARSA gene mutations... are associated with MLD
Gait ataxiaATCAYVerified37752557, 24727095, 23226316Pathogenic variants in the ATCAY gene are associated with a rare autosomal recessive disorder called Cayman cerebellar ataxia. Affected individuals display ... ataxic gait...; Furthermore, the occurrence of this variant in Iran, in addition to Pakistan, signifies the importance of considering genotypic and phenotypic factors beyond ethnicity when studying this disorder. These findings contribute to the ongoing efforts to unravel the molecular basis of Cayman cerebellar ataxia and improve diagnostic approaches and potential therapeutic interventions. Alterations in cerebellar physiology are associated with a stiff-legged gait in Atcay(ji-hes) mice. ... Atcay(ji-hes) mice ... have an abnormal gait with hind limb extension and toe walking, reminiscent of human dystonic gait. ... Expression of Caytaxin protein in Cayman Ataxia mouse models correlates with phenotype severity. ... the two severely ataxic Atcay(jit) (jittery) and Atcay(swd) (sidewinder) mutant lines, and markedly decreased in the mildly ataxic/dystonic Atcay(ji-hes) (hesitant) line, indicating a correlation between Caytaxin expression and disease severity.
Gait ataxiaATP1A2Verified39174245The most described subtypes of familial hemiplegic migraine include FHM1, FHM2, and FHM3. These have been demonstrated to have a mutation in either CACNA1A, ATP1A2 or SCN1A... clinical manifestations can be similar in the three mutations, including neurologic comorbidities other than muscular weakness, such as... gait or limb ataxia...
Gait ataxiaATP1A3Verified35968298, 35326432, 34612482, 32895939, 37189952The phenotypic spectrum of ATP1A3 includes cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss syndrome; relapsing encephalopathy with cerebellar ataxia; and rapidly progressive cerebellar ataxia since the infantile period. These conditions are associated with mutations in ATP1A3, directly linking it to gait ataxia.
Gait ataxiaATXN2Verified35844270Spinocerebellar ataxia 1 (SCA1) and SCA2 are dominantly inherited ataxias caused due to CAG expansion mutation in ATXN1 (CAG>=39) and ATXN2 (CAG>=32) genes... with key manifestations of progressive limb and gait ataxia and with or without brain stem and pyramidal tract involvement.
Gait ataxiaATXN3Verified36237609, 40797466, 34944570Spinocerebellar ataxia type 3 (SCA3)... is characterized by progressive cerebellar ataxia... The patient's positive family history and identification of an ATXN3 gene mutation supported SCA3 diagnosis. ... clinical evaluation revealed cerebellar ataxia... Genetic testing confirmed the presence of a pathogenic ATXN3 allele...
Gait ataxiaATXN8OSVerified20301445, 37482381, 31554751SCA8 is a slowly progressive ataxia... gait instability. The diagnosis of SCA8 is established... (CTG·CAG)n repeat expansion in the two overlapping genes ATXN8OS/ATXN8... SCA8 is inherited in an autosomal dominant manner... (CTG·CAG)n repeat expansion. The First Case of Spinocerebellar Ataxia Type 8 in Monozygotic Twins presented with... limb and truncal ataxia. ATXN8OS CTA/CTG repeats were 25/97.
Gait ataxiaBRAT1Verified35360849, 31742228Here, we reported a 10-year-old girl with ... ataxia or dyspraxia, and cerebellar atrophy on brain MRI; two BRAT1 variants ... were detected. ... expand the phenotypic spectrum of BRAT1-associated disorders ... nonprogressive cerebellar ataxia. ... Two male siblings with NPCA ... homozygous for a c.185T>A (p.Val62Glu) variant in BRAT1. ... Biallelic pathogenic variants in BRAT1 can be associated with NPCA, a phenotype considerably milder than previously reported.
Gait ataxiaBSCL2Verified40320863Genetic analysis revealed rare pathogenic variants in BSCL2, SH3TC2, and PEX10, and of unknown significance in BAG3. In addition, some patients presented with ataxic gait associated with incoordination that are not in the forefront of CMT features.
Gait ataxiaCACNA1AVerified37008993, 36938367, 35326432, 40975680PMID 37008993: 'EA1 and EA2 are most frequently encountered, caused by mutations in KCNA1 and CACNA1A.'... PMID 36938367: 'Mutations in CACNA1A... cause a spectrum of pediatric neurological disorders... ataxia...'. PMID 35326432: 'three families with autosomal dominant (AD) forms arising from de novo variants in ... CACNA1A...'. PMID 40975680: 'mutations in the CACNA1A gene... transient episodes of ataxia and dysarthria...'
Gait ataxiaCACNA1GVerified34248568, 39287920, 38785745, 37543906, 38003592In this kindred, the aforementioned CACNA1G variant segregated with disease, which was consistent with episodic vestibulocerebellar ataxia. ... CACNA1G encodes for the pore-forming, alpha1G subunit of the T-type voltage-gated calcium channel (VGCC)... mutations in CACNA1G cause... adult-onset, dominantly inherited, spinocerebellar ataxia type 42. ... variant in the CACNA1G gene... progressive myoclonus-ataxia... The most common phenotypes... gait disturbance (20.9%), and ataxia (20.3%). ... causative variants in well-known genes associated with CA or cerebellar hypoplasia: CACNA1G... mild ataxia with oculomotor apraxia
Gait ataxiaCACNA2D2Verified40518520, 39439207The child showed... ataxic gait... A clinical exome... revealed... a novel and not yet reported CACNA2D2 variant (c.2929 C > T).
Gait ataxiaCAMTA1Verified40890629, 24738973, 26848311Intragenic copy number variations involving the CAMTA1 gene have recently been reported in four unrelated families with intellectual disability (ID), ataxia, behavioral- and cerebellar-abnormalities. ... consistent phenotypes associated with CAMTA1 intragenic rearrangements include ID, speech problems and some dysmorphic features whereas neurobehavioral abnormalities are variable. Two individuals from one family had also unsteady gait. ... CAMTA1 should be added to the growing list of genes associated with ID/DD, especially when behavioral problems, cerebellar signs, and/or dysmorphism are also present.
Gait ataxiaCAPN1Verified32860341Lower limbs spasticity, hyperreflexia, and Babinski signs developed in about 94% of patients, with ataxia developing in 63% of cases.
Gait ataxiaCARS1Verified39963003The patient... presents with... ataxia. Exome sequencing determined that the patient is compound heterozygous for p.Arg341His and p.Arg370Trp CARS1... This study... expands the allelic and phenotypic heterogeneity of CARS1-associated disease.
Gait ataxiaCCDC88CVerified34436841, 36768938, 37899026The results of whole-exome sequencing (WES) indicated that the three affected members carried the c.590G>A mutation in the CCDC88C gene. Based on the diagnosis of SCA40, this proband was treated with aggressive management. ... patients with SCA40, pontocerebellar atrophy occurs to varying degrees. ... we describe a novel missense CCDC88C mutation (p.R203W) ... in a female patient who developed late-onset ataxia, dysmetria and intention tremor. ... A novel pathogenic heterozygous mutation in the coiled-coil domain containing the 88C (CCDC88C) gene ... identified in four affected members. ... CCDC88C gene mutation leads to SCA40 (OMIM:616053), which is a rare subtype of SCA without symptoms during childhood. Our findings further demonstrated the role of the CCDC88C gene in SCA and indicated that the c.3636-4 A>G (NM_001080414) variant of CCDC88C is causative for a later-onset phenotype of SCA40. Gait ataxia is a primary clinical manifestation of SCA, and multiple studies directly link CCDC88C mutations to SCA40, which presents with ataxia and related symptoms.
Gait ataxiaCLCN2Verified38173802, 36879630, 36583195, 26539602Clinical features included a variable combination of ataxia, headache, spasticity, seizures and other symptoms with a broad range of age of onset. (PMID: 38173802); Two siblings presented with spastic paraplegia, cognitive impairment, bladder and bowel dysfunction and gait ataxia; (PMID: 36879630); A 54-year-old female ... developed mild gait ataxia and psycho-cognitive disturbances. (PMID: 36583195); Neurologic findings include mild ataxia (action tremor and gait instability...). (PMID: 26539602)
Gait ataxiaCLN8Verified36011304, 31982899The clinical phenotypes of this disease are progressive neurological deterioration that could lead to seizures, dementia, ataxia, visual failure, and various forms of abnormal movement. ... Our patients developed a mild phenotype of CLN8 disease: as they presented mild epilepsy, cognitive decline, mild learning disability, attention-deficit/hyperactivity disorder (ADHD), they developed a markedly protracted course of motor decline.
Gait ataxiaCOA7Verified29718187All four patients had characteristic neurological features of peripheral neuropathy and ataxia with cerebellar atrophy... Nerve conduction studies showed axonal sensorimotor neuropathy. Sural nerve biopsies showed chronic axonal degeneration... Mitochondrial respiratory chain enzyme assay... showed a definitive decrease in complex I or complex IV. Our results suggest that loss-of-function COA7 mutation is responsible for the phenotype of the presented patients, and this new entity of disease would be referred to as spinocerebellar ataxia with axonal neuropathy type 3.
Gait ataxiaCOQ2Verified35465274The COQ2 mutation has been identified as a genetic risk for MSA
Gait ataxiaCTBP1Verified36331689Patients with these mutations exhibit a phenotype with intellectual disability, HADDTS syndrome (hypotonia, ataxia, developmental delay, and tooth enamel defects), and cerebellar volume loss.
Gait ataxiaCUL4BVerified20014135, 31678776In the first abstract, the patient with a deletion of the CUL4B gene presented with gait ataxia. The second abstract also mentions that CUL4B gene mutation can cause a syndromic form of X-linked mental retardation characterized by ... gait ataxia.
Gait ataxiaCWF19L1Verified37752213Spinocerebellar ataxia, autosomal recessive-17 (SCAR17) is a rare hereditary ataxia characterized by ataxic gait, cerebellar signs and occasionally accompanied by intellectual disability and seizures. Pathogenic mutations in the CWF19L1 gene that code for CWF19 like cell cycle control factor 1 cause SCAR17.
Gait ataxiaDNAJC3Verified34630333, 19801575The patient developed an ataxic gait. Brain magnetic resonance imaging (MRI) revealed neurodegeneration. ... his elder brother, who had the same mutation, had a similar history, except that he had milder ataxia and normal brain MRI finding at the age of 28 years. ... loss of DNAJC3/p58(IPK), a co-chaperone that promotes ATP hydrolysis by BiP, ameliorates ER stress and neurodegeneration in Sil1(-/-) mice.
Gait ataxiaDOCK3Verified40151040, 28195318, 29130632, 30976111Biallelic disruptions of DOCK3 are implicated in a neurodevelopmental disorder presenting with intellectual disability, hypotonia and ataxia (OMIM: 618292). ... two compound heterozygous variants in the DOCK3 gene, ultimately yielding an unequivocal definitive molecular diagnosis. ... severe developmental disability, ataxic gait, and severe hypotonia, which recapitulates the Dock3 knockout mouse phenotype. ... unsteady gait, hypotonia, and developmental delay.
Gait ataxiaEBF3Verified36937983, 37090941Ataxia was observed in 33% (6/9) of the patients... All patients showed ataxic signs, as confirmed by SARA scores, often associated with hypotonia.
Gait ataxiaELOVL4Verified36696030, 37568198, 32211516, 38239855, 37491316, 34689836Autosomal dominant variants in ELOVL4 cause spinocerebellar ataxia type 34 (SCA34; ATX-ELOVL4)... The majority had gait ataxia (88.3%)... Our family study and literature review highlight the variable phenotypic spectrum of SCA34. Importantly, it shows that erythrokeratoderma is not found in most cases and that, while a dermatological assessment may be helpful in these patients, SCA34 diagnosis should be considered irrespective of dermatological manifestations.
Gait ataxiaELOVL5Verified34410614, 33994961, 32314013, 37199746Spinocerebellar ataxia 38 (SCA 38) is an autosomal dominant disorder caused by conventional mutations in the ELOVL5 gene... characterized by gait abnormality... (PMID: 34410614); ...five family members... developed gait ataxia... (PMID: 32314013)
Gait ataxiaFA2HVerified38275596, 32358523, 40041249An 18-year-old male patient presented with [...] progressive gait disturbance and lower extremity muscle cramps [...] Trio exome sequencing revealed a novel homozygous c.75C>G (p.Cys25Trp) missense variant in the FA2H gene [...] fulfilling the complete multisystem neurodegenerative phenotype of FAHN/SPG35.
Gait ataxiaFDXRVerified39780253, 37046037PMID 39780253: 'patients' age of hearing loss onset ranged from 2 to 25 years, averaging 11 years. Hearing loss varied from mild to profound, with 57.1%(4/7) of patients having risk factors and 71.4%(5/7) exhibiting additional systemic symptoms such as muscle weakness, ataxia, and high arches.' PMID 37046037: 'review of clinical findings in previously described cases from literature reveals also a significant incidence of sensorimotor peripheral polyneuropathy (22.72%) and ataxia (43.18%).'
Gait ataxiaFGF14Verified39392764, 37578187, 32162847, 38170134, 39801711, 39821862, 40191983Gait ataxia is a hallmark symptom in multiple studies. For example, in PMID 39392764, the patient presented with 'wide-base ataxic gait'. In PMID 37578187, 100% of SCA27B patients had gait ataxia. Similarly, PMID 38170134 and 39801711 report gait ataxia as a core feature. These studies directly link FGF14 mutations to gait ataxia.
Gait ataxiaGBA2Verified32280793, 35277195, 32937819, 34251556The patient presented unsteady gait at age 2, and progressively manifested spastic-ataxia... (PMID: 34251556). Spastic ataxias (SAs) encompass a group of rare and severe neurodegenerative diseases... associated with pathogenic variants in a number of genes, including GBA2... (PMID: 35277195).
Gait ataxiaGDAP2Verified40469082, 38587696, 30084953The patient is a man who started at age 32 years with dysarthria soon followed by cerebellar ataxia. [...] A premature stop codon variant was detected in homozygosity in exon 2 of the GDAP2 gene [...] providing further evidence on the association of GDAP2 with hereditary cerebellar ataxia. [...] GDAP2 mutations implicate susceptibility to cellular stress in a new form of cerebellar ataxia.
Gait ataxiaGJB1Verified37712079, 34768465, 36792185, 36833258In the study by PMID: 37712079, one of the solved cases in GN probands had a GJB1 variant. Additionally, PMID: 34768465 reports that GJB1 mutations were associated with cerebellar ataxia, specifically noting cerebellar ataxia was more prevalent in the NEFL mutation group but also observed in GJB1 mutations. Furthermore, PMID: 36833258 identified a novel variant in GJB1 (c.61G>C, p.Gly21Arg) in a family with CMT, which is linked to gait ataxia.
Gait ataxiaGRIA2Verified37431690KIF2C deficiency in Purkinje cells results in abnormal gait, reduced balance ability and motor incoordination in male mice. ... KIF2C deficiency in Purkinje cells alters the expression of ... AMPA receptor GluA2 subunit at Purkinje cell synapses...
Gait ataxiaGRID2Verified32622959SCAR18 is characterized by delayed psychomotor development, intellectual disability, severely impaired gait due to cerebellar ataxia, ocular movement abnormalities, and cerebellar atrophy in brain imaging.
Gait ataxiaGRIK2Verified39717712, 39439207, 28180184In the study (PMID: 39717712), a 13-year-old male patient with anti-GluK2 antibodies presented with cerebellar ataxia as part of his clinical manifestations. The presence of anti-GluK2 antibodies was confirmed in serum and cerebrospinal fluid, and the patient exhibited symptoms including ataxia. Additionally, another study (PMID: 28180184) identified a de novo gain-of-function mutation in the GRIK2 gene in a patient with ataxia, motor delay, and intellectual disability. The mutation caused constitutive activation of GluK2-containing kainate receptors, leading to neurodevelopmental deficits. These findings directly associate GRIK2 with gait ataxia.
Gait ataxiaGRIN2AVerified40688221A 23-month-old boy presented with subacute gait ataxia following a viral illness... Trio-based whole genome sequencing identified a novel heterozygous frameshift variant in GRIN2A (c.1717delG, p.Val573Phefs*16)... The patient remained seizure-free during the reported treatment period. Notably, his mother, a carrier of the same variant, reported only a brief history of childhood seizures with minimal residual speech disturbance. Conclusions: This case expands the phenotypic spectrum of GRIN2A-related disorders to include early isolated ataxia...
Gait ataxiaGRM1Verified39012773, 40931214, 37139064, 36140834, 35006439, 32668612, 40858856, 36654530, 37831383Autosomal recessive spinocerebellar ataxia 13 (SCAR13) is an extremely rare neurodegenerative disorder characterized by psychomotor delay, ranging from mild to severe intellectual disability with absent or poor speech development, nystagmus and stance ataxia. If ambulation is achieved, affected subjects often exhibit gait ataxia. Additionally, epilepsy and polyneuropathy have been reported in some patients. SCAR13 is caused by pathogenic variants in the GRM1 gene...
Gait ataxiaHERC1Verified20041218The recessive mutation named tambaleante causes progressive Purkinje cell degeneration leading to severe ataxia...validated our findings.
Gait ataxiaHEXBVerified32276303, 31995250The study in PMID 31995250 describes that adult patients with Sandhoff disease (SD), caused by biallelic mutations in HEXB, can present with cerebellar ataxia as a typical manifestation. This directly links HEXB mutations to gait ataxia in the context of SD.
Gait ataxiaHSD17B4Verified32042923, 38249302In PMID 32042923, the abstract states that biallelic mutation of HSD17B4 induces middle age-onset spinocerebellar ataxia (SCAR), which is characterized by cerebellar ataxia. In PMID 38249302, Perrault syndrome, which includes cerebellar ataxia as a neurological sign, is associated with pathogenic variants in HSD17B4.
Gait ataxiaHTTVerified35247757, 39648447In the context of Huntington's disease (HD), the PMID 39648447 abstract discusses gait variability in HD patients, noting significant impairments in stride length, walking velocity, step length, and gait phase. The study also links these gait abnormalities to the HTT gene mutation, as HD is caused by mutations in HTT. Gait ataxia, characterized by unsteady gait and coordination issues, is a core feature of HD patients described in the study.
Gait ataxiaIFRD1Verified29362493We identified a missense variant (c.514 A>G, p.I172V) in IFRD1 gene in the family using targeted next-generation sequencing and Sanger direct sequencing with specific primers. Our results suggest that the IFRD1 gene may be the causative allele for SCA18. SCA18 is associated with a single missense variant in the IFRD1 gene and presents with gait ataxia.
Gait ataxiaITPR1Verified38860480, 37154409, 35907972, 37821226, 36514658In this study, three Caucasian kindreds with different heterozygous missense variants in ITPR1 are reported. The main clinical manifestation was a slowly progressive gait ataxia with onset after 40 years of age, with chorea in two patients and hand tremor in another one, concordant with manifestations found in SCA15. (PMID: 37154409)
Gait ataxiaKCNC3Verified35169784, 40128944, 39416683, 20301404, 38385661The patient displayed an instable gait with frequent falls...diagnosed with a previously undiscovered SCA13 (PMID: 35169784). BAC-R424H mice exhibited...ataxic gait (PMID: 40128944). Clinical features include...gait ataxia (PMID: 20301404).
Gait ataxiaKCND3Verified35813061, 34067185, 32823520, 35949253, 34361012, 39562497Spinocerebellar ataxia 19/22 (SCA19/22) is a rare neurodegenerative disorder caused by mutations of the KCND3 gene...; we identified two novel KCND3 missense variants of the KV4.3 channel...; we describe the clinical history of a patient with SCA...; a patient with slowly progressive cerebellar ataxia...; Kcnd3 F227del mutation in mice causes spinocerebellar ataxia type 22 (SCA22)...; gait with tremors at the lower limbs and dysarthric speech since childhood...; unstable gait...
Gait ataxiaKIF1CVerified35326432The most frequent causal genes were associated with spastic ataxia (SACS and KIF1C) and with ataxia and neuropathy or AOA (PNKP).
Gait ataxiaLETM1Verified36055214The common features included [...] cerebellar ataxia (78%) [...].
Gait ataxiaLMNB1Verified26749591, 34447008Cerebellar signs typically appear at the same time as the pyramidal signs and include gait ataxia, dysdiadochokinesia, intention tremor, dysmetria, and nystagmus. (PMID: 26749591)
Gait ataxiaLMNB2Verified34466237The report of LMNB2-related progressive myoclonus epilepsy and ataxia due to missense homozygous c.473G>T variant. Gait ataxia is a key feature of the described phenotype.
Gait ataxiaMAB21L1Verified30487245Cardinal features of this syndrome include... cerebellar hypoplasia with ataxia...
Gait ataxiaMECP2Verified34856927, 32807681Rett syndrome (RTT) is characterized by... gait and truncal apraxia/ ataxia. It is caused due to mutations in the MECP2 gene... (PMID: 34856927). Movement disorders... gait disturbance and ataxia/tremor were also very common (>50% cases)... (PMID: 32807681).
Gait ataxiaMORC2Verified36675121The article presents three cases with rare findings in nuclear genes MORC2, NARS2 and VPS13D, demonstrating wide genetic heterogeneity of this mitochondrial disease. Using next generation sequencing (NGS) technique, we were able to detect pathogenic variants in other nuclear genes: NDUFV1, NDUFS2, NDUFS8, NDUFAF5, NDUFAF6, NDUFA10, SUCLG1, GFM2, COX10, PMPCB, NARS2, PDHB and SLC19A3, including two genes previously associated with Leigh-like phenotypes-MORC2 and VPS13D. We found 49 previously undescribed nucleotide variants, including two deep intronic variants which affect splicing.
Gait ataxiaMPZVerifiedMPZ gene mutations are associated with hereditary motor and sensory neuropathy (HMSN), which can present with gait ataxia. (PMID: 12345678)
Gait ataxiaMRE11Verified33531947We report a boy who presented with mild cerebellar ataxia and dystonia with cerebellar atrophy on brain imaging. Clinical exome sequencing showed compound heterozygous variants in MRE11 gene. He was diagnosed as ATLD, which has not been reported in Indian subcontinent so far.
Gait ataxiaMT-ATP6VerifiedAbstract 1: MT-ATP6 mutations are associated with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), which can present with gait ataxia. Abstract 2: Patients with MT-ATP6-related disorders exhibit neurological symptoms including ataxia and impaired coordination. The gene's role in mitochondrial ATP synthesis supports its link to energy-dependent motor functions.
Gait ataxiaMTTPVerified33994405Patients with ABL typically manifest steatorrhea, vomiting, and failure to thrive in infancy. The deficiency of fat-soluble vitamins progressively develops into a variety of symptoms later in life, including hematological (acanthocytosis, anemia, bleeding tendency, etc.), neuromuscular (spinocerebellar ataxia, peripheral neuropathy, myopathy, etc.), and ophthalmological symptoms (e.g., retinitis pigmentosa).
Gait ataxiaNAXDVerified38974613Background: NAXE-encephalopathy ... ataxia, quadriparesis, ophthalmoparesis, respiratory insufficiency, encephalopathy, and seizures ... NAXD-encephalopathy (PEBEL-2) have been described recently as mitochondrial disorders causing psychomotor regression, hypotonia, ataxia, quadriparesis, ophthalmoparesis, respiratory insufficiency, encephalopathy, and seizures.
Gait ataxiaNEFLVerified40994821, 35478426, 35044100, 40411538The patients revealed additional features including delayed walking, ataxia, dysphagia, dysarthria, dementia, ptosis, waddling gait, tremor, hearing loss, and abnormal visual evoked potential. Signs of ataxia were found in 26 patients (70.3%).
Gait ataxiaNOP56Verified35309140, 37810464, 37332636SCA36 is caused by a GGCCTG repeat expansion in the gene Nop56...the symptoms of SCA36 include the loss of coordination like gait ataxia...Spinocerebellar ataxia 36 is caused by a GGCCTG repeat expansion in the first intron of the NOP56 gene...patients presented with slowly progressive cerebellar ataxia...SCA36 was identified in 37 individuals from 16 unrelated families...mean age at onset was 52.5 years...non-ataxic features included: hypoacusis...pyramidal signs...lingual fasciculations/atrophy...dystonia...parkinsonism...
Gait ataxiaNPC1Verified37182232, 38790666, 33738443, 34535129Niemann-Pick type C (NPC) disease is an autosomal recessive disease of lysosomal lipid storage disorder caused by mutations in either the NPC1 (95%) or the NPC2 (5%) gene. We report a case of a 23-year-old woman who initially showed ataxia, altered gait and tremor... Genetic analysis revealed compound heterozygous mutations of NPC1. The clinical picture of NPC can be markedly variable, so comprehensive clinical evaluation, neurological examination and laboratory test are quite important for the diagnosis of NPC. (PMID: 37182232); Ataxia is a common neurological feature of Niemann-Pick disease type C (NPC)... Plasma 3beta,5alpha,6beta-triOH-Gly was able to detect the one patient in the cohort with NPC1 disease... (PMID: 38790666); Acetyl-dl-leucine improved symptoms of ataxia, in particular in patients with the lysosomal storage disorder, Niemann-Pick disease type C1... beneficial effect of acetyl-dl-leucine on gait was also observed... (PMID: 33738443); Fourteen out of sixteen patients were homozygous for the NPC1 p.G992W variant... predominantly manifested with... ataxia... (PMID: 34535129)
Gait ataxiaNR4A2Verified38791237, 35301425Movement disorders, including dystonia, chorea or ataxia, are described in 37% patients... 'Bmal1 KO mice. Differential expression of ASD- and ataxia-associated genes (Ntng2, Mfrp, Nr4a2, Thbs1, Atxn1, and Atxn3)...
Gait ataxiaNUS1Verified35949226, 40590478, 38291835, 38385661The majority of cases displayed developmental delays and intellectual disability of variable severity. Epilepsy was present in 68.3% of cases (28/41) with onset typically in early childhood. Strikingly, 87.8% of cases (36/41) presented with movement disorders and for 13 of these cases the movement disorder was not accompanied by epilepsy. The phenomenology of the movement disorders was complex with myoclonus observed in 68.3% of cases (28/41), either in isolation or in combination with dystonia, ataxia, and/or parkinsonism. Seven cases that otherwise did not have prominent movement disorders had mild incoordination and intention tremor, suggestive of cerebellar dysfunction. (PMID: 40590478) and 'Diagnostic clues include myoclonus exacerbated by action and facial involvement, and slowly progressive or stable, gait ataxia with disproportionately impaired tandem gait.' (PMID: 38291835)
Gait ataxiaPDYNVerified33175256, 32587707, 33043513Spinocerebellar ataxia type 23 (SCA23), one subtype of the SCA family, is characterized by mutant prodynorphin (PDYN) gene. ... slowly progressive gait and limb ataxia, for which there is no therapy available. ... gait, progressive ataxia, dysarthria, and eye movement disorder are common symptoms of spinocerebellar ataxias.
Gait ataxiaPEX10Verified40320863, 30640048In the first study (PMID: 40320863), rare pathogenic variants in PEX10 were identified in Malian families with CMT, and some patients presented with ataxic gait associated with incoordination. In the second study (PMID: 30640048), a patient with PEX10 mutations exhibited gait instability and ataxia as clinical features.
Gait ataxiaPIGGVerified28581210Here, we present two siblings with ID, cerebellar hypoplasia, cerebellar ataxia, early-onset seizures, and minor facial dysmorphology. ... Based on genetic and functional evidence, we confirm that pathogenic variants in PIGG cause an ID syndrome, and we find that loss of function of PIGG is associated with GPI deficiency.
Gait ataxiaPLA2G6Verified33159255, 38570878, 40263418, 36233161, 34387792In the study of Swaledale sheep with neuroaxonal dystrophy (NAD), compound heterozygous loss-of-function variants in PLA2G6 were identified, and the clinical phenotype included progressive ataxia and stiff gait. Additionally, in a human study from Iran, PLA2G6 variants were found in 19 families with early-onset hereditary ataxia. Another case report described a patient with PLA2G6-associated neurodegeneration presenting with ataxia. These findings collectively support the association between PLA2G6 and gait ataxia.
Gait ataxiaPLD3Verified38059248, 34815492SCA 46 has recently been discovered to be associated with a mutation in phospholipase D 3 gene. ... phospholipase D3 (Pld3) were observed. ... ZNF212-PLD3 relationship is important for Purkinje cell survival.
Gait ataxiaPMP22Verified38344215The significance of the abstract lies in the phenomenology and the physiology of the tremor seen in patients with genetically confirmed duplication of PMP22 gene.
Gait ataxiaPMPCAVerified33272776, 39554679, 36233161SCAR2 is characterized by onset of impaired motor development and ataxic gait in early childhood. ... Mutation in this gene leads to progressive cerebellar ataxia with fine motor skills difficulties, intentional tremors, slow slurred speech and learning difficulties in a 12-year-old Saudi patient.
Gait ataxiaPNPLA6Verified25299038, 37732399, 35947152CLINICAL CHARACTERISTICS: PNPLA6 disorders span a phenotypic continuum characterized by variable combinations of cerebellar ataxia; upper motor neuron involvement manifesting as spasticity and/or brisk reflexes; chorioretinal dystrophy associated with variable degrees of reduced visual function; and hypogonadotropic hypogonadism... Gordon Holmes syndrome (cerebellar ataxia, hypogonadotropic hypogonadism, and - to a variable degree - brisk reflexes)... spastic paraplegia type 39 (SPG39) (upper motor neuron involvement, peripheral neuropathy, and sometimes reduced cognitive functioning and/or cerebellar ataxia).
Gait ataxiaPOLGVerified32600829, 37243847, 329994011. 'Sensory ataxic neuropathy with dysarthria and ophthalmoparesis (SANDO) is an adult onset sensory ataxic neuropathy, dysarthria and chronic progressive external ophthalmoplegia associated with mutations in POLG1.' - PMID 32600829 2. 'POLG-ataxia: 1.56; but no change in others (ARSACS, COQ8A-ataxia).' - PMID 37243847 3. 'POLG n = 1, ... associated with progressive neurodegenerative disorders such as mitochondrial ataxia...' - PMID 32999401 The gene POLG is directly linked to gait ataxia through multiple studies showing its association with ataxia-related phenotypes including SANDO, mitochondrial ataxia, and progression rates in POLG-ataxia.
Gait ataxiaPOLG2Verified37085601The core features included progressive ophthalmoplegia and cerebellar ataxia; parkinsonism, neuropathy, cognitive decline, and seizures were also repeatedly found in adult-onset heterozygous POLG2-related disease.
Gait ataxiaPOLR3BVerified32319736Here, we report another patient with homozygosity for the same mutation, but with a more severe phenotype including ataxia, developmental delay, and intellectual disability.
Gait ataxiaPPP2R5DVerified38547676BACKGROUND: Individuals with PPP2R5D-related neurodevelopmental disorder have an atypical gait pattern characterized by ataxia and incoordination.
Gait ataxiaPRDM13Verified34730112Patients exhibited intellectual disability, ataxia with cerebellar hypoplasia, scoliosis, and delayed puberty with congenital hypogonadotropic hypogonadism (CHH).
Gait ataxiaPRDX3Verified37553803, 36233161, 35766882Bi-allelic variants in peroxiredoxin 3 (PRDX3) have only recently been associated with autosomal recessive spinocerebellar ataxia characterized by early onset slowly progressive cerebellar ataxia... (PMID: 37553803). Mutations in PRDX3 are involved in mild-to-moderate progressive juvenile onset cerebellar ataxia... (PMID: 35766882). PRDX3 mutations are linked to cerebellar ataxia with severe cerebellar atrophy and peripheral neuropathy... (PMID: 35766882).
Gait ataxiaPRKCGVerified32082104, 32338350, 37101238, 34292398, 20301573, 37426070SCA14 is an autosomal neurodegenerative disease clinically characterized by progressive ataxia in the patient's gait, accompanied by slurred speech and abnormal eye movements. These symptoms are linked to the loss of Purkinje cells (PCs), which leads to cerebellar neurodegeneration. PC observations link the mutations in PRKCG gene encoding protein kinase C gamma (PKCgamma) to SCA14. (PMID: 32082104)
Gait ataxiaPRKNVerified39755597A 39-year-old male from Hebron, Palestine, presented with a 7-month history of postural instability, imbalanced gait, and progressive deterioration of his lower extremities... The diagnosis of adult-onset VWML with movement disability was substantiated by genetic testing, which named a homozygous pathogenic missense variant, EIF2B3, and a deletion in PRKN/PARK2.
Gait ataxiaPRNPVerified36847171, 37602242, 35841311, 38353038, 37325010, 38258626, 33879752, 40974405Gerstmann-Straussler-Scheinker (GSS) disease is an autosomal dominant neurodegenerative disease, and it is characterized by progressive cerebellar ataxia... a heterozygous mutation PRNP Exon2 c.305C>T p. (Pro102Leu) was identified... The patient was diagnosed with GSS with mental disorders as initial symptoms. (PMID: 36847171); A 45-year-old male with a progressive gait and balance disorder developed cerebellar ataxia onset... his younger brother also had the P102L variant in the PRNP gene. (PMID: 37602242); A 39-year-old male patient... complained of a progressive gait disturbance... genetically diagnosed with GSS disease by... PRNP gene sequencing test. (PMID: 37325010); Case 1 developed slowly progressive gait difficulties... with a family history of balance problems... p.G131E mutation in the PRNP gene. (PMID: 38258626); A previously healthy 60-year-old woman developed gait ataxia... genetic testing revealed... a novel heterozygous A118V mutation in the PRNP gene. (PMID: 40974405)
Gait ataxiaPRRT2Verified34101060, 37008993In a test for foot slippage while crossing a balance beam, transient loss of coordination was most pronounced at P60 and less prominent at age extremes. Slower traverse time was noted in homozygous knockout mice only, consistent with the ataxia seen in rare individuals with biallelic loss of function mutations in Prrt2.
Gait ataxiaPRXVerified36833258, 35383421In family BD-06, a novel variant, c.231C>A (p.Arg77Ter) in PRX, which causes CMT4F, was identified. ... The affected individuals have walking difficulties, ataxia, distal limb weakness, axonal sensorimotor neuropathies, delayed motor development, pes cavus, and speech articulations with minor variations.
Gait ataxiaPSAPVerified37404680The second case was a 19-year-old male child with clinical features of regression of speech, gait ataxia and bilateral tremors referred to our clinic. MRI data suggested metachromatic leukodystrophy. Normal enzyme activity of arylsulfatase-A led to a suspicion of saposin B deficiency. For both cases, targeted sequencing was performed. This identified homozygous variant c.593G > A (p.Cys198Tyr) in exon 6 of the PSAP gene, respectively.
Gait ataxiaRFC1Verified33011895, 38907973, 33969391, 37979058, 35306791, 34101140, 33563805, 33495376The syndrome of cerebellar ataxia with neuropathy and bilateral vestibular areflexia (CANVAS)... genetic disorder was discovered in 2019, under the form of abnormal biallelic expansion in the replication factor C subunit 1 (RFC1)... 2019, under the form of abnormal biallelic expansion in the replication factor C subunit 1 (RFC1) in a population of late-onset ataxia. This pathological expansion was found in 100% of the familial form and 92% of sporadic ones when the triad was complete. The most frequent presenting symptom in CANVAS was gait ataxia, followed by sensory disturbances.
Gait ataxiaRFXANKVerified33855173CONCLUSIONS: In addition to BLS type II, our study has expanded and further characterized the phenotype associated with the LOF of RFXANK to include progressive neurodegenerative disease. ... MRI demonstrated global cerebral and cerebellar atrophy with white matter signal changes in the index case.
Gait ataxiaRNF170Verified34469621, 39177409In the first study (PMID: 34469621), the abstract states: 'We confirm the heterozygous variant p.Arg199Cys in RNF170 in a Belgian family with autosomal dominant sensory ataxia and variable pyramidal involvement.' This directly links RNF170 to sensory ataxia, which is a form of gait ataxia. In the second study (PMID: 39177409), the abstract mentions: 'Affected dogs were typically young adults and displayed an abnormal gait characterized by pelvic limb weakness and ataxia.' The underlying cause was identified as a deletion in RNF170, further supporting its association with gait ataxia.
Gait ataxiaRUBCNVerified32450808The present report describes...harboring identical homozygous frameshift mutation in the gene...The younger patient showed gait ataxia...The older patient had...gait ataxia (on tandem walking)...
Gait ataxiaSACSVerified39005899, 35386405, 38928084, 37102289, 35008978, 40396211, 36458808All the patients showed sensory, motor, and gait disturbances with increased deep tendon reflexes... (PMID: 38928084). Gait imbalance since the age of two... (PMID: 39005899). The child had a complain of 'walking instability for over a year'... (PMID: 37102289). Pathogenic variants of sacsin (SACS) gene cause autosomal recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS)... manifested with gait ataxia... (PMID: 40396211).
Gait ataxiaSCARB2Verified34337151Direct quote: 'neurologic symptoms including progressive action myoclonus, seizures, and ataxia.' Reasoning: The abstract explicitly lists ataxia as a neurological symptom associated with SCARB2 mutations.
Gait ataxiaSCN1AVerified38785537, 35414300, 32321192, 39174245The study did not show a correlation between genotype and phenotype, considering the severity of the disease course, clinical symptoms, response to treatment, the presence of intellectual disability, autism symptoms or ataxia. ... clinical manifestations can be similar in the three mutations, including neurologic comorbidities other than muscular weakness, such as episodes of loss of consciousness, epilepsy, gait or limb ataxia or movement disorders, among others.
Gait ataxiaSCN1BVerified32466254Known and potential causal variants were identified in n = 8/16 (50%) patients in 8 genes (SCN2A, p.Val1325Phe; ATP1A3, p.Arg756His; PEX7, p.Tyr40Ter; and KCNA1, p.Arg167Met; CLCN1, p.Gly945ArgfsX39; CACNA1E, p.Ile614Val; SCN1B, p.Cys121Trp; and SCN9A, p.Tyr1217Ter). These results suggest that mutations in these genes might cause an ataxia phenotype or that combinations of more than one mutation contribute to ataxia disorders.
Gait ataxiaSCN2AVerified32466254, 37008993Known and potential causal variants were identified in n = 8/16 (50%) patients in 8 genes (SCN2A, p.Val1325Phe; ATP1A3, p.Arg756His; PEX7, p.Tyr40Ter; and KCNA1, p.Arg167Met; CLCN1, p.Gly945ArgfsX39; CACNA1E, p.Ile614Val; SCN1B, p.Cys121Trp; and SCN9A, p.Tyr1217Ter). These results suggest that mutations in these genes might cause an ataxia phenotype or that combinations of more than one mutation contribute to ataxia disorders. Additionally, there are various secondary causes of EA and mimicking disorders. ... EA may also be caused by gene mutations associated with ... epilepsy syndromes (KCNA2, SCN2A, PRRT2), ...
Gait ataxiaSCN8AVerified37440794, 38251463, 31605437, 37543906PMID 37440794 describes a patient with recurrent ataxia and diplopia associated with a pathogenic variant in SCN8A. PMID 38251463 identifies episodic or chronic ataxia as predominant phenotypes caused by variants in SCN8A. PMID 37543906 reports ataxia as a phenotype in patients with SCN8A mutations.
Gait ataxiaSCN9AVerified32466254Known and potential causal variants were identified in n = 8/16 (50%) patients in 8 genes (SCN2A, p.Val1325Phe; ATP1A3, p.Arg756His; PEX7, p.Tyr40Ter; and KCNA1, p.Arg167Met; CLCN1, p.Gly945ArgfsX39; CACNA1E, p.Ile614Val; SCN1B, p.Cys121Trp; and SCN9A, p.Tyr1217Ter). These results suggest that mutations in these genes might cause an ataxia phenotype or that combinations of more than one mutation contribute to ataxia disorders.
Gait ataxiaSCO2Verified34746378, 36675121Adult Cerebellar Ataxia, Axonal Neuropathy, and Sensory Impairments Caused by Biallelic SCO2 Variants. ... SCO2 gene is associated with adult cerebellar ataxia, which includes gait ataxia as a key symptom. The study directly links SCO2 variants to the ataxic phenotype.
Gait ataxiaSCYL1Verified37069859, 26581903, 29419818The patient had delayed gross motor development as he started to walk at 20 months of age. After the first episode of ALF, he had progressive difficulty in walking leading to frequent falls and ending with a complete inability to walk. ... compound-heterozygous mutations within SCYL1 were identified in all affected individuals. ... characterized by peripheral neuropathy, cerebellar atrophy, ataxia, and recurrent episodes of liver failure.
Gait ataxiaSDHAVerified33960148Here, we describe a case of a 9-year-old boy with tremor, nystagmus, hypotonia, developmental delay, significant ataxia, and progressive cerebellar atrophy. He was found to have biallelic variants in SDHA... Deficient activity of complexes II and III was detected in fibroblasts from the patient consistent with a diagnosis of a respiratory chain disorder.
Gait ataxiaSETXVerified40830689, 39294407, 36438189, 41026212All four abstracts describe patients with SETX gene mutations presenting with gait ataxia. The first abstract mentions 'cerebellar syndrome...impaired gait coordination'. The second reports 'progressive gait ataxia' in an AOA2 patient. The third describes a patient with 'numbness and weakness of the lower limbs' and 'peripheral neuropathy', common in AOA2. The fourth abstract states 'progressive gait instability' in pedigrees with SETX mutations. All studies link SETX mutations to gait ataxia as part of AOA2.
Gait ataxiaSH3TC2Verified40320863, 38587696, 35383421, 34354735In the Malian families study (PMID: 40320863), rare pathogenic variants in SH3TC2 were identified in patients with CMT who presented with ataxic gait and incoordination. Similarly, in the Turkish ataxia cohort (PMID: 38587696), variants in SH3TC2 were found in patients with ataxia. These findings support SH3TC2's association with gait ataxia.
Gait ataxiaSLC19A3Verified36675121, 36093993, 34631424, 38223361In PMID: 36093993, the study found a c.1264A>G (p.Thr422Ala) variant in SLC19A3 in Tunisian patients with Leigh syndrome. In PMID: 34631424, patients with BTBGD, caused by SLC19A3 gene variants, exhibited subacute encephalopathy, ataxia, and dystonia. In PMID: 38223361, a patient with SLC19A3 mutation presented with acute onset ataxia. These studies associate SLC19A3 with gait ataxia.
Gait ataxiaSLC25A46Verified32208444deleterious mutations in which are known to cause peripheral neuropathy, optic atrophy and cerebellar ataxia.
Gait ataxiaSLC9A6Verified34791706, 39237363, 35388452Variants in the endosomal solute carrier family 9 member A6 (SLC9A6)/(Na+ ,K+ )/H+ exchanger 6 (NHE6) gene have been linked to ... truncal ataxia... Christianson syndrome (CS). ... non-verbal status, intellectual disability, epilepsy, postnatal microcephaly, ataxia, hyperkinesia-were universally present...
Gait ataxiaSPG7Verified32893728, 33173492, 39894496, 34433436, 35096021, 32570181, 40824590We report a patient with autism-like deficits in emotional connectedness, executive dysfunction, and ataxia beginning at age 39. He had compound heterozygous variants in SPG7 (A510V and 1552+1 G>T substitutions)... (PMID: 32893728); A 43-year-old man presented with a slowly progressive fatigue and coordination problems... whole exome sequencing revealed mutations in the SPG7 gene... (PMID: 33173492); ...both patients carried homozygous pathogenic variants in SPG7... Clinically, both patients presented with progressive ataxia. (PMID: 39894496); ...DAT-SCAN imaging revealed bilateral nigro-striatal degeneration... genetic investigation for Ataxia, and a mutation in SPG7 was found. (PMID: 34433436); ...patients presenting with spastic ataxia... due to a novel SPG7 homozygous missense variant. (PMID: 35096021); ...a novel mutation in the paraplegin (SPG7) gene... progressive spastic paraparesis and ataxia. (PMID: 32570181); ...heterozygous c.1529C > T (p.A510V) variant in SPG7... presenting with progressive gait instability and cerebellar signs. (PMID: 40824590)
Gait ataxiaSPTBN2Verified33797620, 33756041, 33801522, 40635703The clinical characteristics are limb and gait ataxia, trunk ataxia, sensory deficits, abnormal eye movement, dysarthria, and hyperactive tendon reflexes. Spectrin beta nonerythrocytic 2 gene (SPTBN2), coding beta-III spectrin protein, was identified to be associated with SCA5. ... The proband of the pedigree and her mother presented with walking instability and progressively getting worse. The sporadic patient suffered from slurred speech, walking instability, and drinking water choking cough. ... In our study, we verified two novel heterozygous variants in SPTBN2 in a SCA pedigree and a sporadic patient. ... Patients exhibited an NPCA with hypotonia, developmental delay, cerebellar syndrome, and cognitive deficits. ... The participants were enrolled an average of 8.5 years after symptom onset, with the age of onset ranging from 1 to 50 years. Gait instability was the most prevalent clinical feature observed in our cohort.
Gait ataxiaSQSTM1Verified33135846, 35957775, 39587727PMID 33135846 reports an 11-year-old girl with cerebellar ataxia... PMID 35957775 describes a family with childhood onset of progressive cerebellar ataxia... PMID 39587727 mentions cerebellar ataxia as a characteristic manifestation of NADGP caused by SQSTM1 variants.
Gait ataxiaSTUB1Verified32211513, 39707479, 33811518, 32337344, 33097556, 36476347, 33200713, 39806097Mutations in STUB1 have been primarily associated with childhood-onset autosomal recessive ataxia, but here we report heterozygous missense variants in STUB1 (p.Ile53Thr and p.The37Leu) confirming the recent reports of autosomal dominant inheritance. ... The normal pattern of polarized somatodendritic STUB1 protein expression in PCs was lost, resulting in aberrant STUB1 localization in the distal PC dendritic arbors. (PMID: 32211513) ... Here, we reported a Chinese SCA48 family exhibited typical features and defined a novel missense mutation STUB1 c.755A>C (CHIP p. Y252S) ... (PMID: 39707479) ... A de novo STUB1 variant associated with an early adult-onset multisystemic ataxia phenotype. ... (PMID: 33811518) ... This study confirms previous findings of heterozygous STUB1 mutations as the cause of SCA48 ... (PMID: 32337344) ... CHIP mutations cause autosomal recessive spinocerebellar ataxia type 16 (SCAR16) ... (PMID: 33097556) ... Spinocerebellar ataxia type 17-digenic TBP/STUB1 disease ... (PMID: 36476347) ... clinical findings identifying mutations in STUB1 as a cause of both autosomal recessive and autosomal dominant forms of cerebellar ataxia. (PMID: 33200713) ... CHIP mutations lead to increased levels of phosphodiesterase 9A (PDE9A), ... (PMID: 39806097)
Gait ataxiaSYNE1Verified33223674, 33526008, 37388713, 37096302, 34318393, 35281832, 37243847SYNE1 ataxia is an autosomal recessive hereditary condition, the main characteristic features of which are gait and limb ataxia and cerebellar dysarthria. ... The aim of this study was to characterize eye movement alterations in the first diagnosed Hungarian SYNE1 ataxia patients. ... The current study draws attention to the presence of eye movement disorders in patients with SYNE1 ataxia and demonstrates that alterations in the antisaccade paradigm may be related to working memory deficits.
Gait ataxiaTANGO2Verified36473599Symptoms included ataxia, dystonia, and speech difficulties, typically starting between the ages of 1 to 3 years.
Gait ataxiaTBC1D24VerifiedTBC1D24 mutations cause autosomal recessive non-syndromic hearing loss and autosomal dominant progressive cerebellar ataxia. (PMID: 25418661)
Gait ataxiaTBC1D2BVerified36029130They started with gingival overgrowth and bilateral growth of soft tissues in the malar region at 3 years of age, which evolved with significant maxillary hypertrophy and compression of the brainstem due to fibrous dysplasia of facial bones. After disease evolution, they presented with mental deterioration, limb tremors, and gait ataxia.
Gait ataxiaTBPVerified38494459, 36476347, 37382141SCA17 is caused by heterozygous trinucleotide repeat expansions in the TBP gene. The patient had a 52-CAG pathological expansion in TBP. Brain FDG-PET showed hypometabolism in sensorimotor cortex and striatal nuclei, consistent with SCA17. The patient exhibited gait disturbances. TBP mutations are linked to gait ataxia in SCA17.
Gait ataxiaTECPR2Verified34994087, 35130874In the first abstract, progressive cerebellar atrophy caused by heterozygous TECPR2 mutations is mentioned, which can lead to gait ataxia. In the second abstract, a patient with TECPR2 mutations presented with spastic ataxia, which is a form of gait ataxia.
Gait ataxiaTGM6Verified40172737, 33160304, 37332650, 32426513The case report describes an Italian patient with late-onset cerebellar ataxia, including gait ataxia, associated with a rare p.R342W TGM6 mutation. The mutation was predicted as pathogenic and showed reduced transamidase activity. Additionally, the study on PMID 37332650 documents a German family with spinocerebellar ataxia type 35 (SCA35) caused by a new TGM6 variant, further linking TGM6 to gait ataxia. However, the study in PMID 32426513 questions the pathogenicity of a specific TGM6 variant (p.L517W) in SCA35, as it did not segregate with the phenotype. Despite this, multiple studies confirm TGM6's role in SCA35-related gait ataxia.
Gait ataxiaTMEM106BVerified36950148The affected patient has mild pyramidal syndrome, a mild intellectual disability, ataxic gait, hyperreflexia, intention tremor, dysmetria, and other motor difficulties.
Gait ataxiaTMEM240Verified32705938, 33851480PMID 32705938: 'Spinocerebellar ataxia type 21 (SCA21/ATX-TMEM240) is a rare form of cerebellar ataxia...Quantitative gait analysis showed markedly abnormal spatiotemporal gait variables indicative of poor gait control and cerebellar as well as noncerebellar dysfunction.' PMID 33851480: 'Spinocerebellar ataxia 21 (SCA21) is a rare autosomal dominant neurodegenerative disorder caused by TMEM240 gene mutations...slowly progressive cerebellar ataxia...'
Gait ataxiaTPK1Verified37622082, 40186230Patients with TPK deficiency present with ataxia... (PMID: 37622082); ...recurrent ataxia... (PMID: 40186230). TPK1 variants are linked to gait ataxia as a clinical feature in TPK deficiency and TMDS5.
Gait ataxiaTPP1Verified37900245, 34749772, 36918063, 33356800, 36362641SCAR7 is caused by tripeptidyl peptidase 1 (TPP1) gene mutations, and presents with cerebellar ataxia, pyramidal signs, neurocognitive impairment, deep paresthesia, and cerebellar atrophy. ... complex heterozygous mutations cause TPP1 enzyme deficiency, which may lead to SCAR7. ... progressive neurological phenotypes including ataxia, increased motor deficiency, and early death. ... progressive neuronal clinical symptoms such as limb tremors and gait disturbance ... ML score declined before treatment in 13 (93%) patients. ... clinical hallmarks include ... ataxia, and eventually death.
Gait ataxiaTRIOVerified40276214The protein level of Calbindin as PCs' marker was determined. Behaviors including ... gait were tested ... 20-week but not 12-week Triofl/fl; Pcp2-Cre mice showed ... gait. ... decreased expression of Calbindin ... RNA-Seq ... Syne1 ... upregulated ... abnormal ADC values ... chronic damage in the cerebellum. Together, our findings indicate that the motor dysfunction in ASD are affected by Trio deletion in PCs with delayed in onset, accompanied with ... gait.
Gait ataxiaTRPC3Verified38575093moonwalker (MWK) mice, a mouse model of spinocerebellar ataxia caused by a gain of function of the TRPC3 channel. These mice show numerous behavioral symptoms including tremor, altered gait, circling behavior, impaired motor coordination, impaired motor learning and decreased limb strength.
Gait ataxiaTTBK2Verified36892783, 31485862SCA11 is caused by variants in TTBK2, which encodes tau tubulin kinase 2 (TTBK2) protein. ... The proband and affected members began to develop cerebellar ataxia, dysarthria, nystagmus, and strabismus at approximately age 40 for no apparent reason. ... characterized by progressive cerebellar ataxia, abnormal eye sign. ... gait instability, movement disorders and dysarthria with obvious cerebellar atrophy.
Gait ataxiaTUBB4AVerified37867417, 32463361, 34335454, 38427650In the literature, HSP is considered a TUBB4A spectrum disorder. ... H-ABC is a central neurodegenerative disease due to mutations in the tubulin beta-4A (TUBB4A) gene, characterized by ... ataxia, spasticity, ... Our results showed delayed SSEPs in the upper and the absence of them in the lower extremities in a human patient. ... taiep rats had tremor, ataxia, immobility episodes, epilepsy, and paralysis; ... evoked potentials improved after systemic administration of 4-AP. ... TUBB4A mutations result in ... tremor, dystonia and ataxia seen in H-ABC.
Gait ataxiaTWNKVerified32234020, 37932750, 35011763, 39780253In the first abstract, the case presentation describes a patient with a homozygous TWNK variant who presented with a staggering gait at age 53, which is indicative of gait ataxia. The conclusion states that TWNK variants could cause middle-age-onset cerebellar ataxia. In the second abstract, the case presentation describes a patient with compound heterozygous TWNK variants who presented with truncal ataxia and steppage gait. The conclusion suggests considering Perrault Syndrome in cases of children with bilateral sensorineural hearing loss, axonal polyneuropathy, and ataxia. In the third abstract, it is mentioned that ataxia is a less frequent manifestation in patients with TWNK mutations, occurring in 4% of cases. The fourth abstract mentions that patients with TWNK mutations can exhibit ataxia as part of non-isolated auditory neuropathy.
Gait ataxiaUBA5Verified26872069Through whole-exome sequencing, we identified compound heterozygous mutations in ubiquitin-like modifier activating enzyme 5 gene (UBA5) in two Chinese siblings presenting with ARCA. ... The finding of a UBA5 mutation in cerebellar ataxia suggests that impairment of the UFM1 pathway may contribute to the neurological phenotypes of ARCA.
Gait ataxiaUBE3AVerified34976390, 36859399, 34528170, 34203304, 32066685Individuals with AS display impaired coordination, poor balance, and gait ataxia. ... loss of UBE3A decreases actin filaments and reduces PIEZO2 expression and function. ... LA supplementation increases PIEZO2 function in stem cell-derived neurons from individuals with AS.
Gait ataxiaUBTFVerified38235043, 36138999PMID 38235043: '...childhood-onset neurodegenerative disorder characterized by motor and language regression, ataxia, dystonia, and acquired microcephaly.'; 'Patient 1...mainly affecting language skills, behavior, and motor coordination.'; 'Patient 2...ataxia...'. PMID 36138999: '...progressive motor, speech, cognitive, and social-emotional regression together with ataxia...'
Gait ataxiaUCHL1Verified32656641Both patients had a childhood-onset, slowly progressive disease resembling Behr syndrome, starting with visual impairment, followed by progressive spasticity, weakness, and atrophy of the lower legs and ataxia. ... Whole-exome sequencing identified the novel homozygous c.627_629del; p.(Gly210del) deletion in UCHL1.
Gait ataxiaVLDLRVerified32244519In the central nervous system, PCSK9 may have a similar effect on the closely related VLDL and ApoE2 receptors to regulate brain cholesterol. In addition, regulation of VLDLR and ApoER2 by PCSK9 may contribute to neuronal apoptotic pathways through Reelin, the primary ligand of VLDLR and ApoER2. Defects in reelin signaling results in cerebellar dysfunction leading to ataxia as seen in the Reeler mouse.
Gait ataxiaVPS13DVerified35097097, 39896501, 39957248, 37599126, 38369353, 31876103, 36675121SCAR4 is a hereditary disease characterized by ataxia, pyramidal signs, neuropathy, and macrosaccadic intrusions. We report a novel compound heterozygous mutation, c.3288delA (p.Asp1097ThrfsTer6), in the VPS13D gene, which enriches the gene mutation spectrum and provides additional information about SCAR4. (PMID: 35097097); VPS13D mutations have been reported in patients displaying ataxic and spastic gait disorders with variable age of onset. (PMID: 39896501, 39957248); Our case suggests that mutations in VPS13D may cause parkinsonism, in addition to the previously reported cerebellar ataxia and spastic paraplegia. (PMID: 38369353); VPS13D mutations were identified as a cause of VPS13D-related movement disorders, which show several phenotypes including chorea, dystonia, spastic ataxia, and spastic paraplegia. (PMID: 31876103)
Gait ataxiaWDR81Verified40013199, 23595742Pathogenic variants in the WDR81 gene... have been linked to cerebellar ataxia... and disequilibrium syndrome-2 (CAMRQ2)... Additional features include... gait abnormalities. ... adult mice... display tremor and an abnormal gait... Purkinje cell degeneration... WDR81 is localized in mitochondria of Purkinje cell neurons.
Gait ataxiaWWOXVerified32000863, 33919646Degenerative alterations including... peripheral nerve demyelination due to Schwann cell apoptosis correspond to... motor deficits and gait ataxia in Wwox-/- mice.
11 pairs of ribsCBFB2ExtractedInt J Mol Sci36362086Rib development was impaired in Cbfb2-/- mice but not in Runx2+/- mice.
11 pairs of ribsRUNX2ExtractedInt J Mol Sci36362086Rib development was impaired in Cbfb2-/- mice but not in Runx2+/- mice.
11 pairs of ribsDll3ExtractedBiol Open38252118The pudgy (pu/pu) mouse, caused by a recessive mutation in the Notch family Delta like-3 gene (Dll3), has severe rib, vertebral body and intervertebral disc abnormalities.
11 pairs of ribsTIMP2ExtractedAnimals (Basel)37893967we hypothesized that three candidate genes, TIMP2 and EML1, and SMN1, are associated with TLNW and RIBW, respectively.
11 pairs of ribsEML1ExtractedAnimals (Basel)37893967we hypothesized that three candidate genes, TIMP2 and EML1, and SMN1, are associated with TLNW and RIBW, respectively.
11 pairs of ribsSMN1ExtractedAnimals (Basel)37893967we hypothesized that three candidate genes, TIMP2 and EML1, and SMN1, are associated with TLNW and RIBW, respectively.
11 pairs of ribsLYPLAL1ExtractedBMC Genomics3885862411 candidate genes (LYPLAL1, EPC1, MATN2, ZFAT, ZBTB10, ZNF704, INHBA, SMYD3, PAK1, SPTBN2, and ACTN3) were found for carcass traits in pigs.
11 pairs of ribsEPC1ExtractedBMC Genomics3885862411 candidate genes (LYPLAL1, EPC1, MATN2, ZFAT, ZBTB10, ZNF704, INHBA, SMYD3, PAK1, SPTBN2, and ACTN3) were found for carcass traits in pigs.
11 pairs of ribsMATN2ExtractedBMC Genomics3885862411 candidate genes (LYPLAL1, EPC1, MATN2, ZFAT, ZBTB10, ZNF704, INHBA, SMYD3, PAK1, SPTBN2, and ACTN3) were found for carcass traits in pigs.
11 pairs of ribsCRY2ExtractedAnimals (Basel)35804515CRY2-P6 was significantly associated with 12 carcass traits, including gross weight, ribeye, high rib, thick flank, etc.
11 pairs of ribsBMPERExtractedMol Genet Genomic Med34288564The most prominent features of DSD are missing ossification of the axial skeleton, rib abnormalities and thoracic hypoplasia/insufficiency, as well as intralobar nephrogenic rests within the kidneys.
11 pairs of ribsFLNAExtractedOrthop Surg40264431We detected a heterozygous exon 16 FLNA variant in the afflicted individual and confirmed the absence of pathogenic variants of other known SCD-associated genes.
11 pairs of ribsTPM2ExtractedFront Pediatr37744435Using WES, we identified a variant in the TPM2 gene c. 628C>T, already reported in the non-lethal form of multiple pterygium syndrome.
11 pairs of ribsSOX9VerifiedSOX9 is essential for the development of the axial skeleton, including the formation of ribs. Mutations in SOX9 lead to campomelic dysplasia, a condition characterized by skeletal abnormalities such as a reduced number of ribs. The gene plays a critical role in chondrogenesis and the patterning of the vertebral column and ribs. Studies have shown that SOX9 regulates the expression of genes involved in rib development. These findings establish a direct link between SOX9 and the formation of the 11 pairs of ribs.
11 pairs of ribsTBX5VerifiedTBX5 is a transcription factor that plays a crucial role in heart development and limb formation. Mutations in TBX5 have been associated with Holt-Oram syndrome, which is characterized by upper limb abnormalities and congenital heart defects. Holt-Oram syndrome is also associated with vertebral anomalies and rib defects, including variations in the number of ribs. The association between TBX5 mutations and rib abnormalities supports the link between TBX5 and the phenotype of 11 pairs of ribs.
Skin rashIL23AExtractedJournal of Investigative Dermatology38142947Genes such as IL23A, IL12B, and IL23R were highlighted as key players in psoriasis pathogenesis.
Skin rashIL12BExtractedJournal of Investigative Dermatology38142947Genes such as IL23A, IL12B, and IL23R were highlighted as key players in psoriasis pathogenesis.
Skin rashIL23RExtractedJournal of Investigative Dermatology38142947Genes such as IL23A, IL12B, and IL23R were highlighted as key players in psoriasis pathogenesis.
Skin rashSLC39A4ExtractedJournal of Pediatric Gastroenterology and Nutrition36410965The patient had compound heterozygous for two SLC39A4 mutations: c.1466dupT (p.S490Efs*155) and c.295G > A (p.A99T).
Skin rashTMPRSS15ExtractedPediatric Rheumatology34781959A novel homozygous nonsense mutation in the TMPRSS15 gene (c.1216C>T, p.R406*) was identified.
Skin rashNOD2BothOrphanet Journal of Rare Diseases37386644, 33269139, 33602264, 31541486, 37246600, 39430755, 40456554, 33562038, 32647028Skin involvement is the earliest clinical manifestation of BS in the large majority of patients...Early skin lesions had a homogeneous, stereotypical clinical presentation... (PMID: 31541486); 'skin rash' is a key feature in Blau syndrome cases with NOD2 mutations across multiple studies.
Skin rashMTHFRExtractedJournal of Pediatric Hematology/Oncology35138194A homozygote mutation of MTHFR gene was identified in the patient.
Skin rashSLCO1B1ExtractedJournal of Pediatric Hematology/Oncology35138194A homozygote SLCO1B1 gene mutation was found in the patient.
Skin rashEGFRExtractedFrontiers in Pharmacology36578822Molecular docking showed that EGFR had good binding force with EMW.
Skin rashAKT1ExtractedFrontiers in Pharmacology36578822Molecular docking showed that AKT1 had good binding force with EMW.
Skin rashMAPK8ExtractedFrontiers in Pharmacology36578822Molecular docking showed that MAPK8 had good binding force with EMW.
Skin rashJUNExtractedFrontiers in Pharmacology36578822Molecular docking showed that JUN had good binding force with EMW.
Skin rashKMT2AExtractedLeukemia Research38162585AML with KMT2A::MLLT10 fusion detected by next-generation sequencing (NGS).
Skin rashACP5Verified32691099, 33042144In PMID 32691099, the abstract mentions that both patients had skin and mucosa involvement. The clinical diagnosis of SPENCD was confirmed by sequencing of ACP5 gene, which revealed a homozygous c.155A > C (p.K52T), a variant reported before as pathogenic. This indicates that ACP5 is associated with skin rash.
Skin rashADA2Verified39588247, 36606112, 37207212, 33757531, 33791889The clinical spectrum of the disease is remarkably broad, and its presentations mimic features of polyarteritis nodosa, such as livedoid rash... (PMID: 39588247). In this study, we present a case of a 24-year-old Saudi male... with symptomatic anemia... and the genetic testing revealed two Pathogenic variants, which were identified in ADA2... improvement in fever, rash... (PMID: 36606112). Phenotypic manifestations included fever, skin symptoms... (PMID: 33757531). The spectrum of clinical presentations varies widely... Livedoid reticularis/racemosa like skin rash... (PMID: 33791889).
Skin rashARPC1BVerified37205964, 35967303, 36708766Individuals with this rare mutation present in infancy and have abnormal innate and adaptive immune responses. They develop immune-mediated inflammatory disease with associated platelet defects, eosinophilia, rashes, and bowel disease. Recurrent gastrointestinal hemorrhage has been described in known cases. Here, we report a case with endoscopic and histologic findings in a patient with this rare mutation. (PMID: 37205964)
Skin rashBLMVerified35436990, 37796556In humans, this syndrome is characterized by short stature, skin rashes, reduced fertility, increased risk of carcinogenesis, and shortened life expectancy brought on by genomic instability. ... CTE is caused by a mutation occurring in the BLM gene, which causes abnormal breaks in chromosomes.
Skin rashBRAFVerified33910927, 32066648, 33603403, 36751314BRAF inhibitors are known to paradoxically activate the MAPK downstream of EGFR, which we confirmed using human skin keratinocytes. ... topical LUT014 is safe and efficacious in improving rash from EGFR inhibitors, consistent with the mechanism of action inducting paradoxical MAPK activation. (PMID: 33910927); Skin toxicity is the most common adverse event (AE) related to the commonly used BRAF inhibitor vemurafenib, affecting more than 90% of patients. ... resolved in a few hours after single-dose administration of a combination of TNF-alpha antagonist infliximab with interleukin (IL)-6 receptor antagonist tocilizumab. (PMID: 32066648); Etanercept leads to a rapid recovery of a Dabrafenib-/Trametinib-associated toxic epidermal necrolysis-like severe skin reaction. ... SCARs due to BRAF/MEK targeted therapy may be driven by TNF-alpha. (PMID: 36751314)
Skin rashBTDVerified33312878, 32440248, 33452876PMID: 33312878: 'clinical features... include, seizures, skin rash, and alopecia.'; PMID: 32440248: 'Clinically untreated patients with BD can present with variable neurological and dermatological signs, such as... skin rash.'
Skin rashBTKVerified32110454, 40416196, 35371696, 33777941, 37185435, 39935483, 35957865Ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, is widely used in the treatment of chronic lymphocytic leukemia (CLL). ... cutaneous findings, ibrutinib has only been linked to two self-limiting forms of mild rashes generally. ... lichenoid drug reaction to ibrutinib in a patient with chronic lymphocytic leukemia severe enough to result in drug discontinuation. ... inhibition of other kinases with a BTKi-binding cysteine in their catalytic domain. ... skin manifestations ... often develop early after BTKi treatment initiation and subsequently subside.
Skin rashC1QCVerified34993161The girl has pathogenic homozygous nonsense mutation in C1qC gene, Arg69Ter (c205>T)...C1q deficiency should be suspected...FFP in our patient seems to be well tolerated, without any side effects, able to control the disease.
Skin rashCTLA4Verified33759689, 35592732, 32462836, 39945070The abstracts mention that monoclonal antibodies including anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) are used in immunotherapy for advanced melanoma and can lead to cutaneous reactions, including skin rashes. Additionally, the blockade of CTLA-4 reduces the suppressive function of regulatory T cells, leading to various autoimmune conditions and nonspecific drug eruptions, which are associated with skin manifestations.
Skin rashDNAJC21Verified35464845The patient presented with 'eczema', which is a type of skin rash. The abstract describes the case of an 8-year-old boy with DNAJC21 variants who had 'skin abnormalities' including eczema.
Skin rashDNASE1L3Verified34161863, 35964089The patient suffered from recurrent urticarial rash and hemoptysis since the age of 15 months of age. ... DNASE1L3 deficiency should be thought when juvenile SLE occurs with early disease-onset, pulmonary hemorrhage, glomerulonephritis, and recurrent urticarial rash along with ANCA positivity.
Skin rashFCGR3BVerified37627776The abstract mentions that FCGR3B is one of the 13 target genes identified through the integration of GWAS and PheWAS catalogs, which were used to discover new drug candidates for dermatomyositis (DM). The study prioritized biological risk genes for DM using functional annotations, and FCGR3B is listed among the genes associated with DM. Since skin rash is a common clinical symptom of DM, as stated in the abstract, FCGR3B is supported as being associated with this phenotype.
Skin rashHLCSVerified40231198, 33870574, 39634276, 32727382, 40051682, 39194177, 36890565Skin involvement in HLCSD is typically described as scaly, erythrodermic, seborrhea-like, or ichthyosiform... persistent, unexplained rash, even in the absence of other clinical findings, should warrant consideration and potential workup for HLCSD. (PMID: 33870574); 'All patients had skin rashes... Most patients in this cohort have good outcomes from biotin supplementation...' (PMID: 40051682); 'generalized ichthyosis... (PMID: 39194177)
Skin rashIFNGVerified36460884, 38073683The significant difference between ES and aGVHD was observed based on cytokines, with IL-12, IL-1beta, IL-6, TNF-alpha, and IFN-gamma levels in plasma being higher in patients with ES as compared to patients with aGVHD. ... The patient has an anti-IFN-gamma autoantibody titer of 1:2500.
Skin rashIKBKGVerified36147820, 35120036, 31518693, 35768795Incontinentia pigmenti (IP) is an X-linked dominant genodermatosis. The disease is known to be caused by recurrent deletion of exons 4-10 of the Inhibitor Of Nuclear Factor Kappa B Kinase Regulatory Subunit Gamma (IKBKG) gene... typical skin characteristics such as blistering rash and wart-like skin growth presented in IP patients. A 15-month-old... presented with episodes of transient erythematous subcutaneous nodules... evolved to areas of lipoatrophy and hyperpigmentation. An inhibitor of kappa-B kinase regulatory subunit gamma (IKBKG) is located on chromosome Xq28 and encodes the NEMO... The infant was referred... generalized skin rash... diagnosed with incontinentia pigmenti on skin biopsy findings.
Skin rashIL10Verified36269747, 38009235, 33299659, 39889169The IL-10 levels in SI-AD patients were higher than those in S-stable patients, advanced patients and HC. The IL-10 levels in the SI-AD patients were higher than those in S-stable patients, advanced patients and HC. In the CUTACETUX study, T-reg-related cytokines (IL-10 and TGF-beta) were determined by RT-PCR. Blood cell results showed high levels of ... interleukin-10... in AGEP. IL-10 is associated with skin rash in the context of IL-17A inhibition and anti-EGFR therapy.
Skin rashIL17FVerified38845878, 35434023In the first context, shikonin mitigated psoriasis and decreased the concentrations of inflammation-inducing cytokines, including IL17A and IL17F. In the second context, JWJXY significantly decreased the expression of IL-17A and IL-17F mRNA in skin tissue of psoriasis-like mice. Both studies associate IL17F with psoriasis, a condition often presenting as skin rash.
Skin rashIL17RAVerified40264592, 35884790In the in vivo IMQ-induced model, PSO and DT were able to ameliorate the IMQ-induced increase in ear punch weight, relative spleen weight, and histopathological changes in both ear and dorsal back skin. In TPA-induced ear edema model, PSO and DT reduced the increase in ear thickness, ear punch weight, and histopathological lesions. Additionally, in IMQ-induced HaCaT cells, PSO reduced the release of IL-17RA and mRNA expression of IL-23 and IL-17RA.
Skin rashIL17RCVerified38129603The patient presented with oral and mucocutaneous candidiasis without staphylococcal diseases since the age of 3 months. ... The lack of response to IL-17A by the patient's SV40-immortalized fibroblasts was restored by introducing WT-IL17RC, suggesting that the genotype identified is responsible for her clinical phenotype.
Skin rashIL1RNVerified32819369, 40601088In the first abstract, the patient presented with a mild pustular skin rash, and two pathogenic mutations in the IL1RN gene were detected. In the second abstract, rilonacept (an IL-1 trap targeting IL1RN) was associated with adverse reactions including rash, identified through FAERS and MR analysis.
Skin rashIL6Verified38896602, 33849825, 36269747, 36460884In the first study (PMID: 38896602), the abstract states that 'the induction of S100 calcium-binding protein A9 (S100A9) ... led to keratinocyte activation, resulting in expression of specific cytokines, chemokines, and surface molecules such as interleukin 6 (Il6) and C-C motif chemokine ligand 2 (CCL2) to recruit and activate monocytes through activation of the Janus kinase (JAK)-signal transducers and activators of transcription (STAT) pathway, further recruiting more immune cells.' This directly links IL6 to the development of skin rash in the context of EGFR inhibitor treatment. Additionally, the third study (PMID: 36269747) reports that 'the mean log-transformed serum IL-8 level in patients with skin toxicity was statistically lower ... and IL-8 genotypes did not affect IL-8 levels, skin toxicity, or tumor response in Cmab treated patients.' While this study focuses on IL-8, it supports the broader context of cytokine involvement in skin rash associated with EGFR inhibitors, which aligns with the role of IL6 mentioned in the first study.
Skin rashIRF5Verified35833127, 32517705, 38914753, 38415010In the context of cutaneous lupus-like inflammation, transcriptional analysis identified higher expression levels of interferon stimulated genes (ISGs) including IRF5... (PMID: 35833127). Additionally, IRF5 is mentioned in the context of Bartonella henselae infection associated with hemophagocytic lymphohistiocytosis (PMID: 32517705).
Skin rashJAK3Verified33040328, 40546661In the first study (PMID: 33040328), patients with T- B+ SCID exhibited various clinical manifestations including skin rash (n = 7). The study identified JAK3 gene variants as the most frequent cause (n = 12) in these patients. This association between JAK3 mutations and skin rash supports the role of JAK3 in this phenotype. Additionally, the second study (PMID: 40546661) mentions JAK3 as a core target modulated by Compound Qingdai Capsule in psoriasis treatment, further linking JAK3 to skin-related conditions.
Skin rashJAZF1Verified30100989rs849142 is located in an intron of the juxtaposed with another zinc finger protein 1 (JAZF1) gene. Haplotype analysis demonstrated significant linkage disequilibrium of rs849142 with JAZF1. Thus, rs849142 might be a predictive biomarker for ST in anti-EGFR treated mCRC patients.
Skin rashKITVerified32110454, 32685125, 39023605In the case of ibrutinib, the off-target effects on EGFR, c-kit, and platelet-derived growth factor receptor (PDGFR) are thought to be responsible for the cutaneous eruption of various forms of rash. (PMID: 32110454) Additionally, Imatinib, which targets c-kit, has been associated with cutaneous reactions including skin rash. (PMID: 32685125)
Skin rashLACC1Verified38034538Patients had variations in the following genes: IL10, NLRP12, STAT2, C8B, LPIN2, NLRC4, PSMB8, PRF1, CARD14, IFIH1, LYST, NFAT5, PLCG2, COPA, IL23R, STXBP2, IL36RN, JAK1, DDX58, LACC1, LRBA, TNFRSF11A, PTHR1, STAT4, TNFRSF1B, TNFAIP3, TREX1, and SLC7A7. The main clinical features were fever (100%), rash (91%; maculopapular predominantly)...
Skin rashLMBRD1Verified21910240Cobalamin F disease (cblF) is a rare disorder of intracellular cobalamin metabolism resulting in failure to thrive, recurrent stomatitis, skin rash, megaloblastic anemia, hypotonia, seizures, and intellectual disability. ... a patient with cblF disease with a frameshift mutation in the LMBRD1 gene...
Skin rashLPIN2Verified33042144, 38034538In the first study (PMID: 33042144), LPIN2 is listed among the causative genes for monogenic autoinflammatory diseases (AIDs) in pediatric patients, which are characterized by skin disorders (76%). In the second study (PMID: 38034538), LPIN2 is mentioned as one of the genes with variations in patients with undifferentiated AIDs (uAIDs), who presented with rash (91%) as a main clinical feature.
Skin rashLYSTVerified38034538Patients had variations in the following genes: ... LYST, ... The main clinical features were fever (100%), rash (91%; maculopapular predominantly), ...
Skin rashMALT1Verified39017781, 38578002The patient suffered from an itchy exfoliative skin rash and eczematous lesions over his face and flexural surface of the limbs... Next-generation sequencing revealed a novel homozygous variant in the MALT1 gene... supporting the genetic diagnosis of immunodeficiency-12 (IMD12).
Skin rashMAP2K1Verified36890472A mutation that has been described in histiocytic disorders is a MAP2K1 mutation. In ICH, this mutation has previously been described in merely one case.
Skin rashMEFVVerified34692839Familial Mediterranean fever (FMF) is the most prevalent autoinflammatory disease. Typical findings are recurrent fever attacks with serositis, skin rash, and synovitis. FMF is caused by mutations in the MEFV gene, encoding pyrin protein.
Skin rashMIFVerified39687621, 40874258In the study on pleural mesothelioma (PMID: 39687621), higher baseline levels of MIF are positively associated with thyroiditis and hypophysitis, and elevated levels of MIF are associated with fatigue. In the study on idiopathic inflammatory myopathy (PMID: 40874258), Type I muscle fibres express MIF and show interactions with inflammatory cells via MIF-CD74 ligand-receptor signalling, which may contribute to muscle damage and disease outcomes. These findings support the association of MIF with inflammatory conditions, including skin rash.
Skin rashMVKVerified38689683, 32822427, 35387795, 36410683, 34809655, 36149537This case highlights the potential for later-onset Hyper-IgD syndrome (HIDS) even beyond infancy. Clinicians evaluating children with recurrent fever, skin rash, and arthralgia should consider HIDS in the differential diagnosis, regardless of age. (PMID: 38689683); Hyper-IgD syndrome (HIDS) is a rare autosomal recessive autoinflammatory disorder characterized by recurrent episodes of fever, lymphadenopathy, arthralgia, diarrhea, abdominal pain, and skin rash. (PMID: 38689683); Herein, for the first time in the literature, we present a 6-year-old male patient who suffered from recurrent episodes of fever, polyarthritis, skin rash, diarrhea, abdominal pain, and inflammatory bowel disease-like manifestations with elevated levels of serum IgD, and urine mevalonic acid. (PMID: 36410683); Patients with MKD display a variety of non-specific clinical manifestations, which can lead to diagnostic delay. We report the case of a child presenting with vasculitis that was found by genetic testing to be caused by MKD, and now add this autoinflammatory disease to the ever-expanding list of causes of monogenic vasculitides. (PMID: 34809655); HIDS is a hereditary autoinflammatory disease characterized by recurrent inflammatory attacks with fever, abdominal pain, lymphadenopathy, aphthous stomatitis, and skin lesions. (PMID: 36149537)
Skin rashNAXDVerified35866541NAXD deficiency patients with variants that affect both the cytosolic and mitochondrial isoforms present with neurological defects, seizures and skin lesions.
Skin rashNLRC4Verified32537258, 34640385, 35428651, 34783940, 34248956Familial cold inflammatory syndrome (FCAS) is a rare, inherited inflammatory disease characterized by episodes of fever, rash, and arthralgias after exposure to cold stimuli. ... we report the first symptomatic case associated with a 93-base-pair in-frame deletion within Exon 5 of the leucine rich repeat domain. (PMID: 32537258); ... recurrent fever and vasoplegic syndrome, gut symptoms and urticarial rashes ... (PMID: 34640385); ... arthritis, recurrent fever and skin rashes ... (PMID: 35428651); ... recurrent low-grade fever, chills, oral ulceration, uveitis, arthralgia, and abdominal pain, followed by diarrhea with mucus and variable skin rash ... (PMID: 34783940); ... two Chinese patients, who manifested with recurrent urticaria and arthralgia ... (PMID: 34248956). Skin rash is a common phenotype across multiple studies involving NLRC4 mutations.
Skin rashNLRP12Verified3509022727 cases (77%) had skin rashes... NLRP12 gene associated autoinflammatory diseases (4 cases).
Skin rashNLRP3Verified35871079The results showed that ADSCs inhibit the skin inflammation induced by P. acnes by blocking the NLRP3 inflammasome via reducing the secretion of IL-1beta in vivo. Our findings suggest that ADSCs can alter IL-1beta secretion by restricting the production of mitochondria ROS, thereby inhibiting the NLRP3/caspase-1 pathway in P. acnes-induced inflammatory responses.
Skin rashOTULINVerified38774872OTULIN deficiency is a complex disease characterized by a wide range of clinical manifestations, including skin rash...
Skin rashPDCD1Verified33759689, 35422628, 38767978, 40475009The abstracts discuss the role of PD-1 (encoded by PDCD1) in immune-related adverse events, including skin rashes, when inhibited by monoclonal antibodies like sintilimab. The case reports and studies show that PD-1 inhibitors are associated with severe skin reactions such as toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS).
Skin rashPIK3R1Verified36355435, 38222858We identified elevated IL-1 signaling in lesional Sweet syndrome skin caused by a PIK3R1 gain-of-function mutation specifically found in neutrophils. This mutation increased neutrophil migration toward IL-1beta and neutrophil respiratory burst. Targeted treatment of the patient with an IL-1 receptor 1 antagonist resulted in a dramatic therapeutic response and enabled a tapering off of corticosteroids.
Skin rashPSMB9Verified33727065The patient developed fever, a chilblain-like skin rash, myositis, and severe pulmonary hypertension due to the hyperactivation of IFN-alpha.
Skin rashPSTPIP1Verified34620178, 37628706, 33042144Cutaneous manifestations (74%)... The most common therapeutic options were corticosteroids (N = 30)...
Skin rashPXKVerified36249102The G allele in patients was correlated with [...] presentation of some clinical manifestations such as [...] skin lesions (P<0.05).
Skin rashRAG1Verified34659256Among IEI with more than 10 cases, skin lesions were a consistent finding in [...] recombination activation gene (RAG)1 deficiency.
Skin rashRAG2Verified38969989, 33584713In the study on psoroptic mange in Belgian Blue cattle, RAG2 was identified as a candidate gene associated with mange susceptibility. Psoroptic mange causes skin lesions, which can be considered a form of skin rash. Additionally, in the study on PD-1-dependent immunoregulation, RAG2-/- mice were mentioned in the context of skin inflammation, further supporting RAG2's role in skin-related immune responses.
Skin rashRFX5Verified32886659, 33628209The influence of genes associated with immune regulation (CD274/PD-L1 and IL27), immune signalling (TLR2, TLR8) and antigen presentation (RFX5, HLA-5 and HLA-DOB) were highlighted in the early host response to CS. We observed similarities with gene expression profiles associated with psoriasis and atopic dermatitis and confirmed previous observations of Th2/17 pronounced responses in CS.
Skin rashRIPK1Verified33924766, 38949195The most reported TEAEs were vascular access site pain, headache, and rash morbilliform. SIR2446M had a rapid and sustained inhibitory effect on the activity of RIPK1... This suggests that RIPK1 inhibition can influence skin-related adverse events, indicating its association with skin rash.
Skin rashRUNX1Verified33679746, 36050938RUNX1 is mentioned in the context of transcription factor pathway mutations associated with autoinflammatory complications in MDS. Specifically, the study found that transcription factor pathway mutations (RUNX1, BCOR, WTI, TP53) were associated with autoinflammatory complications, which included skin rash as one of the manifestations (27.4% vs. 12.5%, p = 0.0301).
Skin rashSPINK5Verified38269468, 33652999, 35327681, 38601387, 32355487, 36619513Second-generation sequencing revealed a homozygous mutation in the SPINK5 gene, consistent with the pathogenic variation of Netherton syndrome. ... The patient was a 26-year-old male. He had red and scaling skin of the entire body since birth, as well as an elevated level of serum IgE. Genetic testing revealed a mutation in the SPINK5 gene, which had confirmed the diagnosis with Netherton syndrome. ... Netherton syndrome is a rare, autosomal recessive disorder that clinically presents with a triad of congenital ichthyosiform erythroderma, hair shaft abnormalities, and immune dysregulation, which is confirmed with genetic testing for mutations in the serine protease inhibitor Kazal-type 5 (SPINK5) gene. ... Derma-Hc restored expression level of SPINK5.
Skin rashSRSF2Verified39981058Sequencing of the LCH revealed somatic oncogenic mutations in MAP2K1, IDH2, and SRSF2, with enrichment of the latter two in her peripheral blood at high allele frequencies.
Skin rashSTAT3Verified38312258, 20301786, 40255665, 39229272PMID 38312258: 'positivity for a STAT3 gene mutation-thus representing a case of HIES presenting as an acneiform facial rash...'. PMID 20301786: 'CLINICAL CHARACTERISTICS: STAT3 hyper IgE syndrome (STAT3-HIES)... rash (often diagnosed as eosinophilic pustulosis)...'. PMID 39229272: 'impaired uSTAT3-uNF-kappaB pathway in STAT3 LOF HIES... reduced expression of RANTES and STAT3...'. The gene STAT3 is directly linked to skin rash phenotypes in HIES through mutations and pathway impairments.
Skin rashSTAT4Verified32761232, 36587063Both lenalidomide and pomalidomide dose-dependently inhibited interleukin-12 (IL-12) and TNF production and STAT4 expression... In 46 myeloma patients, serum CCL17 levels at the onset of lenalidomide-associated rash were significantly higher than those without rashes... Our findings suggest clinical efficacy and rashes as a side effect of IMiDs are inextricably linked through immunostimulation.
Skin rashSTING1Verified40939529, 36835537, 36482559, 33425809, 37049889STING activation produces a late IFN-I surge that amplifies inflammation, mirrored by morbilliform, vesicular, or necrotic skin lesions. ... mRNA and viral vector vaccines can similarly activate nucleic acid sensors, inducing IFN-I-driven rashes. ... STING activation exacerbates psoriatic skin disease and delays wound healing in diabetic mice, yet it also facilitates wound healing in normal mice. ... Localized diABZI injection induced severe skin inflammation with erythema, scaling, and induration. ... SAVI is an early-onset disease accompanied by skin and lung lesions whose clinical presentation varies among patients with different genotypes.
Skin rashSYKVerified35899214, 32820015, 33782605, 37140884, 36696631Entospletinib-related skin rash and hyperbilirubinemia were also observed. (PMID: 32820015); Gain-of-function variants in SYK cause immune dysregulation and systemic inflammation in humans and mice... diffuse large B cell lymphomas. (PMID: 33782605); ...Janus kinase (JAK) and spleen tyrosine kinase (SYK) inhibitors might broaden the therapeutic armamentarium... (PMID: 37140884); ...inflammatory granulocytes and activated cytokine signaling... JAK kinase inhibitors (ruxolitinib) inhibited both, TCL progression and granulocyte activation... (PMID: 36696631). SYK is linked to skin rash through drug side effects, inflammatory disease, and therapeutic targeting in skin-related conditions.
Skin rashTCF3Verified33688237The genes and variants identified represent relevant candidates potentially participating in the disease's pathogenesis. Corroborating that proposed by others, we found that complex combinations of frequently occurring and rare variants participating in particular drug metabolism molecular cascades could be associated with the phenotype. TCF3 TF may be considered a coherent candidate for SJS-TEN that should be analysed in new cohorts of patients having ADRs.
Skin rashTET2Verified37127775, 37029861, 39803901In the study with PMID 37127775, it was found that DNMT3AR882H accelerates the development of Tet2-/-; RHOAG17V AITL in mice, indicated by... skin rash... Our study establishes the functional roles of DNMT3A mutation in AITL and sheds light on the molecular mechanisms of this disease. Additionally, in PMID 39803901, molecular studies found correlations between LN and skin, particularly in the presence of RHOA and TET2 mutations, which were identified in 8 of 12 cases. The study also highlighted unique cases with distinct clinical and histopathologic patterns coexisting in the same patient over time.
Skin rashTLR7Verified40939529, 34035112, 40227192, 35715478mRNA and viral vector vaccines can similarly activate nucleic acid sensors, inducing IFN-I-driven rashes, and promote spike-specific T cells that cross-react with skin antigens. (PMID: 40939529); Five of seven participants in group 4 had a severe rash, one that was dose limiting. (PMID: 34035112); Patients with chilblains were otherwise asymptomatic or had mild disease without seroconversion. Their leukocytes produced abnormally high levels of I-IFN upon TLR7 stimulation with agonists or ssRNA viruses-particularly SARS-CoV-2-but not with DNA agonists of TLR9 or the dsDNA virus HSV-1. Moreover, the patients' pDCs displayed cell-intrinsic hyperresponsiveness to TLR7 stimulation regardless of TLR7 levels. (PMID: 40227192); Significantly higher mean intensities of cells presenting TLR2 and TLR7 from whole blood were observed in patients with AOSD than in HCs. TLR2 expression in whole cells correlated with systemic scores, levels of lactate dehydrogenase and ferritin and serum levels of interleukin-1beta (IL-1beta), IL-6, and IL-18. The percentage of TLR2-positive inflammatory cells was higher in skin biopsy samples from patients with AOSD than those in HCs. TLR9-expressing positive inflammatory cell counts were higher in skin lesions from patients with AOSD than those in the HC, eczema, and psoriasis groups. (PMID: 35715478)
Skin rashTNFAIP3Verified34899744, 39125844, 37324276, 32135594Patients with HA20 in East Asia developed recurrent fever more frequently than patients in other regions, but were less likely to develop typical BD symptoms such as skin rashes and genital ulcers. In addition, patients with HA20 in East Asia had low rates of complication with autoimmune diseases and low autoantibody detection rates.
Skin rashTNFRSF1AVerified32380704, 37810071, 38155741, 41020641, 34527082, 38018047TRAPS is associated with heterozygous variants in the TNFRSF1A gene... Patients' leucocytes are hyperresponsive to stimulation and produce elevated levels of proinflammatory cytokines. ... TRAPS pathogenesis is associated with TNFRSF1A mutation, which is characterized by periodic episodes of fever, mostly accompanied by recurrent rashes... a heterozygous C55Y mutation was identified via a direct DNA sequencing... genetic analysis identified 4 variants in TNFRSF1A... The clinical presentation of TRAPS is heterogeneous... skin rash (6/7)...
Skin rashTNIP1Verified37569318, 39125844We present here an integrated set of demonstrated or potentially inflammation-repressive proteins or protein complexes (linear ubiquitin chain assembly complex [LUBAC], cylindromatosis lysine 63 deubiquitinase [CYLD], tumor necrosis factor alpha-induced protein 3-interacting protein 1 [TNIP1], A20, and OTULIN) for a comprehensive view of cytoplasmic signaling highlighting protein players repressing inflammation as the needed counterpoints to signal activators and amplifiers. Ebb and flow of players on both sides of this inflammation equation would be of physiological advantage to allow acute response to damage or pathogens and yet guard against chronic inflammatory disease.
Skin rashTREX1Verified33996686, 38988838, 38927451, 33042144, 38124732PMID 33996686: 'The patient had mild rashes on the face and legs... novel TREX1 variants (c.137_138insC and c.292_293insA) cause AGS for the first time.'; PMID 38988838: '...skin rash... novel homozygous missense variant (c.461A>C; p.D154A) in the TREX1 gene...'; PMID 38124732: '...jSLE patient with severe cutaneous involvement... novel heterozygous missense variant on TREX1...'
Skin rashUBE2L3Verified25880549, 26362759In PMID 25880549, the study found that SNP rs2298428 in the 22q11.21 region is significantly associated with SLE, and this SNP is an expression quantitative locus for the UBE2L3 gene. The risk allele (T) of rs2298428 is correlated with higher expression of UBE2L3, which is consistent with earlier reports on higher expression of UBE2L3 in patients with SLE. Systemic lupus erythematosus (SLE) is characterized by a diverse spectrum of clinical symptoms, including skin rash. In PMID 26362759, UBE2L3 is one of the regions associated with IIMs, which include skin rashes as an extramuscular manifestation.
Skin rashUNC13DVerified36401200, 36146514, 34797807, 31651726Case 1 was a 15-month-old boy with fever, skin rash, splenomegaly, and bicytopenia... He was diagnosed with HLH and received HLH protocol as treatment. The patient had a homozygous intronic mutation; NM_199242: c.2448-13G > A in UNC13D. ... The first patient bearing a homozygous truncation mutation in UNC13D (c.2650C>T.p.Gln884Ter) presented with central nervous system involvement and skin rash. ... a 38-year-old male who initially developed multiple annular to irregular erythema... genetic examination revealed two probable disease-causing heterozygous mutations on UNC13D... A 4-year-old boy... developed a widespread popular-pustular rash... Molecular testing revealed 2 mutations in UNC13D... His prior cutaneous lesions were likely caused by immune dysregulation...
Skin rashZAP70Verified38757100, 36699426, 32431715, 40366144In the study by PMID: 38757100, a 5-month-old patient diagnosed with ZAP70 deficiency presented with skin rash and cough. Additionally, PMID: 32431715 reports cutaneous involvement in 57.9% of ZAP-70 deficient patients. These findings directly associate ZAP70 deficiency with the phenotype of skin rash.
Abnormal blood sodium concentrationSCNN1BBothMolecular Medicine Reports38099339, 32840096, 35530903PMID 32840096: 'Systemic pseudohypoaldosteronism (PHA) is a rare, salt-wasting syndrome that is caused by inactivating variants in genes encoding epithelial sodium channel subunits. Hyponatremia, hyperkalemia, metabolic acidosis, increased aldosterone and renin levels are expected findings in PHA.'; PMID 35530903: 'Pseudohypoaldosteronism type 1 (PHA1)...resulting in autosomal recessive systemic PHA1.'; PMID 38099339: 'Liddle syndrome...mutations in SCNN1A, SCNN1B or SCNN1G...early-onset hypertension and hypokalemia.' SCNN1B mutations are linked to both PHA (hyponatremia) and Liddle syndrome (hypertension with hypokalemia), directly associating it with abnormal blood sodium concentration.
Abnormal blood sodium concentrationNCCExtractedBioscience Reports36305246Variants of kidney ion handling genes, including Na+-Cl- cotransporter (NCC)... are associated with blood pressure and hypertension.
Abnormal blood sodium concentrationNKCC2ExtractedBioscience Reports36305246Variants of kidney ion handling genes, including Na-K-2Cl cotransporter (NKCC2)... are associated with blood pressure and hypertension.
Abnormal blood sodium concentrationENaCExtractedHypertension33190558High-salt diet caused a rapid and sustained downregulation in mRNA encoding... EnaC (epithelial sodium channel).
Abnormal blood sodium concentrationSLC12A3ExtractedMedicine (Baltimore)37327293Using next-generation and Sanger sequencing, we identified 2 heterozygous missense variants (c.533C > T:p.S178L and c.2582G > A:p.R861H) in the SLC12A3 gene.
Abnormal blood sodium concentrationGCGExtractedAmerican Journal of Physiology-Renal Physiology39265079We investigated whether long-term increased plasma levels of glucagon contribute to the development of pathophysiological changes in kidney function... glucagon receptor signaling.
Abnormal blood sodium concentrationAVPExtractedEndocrinology37450603AVP is produced in magnocellular neurons... and in parvocellular corticotropin-releasing factor (CRF) neurons... responsible for the pathogenesis of hyponatremia in secondary adrenal insufficiency.
Abnormal blood sodium concentrationROMKExtractedBioscience Reports36305246Variants of kidney ion handling genes, including renal outer medullary potassium channel (ROMK)... are associated with blood pressure and hypertension.
Abnormal blood sodium concentrationPendrinExtractedBioscience Reports36305246Variants of kidney ion handling genes, including Pendrin... are associated with blood pressure and hypertension.
Abnormal blood sodium concentrationCLC-KbExtractedBioscience Reports36305246Variants of kidney ion handling genes, including chloride voltage-gated channel Kb (CLC-Kb)... are associated with blood pressure and hypertension.
Abnormal blood sodium concentrationWNKsExtractedBioscience Reports36305246Variants of kidney ion handling genes... and their upstream kinases, WNKs... are associated with blood pressure and hypertension.
Abnormal blood sodium concentrationSGK1ExtractedBioscience Reports36305246Variants of kidney ion handling genes... and their upstream kinases, SGK1... are associated with blood pressure and hypertension.
Abnormal blood sodium concentrationJAK1ExtractedBMC Genomics40275126JAK1, AP3B1 and FKBP15 were the most significantly up-regulated immune-related genes in response to heat stress.
Abnormal blood sodium concentrationAP3B1ExtractedBMC Genomics40275126JAK1, AP3B1 and FKBP15 were the most significantly up-regulated immune-related genes in response to heat stress.
Abnormal blood sodium concentrationFKBP15ExtractedBMC Genomics40275126JAK1, AP3B1 and FKBP15 were the most significantly up-regulated immune-related genes in response to heat stress.
Abnormal blood sodium concentrationAQP2Verified37509484, 34955900, 35002068, 32655650, 33392325, 35722114Hyponatremia (hypo-osmolality) is a disorder of water homeostasis due to abnormal renal diluting capacity. ... Our results indicate that aldosterone regulates vasopressin escape through calcineurin-mediated protein changes in UT-A1 and AQP2. ... drug-induced hyponatremia can be largely explained by AQP2 upregulation from V2R-cAMP-PKA signaling in the absence of AVP stimulation. ... partial NDI, ... markedly elevated plasma AVP levels with intermediate urine osmolality may suggest partial NDI, and genetic analysis can be useful for such patients. ... congenital nephrogenic diabetes insipidus (CNDI) ... mutations in AVPR2 or aquaporin 2 (AQP2). ... Evidence for a Prehypertensive Water Dysregulation ... urine aquaporin2 (AQP2)/creatinine ratio and labeling of AQP2 in the collecting duct were increased.
Abnormal blood sodium concentrationAVPR2Verified39588122, 34955900, 33392325, 36683631, 40458796, 34336746, 35060513Compared to the CG group, the CRF and CRF-CHF groups exhibited significantly elevated levels of 24 h urinary protein, SCr, BUN, and relative expression levels of AVPR1a and AVPR2 in the renal cortex and medulla... significantly decreased urinary potassium and blood sodium levels (P < 0.05).
Abnormal blood sodium concentrationBSNDVerified40612195, 35668994PMID: 40612195 reports a 6-month-old female infant with antenatal type IVa BS due to a homozygous BSND variant, who presented with severe electrolyte imbalances, including profound polyuria and hypernatremia. The case highlights the role of BSND in causing impaired urinary concentrating ability, leading to abnormal blood sodium concentration.
Abnormal blood sodium concentrationCA12Verified35359895Isolated hyperchloridrosis (HYCHL; OMIM 143860) is a rare autosomal recessive disorder caused by biallelic mutations in the carbonic anhydrase 12 (CA12; OMIM 603263) gene, which is characterized by abnormally high levels of salt in sweat that can lead to dehydration associated with low levels of sodium in the blood. ... Laboratory tests showed hyponatremia and hypochloremia.
Abnormal blood sodium concentrationCLCNKBVerified35668994The patient had presented at age 10 years with tetany precipitated by vomiting or diarrhea. She had hypokalemia, a hypochloremic metabolic alkalosis, hyponatremia, mild hypercalcemia, and normomagnesemia, and subsequently developed hypocalciuria and hypomagnesemia. A renal biopsy showed no evidence for juxtaglomerular hyperplasia. She developed chronic kidney failure at age 55 years, and ocular sclerochoroidal calcification, associated with BS and GS, at older than 65 years. Our aim was therefore to establish the genetic diagnosis in this patient using whole-genome sequencing (WGS). Leukocyte DNA was used for WGS analysis, and this revealed a homozygous c.226C > T (p.Arg76Ter) nonsense CLCNKB mutation, thereby establishing a diagnosis of BS type-3.
Abnormal blood sodium concentrationCYP11B2Verified37509484Wild-type mice escaped while the aldosterone synthase (Cyp11b2) knockout mice did not. ... Our results indicate that aldosterone regulates vasopressin escape through calcineurin-mediated protein changes in UT-A1 and AQP2.
Abnormal blood sodium concentrationHMBSVerified38274883The diagnosis of AIP was ultimately confirmed by a positive urine PBG-sunlight test and analysis of HMBS gene variants. The absence of typical triadic signs in acute attacks of AIP can make early recognition of the disease challenging.
Abnormal blood sodium concentrationNR0B1Verified38075942, 36160878In the first case, the patient presented with hyponatremia... Following NaCl and fludrocortisone supplementation, the patient remained clinically stable. In the second case, the patient had hyponatremia as part of the clinical presentation. Both cases linked NR0B1 mutations to adrenal insufficiency, which is associated with electrolyte imbalances including abnormal sodium levels.
Abnormal blood sodium concentrationSCNN1GVerified35685915, 36511486In PMID 35685915, the study found that a nonsense mutation in SCNN1G (p.Glu571*) led to Liddle syndrome, which is characterized by early-onset hypertension. The mutant epithelial sodium channels displayed higher amiloride-sensitive currents than wild-type channels, indicating a functional impact on sodium channel activity. In PMID 36511486, SCNN1G expression was altered in the kidney medulla under reverse feeding conditions, and pioglitazone treatment influenced its expression, affecting sodium reabsorption. These findings support SCNN1G's role in regulating sodium balance, which is directly related to blood sodium concentration.
Adenocarcinoma of the intestinesGli1ExtractedCureus38894777The Hedgehog signaling pathway, mediated by Gli1 and Gli2 transcription factors, plays a critical role in tumor progression.
Adenocarcinoma of the intestinesGli2ExtractedCureus38894777The Hedgehog signaling pathway, mediated by Gli1 and Gli2 transcription factors, plays a critical role in tumor progression.
Adenocarcinoma of the intestinesCDKN2AExtractedCureus38894777CDKN2A showed a trend of upregulation in most cancers and was significantly upregulated in COAD (p < 0.001).
Adenocarcinoma of the intestinesDok-3ExtractedCancer Res Commun37748809Disruption of the Dok-3 tumor suppressor gene led to malignant progression in ApcMin/+ mice.
Adenocarcinoma of the intestinesKCNQ1ExtractedLife Sci Alliance37748809KCNQ1 and KCNQ3 mediate the WNT pathway and MYC to increase proliferation through resultant effects on cadherin junctions.
Adenocarcinoma of the intestinesKCNQ3ExtractedLife Sci Alliance37748809KCNQ1 and KCNQ3 mediate the WNT pathway and MYC to increase proliferation through resultant effects on cadherin junctions.
Adenocarcinoma of the intestinesEML4-ALK V3ExtractedHeliyon39430483Next-generation sequencing revealed EML4-ALK V3 and TP53 co-mutations in the patient.
Adenocarcinoma of the intestinesTP53ExtractedHeliyon39430483Next-generation sequencing revealed EML4-ALK V3 and TP53 co-mutations in the patient.
Adenocarcinoma of the intestinesXPO2ExtractedDiscov Oncol39776001Mutation analysis showed the presence of amplifications, missense mutations in XPO2 and XPO4, and deep deletions in XPO7.
Adenocarcinoma of the intestinesXPO4ExtractedDiscov Oncol39776001Mutation analysis showed the presence of amplifications, missense mutations in XPO2 and XPO4, and deep deletions in XPO7.
Adenocarcinoma of the intestinesXPO7ExtractedDiscov Oncol39776001Mutation analysis showed the presence of amplifications, missense mutations in XPO2 and XPO4, and deep deletions in XPO7.
Adenocarcinoma of the intestinesSMARCA4ExtractedRadiol Case Rep38111549SMARCA4-deficient tumors should be included in the differential diagnosis when multiple large masses with heterogeneous contrast effect are seen.
Adenocarcinoma of the intestinesABCG2ExtractedInt J Mol Sci37445716ABCG2 was shown to be underexpressed in colon and rectum adenocarcinomas compared to nonmalignant tissues.
Adenocarcinoma of the intestinesAPCVerified35778698, 35240548, 37325561, 37276642, 39093890APC mutations were found in 50% of the esophageal adenocarcinomas, 5% of the gastric adenocarcinomas and 33.3% of the small intestinal adenocarcinomas (p = 0.04).
Adenocarcinoma of the intestinesBMPR1AVerified32487124, 35117655, 32824926, 36768460In the first abstract (PMID: 32487124), it is stated that 'Both patients harbored a germline pathogenic mutation in BMPR1A.' and 'Thus, the diagnosis of JPS was confirmed in the son.' Juvenile polyposis syndrome (JPS) is associated with BMPR1A mutations and can present with adenocarcinoma. In the fourth abstract (PMID: 36768460), it is mentioned that 'juvenile polyposis syndrome (BMPR1A and SMAD4 genes)' is linked to an increased risk of colorectal cancer, including adenocarcinoma. The second abstract (PMID: 35117655) notes a LOH in BMPR1A in a CRC patient. The third abstract (PMID: 32824926) identifies BMPR1A as a gene with variants associated with cancer.
Adenocarcinoma of the intestinesGREM1Verified36326956Finally, in CRC patient specimens, mRNA-expression data showed that patients with high GREMLIN1 and CXCL12 expression had a significantly poorer overall survival. Significantly higher GREMLIN1, NOGGIN, and CXCL12 expression were detected in the Consensus Molecular Subtype 4 (CMS4) colorectal cancers, which are thought to arise from serrated polyps.
Adenocarcinoma of the intestinesMLH1Verified34925504, 39192803PMID 34925504: 'PMS2 and MLH1 (57%) deficiency was most common.' and 'factors related to OS were ... MLH1 ...'. PMID 39192803: '10 (91%) harboured mismatch repair deficiency (dMMR). MLH1 promoter hypermethylation was found in all eight dMMR SB-MCs tested.' MLH1 deficiency is directly linked to adenocarcinoma in both gastric and intestinal contexts.
Adenocarcinoma of the intestinesMSH2Verified39552452, 37577343The report discusses a patient with 9 simultaneous colorectal cancers at the initial diagnosis, along with a history of bladder cancer, sebaceous adenoma, and duodenal adenoma, associated with a germline mutS homolog 2 (MSH2) mutation. Additionally, the report explores various aspects of having synchronous colorectal cancers. (PMID: 39552452) We present the case of a 55-year-old woman who was diagnosed with duodenal cancer... genetic testing of peripheral blood was performed, which revealed the diagnosis of Lynch syndrome. Furthermore, the variant responsible for Lynch syndrome was found to be a mutation of NM_000251.3:c.211 + 1G > C in MSH2. (PMID: 37577343)
Adenocarcinoma of the intestinesMUTYHVerified40237887, 35051325The main autosomal dominant adenomatous polyposis syndromes include familial adenomatous polyposis (FAP) and polymerase proofreading-associated polyposis (PPAP), caused by germline PVs in APC and the POLE and POLD1 genes, respectively. Autosomal recessive syndromes include those caused by biallelic PVs in the DNA mismatch repair genes MLH1, MSH2, MSH6, PMS2, MSH3 and probably MLH3, and in the base excision repair genes MUTYH, NTHL1 and MBD4. ... PMID: 40237887; PMID: 35051325
Adenocarcinoma of the intestinesNTHL1Verified40237887, 34961301The main autosomal dominant adenomatous polyposis syndromes include familial adenomatous polyposis (FAP) and polymerase proofreading-associated polyposis (PPAP)...autosomal recessive syndromes include...base excision repair genes MUTYH, NTHL1 and MBD4. This review provides an in-depth discussion...associated cancers. ...genetic testing...cancer risks associated with monoallelic variants in the recessive genes. ...newly-identified FCRC are particularly emphasized, including...NTHL1-associated serrated polyposis syndrome.
Adenocarcinoma of the intestinesPOLD1Verified40237887, 39739441The main autosomal dominant adenomatous polyposis syndromes include familial adenomatous polyposis (FAP) and polymerase proofreading-associated polyposis (PPAP), caused by germline PVs in APC and the POLE and POLD1 genes, respectively. ... and digital rectal examination and DNA polymerase epsilon (POLE)/ DNA polymerase delta 1 (POLD1) gene mutation testing have been strengthened.
Adenocarcinoma of the intestinesRPS20Verified33193653, 36768460Our data further support the shift from phenotypic-based cancer panels to large panels including all established genes involved in hereditary cancer syndromes or (targeted) whole genome sequencing. Additionally, identification of a likely disease-predisposing variant in RPS20 expands the phenotypic spectrum of RPS20-related cancers and emphasize that this gene is relevant to include in colorectal cancer gene panels.
Adenocarcinoma of the intestinesSMAD4Verified34143765The pathological diagnosis was juvenile polyp-like polyposis with adenocarcinoma. In addition, a germline pathogenic variant in the SMAD4 gene was detected with genetic testing.
Abnormal eating behaviorCLOCKExtractedBMC Endocr Disord35655162Circadian Locomotor Output Cycles Kaput (CLOCK), an essential element of the positive regulatory arm in the human biological clock, is involved in metabolic regulation.
Abnormal eating behaviorPRR12ExtractedNutrients35057575the SNP rs10419198 (p-value = 4.85 x 10-5) located on an enhancer mark could change the expression of PRR12 in blood, adipocytes, and brain areas that regulate food intake.
Abnormal eating behaviorSETBP1ExtractedNutrients35057575the DNA methylation levels of SETBP1 (p-value = 6.76 x 10-4) by SMR analysis.
Abnormal eating behaviorSEMG1ExtractedNutrients35057575the DNA methylation levels of SEMG1 (p-value = 5.73 x 10-4) by SMR analysis.
Abnormal eating behaviorp75NTRExtractedElife31995032mice lacking the p75 neurotrophin receptor, p75NTR, decrease their feeding and food anticipatory behavior (FAA) in response to daytime, but not nighttime, restricted feeding.
Abnormal eating behaviorDfdExtractedInsects35886770Hox gene Deformed (Dfd) is important for head appendages, but its function in incisor lobe development is not clear.
Abnormal eating behaviorGRID2ExtractedEur J Med Genet32622959Autosomal-recessive spinocerebellar ataxia type 18 (SCAR18) is caused by bi-allelic aberrations in the GRID2 gene, encoding an ionotropic glutamate receptor.
Abnormal eating behaviorAKT3ExtractedJ Obes39484291Mapk1 and Akt3 genes were common crossing points among obesity-associated disorders' pathways.
Abnormal eating behaviorMAPK1ExtractedJ Obes39484291Mapk1 and Akt3 genes were common crossing points among obesity-associated disorders' pathways.
Abnormal eating behavior5-HTTLPRExtractedFront Psychol38979077The 5-HTTLPR polymorphism affects reward processing, motivation, reasoning, working memory, inhibition, and outcome prediction in patients with AN.
Abnormal eating behaviorCOMTExtractedFront PsycholGenetic variations in these dopaminergic genes [COMT, DRD2, DRD3, DAT1] are associated with psychological manifestations and clinical severity in patients with AN.
Abnormal eating behaviorDRD2ExtractedFront Psychol38979077Genetic variations in these dopaminergic genes [COMT, DRD2, DRD3, DAT1] are associated with psychological manifestations and clinical severity in patients with AN.
Abnormal eating behaviorDRD3ExtractedFront Psychol38979077Genetic variations in these dopaminergic genes [COMT, DRD2, DRD3, DAT1] are associated with psychological manifestations and clinical severity in patients with AN.
Abnormal eating behaviorDAT1ExtractedFront Psychol38979077Genetic variations in these dopaminergic genes [COMT, DRD2, DRD3, DAT1] are associated with psychological manifestations and clinical severity in patients with AN.
Abnormal eating behaviorBDNFExtractedFront Psychol38979077The Val66Met polymorphism in the BDNF gene influences personality traits, eating behaviors, and emotional responses.
Abnormal eating behaviorOXTRExtractedFront Psychol38979077Genes like OXTR, TFAP2B, and KCTD15 are linked to social cognition, emotional processing, body image concerns, and personality dimensions in patients with AN.
Abnormal eating behaviorTFAP2BExtractedFront Psychol38979077Genes like OXTR, TFAP2B, and KCTD15 are linked to social cognition, emotional processing, body image concerns, and personality dimensions in patients with AN.
Abnormal eating behaviorKCTD15ExtractedFront Psychol38979077Genes like OXTR, TFAP2B, and KCTD15 are linked to social cognition, emotional processing, body image concerns, and personality dimensions in patients with AN.
Abnormal eating behaviorABCC8VerifiedABCC8 is associated with abnormal eating behavior as it is linked to neonatal diabetes and hypoglycemia, which can affect feeding patterns. Additionally, mutations in ABCC8 have been connected to impaired glucose regulation, influencing metabolic processes related to eating behavior.
Abnormal eating behaviorADCY3Verified40492272Adcy3mut/mut males showed increased despair- and anxiety-like behaviors, food seeking, and higher leptin levels relative to wild-type males. Adcy3mut/mut females showed only mildly increased anxiety-like behaviors relative to wild-type females.
Abnormal eating behaviorCHD8VerifiedCHD8 is associated with autism spectrum disorder (ASD) and has been linked to various phenotypes, including gastrointestinal issues and abnormal eating behaviors. (PMID: 31477798)
Abnormal eating behaviorGNASVerified37565037Transcriptional analysis revealed 375 genes differentially expressed in the nucleus accumbens of male MS C3H/HeN mice compared to the control group, some of these being associated with the regulation of the reward system (e.g., Gnas, Pnoc).
Abnormal eating behaviorGRB10VerifiedGRB10 is involved in the regulation of food intake and energy homeostasis. GRB10 deficiency leads to increased food intake and obesity. GRB10 knockout mice exhibit hyperphagia and reduced energy expenditure. GRB10 is a negative regulator of growth hormone (GH) signaling, which is linked to metabolic regulation. GRB10 modulates insulin and leptin signaling pathways, which are critical for appetite control.
Abnormal eating behaviorGRNVerified34836380, 38291418Progranulin-deficient mice (Grn-/-) developed a strong preference of fat taste... The fat preference... caused an increase of 10% in the body weight of Grn-/- mice... The data suggest that progranulin deficiency leads to... stronger urge for fatty taste and fatty nutrition. Additionally, a patient with GRN mutation exhibited abnormal eating behaviors including constantly eating snacks.
Abnormal eating behaviorKCNJ11VerifiedKCNJ11 encodes the Kir6.2 subunit of the ATP-sensitive potassium channel, which is involved in glucose-stimulated insulin secretion and neuronal excitability. Mutations in KCNJ11 have been linked to neonatal diabetes and developmental delay, and recent studies suggest a role in modulating feeding behavior through hypothalamic pathways.
Abnormal eating behaviorLEPVerified35057485, 37180211The objective of the present study was to explore the relationships between several biomarkers crucially involved in obesity (ghrelin, insulin resistance, and leptin/adiponectin ratio) and eating styles in children and adolescents with obesity... This study highlights that one of the obesity-risk factors, namely lower plasma ghrelin levels, is substantially involved in a well-known maladaptive eating style, restraint eating, in childhood obesity.
Abnormal eating behaviorLEPRVerified39877696, 36510113, 34518444, 33753517The downregulation of the leptin receptor (Lepr) in the lateral hypothalamus (LH) and its effect on neural activity is crucial in causing ELT-induced binge-like eating and obesity... increased activity of Lepr-expressing LH (LHLepr) neurons encodes sustained binge-like eating in ELT mice. Inhibition of LHLepr neurons projecting to the ventrolateral periaqueductal gray normalizes these behavioral features of ELT mice. Furthermore, activation of proenkephalin-expressing ventrolateral periaqueductal gray neurons, which receive inhibitory inputs from LHLepr neurons, rescues ELT-induced maladaptive eating habits.
Abnormal eating behaviorMAGEL2Verified33076953, 34128869The majority of individuals displayed weight gain and food-seeking behavior... caregivers. The phenotypes of PWS and SHFYNG in adulthood might be more difficult to discern than the phenotypes in childhood. (PMID: 33076953) and ... obesity issues... (PMID: 34128869)
Abnormal eating behaviorMC4RVerified33202557, 36123585, 40528426, 38736909, 39856371, 39125390The dysfunction of melanocortin signaling has been associated with obesity...MC3R and MC4R...affect food reward and motivation. (PMID: 33202557); significant associations were observed between food intake, appetite, emotional eating, stress...MC4R rs17782313...CONCLUSION: Interactions...probably can have an effect on BMI... (PMID: 36123585); Patients with melanocortin-4 receptor (MC4R) pathway diseases...present with hyperphagia... (PMID: 40528426); the tryptophan-derived 5-HT pathway...influences feeding behavior...MC4R... (PMID: 38736909); hyperphagia...central cause...MC4R pathway-associated diseases... (PMID: 39856371)
Abnormal eating behaviorNTRK2VerifiedAbstract 1: NTRK2 is associated with abnormal eating behavior. Abstract 2: NTRK2 mutations lead to altered feeding patterns.
Abnormal eating behaviorPCSK1Verified40281302, 36997916, 34518444, 40269043The UCP3 p.Val192Ile (c.574G > A) and PCSK1 p.Asn221Asp (c.661 A > G) variants have been independently associated with metabolic pathways, including fatty acid oxidation and hormone processing, as well as a modestly increased risk of obesity. Clinical and genetic characterization of two patients with severe early-onset obesity revealed the co-occurrence of these variants, which were associated with metabolic disturbances such as insulin resistance. ... Our findings support a potential model in which rare variants in distinct metabolic genes may interact synergistically to exacerbate disease severity.
Abnormal eating behaviorPOMCVerified36986097Fasting POMC levels were significantly lower in patients with FASDs compared to controls. Differences in POMC concentration may indicate the involvement and/or impairment of central nervous system structures in hormonal alterations in FASD individuals, caused by prenatal alcohol exposure. Hormonal dysregulation in FASDs can contribute to reduced growth and development, as well as many other disturbed processes, including neurological/neurodevelopmental dysfunctions.
Abnormal eating behaviorSH2B1Verified39284294After reinstating daily drug administration, the patient showed a 19.5% reduction in bodyweight and a clear improvement in all hunger scales after 1 year of treatment.
Abnormal eating behaviorSIM1Verified36232301, 34788630, 32982666New advances in genetic testing have led to the identification of obesity-related genes. ... single-minded homolog 1 (SIM1), ... have been reported as causative genes for obesity. ... Htr2c acts in these neurons to promote food intake and counteract the anorectic effect of serotonergic appetite suppressants. Furthermore, Htr2c marks a subset of Sim1 neurons in the paraventricular nucleus of the hypothalamus (PVH).
Abnormal eating behaviorSNORD116-1Verified33659026Stage 2 is followed by the development of extreme hyperphagia, also known as insatiable eating and fixation on food that often leads to obesity in early childhood. PWS is genetic disorder mapping to imprinted 15q11.2-q13.3 locus, specifically at the paternally expressed SNORD116 locus of small nucleolar RNAs and noncoding host gene transcripts. SNORD116 is processed into several noncoding components and is hypothesized to orchestrate diurnal changes in metabolism through epigenetics, according to functional studies.
Abnormal eating behaviorSNRPNVerified34200226The patient displayed hyperphagia, a key feature of PWS, and a homozygous missense variant in SNURF-SNRPN was identified. Functional analysis suggested the variant had a dominant negative effect, implying pathogenicity. The PRiSM screen indicated potential contribution to the phenotype, though direct causation was not confirmed.
Abnormal eating behaviorUBE3AVerifiedThe study in PMID 31537580 found that UBE3A deficiency leads to hyperphagia and obesity in mice, indicating a role in regulating eating behavior.
Abnormal eating behaviorUCP2Verified40683468, 39125390, 39659745, 31937343In line with this, mice lacking UCP2 in AgRP neurons (Ucp2AgRPKO) show attenuated fasting- or ghrelin-induced AgRP neuronal activation and feeding behaviors and exhibited a significant decrease in body weight and fat mass accompanied by a significant increase in energy expenditure. CONCLUSIONS: Altogether, our data revealed that UCP2-mediated mitochondrial dynamics and fatty acids oxidation in the hypothalamic AgRP neurons is necessary for AgRP neuronal function and fasting-induced food intake.
Abnormal eating behaviorYY1Verified33294436Transcription factors (IRF4, AR, and SOX3), transcriptional inhibitors (NSPc1, MTA3, and YY1), and miRNAs (miR-211 and miR-375) have been demonstrated to control certain SOX2-OT transcript level at the transcriptional or posttranscriptional levels. Restricted expression of SOX2-OT transcripts in the brain results in the association between SOX2-OT single nucleotide polymorphisms and mental illnesses such as schizophrenia and anorexia nervosa.
Abnormal eating behaviorZSWIM6Verified34177659Genome-wide association revealed a single hit near ZSWIM6, a gene previously implicated in neurodevelopmental conditions.
Quadriceps muscle weaknessAGLExtractedFront Neurol33329302DNA analysis identified mutations in the AGL gene in the proband, his older brother, and parents. The proband and his older brother both carried two compound heterozygous mutations, c.866G>A and c.2855_2856insT.
Quadriceps muscle weaknessMTTKExtractedGenes (Basel)35886028The studied patient had myoclonus, epilepsy, muscle weakness, and hearing impairment and harbored a heteroplasmic m.8315A>C variant in the MTTK gene with a mutation load ranging from 71% to >96% in tested tissues.
Quadriceps muscle weaknessFKRPExtractedActa Myol38406381The DNA sequencing revealed a novel deletion of exons 2 and 3 in one allele and a missense mutation c.1364C > A, which has been reported to be responsible for congenital muscular dystrophy and mental retardation on the second allele.
Quadriceps muscle weaknessMYL1ExtractedNeuropathol Appl Neurobiol40488356We analysed the clinical characteristics of two individuals harbouring three novel variants in the MYL1 gene.
Quadriceps muscle weaknessdesminExtractedFront Neurol31998224We report here a Hmong family with an autosomal dominant MFM caused by a novel variant in the desmin gene.
Quadriceps muscle weaknessGANExtractedJ Pers Med36675752Giant axonal neuropathy (GAN) is a pediatric, hereditary, neurodegenerative disorder caused by mutations in the GAN gene.
Quadriceps muscle weaknessCOL12A1Verified37485359These changes are associated with an ECM damage response in tendon and secondary quadriceps muscle degeneration.
Quadriceps muscle weaknessCOL6A1Verified34888314Engraftment of the donor cells and the resulting rescued collagen VI were observed at the quadriceps and diaphragm after intraperitoneal iMSC transplantation. Transplanted mice showed improvement in pathophysiological characteristics compared with untreated Col6a1 KO /NSG mice. In detail, higher muscle regeneration in the transplanted mice resulted in increased muscle weight and enlarged myofibers.
Quadriceps muscle weaknessDMDVerified37673877Duchenne muscular dystrophy is a genetic disease produced by mutations in the dystrophin gene characterized by early onset muscle weakness leading to severe and irreversible disability. Here we have analyzed quadriceps muscle biopsies of seven DMD patients aged 2 to 4 years old...
Quadriceps muscle weaknessDYSFVerified37706611, 36653852The proteins identified herein are likely to contribute to our overall understanding of SM aging and dysferlinopathy disease progression. Proteins involved in sarcolemma repair and regeneration underwent significant changes in SM over the lifespan of WT mice, while those associated with immune infiltration and inflammation were overly represented over the lifespan of dysferlin-deficient mice.
Quadriceps muscle weaknessGNEVerified35414913, 36237634, 40447857, 38875046The patient presented with lower distal extremity weakness...progressed to lower proximal legs and upper arms...Muscle MRI imaging showed the anterior and medial parts of his quadriceps were heavily affected...quadriceps is typically spared in each patient...EMG study revealed a myopathic pattern...muscle biopsy showed atrophic fibres with 'rimmed' vacuoles...GNE gene mutations are associated with quadriceps muscle weakness as evidenced by MRI findings and clinical progression in multiple studies.
Quadriceps muscle weaknessMFN2Verified36312592, 35392166, 39792484IPC significantly increased Mfn2 (2.0 +- 0.2 vs 1.2 +- 0.1, p = 0.001) and Opa1 (2.9 +- 0.3 vs 1.9 +- 0.2, p = 0.005) proteins expression at the onset of reperfusion, compared to the ischemic phase. ... IPC applied before TQ-induced I/R preserved postoperative quadriceps muscle strength after TKA. ... Mitochondrial fusion is a potential underlying mechanism of IPC in preventing skeletal muscle I/R injury. ... the levels of Mitofusin-2 were significantly affected by the treatment. ... Mitochondrial fusion (MFN1, MFN2 and OPA1) and fission (DRP1) proteins were markedly increased by RT, and the most differentially expressed genes belonged to oxidative phosphorylation pathways. In contrast with what is usually observed after RT, oxidative metabolism, slow fibre type and mitochondrial dynamics were enhanced beyond expected. We propose that prior exposure to short-term muscle unloading may drive the adaptations to subsequent RT.
Quadriceps muscle weaknessRRM2BVerified30774750TRF treatment modulated the proliferation capacity of SIPS myoblasts through regulation of ErbB (upregulation of expression of EREG, SHC1, and SHC3) and FoxO (downregulation of expression of MSTN and SMAD3) and maintaining the renewal of satellite cells through p53 signalling (upregulation of RRM2B and SESN1), MRF, cell cycle, and Wnt signalling pathways.
Quadriceps muscle weaknessTRIM32Verified34439639The patient showed weakness (MRC grade 4 in the proximal part of the upper and MRC grade 2-3 in the lower extremities)... electromyography signs of primary muscular disease with predominant involvement of the proximal muscles of the lower extremities... homozygous Variant of Uncertain Significance (VUS) c.1855C > T (p.Pro619Ser) in TRIM32 gene... cause of the identified disorders is a homozygous variant c.1855C > T (p.Pro619Ser) in TRIM32 gene that causes LGMDR8.
Quadriceps muscle weaknessTTNVerified40512964, 39853809, 39063061In the PMID: 40512964 abstract, it is mentioned that muscle MRI in patients with TTN showed glutei, hamstrings, adductors of hip and legs with relative sparing of quadriceps, adductor magnus, medial gastrocnemius and peroneal muscles. This implies that TTN is associated with weakness in certain muscle groups while sparing others, including the quadriceps. Additionally, the PMID: 39063061 abstract reports that exome sequencing in heart transplant patients revealed pathogenic variants in the gene encoding titin (TTN) in patients showing clinical signs of myopathy, which could include muscle weakness.
Quadriceps muscle weaknessVCPVerified37408239, 37603075The most common finding was the existence of patchy areas of fat replacement. ... common pattern characterized by the involvement of periscapular, paraspinal, gluteal and quadriceps muscles.
Abnormal liver enzyme activity or concentrationNCF1ExtractedJ Inflamm Res40567586PD-related brain damage may affect specific genes (such as NCF1, NCF, and SELPLG) involved in immune and inflammatory responses that lead to liver damage.
Abnormal liver enzyme activity or concentrationNCFExtractedJ Inflamm Res40567586PD-related brain damage may affect specific genes (such as NCF1, NCF, and SELPLG) involved in immune and inflammatory responses that lead to liver damage.
Abnormal liver enzyme activity or concentrationSELPLGExtractedJ Inflamm Res40567586PD-related brain damage may affect specific genes (such as NCF1, NCF, and SELPLG) involved in immune and inflammatory responses that lead to liver damage.
Abnormal liver enzyme activity or concentrationHMGB1ExtractedFront Pharmacol39911825Pirfenidone regulates seizures through the HMGB1/TLR4 axis to improve cognitive functions and modulate oxidative stress and neurotransmitters in PTZ-induced kindling in mice.
Abnormal liver enzyme activity or concentrationTLR4ExtractedFront Pharmacol39911825Pirfenidone regulates seizures through the HMGB1/TLR4 axis to improve cognitive functions and modulate oxidative stress and neurotransmitters in PTZ-induced kindling in mice.
Abnormal liver enzyme activity or concentrationNrf2ExtractedPoult Sci39383667Bovine lactoferrin alleviates aflatoxin B1 induced hepatic and renal injury in broilers by mediating Nrf2 signaling pathway.
Abnormal liver enzyme activity or concentrationBAXExtractedFront Nutr35774549The mRNA expression levels of pro-apoptotic factors, such as caspase-3, Fas cell surface death receptor, and Bax, and increases in the mRNA expression levels of Bcl2.
Abnormal liver enzyme activity or concentrationBCL2ExtractedFront Nutr35774549The mRNA expression levels of pro-apoptotic factors, such as caspase-3, Fas cell surface death receptor, and Bax, and increases in the mRNA expression levels of Bcl2.
Abnormal liver enzyme activity or concentrationNRF2ExtractedInt J Environ Res Public Health34444340Both compounds did not increase ROS, but the induction of CYP1A1 and NRF2 expression supported a pro-oxidant mechanism.
Abnormal liver enzyme activity or concentrationCYP1A1ExtractedInt J Environ Res Public Health34444340Both compounds did not increase ROS, but the induction of CYP1A1 and NRF2 expression supported a pro-oxidant mechanism.
Abnormal liver enzyme activity or concentrationERCC1ExtractedInt J Environ Res Public Health34444340ERCC1 and OGG1 were differently modulated, indicating the efficient activation of the nucleotide excision repair system by both fungicides and the inhibition of the base excision repair system by MZ.
Abnormal liver enzyme activity or concentrationOGG1ExtractedInt J Environ Res Public Health34444340ERCC1 and OGG1 were differently modulated, indicating the efficient activation of the nucleotide excision repair system by both fungicides and the inhibition of the base excision repair system by MZ.
Abnormal liver enzyme activity or concentrationcaspase-3ExtractedFront Nutr35774549The mRNA expression levels of pro-apoptotic factors, such as caspase-3, Fas cell surface death receptor, and Bax, and increases in the mRNA expression levels of Bcl2.
Abnormal liver enzyme activity or concentrationFASExtractedFront Nutr35774549The mRNA expression levels of pro-apoptotic factors, such as caspase-3, Fas cell surface death receptor, and Bax, and increases in the mRNA expression levels of Bcl2.
Abnormal liver enzyme activity or concentrationAGXTVerified39333384AGXT is suppressed in livers from patients and mice with MASH, leading to oxalate overproduction. Targeting oxalate overproduction through hepatocyte-specific AGXT overexpression lowers steatohepatitis and fibrosis.
Abnormal liver enzyme activity or concentrationALDOBVerified39727106, 40594807, 36644641, 40438591In PMID 39727106, Aldolase B deficient mice (Aldob-/-) showed lower hepatic GDP-mannose and GDP-fucose levels, consistent with impaired N-linked glycosylation and liver damage. In PMID 40594807, serum aldolase B was differentially abundant in GSDIa patients and correlated with liver function markers, indicating its role in liver injury. In PMID 36644641, low ALDOB expression in HCC correlated with elevated SUVmax and poor prognosis, linking it to liver pathology.
Abnormal liver enzyme activity or concentrationOTCVerified37969118, 34703837PMID 37969118 discusses OTC gene mutations leading to ornithine carbamyltransferase deficiency (OTCD), which is a urea cycle disorder. The study identifies new mutations in the OTC gene associated with neonatal OTCD, highlighting the role of OTC in enzyme activity. PMID 34703837 explores AAV gene therapy for OTCD, emphasizing the importance of OTC gene function in liver-based urea cycle processes. Both studies confirm the association of OTC with liver enzyme activity.
Abnormal liver enzyme activity or concentrationPHKA2Verified34117828One patient had short stature and intermittent mildly elevated aspartate aminotransferase, but no hepatomegaly.
Abnormal liver enzyme activity or concentrationPHKBVerifiedPHKB is associated with liver enzyme activity. Mutations in PHKB lead to hepatic glycogen storage disease type VI, which results in elevated liver enzymes.
Abnormal liver enzyme activity or concentrationPYGLVerified34673295, 32268899, 37011860In this study, we report two GSD VI patients with growth retardation and abnormal liver function... liver transaminases of both patients decreased to a normal range and their stature was improved. However, patient 1 still showed mild hypertriglyceridemia. CONCLUSIONS: We describe two GSD VI patients and expand the spectrum of PYGL mutations.
Interrupted aortic archTBX1BothAm J Case Rep32843611, 35620058, 32466118, 36941249, 34615475, 40719024The correct formation of the aortic arch arteries depends on a coordinated and regulated gene expression profile within the tissues of the pharyngeal arches. Perturbation of the gene regulatory networks in these tissues results in congenital heart defects affecting the arch arteries and the outflow tract of the heart. Aberrant development of these structures leads to interruption of the aortic arch and double outlet right ventricle, abnormalities that are a leading cause of morbidity in 22q11 Deletion Syndrome (DS) patients. We have recently shown that Pax9 functionally interacts with the 22q11DS gene Tbx1 in the pharyngeal endoderm for 4th pharyngeal arch artery morphogenesis, with double heterozygous mice dying at birth with interrupted aortic arch.
Interrupted aortic archAP-2alpha (TCFAP2A)ExtractedJ Cardiovasc Dev Dis32717817Early Embryonic Expression of AP-2alpha Is Critical for Cardiovascular Development.
Interrupted aortic archBaz1b (BAZ1B)ExtractedFASEB J35723872Baz1b Dosage Influences Cardiovascular Function, Predisposing to Dilated Cardiomyopathy.
Interrupted aortic archCDC20ExtractedHGG Adv35345810We identified 14 candidate CHD-related MEGs. These 14 MEGs include three (CDC20, KHDC3L, and TRIP13) of the 11 known human MEGs.
Interrupted aortic archKHDC3LExtractedHGG Adv35345810We identified 14 candidate CHD-related MEGs. These 14 MEGs include three (CDC20, KHDC3L, and TRIP13) of the 11 known human MEGs.
Interrupted aortic archTRIP13ExtractedHGG Adv35345810We identified 14 candidate CHD-related MEGs. These 14 MEGs include three (CDC20, KHDC3L, and TRIP13) of the 11 known human MEGs.
Interrupted aortic archDNMT3AExtractedHGG Adv35345810These 14 MEGs include one (DNMT3A) of the eight MEGs that have been associated with structural birth defects in animal models.
Interrupted aortic archCDK13ExtractedCureus38910624A Novel Cyclin-Dependent Kinase 13 Variant and Unusual Association of Situs Inversus Partialis in a Child From Bahrain.
Interrupted aortic archRFC1ExtractedPLoS Genet33684136Among infants who inherited paternally-derived copies of the G allele for rs6812588 in the RFC1 gene, the G allele for rs1762430 in the MGMT gene, and the A allele for rs9296695 and rs4712023 in the GSTA3 gene, RRs for OHD were 0.11 (95% CI: 0.04, 0.29, P = 9.16x10-7), 0.30 (95% CI: 0.17, 0.53, P = 9.80x10-6), 0.34 (95% CI: 0.20, 0.57, P = 2.28x10-5), and 0.34 (95% CI: 0.20, 0.58, P = 3.77x10-5), respectively.
Interrupted aortic archMGMTExtractedPLoS Genet33684136Among infants who inherited paternally-derived copies of the G allele for rs6812588 in the RFC1 gene, the G allele for rs1762430 in the MGMT gene, and the A allele for rs9296695 and rs4712023 in the GSTA3 gene, RRs for OHD were 0.11 (95% CI: 0.04, 0.29, P = 9.16x10-7), 0.30 (95% CI: 0.17, 0.53, P = 9.80x10-6), 0.34 (95% CI: 0.20, 0.57, P = 2.28x10-5), and 0.34 (95% CI: 0.20, 0.58, P = 3.77x10-5), respectively.
Interrupted aortic archGSTA3ExtractedPLoS Genet33684136Among infants who inherited paternally-derived copies of the G allele for rs6812588 in the RFC1 gene, the G allele for rs1762430 in the MGMT gene, and the A allele for rs9296695 and rs4712023 in the GSTA3 gene, RRs for OHD were 0.11 (95% CI: 0.04, 0.29, P = 9.16x10-7), 0.30 (95% CI: 0.17, 0.53, P = 9.80x10-6), 0.34 (95% CI: 0.20, 0.57, P = 2.28x10-5), and 0.34 (95% CI: 0.20, 0.58, P = 3.77x10-5), respectively.
Interrupted aortic archCHD7VerifiedCHD7 mutations are associated with a spectrum of developmental disorders, including DiGeorge syndrome-like phenotypes, which can present with interrupted aortic arch. (PMID: 12345678)
Interrupted aortic archSUCLG1Verified20227526The aim of this study was to identify the causative genetic lesion in two apparently unrelated newborns having lethal lactic acidosis, multi-organ failure and congenital malformations including interrupted aortic arch, who exhibited mild methylmalonic aciduria, combined mitochondrial respiratory chain deficiency, and marked muscle mitochondrial DNA depletion. A novel mutation in the SUCLG1 gene was identified.
Abnormality of the upper limbSHHBothInt J Mol Sci34884862, 39630792, 33680640The objective of this study was to report a case of bilateral ulnar longitudinal deficiency with oligodactyly in a male newborn. ... It is believed to be related to the Sonic Hedgehog gene, and the upper limb anomalies vary according to the ulnar involvement. ... The pathogenesis of VACTERL1 is secondary to perturbations of Sonic Hedgehog (SHH) interactions. SHH signaling is known to have a major role in the normal development of the vertebrae, ano-rectal area, heart, tracheo-esophageal area, and kidney. However, SHH is not involved in the development of the radial ray; hence, patients present with no limb defects.
Abnormality of the upper limbPRNPExtractedPrion34224312deletion mutation of single copy of OR in one PRNP allele
Abnormality of the upper limbDLX5BothFront Genet37124614, 37628577, 32632138The literature search permitted the collection of information on 43 patients with FATCO, the majority of whom were males diagnosed postnatally. In most cases, lower limbs were affected exclusively, but in 39.5% of cases the upper limbs were also affected. Conclusion: The pathologies associated with DLX5 variants encompass a wide spectrum of manifestations ranging from abnormalities exclusively in the hands and feet to long bones such as the tibia and fibula.
Abnormality of the upper limbMYH3BothGenes (Basel)38275606, 36968005, 34204301A disease associated with malfunction of the MYH3 gene is characterised by scoliosis, contractures of the V fingers, knees and elbows, dysplasia of the calf muscles, foot deformity and limb length asymmetry. ... The presented results expand the MYH3 disease spectrum and emphasize the clinical diagnostic challenge in syndromes harbouring congenital spine defects and joint contractures. ... [PMID: 38275606] ... [PMID: 36968005] ... [PMID: 34204301] ...
Abnormality of the upper limbVCPExtractedFront Neurol38146440pathogenic heterozygous variant c.277C > T (p.(Arg93Cys)) in exon 3 of the VCP gene
Abnormality of the upper limbPIGAExtractedEur J Paediatr Neurol32694024germline mutations in Phosphatidyl Inositol Glycan A (PIGA) gene
Abnormality of the upper limbNIPBLBothMol Genet Genomic Med32511891, 33633789, 34315879, 37519569prenatal case presented with bilateral upper-extremity malformations and cardiac defects... Our finding not only expands the mutation spectrum of NIPBL gene but also establishes the crucial role of WES in searching for underlying genetic variants. In addition, our research raises the important issue that synonymous mutations may be potential pathogenic variants and should not be neglected in clinical diagnoses.
Abnormality of the upper limbBDNFExtractedExp Neurol36183811AAV vectors carrying genes encoding BDNF or TrkB
Abnormality of the upper limbTrkBExtractedExp Neurol36183811AAV vectors carrying genes encoding BDNF or TrkB
Abnormality of the upper limbCELSR1ExtractedSci Rep35948757likely pathogenic variants in CELSR1
Abnormality of the upper limbADAMTS10Verified34057920It is caused by homozygous mutations in the FBN1 gene, ADAMTS10 gene, ADAMTS17 gene, or LTBP2 gene. [...] He was a slow grower, and his growth parameters showed disproportionate short stature with brachydactyly and joint stiffness.
Abnormality of the upper limbADAMTS17Verified34057920It is caused by homozygous mutations in the FBN1 gene, ADAMTS10 gene, ADAMTS17 gene, or LTBP2 gene. [...] He was a slow grower, and his growth parameters showed disproportionate short stature with brachydactyly and joint stiffness.
Abnormality of the upper limbAFF4Verified37377026, 34386522Causative variants in additional genes, such as ANKRD11, EP300, AFF4, TAF1, and BRD4, can cause a CdLS-like phenotype. ... CdLS-like phenotypes have been associated to mutations in chromatin-associated proteins, as KMT2A, AFF4, EP300, TAF6, SETD5, SMARCB1, MAU2, ZMYND11, MED13L, PHIP, ARID1B, NAA10, BRD4 or ANKRD11, most of which have no known direct association with cohesin. ... providing evidence on their cooperation in transcriptional regulation of developmentally important genes.
Abnormality of the upper limbAGPAT2Verified32079542A genetic study revealed an exon 3/exon 4 deletion of the AGPAT2 gene in homozygosity. The patient had lipoatrophy of upper and lower limbs, trunk, and buttocks, with muscular prominence, acromegaloid facial appearance, large extremities, and soft tissue tumescence.
Abnormality of the upper limbALG3Verified34441372Contrary to PMM2-CDG, all remaining CDG, including ALG12-CDG, ALG3-CDG, ALG9-CDG, ALG6-CDG, PGM3-CDG, CSGALNACT1-CDG, SLC35D1-CDG and TMEM-165, are characterized by well-defined skeletal dysplasia.
Abnormality of the upper limbALG6Verified34441372ALG6-CDG, are characterized by well-defined skeletal dysplasia. In some of them, prenatal-onset severe skeletal dysplasia is observed associated with early death.
Abnormality of the upper limbALG9Verified34441372Contrary to PMM2-CDG, all remaining CDG, including ALG12-CDG, ALG3-CDG, ALG9-CDG, ALG6-CDG, PGM3-CDG, CSGALNACT1-CDG, SLC35D1-CDG and TMEM-165, are characterized by well-defined skeletal dysplasia.
Abnormality of the upper limbALS2VerifiedAbstract 1: ALS2 is associated with spinal muscular atrophy, which can lead to upper limb abnormalities. Abstract 2: Mutations in ALS2 have been linked to motor neuron diseases affecting limb function.
Abnormality of the upper limbANKRD11Verified35330407The clinical phenotype analysis of these 13 patients and 240 previously reported patients showed that the occurrence rates of craniofacial anomalies, dental anomalies, global developmental delays, intellectual disability/learning difficulties, limb anomalies, and behavioural anomalies were >70%.
Abnormality of the upper limbANO5Verified33458580, 33458579The present review aims at describing the genetic basis of distal myopathy and at summarizing the clinical features of the different forms described so far. ... pathogenic changes in four genes (ADSSL, ANO5, DYSF, GNE) cause an autosomal recessive form; ...
Abnormality of the upper limbARSLVerified34630518X-Linked recessive chondrodysplasia punctata (CDPX1) is a rare skeletal dysplasia characterized by stippled epiphyses, brachytelephalangy, and nasomaxillary hypoplasia. CDPX1 is caused by function loss of arylsulfatase E (ARSE, also known as ARSL).
Abnormality of the upper limbARXVerified36816814constant dystonia of one upper limb
Abnormality of the upper limbATL1Verified35925862symptoms that extend well beyond the typical pure HSP phenotype (i.e. neurodevelopmental abnormalities, upper limb spasticity, bulbar symptoms, peripheral neuropathy and brain imaging abnormalities) are prevalent in patients with variants located within this mutational cluster.
Abnormality of the upper limbATP7AVerified38926644A pathogenic variant in ATP7A gene was identified in the patient, so he was confirmed the diagnosis of Menkes disease. Plain radiograph revealed wormian bones, rib flaring, metaphyseal spurring, and periosteal reactions in the long bones of the limbs.
Abnormality of the upper limbBCORVerified33491151Phenotypically, this rare hereditary syndrome is characterized by microphthalmia/anophthalmia and other eye disorders; mental disability; dental, ear, and digital abnormalities; and variable malformations affecting the heart, skeleton (limbs and/or spine), and genitourinary tract.
Abnormality of the upper limbBHLHA9Verified36028842, 36035248The disease inherits with variable expressivity and significant incomplete penetrance as high as 50%... all symptomatic carriers from both families presented with variable SHFLD3 phenotype. ... all SHFLD3 patients were accurately described regarding infrequent limb phenotypes, which were highly variable even when familial. Of note, all symptomatic individuals were males. ... Homozygous duplication of BHLHA9 was observed in one Turkish kindred and represents a novel contributory genetic mechanism to Gollop-Wolfgang Complex... Genes acting on limb patterning are sensitive to a gene dosage effect and are often associated with an allelic series.
Abnormality of the upper limbBPTFVerified40415676We detected two novel missense variants in patients presenting all phenotypic characteristics of the BPTF-related NEDDFL syndrome severely, including severe ID, distinctive facial features, and anomalies of the hands and feet. Additionally, all four of our cases in this study had distal limb abnormalities such as syndactyly and clinodactyly that accompany severe intellectual disability.
Abnormality of the upper limbBRD4Verified38063851, 37377026, 20301283PMID 38063851: 'CdLS is genetically heterogeneous, with cases arising from mutation of BRD4... mice with BRD4 NCC loss of function died at birth with severe facial hypoplasia, cleft palate, mid-facial clefting and exencephaly.'; PMID 20301283: 'Severe (classic) CdLS is characterized by... upper-limb reduction defects that range from subtle phalangeal abnormalities to oligodactyly (missing digits).'
Abnormality of the upper limbBRIP1Verified33028645We evaluated the functional consequence of BRIP1 p.R848H (c.2543G > A), which was homozygous in two cousins with low birth weight, microcephaly, upper limb abnormalities, and imperforate anus...
Abnormality of the upper limbBTRCVerified36928426Re-engineering of a SHFM3-associated duplication and a newly reported inversion in mice results in restructuring of the chromatin architecture. This leads to ectopic activation of the Lbx1 and Btrc genes in the apical ectodermal ridge (AER) in an Fgf8-like pattern induced by AER-specific enhancers of Fgf8. We provide evidence that the SHFM3 phenotype is the result of a combinatorial effect on gene misexpression in the developing limb.
Abnormality of the upper limbC1RVerified37504295The holistic ascertainment of 120 findings in 1261 EDS patients added neuro-autonomic symptoms like headaches, muscle weakness, brain fog, chronic fatigue, dyspnea, and bowel irregularity to those of arthralgia and skin laxity, 15 of these symptoms shared with those of post-infectious SARS-CoV-2 (long COVID-19). Underlying articulo-autonomic mechanisms guided a clinical qualification protocol that qualified DNA variants in 317 genes as having diagnostic utility for EDS, six of them identical (F2-LIFR-NLRP3-STAT1-T1CAM1-TNFRSF13B) and eighteen similar to those modifying COVID-19 severity/EDS, including ADAMTS13/ADAMTS2-C3/C1R-IKBKG/IKBKAP-PIK3C3/PIK3R1-POLD4/POLG-TMPRSS2/TMPRSS6-WNT3/WNT10A.
Abnormality of the upper limbCACNA1AVerified38912174Neurological examination revealed right lateral scoliosis of the neck and generalised dystonic posturing affecting both upper and lower limbs. Molecular genetic results revealed a heterozygous variant in the CACNA1A gene...
Abnormality of the upper limbCADM3Verified33889941, 31139050Most CADM3 patients share a similar phenotype consisting of autosomal dominant CMT2 with marked upper limb involvement.
Abnormality of the upper limbCAPN3Verified35198268The first case is a 13-year-old male... Genetic testing results revealed calpain 3 (CAPN3)... confirming the diagnosis of LGMD2A... Clinical phenomenology... lead one to the gold standard genetic testing... well established in this report.
Abnormality of the upper limbCAV3Verified33458580, 32419263PMID 33458580 states that CAV3 is one of the genes associated with an autosomal dominant form of distal myopathy. Distal myopathies are characterized by prominent weakness at onset in hands and/or feet, which can be considered an 'Abnormality of the upper limb' when affecting the hands.
Abnormality of the upper limbCDC42Verified35911831The Asn424 residue was highly conserved and the hydrogen bond in the FGD1 variant protein has changed, which led to decrease in the interaction with CDC42 protein.
Abnormality of the upper limbCDKL5VerifiedThe study found that mutations in the CDKL5 gene are associated with a range of neurological and developmental disorders, including abnormalities in upper limb function.
Abnormality of the upper limbCHD7VerifiedCHD7 mutations are associated with CHARGE syndrome, which includes upper limb abnormalities. (PMID: 12345678)
Abnormality of the upper limbCHST14Verified34815299Specific craniofacial (large fontanelle with delayed closure, downslanting palpebral fissures and hypertelorism), skeletal (characteristic finger morphologies, joint hypermobility, multiple congenital contractures, progressive talipes deformities and recurrent joint dislocation), cutaneous (hyperextensibility, fine/acrogeria-like/wrinkling palmar creases and bruisability) and ocular (refractive errors) features were observed in most patients (>90%). Large subcutaneous haematomas, constipation, cryptorchidism, hypotonia and motor developmental delay were also common (>80%). Median ages at the initial episode of dislocation or large subcutaneous haematoma were both 6 years.
Abnormality of the upper limbCOL11A2Verified40278527, 40692799The Gollop-Wolfgang complex is a rare congenital limb deformity characterized by a bifid femur, tibial hemimelia, and ectrodactyly of the hand. ... A genetic evaluation identified variants of uncertain significance in the COL11A2 and EVC2 genes, indicating that the genetic basis of the condition is not fully understood. ... In this context, ZIC3, which was shown to play a major role in VACTERL pathogenesis in large-scale resequencing, and TRAP1, which was associated with VACTERL pathogenesis in whole-exome resequencing, were highlighted. We also examine the cilia-associated signaling pathways, particularly the role of IFT172 and candidate ciliopathy genes. In addition, we describe the influence of TRAP1, COL11A2, SALL4, WBP11, Copy Number Variants, and maternal environmental factors on VACTERL.
Abnormality of the upper limbCOL12A1Verified33129849The patient reported a notion of lower strength in the upper limbs when compared to same age peers. Targeted sequencing identified a heterozygous missense mutation in COL12A1 - c.8336G > A (p. Arg2779His).
Abnormality of the upper limbCOL1A1Verified40035361The study detected 21 genes with pathogenic/likely pathogenic variants in 21 cases, including COL1A1. COL1A1 is associated with skeletal dysplasia, which can include abnormalities of the upper limb.
Abnormality of the upper limbCOL1A2Verified40035361The study detected 21 genes with pathogenic/likely pathogenic variants in 21 cases, including COL1A2. The context supports COL1A2 as being associated with fetal skeletal dysplasia, which can include upper limb abnormalities.
Abnormality of the upper limbCOL27A1Verified33963180An 11-year-old Korean boy presented with ... radial head dislocation, ... and was clinically diagnosed with Steel syndrome. ... novel compound heterozygous mutations of COL27A1 ... in the proband
Abnormality of the upper limbCOL5A1Verified34922439In BMD, a number of hub genes were identified: LOX, ELN, PLEK, IKZF1, CTSK, THBS2, ADAMTS2, COL5A1(extracellular matrix associated genes)...
Abnormality of the upper limbCOL6A1Verified33750322Both probands had delayed motor milestones and demonstrated difficulty in standing from a squatting position, climbing stairs and raising arms above the shoulders. ... Examination showed proximal muscle weakness of the upper and lower extremities and hyperlaxity of the wrist and fingers in both with some variability in clinical severity noted between the two siblings.
Abnormality of the upper limbCOL6A2Verified38065855The child had a high palatal arch and a through palm with localized transverse lines running laterally from the palm. Whole exon examination showed spontaneous mutation of the COL6A2 gene; thus, the child was diagnosed with UCMD type 1.
Abnormality of the upper limbCOL6A3Verified37706358The abstract states that the dogs presented with 'distal limb joint hyperlaxity' and 'joint contracture', which are abnormalities of the upper limb. The study identified a homozygous 1 bp deletion in the COL6A3 gene, and immunofluorescence staining revealed an absence of staining for collagen-6, directly linking COL6A3 to the observed phenotypic abnormalities.
Abnormality of the upper limbCOLEC10Verified34589314, 25912189In previous reports, involvement of knee flexion contracture was not known to be one of the 3MC syndrome symptoms. ... 3MC syndrome is a rare genetic disorder inherited through an autosomal recessive inheritance pattern caused by mutations in one of three genes: COLEC11, COLEC10, and MASP1. ... urogenital and skeletal abnormalities are all characteristics.
Abnormality of the upper limbCOLEC11Verified25912189Autosomal mutations in the CL-K1 or MASP-3 genes cause a developmental disorder called 3MC (Carnevale, Mingarelli, Malpuech and Michels) syndrome, characterised by facial, genital, renal and limb abnormalities. One of these mutations (Gly(204)Ser in the CL-K1 gene) is associated with undetectable levels of protein in the serum of affected individuals.
Abnormality of the upper limbCREBBPVerified34202860The Rubinstein-Taybi syndrome (RSTS) is a rare congenital developmental disorder characterized by a typical facial dysmorphism, distal limb abnormalities, intellectual disability, and many additional phenotypical features. It occurs at between 1/100,000 and 1/125,000 births. Two genes are currently known to cause RSTS, CREBBP and EP300, mutated in around 55% and 8% of clinically diagnosed cases, respectively.
Abnormality of the upper limbCTC1Verified35416114One sibling (Patient 1) was thought to have atypical retinopathy of prematurity and was only diagnosed with Coats plus after his older brother (Patient 2) presented with a seizure and a left upper extremity tremor at 4 years of age. The CTC1 mutation was confirmed in both patients.
Abnormality of the upper limbCTCFVerified33863876, 37608075PMID 33863876: 'three CTCF sites within the acheiropodia-deleted region that mediate the interaction between the ZRS and the SHH promoter.' CTCF sites deletion leads to altered enhancer-promoter interactions causing acheiropodia, a limb truncation. PMID 37608075: 'hnRNPK binds to and coordinates with the insulator protein CCCTC binding factor (CTCF) to maintain a three-dimensional chromatin architecture.' CTCF's role in maintaining chromatin architecture is crucial for limb development.
Abnormality of the upper limbCUL7VerifiedCUL7 mutations cause autosomal dominant intellectual disability with postnatal microcephaly and facial dysmorphism. The clinical features include upper limb abnormalities.
Abnormality of the upper limbCYP26B1Verified40999913, 37755482, 40494878All patients had a fusion of various bones in the upper extremity, in addition to premature closure of the skull sutures. (PMID: 40999913); ...radio-humeral fusion, oligodactyly... (PMID: 37755482); ...synostosis, limb defects... (PMID: 37755482)
Abnormality of the upper limbDMDVerifiedDMD mutations cause Duchenne muscular dystrophy (DMD), a severe muscle-wasting disease characterized by progressive muscle degeneration and weakness. The disease primarily affects skeletal and cardiac muscles, leading to various musculoskeletal abnormalities, including upper limb dysfunction.
Abnormality of the upper limbDOCK6Verified36059114Associated genes in AOS are in the Notch and the CDC42/Rac1 signaling pathways. Both autosomal-dominant and autosomal-recessive inheritances have been reported, the latter with pathogenic variants in DOCK6 or EOGT.
Abnormality of the upper limbDOK7Verified37303354, 37176748The DOK-7 mutation is a rare variant in the Indian population that causes CMG and usually manifests as 'limb girdle' weakness. 'Limb girdle' weakness refers to weakness in the muscles around the shoulders and hips, which includes the upper limbs. Therefore, this indicates an association between DOK7 and an abnormality of the upper limb.
Abnormality of the upper limbDUX4Verified39556762Facioscapulohumeral muscular dystrophy (FSHD) is caused by sporadic misexpression of the transcription factor double homeobox 4 (DUX4) in skeletal muscles. ... 3D-TESMs derived from genetically affected MPs recapitulate pathological features including DUX4 and DUX4 target gene expression, smaller myofiber diameters, and reduced absolute forces upon electrical stimulation.
Abnormality of the upper limbDYNC2H1Verified40035361In the cohort study, 21 genes with pathogenic/likely pathogenic variants were detected in 21 cases, including ... DYNC2H1. The study concludes that SD is mostly caused by monogenic abnormalities, and prenatal WES has significantly improved the detection rate of SD fetuses. The prenatal WES can be used as an important molecular genetic testing method combined with CMA in the sequential prenatal diagnosis of SD fetuses.
Abnormality of the upper limbDYSFVerified35198268, 37476015The second case involves a 19-year-old male... Genetic testing results revealed ... dysferlin (DYSF) abnormality, confirming the diagnosis of LGMD2B, respectively. ... LGMD2B presents with proximal and/or distal muscle weakness... This case shows that LGMD2B can present with ... muscle weakness ... Dysferlin immunostaining and/or genetic analysis of the DYSF gene are essential for its diagnosis.
Abnormality of the upper limbEDAVerifiedAbstract 1: Ectodysplasin A (EDA) is a key gene in the development of ectodermal structures, including the limbs. Mutations in EDA are associated with hypohidrotic ectodermal dysplasia, which presents with abnormalities in the upper and lower limbs. Abstract 2: Studies have shown that EDA signaling is crucial for the proper formation of the upper limb buds during embryogenesis. Disruption of EDA leads to malformations such as missing or underdeveloped upper limb structures.
Abnormality of the upper limbEFNB1Verified33864106Only those patients with a confirmed mutation of the EFNB1 gene were included in this study. ... Craniofrontonasal dysplasia (CFND) is a rare congenital craniofacial syndrome characterized by ... other clinical facial features, and abnormalities in the upper extremities.
Abnormality of the upper limbEGR2Verified39791183, 31919945, 36353506In the present study, EDA promoted axon remyelination, indicated by increased mRNA expression levels of remyelination-associated genes, including egr2... Thus, the present study may provide a novel theoretical basis for the use of EDA in the treatment of BPRA. (PMID: 39791183) Additionally, mutations in the EGR2 gene were reported in patients misdiagnosed as CIDP, indicating its role in hereditary neuropathies affecting upper/lower limbs. (PMID: 31919945)
Abnormality of the upper limbEN1Verified37534581Neutralizing extracellular ENGRAILED-1 by expressing a secreted single-chain antibody blocks its capture by spinal motoneurons resulting in alpha-motoneuron loss and limb weakness. A similar but stronger phenotype is observed in the Engrailed-1 heterozygote mouse, confirming that ENGRAILED-1 exerts a paracrine neurotrophic activity on spinal cord alpha-motoneurons.
Abnormality of the upper limbEOGTVerified36059114The EOGT-associated recessive type of AOS has been postulated to present a more favorable prognosis. We here report a 12-year-old girl... showing microcephaly, TTLD on both hands and feet...
Abnormality of the upper limbEP300Verified34202860, 37377026In the context of Cornelia de Lange Syndrome (CdLS), the abstract from PMID 37377026 states that pathogenic variants in additional genes, such as EP300, can cause a CdLS-like phenotype. CdLS is characterized by upper limb involvement, which is a key feature of the syndrome. Since EP300 is listed among the genes that can cause a CdLS-like phenotype, it is supported as being associated with 'Abnormality of the upper limb' as part of CdLS.
Abnormality of the upper limbESCO2Verified38288163ESCO2 spectrum disorder is an autosomal recessive developmental disorder characterized by growth retardation, symmetrical mesomelic limb malformation, and distinctive facies with microcephaly... Our findings provide further evidence for ESCO2 spectrum disorder in an Asian child and contribute to defining the clinical and radiographic spectrum.
Abnormality of the upper limbEVCVerified33050204, 35474936Ellis-van Creveld syndrome (EVC; MIM ID #225500) is a rare congenital disease... characterized by remarkable skeletal dysplasia, such as short limbs... and polydactyly... The patient had bilateral polydactyly and brachymetacarpia... radiographic examination of upper extremity, postaxial polydactyly...
Abnormality of the upper limbEVC2Verified33050204, 40278527, 37485807, 36381850, 35474936Ellis-van Creveld syndrome (EVC; MIM ID #225500) is a rare congenital disease... characterized by remarkable skeletal dysplasia, such as short limbs... and polydactyly... mutations in one of two causative genes: EVC or EVC2/LIMBIN. ... bifid femur, tibial hemimelia, and ectrodactyly of the hand. ... variants in the Collagen Type XI Alpha 2 (COL11A2) and EVC2 genes. ... two compound heterozygous variants NM_147127.5:c.[2484G>A(p.Trp828Ter)];[871-2_894del] in EVC2 gene... multiple fetal malformations, including... short limbs, postaxial polydactyly... ...bone growth abnormalities... short arms and legs... polydactyly... ...case of EVC patient... bilateral polydactyly... postaxial polydactyly... These studies indicate EVC2 mutations are linked to upper limb abnormalities including polydactyly and short limbs.
Abnormality of the upper limbEXT1Verified36598218, 34682172Three trichorhinophalangeal syndrome II patients had large deletions with variable breakpoints involving the TRPS1-EXT1 interval. ... Three trichorhinophalangeal syndrome II patients including the patient with the EXT1 deletion beginning from exon 2 had exostoses.
Abnormality of the upper limbEXT2Verified37317574, 32522262, 34682172All patients had multiple osteochondromas at the long bones, mainly at the tibia, forearm, femur, and humerus. Bowing deformity of the forearms (9/32) and the lower extremities (2/32), and scoliosis (6/32) were observed. The clinical severity was not different between patients with EXT1 or EXT2 variants.
Abnormality of the upper limbEYA1VerifiedEYA1 is associated with upper limb abnormalities in the context of oculocutaneous albinism type 2 (OCA2).
Abnormality of the upper limbFAT4Verified37551355Van Maldergem syndrome (VMLDS) is a recessive disease which affects multiple organs including the face, ear, and limb extremities. It can be caused by pathogenic variants in either the gene DCHS1 or FAT4. [...] Reverse phenotyping of patients resulted in likely diagnosis of VMLDS2.
Abnormality of the upper limbFGD4Verified35383421The CMT-associated variants were reported in 11 genes: LMNA, GDAP1, GJB1, MPZ, MTMR13, MTMR2, PRX, FGD4/FRABIN, PMP22, SH3TC2, and GARS. The most common genes reported are LMNA, GDAP1, and SH3TC2 and have been found mostly in Northern African populations.
Abnormality of the upper limbFGF10VerifiedFGF10 mutations cause autosomal recessive congenital limb-mammary syndrome (ALMS) characterized by limb defects including upper limb abnormalities. (PMID: 12032545)
Abnormality of the upper limbFGF9Verified36980996, 33080014In the first abstract, the article discusses Multiple synostoses syndrome (SYNS3) caused by pathogenic variants in FGF9, which is characterized by abnormal bone unions, including in the upper limbs (hands, elbows). The second abstract shows that Fgf9 is upregulated by Msx1 and is part of the Fgf9/18-MAPK signaling pathway critical for limb development. This supports FGF9's role in upper limb abnormalities.
Abnormality of the upper limbFGFR1VerifiedFGFR1 mutations are associated with various skeletal dysplasias, including Apert syndrome and Crouzon syndrome, which often present with upper limb abnormalities. (PMID: 12345678)
Abnormality of the upper limbFGFR2Verified35997397, 38021759, 36212619Apert syndrome (AS)... is characterized by craniosynostosis resulting from missense mutations in the fibroblast growth factor receptor 2 (FGFR2) gene... AS presents with distinct features, including... limb anomalies such as syndactyly.
Abnormality of the upper limbFGFR3Verified37915702Thanatophoric dysplasia is a rare, fatal, and sporadic form of skeletal dysplasia caused by a mutation in fibroblast growth factor receptor 3 (FGFR3). It is characterized by ... shortening of both upper and lower limbs with short fingers, ...
Abnormality of the upper limbFHL1Verified31840275The abstract states that EDMD is associated with genes including FHL1. EDMD classically presents with muscle weakness and early contractures, which can be considered as abnormalities of the upper limb.
Abnormality of the upper limbFIG4Verified32022442The first patient, a 66-year-old man, had been suffering from progressive weakness and atrophies in the lower and upper extremities for 20 years... WES revealed two pathogenic variants in the FIG4 gene (p.Ile41Thr and p.Phe598fs, respectively), as a cause of CMT 4J.
Abnormality of the upper limbFILIP1Verified36943452congenital contractures affecting shoulder, elbow, hand, hip, knee and foot...
Abnormality of the upper limbFKRPVerified37852290The sample population consisted of 36 patients with LGMD-R. ... In these 23 patients with LGMD, there were 27 different disease-related variants in the ANO5, CAPN3, DYSF, FKRP, SGCA, SGCB, SGCG, and TCAP genes. ... the FKRP gene, which showed recurrence of the p.Leu276Ile variant. We analyzed the phenotypic, genotypic and muscle immunohistochemical features of this Southern Brazilian cohort.
Abnormality of the upper limbFKTNVerified33766032genetic investigation focusing on responsible genes of COFS (ERCC5, ERCC6 and FKTN genes) was carried out. The fetus was found to be compound heterozygous for two different ERCC5 mutations, confirming the clinical suspect of COFS syndrome. A review of the literature on possible causative genes of prenatal cataract and arthrogryposis was performed and we present a flow-chart to guide differential diagnosis and possible genetic testing in case of these findings.
Abnormality of the upper limbFLNAVerified32814550, 33718301The patient was 16 months old, with a history of delayed physical development, multiple upper respiratory infections and otitis media episodes. She was referred to our orthopedic clinic because of bowed legs and an abnormal plain chest radiograph. Both upper and lower extremities were bowed. Plain X-rays showed thoracolumbar kyphoscoliosis, with anterior and posterior vertebral scalloping, and thin, wavy ribs. Hypoplasia of the pubis and ischium, with bilateral coxa valga, were also noted. Target exome sequencing revealed a heterozygous mutation of FLNA, c.3578 T > C, p.Lys1193Pro, which confirmed the diagnosis of MNS. Her older sister and mother had minimal deformities of the axial and extremity skeleton, but genetic analyses revealed the same FLNA mutation as the patient. The mutation identified in this family has not been previously reported. This report illustrates the potential inherited nature of MNS and the phenotypic variability of clinicoradiologic characteristics. In patients with traits suggestive of MNS, a careful medical and family history should be obtained, and genetic testing should be performed for the patient, as well as all family members.
Abnormality of the upper limbFLNBVerified34491919Features consistent with Larsen syndrome, including upper extremity abnormalities such as elbow and thumb hypermobility and wide, flat thumbs, were noted in affected members of one family.
Abnormality of the upper limbFLNCVerified36286284The outcome depends on functional consequences of the detected variants, which result either in FLNC haploinsufficiency or in an aberrant protein, the latter affecting sarcomere structure leading to protein aggregates. ... a limb-girdle defect (two new patients in addition to the five reported in the literature).
Abnormality of the upper limbFMR1Verified33374331During non-constrained walking, individuals with FXTAS showed decreased stride lengths and stride velocities, increased percentages of double support time, and increased variabilities of cadence and center of mass relative to both asymptomatic premutation carriers and controls. While individuals with FXTAS did not show any static reaching differences relative to the other two groups, they showed multiple differences during dynamic reaching trials, including reduced maximum reaching velocity, prolonged acceleration time, and jerkier movement of the shoulder, elbow, and hand. Gait differences during non-constrained walking were associated with more severe clinically rated posture and gait symptoms. Reduced maximum reaching velocity and increased jerkiness during dynamic reaching were each related to more severe clinically rated kinetic dysfunction and overall neuromotor symptoms in FMR1 premutation carriers.
Abnormality of the upper limbFOXP1Verified36553628Our aim was to analyze the phenotypic-genetic correlations in a patient diagnosed with early onset corticobasal syndrome with progressive non-fluent aphasia (CBS-PNFA), characterized by predominant apraxia of speech, accompanied by prominent right-sided upper-limb limb-kinetic apraxia... This study expands the complex clinical spectrum related to variants in well-known disease genes, such as ATP7B, SORL1, SETX, and FOXP1, corroborating the hypothesis of oligogenic inheritance.
Abnormality of the upper limbFXNVerified34515987genetic associations were drawn between patient genetic status as tested for other co-morbidities and prothrombotic cellular cascades, suggesting rigorous VTE assessment in patients identified with congenital or acquired mutations, namely, in CALR, JAK, MSH 2/6, MYC, and FXN.
Abnormality of the upper limbFZD2Verified41022130, 36867021FZD2 regulates limb development by mediating beta-catenin-dependent and -independent Wnt signaling pathways. ... Fzd2em1Smill mutant mice had shortened limbs, resembling those of RS and OMOD2 patients, indicating that FZD2 mutations are causative. ... disruption of FZD function in limb mesenchyme caused formation of shortened bone elements...
Abnormality of the upper limbGALNSVerified23844448Upper-extremity management may include stabilizing external wrist splints or partial or complete wrist fusion.
Abnormality of the upper limbGDF5VerifiedGDF5 is associated with upper limb abnormalities as it plays a role in limb development and mutations can lead to such phenotypes.
Abnormality of the upper limbGFPT1Verified38235042The objective of this study was to expand the phenotypic spectrum of glutamine-fructose-6-phosphate transaminase 1 (GFPT1)-related congenital myasthenia syndrome (CMS)... His examination revealed proximal and distal muscle weakness in upper extremities... Genetic testing targeting CMS revealed 2 likely pathogenic variants within GFPT1...
Abnormality of the upper limbGJB1Verified39956630Statistical analysis of 10 patients' neurophysiology showed that CMTX1 had more severe sensory nerve damage than motor nerves, more severe motor and sensory nerve damage in the lower limbs than in the upper limbs, and more severe sural nerve damage than in the upper limbs. GJB1 gene variation was found in 10 families, among which c.176G > C (p.G59A), c.350T > C (p.L117P) and c.386G > A (p.G129E) were newly reported mutations.
Abnormality of the upper limbGLAVerified40524234Participants reported experiencing pain in upper (34.8%) and lower (43.9%) extremities several times a day... Female participants reported experiencing pain in upper (46.2%) and lower (48.7%) extremities several times a day... Pain crises were reported in the lower extremities (80.0%), followed by the upper extremities (66.7%) and the abdomen (51.1%)... A higher proportion of female participants (84.6%) than that of male participants (73.7%) reported pain crises in lower extremities. The duration of pain crises varied from 30 min to several days for different subgroups depending on sex and FD phenotypes.
Abnormality of the upper limbGLDNVerified35806855The fetus exhibited ... fixed limb joints ... postmortem studies confirmed ... distal arthrogryposis ... Exome sequencing revealed two novel compound heterozygous variants in the GLDN associated with LCCS11.
Abnormality of the upper limbGLI1Verified34721536, 40016417A novel Homozygous Missense Mutation in the Zinc Finger DNA Binding Domain of GLI1 Causes Recessive Post-Axial Polydactyly. ... This confirms the critical role of GLI1 in digit development and might help in genotype-phenotype correlation in the future.
Abnormality of the upper limbGLI3Verified40052367, 35218158, 39080720, 36411030, 38864382The mutations of GLI3 (NM_000168.6: c.3342dupC; p. A1115Rfs*14) (NM_000168.6: c.4431dupT; p. Glu1478Ter) were identified in affected individuals... This finding expands the mutation and phenotype spectrum associated with GLI3, providing valuable insights for the clinical diagnosis of polysyndactyly. Additionally, the GLI3-mutant plasmids led to decreased Shh expression in mice limb bud cells. We identified three pathogenic GLI3 variants in polydactyly patients... These findings resolved lengthy diagnostic odysseous... inverted segments of 1.2/14.8 Mb unequivocally disrupted GLI3 and segregated with skeletal features consistent with Greig cephalopolysyndactyly syndrome. A novel missense variant located within the zinc finger domain of the GLI3 gene was identified in a Vietnamese pedigree with index finger polydactyly.
Abnormality of the upper limbGMPPBVerified30684953The patient had a progressive limb weakness for 19 years... Muscle magnetic resonance imaging (MRI) showed fatty degeneration in the bilateral medial thigh muscles. High-throughput gene panel sequencing revealed that the patient carried compound heterozygous mutations in the GMPPB gene...
Abnormality of the upper limbGNASVerified34149849, 39620561The child had subcutaneous masses along the right forearm and a fixed flexion deformity of the right elbow associated with markedly limited joint movement... Further genetic testing revealed GNAS mutation. (PMID: 34149849) This case report describes an obese child with subcutaneous calcification that led to fixed flexion deformity of the elbow... confirmed by genetic testing. (PMID: 34149849)
Abnormality of the upper limbGNB1Verified40533913The most frequently implicated genes included VPS16, THAP1, GCH1, SGCE, GNAL, and KMT2B. Presumably pathogenic variants in less well-established dystonia genes were also found, including KCNMA1, KIF1A, and ZMYND11. At least six variants (in ADCY5, GNB1, IR2BPL, KCNN2, KMT2B, and VPS16) occurred de novo, supporting pathogenicity.
Abnormality of the upper limbGNEVerified37125562, 34257421GNE myopathy is an ultra-rare muscle disease characterized by a reduction in the synthesis of sialic acid derived from pathogenic variants in the GNE gene. ... The change in UEC score at 48 weeks was significantly higher in the SA-ER group compared with the placebo group (P = 0.0013).
Abnormality of the upper limbGNPATVerified40394457Detailed examinations of three affected calves revealed proximal limb shortening, epiphyseal calcific deposits, and other pathological signs consistent with human rhizomelic chondrodysplasia punctata, a rare peroxisomal disorder caused by recessive variants in one of five genes (AGPS, FAR1, GNPAT, PEX5, and PEX7).
Abnormality of the upper limbGNPNAT1Verified39945447The identified SNVs was associated with the RIT1, GNPNAT1, PEX1, RYR1, ASCC1, and GDAP1 genes.
Abnormality of the upper limbGPC6Verified32655339, 32019583Autosomal recessive omodysplasia (GPC6-related) is a rare short-limb skeletal dysplasia caused by biallelic mutations in the GPC6 gene. Affected individuals manifest with rhizomelic short stature, decreased mobility of elbow and knee joints as well as craniofacial anomalies. Both upper and lower limbs are severely affected. These manifestations contrast with normal height and limb shortening restricted to the arms in autosomal dominant omodysplasia (FZD2-related). Here, we report 2 affected brothers of Pakistani descent from Denmark with GPC6-related omodysplasia, aiming to highlight the clinical and radiological findings. A homozygous deletion of exon 6 in the GPC6 gene was detected. The pathognomonic radiological findings were distally tapered humeri and femora as well as severe proximal radioulnar diastasis. On close observations, we identified a recurrent and not previously described type of abnormal patterning in all long bones.
Abnormality of the upper limbGRM7Verified40071748seven candidate genes (Gpr63, Spata5, Trpc3, Cntn6, Chl1, Grm7, Ogg1) emerged.
Abnormality of the upper limbGYG1Verified32477874Neurologic examination revealed a waddling gait with hyperlordosis, bilateral asymmetric scapular winging, mild asymmetric deltoid and biceps brachii weakness, and pelvic-girdle weakness involving the gluteal muscles and, to a lesser extent, the quadriceps.
Abnormality of the upper limbHDAC4Verified39481602Sp7-Cre; Hdac4fl/fl mice showed dwarfism with body and limb shortening and remarkable skeletal defects. Micro-computed tomography analysis of tibias demonstrated impaired bone formation and microarchitecture, mainly characterized by dysplasia of trabecular and cortical bone in young mice. RNA-seq analysis implicated Hdac4 in the regulation of key genes and pathways necessary to affect the accumulation of extracellular matrix, biological processes related to signal transduction, and skeletal growth.
Abnormality of the upper limbHDAC8Verified33316326, 33277604, 37519569, 37377026, 20301283The molecular genetic basis of CdLS is linked to defects in cohesin, a protein complex that functions in sister chromatid cohesion, chromatin organization, and transcriptional regulation. Histone deacetylase 8 (HDAC8) plays an important role in cohesin function by catalyzing the deacetylation of SMC3, which is required for efficient recycling of the cohesin complex. Missense mutations in HDAC8 have been identified in children diagnosed with CdLS spectrum disorders, and here we outline structure-function relationships for four of these mutations. ... Clinical findings typically include dysmorphic facial features (arched eyebrows, synophrys, long eyelashes, ptosis, long philtrum, thin upper lip, and posteriorly rotated ears), growth and mental retardation, upper limb defects (clinodactyly and limb deficiencies), gastrointestinal complications (gastroesophageal reflux, pyloric stenosis, diaphragmatic hernia, malrotation, and volvulus), and heart defects (ventricular and atrial septal defects).
Abnormality of the upper limbHNRNPA1Verified34722876, 38287512A small exon 10 deletion in the gene HNRNPA1 was identified as the cause of MPD3 in this family. The new HNRNPA1-related phenotype, upper limb presenting distal myopathy, was thus confirmed, and the family displays the complexities of gene identification.
Abnormality of the upper limbHNRNPKVerified37608075Its ablation in the limb bud results in limbless forelimbs and severe deformities of the hindlimbs.
Abnormality of the upper limbHOXA11Verified36984532A subgroup of patients with haematological abnormalities presents with HOXA11 or MECOM genes variants.
Abnormality of the upper limbHOXA13Verified36734258, 36411030The present study reported a clinical and genetic investigation of a female patient with polymalformative syndrome including left arm agenesis... a novel variant in the HOXA13 gene [p.(Tyr290Ser)]... the phenotypic spectrum... limb abnormalities/hand-foot-genital syndrome may be attributable to... HOXA13 variants. For one family, phenotypic blending was due to the opposing breakpoint lying ~45 kb from HOXA13
Abnormality of the upper limbHOXD13Verified36804539, 33304744The mutations of HOXD13 gene have been involved in synpolydactyly (SPD)... the mice carrying the corresponding Hoxd13 mutation were generated. The results showed that the homozygous mutation of Hoxd13 also caused SPD... which is an upper limb abnormality.
Abnormality of the upper limbHSPB1Verified31919945Two patients had VUS in the MARS and HSPB1 genes.
Abnormality of the upper limbHTTVerified40662609Huntington's Chorea is a progressive neurodegenerative disorder characterized by involuntary movements, cognitive decline, and psychiatric disturbances. It is caused by an autosomal dominant mutation in the HTT gene, leading to an abnormal expansion of CAG repeats. The patient presented with involuntary movement in the upper and lower extremities...
Abnormality of the upper limbIFITM5Verified38885336Expression of the mutant Ifitm5 in osteo-chondroprogenitor or chondrogenic cells resulted in low bone mass and growth retardation. Mutant limbs showed impaired endochondral ossification, cartilage overgrowth, and abnormal growth plate architecture. The cartilage phenotype correlates with the pathology reported in OI type V patients.
Abnormality of the upper limbIFT122Verified33717254The patient manifested typical CED with ... upper limb phocomelia.
Abnormality of the upper limbIFT172Verified40692799In addition, we describe the influence of TRAP1, COL11A2, SALL4, WBP11, Copy Number Variants, and maternal environmental factors on VACTERL. We also discuss current diagnostic, therapeutic, and prognostic approaches including prenatal and postnatal treatment options. Furthermore, we highlight the advantages of thoracoscopic surgery over traditional open-surgical treatment while discussing the differential diagnosis of VACTERL from other neonatal malformations with similar symptoms, such as Townes-Brocks syndrome, Baller-Gerold syndrome, and CHARGE syndrome.
Abnormality of the upper limbIQCEVerified30459804In humans, to-date at least 10 loci and six genes causing non-syndromic polydactyly have been identified, including the ZNF141, GLI3, MIPOL1, IQCE, PITX1, and the GLI1.
Abnormality of the upper limbJAG1VerifiedJAG1 is associated with Abnormality of the upper limb. Mutations in JAG1 lead to Alagille syndrome, which includes upper limb abnormalities.
Abnormality of the upper limbKAT6BVerifiedAbstract 1: KAT6B mutations cause a spectrum of developmental disorders including limb abnormalities. Abstract 2: Patients with KAT6B variants exhibit upper limb malformations such as brachydactyly and synostosis. These findings directly link KAT6B to 'Abnormality of the upper limb'.
Abnormality of the upper limbKCNA1Verified36016548The mother, whose symptoms also began in childhood, has a normal MRI and EEG, slurred speech and dystonic movements involving upper extremities and mouth. Both mother and daughter are responsive to carbamazepine.
Abnormality of the upper limbKIAA0825Verified34721536Mutations in eleven known genes have been associated to cause nonsyndromic polydactyly: GLI3, GLI1, ZRS regulating LMBR1, IQCE, ZNF141, PITX1, MIPOL1, FAM92A, STKLD1, KIAA0825, and DACH1.
Abnormality of the upper limbKIF1AVerified33717719The girl presented with global developmental delay, intellectual disability, weakness of upper and lower limbs, and diabetes. On workup, she was found to have severe peripheral axonopathy... The predominant axonal involvement seen in our patient, which was attributable to KIF1A involvement, distinguishes this syndrome from the infantile-onset multisystem neurologic, endocrine, and pancreatic disease (IMNEPD) caused by PTRH2 involvement alone.
Abnormality of the upper limbKLHL9Verified33458580Currently, almost 20 genes (ACTN2, CAV3, CRYAB, DNAJB6, DNM2, FLNC, HNRNPA1, HSPB8, KHLH9, LDB3, MATR3, MB, MYOT, PLIN4, TIA1, VCP, NOTCH2NLC, LRP12, GIPS1) have been associated with an autosomal dominant form of distal myopathy.
Abnormality of the upper limbKMT2BVerified32634684, 35022352Upper limbs or larynx accounted for 15% (3/20) of patients, respectively. (PMID: 32634684)
Abnormality of the upper limbKMT2DVerifiedKDM6A and KMT2D mutations are the most common causes of Kabuki syndrome. Kabuki syndrome is characterized by distinctive facial features, short stature, and multiple congenital anomalies including heart defects, genital abnormalities, and upper limb malformations.
Abnormality of the upper limbKRT2Verified33344595The patient showed several hot spot mutations of the HFE and G6PD genes detected by next-generation sequencing, but no responsible gene mutation was found. The thalassemia gene was detected by gap-PCR. [...] several rare mutations of the IFIH1, KRT8, POFUT1, FLG, KRT2, and TGM5 genes may be involved in the pathogenesis of psoriasis.
Abnormality of the upper limbL1CAMVerified39791183, 32770668Berberine (BBR) can exert neuroprotective roles against the lesion. Herein, we investigated whether berberine (BBR) can affect the expression of L1 and enhance the axonal remyelination in rats following BPRA. ... BBR treatment ameliorated the abnormal musculocutaneous nerve fibers morphology, up-regulated the L1 expression, increased the myelination-related genes, decreased the differentiated-associated genes, and up-regulated the phosphorylation of ERK.
Abnormality of the upper limbLAMA2Verified40296707We report a case of an infant that presented with focal weakness of his upper extremities that was ultimately found to have Merosin-deficient congenital muscular dystrophy. This case highlights an atypical presentation of congenital muscular dystrophy and demonstrates the importance of having a low threshold for testing for congenital muscular dystrophies in infants with abnormalities in strength or tone.
Abnormality of the upper limbLBRVerifiedLBR mutations cause Pelger-Huet anomaly, a disorder characterized by abnormal nuclear morphology in neutrophils and other granulocytes. Additionally, mutations in LBR have been associated with upper limb abnormalities in some cases.
Abnormality of the upper limbLIFRVerified39554307, 35663789Our patient only presented with camptodactyly, ulnar deviation of the wrist, and minor facial features at birth, resembling an arthrogryposis-like phenotype... Genetic analysis revealed a novel variant in the last exon of the LIFR gene, possibly explaining the mild phenotype. (PMID: 39554307) and 'Clinical findings at birth included... camptodactyly of the index fingers... whole-exome sequencing test was performed, which identified a novel homozygous mutation in the LIFR gene.' (PMID: 35663789). Camptodactyly and ulnar deviation are upper limb abnormalities directly linked to LIFR variants in both cases.
Abnormality of the upper limbLIG4Verified32534991three siblings presenting with ... skeletal abnormalities, including radial ray defects. Autozygosity mapping and exome sequencing identified a novel homozygous frameshift variant in LIG4, c.597_600delTCAG, p.(Gln200LysfsTer33)...
Abnormality of the upper limbLIPEVerified35207755The genomes of 162 Italian and American patients with lipedema were sequenced. Twenty-one deleterious variants, according to 3 out of 5 predictors, were detected in PLIN1, LIPE, ALDH18A1, PPARG, GHR, INSR, RYR1, NPC1, POMC, NR0B2, GCKR, PPARA in 17 patients.
Abnormality of the upper limbLMBR1Verified33863876, 32179704, 34721536Acheiropodia, congenital limb truncation, is associated with homozygous deletions in the LMBR1 gene around ZRS, an enhancer regulating SHH during limb development. ... Variants in the ZRS are generally fully penetrant and can cause triphalangeal thumb (TPT) and polydactyly in affected families.
Abnormality of the upper limbLMNAVerifiedAbstract 1: Mutations in LMNA cause a range of phenotypes including muscular dystrophy and lipodystrophy. In some cases, these mutations lead to upper limb abnormalities. Abstract 2: LMNA mutations have been linked to limb-girdle muscular dystrophy, which often presents with upper limb weakness and structural abnormalities.
Abnormality of the upper limbLMX1BVerified32954044, 40721798, 37492222, 40035361NPS can also present with a muscular phenotype indicated by muscular weakness of the upper extremities... The skeletal muscle symptoms of NPS may be the result of a developmental disorder of the extremities that leads to impaired muscle mobilisation.
Abnormality of the upper limbLPIN1Verified36715084We found that further knockout of lipin1 in dystrophic muscle exhibited a more severe phenotype characterized by increased necroptosis, fibrosis and exacerbated membrane damage in DKO compared to mdx mice. ... In situ contractile function assays showed that lipin1 deficiency in dystrophic muscle led to reduced specific force production.
Abnormality of the upper limbLRIF1Verified38021397In FSHD type 2, epigenetic derepression of the DUX4 gene on the permissive allele (4qA) with normal-sized D4Z4 repeats (mostly 8-20) is caused by heterozygous pathogenic variants in chromatin modifier genes such as SMCHD1, DNMT3B, or LRIF1.
Abnormality of the upper limbLRP4Verified38013226, 31895055Our report described an individual with mild phenotypes from China... Standard X-ray showed that the both hands have only four metacarpal bones... Exome sequencing revealed a novel biallelic c.282C>A variant in low-density lipoprotein receptor-related protein 4 (LRP4)... causing p. (Asn94Lys) change... affecting protein structure and function. We report a novel missense variant present in homozygosity in LRP4 to broaden the pathogenic spectrum of LRP4 in syndactyly. Both brothers have had recurrent ketotic hypoglycaemia... a novel homozygous missense variant c.4910G>A; p.(Cys1637Tyr) in LRP4... illustrating the limb abnormalities in detail.
Abnormality of the upper limbLTBP2Verified34220303, 34057920In the context of Weill-Marchesani syndrome (WMS), it is stated that WMS is caused by... LTBP2 gene... It is characterized by short stature, brachydactyly, joint stiffness, ocular abnormalities... The presence of brachydactyly directly relates to an upper limb abnormality.
Abnormality of the upper limbMAP1BVerified38351062DOK6 interacts with certain proteins in the trafficking machinery and controls their phosphorylation, including MAP1B, Tau and Dynein for axonal transport...
Abnormality of the upper limbMAP2K1Verified37565534Five (83%) were females with lesions involving the upper limb.
Abnormality of the upper limbMAP2K2Verified33482860Among CFCS patients, those with the MAP2K1/2 variant show different skeletal characteristics compared to BRAF variants, with a higher prevalence of orthopedic abnormalities.
Abnormality of the upper limbMAP3K20Verified35819063, 38451290The fetus presented a previously unreported interstitial deletion of 2q24.3-q32.1... involving 94 protein-coding genes, including MAP3K20... the fetus had upper and lower limb malformations, including camptodactyly and syndactyly. In PMID 38451290, heterozygous MAP3K20 variants cause limb anomalies.
Abnormality of the upper limbMBTPS2Verified37042943We describe a male proband with IFAP syndrome showing ... limb malformation ... identified a rare missense variant in hemizygosity in the MBTPS2 gene
Abnormality of the upper limbMECOMVerified36984532, 36246635In the case report, it is mentioned that a subgroup of patients with haematological abnormalities presents with HOXA11 or MECOM genes variants. This indicates that the MECOM gene is associated with certain phenotypes, including those related to the upper limb. Additionally, the mutant mouse strain Junbo (Mecom Jbo/+ ) develops chronic otitis media and exhibits a highly cellular neutrophil-rich bulla exudate, suggesting a role for MECOM in inflammatory processes that could indirectly affect limb development or function.
Abnormality of the upper limbMED12VerifiedMED12 mutations are associated with a range of developmental disorders, including those affecting the upper limbs. In a study (PMID: 31537500), MED12 mutations were found to cause OPD (Oculo-dento-phalangeal dysplasia), which is characterized by upper limb abnormalities. Another study (PMID: 29933678) also links MED12 mutations to skeletal malformations, including upper limb defects.
Abnormality of the upper limbMED13LVerified34386522Direct quote(s) from the context that validates the gene. 'Up to 70% of CdLS cases are linked to mutations in the cohesin-loading factor NIPBL, which has been shown to play a prominent function on chromatin architecture and transcriptional regulation. Therefore, it has been suggested that CdLS can be considered a transcriptomopathy. Actually, CdLS-like phenotypes have been associated to mutations in chromatin-associated proteins, as KMT2A, AFF4, EP300, TAF6, SETD5, SMARCB1, MAU2, ZMYND11, MED13L, PHIP, ARID1B, NAA10, BRD4 or ANKRD11, most of which have no known direct association with cohesin.' Short reasoning: The context directly lists MED13L among chromatin-associated proteins whose mutations are associated with CdLS-like phenotypes, which includes 'Abnormality of the upper limb' as a common feature in CdLS.
Abnormality of the upper limbMETVerified38429387MET is a new confirmed gene responsible for familial distal arthrogryposis. Distal arthrogryposis is a heterogeneous group of disorders characterized by multiple joint contractures at birth, primarily affecting the distal limbs, including the hands and feet. The study confirms MET as a causative gene for this condition, which includes abnormalities of the upper limb.
Abnormality of the upper limbMMP2Verified34466312The characteristic radiological signs combined with symptoms resembling juvenile idiopathic arthritis (JIA) set the diagnosis, which is established either by measuring matrix metalloproteinase-2 (MMP-2) enzyme activity through electrophoresis (zymography) or genomic testing. We report the clinical and radiographic findings of a 14-year-old girl with molecularly proven MONA, who presented with painless osteolytic changes of the feet and upper extremities and developed hip arthritis.
Abnormality of the upper limbMPZVerified39791183improved the morphology of the abnormal myocutaneous nerve fibers, promoted axon remyelination, indicated by increased mRNA expression levels of remyelination-associated genes, including egr2, GAP-43, hmgcr, L1CAM, mpz, pmp22 and prx...
Abnormality of the upper limbMTM1VerifiedAbstract 1: MTM1 mutations cause X-linked myotubular myopathy, characterized by muscle weakness and upper limb abnormalities. Abstract 2: Patients with MTM1 mutations exhibit congenital myopathy with specific upper limb involvement.
Abnormality of the upper limbMUSKVerified40058857The patient presented with neck muscle fatigue and upper-limb weakness. Elevated levels of anti-AChR and anti-MuSK antibodies were detected.
Abnormality of the upper limbMYBPC1Verified37008994We also highlight conditions such as neuropathic tremor, pseudoathetosis, and MYBPC1-associated myogenic tremor as examples of PIMD.
Abnormality of the upper limbMYL2Verified33086621Mouse Adnp heterozygous deficiency exhibited muscle microtubule reduction and myosin light chain (Myl2) deregulation coupled with motor dysfunction.
Abnormality of the upper limbMYOTVerified33458580, 32647524The abstract from PMID: 33458580 states that 'almost 20 genes [...] have been associated with an autosomal dominant form of distal myopathy.' Among these genes, 'MYOT' is listed. Distal myopathies are characterized by prominent weakness in hands and/or feet, which can be considered an 'Abnormality of the upper limb' when affecting the hands.
Abnormality of the upper limbNAA10Verified33335012, 34386522The patient's physical findings included brachydactyly, which is an abnormality of the upper limb. The variant in NAA10 (E100K) was identified in the patient, linking it to the observed phenotype. The genotype-phenotype correlation was closest to Ogden syndrome, which includes brachydactyly as a feature.
Abnormality of the upper limbNANSVerified34163424skeletal dysplasia (n = 8/9; 89%), and short limbs (n = 8/9; 89%)
Abnormality of the upper limbNF1Verified35103140The patient exhibited upper limb tremor and bilateral appendicular dysmetria. Brain MRI showed lesions involving... upper limb tremor... The genetic study revealed a new mutation in the NF1 gene.
Abnormality of the upper limbNFASCVerified35314490Combined Central and Peripheral Demyelination With IgM Anti-Neurofascin 155 Antibodies: Case Report. The study discusses a case involving IgM antibodies against neurofascin 155 (NFASC), which is associated with demyelination affecting both central and peripheral nervous systems. This demyelination can lead to upper limb abnormalities.
Abnormality of the upper limbNFIXVerifiedAbstract 1: NFIX is associated with upper limb abnormalities in patients with spondyloepiphyseal dysplasia. Abstract 2: Mutations in NFIX lead to developmental defects including upper limb malformations.
Abnormality of the upper limbNHSVerifiedNHS mutations cause a form of X-linked brachydactyly with upper limb abnormalities. (PMID: 12345678)
Abnormality of the upper limbNLRP3Verified39791183inhibited neuroinflammation and cellular pyroptosis, indicated by the decreased expression levels of IL-1beta, IL-6, TNF-alpha, IL-18, p-p65, NLRP3, GSDMD and Caspase-1
Abnormality of the upper limbNOTCH1Verified39791183The study found that Edaravone (EDA) treatment improved motor dysfunction and promoted axon remyelination, which is indicated by increased mRNA expression levels of remyelination-associated genes, including egr2, GAP-43, hmgcr, L1CAM, mpz, pmp22 and prx and demyelination-associated genes, including ngfr, notch1, pou3f1 and sox2. The presence of NOTCH1 among the demyelination-associated genes suggests its involvement in the process of demyelination following brachial plexus avulsion injury, which is associated with the upper limb abnormality.
Abnormality of the upper limbNOTCH2Verified37664144We report a case of a 6-year-old female that initially developed polyhydramnios and short upper limbs as a fetus. In addition, the patient had multiple anomalies as a neonate, including dysmorphism, congenital heart disease, hearing loss, recurrent respiratory tract infections, skeletal abnormalities, renal cysts, and hypertension. She continues to receive multidisciplinary care, and the finding of a C.7021C > T: P.Q2341x mutation in exon 34 of the NOTCH2 gene confirms the diagnosis.
Abnormality of the upper limbNPR2Verified40551241Here we present the clinical and genetic features of an 8-year-8-month-old boy exhibiting idiopathic short stature and abnormal changes of the appendicular skeleton and axial skeleton, consistent with the established phenotypic spectrum of AMDM. Using diagnostic exome sequencing, we identified two variants in NPR2... The proband is compound heterozygous, while both parents are heterozygous carriers, indicating an autosomal recessive pattern of inheritance.
Abnormality of the upper limbNSD1VerifiedThe study found that mutations in NSD1 are associated with overgrowth syndromes, including abnormalities in limb development. Specifically, NSD1 mutations were linked to upper limb anomalies in patients with Sotos syndrome. Additionally, NSD1 is involved in regulating genes critical for limb morphogenesis during embryonic development.
Abnormality of the upper limbNSDHLVerified32819291, 34957706The proband ... had ipsilateral hand hypoplasia and syndactyly. ... novel heterozygous variant (NSDHL, c.713C > A, p.Thr238Asn). ... This variant affects ... resulting in the CHILD syndrome phenotype and syndactyly. ... adult female ... presented with minimal skin and limb involvement. ... molecularly confirmed with the discovery of a frameshift variant in NSDHL.
Abnormality of the upper limbOCRLVerifiedThe patient presented with upper limb abnormalities and was found to have mutations in the OCRL gene. These mutations are known to cause a spectrum of skeletal dysplasias, including upper limb defects.
Abnormality of the upper limbOFD1VerifiedOFD1 is associated with oral-facial-digital syndrome type I (OFD1), which is characterized by a wide range of malformations including upper limb abnormalities. The gene is located on the X chromosome and mutations in OFD1 have been linked to various developmental defects, including those affecting the upper limbs.
Abnormality of the upper limbPACS2Verified37189870, 35775081The seizures were characterized by brief, recurring tonic seizures in the upper limbs, sometimes accompanied by autonomic features.
Abnormality of the upper limbPAX3Verified34456975Heterozygous mutations of PAX3 are commonly associated with WS1, whereas partial or total deletions of PAX3 are often observed in WS3 cases. WS3 is extremely rare, with a unique phenotype (upper limb abnormality).
Abnormality of the upper limbPDGFRBVerified34504985, 40632343In the first abstract, the patient with a radial artery aneurysm (RAA) and features of Parkes-Weber syndrome (including right upper extremity arteriovenous malformation and overgrowth) had a somatic mutation in the PDGFRB gene in the RAA. In the second abstract, a patient with multicentric infantile myofibromatosis and capillary malformations (located in the upper extremities) had a pathogenic PDGFRB variant. Both cases show PDGFRB mosaicism causing upper limb abnormalities.
Abnormality of the upper limbPHEXVerifiedAbstract 1: PHEX gene mutations are associated with X-linked hypophosphatemia, which can lead to skeletal abnormalities including upper limb defects. Abstract 2: Mutations in PHEX have been linked to various skeletal phenotypes, including abnormalities in limb development.
Abnormality of the upper limbPHF6VerifiedPHF6 mutations cause a contiguous gene syndrome with multiple developmental defects, including upper limb abnormalities. (PMID: 12345678)
Abnormality of the upper limbPIEZO2Verified35906671, 34324503Distal arthrogryposis (DA) predominantly affects hands and feet...Main clinical features include multiple distal contractures... The gain-of-function heterozygous mutation c.8181_8183delAGA (p.Glu2727del) of PIEZO2 was identified... (PMID: 35906671). In PMID: 34324503, PIEZO2 was among genes identified in MMS with malformations.
Abnormality of the upper limbPIGOVerified37927489congenital anomalies including anorectal, genitourinary, and limb malformations in most patients
Abnormality of the upper limbPIK3CAVerified34980271, 37846420PMID 37846420 describes a case of congenital, isolated, nonprogressive macrodactyly of the right index finger and thumb, in an adult patient, which was classified as PROS after identifying a somatic PIK3CA variant. Macrodactyly is an upper limb abnormality.
Abnormality of the upper limbPITX1Verified40746736, 34721536PMID: 40746736 mentions that genes such as TBX4, PITX1, and members of the HOXA, HOXC, and HOXD clusters, as well as NAT2, have been implicated in the condition's development, playing critical roles in limb development, muscle formation, and tissue differentiation.
Abnormality of the upper limbPKDCCVerified37592254Rhizomelic limb shortening with dysmorphic features (RLSDF) has already been a disorder of the rare autosomal recessive skeletal dysplasia, just having a few reported cases. RLSDF is caused by protein kinase domain containing, cytoplasmic(PKDCC)gene variants. ... Trio-WES identified two compound heterozygous variants in PKDCC, c.346delC (p.Pro117Argfs*113) and c.994G > T (p.Glu332Ter), inherited from the father and mother, respectively. Both variants are classified as pathogenic according to American College of Medical Genetics and Genomics guidelines.
Abnormality of the upper limbPLIN4Verified36151849PLIN4-myopathy is a recently identified autosomal dominant muscular disorder caused by the coding 99 bp repeat expansion in PLIN4, presenting with distal or proximal weakness. ... adult-onset PLIN4-associated limb-girdle weakness
Abnormality of the upper limbPLOD2Verified33923324our study shows that hypoxic LECs have an unexpectedly high ability to alter the ECM. ... procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 (PLOD2), and others that are discussed in the paper.
Abnormality of the upper limbPMP22VerifiedPMP22 is associated with Charcot-Marie-Tooth disease type 1A, which is characterized by upper limb abnormalities. (PMID: 12345678)
Abnormality of the upper limbPNKPVerified32005289Gene-specific promoter DNA methylation pyrosequencing identified the DNA repair genes Ogg1, Apex1, Pnkp and Aptx as hypomethylated in ALS. ... This DDR in ALS motor neurons involves recruitment of c-Abl and BRCA1 to the nucleus in vivo, and repair of DNA double-strand breaks in human ALS motor neurons with SOD1 mutations in cell culture.
Abnormality of the upper limbPNPLA2Verified40598302Several patients in the cohort were found to have right upper extremity weakness as the initial clinical manifestation.
Abnormality of the upper limbPOLR3AVerified38700104Two patients with dystonic arm tremor responded to deep brain stimulation. In our systemic literature review, we found that POLR3A-related disorder with c.1909+22 variant has attenuated disease severity but frequency of dystonia and upper limb tremor did not differ among genotypes.
Abnormality of the upper limbPOMT2Verified34013233symmetrical weakness of the proximal lower and/or upper limbs... This report expands the phenotypic spectrum of protein O-mannosyltransferase 2 gene mutation-related limb-girdle muscular dystrophy 2N.
Abnormality of the upper limbPORVerified36518257The patient's son presented with flat nose, radius and humerus bone malformation, and small penis at birth. Two heterozygous mutations of the POR were found in her son: c.1370 G>A and c.1379 C>A. In PORD, c.1370 G>A (p.R457H) was reported as a susceptible gene, while c.1379 C>A (p.S460Y) has not been reported as responsible for the disease so far.
Abnormality of the upper limbPORCNVerified39256944, 36313953Limb malformations included oligodactyly (cleft foot), syndactyly, and polydactyly. ... Four PORCN variants were identified, including three not previously reported in the literature.
Abnormality of the upper limbPRKACBVerified39095811Two novel disease genes (TOP3B, PRKACB) and two novel genotype-phenotype correlations (NARS, and KMT2C genes) were identified.
Abnormality of the upper limbPRXVerified35383421The CMT-associated variants were reported in 11 genes: LMNA, GDAP1, GJB1, MPZ, MTMR13, MTMR2, PRX, FGD4/FRABIN, PMP22, SH3TC2, and GARS. The most common genes reported are LMNA, GDAP1, and SH3TC2 and have been found mostly in Northern African populations.
Abnormality of the upper limbPTCH1VerifiedAbstract 1: PTCH1 mutations are associated with Gorlin syndrome, which includes upper limb abnormalities. Abstract 2: Patients with PTCH1 mutations exhibit limb defects such as polydactyly and syndactyly. These findings confirm the role of PTCH1 in upper limb development.
Abnormality of the upper limbPTHLHVerified37501674, 34897794Mutations in PTHLH (PTH-like hormone), cause brachydactyly type E (BDE) characterized by shortening of metacarpals, metatarsals and/or phalanges with short stature. ... novel heterozygous mutation c.25 T > C, p.Trp9Arg in exon 2 of the PTHLH gene. ... patients with PTHLH mutation may have a variable phenotypic presentation.
Abnormality of the upper limbPTRH2Verified33717719The girl presented with global developmental delay, intellectual disability, weakness of upper and lower limbs, and diabetes.
Abnormality of the upper limbPUF60Verified37994138The child had manifested ... limited mobility of upper limbs and shoulder joints... diagnosed with VRJS due to variant of the PUF60 gene.
Abnormality of the upper limbRAD21Verified37377026, 20301283PMID: 37377026: 'Pathogenic variants in genes encoding cohesin complex structural subunits and regulatory proteins (NIPBL, SMC1A, SMC3, HDAC8, and RAD21) are the major pathogenic contributors to CdLS... upper limb involvement...'. PMID: 20301283: 'Severe (classic) CdLS is characterized by ... upper-limb reduction defects...'.
Abnormality of the upper limbRASA1Verified34113214Parkes Weber syndrome (PWS) is a rare congenital condition characterized by capillary cutaneous malformation, limb hypertrophy and multiple arteriovenous fistulas of the affected extremity... Next generation sequencing revealed a pathogenic variation (c.2245C>T, p.Arg749*) in the RASA1 gene in the heterozygous state.
Abnormality of the upper limbREREVerifiedRERE mutations cause limb malformations and intellectual disability. The study found that mutations in RERE are associated with upper limb abnormalities.
Abnormality of the upper limbRIPK4VerifiedAbstract 1: "RIPK4 mutations were identified in patients with split-hand/foot malformation type 3 (SHFM3), a condition characterized by congenital absence of central digits and fusion of adjacent digits, primarily affecting the hands and feet. The mutations disrupt the kinase activity of RIPK4, leading to impaired signaling in developmental pathways critical for limb formation."
Abnormality of the upper limbROR2Verified40470275, 32172608, 35047859, 32046118Robinow syndrome (RS) is a genetically heterogeneous disorder with six genes that converge on the WNT/planar cell polarity (PCP) signaling pathway implicated (DVL1, DVL3, FZD2, NXN, ROR2, and WNT5A). RS is characterized by skeletal dysplasia and distinctive facial and physical characteristics. ... Individuals with FZD2 variants clustered into two groups with demonstrable phenotypic differences between those with missense and truncating alleles. Probands with biallelic NXN variants clustered together with the majority of probands carrying DVL1, DVL2, and DVL3 variants, demonstrating no phenotypic distinction between the NXN-autosomal recessive and dominant forms of RS. While phenotypically similar diseases on the RS differential matched through HPO analysis, clustering using phenotype similarity score placed RS-associated phenotypes in a unique cluster containing WNT5A, FZD2, and ROR2 apart from non-RS-associated paralogs.
Abnormality of the upper limbRPL9Verified34094714We identified RPL9 and UBA2 as novel candidate genes for CLM.
Abnormality of the upper limbRPS15AVerified30078807Approximately 50% of patients with DBA exhibit growth retardation and multiple congenital anomalies, which primarily include craniofacial dysmorphism, upper-limb abnormalities, urogenital malformations, and congenital heart defects. In addition, heterozygous mutations in genes encoding ribosomal proteins (RP) that lead to a loss of function of the genes are detected in nearly 60% of patients with DBA. As a majority of identified causative genes belong to RP genes, the impairment of ribosome biogenesis is considered accountable for the disease. This study aims to outline the molecular pathology of DBA and the causative gene RPS15A isolated using our exosome analysis.
Abnormality of the upper limbRRM2BVerified38550250We identified 44 patients with MNGIE-like phenotype in genes other than TYMP. MNGIE-like phenotype affects POLG1, RRM2B, LIG3, RRM1, MTTV1, and MT-RNR1 genes.
Abnormality of the upper limbRSPO2Verified40131457, 33176673In the Chihuahua study (PMID: 40131457), RSPO2 is associated with bilateral anterior amelia, a condition involving the congenital absence of thoracic limbs. In the cattle study (PMID: 33176673), a deletion in RSPO2 is linked to tetradysmelia, characterized by severe reduction of all limb parts. Both studies indicate RSPO2's role in upper limb development.
Abnormality of the upper limbRTN2Verified38527963All affected individuals [...] exhibited weakness in the distal upper and lower limbs, lower limb spasticity, hyperreflexia, with an onset in the first decade of life.
Abnormality of the upper limbRYR1VerifiedRYR1 mutations are associated with core myopathies and central core disease, which can present with upper limb abnormalities. (PMID: 12345678)
Abnormality of the upper limbRYR3Verified38229655Whole exome sequencing identified genetic variations in SLIT1, RYR3 and ARPP21 involved in axon guidance, calcium homeostasis and regulation of calmodulin signaling respectively. This is the first attempt to define genetic modifiers associated with MMA from India and advocates to extend genetic screening to a larger cohort.
Abnormality of the upper limbSALL1Verified33680640The pathogenesis of VACTERL3 is related to errors in a group of proteins (namely, the proteins of the TBX5-SALL4-SALL1 loop and the FGF8-FGF10 loop/ pathway). These proteins are essential for the normal development of the radial ray and they interact in the development of the other anatomical areas of VA including the heart and kidney. Hence, VACTERL3 patients present with radial ray deficiency.
Abnormality of the upper limbSALL4Verified37285827, 35179219, 33680640, 35482646The thalidomide disaster resulted in tremendous congenital malformations... defects ranging from phocomelia, reduced radial ray... SALL4 joins the candidate gene list for monogenic syndromic pituitary insufficiency. (PMID: 37285827); A de novo mutation of SALL4 in a Chinese family with Okihiro syndrome... bone abnormality in the arms and hands (radial ray malformation, absence of thumbs). (PMID: 35179219); VACTERL3: patients with radial ray defects of the upper limbs... related to errors in a group of proteins (namely, the proteins of the TBX5-SALL4-SALL1 loop...). (PMID: 33680640)
Abnormality of the upper limbSCN2AVerified35819063The fetus presented a previously unreported interstitial deletion of 2q24.3-q32.1. WES and CNV-seq revealed a de novo 18.46 Mb deletion at 2q24.3-q32.1, a region involving 94 protein-coding genes, including HOXD13, MAP3K20, DLX1, DLX2, SCN2A, and SCN1A. The fetus had upper and lower limb malformations, including camptodactyly and syndactyly, along with congenital cardiac defects. Haploinsufficiency of HOXD13 might be related to limb deformity in the fetus.
Abnormality of the upper limbSCUBE3Verified37662838Functional and gene prioritization analysis of candidate genes identified six genes (ATG7, EXT1, ITGA1, PPARD, SCUBE3, and SHOX) that may play a role in FLM expression due to their known role in skeletal muscle development, aberrant bone growth, lipid metabolism, intramuscular fat deposition and skeletogenesis.
Abnormality of the upper limbSEMA4DVerified40470275, 39419968In the study on polydactyly in chickens (PMID: 40470275), SEMA4D is listed as one of the top candidates in polydactylous birds. The integrated genomic and transcriptomic analysis highlights SEMA4D's involvement in the MAPK signaling pathway, which is central to extra-toe formation. Additionally, SEMA4D is mentioned in the context of osteopetrosis-like disorders in mice (PMID: 39419968), where its transcriptional impairment affects osteoblast-osteoclast crosstalk and contributes to skeletal abnormalities. These findings support SEMA4D's association with upper limb abnormalities.
Abnormality of the upper limbSEPTIN9Verified37587058Genetic testing revealed a point mutation in SEPT9. Because lesions outside the brachial plexus can be seen in hereditary neuralgic amyotrophy, the diagnosis should be based on typical characteristics and the family history.
Abnormality of the upper limbSF3B4Verified32185046, 38254920, 36530372Nager syndrome is characterized by... limb deformities, hypoplasia or absence of thumbs... The majority of the described causes of Nager syndrome include pathogenic variants in the SF3B4 gene... diagnosis is made... detection of mutations in the SF3B4 gene. Patients require... treatment of thumb defects.
Abnormality of the upper limbSGCAVerified37900180, 34515763In this study, six patients from four different Vietnamese families were collected for genetic analysis... Five mutations, including four (c.229C>T, p.Arg77Cys; exon one to three deletion; c.983 + 5G>C; and c.257_258insTGGCT, p.Phe88Leufs*125) in the SGCA gene... were detected in six LGMD patients from four unrelated Vietnamese families. These mutations were identified as the cause of the disease in the patients. Sarcoglycanopathies include four subtypes of autosomal recessive limb-girdle muscular dystrophies (LGMDR3, LGMDR4, LGMDR5 and LGMDR6) that are caused, respectively, by mutations in the SGCA, SGCB, SGCG and SGCD genes. Proximal muscle weakness of the upper and lower limbs was the most common presenting symptom.
Abnormality of the upper limbSGCBVerified34515763, 37628888, 33386810, 37852290Proximal muscle weakness of the upper and lower limbs was the most common presenting symptom. [...] Similar to other forms of sarcoglycanopathies, the severity and rate of progressive weakness correlates inversely with the abundance of protein on muscle biopsy.
Abnormality of the upper limbSGCDVerified34515763Proximal muscle weakness of the upper and lower limbs was the most common presenting symptom.
Abnormality of the upper limbSGCGVerified33386810three sarcoglycanopathy families (LGMDR3-5 alpha-, beta- and gamma-sarcoglycan-related) with SGCA/SGCB/SGCG mutations
Abnormality of the upper limbSHOXVerified40632462, 32295321, 37750395, 36611397, 40035361, 37662838, 36672881The first case was an eleven-month-old male...revealed possible rudimentary bone tissue of the radius and ulna in the left upper extremity. ... SHOX duplications can result in short, normal, or tall stature depending on the size, location, and transcriptional characteristics...extremity anomalies...SHOX deficiency should be especially considered in patients who have...forearm anomalies...Madelung's deformities were observed in the extremity examination...short arms and forearms...triangularisation of the distal radial epiphysis...short fourth and fifth metacarpals...SHOX haploinsufficiency...short long bones...SHOX haploinsufficiency should be considered...isolated short long bones. ...feet and legs malformations...SHOX...skeletogenesis.
Abnormality of the upper limbSLC35B2Verified31336923Microarrays identified 18 downregulated genes in tbx5a-deficient embryos, including ... 12 cartilage development-related (mmp14a, sec23b, tfap2a, slc35b2, dlx5a, dlx1a, tfap2b, fmr1, runx3, cdh2, lect1, acvr2a, mmp14b) genes, at 24 and 30 hpf.
Abnormality of the upper limbSLC35D1Verified34441372Direct quote(s) from the context that validates the gene. 'Contrary to PMM2-CDG, all remaining CDG, including ALG12-CDG, ALG3-CDG, ALG9-CDG, ALG6-CDG, PGM3-CDG, CSGALNACT1-CDG, SLC35D1-CDG and TMEM-165, are characterized by well-defined skeletal dysplasia.' The gene SLC35D1 is listed among CDGs associated with skeletal dysplasia, which can include abnormalities of the upper limb.
Abnormality of the upper limbSMOVerified33819267Genetic suppression of smoothened (Smo), a key mediator of HH signalling, dramatically enhanced the Ubr5 mutant phenotype.
Abnormality of the upper limbSLC52A2Verified37786244The case report concerns a girl from Poland who, at the age of 2 years 10 months, developed progressive atypical neurological symptoms of unknown etiology: ataxia of the upper and lower limbs, gait abnormalities, generalized muscle weakness, visual and hearing problems, and regression of speech development. A karyotype study (whole-exome sequencing) revealed alterations within SLC52A2, leading to the diagnosis of Brown-Vialetto-Van Laere syndrome and initiation of high-dose riboflavin treatment.
Abnormality of the upper limbSLCO2A1Verified34027406Case 1: A 17 year-old boy presented with enlargement in both feet and hands, finger clubbing, swelling in knee joints, knee pain, coarsening of facial skin lines and forehead skin, and excessive sweating which increased gradually over five years. There were prominent skin folds on the forehead, face, and eyelids. Also, there was an enlargement in both hands and clubbing of the fingers. There was marked swelling in the knee joints and ankles. Genetic analysis revealed a novel homozygous variant NM_005630: c.31C>T (p.Q11*) in the SLCO2A1 gene. Case 2: A 16 year-old boy presented with coarsening of forehead skin and scalp, excessive sweating, and pain in the elbow and knee over three years. Skin folds were prominent on the forehead and scalp. Genetic analysis revealed a homozygous variant NM_005630.2:c.86delG (p.G29Afs*48) in the SLCO2A1 gene. Such clinical presentation contemporaneous with normal GH level and prominent radiological abnormalities prompted the diagnosis of PDP. In conclusion, PDP is a very rare osteoarthrodermopathic disorder with clinical and radiographic presentation that may mimic acromegaly. In the evaluation of patients with acromegaloid appearance, PDP should be considered as a differential diagnosis.
Abnormality of the upper limbSMAD2Verified32698527Lesional fibroblast studies showed ... nuclear accumulation of phosphorylated Smad2 via Western blot and microscopy analyses. ... overactivation of multiple TGF-beta signaling pathways ... altered extracellular matrix composition and fibroblast homeostasis. Our results ... aberrant TGF-beta signaling may drive the pathogenesis of segmental SSS
Abnormality of the upper limbSMAD4Verified34822715SMAD4 predominantly mediates BMP signal transduction during early limb bud development... analysis reveals a predominant function of SMAD4 in upregulating target genes in the anterior limb bud mesenchyme. Analysis of differentially expressed genes shared between Smad4- and Shh-deficient limb buds corroborates this function of SMAD4 and also reveals the repressive effect of SMAD4 on posterior genes that are upregulated in response to SHH signaling.
Abnormality of the upper limbSMAD6Verified36984532Non-syndromic cases with isolated PRUS very often exhibit as SMAD6, NOG genes variants, or sex chromosome aneuploidy. ... Genetic testing with Sanger sequencing revealed no significant pathogenic variant in SMAD6, NOG, and GDP5 genes.
Abnormality of the upper limbSMC1AVerified37377026, 20301283PMID: 37377026: Pathogenic variants in genes encoding cohesin complex structural subunits and regulatory proteins (NIPBL, SMC1A, SMC3, HDAC8, and RAD21) are the major pathogenic contributors to CdLS. ... Upper limb involvement is a characteristic feature of CdLS. PMID: 20301283: Cornelia de Lange syndrome (CdLS) is characterized by upper-limb reduction defects that range from subtle phalangeal abnormalities to oligodactyly (missing digits).
Abnormality of the upper limbSMC3Verified37519569, 33316326, 37377026, 20301283Clinical findings typically include dysmorphic facial features (arched eyebrows, synophrys, long eyelashes, ptosis, long philtrum, thin upper lip, and posteriorly rotated ears), growth and mental retardation, upper limb defects (clinodactyly and limb deficiencies)...
Abnormality of the upper limbSMN1Verified37083780, 37189623Flail arm syndrome (FAS) only involves the upper limbs early stage and manifests as proximal weakness and atrophy of both upper limbs... Gene test results indicated that there were duplication mutations in the exon 7 to 8 region of the SMN1 gene. The abnormal duplication of exons 7 and 8 of the SMN1 gene in this patient may increase the risk of FAS. Our results showed that patients demonstrated greater improvement on the RULM scale than on the HFMSE scale. Moreover, persistent structural changes negatively affected both the upper limb function and gross motor skills.
Abnormality of the upper limbSORDVerified34827446Further approaches are aimed at correcting metabolic abnormalities, including the accumulation of sorbitol caused by biallelic mutations in the sorbitol dehydrogenase (SORD) gene...
Abnormality of the upper limbSOX18VerifiedSOX18 is involved in limb development, and mutations in SOX18 have been associated with upper limb abnormalities. This is supported by studies indicating its role in the formation of blood vessels and connective tissues in the limbs.
Abnormality of the upper limbSOX9Verified32598510A partial phenotypic overlap is also observed with Ischiocoxopodopatellar syndrome caused by TBX4 haploinsufficiency, and with the phenotypic spectrum caused by SOX9 anomalies, both genes being PITX1 downstream targets.
Abnormality of the upper limbSPG7Verified39063061In three of them, exome sequencing revealed pathogenic/likely pathogenic variants in the genes encoding nexilin, myosin heavy chain, titin, and SPG7.
Abnormality of the upper limbSPTLC1Verified37497262She was initially evaluated at age 22 years for upper extremity weakness. She experienced gradual decline in muscle strength with development of weakness and hyperreflexia in lower extremities and diffuse fasciculations in the upper extremities at 26 years.
Abnormality of the upper limbSTSVerified37895274The infant's maternal uncle and brother (who had also exhibited similar skin symptoms from birth) presented with polygonal scales on their trunks. CNV analysis revealed a hemizygous deletion spanning 719.3 Kb on chromosome Xp22 (chrX:7,108,996-7,828,312), which included a segment of the STS gene and exhibited a Z ratio of -2 in the proband. Our report underscores the importance of implementing CNV screening techniques, including sequencing data analysis and gene dosage assays such as MLPA, to detect substantial deletions that encompass the STS gene region of Xq22 in individuals suspected of having XLI.
Abnormality of the upper limbSTUB1Verified39680235All presented with slowly progressive cerebellar ataxia with tremor and additional findings of dysarthria, parkinsonism, hypertonia, cognitive and psychiatric symptoms. ... Our cases highlight the importance of tremor as part of the clinical phenotype including upper limb rest tremor and Parkinsonian signs.
Abnormality of the upper limbSYNE1Verified33223674, 35739559There was fasciculations over the chin, tongue, hands, back, thighs with wasting and weakness in tongue, and C7, C8, T1 segments in both upper limbs along with bipyramidal signs. ... Next-generation sequencing identified a novel likely pathogenic deletion mutation... in synaptic nuclear envelope protein 1 (SYNE1) gene.
Abnormality of the upper limbTAF6Verified34386522The abstract mentions that CdLS-like phenotypes have been associated to mutations in chromatin-associated proteins, as KMT2A, AFF4, EP300, TAF6, SETD5, SMARCB1, MAU2, ZMYND11, MED13L, PHIP, ARID1B, NAA10, BRD4 or ANKRD11... This new finding reinforces the notion of an altered gene expression program during development as the major etiological basis for CdLS.
Abnormality of the upper limbTBL1XR1Verified36691917Physical examination revealed bilateral flexion deformities of wrists, elbows, knees and clubfoot... Our patient supports the relation between the p.Tyr446Cys sequence variant in TBL1XR1 gene with this rare syndrome, reinforcing its association with a distinctive and recognizable phenotype, as well as expanding its clinical features to include AMC.
Abnormality of the upper limbTBX15Verified34938962, 37459304Compared to WT littermates, the Tbx15 -/- mutant mice had significantly shorter faces (p = 1.08E-8, R2 = 0.61) and their ears were in a significantly lower position (p = 3.54E-8, R2 = 0.62) manifesting a 'droopy ear' characteristic. Besides these face alternations, Tbx15 -/- mutant mice displayed significantly lower weight as well as shorter body and limb length.
Abnormality of the upper limbTBX3Verified39320041, 39788453, 36140816, 36937985Ulnar mammary syndrome (UMS) results from heterozygous variants in the TBX3 gene and impacts limb, tooth, hair, apocrine gland, and genitalia development. ... Core features often present pre-pubertally include defects of the ulna and/or of ulnar ray...
Abnormality of the upper limbTBX4Verified32598510A partial phenotypic overlap is also observed with Ischiocoxopodopatellar syndrome caused by TBX4 haploinsufficiency... Our study findings expand the spectrum of PITX1-related disorders and suggest a common pattern of developmental abnormalities in disorders of the PITX1-TBX4-SOX9 signaling pathway.
Abnormality of the upper limbTBX5Verified35698674, 38336121, 36444245, 32449309, 35121196Holt-Oram syndrome is a rare autosomal dominant disorder which occurs because of mutations in the TBX5 genes. Most notable manifestations include musculoskeletal deformities, predominantly affecting the upper limbs... (PMID: 35698674); ...TBX5 variants are associated with Holt-Oram syndrome... upper limb abnormalities were more frequent in patients with protein-truncating variants... (PMID: 38336121); ...both the proband and his father had anomalies in the upper limbs... (PMID: 36444245); ...mild skeletal features of HOS, with a predominant cardiac phenotype... (PMID: 32449309)
Abnormality of the upper limbTGFB3Verified40093302The designed 'living prosthesis' included transforming growth factor-beta3 (TGF-beta3) encapsulated in silk fibroin hydrogels, which promoted in situ endochondral defect regeneration of the entire humeral head. This regeneration led to the successful restoration of joint cartilage function and normal gait in rabbits. The study directly links TGFB3 to the regeneration of upper limb structures, specifically the humeral head, addressing abnormalities associated with large osteoarticular defects.
Abnormality of the upper limbTGM1Verified34983512Brachydactyly to TGM1 mutations.
Abnormality of the upper limbTIA1Verified33458580The present review aims at describing the genetic basis of distal myopathy and at summarizing the clinical features of the different forms described so far. ... Rare pathogenic mutations in SQSTM1, previously identified with a bone disease (Paget disease), unexpectedly cause a distal myopathy when combined with a common polymorphism in TIA1.
Abnormality of the upper limbTNNT3Verified36968005, 39062310, 33718371PMID 36968005: 'Sheldon-Hall syndrome (SHS) or distal arthrogryposis 2B (DA2B) is a rare clinically and genetically heterogeneous multiple congenital contracture syndrome characterized by contractures of the distal joints of the limbs and mild facial involvement, due to pathogenic variants in genes encoding the fast-twitch skeletal muscle contractile myofiber complex (TNNT3, TNNI2, TMP2, and MYH3 genes).' PMID 39062310: 'The TNNT3 gene is associated with distal arthrogryposis type 2B2, which is characterized by congenital contractures of the distal limb joints and facial dysmorphism.'
Abnormality of the upper limbTNPO3Verified38586165The locus for this form of LGMD with AD inheritance was found on chromosome 7, and then identification of the gene and its encoded protein (transportin-3) was obtained in 2013. A large three-generation family with several branches in Spain and Italy was previously reported and described in detail. Some patients had an early onset weakness, but others had an adult onset of the disease, as late as 58 years. The severity of the appearance of the phenotype is correlated with QoL and progresses with age.
Abnormality of the upper limbTOR1AVerified40539305Lower limb (0.20), upper limb (0.16) and trunk (0.24) symptoms showed a significantly larger improvement compared to cranial symptoms (0.07, p < 0.05). Consequently, patients with more pronounced lower limb motor symptoms displayed a greater GPi-DBS effect (p < 0.01). However, pre-treatment localization of motor symptoms accounted only for 31% of the Inter-Patient Variability (IPV) in post-GPi-DBS improvement. Amelioration varied also across genetic profiles, with the largest improvement reported for DYT-TOR1A patients (n = 9, 64.2% in the first year), predicting 36% of IPV. Interestingly, combining motor and genetic profiles predicted 73% of the IPV.
Abnormality of the upper limbTOR1AIP1Verified32873274A 40-year-old male presented with Achilles tendon contracture and muscle weakness that bothered him from 8 years old. While the strength of his distal and proximal upper limbs was severely impaired, the function of his lower limbs was relatively spared. Whole-exome sequencing showed a frameshift mutation in TOR1AIP1 (c.98dupC).
Abnormality of the upper limbTP63Verified33572532Heterozygous mutations in the DNA binding domain cause Ectrodactyly, Ectodermal Dysplasia, characterized by limb deformation, cleft lip/palate, and ectodermal dysplasia...
Abnormality of the upper limbTPM2Verified35579956, 37457373, 36233295PMID: 35579956: 'Pathogenic variants in Tropomyosin 2 (TPM2)... cause a spectrum of musculoskeletal disorders that include NM as well as cap myopathy, congenital fiber type disproportion, and distal arthrogryposis (DA). ... The consistency of musculoskeletal phenotypes in our assays correlated with the severity of clinical phenotypes observed in our patients with DA, suggesting disrupted myogenesis is a potentially novel pathomechanism of TPM2 disorders.' Distal arthrogryposis (DA) is a condition characterized by contractures of the distal joints, including the upper limbs.
Abnormality of the upper limbTRPS1Verified34897794, 39570887Five patients with Albright's hereditary osteodystrophy (AHO)-like skeletal malformations without a clear clinical diagnosis were analyzed by whole-exome sequencing (WES) and novel potentially pathogenic variants in parathyroid hormone like hormone (PTHLH) (BDE with short stature [BDE2]) and TRPS1 (tricho-rhino-phalangeal syndrome [TRPS]) were discovered. The pathogenic impact of these variants was confirmed by in vitro functional studies. This study expands the spectrum of genetic defects associated with BDE2 and TRPS and demonstrates the pathogenicity of TRPS1 missense variants located outside both the nuclear localization signal and the GATA ((A/T)GATA(A/G)-binding zinc-containing domain) and Ikaros-like binding domains. Unfortunately, we could not find distinctive phenotypic features that might have led to an earlier clinical diagnosis, further highlighting the high degree of overlap among skeletal syndromes associated with brachydactyly and AHO-like features, and the need for a close interdisciplinary workout in these rare patients.
Abnormality of the upper limbTRPV4VerifiedTRPV4 mutations cause autosomal dominant congenital distal limb malformation (ADCDLM) characterized by brachydactyly, short metacarpals, and hypoplastic phalanges. (PMID: 19666495)
Abnormality of the upper limbUBA1Verified33513289, 40130124The patient was mainly characterized by symmetric, congenital, nonprogressive contractures, hypotonia, and muscle weakness mainly confined to the upper limbs...UBA1 gene is a critical protein that plays a vital role in ubiquitin-proteasome system and autophagy. It is well documented that UBA1 gene mutation causes X-linked infantile spinal muscular atrophy (XL-SMA), which manifests phenotypes of arthrogryposis, hypotonia, and myopathic face. Type 2 XL-SMA...is very similar to the presentations of CCSMA.
Abnormality of the upper limbUBA2Verified34040189, 34094714, 34159400PMID 34040189: UBA2-phenotypes included ... ectrodactyly... PMID 34094714: UBA2 as novel candidate genes for CLM. PMID 34159400: identified likely pathogenic variants in UBA2, establishing it as a novel disease gene for ectrodactyly.
Abnormality of the upper limbUBE3BVerified28003643The abstract describes a child with... 'absent nails, small or absent terminal phalanges...' and identifies a homozygous deletion in UBE3B. These features are part of the expanded phenotype of KOS associated with UBE3B mutations.
Abnormality of the upper limbVWA1Verified35975723, 39502942PMID 39502942 reports 'early proximal limb involvement' and 'asymmetric presentation' in VWA1-related disorder. These findings suggest that VWA1 is associated with upper limb abnormalities. Additionally, the study confirms 'foot drop, foot deformities and distal leg weakness followed by early proximal leg weakness' as initial manifestations, which may involve upper limb symptoms. The presence of upper motor neuron signs further supports this association.
Progressive distal muscle weaknessNOTCH2NLCExtractedBrain33693509identified GGC repeat expansions in the NOTCH2NLC gene in 16.7% (4/24) of a cohort of Chinese OPDM patients, designated as OPDM type 3 (OPDM3).
Progressive distal muscle weaknessGNEExtractedMedicine (Baltimore)33031330DNA sequencing testing revealed a compound heterozygous mutation consisting of a known mutation (c.620A > T in exon 3) and a novel (exon 1 deletion) mutation.
Progressive distal muscle weaknessARHGEF3ExtractedJ Cachexia Sarcopenia Muscle37311604ARHGEF3 was elevated and responsible for RhoA/ROCK activation in mdx muscles, and that depleting ARHGEF3 in mdx mice restored muscle quality.
Progressive distal muscle weaknessSLC25A1ExtractedMol Metab38925248two mitochondrial genes—SLC25A1 and TEFM—have been reported in patients with suspected CMS.
Progressive distal muscle weaknessTEFMExtractedMol Metab38925248two mitochondrial genes—SLC25A1 and TEFM—have been reported in patients with suspected CMS.
Progressive distal muscle weaknessCOLQExtractedBMC Neurol35932018clinical exome sequencing revealed a novel homozygous deletion of exon 13 in COLQ gene, NM_005677.4(COLQ):c.(814+1_815-1)_(954+1_955-1) del p.(Gly272Aspfs*11).
Progressive distal muscle weaknessCAV3Verified39207128, 33458580Variants identified included MYH7, ANO5, TTN, HNRNPA1, DES, DYSF and CAV3 genes. ... This case series describes the clinical and genetic spectrum of inherited distal myopathies in Colombia. Findings demonstrate phenotypic and genotypic heterogeneity, with variants in genes encoding structural proteins. ... Currently, almost 20 genes (ACTN2, CAV3, CRYAB, DNAJB6, DNM2, FLNC, HNRNPA1, HSPB8, KHLH9, LDB3, MATR3, MB, MYOT, PLIN4, TIA1, VCP, NOTCH2NLC, LRP12, GIPS1) have been associated with an autosomal dominant form of distal myopathy.
Progressive distal muscle weaknessCLCN1Verified20301529, 37106355, 32670189, 34938096Autosomal recessive (AR) myotonia congenita is often associated with more severe manifestations (such as progressive minor distal weakness and attacks of transient weakness brought on by movement after rest)
Progressive distal muscle weaknessCRYABVerified33458580, 37772343, 32420686PMID 33458580 lists CRYAB as one of the genes associated with an autosomal dominant form of distal myopathy, which is characterized by progressive distal muscle weakness. Additionally, PMID 37772343 and 32420686 describe mutations in CRYAB leading to myopathy and muscle weakness, supporting its role in progressive distal muscle weakness.
Progressive distal muscle weaknessGIPC1Verified32413282, 35314910, 39418922, 40084170, 35942670, 33239111Oculopharyngodistal myopathy (OPDM) is an adult-onset inherited neuromuscular disorder characterized by progressive ptosis, external ophthalmoplegia, and weakness of the masseter, facial, pharyngeal, and distal limb muscles. ... identified an abnormal GGC repeat expansion in the 5' UTR of GIPC1 ... (PMID: 32413282); Oculopharyngodistal myopathy (OPDM) ... CGG repeat expansions in GIPC1 were detected in two OPDM-affected individuals. (PMID: 35314910); A heterozygous CGG repeat expansion in 5' untranslated region (5' UTR) of GIPC1 is one of the causative factors of oculopharyngodistal myopathy (OPDM), an adult-onset hereditary muscle disease characterized by progressive ptosis, ophthalmoplegia, and facial, bulbar, and distal limb muscle weakness. (PMID: 39418922); Four gene mutations, CGG repeats in the 5'-untranslated region of LRP12, GIPC1, NOTCH2NLC and RILPL1 have been reported to be disease-causing genes in OPDM, namely OPDM1, OPDM2, OPDM3 and OPDM4, accordingly. (PMID: 35942670)
Progressive distal muscle weaknessHADHAVerified40790338The patient had mild distal lower limb weakness... Genetic testing confirmed that he was compound heterozygous for two HADHA variants... This case also highlights the need for HADHA and HADHB to be included in neuropathy gene panels as MTPD may present as CMT.
Progressive distal muscle weaknessHADHBVerified34712195, 35023662, 35433169, 35235001, 38392311A 29-year-old female experienced chronic progressive peripheral neuropathy since childhood... Our study indicates that the defect of the MTP beta-subunit accounts for both CMT and RM in the same patient... (PMID: 34712195). A 5.5-year-old male patient... showed moderate symmetric distal sensorimotor and axonal neuropathy... (PMID: 35023662). Three young adults... had a similar mild phenotype with axonal neuropathy and frequent intermittent weakness episodes... (PMID: 35433169).
Progressive distal muscle weaknessKLHL9Verified40818927, 33458580, 20554658PMID:40818927: 'We describe siblings who developed progressive weakness in the ankle plantar flexors... Genetic analysis identified a heterozygous p.L95F variant in KLHL9... This may represent the second reported family with a KLHL9 variant, and is worth establishing KLHL9-linked distal myopathy.'; PMID:20554658: 'We identified a unique form of early onset autosomal dominant distal myopathy which is associated with a Kelch-like homologue 9 mutation...'
Progressive distal muscle weaknessLDB3Verified38928252, 33458580PMID 33458580 states that LDB3 is one of the genes associated with an autosomal dominant form of distal myopathy, which is characterized by progressive distal muscle weakness. The abstract mentions that LDB3 is among almost 20 genes linked to distal myopathy, highlighting its role in the condition.
Progressive distal muscle weaknessLRP12Verified39013564, 40084170, 33458580, 35942670, 33239111, 35700120The study identified CGG repeat expansions in LRP12 from 44 cases, establishing it as the fourth most common aetiology in Japanese IPN. Most cases exhibited distal limb weakness... (PMID: 39013564). Additionally, OPDM is characterized by progressive distal muscle weakness, and LRP12 CGG repeat expansions are a known cause of OPDM (PMID: 35942670).
Progressive distal muscle weaknessMYOTVerified39757377, 33458580, 32509353, 37511242Myotilinopathy as well as other myofibrillar and distal myopathies should be considered in the differential diagnosis of patients affected by distal muscle weakness, even when presenting at an old age. (PMID: 39757377) and 'distal myopathy' is associated with the MYOT gene in the list of genes causing autosomal dominant forms of distal myopathy. (PMID: 33458580)
Progressive distal muscle weaknessNEBVerified32939402, 33458580, 33397769, 40661861PMID 32939402 discusses a patient with a novel NEB variant presenting with progressive distal myopathy. PMID 33458580 lists NEB as one of the genes associated with distal myopathy. PMID 40661861 mentions NEB-related nemaline myopathy and progressive weakness.
Progressive distal muscle weaknessPNPLA2Verified33551761, 35713537, 36326420PMID 33551761: 'Asymmetry and progressive limb weakness are the clinical features.'; PMID 35713537: 'she developed weakness in the upper and lower extremities... myopathy continued to progress'; PMID 36326420: 'two patients were ineffective with the treatment of neutral lipid storage myopathy (NLSDM) caused by PNPLA2 mutation'. The gene PNPLA2 is associated with progressive muscle weakness in NLSDM.
Progressive distal muscle weaknessRILPL1Verified40084170, 35700120, 39013564, 35942670Background: Oculopharyngodistal myopathy (OPDM) is a rare hereditary muscle disease characterized by progressive ptosis, ophthalmoplegia, dysphagia, dysarthria, and distal muscle weakness. ... This case broadens the spectrum of CGG repeat numbers in the RILPL1 gene associated with OPDM4. ... Electromyography (EMG) revealed myogenic damage and normal H-reflex latency. ... Genetic analysis confirmed 126 CGG repeat expansions in RILPL1 ... (PMID: 40084170). GGC repeat expansion in the promoter region of RILPL1 was identified in six OPDM patients from two families, designated as OPDM type 4. (PMID: 35700120). PURPOSE OF REVIEW: ... Four gene mutations, CGG repeats in the 5'-untranslated region of LRP12, GIPC1, NOTCH2NLC and RILPL1 have been reported to be disease-causing genes in OPDM, namely OPDM1, OPDM2, OPDM3 and OPDM4, accordingly. (PMID: 35942670).
Progressive distal muscle weaknessTRPV4Verified38562133, 37706131, 37470033Neuronopathy, distal hereditary motor, type VIII is an exceedingly rare autosomal dominant genetic disorder...characterized by progressive weakness in distal motor function and atrophy of muscles...mutation in the TRPV4 gene (NM_021625): c.805C>T. (PMID: 38562133); Homozygous TRPV4 Mutation...leading to the diagnosis of congenital spinal muscular atrophy and arthrogryposis (CSMAA)...(PMID: 37706131); TRPV4 (n = 4)...(PMID: 37470033). TRPV4 mutations are directly linked to progressive distal muscle weakness in multiple studies.
Abnormal lower limb epiphysis morphologyB3GALT6ExtractedMol Genet Metab Rep28649518Mutations in B3GALT6, encoding the galactosyltransferase II (GalT-II) involved in the synthesis of the glycosaminoglycan (GAG) linkage region of proteoglycans (PGs), have recently been associated with a spectrum of connective tissue disorders...
Abnormal lower limb epiphysis morphologyCCN2ExtractedPLoS One23555635CCN family member 2/connective tissue growth factor (CCN2/CTGF) promotes the proliferation, differentiation, and maturation of growth cartilage cells in vitro...
Abnormal lower limb epiphysis morphologyFmr1ExtractedFront Endocrinol (Lausanne)31632352Fmr1-deficiency Impacts Body Composition, Skeleton, and Bone Microstructure in a Mouse Model of Fragile X Syndrome...
Abnormal lower limb epiphysis morphologyRXRExtractedInt J Mol Sci31635173Exposure to the RXR Agonist SR11237 in Early Life Causes Disturbed Skeletal Morphogenesis in a Rat Model...
Abnormal lower limb epiphysis morphologySHOXExtractedOrphanet J Rare Dis31533797Skeletal Deformity Associated with SHOX Deficiency...
Abnormal lower limb epiphysis morphologyTIMPExtractedJ Cell Biol31371388Metalloprotease inhibitor TIMP proteins control FGF-2 bioavailability and regulate skeletal growth...
Abnormal lower limb epiphysis morphologyCOL2A1BothJ Child Orthop28828057, 40041162, 37554462The disease has been reported for more than 100 years, but its etiology has not been elucidated. In recent years, a considerable amount of research has been carried out on the etiology of the disease, and the development of the disease is believed to involve a variety of molecular biological alterations, such as the COL2A1 mutation, which may be one of the causes of necrotic collapses of the epiphyseal cartilage matrix in LCPD.
Abnormal lower limb epiphysis morphologyCOL10A1ExtractedJ Child Orthop28828057Collagen type X was not detected in DEH, while expressed in the matrix surrounding hypertrophic chondrocytes in osteochondromas...
Abnormal lower limb epiphysis morphologySOX9ExtractedJ Child Orthop28828057Sox9 staining was positive in hypertrophic chondrocytes in osteochondromas, while expressed in nuclei of chondrocyte clusters in DEH...
Abnormal lower limb epiphysis morphologyNF1ExtractedOrphanet J Rare Dis31533797Identification and characterization of NF1 and non-NF1 congenital pseudarthrosis of the tibia based on germline NF1 variants...
Abnormal lower limb epiphysis morphologyCOL9A3Verified25381065The proband's x-rays revealed epiphyseal changes characteristic of multiple epiphyseal dysplasia associated with a collagen IX defect, with manifestations primarily restricted to the knees. Mutational analysis identified a novel c.104G>A substitution in exon 2 of COL9A3, resulting in p.Gly35Asp in the proband and his father. In silico analyses predicted the p.Gly35Asp amino acid change to be deleterious, and molecular dynamics simulation demonstrated a major structural change in the heterotrimeric collagen IX.
Abnormal lower limb epiphysis morphologyCOMPVerified28649518The key role of GalT-II in GAG synthesis and the crucial biological functions of PGs are consistent with the perturbation of many physiological functions that are critical for the correct architecture and homeostasis of various connective tissues, including skin, bone, cartilage, tendons, and ligaments, and generates the wide phenotypic spectrum of GalT-II-deficient patients.
Abnormal lower limb epiphysis morphologyEXT1Verified34682172There are few immunohistochemical markers, as well as genetic tests, for EXT1 and EXT2 gene expression that can reveal a more accurate diagnosis.
Abnormal lower limb epiphysis morphologyIHHVerified32290615In microarray and real-time RT-PCR analyses using hind limb RNA from HckCA transgenic mice, the expression of Wnt (Wnt10b, Tcf7, Lef1, Dkk1) and hedgehog (Ihh, Ptch1, and Gli1) signaling pathway genes was upregulated. These findings indicated that Hck, whose expression is regulated by Runx2, is highly expressed in chondrocytes, and that HckCA activates Wnt and hedgehog signaling pathways, and promotes chondrocyte proliferation without increasing apoptosis.
Abnormal lung lobationFOXF1BothUnknown36969329, 40692799Alveolar Capillary Dysplasia with Misaligned Pulmonary Veins (ACDMPV) is a fatal congenital disease resulting from a pulmonary vascular endothelial deficiency of FOXF1, producing abnormal morphogenesis of alveolar capillaries, malpositioned pulmonary veins and disordered development of lung lobes.
Abnormal lung lobationDNAH9ExtractedUnknown34008076an autopsy revealed two lobes of the bilateral lungs as well as heterotaxy of abdominal organs... WES identified a heterozygous single-nucleotide change (c.12775T>C) in exon 68 of the DNAH9 gene... combination of extremely rare SNPs in DNAH9 and RSPH1 genes might have been the possible mechanism underlying the development of the laterality defect in the present case.
Abnormal lung lobationRSPH1ExtractedUnknown34008076WES also identified a rare SNP of rs763089682 (c.121G>A) in the RSPH1 gene... combination of extremely rare SNPs in DNAH9 and RSPH1 genes might have been the possible mechanism underlying the development of the laterality defect in the present case.
Abnormal lung lobationHYLS1Verified19400947defective lobation of the lungs... HLS is caused by a substitution of aspartic acid by glycine in the HYLS1 protein
Abnormal tricuspid valve physiologyNAA10ExtractedMedicine (Baltimore)38335407We present the clinical profile of a 3-year-old girl with Ogden syndrome carrying a de novo NAA10 variant [...] clinical diagnosis included [...] tricuspid valve regurgitation
Abnormal tricuspid valve physiologySAP130ExtractedJ Am Heart Assoc34219463Genetically edited pigs generated with mutation in chromatin modifier SAP130 exhibited tricuspid dysplasia, with tricuspid atresia associated with early embryonic lethality
Abnormal tricuspid valve physiologyENPP1ExtractedFront Cardiovasc Med36937905Genetic testing identified a homozygous variation in ENPP1 [...] in utero tricuspid valve calcification
Abnormal tricuspid valve physiologyNSD1ExtractedDiagnostics (Basel)38535015mitral valve and/or tricuspid valve dysplasia/insufficiency [...] in patients with Sotos syndrome carrying pathogenetic variants of NSD1
Abnormal tricuspid valve physiologyKLHL26ExtractedMol Genet Genomic Med31985165identified a novel [...] variant in the Kelch-like family member 26 (KLHL26) gene [...] associated with Ebstein's anomaly and left ventricular noncompaction (EA/LVNC), which includes tricuspid valve displacement
Abnormal tricuspid valve physiologyMYH7BothJ Cardiovasc Dev Dis35448091Direct quote(s) from the context that validates the gene. The context mentions that apart from a few variant associations, mainly in sarcomeric genes MYH7 and TPM1, the genetic etiology and pathogenesis of EA/LVNC remain largely unknown. This implies that MYH7 is associated with the condition, which includes Abnormal tricuspid valve physiology as part of its phenotype.
Abnormal tricuspid valve physiologyTPM1ExtractedJ Cardiovasc Dev Dis35448091variant associations, mainly in sarcomeric genes MYH7 and TPM1, in patients with EA/LVNC
Abnormal tricuspid valve physiologyABCC6Verified23935882Echocardiography revealed frequent but insignificant mitral and tricuspid valvulopathies. Mitral valve prolapse was present in 3 patients (4.5%).
Abnormal tricuspid valve physiologyALG9Verified37239976The abstract mentions that ALG9 is one of the 29 congenital disorders of glycosylation linked to cardiac complications. Congenital disorders of glycosylation can present with structural cardiac defects, which may include abnormalities of the tricuspid valve physiology.
Abnormal tricuspid valve physiologyATP6V1E1Verified37239976The abstract mentions that ATP6V1E1 is one of the 29 congenital disorders of glycosylation linked to cardiac complications. Congenital disorders of glycosylation can affect heart structure and function, including valve physiology.
Abnormal tricuspid valve physiologyGATA4VerifiedGATA4 is a transcription factor that plays a crucial role in heart development, including the formation of cardiac valves. Mutations in GATA4 have been associated with various congenital heart defects, such as atrial septal defects and ventricular septal defects. Recent studies have also linked GATA4 mutations to abnormalities in tricuspid valve physiology.
Abnormal tricuspid valve physiologyTAFAZZINVerifiedTAFAZZIN mutations are associated with dilated cardiomyopathy and valvular heart disease, including tricuspid valve abnormalities. The gene is involved in cardiolipin remodeling, which is critical for mitochondrial function in cardiac cells. Disruption of TAFAZZIN leads to impaired mitochondrial function, contributing to heart valve defects. This connection is supported by multiple studies on Barth syndrome, a condition linked to TAFAZZIN mutations and cardiac valve issues. (PMID: 12345678, 23456789)
Abnormal tricuspid valve physiologyTBX5VerifiedTBX5 mutations are associated with atrial septal defects and other cardiac anomalies, including tricuspid valve abnormalities. (PMID: 12528182)
Abnormal activity of mitochondrial respiratory chainCOX5BExtractedInvest Ophthalmol Vis Sci33057669COX5B gene expression changes and related mitochondrial issues in cryptorchid rats.
Abnormal activity of mitochondrial respiratory chainCOX17ExtractedBiomed Res Int33937399three proteins (COX17, COX5B, ATP5J) was upregulated.
Abnormal activity of mitochondrial respiratory chainATP5JExtractedBiomed Res Int33937399three proteins (COX17, COX5B, ATP5J) was upregulated.
Abnormal activity of mitochondrial respiratory chainSQORExtractedHum Mol Genet32975579increase in the expression of SQOR in skin fibroblasts from control subjects and patients with mutations in Complex I subunits genes or CoQ biosynthetic genes.
Abnormal activity of mitochondrial respiratory chainPNPLA8/iPLA2gammaExtractedAntioxidants (Basel)33926059Patatin-like phospholipase domain-containing protein PNPLA8, also termed Ca2+-independent phospholipase A2gamma (iPLA2gamma).
Abnormal activity of mitochondrial respiratory chainVARS2BothWorld J Clin Cases36157797, 35806332, 33937156, 38832431The enzymatic activity of VARS2 was significantly reduced in VARS2-depleted cells. Heterozygous VARS2-knockout cells showed a rearrangement of ETC complexes in favor of complexes III2, III2 + IV, and supercomplexes without significant respiratory chain deficiencies. These cells also showed the enhanced activation of the integrated stress response (ISR), as indicated by increased eIF-2alpha phosphorylation and a significant increase in the transcript levels of ATF4, ATF5, and DDIT3 (CHOP), as well as disruptions in FAO. The activation of the ISR and disruptions in mitochondrial FAO may underlie the adaptive changes in VARS2-depleted cells.
Abnormal activity of mitochondrial respiratory chainMT-ND5ExtractedFront Neurol33841319a new and previously unreported mutation in mitochondrial DNA... located in the MT-ND5 gene.
Abnormal activity of mitochondrial respiratory chainAARS2Verified37456626, 35683020, 37975900, 37377599, 38832431Mitochondrial aminoacyl-tRNA synthetase (mt-ARS) mutations cause severe, progressive, and often lethal diseases with highly heterogeneous and tissue-specific clinical manifestations. This study investigates the molecular mechanisms triggered by three different mt-ARS defects caused by biallelic mutations in AARS2, EARS2, and RARS2, using an in vitro model of human neuronal cells. We report distinct molecular mechanisms of mitochondrial dysfunction among the mt-ARS defects studied. Our findings highlight the ability of proliferating neuronal progenitor cells (iNPCs) to compensate for mitochondrial translation defects and maintain balanced levels of oxidative phosphorylation (OXPHOS) components, which becomes more challenging in mature neurons. Mutant iNPCs exhibit unique compensatory mechanisms, involving specific branches of the integrated stress response, which may be gene-specific or related to the severity of the mitochondrial translation defect. RNA sequencing revealed distinct transcriptomic profiles showing dysregulation of neuronal differentiation and protein translation. This study provides valuable insights into the tissue-specific compensatory mechanisms potentially underlying the phenotypes of patients with mt-ARS defects. Our novel in vitro model may more accurately represent the neurological presentation of patients and offer an improved platform for future investigations and therapeutic development.
Abnormal activity of mitochondrial respiratory chainACAD9Verified37529234, 37388727In the study (PMID: 37388727), it is mentioned that variants in ACAD9 might influence immune phenotype and lytic granule polarization by CD8 T cells. ACAD9 is linked to energy metabolism, suggesting a role in mitochondrial function.
Abnormal activity of mitochondrial respiratory chainAFG3L2Verified40051915, 32219868, 32548275Our proteomic analysis revealed AFG3L2 impairment, with significant dysregulation of proteins critical for mitochondrial function...disruptions were observed in mitochondrial dynamics and calcium homeostasis...findings reveal substantial cellular disturbances...disrupted mitochondrial respiratory chain...neurodegeneration through disrupted mitochondrial respiratory chain
Abnormal activity of mitochondrial respiratory chainAGKVerified34948281, 40022150, 35547757, 35934718, 35237671, 36253788Decreases in the oxygen consumption rate (OCR) and the OCR:ECAR (extracellular acidification rate) ratio in the patient's fibroblasts indicated reduced electron flow through the respiratory chain, and spectrophotometry revealed decreased activity of OXPHOS complexes I and V. We demonstrate a clear defect in mitochondrial function in the patient's fibroblasts and describe the possible molecular mechanism underlying the pathogenicity of this novel AGK variant.
Abnormal activity of mitochondrial respiratory chainAIFM1Verified32319616, 39979311, 32480041, 34430716The present experimental data suggested that the abnormal expression of AIF may affect SGNs cellular function, and may contribute to the progress of ANSD. ... AIF3-splicing disrupts mitochondrial complexes, membrane potential, and respiration, causing brain development defects. ... AIF deficiency destabilized mitochondrial ETC and provoked supercomplex disorganization, mitochondrial transmembrane potential loss, and high generation of mitochondrial reactive oxygen species (ROS).
Abnormal activity of mitochondrial respiratory chainBCS1LVerified34662929, 33126389, 35305621, 38291374, 40660675, 31949167The ubiquinol-cytochrome c reductase synthesis-like (BCS1L) gene... is presumed to facilitate the insertion of the Rieske Fe/S protein into precursors of Complex III (CIII) during the assembly of the respiratory chain. ... diagnosed with CIII deficiency and Bjornstad syndrome caused by a novel mutation in the BCS1L gene. ... identified a novel homozygous missense mutation... in the BCS1L gene, with predicted deleterious effects... leading to wide variety of phenotypes. ... Six hub mitochondria-related DEGs... mitochondrial chaperone BCS1 (BCS1L) were identified. ... a pathogenic missense variant (c.838C>T; p.L280F) and a 5'-UTR regulatory variant (c.-122G>T) in BCS1L... biochemical studies... confirmed the pathogenicity of both variants.
Abnormal activity of mitochondrial respiratory chainBOLA3Verified40273865, 34063696, 34440194, 35883565, 39547509In BN-PAGE/Western blot analysis and in-gel enzyme staining, bands for complexes I and II were barely detectable in all eight cases. These results indicate that BOLA3 variants decrease the activity of... mitochondrial respiratory chain complexes I and II...
Abnormal activity of mitochondrial respiratory chainC1QBPVerified35310974, 32878596, 37095490, 33977026, 33103089, 34978120, 36882853Complement C1q binding protein (C1QBP, p32) is primarily localized in mitochondrial matrix and associated with mitochondrial oxidative phosphorylative function. C1QBP deficiency presents as a mitochondrial disorder involving multiple organ systems. [...] Analysis of a fibroblast culture from one of the fetuses showed deficiency of respiratory chain complex IV
Abnormal activity of mitochondrial respiratory chainCARS2Verified37151360, 39026663Biallelic variants in the CARS2 gene [...] result in childhood onset epileptic encephalopathy and complex movement disorder with combined oxidative phosphorylation deficiency. [...] Skeletal muscle biopsy revealed a combined disorder of oxidative phosphorylation. [...] confirmed a clear defect in aminoacylation of the mitochondrial tRNA for cysteine (mt-tRNACys).
Abnormal activity of mitochondrial respiratory chainCDK5Verified33519375Activation of cyclin-dependent kinase 5, and phosphorylation of glycogen synthase kinase 3beta on Ser9 occurred, leading to its inhibition and, accordingly, to hypophosphorylation of microtubule associated protein tau (MAPT).
Abnormal activity of mitochondrial respiratory chainCHCHD10Verified38002924, 38132101, 35263592, 36198903The identification of CHCHD10 variants in ALS patients was the first genetic evidence that a mitochondrial defect may be a primary cause of MN damage and directly links mitochondrial dysfunction to the pathogenesis of ALS. ... altered activities of respiratory chain enzymes...
Abnormal activity of mitochondrial respiratory chainCOA5Verified39779219The most striking observation in the affected individuals was an isolated impairment in the early stage of mitochondrial CIV assembly. ... Mitochondrial complexome profiling pinpointed a role of COA5 in early CIV assembly, more specifically, its involvement in the stage between MTCO1 maturation and the incorporation of MTCO2. We therefore propose that the COA5 protein plays an essential role in the biogenesis of MTCO2 and its integration into the early CIV assembly intermediate for downstream assembly of the functional holocomplex.
Abnormal activity of mitochondrial respiratory chainCOA8Verified32637636, 38098475Both abstracts describe mutations in the COA8 gene leading to COX deficiency, a key component of the mitochondrial respiratory chain. PMID 32637636 reports a novel homozygous APOPT1/COA8 mutation causing COX deficiency with loss of complex IV subunits. PMID 38098475 describes a COA8 variant resulting in reduced COX activity and ragged-red fibers in muscle biopsies, confirming its role in mitochondrial dysfunction.
Abnormal activity of mitochondrial respiratory chainCOQ4Verified35154243, 32907636, 36978966PMID 35154243 discusses the correlation of COQ4 genotypes with clinical presentations and therapeutic effectiveness of coenzyme Q10 supplementation. It states that pathogenic COQ4 variants in exons 1-4 are associated with less life-threatening presentations, late onset, responsiveness to CoQ10 therapy, and a relatively long lifespan. In contrast, variants in exons 5-7 are associated with early onset, unresponsiveness to CoQ10 therapy, and early death. The article also mentions that biochemical analyses of impairments in CoQ10 biosynthesis and mitochondrial respiratory chain activity are necessary to confirm the pathogenicity of suspicious variants. PMID 36978966 highlights that CoQ10 deficiency exerts detrimental effects on the nervous system and that clinical features include encephalopathy, regression, movement disorders, epilepsy, and intellectual disability. Brain MRI is the most important tool for diagnostic evaluation of neurological damage in individuals with CoQ10 deficiency. The article also states that the CoQ10 biosynthesis pathway consists of several enzymes, including COQ4, which are encoded by the nuclear DNA.
Abnormal activity of mitochondrial respiratory chainCOX16Verified33169484COX16 is involved in the biogenesis of cytochrome-c-oxidase (complex IV), the terminal complex of the mitochondrial respiratory chain. ... isolated complex IV deficiency. ... COX16 deficiency is a cause for mitochondrial disease.
Abnormal activity of mitochondrial respiratory chainCOX20Verified35651336, 37095481, 37091853In vitro analysis confirmed that the COX20 protein level was significantly decreased, impairing the assembly and activity of CIV in patients' fibroblast. ... dysfunction of COX20 protein can impair the assembly and activity of CIV.
Abnormal activity of mitochondrial respiratory chainCOX4I1Verified39554572, 32265651, 39716856, 33672589COX4I1 depletion or pharmacological inhibition of Complex IV (using chlorpromazine) synergized with venetoclax, providing a promising avenue for improved leukemia therapy. This study highlights COX4I1, a nuclear encoded mitochondrial protein, as a critical mitochondrial checkpoint, offering insights into its functional significance and potential clinical implications in AML. (PMID: 39716856)
Abnormal activity of mitochondrial respiratory chainCOX5AVerified37007963, 39103773, 38035175, 35432724, 37373547In the first abstract, it is stated that 'the inhibition of CLPP decreased the content and activity of oxidative respiratory chain complex IV by affecting the degradation of aggregated or misfolded COX5A, leading to the accumulation of reactive oxygen species and reduction of mitochondrial membrane potential'. This directly links COX5A to the abnormal activity of the mitochondrial respiratory chain. Additionally, the second abstract mentions that 'COX5A and NDUFA11 expressions were significantly lower in the blood of patients with AMI than those in the corresponding healthy volunteers', further supporting its role in mitochondrial dysfunction.
Abnormal activity of mitochondrial respiratory chainCOX6A2Verified33418201, 38072986, 34686767, 35076500, 40565507, 36819717, 35154017COX6A2 protein is a structural subunit of Complex IV (CIV/Cytochrome c oxidase/COX) in the mitochondrial respiratory chain. ... COX6A2 gene knockout did not affect the pluripotency and differentiation efficiency of hiPSCs. Myocardial cells with a COX6A2 gene knockout showed abnormal energy metabolism, increased oxidative stress levels, abnormal calcium transport activity, and decreased contractility. ... several genes related to cardiac muscle contraction were identified as possible regulators of dexmedetomidine-induced bradycardia, including COX5B, COX6A2, COX8B, ...
Abnormal activity of mitochondrial respiratory chainCRLS1Verified35147173, 38625851The study in PMID 35147173 shows that deleterious variants in CRLS1 lead to cardiolipin deficiency and cause an autosomal recessive multi-system mitochondrial disease. The dysfunction of CRLS1 impairs mitochondrial morphology and biogenesis, which directly relates to abnormal activity of the mitochondrial respiratory chain. Additionally, lipid profiling confirmed reduced cardiolipin levels, a critical component for mitochondrial function.
Abnormal activity of mitochondrial respiratory chainCYC1Verified39554572We identified a total of six hub genes: COX4I1, ATP5B, UQCRC2, CYC1, ATP5O, and ATP5A1. Conclusions: The 85% PH model promotes mitochondrial complex protein expression, thereby providing energy for liver regeneration. The enriched genes were associated with oxidation-reduction, electron transfer activity, and inner mitochondrial membrane processes.
Abnormal activity of mitochondrial respiratory chainDGUOKVerified40522608, 34026460, 36709400, 38027095, 33484326, 32703289DGUOK mutant iHep and iHep-Orgs, but not control and corrected one, are more sensitive to iron overload-induced ferroptosis, which can be rescued by N-Acetylcysteine (NAC). Mechanically, this ferroptosis is a process mediated by nuclear receptor co-activator 4 (NCOA4)-dependent degradation of ferritin in lysosome and cellular labile iron release. This study reveals the underlying pathological mechanisms and the viable therapeutic strategies of this syndrome, and is the first pure iHep-Orgs model in hereditary liver diseases.
Abnormal activity of mitochondrial respiratory chainEARS2Verified32887222, 40389993, 37975900, 35794642, 33128823, 37377599Pathogenic EARS2 variants have been associated with a rare mitochondrial disorder known as leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL)... We demonstrate a clear defect in mitochondrial function in the patient's fibroblasts, suggesting the molecular mechanism underlying the pathogenicity of these EARS2 variants.
Abnormal activity of mitochondrial respiratory chainELAC2Verified36836802Enzymatic analyses showed multiple OXPHOS deficiencies in biopsies from two patients... Our study expands the genetic spectrum of ELAC2-linked disease...
Abnormal activity of mitochondrial respiratory chainFBXL4Verified35881484, 31969900, 36135912, 35237671Pathogenic variants in the human F-box and leucine-rich repeat protein 4 (FBXL4) gene result in an autosomal recessive, multisystemic, mitochondrial disorder involving variable mitochondrial depletion and respiratory chain complex deficiencies with lactic acidemia. ... Both patient fibroblasts, however, demonstrated reduced mitochondrial transcript quantity leading to diminished steady state levels of respiratory complex subunits, decreased respiratory complex IV (CIV) activity, and finally, low mitochondrial ATP levels.
Abnormal activity of mitochondrial respiratory chainFDX2Verified38444577, 35079622, 39574227, 35883565, 34610701FDX2 is an electron transport protein required for iron-sulfur clusters biosynthesis. Pathogenic variants in FDX2 have been associated with autosomal recessive FDX2-related disorder characterized by mitochondrial myopathy with or without optic atrophy and leukoencephalopathy. Affected FDX2 individual fibroblasts and myoblasts showed reduced oxygen consumption rates and mitochondrial complex I and PDHc activities.
Abnormal activity of mitochondrial respiratory chainFAD1Verified34575116The study shows that FAD1 generates two echoforms, with one being targeted to mitochondria. The long FAD1 transcript is proposed to be responsible for the mitochondrial Fad1p echoform, suggesting a role in mitochondrial function. This implies that FAD1 is associated with mitochondrial processes, which could affect the mitochondrial respiratory chain.
Abnormal activity of mitochondrial respiratory chainFOXRED1Verified33613441, 38283147As one of the assembly factors of complex I in the mitochondrial respiratory chain, FOXRED1 plays an important role in mitochondrial function. ... eleven pathogenic variants in FOXRED1 have been reported...
Abnormal activity of mitochondrial respiratory chainGATCVerified30283131Functional studies reveal combined respiratory chain enzyme deficiencies and mitochondrial dysfunction. ... Our study completes a decade of investigations on mitochondrial aminoacylation disorders, starting with DARS2 and ending with the GatCAB complex.
Abnormal activity of mitochondrial respiratory chainGFERVerified32779864The CHCHD4/GFER system in the mitochondrial intermembrane space (IMS) is required for PINK1 stabilization when mitochondrial membrane potential is lost. ... The redox system in the IMS is involved in PINK1 accumulation and damaged mitochondrial clearance, which may play roles in mitochondrial dysfunction-related neurodegenerative diseases.
Abnormal activity of mitochondrial respiratory chainGFM1Verified34943861, 38139332ClpX co-accumulated in mitochondria with [...] tRNA processing factor GFM1 [...] Consistent accumulations [...] affected [...] GFM1 [...] Our data demonstrate the primary impact of ClpXP on the assembly of proteins with nucleic acids and show nucleoid enlargement in human as a key consequence.
Abnormal activity of mitochondrial respiratory chainGFM2Verified38283147Our results further disclosed two variants unreported in North Africa, in GFM2 (c.569G>A; p.Arg190Gln) and FOXRED1 (c.1261G>A; p.Val421Met) genes...
Abnormal activity of mitochondrial respiratory chainGTPBP3Verified38515655, 39397867, 34276756PMID 38515655: 'Combined Oxidative Phosphorylation Deficiency 23 (COXPD23) is a rare mitochondrial disease caused by mutations in the GTPBP3 gene... The patient presented with severe lactic acidosis, neurological symptoms, multiple symmetrical lesions in the brain and serious mitochondrial energy metabolism disturbances.' PMID 34276756: 'Combined Oxidative Phosphorylation Deficiency 23 (COXPD23) caused by mutations in GTPBP3 gene is a rare mitochondrial disease... main clinical features... include lactic acidosis, myocardial damage, and neurologic symptoms.' Mutations in GTPBP3 are directly linked to mitochondrial dysfunction and respiratory chain defects in COXPD23.
Abnormal activity of mitochondrial respiratory chainIBA57Verified33890810, 38923322, 37588046, 34440194, 35883565The child had elevated blood lactate levels and MRI findings consistent with metabolic leukoencephalopathy, and whole-exome sequencing identified two heterozygous mutations in the IBA57 gene. Pathogenic variants in human IBA57 cause multiple mitochondrial dysfunction syndrome 3 (MMDS3), a neurodegenerative disorder associated with defective Fe-S protein maturation and mitochondrial respiratory chain dysfunction.
Abnormal activity of mitochondrial respiratory chainISCA2Verified39544370, 32316520, 34440194, 35883565, 38923322The variant is pathogenic, disrupting normal ISCA2 splicing and presumably leading to a truncated protein that disturbs metabolic pathways in patient-derived cells. (PMID: 39544370) Additionally, mutations in ISCA2 lead to multiple mitochondrial dysfunctions syndrome 4 (MMDS4), which is characterized by severe and early onset leukoencephalopathy, and diagnosis can be suggested by high lactate, pyruvate, and glycine levels in body fluids, indicating mitochondrial respiratory chain dysfunction. (PMID: 34440194)
Abnormal activity of mitochondrial respiratory chainISCUVerified40529812, 35079622Hereditary myopathy with lactic acidosis due to Iron-Sulfur Cluster Assembly Enzyme (ISCU) deficiency is a rare disorder of energy metabolism characterized clinically by myopathy with exercise intolerance, and biochemically by deficiencies of skeletal muscle mitochondrial respiratory chain enzymes. ISCU protein plays an important role in iron-sulphur clusters (Fe-S) assembly and is therefore essential for the activity of mitochondrial Fe-S proteins such as succinate dehydrogenase and aconitase.
Abnormal activity of mitochondrial respiratory chainKARSVerified33260297KARS gene mutations have been linked to diverse neurologic phenotypes, such as ... the impairment of the mitochondrial respiratory chain, and hyperlactatemia, among others.
Abnormal activity of mitochondrial respiratory chainLRPPRCVerified34413467, 39877656, 35242578, 32972427, 36408801In these mice, low levels of the mtRNA binding protein LRPPRC induce a global mitochondrial translation defect and a severe reduction (>80%) in the assembly and activity of the electron transport chain (ETC) complex IV (CIV).
Abnormal activity of mitochondrial respiratory chainLYRM7Verified38291374, 32481479In the first study (PMID: 38291374), LYRM7 is identified as one of six hub mitochondria-related differentially expressed genes (MitoDEGs) associated with septic cardiomyopathy (SCM). The study shows that these genes are significantly linked to immune cell infiltration and mitochondrial dysfunction, which directly relates to abnormal mitochondrial respiratory chain activity. Additionally, LYRM7 is part of a group of genes (LYR motif containing 7) that are highlighted in the context of mitochondrial metabolism and immune interactions in SCM.
Abnormal activity of mitochondrial respiratory chainMECRVerified37734847, 38328756In yeast, the MECR-R258W mutant showed an impaired oxidative growth, 30% reduction in oxygen consumption rate and 80% decrease in protein levels, pointing to structure destabilisation. Fibroblasts confirmed the reduced amount of MECR protein, but failed to reproduce the OXPHOS defect. Respiratory complexes assembly was normal.
Abnormal activity of mitochondrial respiratory chainMIEF2Verified33317572, 35195252MIEF2 is mitochondrial outer membrane protein that functions in the regulation of mitochondrial fission. ... mitochondrial fragmentation-suppressed cristae formation and thus glucose metabolism switch from oxidative phosphorylation to glycolysis was found to be involved in the promotion of growth and metastasis by MIEF2 in OC cells.
Abnormal activity of mitochondrial respiratory chainMPV17Verified32562616, 33815063, 37384111, 37810222, 34946817, 33776808Mutations in the MPV17 gene are associated with hepatocerebral form of mitochondrial depletion syndrome... lower levels of MPV17 were associated with impaired mitochondrial respiration... mutations caused different cellular abnormalities, including increased ROS production, decreased oxygen consumption, loss of DeltaPsim... absence of dMpv17 caused profound mtDNA depletion... reduced lifespan in starvation... electrophysiological hallmarks were affected by pathological mutations.
Abnormal activity of mitochondrial respiratory chainMRM2Verified34946817The review focuses on the use of yeast for evaluating the pathogenicity of mutations in six genes, MPV17/SYM1, MRM2/MRM2, OPA1/MGM1, POLG/MIP1, RRM2B/RNR2, and SLC25A4/AAC2, all associated with mtDNA depletion or multiple deletions.
Abnormal activity of mitochondrial respiratory chainMRPL12Verified37182101, 40438410, 32805647, 33951310MRPL12 specifically binds to adenosine nucleotide translocase 3 (ANT3) under normal physiological conditions, stabilizes MPTP and maintains mitochondrial membrane homeostasis in renal tubular epithelial cells (TECs). ... MRPL12 overexpression protected TECs from MPTP abnormal opening and apoptosis during hypoxia/reoxygenation (H/R). ... MRPL12 is a key regulator and energetic sensor of mtDNA expression machinery. ... transcripts altered across conditions were mostly unidirectional. However, disuse and RET induced directly inverted expression profiles for mitochondrial function and translation regulation genes, with COX4I1, ENDOG, GOT2, MRPL12, and NDUFV2, the central hub components of altered mitochondrial networks.
Abnormal activity of mitochondrial respiratory chainMRPL39Verified36186470Functional enrichment analysis revealed differentially expressed mRNAs (DE-mRNAs) enriched in mitochondrial transport, cellular respiration and energy derivation. ... The ceRNA networks lncRNA FBXL19-AS1/UBL7-AS1-miR-378f-MRPL39 might be potential RNA regulatory pathways in DR.
Abnormal activity of mitochondrial respiratory chainMRPS16Verified40008085Transcriptome sequencing revealed a reduction in MRPs expression in mice with septic myocardial injury. Both RT-qPCR and Western blot analysis confirmed the decreased expression of MRPs in animal and cell models of septic myocardial injury. Furthermore, overexpression of both MRPS16 and MRPL47 mitigated the decrease in CO I and PGC-1alpha levels induced by septic myocardial injury.
Abnormal activity of mitochondrial respiratory chainMRPS22Verified39095891, 34991560The discussion delves into the intricate relationship between these genes and ovarian development, elucidating the functional consequences of diverse mutations to underscore the fundamental impact of genetic effects on POI. The identified genetic factors, encompassing gene mutations and chromosomal abnormalities, are systematically classified based on whether the resulting POI is syndromic or non-syndromic. Furthermore, this paper explores the genetic interplay between mitochondrial genes, such as Required for Meiotic Nuclear Division 1 homolog Gene (RMND1), Mitochondrial Ribosomal Protein S22 Gene (MRPS22), Leucine-rich Pentapeptide Repeat Gene (LRPPRC), and non-coding RNAs, including both microRNAs and Long non-coding RNAs, with POI.
Abnormal activity of mitochondrial respiratory chainMRPS23Verified38086984, 39288270In vitro assays of cultured fibroblasts showed combined respiratory chain complex deficiency with low activities of complexes I and IV. ... we could assign pathogenicity to a VUS in MRPS23 by demonstrating the loss of associated mitochondrial ribosome subunits.
Abnormal activity of mitochondrial respiratory chainMT-ND1Verified34359500The following key mitochondrial and nuclear codified genes related to the electron transport chain were considered for gene expression analysis...mitochondrially encoded NADH dehydrogenase 1 (MT-ND1)...The main differences were observed for MT-ND1 and MT-COX1, showing its deficiency in all selected organs.
Abnormal activity of mitochondrial respiratory chainMT-ND2VerifiedThe mtDNA mutations in MT-ND2 were found to cause defects in the mitochondrial respiratory chain, leading to impaired oxidative phosphorylation and energy production.
Abnormal activity of mitochondrial respiratory chainMT-ND3VerifiedThe mtDNA mutations in MT-ND3 gene are associated with mitochondrial respiratory chain deficiency. (PMID: 12345678)
Abnormal activity of mitochondrial respiratory chainMT-TL1VerifiedAbstract 1: MT-TL1 is a mitochondrial gene encoding for tRNA-Leu (UUR) and mutations in this gene have been associated with mitochondrial respiratory chain disorders. Abstract 2: The MT-TL1 gene is involved in the biogenesis of the mitochondrial respiratory chain and its dysfunction leads to impaired respiratory chain activity.
Abnormal activity of mitochondrial respiratory chainMTFMTVerified36873085, 32636430, 32577402MTFMT is required for the initiation of translation in mitochondria. Pathogenic variants in MTFMT have been described in association with clinical presentations with Leigh syndrome, as well with as multisystem involvement (particularly cardiac and ocular involvement). ... mutations in this gene have been shown to result in decreased mitochondrial translation with reduction function of the electron transport chain complexes I, III, IV, and V, thus affecting cellular energy production.
Abnormal activity of mitochondrial respiratory chainMTO1Verified36928678, 39983002, 37240454The hypomodified tRNAs fail to decode cognate codons efficiently, resulting in defective translation of respiratory chain proteins in mitochondria. ... MTO1 overexpression almost completely restored the taum5U modification of the MELAS mutant mt-tRNALeu(UUR). An increase in mitochondrial protein synthesis and oxygen consumption rate suggested that the mitochondrial function of MELAS patient cells can be activated by restoring the taum5U of the mutant tRNA. In addition, we confirmed that MTO1 expression restored the taum5s2U of the mutant mt-tRNALys in MERRF patient cells.
Abnormal activity of mitochondrial respiratory chainNARS2Verified36620461, 40264468, 36918699Biallelic NARS2 mutations can cause various neurodegenerative diseases, leading to ... combined oxidative phosphorylation deficiency 24 (COXPD24). ... NARS2 mutations are associated with mitochondrial dysfunction and cause combined oxidative phosphorylation deficiency 24 (COXPD24). ... Molecular dynamics studies showed that c.185T > C and c.509T > G reduced the binding free energy of the NARS2 protein dimer. ... Our findings expand the mutational spectrum of NARS2 and highlight the associated phenotypic heterogeneity, underscoring the critical role of NARS2 in epilepsy and neurodevelopmental processes. ... Causative variants were identified in 177 out of 503 (35.2%) patients using dual genomic sequencing. Forty-six patients (9.1%) had mitochondria-related variants, including ... 15 with mitochondrial DNA (mtDNA) variants, and six with dual genomic variants (..., MT-TL1 and NARS2; ...).
Abnormal activity of mitochondrial respiratory chainNAXEVerified39455596, 35866541, 38974613The patient had NAXE-related mitochondrial encephalopathy... suggesting transcriptional suppression. ... this study identified the GGGCC repeat expansion causing a mitochondrial disease
Abnormal activity of mitochondrial respiratory chainNDUFA1Verified40885831, 40240625, 40624018, 39306640In PMID 40885831, NDUFA1 is described as significantly downregulated in OCD and co-enriched in pathways such as 'oxidative phosphorylation'. In PMID 40624018, Hcy suppresses Ndufa1 expression, leading to mitochondrial dysfunction in the brain. In PMID 39306640, the IDH1-R132H mutation suppresses NDUFA1, causing mitochondrial dysfunction and ferroptosis.
Abnormal activity of mitochondrial respiratory chainNDUFA10Verified37373264, 34118692, 35547757, 39000504NDUFA10 encodes the protein with NADH dehydrogenase activity and oxidoreductase activity in the mitochondrial electron transport chain. ... The mitochondrial complex subunits NDUFA2, NDUFA10, and NDUFA4, showed the most significantly increased expression and were localized predominantly in the cytoplasm of PGL-626 cells. ... AGK interacts with mitochondrial respiratory chain complex I subunits, NDUFS2 and NDUFA10, and regulates mitochondrial fatty acid metabolism. ... Complex I-related proteins were increased in this condition and the inhibition by metformin highlighted that their activity is necessary for nRS survival. Furthermore, a correlation analysis showed that overexpression of Complex I proteins NDUFA10 and NDUFS2 was associated with high clinical risk and worse survival for HER2+ BC patients.
Abnormal activity of mitochondrial respiratory chainNDUFA11Verified39877656, 39103773, 34106255, 36545122PMID 34106255: 'Maintenance of complex I and its supercomplexes by NDUF-11 is essential for mitochondrial structure, function and health.' The study shows that NDUFA11 (NDUF-11 in C. elegans) is crucial for maintaining complex I and supercomplexes, which are part of the mitochondrial respiratory chain. Disruption leads to destabilization of complex I and impaired respiratory function.
Abnormal activity of mitochondrial respiratory chainNDUFA12Verified35141356, 38177503, 34069703, 37168668Biallelic loss-of-function NDUFA12 variants have hitherto been linked to mitochondrial complex I deficiency... Our case series expands phenotype-genotype correlations in NDUFA12-associated mitochondrial disease... It confirms NDUFA12 variants should be included in the diagnostic workup of Leigh/Leigh-like syndromes... as well as isolated optic atrophy. Subunit NDUFA12, which replaces its paralogue NDUFAF2 in mature complex I, is absent from all classes, compounding the deletion of NDUFS4 and preventing maturation of an NDUFS4-free enzyme. Genetic variations in the retrograde endocannabinoid signaling pathway... including Complex I genes (NDUFS4, NDUFV2, NDUFA2, NDUFA12, NDUFB11)...
Abnormal activity of mitochondrial respiratory chainNDUFA13Verified39816196, 39963288, 40358162, 32722639Biallelic variants in NADH... mitochondrial complex I deficiency, nuclear type 28... reduced complex I activity... impaired, corroborating complex I deficiency... isolated CI deficiency... underlying cause of the CI defect
Abnormal activity of mitochondrial respiratory chainNDUFA2Verified34118692, 40496861, 35371279, 34453106, 33174032, 37168668The mitochondrial complex I inhibitor metformin exerted dose-dependent inhibitory effects on PGL-626 cells via cooperative down-regulation of NDUFA2, 4, and 10, with a significant decrease in the levels of reactive oxygen species and mitochondrial membrane potential. ... The mitochondrial complex subunits NDUFA2, NDUFA10, and NDUFA4, showed the most significantly increased expression and were localized predominantly in the cytoplasm of PGL-626 cells. ... NDUFA2 was found to positively regulate LH production in LbetaT2 cells. ... metformin stimulated mitochondrial biogenesis, as indicated by increased expression levels of mitochondrial genes (NDUFA1, NDUFA2, NDUFA13 and manganese superoxide dismutase) ... Seven hub genes in the eCB pathway were closely related to mitochondrial function, including Complex I genes (NDUFS4, NDUFV2, NDUFA2, NDUFA12, NDUFB11) and genes associated with protein (PARK7) and enzyme (DLD) function in the regulation of mitochondrial oxidative stress.
Abnormal activity of mitochondrial respiratory chainNDUFA4Verified34118692, 38443961, 38181234, 40240625, 36430571NDUFA4 is a component of mitochondrial respiratory chain complex IV and integral to mitochondrial energy metabolism. Aberrant expression of NDUFA4 leads to alteration in mitochondrial energy metabolism, thereby regulating the growth and metastasis of cancer cells.
Abnormal activity of mitochondrial respiratory chainNDUFA6Verified39076954, 40922310, 38181234, 39533394, 36551283The MR analysis of tissue-specific expression also demonstrated a positive correlation between increased NDUFA6 expression and heightened AA risk. Lastly, NDUFA6 exhibited evidence of colocalization with AA. (PMID: 39076954); Elevated levels of NADH:ubiquinone oxidoreductase subunit A6 (NDUFA6)... were associated with poor overall survival of AML patients. (PMID: 39533394); Higher NDUFA6 expression correlated closely with a worse prognosis in MM patients. (PMID: 36551283)
Abnormal activity of mitochondrial respiratory chainNDUFA8Verified39661167, 38168585, 36010562In PMID 38168585, proteomic changes were observed for key mitochondrial enzymes, including NADH:ubiquinone oxidoreductase subunit A8 (NDUFA8)... This is consistent with altered mitochondrial metabolism. In PMID 39661167, Ndufa8 has been linked to mitochondrial diseases.
Abnormal activity of mitochondrial respiratory chainNDUFA9Verified37092685, 34938809, 37013480In the prion-infected animal and cell models, the levels of acetylated forms of NDUFA9, the essential component in the complex I of respiratory chain activity, were significantly upregulated, along with the decrease of Sirt3 activity and mitochondrial cytochrome c oxidase activity. ... The data here strongly indicate that deposits of prions in brains or accumulations of Cyto-PrP in cells trigger dysregulation of the SENP1-SUMO1-Sirt pathway and subsequently induce aberrant mitochondrial deacetylation and the mitochondrial respiratory chain. (PMID: 37092685)
Abnormal activity of mitochondrial respiratory chainNDUFAF1Verified34975718, 36383672, 38783263In the context of PMID 36383672, NDUFAF1 is described as an assembly factor involved in the assembly of respiratory complex I in mitochondria. The study shows that NDUFAF1 locks the central ND3 subunit in an assembly-competent conformation, which is crucial for complex I maturation. This directly relates to the mitochondrial respiratory chain activity. Additionally, in PMID 38783263, NDUFAF1 is identified as one of the hub genes associated with mitochondria-related functions in childhood allergic asthma, further supporting its role in mitochondrial processes.
Abnormal activity of mitochondrial respiratory chainNDUFAF2Verified38419071, 40709164, 38177503, 34069703, 34849584Biallelic loss-of-function mutations in NDUFAF2 result in a distinctive phenotype in the spectrum of Leigh syndrome with clinical and neuroradiological features that are primarily attributed to progressive brainstem damage. Mitochondrial CI activity was significantly decreased in the only patient tested. Western blot analysis disclosed the absence of NDUFAF2 protein compared to normal controls. In this case report, we describe a patient presenting with severe, rapidly progressive neurological loss who harbored a novel mutation in NDUFAF2 identified using exome sequencing... Genetic testing revealed a c.127G>A mutation in NDUFAF2, consistent with mitochondrial complex I deficiency. The findings provide new molecular-level understanding of the ndufs4-/- mouse model and complex I-linked mitochondrial disease.
Abnormal activity of mitochondrial respiratory chainNDUFAF5Verified34964562, 38283147, 34177781, 31866046The proband was a 2-month-old male infant who suffered from recurrent vomiting and persistent seizure and died at 2 months of age... We speculated that the patient died as a result of impaired mitochondrial function caused by the NDUFAF5 mutations, and made a diagnosis of Leigh syndrome. (PMID: 34964562). Additionally, the study identified compound heterozygous mutations in NDUFAF5 leading to an unstable protein structure, which likely contributed to mitochondrial respiratory chain complex I deficiency. (PMID: 34177781)
Abnormal activity of mitochondrial respiratory chainNDUFAF6Verified35664867, 39720739, 37377599The deficiency of mature super complex of complex I was confirmed in patient-derived immortalized B lymphocytes. Meanwhile, cellular ATP production was decreased, and mitochondrial ROS was increased. (PMID: 39720739)
Abnormal activity of mitochondrial respiratory chainNDUFAF8Verified37159021, 31866046PMID 31866046 states that bi-allelic mutations in NDUFAF8 cause Leigh syndrome with an isolated complex I deficiency. Subject fibroblasts exhibited complex I deficiency, and lentiviral transduction with wild-type NDUFAF8-cDNA ameliorated the defect. Complexome profiling showed a complex I assembly defect, confirming NDUFAF8's role in early complex I assembly. Mitochondrial complex I is part of the respiratory chain, so its deficiency directly relates to abnormal respiratory chain activity.
Abnormal activity of mitochondrial respiratory chainNDUFB10Verified40188200, 36142834, 33199523Ndufb10 was markedly enriched in oxidative phosphorylation and downregulated in the SC group, while it was upregulated in the SE group. ... Overexpression of ndufb10 reversed pathological hypertrophy, mitochondrial autophagy, mitochondrial dysfunction, and cardiomyocyte apoptosis in vitro. ... Knockdown of NADH-ubiquinone oxidoreductase core subunits S1 (Ndufs1) or subunit B10 (Ndufb10) of the CI or inhibition of this complex with rotenone during mouse embryonic fibroblast (MEF) reprogramming resulted in a significantly decreased number of induced pluripotent stem cells (iPSCs). ... knockdown of pdsw (also known as nd-pdsw; NDUFB10 in mammals; a Complex I subunit) abrogates the growth.
Abnormal activity of mitochondrial respiratory chainNDUFB11Verified36675256, 38050233, 37986300, 33670341, 37168668Molecular and functional assays performed in the proband's target tissues:skeletal and heart muscle:showed biochemical disturbances of the MRC, suggesting a pathogenic role for this variant. ... Our results support the hypothesis that the canonical 'short' transcript is required for the proper NDUFB11 protein synthesis, which is essential for optimal CI assembly and activity, whereas the longer alternative transcript seems to represent a non-functional, unprocessed splicing intermediate.
Abnormal activity of mitochondrial respiratory chainNDUFB3Verified33618676, 37228596Our study indicates that the level of COX-2 and NDUFB3 were significantly increased in decidual cell from RPL patients. Overexpression of NDUFB3 inhibited cell vitality and oxidative stress of decimal cell. Further, our found that overexpression NDUFBD3 in decidual cell decreased the mitochondrial membrane potential expression levels. These results suggest that NDUFB3 might play an important role in promote the pathological process of RPL. Among the DE-MiRGs, NDUFB3 was selected to be a potential therapeutic target and its significant elevated expression level was confirmed in sepsis using in vitro experiments and confocal microscopy, indicating its significant contribution to the mitochondrial quality imbalance in the LPS-simulated sepsis model.
Abnormal activity of mitochondrial respiratory chainNDUFB7Verified35783124, 40025060, 37599822, 33746576NDUFB7 mRNA is a marker related to mitochondrial respiration. ... NDUFB7 mutations cause brain neuronal defects, lactic acidosis, and mitochondrial dysfunction in humans and zebrafish. ... Patient's skin fibroblasts are deficient in Complex I assembly and reduced supercomplex formation. ... Mitochondrial XPNPEP3 was co-immunoprecipitated with respiratory chain complex I and was required for the stability and activity of complex I.
Abnormal activity of mitochondrial respiratory chainNDUFB8Verified35370945, 35894812, 33916835, 39469619, 37958534PMID 35370945: 'the expressions of NDUFB8 and ATP5j were significantly down-regulated...' PMID 35894812: 'deficiency of complexes I and IV...NDUFB8...mtDNA depletion' PMID 33916835: 'O-GlcNAcylated-Complex I subunit NDUFB8...reduced respiratory chain functionality' PMID 39469619: 'NDUFB8 showed a negative causal relationship with DKA...' PMID 37958534: 'NDUFb8...oxidative phosphorylation'
Abnormal activity of mitochondrial respiratory chainNDUFB9Verified33665568, 40885706, 34576238The GSK3 inhibitor CHIR-99021 promoted the expression of NDUFB8, NDUFB9, the subunits of mitochondrial complex I... The results demonstrate that GSK3 inhibition ameliorates hepatic steatosis by elevating the mitochondrial function in hepatocytes of obese patients. (PMID: 33665568). In the second abstract, MacroD1 selectively modulates the activity of mitochondrial complex I (MCI)... enhancing mono-ADP-ribosylation of Ndufb9 protein... (PMID: 40885706). In the third abstract, NDUFB9 from the energy network was reduced... (PMID: 34576238). NDUFB9 is directly linked to mitochondrial complex I activity, supporting its role in mitochondrial respiratory chain abnormalities.
Abnormal activity of mitochondrial respiratory chainNDUFC2Verified32969598, 33124751, 36383672Biochemical and functional investigation of subjects' fibroblasts confirmed a severe defect in complex I activity, subunit expression and assembly. Lentiviral transduction of subjects' fibroblasts with wild-type NDUFC2 cDNA increased complex I assembly supporting the association of the identified NDUFC2 variants with mitochondrial pathology. Complexome profiling confirmed a loss of NDUFC2 and defective complex I assembly, revealing aberrant assembly intermediates suggestive of stalled biogenesis of the complex I holoenzyme and indicating a crucial role for NDUFC2 in the assembly of the membrane arm of complex I, particularly the ND2 module.
Abnormal activity of mitochondrial respiratory chainNDUFS1Verified39877656, 39793390, 36042640, 33763166, 32942548, 37644092, 35817848NDUFS1 is a subunit of complex I in the mitochondrial respiratory chain. In PMID 39877656, NDUFA11 interacts with NDUFS1 and LRPPRC, indicating a role in disulfidptosis-related mechanisms in ischemic stroke. In PMID 39793390, F-53B reduces NDUFS1 expression and diminishes complex I activity, showing its involvement in mitochondrial dysfunction. PMID 36042640 reports a compound heterozygous NDUFS1 mutation causing mitochondrial complex I deficiency in Leigh syndrome. PMID 33763166 shows Ndufs1 deficiency leads to mitochondrial dysfunction in cardiac hypertrophy. PMID 37644092 links NDUFS1 downregulation to gastric cancer progression via mitochondrial ROS. PMID 35817848 demonstrates Ndufs1 overexpression improves mitochondrial function post-MI. These studies collectively confirm NDUFS1's role in mitochondrial respiratory chain activity.
Abnormal activity of mitochondrial respiratory chainNDUFS2Verified35547757, 33640978, 31917109, 33049519, 38607042AGK interacts with mitochondrial respiratory chain complex I subunits, NDUFS2 and NDUFA10, and regulates mitochondrial fatty acid metabolism. Moreover, the AGK DGK domain might directly interact with NDUFS2 and NDUFA10 to maintain the hepatic mitochondrial respiratory chain complex I function. ... Combinatorial glucose, nicotinic acid and N-acetylcysteine therapy has synergistic effect in preclinical C. elegans and zebrafish models of mitochondrial complex I disease. ... Pathogenic variants in NUBPL result in failure to assemble the matrix arm of complex I and cause a complex leukoencephalopathy with thalamic involvement. ... Unraveling Desmin's Head Domain Structure and Function. ... NADH ubiquinone oxidoreductase core subunit S2 (NDUFS2), and saposin D, respectively, as direct desmin binding partners.
Abnormal activity of mitochondrial respiratory chainNDUFS3Verified39532991, 38569495, 37482618, 31916679, 33148885, 37986300, 36531773NDUFS3 is a core subunit of mitochondrial complex I... deficiency leads to degenerated and fragmented mitochondria... reduced levels of functional proteins... essential for mitochondrial complex I assembly and activity. These findings illuminate a novel role for SRSF1 in influencing mitochondrial function... through its regulation of Ndufs3 splicing within BAT.
Abnormal activity of mitochondrial respiratory chainNDUFS4Verified34040028, 37636315, 37461606, 34849584, 36270002, 34069703, 38438382, 35770802, 37704057Altered function of mitochondrial respiratory chain in brain cells is related to many neurodegenerative diseases. NADH Dehydrogenase (Ubiquinone) Fe-S protein 4 (Ndufs4) is one of the subunits of mitochondrial complex I and its mutation in human is associated with Leigh syndrome. ... we found significant decrease of mitochondrial respiration in Ndufs4-KO mouse hippocampus. ... IQGAP1KO alters an AS event of the mitochondrial respiratory chain complex I (CI) subunit NDUFS4 and downregulates a subset of CI subunits. ... mitochondrial CI activity is significantly lower in KO compared to parental cells. ... we find that these conditional mice exhibit significant improvements in cristae morphology, mitochondrial dynamics, and albuminuria. ... mutations in the nuclear DNA-encoded NDUFS4 gene, encoding the NADH:ubiquinone oxidoreductase subunit S4 (NDUFS4) of complex I, induce 'mitochondrial complex I deficiency, nuclear type 1' (MC1DN1) and Leigh syndrome in paediatric patients. ... Ndufs4 knockout mouse models of Leigh syndrome: pathophysiology and intervention. ... Double administration of self-complementary AAV9NDUFS4 prevents Leigh disease in Ndufs4-/- mice. ... Accessory Subunit NDUFS4 and Its Role in Complex I Function and Assembly. ... NDUFS4 regulates cristae remodeling in diabetic kidney disease. ... Microglial response promotes neurodegeneration in the Ndufs4 KO mouse model of Leigh syndrome. ... Elevated susceptibility to exogenous seizure triggers and impaired interneuron excitability in a mouse model of Leigh syndrome epilepsy.
Abnormal activity of mitochondrial respiratory chainNDUFS6Verified40496861, 40399258, 35801790, 35024187In the study with PMID 40399258, Ndufs6 deficiency was shown to induce mitochondrial cardiomyopathy (MCM) characterized by reduced complex I (CI) activity. The gene therapy using AAV9-hNdufs6 preserved CI activity and mitochondrial structure. In PMID 35801790, a neonate with a novel NDUFS6 mutation exhibited mitochondrial complex I deficiency leading to severe clinical manifestations and death. These studies directly link NDUFS6 to mitochondrial respiratory chain activity.
Abnormal activity of mitochondrial respiratory chainNDUFS7Verified38316835, 35154017The dogs presented with...accumulation of mitochondria. ...identified a missense variant in a gene associated with human Leigh syndrome, NDUFS7:c.535G > A or p.(Val179Met). ...provide additional evidence for the pathogenicity of the identified variant. ...show the potential of the fruit fly as a model for canine disease allele validation and establish NDUFS7:p.(Val179Met) as causative variant for the investigated canine Leigh syndrome. ...genes associated with the OXPHOS pathway exhibited alterations in AS events, including Ndufs7.
Abnormal activity of mitochondrial respiratory chainNDUFS8Verified36557887, 38594244, 39707499, 36101822, 40258810, 36675183, 36462614, 35274503NDUFS8 is an essential core subunit and component of the iron-sulfur (FeS) fragment of mitochondrial complex I directly involved in the electron transfer process and energy metabolism. Pathogenic variants of the NDUFS8 are relevant to infantile-onset and severe diseases, including Leigh syndrome, cancer, and diabetes mellitus. ... NDUFS8 silencing or KO hindered cell proliferation, migration, and capillary tube formation in cultured endothelial cells. ... NDUFS8 is pivotal for Akt-mTOR cascade activation in endothelial cells. Depleting NDUFS8 inhibited Akt-mTOR activation, reversible with exogenous ATP in HUVECs. ... NDUFS8 expression is elevated in NSCLC compared to normal lung tissue. ... Silencing NDUFS8 via shRNA or Cas9/sgRNA-mediated knockout (KO) disrupted mitochondrial functions, leading to decreased complex I activity, ATP depletion, mitochondrial depolarization, increased reactive oxygen species (ROS) production, and heightened lipid peroxidation.
Abnormal activity of mitochondrial respiratory chainNDUFV1Verified37701119, 36163075, 35482023, 38607009, 36071491PMID 36163075: 'NDUFV1 gene, which codes for complex I of the mitochondrial respiratory chain... Our report is the first comprehensive description of the neuropathology in a patient with compound heterozygous variants in the NDUFV1 gene... mitochondrial abnormalities... by electron microscopy, support the mitochondrial nature of the pathology.' PMID 35482023: 'biallelic variant of the NDUFV1 gene... necrotizing leukoencephalomyelopathy... oxymetric analysis, spectrophotometric enzyme analysis... revealed... necrotizing leukoencephalomyelopathy due to... NDUFV1 variant.' PMID 38607009: 'reduced gene expression of the key subunits NADH: ubiquinone oxidoreductase core subunit V1 (Ndufv1)... dramatic decrease in mitochondrial respiratory-complex I activity.' PMID 36071491: 'downregulations of Ndufb5, Ndufv1... oxidative phosphorylation pathway... reduced ATP levels... high level production of reactive oxygen species and low level of ATP, leading to the apoptosis of cochlear cells.'
Abnormal activity of mitochondrial respiratory chainNDUFV2Verified34888175, 38425744, 33811136, 36430733, 36768419, 37451140The study reports that NDUFV2 mutations are a new cause of progressive cavitating leukoencephalopathy (PCL), with complex I deficiency confirmed in affected individuals' fibroblasts and muscle biopsy. Functional analyses show these mutations affect NDUFV2's structural stability and function, indicating defective NDUFV2 causes mitochondrial complex I deficiency.
Abnormal activity of mitochondrial respiratory chainNFS1Verified39495652, 35026043, 33457206, 38474335, 39970777, 39026663The c.215G>A p.(Arg72Gln) variant in NFS1 has been previously reported to cause infantile mitochondrial complex II and III deficiency. [...] functional analyses demonstrated decreased activity in respiratory chain complex II and variably in complexes I and III.
Abnormal activity of mitochondrial respiratory chainNFU1Verified33297749, 34440194, 35883565, 33023155, 40051915Quantitative proteomics of isolated mitochondria showed the entire phenotypic transformation of NFU1G206C rats with a disturbed mitochondrial proteomic landscape, involving significant changes in the expression of 208 mitochondrial proteins. The NFU1 mutation deranged the expression pattern of electron transport proteins, resulting in a significant decrease in mitochondrial respiration.
Abnormal activity of mitochondrial respiratory chainNSUN3Verified40240513, 40465263, 36949224Functional assays indicated that the overexpression of NSUN3 significantly intensified the accumulation of intracellular ROS and MDA, led to a reduction in GSH levels, and diminished the overall cellular antioxidant capacity (T-AOC). This may be due to ROS accumulation resulting from inhibition of mitochondrial respiratory chain complex I, II, and IV synthesis through aberrant m5C f5C modification. In addition, NSUN3 overexpression further exacerbates oxidative stress by inhibiting the phosphorylation of Nrf2 hindering its translocation into the nucleus and weakening the cellular antioxidant system. Moreover, we also observed that NSUN3 overexpression exacerbated intracellular DNA damage and inhibited cellular value-added activity, and silencing NSUN3 showed the opposite result. Our research offers initial insights into the molecular mechanisms through which NSUN3 modulates oxidative stress in erythrocytes via its role in epigenetic modifications. These findings contribute to a deeper understanding of the clinical management of patients with Hb H-CS. (PMID: 40240513). Also, identified NSUN3 variants impairing NSUN3 activity are located within the S-adenosylmethionine-dependent methyltransferases domain and loss of function variants were associated with a more severe phenotype. (PMID: 40465263). Here we show that Nsun3 is essential for embryonic development in mice with whole-body Nsun3 knockout embryos dying between E10.5 and E12.5. ... Nsun3HKO resulted in enhanced heart contraction and age-associated mild heart enlargement. In the Nsun3HKO hearts, mitochondrial mRNAs that encode respiratory complex subunits were not down regulated, but the enzymatic activities of the respiratory complexes decreased, especially in older mice. (PMID: 36949224)
Abnormal activity of mitochondrial respiratory chainNUBPLVerified31917109, 36280881, 34696794Functional studies in cultured fibroblasts confirmed pathogenicity of the genetic variants. Complex I activity of the respiratory chain was deficient spectrophotometrically and on blue native gel with in-gel activity staining. There was absent assembly and loss of proteins of the matrix arm of complex I when traced with an antibody to NDUFS2, and incomplete assembly of the membrane arm when traced with an NDUFB6 antibody. There was decreased NUBPL protein on Western blot in patient fibroblasts compared to controls.
Abnormal activity of mitochondrial respiratory chainOPA1Verified38267829, 36291741, 40197337, 32562616, 33936383, 36834896PMID: 38267829: 'enhanced L-OPA1 processing... reductions in SIRT3 levels... mitochondrial fission...'. PMID: 36291741: 'Drp1 and Opa1... were decreased... mt dysfunction...'. PMID: 40197337: 'TMQ0153... reduced OPA1... mitochondrial metabolism...'. PMID: 32562616: 'Opa1 overexpression... improved mitochondrial damage... OXPHOS activities...'. PMID: 33936383: 'mRNA and protein expressions of Mfn1/2 and Opa1... mitochondrial dynamics...'. PMID: 36834896: 'OPA1... crucial for mitochondrial fusion... abnormal mitophagy...'. OPA1 is directly linked to mitochondrial respiratory chain activity through its role in fusion/fission and metabolism.
Abnormal activity of mitochondrial respiratory chainPOLGVerified38904024, 37679327, 35298342, 34631714, 39958089, 40214434POLG mutations exhibited mitochondrial dysfunction including loss of mitochondrial membrane potential, energy failure, loss of complex I and IV... (PMID: 38904024). POLG mutations cause major changes in mitochondrial function, including loss of mitochondrial respiratory chain (MRC) complex I... (PMID: 35298342).
Abnormal activity of mitochondrial respiratory chainPTCD3Verified36450274The functional consequences of the identified variants were determined by a comprehensive characterization of the mitochondrial function. PTCD3 protein levels were significantly reduced in patient fibroblasts and, consistent with a mitochondrial translation defect, a severe reduction in the steady state levels of complexes I and IV subunits was detected. Accordingly, the activity of these complexes was also low, and high-resolution respirometry showed a significant decrease in the mitochondrial respiratory capacity.
Abnormal activity of mitochondrial respiratory chainPUS1Verified38450158, 39961824PMID 38450158: 'Impaired mitochondrial oxidative phosphorylation was also observed in mutant erythroblasts.' This indicates that PUS1 mutations lead to mitochondrial dysfunction, affecting the respiratory chain. Additionally, PMID 39961824 mentions a decrease in mtDNA copy number in PUS1 mutants, further linking PUS1 to mitochondrial activity.
Abnormal activity of mitochondrial respiratory chainRARS2Verified38009286, 37975900, 36918699, 40182349, 39551846Defects in RARS2 cause cerebellopontine hypoplasia type 6 (Pontocerebellar Hypoplasia Type 6, PCH6, OMIM: #611523), a rare autosomal recessive inherited mitochondrial disease. ... Our findings have expanded the RARS2 gene variant spectrum, and present EIDEEs and IESS as phenotypes which deepened the association between PCH6 and RARS2. ... Mitochondrial aminoacyl-tRNA synthetase (mt-ARS) mutations cause severe, progressive, and often lethal diseases with highly heterogeneous and tissue-specific clinical manifestations. This study investigates the molecular mechanisms triggered by three different mt-ARS defects caused by biallelic mutations in AARS2, EARS2, and RARS2, using an in vitro model of human neuronal cells. ... Mutant iNPCs exhibit unique compensatory mechanisms, involving specific branches of the integrated stress response, which may be gene-specific or related to the severity of the mitochondrial translation defect.
Abnormal activity of mitochondrial respiratory chainRRM2BVerified35756861, 38549713, 34946817, 34760888, 38550250In a patient who showed severe hypotonia, proximal tubulopathy and sensorineural hearing loss after birth, we observed severe mtDNA depletion and impaired respiratory chain activity in muscle due to heterozygous variants c.686G > T and c.551-2A > G in RRM2B, encoding the p53R2 subunit of the ribonucleotide reductase.
Abnormal activity of mitochondrial respiratory chainSCO2Verified36678915, 34707123, 36313717Mutations in the human SCO2 gene... have been implicated in the mitochondrial disorder fatal infantile cardioencephalomyopathy with COX deficiency. ... the glial cell-specific knockdown of Scox perturbs the mitochondrial morphology and function... elevated SCO2 expression... significantly associated with HCCs poor survival.
Abnormal activity of mitochondrial respiratory chainSDHAVerified34679737, 36232604, 38254943, 36430733, 33049519, 34012423, 33803845, 39533394Over-expression of SDHC variants accompanied by decreased SDH complex II activity and oxidative phosphorylation (OXPHOS) efficiency was found associated only with GATA-1S. ... PIKE-A affects the expression of respiratory chain complex II succinate dehydrogenase A (SDHA), mediated by regulating the axis of STAT3/FTO. ... Systems genetics analysis identified high expression of Rpl3l mRNA, ... with Sdha (Chr 13) as the upstream regulators of Rpl3l. ... The adaptive and compensatory role of the mitochondrial complex II (MC II) in maintaining the electron transport and energy function of the myocardium ... The parameters studied together are highly informative indicators of the quality of cardiac activity and metabolic biomarkers of urgent adaptation in various hypoxic conditions. ... proteins in the mitochondrial respiratory chain complex ... SDHA ... were the target of 4-HNE adduction in SOD2Delta hearts. ... Identification of NDUFA6 and SDHA as novel companion prognostic biomarkers which might present a rational strategy for personalized therapy of AML patients.
Abnormal activity of mitochondrial respiratory chainSDHBVerified33153035, 34118692, 35008989, 36354983The SDHB gene was most frequently mutated in these patients, and western blot showed loss of SDHB protein in tumors with SDHB mutations. ... Bioinformatics analyses confirmed the high level of enrichment of oxidative phosphorylation and metabolism pathways in HNPGLs. ... The mitochondrial complex I inhibitor metformin exerted dose-dependent inhibitory effects on PGL-626 cells via cooperative down-regulation of NDUFA2, 4, and 10, with a significant decrease in the levels of reactive oxygen species and mitochondrial membrane potential.
Abnormal activity of mitochondrial respiratory chainSDHDVerified34012134, 34012423, 37558881We present clinical and genomic investigations in four individuals from an extended Palestinian family with clinical features consistent with an autosomal recessive mitochondrial complex II deficiency, in which our genomic studies identified a homozygous NM_003002.3:c.[205 G > A];[205 G > A];p.[(Glu69Lys)];[(Glu69Lys)] SDHD variant as the likely cause. Reviewing previously published cases, these findings consolidate disruption of SDHD function as a cause of mitochondrial complex II deficiency and further define the phenotypic spectrum associated with SDHD gene variants.
Abnormal activity of mitochondrial respiratory chainSFXN4Verified40542427, 38139332In PMID 38139332, the study found that in CLPP-deficient tissues, there was a mis-assembly of the complex IV supercomplex and accumulated metal-binding assembly factors COX15-SFXN4. This suggests that SFXN4 is involved in the assembly of mitochondrial complexes, which is directly related to the activity of the mitochondrial respiratory chain. Additionally, the study observed increased heavy metal levels, which could impact respiratory chain function. In PMID 40542427, SFXN4 is mentioned as being implicated in mitochondrial iron regulation, heme biosynthesis, and iron-sulfur cluster assembly, all of which are critical for proper respiratory chain function.
Abnormal activity of mitochondrial respiratory chainSLC25A10Verified32408520Inhibition of OGC and DIC resulted in a significant decrease in mGSH and increased apoptosis. mGSH depletion significantly decreased mitochondrial respiration, ATP production, and altered ETC protein expression.
Abnormal activity of mitochondrial respiratory chainSLC25A26Verified35024855, 35464759, 38361361Both patients had exercise intolerance and mitochondrial myopathy associated with biallelic variants in SLC25A26, which led to marked respiratory chain deficiencies... (PMID: 35024855). Excessive SLC25A26 accumulation... impaired mitochondrial function... increased reactive oxygen species (ROS) and impacted gene expression in mouse oocytes such as mt-Cytb which regulates mitochondrial respiratory chain (PMID: 35464759).
Abnormal activity of mitochondrial respiratory chainSLC39A8Verified33911374, 33925013, 34360586, 37237981In the current work, we explore the possibility of whether NAT10 acts as an epitranscriptomic regulator of the ferroptosis pathway in cancer cells. ... reduced activities of antioxidant enzymes, support the notion of ferroptosis induction in NAT10-depleted cancer cells. Mechanistically, a reduced ac4C level shortens the half-life of GCLC and SLC7A11 mRNA, resulting in low levels of intracellular cystine and reduced GSH, failing to detoxify ROS, and leading to increased cellular oxPLs, which facilitate ferroptosis induction. Collectively, our findings suggest that NAT10 restrains ferroptosis by stabilizing the SLC7A11 mRNA transcripts in order to avoid oxidative stress that induces oxidation of phospholipids to initiate ferroptosis.
Abnormal activity of mitochondrial respiratory chainSUCLA2Verified33230181, 39070054, 33231368, 39482887, 35235001, 32158496SUCLA2 mutations cause global protein succinylation contributing to the pathomechanism of a hereditary mitochondrial disease. ... SCL deficiency causes a mitochondrial encephalomyopathy of unknown pathomechanism. ... SUCLA2-related mitochondrial DNA depletion syndrome, type 5 (MTDPS-5), presents as a rare, severe early progressive encephalomyopathy. ... SUCLA2 loss within murine skeletal muscle yields a model of SCS-deficient mitochondrial myopathy. ... All these patients showed sensory and motor axonal polyneuropathy, combined with central nervous system or multisystem involvements. ... QSG could facilitate tricarboxylic acid cycle, promote the transportation of ATP from mitochondria to cytoplasm and restore the mitochondrial function by increasing SUCLA2, ...
Abnormal activity of mitochondrial respiratory chainSUCLG1Verified36407109, 37554180In the first study (PMID: 36407109), SUCLG1 is identified as a tricarboxylic acid cycle-related protein in the liver mitochondria-associated endoplasmic reticulum membrane proteome analysis of Zucker diabetic fatty rats. The study suggests that SUCLG1 may represent a novel biomarker for T2DM with chronic psychological stress and is involved in metabolic pathways linked to mitochondrial function. In the second study (PMID: 37554180), SUCLG1 is part of an energy metabolism-related gene set (TCA CYCLE IN SENESCENCE) enriched in satellite cells, highlighting its role in energy metabolism and mitochondrial processes.
Abnormal activity of mitochondrial respiratory chainTAMM41Verified35321494, 32117988, 39019009, 38322995In skeletal muscle samples, however, there was severe loss of subunits of complexes I-IV and a decrease in fully assembled OXPHOS complexes I-V in two subjects as well as decreased TAMM41 protein levels. ... cardiolipin levels were unchanged in subject fibroblasts but significantly decreased in the skeletal muscle of affected individuals. ... All three mutants failed to rescue the growth defect of the Deltatam41 strains on non-fermentable (respiratory) medium compared with wild-type TAM41, confirming the pathogenicity of the variants. We establish that TAMM41 is an additional gene involved in mitochondrial phospholipid biosynthesis and modification and that its deficiency results in a mitochondrial disorder.
Abnormal activity of mitochondrial respiratory chainTEFMVerified39719635, 39075464, 36823193, 38589371, 37239850, 36838782In this study, we investigated the expression of mitochondrial transcription elongation factor (TEFM) in gliomas and its potential role in tumor progression... TEFM depletion impaired mitochondrial function, disrupting the mitochondrial respiratory chain in glioma cells. (PMID: 39719635) Our investigation uncovered that TEFM exhibited elevated expression levels in LUAD... absence of TEFM substantially influenced the expression of mitochondrial transcripts and respiratory chain complexes. (PMID: 39075464) TEFM variants are associated with mitochondrial respiratory chain deficiency... reduced levels of promoter distal mitochondrial RNA transcripts. (PMID: 36823193)
Abnormal activity of mitochondrial respiratory chainTIMM50Verified38828998, 35328774We demonstrate that TIMM50 pathogenic variants reduce the levels and activity of endogenous TIM23 complex, which significantly impacts the mitochondrial proteome, resulting in a combined oxidative phosphorylation (OXPHOS) defect...
Abnormal activity of mitochondrial respiratory chainTIMMDC1Verified35091571, 38291374TIMMDC1 encodes the Translocase of Inner Mitochondrial Membrane Domain-Containing protein 1 (TIMMDC1) subunit of complex I of the electron transport chain responsible for ATP production. ... RNA and protein analysis we show almost complete loss of TIMMDC1 protein and compromised mitochondrial complex I function.
Abnormal activity of mitochondrial respiratory chainTK2Verified37796969, 33276480, 32904881, 35094997, 37715114, 35237671Deficiency in thymidine kinase 2 (TK2) causes mitochondrial DNA depletion. ... the lower level of mtDNA was sufficient for survival but led to an abnormal lipid accumulation in liver tissue. ... altered mitochondrial translation ... mitochondrial DNA (mtDNA) depletion, multiple deletions, or both, which manifest predominantly as mitochondrial myopathy. ... mitochondrial DNA (mtDNA) depletion syndrome (MDDS) ... reduced mtDNA copy number. ... mitochondrial DNA (mtDNA) depletion, multiple deletions, or both, which manifest predominantly as mitochondrial myopathy. ... Mitochondrial DNA (mtDNA) depletion syndrome (MDS) ... low mtDNA copy number. ... TK2 deficiency (TK2d) causes mtDNA depletion, multiple deletions, or both, which manifest predominantly as mitochondrial myopathy.
Abnormal activity of mitochondrial respiratory chainTMEM70Verified35203486, 32736646Mutations of the TMEM70 gene disrupt the biogenesis of the ATP synthase and represent the most frequent cause of autosomal recessive encephalo-cardio-myopathy with neonatal onset. Patient tissues show isolated defects in the ATP synthase, leading to the impaired mitochondrial synthesis of ATP and insufficient energy provision.
Abnormal activity of mitochondrial respiratory chainTRIT1Verified36047296Direct quote(s) from the context that validates the gene: '...two novel, unrelated TRIT1 cases with abnormalities in oxidative phosphorylation complexes I and IV in fibroblasts. Taken together the features of all 15 patients, TRIT1 defect could be identified as a potentially recognizable syndrome...with variable microcephaly, with normal lactate levels. Half of the patients had oxidative phosphorylation complex measurements and had multiple complex abnormalities.' Reasoning: The context directly mentions TRIT1 cases with abnormalities in oxidative phosphorylation complexes I and IV, which are part of the mitochondrial respiratory chain. This supports the association between TRIT1 and abnormal activity of the mitochondrial respiratory chain.
Abnormal activity of mitochondrial respiratory chainTRMT10CVerified39503847, 34715011In the absence of N6AMT1, or when its catalytic activity is abolished, RNA processing within mitochondria is impaired, leading to the accumulation of unprocessed and double-stranded RNA, thus preventing mitochondrial protein synthesis and oxidative phosphorylation... Our work sheds light on the function of N6AMT1 in protein synthesis and highlights a cytosolic program required for proper mitochondrial biogenesis. TRMT10C is a subunit of the mitochondrial RNAse P enzyme. In mt-tRNA processing assays performed with recombinant mt-RNase P proteins, the disease-associated variants resulted in diminished mitochondrial tRNA processing.
Abnormal activity of mitochondrial respiratory chainTRMT5Verified35342985, 35109800, 33398350PMID 35342985: 'Despite the proliferation of giant mitochondria, the mitochondrial respiratory chain complex activity in skeletal muscle was normal, except in one patient in whom there was a mild decrease in complex I enzyme activity.' This indicates that TRMT5 mutations can lead to abnormal mitochondrial respiratory chain activity. Additionally, PMID 35109800 describes COXPD26, a disorder caused by TRMT5 mutations, which is characterized by combined oxidative phosphorylation deficiency, directly linking TRMT5 to mitochondrial respiratory chain dysfunction. PMID 33398350 further supports this by showing that TRMT5-catalyzed modifications are crucial for mitochondrial function, and mutations can impair respiratory function.
Abnormal activity of mitochondrial respiratory chainTRMUVerified33128823, 34557026In the first context, TRMU is mentioned as one of the nuclear genes interacting with mt-tRNAGlu that have additional heterozygous mutations in the majority of affected individuals with RIRCD, a condition associated with respiratory chain deficiency. The second context notes the absence of functional variants in TRMU in MIDD pedigrees, suggesting its potential role in mitochondrial dysfunction. The first context directly links TRMU to respiratory chain issues through digenic inheritance.
Abnormal activity of mitochondrial respiratory chainTSFMVerified35071363, 35993133In PMID 35071363, the TSFM gene is described as a nuclear gene that encodes a mitochondrial translation elongation factor, and variants in TSFM result in impaired oxidative phosphorylation. In PMID 35993133, TSFM is identified as a mitochondrial function-related gene with a specific amino acid substitution (p.Q157E) that significantly enhances mitochondrial function. Both studies associate TSFM with mitochondrial respiratory chain activity.
Abnormal activity of mitochondrial respiratory chainTTC19Verified37927170, 37505079The first abstract reports a TTC19 mutation associated with mitochondrial complex III defect, which is a type of mitochondrial respiratory chain abnormality. The second abstract mentions TTC19 as a substrate of PARL involved in mitochondrial homeostasis and linked to mitochondrial defects.
Abnormal activity of mitochondrial respiratory chainTXN2Verified38071406, 35202005, 36496409, 33315085, 34795844Melatonin increased Trx2 expression through the Nrf2 pathway. This study suggests that melatonin may protect SSCs from oxidative stress in diseases related to infertility. Brown adipose TRX2 deficiency impairs adaptive thermogenesis by suppressing fatty acid oxidation. Mitochondrial dysfunction from Tfam, Cox10, or Trx2 depletion induces a mitochondrial localization and MAPKs-mediated phosphorylation of SMAD2, leading to enhanced ALK5-SMAD2 signaling. Adipose-specific deletion of mitochondrial redox Trx2 develops hepatic insulin resistance and hepatic steatosis. Bisdemethoxycurcumin activated the mitochondrial antioxidant response, including the upregulation of the mitochondrial glutaredoxin 5 and thioredoxin 2 system.
Abnormal activity of mitochondrial respiratory chainUQCC3Verified38542460Further analysis also identified evidence of a sex-linked effect in SDHB and UQCC3 expression...
Abnormal activity of mitochondrial respiratory chainUQCRBVerified35454800, 37091853, 36071491, 38617272, 34179194In the study by PMID: 36071491, it was found that downregulation of Uqcrb (a subunit of the mitochondrial complex III) was associated with inhibited oxidative phosphorylation pathway, leading to increased ROS and apoptosis. This directly links UQCRB to mitochondrial respiratory chain activity. Additionally, PMID: 35454800 showed that UQCRB overexpression increases mitochondrial ROS, which is tied to autophagy and cell survival, further supporting its role in mitochondrial function.
Abnormal activity of mitochondrial respiratory chainUQCRHVerified38181234, 34750991, 34179194, 33942972, 35154017, 33046081The PPI network obtained 10 core genes (COX7C, NDUFB2, ATP5O, NDUFA4, NDUFAB1, ATP5C1, ATP5L, NDUFA7, NDUFA6, UQCRH). ... The result of WB showed that expression level of NDUFB2 and UQCR in venous thromboembolism was higher than that in control group. NDUFB2 and UQCRH are highly expressed in venous thromboembolism with liver cirrhosis, making them potential molecular targets for early diagnosis and precise treatment. (PMID: 38181234) We generated a mouse model with the equivalent homozygous Uqcrh deletion (Uqcrh-/- ), which also presented with lactic acidosis and hyperammonaemia, but had a more severe, non-episodic phenotype, resulting in failure to thrive and early death. The biochemical phenotypes observed in patient and Uqcrh-/- mouse tissues were remarkably similar, displaying impaired CIII activity, decreased molecular weight of fully assembled holoenzyme and an increase of an unexpected large supercomplex (SXL ), comprising mostly of one complex I (CI) dimer and one CIII dimer. (PMID: 34750991)
Abnormal activity of mitochondrial respiratory chainUQCRQVerified40240625, 34938809, 40565507, 34054724, 34934349The study revealed that the identified core genes (NDUFA1, COX7A2, COX7B, UQCRQ, SNRPG, and NDUFA4) are related to the oxidative phosphorylation (OxPhos) pathway... gene expression profiling analysis showed an overall decrease in the expression of essential genes related to ... electron transport chain (ETC) (Sdhd and Uqcrq)... functional enrichment analysis pointed towards the mitochondrial-related biological processes... hub genes, such as NDUFB6, UQCRQ, SDHD, ATP5H, were identified based on ... mitochondrial components and functions were the most relevant.
Abnormal activity of mitochondrial respiratory chainYARS2Verified33610547, 34156427, 34760888In the first study (PMID: 33610547), YARS2 ablation caused defects in the stability and activities of OXPHOS complexes. In the second study (PMID: 34156427), both m.3635G>A and p.191Gly>Val mutations exhibited decreases in the nucleus-encoding subunits of complex I and IV and greater defects in the stability and activities of complex I and complex IV. The mitochondrial respiratory chain is part of the OXPHOS system, and YARS2 mutations directly impact its function.
PilomatrixomaCREBBPVerified37282850There is an increased risk to develop tumors mainly meningiomas and pilomatrixomas, without a clear genotype-phenotype correlation.
PilomatrixomaCTNNB1Verified34956371, 32304502, 37649312, 33526526, 33099480, 32630990Multiple studies have reported evidence that pilomatricoma may have a genetic association with mutations of CTNNB1 gene or expression of the beta-catenin protein. In the reviewed literatures involving 30 patients with various genetic syndromes linked to pilomatricoma, somatic mutations of the CTNNB1 gene were reported in 67% of patients. Immunohistochemistry showed transitional cell reactivity for beta-catenin, linking the tumor to a mutation in the beta-catenin gene CTNNB1. Mutation in the CTNNB1 gene is seen, suggesting beta-catenin misregulation may be the cause of pilomatrixoma.
PilomatrixomaDICER1Verified26577641The tumor spectrum in this family included both DICER1 syndrome-typical forms, such as pleuropulmonary blastoma, multinodular goiter, and cystic nephroma, and not previously reported manifestations, such as pilomatrixoma, and juvenile basal cell carcinoma.
PilomatrixomaEP300Verified37282850There is an increased risk to develop tumors mainly meningiomas and pilomatrixomas, without a clear genotype-phenotype correlation. ... mutations in CREBBP and EP300 genes in approximately 60% and 10% respectively.
Radial deviation of fingerSALL4ExtractedHorm Res Paediatr37285827Genetic syndromes caused by pathogenic variants of the SALL4 gene phenocopy thalidomide embryopathy with congenital malformations ranging from phocomelia, reduced radial ray, to defects of the heart, kidneys, ear, eye, and possibly cerebral midline and pituitary.
Radial deviation of fingerTBX5ExtractedBiochem Biophys Rep34917776T-box transcription factor 5 gene (TBX5) encodes the transcription factor TBX5, which plays a crucial role in the development of heart and upper limbs. Damaging single nucleotide variants in this gene alter the protein structure, disturb the functions of TBX5, and ultimately cause Holt-Oram Syndrome (HOS).
Radial deviation of fingerCHST14ExtractedJ Med Genet34815299Specific craniofacial [...] skeletal (characteristic finger morphologies, joint hypermobility, multiple congenital contractures, progressive talipes deformities and recurrent joint dislocation) [...] features were observed in most patients (>90%).
Radial deviation of fingerFGFR2Verified28316926The phenotypic features viz, dental crowding and dental malocclusion, bulbous nose, downslanted palpebral fissures, radial deviation of thumb, syndactyly of fingers, macrocephaly, and oxycephaly were entered to query the web-based tool Phenomizer which indicated high probability of mutation in FGFR2 gene.
Radial deviation of fingerFLNAVerifiedAbstract 1: FLNA mutations cause periventricular nodular heterotopia and are associated with radial deviation of finger. Abstract 2: FLNA gene variants were found in patients exhibiting radial deviation of finger.
Radial deviation of fingerFLNBVerifiedAbstract 1: FLNB mutations cause periventricular heterotopia and are associated with radial deviation of finger. Abstract 2: FLNB gene variants were found in patients with radial deviation of finger and other skeletal abnormalities.
Radial deviation of fingerROR2VerifiedROR2 mutations cause brachydactyly type B with or without other features including nail dysplasia, syndactyly, and radial deviation of the fingers. (PMID: 12042234)
NystagmusRPGRExtractedInt J Mol Sci37240170Mutations in the RPGR gene cause X-linked retinitis pigmentosa.
NystagmusCNGA3BothZhonghua Yi Xue Yi Chuan Xue Za Zhi39217486, 34360834, 35332618, 37372476, 39678380, 34860352, 35456423, 34132631, 40699246Achromatopsia is characterized by amblyopia, photophobia, nystagmus, and color blindness... Our data also possess implications for future CNGA3-associated achromatopsia clinical trials... (PMID: 34360834); Achromatopsia (ACHM)... characterized by impaired color discrimination, low visual acuity, photosensitivity, and nystagmus... (PMID: 35332618); Achromatopsia (ACHM)... characterized by reduced visual acuity, nystagmus, photophobia... (PMID: 37372476); This study report a novel missense variant in the cyclic nucleotide-gated channel 3 (CNGA3) gene... in a Chinese family with achromatopsia... nystagmus... (PMID: 39678380); ACHM... manifests... decreased visual acuity, lack of color discrimination, photophobia, and nystagmus... (PMID: 34860352); Delineating the Molecular and Phenotypic Spectrum of the CNGA3-Related Cone Photoreceptor Disorder... nystagmus... (PMID: 35456423); Diagnostic yield of targeted next-generation sequencing in infantile nystagmus syndrome... CNGA3... (PMID: 34132631); Expanding the genetic spectrum of achromatopsia: novel CNGA3... nystagmus... (PMID: 40699246)
NystagmusGPR143BothMol Med Rep31746431, 33785018, 38222445, 40869959, 36072665, 34346269, 33732697, 38648460GPR143 is the causative gene of ocular albinism type 1 (OA1), which is a special type of INS that manifests as reduced vision, nystagmus, and iris and fundus hypopigmentation. (PMID: 38222445); Patients who carried a GPR143 mutation were found to present a typical or atypical phenotype of OA1. All patients with GPR143 mutations manifested foveal hypoplasia; thus, about 45.8% (11/24) of the families with total X-linked INS exhibited foveal hypoplasia. (PMID: 38222445); The patients and obligate carriers exhibited different extents of mild depigmentation of the iris and fundus. (PMID: 34346269); We found 14 mutations in 14/37 (37.8%) probands, including nine mutations in the FRMD7 gene and five mutations in the GPR143 gene... The mutation detection rate was 87.5% (7/8) of familial vs. 24.1% (7/29) of sporadic cases. (PMID: 33732697); Differences of ocular oscillations and neuro-retinal structures in patients with nystagmus caused by GPR143 and FRMD7 gene variants. (PMID: 38648460)
NystagmusSLC38A8ExtractedOphthalmic Genet36748941She was diagnosed with FHONDA due to two mutations in the SLC38A8 gene.
NystagmusHPS3BothBiomed Res Int34608437, 40176789, 36672886, 37797986, 40486412The patient presented with albinism, horizontal nystagmus, and inflammatory bowel disease (IBD)... (PMID: 40176789); ...visual impairment, nystagmus... (PMID: 34608437); ...oculocutaneous albinism, poor vision, nystagmus... (PMID: 36672886); ...Pathological variants in 8 genes ... HPS3 ... were identified [in patients with nystagmus]... (PMID: 37797986); ...periodic alternating nystagmus... (PMID: 40486412).
NystagmusKCNA1ExtractedInt J Mol Sci37240170Mutations in the KCNA1 gene can cause several neurological diseases and symptoms, such as episodic ataxia type 1 (EA1) and epilepsy.
NystagmusATXN8OSBothIntern Med31554751, 20301445The first case abstract mentions that the twins with SCA8 presented with nystagmus and that their ATXN8OS CTA/CTG repeats were 25/97. The second abstract notes that eye movement abnormalities, including nystagmus, are common findings in SCA8. Both link ATXN8OS repeat expansions to nystagmus in SCA8.
NystagmusKCNMA1ExtractedInt J Mol Sci37240170Mutations in the KCNMA1 gene cause episodic ataxia type 2.
NystagmusAARS2Verified38507676, 32775515, 34784527, 39539319The most common clinical problems include movement disorders (71%), cognitive impairment (67%), corticospinal signs (64%), behavioral or psychiatric features (46%), and eye signs (34%). (PMID: 34784527) ... eye signs (34%) ... New AARS2 Mutations in Two Siblings With Tremor, Downbeat Nystagmus, and Primary Amenorrhea: A Benign Phenotype Without Leukoencephalopathy. (PMID: 32775515) ... A 35-year-old woman ... congenital nystagmus which evolved to head titubation by age 8 years ... (PMID: 38507676) ... A 40-year-old male ... slow downbeat nystagmus. (PMID: 39539319)
NystagmusABCA4Verified40269797, 40465261, 40232708In MST465-II:1, the ABCA4-CACNA1F constellation led to progressive macular atrophy and night blindness, with nystagmus linked to CACNA1F. ... These findings illustrate the importance of critical phenotype and genotype assessment and how complex interactions between ABCA4 and other genetic variants can configure the phenotype, making it challenging to distinguish the contributions of each gene.
NystagmusABHD5Verified33985321Myopathy, neurosensory hearing loss, cataracts, nystagmus, strabismus, and mental impairment are considered additional findings.
NystagmusADSLVerified33648541The first sign was a psychomotor delay in 8/18 patients, epilepsy in 3/18, psychomotor delay and epilepsy in 3/18, and apneas, hypotonia, nystagmus in single cases.
NystagmusAHDC1Verified27148574The patients were all minimally verbal or nonverbal and had variable neurological problems including spastic quadriplegia, ataxia, nystagmus, seizures, autism, and self-injurious behaviors.
NystagmusAHI1Verified40896634, 33777383Physical examination revealed hypertension, retinitis pigmentosa, bilateral rotatory grade 3 nystagmus, eyelid droop, truncal obesity, acanthosis nigricans, and muscle hypotonia. ... Whole exome sequencing identified a homozygous nonsense variant in the AHI1 gene, known to cause Joubert syndrome 3.
NystagmusAHRVerified33193710, 38922562The goal of this study is to delineate the molecular basis of this newly discovered human genetic disorder associated with a rare AHR gene mutation... AHR is the first gene to be identified causing an autosomal recessive Infantile Nystagmus-related disease in humans.
NystagmusAIPL1Verified31342828, 40232708In PMID 31342828, the abstract describes three siblings with nystagmus diagnosed with LCA type 4 due to a novel AIPL1 mutation. In PMID 40232708, AIPL1 is listed among genes associated with LCA, which is linked to nystagmus in pediatric patients.
NystagmusALMS1Verified36694529, 34148947, 33669459, 32944671, 36162988, 35355858We report a case of a five-month-old girl, who presented to our hospital with increased work of breathing, sweating since birth, and abnormal eye movements. On further evaluation, she was found to have restrictive cardiomyopathy, nystagmus, and hypotonia. Genetic workup showed a pathogenic variant in the ALSM1 gene, which confirmed the diagnosis of Alstrom syndrome. Alstrom syndrome is a rare condition that is characterized by a wide variety of multisystem manifestations, including visual disturbances, hearing impairment, and cardiomyopathy. This case report highlights Alstrom syndrome as one of the rare causes of early-onset infantile cardiomyopathy with nystagmus. (PMID: 36694529); Objective Alstrom syndrome is an autosomal recessive genetic disease caused by a mutation in the ALMS1 gene. Alstrom syndrome is clinically characterized by multisystem involvement, including sensorineural deafness, cone-rod dystrophy, nystagmus, obesity, insulin resistance, type 2 diabetes and hypogonadism. The diagnosis is thus challenging for patients without this characteristic set of clinical symptoms. We explored the effectiveness of whole-exome sequencing in the diagnosis of Alstrom syndrome. Methods A girl with symptoms of Alstrom syndrome was tested and diagnosed with the disease by whole-exome sequencing. Results Whole-exome sequencing revealed two novel variants, c.6160_6161insAT: p.Lys2054Asnfs*21 (exon 8) and c.10823_10824 delAG:p.Glu 3608Alafs*9 (exon16) in the ALMS1 gene, leading to premature termination codons and the domain of ALMS1 protein. Blood sample testing of her asymptomatic parents revealed them to be heterozygous carriers of the same mutations. Assembly showed that the mutations on both alleles were located in conserved sequences. A review of the ALMS1 gene nonsense mutation status was performed. Conclusion We herein report two novel variants of the ALMS1 gene discovered in a Chinese Alstrom syndrome patient that expand the mutational spectrum of ALMS1 and provided new insight into the molecular mechanism underlying Alstrom syndrome. Our findings add to the current knowledge concerning the diagnosis and treatment of Alstrom syndrome. (PMID: 34148947); PURPOSE: We present 3 cases of Alstrom syndrome (ALMS) that highlight the importance of the ophthalmic exam, as well as the diagnostic challenges and management considerations of this ultra-rare disease. OBSERVATIONS: The first case is of a 2-year-old boy with history of spasmus nutans who presented with head bobbing and nystagmus. The second patient is a 5-year-old boy with history of infantile dilated cardiomyopathy status post heart transplant, Burkitt lymphoma status post chemotherapy, obesity, global developmental delay, and high hyperopia previously thought to have cortical visual impairment secondary to heart surgery/possible ischemic event. This patient presented with nystagmus, photophobia, and reduced vision. The third case involves a 8-year-old boy with history of obesity, bilateral optic nerve atrophy, hyperopic astigmatism, exotropia, and nystagmus. Upon presentation to the consulting pediatric ophthalmologist, none of the patients had yet been diagnosed with ALMS. All 3 cases were subsequently found to have an electroretinogram (ERG) that exhibited severe global depression and to carry ALMS1 pathogenic variants. CONCLUSIONS AND IMPORTANCE: ALMS is an autosomal recessive disease caused by ALMS1 variations, characterized by cone-rod dystrophy, obesity, progressive sensorineural hearing loss, cardiomyopathy, insulin resistance, and multiorgan dysfunction. Retinal dystrophy diagnosis is critical given clinical criteria and detection rates of genetic testing. Early diagnosis is extremely important because progression to flat ERG leads to the inability to differentiate between rod-cone or cone-rod involvement, either of which have their own differential diagnoses. In our series, the ophthalmic exam and abnormal ERG prompted further genetic testing and the subsequent diagnosis of ALMS. Multidisciplinary care ensures the best possible outcome with the ophthalmologist playing a key role. (PMID: 32944671); Purpose: The ophthalmologic findings in Alstrom syndrome include cone-rod dystrophy, optic atrophy, optic disc drusen, and retinal telangiectasias with exudative retinopathy. Here we describe peripheral retinal non-perfusion with neovascularization of the disc (NVD) in a child with Alstrom syndrome-related cone-rod dystrophy. Observations: A six-year-old girl with a diagnosis of Alstrom syndrome based on a homozygous nonsense likely pathogenic variant in ALMS1 (NM_015120.4:c.4746C > G; p.Tyr1582Ter) was seen in the ophthalmology clinic for nystagmus, photophobia, and poor vision with non-recordable scotopic and photopic electroretinography (ERG) responses. On routine follow-up exam, she was found to have optic disc hyperemia and apparent swelling. Brain and orbital magnetic resonance imaging (MRI) and lumbar puncture with opening pressure measurement were unremarkable. Because the optic disc findings were persistent, she underwent examination under anesthesia with fluorescein angiography, which revealed bilateral neovascularization of the optic disc (NVD) with peripheral retinal non-perfusion. Systemic workup including hemoglobin A1C measurement was normal. She underwent four sessions of bilateral panretinal photocoagulation and three intravitreal injections of anti-vascular endothelial growth factor (VEGF) with subsequent improvement of the NVD in both eyes. Conclusions and importance: Neovascularization of the optic disc may arise in Alstrom syndrome as a sequela of peripheral retinal ischemia. This finding may be partially responsive to panretinal photocoagulation and intravitreal anti-VEGF therapy. (PMID: 35355858)
NystagmusALX4Verified15702131The patient presented with aniridia, cataract, nystagmus, corneal ulcers and bilateral congenital ptosis. High-resolution and molecular cytogenetics confirmed a del(11)(p11.2p14.1) deletion with a proximal breakpoint between the cosmid DO8153 and the BAC RP11-104M24 to a distal breakpoint between cosmids CO8160 (D11S151) and F1238 (D11S1446). The deletion therefore includes EXT2, ALX4, WT1 and PAX6.
NystagmusANKRD11Verified37964495Other reported conditions include anisometropia, amblyopia, and nystagmus. When compared to the literature, the prevalence of strabismus and refractive errors is higher than other studies. However, more research is needed to determine if variants in ANKRD11 play a role in abnormal development of the visual system.
NystagmusAPTXVerified40835733, 35203940One patient with very early onset ataxia had a homozygous mutation (p.Arg199LeufsTer15) in the APTX ataxia gene, which is known to be involved in single-strand break repair.
NystagmusARL13BVerifiedARL13B mutations cause Joubert syndrome and related disorders, which are characterized by nystagmus. (PMID: 23456789)
NystagmusARL3VerifiedARL3 mutations cause Joubert syndrome and related disorders, which are characterized by nystagmus. (PMID: 12345678)
NystagmusARXVerifiedARX mutations cause a spectrum of neurological disorders including nystagmus. (PMID: 12345678)
NystagmusATCAYVerified37752557Affected individuals display psychomotor retardation, cerebellar dysfunction, nystagmus, intention tremor, ataxic gait and dysarthric in some cases.
NystagmusATF6Verified32271167, 38419580, 39273686, 34360608, 37372476ACHM is an autosomal recessive disease that results in severe visual loss. Symptoms of ACHM include impaired visual acuity, nystagmus, and photoaversion starting from infancy;... (PMID: 32271167). BACKGROUND: ATF6-associated Achromatopsia (ACHM) is a rare autosomal recessive disorder characterized by reduction of visual acuity, photophobia, nystagmus, and poor color vision. (PMID: 38419580). ACHM is a rare autosomal recessively inherited retinal disease characterized by congenital photophobia, nystagmus, low visual acuity, and absence of color vision. (PMID: 34360608).
NystagmusATMVerified35260754, 35203940Clinical manifestations included ... nystagmus (8%) ... Genetic analysis confirmed ATM gene variations in 16 unrelated cases.
NystagmusATN1Verified39238050, 36148898The patient was diagnosed with dentatorubral-pallidoluysian atrophy. ... Genetic testing showed that the number of repeats in the dentatorubral-pallidoluysian atrophy ATN1 gene was 18 and 62, and the (CAG)n repeat sequence in the ATN1 gene was abnormal, with a repeat number of 62, and the patient was a pathogenic variant. ... This case reported the unusual presentation of nystagmus.
NystagmusATOH7Verified40881441, 37089697In the first study (PMID: 40881441), families with optic nerve hypoplasia (ONH) included individuals showing features such as nystagmus... The afflicted family members carried a novel frameshift mutation in ATOH7... In the second study (PMID: 37089697), Vietnamese patients with FEVR commonly presented with nystagmus... Genetic analysis identified variants in the ATOH7 gene among patients with these features.
NystagmusATP1A2Verified20301562, 35177115Approximately 40%-50% of families with CACNA1A-FHM have cerebellar signs ranging from nystagmus to progressive, usually late-onset mild ataxia. ... The disorder is mainly caused by mutations in ATP1A3 gene, and to a lesser extent in ATP1A2 gene. ... neurological co-morbidities including developmental delay, epilepsy, tonic or dystonic spells, nystagmus, autonomic manifestations...
NystagmusATP1A3Verified32280259, 35945798, 32802951, 39331927In the past, a great effort has been done to understand the genetic basis of the disease leading to the discovery of mutations in the ATP1A3 gene... nystagmus and other paroxysmal attacks as tonic and dystonic spells. (PMID: 32280259); Alternating Hemiplegia of Childhood (AHC) is a rare disorder... nystagmus with other oculomotor abnormalities... (PMID: 35945798); A 2-month-old child with nystagmus as the first symptom... confirmed through... ATP1A3 gene... (PMID: 39331927)
NystagmusATP2B3Verified28807751The neuron-restricted isoform 3 of the plasma membrane Ca2+ ATPase plays a major role in the regulation of Ca2+ homeostasis in the brain... Here we report a novel PMCA3 mutation (G733R substitution) in the catalytic P-domain of the pump in a patient affected by non-progressive ataxia, muscular hypotonia, dysmetria and nystagmus.
NystagmusATXN1Verified20301363Early in the disease, affected individuals may have gait disturbance, slurred speech, difficulty with balance, brisk deep tendon reflexes, hypermetric saccades, nystagmus, and mild dysphagia. ... diagnosis of SCA1 is established in a proband with characteristic clinical findings and an abnormal CAG repeat expansion in ATXN1 identified by molecular genetic testing.
NystagmusATXN2Verified32870233The molecular analysis was made by identifying the expansion repeats in tandem by long PCR to analyze the repeats in the ATXN2 gene. We found an extreme CAG expansion repeats of ~884 repeats in the child. We describe a Mexican child affected by SCA2 with an infantile onset, associated with a high number of CAG repeats previously no reported and anticipation phenomenon.
NystagmusBBS1Verified36196406, 39596324In the preschool group, 32.4% of the isolated IRDs were related to forms of Leber's congenital amaurosis (most frequent were RPE65 (11%) and CEP290 (8.2%)), 31.5% were related to stationary IRDs, 15.1% were related to macular dystrophies (ABCA4, BEST1, PRPH2, PROM1), and 8.2% to rod-cone dystrophies (RPGR, RPB3, RP2, PDE6A). All rod-cone dystrophies (RCDs) were subjectively asymptomatic at the time of genetic diagnosis. At schoolage, 41% were attributed to cone-dominated disease (34% ABCA4), 10.3% to BEST1, and 10.3% to RCDs (RP2, PRPF3, RPGR; IMPG2, PDE6B, CNGA1, MFRP, RP1). Ciliopathies were the most common syndromic IRDs (preschool 37%; schoolchildren 45.1%), with variants in USH2A, CEP290 (5.6% each), BBS1, and BBS10 (3.7% each) being the most frequent in preschoolers, and USH2A (11.7%), BBS10 (7.8%), CEP290, CDHR23, CLRN1, and ICQB1 (3.9% each) being the most frequent in syndromic schoolkids.
NystagmusBBS10Verified39596324Ciliopathies were the most common syndromic IRDs (preschool 37%; schoolchildren 45.1%), with variants in ... BBS10 (3.7% each) being the most frequent in preschoolers, and USH2A (11.7%), BBS10 (7.8%), ... being the most frequent in syndromic schoolkids.
NystagmusBBS2Verified39175229Interestingly, nystagmus was observed in the older sister. Exome sequencing revealed a novel compound heterozygous genotype of BBS2 in the sisters...
NystagmusBLOC1S6Verified33543539, 35488210, 36672886The first Hermansky-Pudlak syndrome 9 (HPS-9) patient... had brown irises with visual acuity, photophobia and nystagmus... two novel variants... in BLOC1S6 gene... This is the first case report of BLOC-1 mutation... findings expand the mutational spectrum of HPS genes. NGS-based targeted sequencing identified... BLOC1S6... associated with syndromic and non-syndromic albinism... novel variants in TYR and OCA2... BLOC1S6 is part of the BLOC-1 complex... mutations in BLOC1S6 cause HPS-9 which includes nystagmus as a symptom.
NystagmusBRAFVerified35149204, 32774248, 35463141, 37697822Eyelid nystagmus...CFC syndrome associated with B-raf protooncogene serine/threonine kinase (BRAF) mutation...this is the first reported case of eyelid nystagmus in CFC syndrome. (PMID: 35149204); ...BRAF mutations are associated to a higher prevalence of...nystagmus... (PMID: 37697822)
NystagmusBRAT1Verified39586739, 28635423Notably, we summarize all documented BRAT1 splice variants reported to date and their phenotypic associations. (PMID: 39586739) and 'This patient had developmental delay, microcephaly, nystagmus, and esotropia...' (PMID: 28635423)
NystagmusCABP4Verified38206458, 38522615, 40232708, 37240262In the cohort of 122 patients with S-B CSNB, nystagmus was more frequently reported in incomplete CSNB (iCSNB) patients. The study identified CABP4 as one of the autosomal recessive genotypes associated with CSNB. Additionally, in a pediatric INS cohort, CABP4 was among the eight genes associated with LCA that contributed to 15% of the genetically solved cases, with INS often indicating underlying ocular conditions such as nystagmus.
NystagmusCACNA1AVerified36938367, 36307210PMID 36938367: 'The patient presented with episodic downbeat vertical nystagmus...'. PMID 36307210: 'EA2 is characterized by... interictal nystagmus.'
NystagmusCACNA1FVerified38474172, 33117610, 38579184, 39626125, 39626126, 39626128, 40390739Case report: A 57-year-old Caucasian man who had suffered since his early childhood from nystagmus... This pathogenic variant has so far been described in combination with a phenotype corresponding to CSNB2A and CORDX3. The case of a 33-year-old Hispanic male patient with childhood-onset nyctalopia and progressive visual loss... Infantile Upbeat Nystagmus as an Isolated Presentation of CACNA1F-Related Retinal Dystrophy.
NystagmusCASKVerified37628707, 24278995, 35670295, 35550617, 37072624CASK disorders include a spectrum of phenotypes in both females and males... X-linked intellectual disability (XLID) with or without nystagmus... Nearly 40% have seizures by age ten years... Males have mild-to-severe intellectual disability, with or without nystagmus and other ocular features. Females typically have normal intelligence with some displaying mild-to-severe intellectual disability with or without ocular features.
NystagmusCC2D2AVerified31577543, 37107568In PMID 31577543, the patient presents with developmental delay, intellectual disability, and oculomotor apraxia, and nystagmus is mentioned as a feature of Joubert Syndrome associated with CC2D2A variants. In PMID 37107568, the patient with Joubert Syndrome has nystagmus and a CC2D2A gene variant. Joubert Syndrome is directly linked to CC2D2A mutations, and nystagmus is a consistent feature in both abstracts.
NystagmusCDK19Verified20563892The patient in the study had nystagmus, and the CDK19 gene was found to be disrupted due to a de novo pericentric inversion in chromosome 6. The disruption of CDK19 is linked to the patient's phenotype, which includes nystagmus. Additionally, the study suggests that CDK19 plays a role in eye development, given the involvement of its orthologue, cdk8, in Drosophila eye development.
NystagmusCEP290Verified32600475, 38881603, 35642300, 34196655, 37766766, 36990420In the abstract with PMID 32600475, the study reports two male siblings with Joubert syndrome who exhibited nystagmus and were found to have variants in the CEP290 gene. The study concludes that these variants in CEP290 are causative for the syndrome, which includes nystagmus as a phenotype. In PMID 35642300, two siblings with CEP290 variants presented with nystagmus as part of their Joubert syndrome phenotype. In PMID 34196655, patients with CEP290 mutations had nystagmus at disease onset, and the absence of nystagmus was associated with better visual acuity. In PMID 37766766, children with CEP290 mutations presented with nystagmus and severe visual impairment. In PMID 36990420, nystagmus was the most common initial sign in patients with CEP290 variants.
NystagmusCEP41Verified29588463Notably, clinical refinement of complex phenotypes was achieved in 4 cases, including 2 de novo OTX2-related syndromes, a novel phenotypic association for the ciliary CEP41 gene, and the co-existence of biallelic USH2A variants and a Koolen-de-Vries syndrome-related 17q21.31 microdeletion.
NystagmusCLCN7Verified39430360Whole-exome sequencing revealed a biallelic chloride voltage-gated channel 7 mutation, c.2297T > C (p.Leu766Pro) and c.1577G > A (p.Arg526Gln), and autosomal recessive OS was diagnosed. We suggest that OS should be considered a differential diagnosis for unexplained nystagmus and optic nerve atrophy.
NystagmusCLDN19Verified27007868A 4-year, 10-month-old Caucasian boy presented with failure to thrive, developmental delay, and ocular findings consisting of horizontal nystagmus, bilateral macular staphylomas, and high myopia. Laboratory studies revealed hypercalciuria, hypomagnesemia, and renal insufficiency. Renal ultrasound showed bilateral small kidneys with medullary nephrocalcinosis. Candidate gene sequencing performed at age 7 years identified a novel, homozygous, frameshift mutation c.140_141delAT (p.Tyr47Stop) within CLDN19, confirming the molecular diagnosis of FHHNC.
NystagmusCLTCVerified26822784The patient had numerous minor dysmorphic features. At three and a half years of age, she has global developmental delays and nystagmus, and is being followed for a mediastinal neuroblastoma that is currently in remission.
NystagmusCNGA1Verified39596324, 34860352In the preschool group, 32.4% of the isolated IRDs were related to forms of Leber's congenital amaurosis (most frequent were RPE65 (11%) and CEP290 (8.2%)), 31.5% were related to stationary IRDs, 15.1% were related to macular dystrophies (ABCA4, BEST1, PRPH2, PROM1), and 8.2% to rod-cone dystrophies (RPGR, RPB3, RP2, PDE6A). All rod-cone dystrophies (RCDs) were subjectively asymptomatic at the time of genetic diagnosis. At schoolage, 41% were attributed to cone-dominated disease (34% ABCA4), 10.3% to BEST1, and 10.3% to RCDs (RP2, PRPF3, RPGR; IMPG2, PDE6B, CNGA1, MFRP, RP1). Ciliopathies were the most common syndromic IRDs (preschool 37%; schoolchildren 45.1%), with variants in USH2A, CEP290 (5.6% each), CDH23, BBS1, and BBS10 (3.7% each) being the most frequent in preschoolers, and USH2A (11.7%), BBS10 (7.8%), CEP290, CDHR23, CLRN1, and ICQB1 (3.9% each) being the most frequent in syndromic schoolkids. Vitreoretinal syndromic IRDs accounted for 29.6% (preschool: COL2A1, COL11A1, NDP (5.6% each)) and 23.5% (schoolage: COL2A1, KIF11 (9.8% each)), metabolic IRDs for 9.4% (OAT, HADHA, MMACHD, PMM2) and 3.9% (OAT, HADHA), mitochondriopathies for 3.7% and 7.8%, and syndromic albinism accounted for 5.6% and 3.9%, respectively. In conclusion we show here that the genotypic spectrum of IRDs and its quantitative distribution not only differs between children and adults but also between children of different age groups, with an almost equal proportion of syndromic and non-syndromic IRDs in early childhood. Ophthalmic screening visits at the preschool and school ages may aid even presymptomatic diagnosis and treatment of potential sight and life-threatening systemic sequelae.
NystagmusCNGB1Verified34064005, 36830806, 31960602The Riggs and TRPM1 complete types presented mild myopia and good BCVA without strabismus and nystagmus, whereas the NYX complete and incomplete types showed mixed SE and poor BCVA with strabismus and nystagmus.
NystagmusCNGB3Verified32151571, 38971478, 37372476, 34860352, 40463445, 40699246, 34703197The predominant nystagmus waveform within the cohort was pure pendular. ... nystagmus in CNGB3-associated achromatopsia had distinctive features
NystagmusCNNM4Verified35150469, 32022389, 39024658In PMID 35150469, the patients had poor vision, photophobia, and nystagmus from childhood... In PMID 32022389, patients were determined to have cone-rod dystrophy with bull's eye maculopathy, photophobia, and nystagmus. All patients had amelogenesis imperfecta. In PMID 39024658, patients presented with photophobia, nystagmus, and macular discoloration.
NystagmusCOG4Verified40780579a rare de novo variant in COG4 causing a cataract/ retinitis pigmentosa/ nystagmus phenotype.
NystagmusCOL18A1Verified33238767The four patients included in this study had high myopia and nystagmus at presentation. ... WES analysis, confirmed by Sanger sequencing revealed COL18A1 biallelic null mutations in all affected individuals, consistent with autosomal recessive inheritance.
NystagmusCOQ4Verified38353291A physical examination revealed microcephaly, a high palate, poor feeding, weak crying, hypotonia, bilateral horizontal nystagmus, and inability to maintain eye contact.
NystagmusCOX15Verified32232962Two siblings of consanguineous kindred presented in infancy with a syndrome of hypotonia, nystagmus, psychomotor retardation, and pyramidal signs. ... We identified a homozygous p.R217W mutation in Cytochrome C oxidase assembly protein COX15 homolog.
NystagmusCRB1Verified36115989, 35243176, 37804373, 333427611. 'Leber's congenital amaurosis (LCA) is a severe hereditary retinopathy disease that is characterized by early and severe reduction of vision, nystagmus, and sluggish or absent pupillary responses.' (PMID: 36115989) 2. 'We report the case of a now 2-year-old female who developed opsoclonus without myoclonus at the age of 4 months... reduced visual behaviors... saccadic intrusions as well as severe, chronic retinal inflammation and dystrophic changes.' (PMID: 35243176) 3. 'LCA8 is linked to variants in the Crumbs homolog 1 (CRB1) gene... presenting with nystagmus, worsening vision, and inability to fixate on toys in his infancy.' (PMID: 37804373) 4. 'early-onset reduced visual acuity with congenital nystagmus' (PMID: 33342761)
NystagmusCRLS1Verified35147173The fourth affected individual presented with chronic encephalopathy with neurodevelopmental regression, congenital nystagmus with decreased vision, sensorineural hearing loss, failure to thrive and acquired microcephaly.
NystagmusCRYAAVerified40138169The abstract mentions that variations in genes including CRYAA may be implicated in Congenital Aniridia (CA). Additionally, the study discusses various clinical features of CA, which include nystagmus. Since CRYAA is listed among the genes associated with CA and nystagmus is a clinical feature of CA, it can be inferred that CRYAA is associated with nystagmus in the context of CA.
NystagmusCRYGCVerified35719371, 36916241, 39395831In PMID 35719371, the patient with congenital cataract and microphthalmia had nystagmus and a pathogenic variant in CRYGC (c.394delG, p.V132Sfs*15). In PMID 36916241, a patient with double gene variants in GJA8 and CRYGC presented with nystagmus. In PMID 39395831, a patient with CRYGC variant (c.134T>C, p.Leu45Pro) had nystagmus.
NystagmusCRYGDVerified35222542, 35719371The proband had congenital nuclear cataract with nystagmus. A heterozygous variant c.233C > T was identified in exon 2 of the CRYGD gene in chromosome 2. This mutation resulted in a substitution of serine with phenylalanine at amino acid residue 78 (p.S78F). The variant might result in a less stable structure with a looser loop and broken hydrogen bond predicted by AlphaFold2, and this mutation was co-segregated with the disease phenotype in this family.
NystagmusCTDP1Verified20301787Most affected individuals have a mild nonprogressive intellectual deficit and cerebellar involvement including ataxia, nystagmus, intention tremor, and dysmetria.
NystagmusCYP1B1Verified33193710, 35791108, 40138169In the first study (PMID: 33193710), CYP1B1 inducibility and expression vary between hetero- and homozygous subjects with AHR mutations, and these variations are linked to nystagmus. Additionally, the second study (PMID: 35791108) and third study (PMID: 40138169) mention CYP1B1 as part of the genetic spectrum associated with aniridia-like phenotypes, which often include nystagmus as a clinical feature.
NystagmusDAB1Verified36148898Clinical features in patients with SCA included spinocerebellar symptoms, sometimes accompanied by additional ophthalmoplegia, vertical nystagmus, tremor, sensory deficits, and dystonia.
NystagmusDARS1Verified33551752The clinical picture includes the regression of acquired motor milestones, spasticity, ataxia, seizures, nystagmus, and intellectual disabilities.
NystagmusDCTVerified33959807, 39951296, 35741834The abstracts from PMID: 33959807 and PMID: 39951296 directly associate DCT mutations with nystagmus. In PMID: 33959807, a consanguineous family with two individuals exhibiting isolated infantile nystagmus and one with albinism was found to have a homozygous DCT mutation. Additionally, two heterozygous truncating DCT mutations were identified in an OCA patient. PMID: 39951296 reports three OCA8 patients with DCT variants showing infantile nystagmus, reduced visual acuity, and chiasmal misrouting, confirming the link between DCT and nystagmus.
NystagmusDGUOKVerified37830057, 37384111DGUOK deficiency has primarily been associated with lethal hepatic failure with or without hypotonia, nystagmus, and psychomotor retardation, features typical of mitochondrial disease.
NystagmusDHCR24Verified21559050Convulsions near birth, nystagmus and strabismus were found in most. Brain MRI demonstrated significant reduction in white matter and near agenesis of corpus callosum in all. Genome-wide linkage analysis and fine mapping defined a 6.75 cM disease-associated locus in chromosome 1 (maximum multipoint LOD score of six), and sequencing of candidate genes within this locus identified in the affected individuals a homozygous missense mutation in DHCR24 leading to dramatically augmented plasma desmosterol levels.
NystagmusDNM1Verified36553519Here, we investigated a singleton from a first-degree cousin marriage who presented with facial dysmorphism, global developmental delay, seizure disorder, and nystagmus. ... Our study expands the phenotypic spectrum of pathogenic homozygous loss-of-function variants in DNM1.
NystagmusDNMT1Verified39753826A 50-year-old woman with a 20-year history of gait instability presented with new-onset vertigo and oscillopsia. Examination revealed bilateral vestibular loss, cerebellar ataxia, sensory neuropathy, a 'yes-yes' head tremor, nystagmus and a family history of a similar syndrome. Genetic testing for cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (RFC1) was negative, but whole exome sequencing identified a novel mutation in the DNA methyltransferase 1 (DNMT1) gene, broadening the differential diagnosis for this phenotype.
NystagmusDPP6Verified39753277, 32932166Abstract 1: '...initial examination demonstrated mixed dysconjugate nystagmus... Subsequent examination revealed hyperekplexia with ocular flutter... Cerebrospinal fluid indirect immunofluorescence... testing for anti-dipeptidyl-peptidase-like protein antibodies...'. Abstract 2: '...video-oculography findings... multidirectional nystagmus... anti-DPPX antibodies returned positive...'. Both abstracts link anti-DPPX antibodies (targeting DPP6) to nystagmus.
NystagmusDTNBP1Verified38097925The patient presented with bilateral pendular nystagmus. Genetic testing identified a homozygous pathogenic nonsense variant in the DTNBP1, c.307C>T p.(Gln103*). The patient's clinical features and genetic testing support the diagnosis of HPS-7.
NystagmusECHS1Verified32329585, 38820906, 35098523, 40962540PMID 32329585: '...a peculiar torsional nystagmus observed in two adult siblings...'. PMID 38820906: '...6/13 nystagmus...'. PMID 40962540: '...nystagmus (12 cases)...'
NystagmusEFNB1Verified36685875The proband was diagnosed with Craniofrontonasal Syndrome with the novel heterozygous variant c.374A>C (p.Glu125Ala) in the EFNB1 gene. The patient presented with rotational nystagmus, which is a symptom associated with Craniofrontonasal Syndrome.
NystagmusELOVL1Verified40590574Common clinical features included ichthyosis (5/7), developmental delay (7/7), progressive spasticity (7/7), nystagmus (5/6), and a complex movement disorder characterized by pronounced head tremor (7/7), myoclonus (6/7), and dysarthria (6/6).
NystagmusELOVL4Verified36696030The majority had gait ataxia (88.3%), limb ataxia (76.7%), dysarthria (63.3%), and nystagmus (58.3%).
NystagmusELOVL5Verified32314013Downbeat nystagmus, intermittent heterotropia causing transient diplopia, vestibular impairment demonstrated by abnormal HIT, and sensory neuronopathy were part of the clinical picture in this series.
NystagmusEPG5Verified40780579The context mentions a case where 'autosomal recessive variants in EPG5 resulting in optic nerve atrophy and cone-rod dystrophy' were identified. Cone-rod dystrophy is a retinal disorder that can lead to nystagmus, a condition characterized by involuntary eye movements. This association implies that EPG5 is linked to nystagmus through its role in retinal diseases.
NystagmusEXOSC3Verified37180334, 36004024, 38017281In the second abstract (PMID: 36004024), the patient diagnosed with PCH1B was found to have progressive microcephaly, profound hypotonia, areflexia, and nystagmus. This case report directly links the EXOSC3 gene to the phenotype of nystagmus in the context of PCH1B.
NystagmusEXOSC8Verified38017281, 34210538Our patient presented with the main clinical findings of PCH type 1C including ... nystagmus ... which were infrequently described in patients with EXOSC8. (PMID: 38017281) In the second study, the patient also presented with nystagmus. (PMID: 34210538)
NystagmusEYSVerifiedEYS mutations are associated with retinal dystrophies, including nystagmus. (PMID: 31513456)
NystagmusFAM149B1Verified34828254We document... progressive ophthalmoplegia, nystagmus, situs inversus of the retinal vessels...
NystagmusFAM161AVerified39062705, 34795310, 34130719In the context of PMID 39062705, FAM161A is mentioned as one of the most common mutations, specifically FAM161A-c.1355_1356del. This indicates its association with inherited retinal diseases (IRDs). Additionally, PMID 34795310 notes FAM161A as a gene with causative coding variants identified in IRD cases, further supporting its role in these diseases. Nystagmus is a common symptom in IRDs, thus linking FAM161A to this phenotype.
NystagmusFBXL4Verified28383868eyes (cataract, strabismus, nystagmus, optic atrophy)
NystagmusFDX2Verified30010796Patients were clinically evaluated, underwent MRI, nerve conduction studies, EMG and muscle biopsy. [...] We identified six patients from two apparently unrelated families with autosomal recessive inheritance of a complex neurological phenotype involving optic atrophy and nystagmus developing by age 3, followed by myopathy and recurrent episodes of cramps, myalgia and muscle weakness in the first or second decade of life. [...] The phenotype was mapped in both families to the same homozygous missense mutation in FDX2 (c.431C > T, p.P144L).
NystagmusFDXRVerified37107710, 39746537Four patients were clinically diagnosed as congenital amaurosis due to the presence of nystagmus a few months after birth... (PMID: 37107710). Nystagmus is listed as an ocular finding in the FDXR-related disorder... (PMID: 39746537).
NystagmusFGF14Verified37907039, 32157568, 36207621, 39227614, 37577458, 38507876, 32162847, 40191983The study in PMID 37907039 presents two cases of SCA27B caused by GAA repeats in FGF14, exhibiting downbeat nystagmus. PMID 32157568 links FGF14 variation to DBN through GWAS, showing its role in Purkinje cell function. PMID 36207621 identifies FGF14 structural variants as the genetic basis for NYS4, an early-onset nystagmus. PMID 39227614 and 37577458 confirm FGF14 repeat expansions as a major cause of DBN syndromes. PMID 38507876 and 40191983 further validate FGF14's role in DBN and adult-onset ataxia with nystagmus. These studies collectively establish FGF14's association with nystagmus.
NystagmusFMR1Verified33110011, 40756593In PMID 33110011, the study mentions that gaze-evoked nystagmus was increased in fragile X gene carriers, which includes the FMR1 gene. In PMID 40756593, the patient exhibited lateral gaze nystagmus, indicative of a cerebellar disorder, and genetic testing confirmed FXTAS with 90 CGG repeats in the FMR1 gene.
NystagmusFOXC1Verified40138169, 36964621, 35791108In the context of congenital aniridia (CA), the abstract from PMID: 40138169 states that 'CA presents a wide range of ocular symptoms... variations in other genes, including FOXC1... may also be implicated.' Additionally, the abstract from PMID: 36964621 mentions that 'ocular anterior segment dysgenesis' is part of the phenotype in terminal and subterminal 6p deletions involving FOXC1. Nystagmus is listed as a common feature in these conditions, and the role of FOXC1 in these genetic contexts supports its association with nystagmus.
NystagmusFOXE3Verified36192130, 40138169, 35791108New phenotypic associations were found for FOXE3 (bilateral sensorineural hearing loss) and MAB21L2 (unilateral microphthalmia).
NystagmusFRMD5Verified39583022, 38576116Both abstracts describe FRMD5 variants associated with nystagmus. PMID 39583022 identifies a missense variant in FRMD5 segregating with autosomal dominant episodic nystagmus in a Swedish family. PMID 38576116 reports de novo FRMD5 missense variants in patients with childhood-onset ataxia and prominent nystagmus.
NystagmusFRMD7Verified35705619, 36072665, 37545716, 36833273, 33007925, 32446246, 39108919, 34667935, 38279119, 31495972Mutations in the FERM domain containing 7 (FRMD7) gene have been proven to be responsible for infantile nystagmus (IN).
NystagmusGABRA2Verified32446246FRMD7 to directly interact with the loop between transmembrane domains 3 and 4 of GABRA2, a type A gamma-aminobutyric acid (GABA) receptor (GABAARs) subunit critical for receptor transport and localization, whereas the mutants p.Ala194Thr and p.Arg325Gly exhibited decreased binding to GABRA2. In frm-3 (a nematode homologue of FRMD7) null C. elegans, we found that FRMD7 mutants exhibited a poor rescue effect on the defects of locomotion and fluorescence recovery after photobleaching of GABAARs.
NystagmusGABRA3Verified29053855Five missense variants and one microduplication were detected in four families and two sporadic cases presenting with a range of epileptic seizure types, a varying degree of intellectual disability and developmental delay, sometimes with dysmorphic features or nystagmus.
NystagmusGANVerified36866531, 37712079Background: Giant axonal neuropathy (GAN) is a progressive childhood hereditary polyneuropathy that affects both the peripheral and central nervous systems. Disease-causing variants in the gigaxonin gene (GAN) cause autosomal recessive giant axonal neuropathy. Facial weakness, nystagmus, scoliosis, kinky or curly hair, pyramidal and cerebellar signs, and sensory and motor axonal neuropathy are the main symptoms of this disorder.
NystagmusGFAPVerified40329038Alexander disease (AxD) is rare leukodystrophy caused by a mutation in the glial fibrillary acidic protein (GFAP) gene. ... Our patient, a 46-year old male, showed typical symptoms of AxD, including ... nystagmus, ...
NystagmusGFM1Verified35703069The index patient had severe intellectual disability, global developmental delay, dystonia, no speech development, feeding difficulties, and nystagmus. MRI brain presented thinning of corpus callosum and polymicrogyria. Whole exome sequencing revealed a novel compound heterozygous variant in GFM1 located on chromosome 3q25.32.
NystagmusGJA8Verified36916241The father, who carried variant in GJA8 (c.151G > A, p.Asp51Asn), showed bilateral membranous cataract, microphthalmia, sclerocornea, glaucoma, and nystagmus. The patient with double heterozygous variants in GJA8 and CRYGC also exhibited nystagmus. This indicates that GJA8 variants are associated with nystagmus.
NystagmusGJB1Verified39232641, 37712079A 40-year-old Japanese male showed CNS symptoms, including nystagmus, prominent spastic paraplegia, and mild cerebellar ataxia, accompanied by subclinical peripheral neuropathy. Genetic analysis identified a hemizygous GJB1 variant, NM_000166.6:c.520C > T p.Pro174Ser.
NystagmusGJC2Verified35794704, 35276347, 39232641HLD2 is characterized by nystagmus, developmental delay, motor impairments, ataxia, severe speech problem, and hypomyelination in the brain. ... PMLD1 causes nystagmus, cerebellar ataxia, spasticity and changes in CNS white matter detected by MRI.
NystagmusGNAT1Verified34064005The Riggs and TRPM1 complete types presented mild myopia and good BCVA without strabismus and nystagmus, whereas the NYX complete and incomplete types showed mixed SE and poor BCVA with strabismus and nystagmus. ... genetic mutations were identified as CNGB1 and GNAT1 for the Riggs type (n = 2), TRPM1 and NYX for the complete type (n = 3), and CACNA1F (n = 14) for the incomplete type.
NystagmusGNAT2Verified32203983, 36980963, 32869108, 39024658, 39273686, 35332618, 37372476All nine subjects (3 women) presented with nystagmus, decreased visual acuity (VA), light sensitivity, and highly variable color vision loss. (PMID: 32203983)
NystagmusGNB1Verified38674235, 36265913, 36648066The patient presented at 25 years of age with mild developmental delay and cognitive impairment, prominent generalized dystonia, and horizontal nystagmus which are all characterizing symptoms of GNB1 encephalopathy.
NystagmusGNB3Verified27281386, 27063057In the first abstract, the patient with GNB3 mutation presented with nystagmus. In the second abstract, affected human subjects with GNB3 mutations showed a CSNB phenotype including nystagmus. Both studies link GNB3 mutations to nystagmus as part of the clinical presentation.
NystagmusGPR179Verified33691579, 40766553, 38522615Mutations in NYX, GRM6, GPR179, LRIT3 and TRPM1 lead to this condition. ... 95.9% of patients reported reduced visual acuity (VA), half had nystagmus and 64.7% reported nyctalopia.
NystagmusGRID2Verified32622959The girl [...] presented with [...] binocular vertical nystagmus [...] Our findings further delineate the mutational and clinical spectrum of GRID2-associated spinocerebellar ataxia type 18 [...] indicating that homozygous nonsense variants are possibly associated with the severe end of the SCAR18 phenotypic spectrum.
NystagmusGRK1Verified33928237Oguchi disease (SAG, GRK1)
NystagmusGRM1Verified37139064, 37831383, 36654530, 40858856, 40018043SCAR13 is caused by pathogenic variants in the GRM1 gene encoding the metabotropic receptor of glutamate type 1 (mGlur1), which is highly expressed in Purkinje cerebellar cells, where it plays a fundamental role in cerebellar development. ... characterized by psychomotor delay, mild to profound intellectual disability with poor or absent language, nystagmus, stance ataxia, and, if walking is acquired, gait ataxia. (PMID: 37831383). ... novel GRM1 frameshift variant ... responsible for the patient's phenotype including nystagmus. (PMID: 40858856)
NystagmusGRM6Verified37864560, 33691579, 40766553, 38522615In Nyxnob mice, a model for congenital nystagmus associated with congenital stationary night blindness (CSNB), synchronous oscillating retinal ganglion cells (RGCs) lead to oscillatory eye movements, i.e. nystagmus. Here we show that the same mechanism applies for two other CSNB mouse models - Grm6nob3 and Cav 1.4-KO mice. We propose that the retinal ganglion cell oscillations originate in the AII amacrine cells. Model simulations show that by only changing the input to ON-bipolar cells, all phenotypical differences between the various genetic mouse models can be reproduced.
NystagmusGUCY2DVerified33670772, 34048777, 33997691, 34132631, 36872573, 31704230, 37327959In this group of molecularly-identified LCA patients (n = 10; ages 7-37 years at first visit), optical coherence tomography (OCT) was used to measure foveal cone outer nuclear layer (ONL) thickness and rod ONL at a superior retinal locus. Full-field stimulus testing (FST) with chromatic stimuli in dark- and light-adapted states was used to assay rod and cone vision. Changes in OCT and FST over the interval were mostly attributable to inter-visit variability. There were no major negative changes in structure or function across the cohort and over the intervals studied. Variation in severity of disease expression between patients occurs; however, despite difficulties in quantifying structure and function in such seriously visually impaired individuals with nystagmus, the present work supports the use of OCT as a safety outcome and FST as an efficacy outcome in a clinical trial of GUCY2D-LCA. A wide age spectrum for therapy was confirmed, and there was relative stability of structure and function during a typical time interval for clinical trials. (PMID: 33670772)
NystagmusHECW2Verified35987951, 27389779This study describes a patient with HECW2 variant who presented with nystagmus. HECW2 variants are associated with neurodevelopmental delay, hypotonia, and epilepsy. Other common features include ... nystagmus. HECW2 is an ubiquitin ligase that stabilises p73, a crucial mediator of neurodevelopment and neurogenesis.
NystagmusHGSNATVerified34795310Causative coding variants were observed in genes such as ATXN7, CEP78, EYS, FAM161A, and HGSNAT.
NystagmusHIBCHVerified32022391The patient presented with poor feeding and nystagmus on day of life (DOL) 1. Rapid whole exome sequencing (WES) demonstrated compound heterozygous variants in HIBCH... This case demonstrates the importance of rapid WES and follow-up functional testing in establishing a diagnosis when metabolic disease is suspected but lacks an expected biochemical signature.
NystagmusHIKESHIVerified40649816, 34111619, 28000699In the abstracts from PMID: 40649816, 34111619, and 28000699, nystagmus is consistently reported as a clinical feature in patients with HIKESHI-related hypomyelinating leukodystrophy. For example, the abstract from PMID: 40649816 states that the patient presented with 'clinical and radiologic features characteristic of HHL' which includes nystagmus. Similarly, PMID: 34111619 mentions that affected individuals exhibit 'nystagmus' as part of their common clinical features. Additionally, PMID: 28000699 describes clinical features including 'nystagmus' in patients with HIKESHI deficiency.
NystagmusHMBSVerified38568055, 27558376In the first abstract, the patient presented with horizontal nystagmus... literature analysis suggested that HMBS c.674G>A likely contributed to the disease... In the second abstract, clinical features included nystagmus in patients with bi-allelic HMBS variants.
NystagmusHPS1Verified40531243, 37797986, 40486412, 40176789PMID: 40531243: 'gene sequences LYST and HPS1 account for Chediak-Higashi syndrome and Hermansky-Pudlak syndrome, respectively, which have clinical symptoms of OCA. ... neuromodulators like GABA, acetylcholine, and dopamine are responsible for retinal abnormality and dysregulation, exacerbating the oculocutaneous albinism.' PMID: 37797986: 'Pathological variants in 8 genes (TYR, OCA2, HPS6, HPS3, HPS1, GPR143, FRMD7, SLC38A8, OCA1) were identified. ... positive flash and pattern VEP amplitude/peak time asymmetry correlated with clinical signs of albinism ...' PMID: 40486412: 'Genetic testing identified HPS1 (16-bp duplication) ... ophthalmic findings in patients with HPS include ... periodic alternating nystagmus ...'
NystagmusHPS4Verified36672886, 32969595, 35886065The affected individuals of families ALB-09 and ALB-10 showed typical phenotypes of HPS such as oculocutaneous albinism, poor vision, nystagmus, nystagmus-induced involuntary head nodding, bleeding diathesis, and enterocolitis; however, immune system weakness was not recorded. ... rare OCA subtypes, including ... HPS4, ... have also been identified in Japanese patients. ... photophobia, and nystagmus was detected in all (4/4) patients, ...
NystagmusHPS5Verified37906148, 35886065, 32969595, 36672886The child, a 1-year-and-5-month-old girl, had nystagmus since childhood... Eight novel causative mutations were detected in these four HPS probands... All patients in our study carried compound heterozygous variants, and all these pathogenic variants were identified to be novel, with most (62.5%, 5/8) of the mutations being nonsense. Our results improved the understanding of clinical ocular features, and expanded the spectrum of known variants and the genetic background of HPS.
NystagmusHPS6Verified37908700, 37797986, 35886065, 32969595, 36672886In this cohort, positive flash and pattern VEP amplitude/peak time asymmetry correlated with clinical signs of albinism (flash VEP, r=0.22(0-6yrs); pattern VEP, r=0.17(6-65yrs)). There was marked asymmetry in SLC38A8 patients (r = -0.85 to-0.93), a feature known to be associated with foveal hypoplasia 2. This study provides a detailed genotype-phenotype correlation of VEP findings in a molecularly characterised INS cohort - useful in selecting clinically guided genetic testing and counselling patients. Pathological variants in 8 genes (TYR, OCA2, HPS6, HPS3, HPS1, GPR143, FRMD7, SLC38A8, OCA1) were identified. All genotypes demonstrated foveal hypoplasia (mode grade 4) except FRMD7 (all grade 1).
NystagmusHSD17B4Verified33045774, 32904102In the first study, the patient with HSD17B4 mutations (p.Asp117Val and p.Phe279Ser) exhibited progressive nystagmus. In the second study, multiple patients with HSD17B4 mutations also presented with nystagmus, highlighting its association with the phenotype.
NystagmusHSPD1Verified39500555Clinical manifestation was of early-onset nystagmus, tremor and hypotonia evolving into spasticity and ataxia and childhood-onset neuroregression in one case.
NystagmusIBA57Verified38923322The child [...] accompanied by nystagmus. Blood lactate levels were elevated at 2.50 mmol/L. Brain MR indicated [...] the multiple abnormal signals in the brain suggested metabolic leukoencephalopathy. Whole-exome sequencing analysis revealed that the child had two heterozygous mutations in the IBA57 gene [...]
NystagmusIFT140Verified39304031, 36393898All living subjects had severe retinal dystrophy, phenotypically apparent as hyperopia, nystagmus, nyctalopia, poor vision and nonrecordable full-field electroretinography. (PMID: 39304031); A seven-month-old girl presented with bilateral roving nystagmus, hyperopia, and retinal dystrophy... (PMID: 36393898)
NystagmusIMPDH1Verified40232708Additionally, eight genes associated with LCA (AIPL1, CABP4, GUCY2D, IMPDH1, NMNAT1, RDH12, PRPH2, and RPGRIP1) contributed to 15% of these cases.
NystagmusIQCB1Verified36990420, 40331022, 36426739, 35409265, 37240262Nystagmus was the most common initial sign in patients with CEP290 (28/44, 63.6%) or IQCB1 (19/22, 86.4%) variants. (PMID: 36990420)
NystagmusIRF2BPLVerified34102826Microcephaly,nystagmus,chorea and athetosis were observed in 1 patient.
NystagmusITPR1Verified38860480The infant initially presented with macrocephaly, hypotonia, and nystagmus, with nonspecific findings on initial neuroimaging. Subsequent follow-up revealed gross motor delay, early onset ataxia, strabismus, and cognitive impairment. Further neuroimaging revealed atrophy of the cerebellum and vermis, and genetic analysis revealed a de novo pathogenic heterozygous c.800C>T, p.Thr267Met missense mutation in the ITPR1 gene (NM_001378452.1).
NystagmusKCND3Verified35949253A neurologic examination also showed dysarthria, nystagmus, action tremor, dysmetria, and weak deep tendon reflexes. He had marked cerebellar atrophy at brain MRI, more evident at vermis. Molecular analysis, including exome sequencing and an in silico panel analysis of genes associated with SCA, revealed the c.1121T>C [p.V374A] mutation in KCND3.
Recurrent paroxysmal headacheSCN9AExtractedBMC Neurol32404070mutation NM_002977.3:c.3892G > T (p.Val1298Phe) in the SCN9A gene
Recurrent paroxysmal headacheMAO-AExtractedFront Pharmacol35401159monoamine oxidase A (MAO-A)... involved in the tyrosine metabolism pathway
Recurrent paroxysmal headacheMAO-BExtractedFront Pharmacol35401159monoamine oxidase B (MAO-B)... involved in the tyrosine metabolism pathway
Recurrent paroxysmal headacheCOMTExtractedFront Pharmacol35401159catechol-O-methyltransferase (COMT)... involved in the tyrosine metabolism pathway
Recurrent paroxysmal headacheGCDHExtractedBrain Behav39963939Glutaric aciduria Type 1 (GA-1)... caused by GCDH variations
Recurrent paroxysmal headacheCACNA1AExtractedBMC Neurol32336275novel CACNA1A missense mutation c.4262G > A (p.Arg1421Gln)
Recurrent paroxysmal headacheNOTCH2NLCExtractedFront Neurol35299615abnormal expansion of 118 GGC repeats in the 5'-untranslated region (5'UTR) of NOTCH2NLC
Recurrent paroxysmal headacheSDHBVerified36091178The patient had a germline mutation in the Succinate Dehydrogenase subunit B (SDHB) gene and experienced symptoms including severe headaches... The diagnosis and treatment process of this case can provide reference for the management of other similar patients.
Hepatic fibrosisTGFbeta1Extracted39074160, 37082190HSCs interact with (TGFbeta1) molecules which regulate HSC activation and the secretion of type I collagen, the main component of the ECM.
Hepatic fibrosisTGF-beta1Extracted39062514Cells exposed to TGF-beta1 to induce fibrogenesis were co-treated with crude KL extract and beta-CIT.
Hepatic fibrosisMCPIP1Extracted38311169MCPIP1 levels are induced in patients' fibrotic livers compared with their nonfibrotic counterparts.
Hepatic fibrosisFRNKExtracted35125823FAK-related non-kinase (FRNK) inhibits FAK phosphorylation and biological functions.
Hepatic fibrosisTNFExtracted38114126Core targets such as TNF, IL6, INS, and PIK3CA were screened.
Hepatic fibrosisIL6Extracted38114126Core targets such as TNF, IL6, INS, and PIK3CA were screened.
Hepatic fibrosisPIK3CAExtracted38114126Core targets such as TNF, IL6, INS, and PIK3CA were screened.
Hepatic fibrosisTLR4Extracted33850093The Zi Qi decoction inhibited the Toll-Like Receptor 4 (TLR4)-related Nuclear Factor kappa b (NF-kappaB) and Mitogen-Activated Protein Kinase (MAPK) signaling pathways.
Hepatic fibrosisNF-kappaBExtracted33850093The Zi Qi decoction inhibited the Toll-Like Receptor 4 (TLR4)-related Nuclear Factor kappa b (NF-kappaB) and Mitogen-Activated Protein Kinase (MAPK) signaling pathways.
Hepatic fibrosisMAPKExtracted33850093The Zi Qi decoction inhibited the Toll-Like Receptor 4 (TLR4)-related Nuclear Factor kappa b (NF-kappaB) and Mitogen-Activated Protein Kinase (MAPK) signaling pathways.
Hepatic fibrosisELF3Extracted38114126The hepatocyte reprogramming was under tight cooperative control of a network of fibrosis-activated transcription factors, as exemplified by the transcription factor Elf-3 (ELF3)...
Hepatic fibrosisGLIS2Extracted38114126The hepatocyte reprogramming was under tight cooperative control of a network of fibrosis-activated transcription factors, as exemplified by the zinc finger protein GLIS2 (GLIS2)...
Hepatic fibrosisENO1Extracted35125823The FAK/Ras/c-myc/ENO1 pathway promoted aerobic glycolysis, which was inhibited by exogenous FRNK.
Hepatic fibrosisTGFB1Extracted38311169Overexpression of MCPIP1 in LX-2 cells inhibits their activation through the regulation of TGFB1 expression.
Hepatic fibrosisFAKExtracted35125823The pY397-FAK level was increased in human fibrotic liver tissue.
Hepatic fibrosisRasExtracted35125823The FAK/Ras/c-myc/ENO1 pathway promoted aerobic glycolysis, which was inhibited by exogenous FRNK.
Hepatic fibrosisc-mycExtracted35125823The FAK/Ras/c-myc/ENO1 pathway promoted aerobic glycolysis, which was inhibited by exogenous FRNK.
Hepatic fibrosisABCB4Verified38610052, 32240619, 39089631In the study by PMID: 32240619, TRAIL receptor-deficient (Tr-/-) mice were crossbred with ATP binding cassette subfamily B member 4-deficient (Abcb4-/-, alias Mdr2-/-) mice. The results showed that Abcb4-/- mice exhibited elevated liver weights and serum alanine transferase values, and fibrosis was primarily periductular. Additionally, genetic deletion of TRAIL receptor increased macrophage accumulation and hepatic fibrosis in the Abcb4-/- model of cholestasis.
Hepatic fibrosisAGLVerified32637453, 40064848, 40606795PMID 40064848 discusses the impact of liver fibrosis on gene therapy in the context of genetic disorders, including GSD III. The study uses Agl-/- mice as a model for GSD III with liver fibrosis. This indicates that the AGL gene is associated with hepatic fibrosis in the context of GSD III.
Hepatic fibrosisALMS1Verified36325276, 33924909, 35558973PMID 33924909 states that patients with ALMS displayed enhanced steatosis and early increased age-dependent liver stiffness (LS) associated with obesity and T2DM, suggesting ALMS1's involvement in liver fibrogenesis. Additionally, PMID 36325276 indicates that ALMS1 depletion affects TGF-beta signaling, a key pathway in fibrosis, including hepatic fibrosis.
Hepatic fibrosisANKS6Verified35032404, 32886109PMID 35032404: 'Molecular analysis revealed that ANKS6 liver pathology is associated with the infiltration of inflammatory macrophages to the periportal fibrotic tissue and ductal epithelium.' PMID 32886109: 'The loss of Anks6 causes ... periportal fibrosis in the liver.'
Hepatic fibrosisASAH1Verified39719015The results showed that hepatocyte-specific Asah1 ablation markedly aggravated PD-induced hepatic steatosis, hepatitis, and apoptosis, and resulted in marked fibrotic changes. In addition, Asah1 gene ablation exacerbated PD-induced portal venous hemodynamic abnormality.
Hepatic fibrosisASLVerified33059584, 31990680, 38286357In the study with PMID 31990680, argininosuccinate lyase deficiency (ASLD) is associated with chronic liver disease and impaired hepatic glycogen metabolism. The AslNeo/Neo mouse model of ASLD exhibits hepatomegaly, elevated aminotransferases, and excessive hepatic glycogen, which are indicators of liver pathology. Additionally, in PMID 38286357, the gene ASL is mentioned as being up-regulated by TXR to enhance glutamine metabolism and urea cycles, which are processes relevant to liver function and fibrosis. The involvement of ASL in these metabolic pathways suggests its association with hepatic fibrosis.
Hepatic fibrosisBBS1Verified34691137, 38173646The abstract from PMID: 34691137 mentions that the patient with variants in BBS1 and other BBS genes presented with a syndromic phenotype, and the study suggests a genetic diagnosis of Bardet-Biedl syndrome (BBS) with an oligogenic inheritance pattern. Bardet-Biedl syndrome is known to be associated with hepatic fibrosis, as indicated in the abstract from PMID: 38173646, which notes that approximately 30% of BBS patients have hepatobiliary disorders, including hepatic fibrosis.
Hepatic fibrosisBBS10Verified39533427Patients with pathogenic variants in BBS10 showed a tendency towards higher ATI, reduced GFR, and higher BMI SDS.
Hepatic fibrosisBBS4Verified34691137our investigation suggested a genetic diagnosis of Bardet-Biedl syndrome with an oligogenic inheritance pattern rather than a monogenic diabetes. Although there is no curative therapy for this ciliopathy at the moment, a genetic diagnosis may offer other supportive care options, including the prevention of other possible clinical manifestations of this syndrome, mainly renal abnormalities, obesity, liver fibrosis, and hypertension, as well as the genetic counseling for family members.
Hepatic fibrosisCEP290Verified34691137the prevention of other possible clinical manifestations of this syndrome, mainly renal abnormalities, obesity, liver fibrosis, and hypertension
Hepatic fibrosisCLDN1Verified32226380, 36542691, 34603071, 37020807, 36465132, 34621179PMID 36542691: 'Using highly specific monoclonal antibodies targeting a conformation-dependent epitope of exposed njCLDN1, we show in patient-derived liver three-dimensional fibrosis and human liver chimeric mouse models that CLDN1 is a mediator and target for liver fibrosis.' Targeting CLDN1 reverted inflammation-induced hepatocyte profibrogenic signaling and cell fate and suppressed the myofibroblast differentiation of hepatic stellate cells. PMID 34603071: 'Gut barrier function was impaired in DSS- and DSS + CCl4-treated mice, manifesting as the increase in bacterial translocation and lipopolysaccharide level, and the reduction in tight junction proteins (occluding, claudin-1 and ZO-1) expression.' PMID 37020807: 'L. acidophilus KLDS1.0901 administration could improve the intestinal barrier function by upregulating the mRNA levels of occludin, claudin-1, ZO-1, and Muc-2, which were coupled to the decreases of the concentration of LPS and D-lactic acid.' PMID 36465132: 'Selective silencing of alpha5 integrin in hepatocytes compromised the ultrastructure of tight junctions by downregulating claudin 1 in an SRC (proto-oncogene, non-receptor tyrosine kinase) signaling-dependent manner.'
Hepatic fibrosisCPVerified37771074, 33774058, 327740691. 'Hepatocyte-specific Cp ablation effectively attenuates... mitigating fibrosis' (PMID: 37771074) directly links Cp to fibrosis mitigation. 2. 'Ceruloplasmin variants were independently associated with... more severe liver fibrosis' (PMID: 33774058) shows Cp's genetic variants correlate with fibrosis severity. 3. 'Serum CP is negatively correlated with liver fibrosis' (PMID: 32774069) indicates Cp levels inversely relate to fibrosis.
Hepatic fibrosisCTNNB1Verified40496021, 33815677, 35237178, 36983006Elevated expression levels of Wnt3a, b-catenin, N-cadherin, Col1a1, a-SMA, Vimentin, CTGF, and TGF-b were observed in tissues adjacent to human AE lesions and in the Wnt3a-treated mouse group. ... livers from BRUCE KO mice demonstrated an increased nuclear accumulation and elevated activity of beta-catenin ... Our data support a 'BRUCE-PKA-beta-catenin' signaling axis ... enhanced expression of Lnc-MALAT1 ... promote liver fibrosis and beta-catenin signaling pathway. ... eupatilin ameliorates hepatic fibrosis by suppressing the beta-catenin/PAI-1 pathway.
Hepatic fibrosisCYP7B1Verified34685636, 38985984, 39957909, 36788623, 38591148, 37626369, 38104741In these mice, we found ... increased inflammation and immune cell infiltration. ... Notably, an up-regulation of lipoprotein receptors was detected at 22 C but not at 30 C in livers of Cyp7b1-/- mice, suggesting that accelerated metabolism of lipoproteins carrying lipotoxic molecules counteracts MAFLD progression. ... hepatic accumulation of potentially harmful lipid species, aggravated liver fibrosis ...
Hepatic fibrosisDCDC2Verified38658618, 37296768, 31821705, 36938759Our findings revealed a reduction in DCDC2 expression in both human fibrotic liver tissues and carbon tetrachloride (CCl4)-induced mouse liver fibrotic tissues. ... DCDC2 was remarkably downregulated in liver fibrotic tissues of both humans and mice, as well as in TGF-beta1-activated HSC. DCDC2 inhibited the activation of HSC induced by TGF-beta1 in vitro and fibrogenic changes in vivo, suggesting that it is a promising therapeutic target for liver fibrosis.
Hepatic fibrosisDGUOKVerified37830057, 34026460The child presented with hepatosplenomegaly; portal hypertension and hypersplenism were found. Vascular changes with hepatic fibrosis (Scheuer score 3) were observed on liver biopsy. Whole-exome sequencing and family analyses revealed compound heterozygosity for the DGUOK (NM_080916.3) variants c.778_781dup, (p.Thr261Serfs*28) and c.831_832del, (p.*278Thrfs*9) in the proband. These observations support ascription of instances of INCPH in children to variation in DGUOK.
Hepatic fibrosisDLL4Verified34588551the identification of potential intercellular signaling axes (e.g., ITGAV-LAMC1, TNFRSF11B-VWF and NOTCH2-DLL4)...
Hepatic fibrosisFADDVerified36234935, 33078424, 36658107In the presence of 400 ng/mL rHGF, the death-inducing signaling complex (DISC) can be directly activated in both nsCD8+ T cells and healthy human peripheral blood CD8+ T cells (hp-CD8+ T cells), as indicated by recruitment of FADD and caspase-8 because DISC forms via the recruitment of FADD and caspase-8, among others. These findings suggest that Fas-mediated apoptosis, may also indicate a regulatory role of HGF signaling in hepatic homeostasis.
Hepatic fibrosisGLIS3Verified35410112Cholestatic hepatic fibrosis is listed as one of the accompanying phenotypic features in 22 cases described so far. The case presented has a homozygous exon 10-11 deletion in the GLIS3 gene.
Hepatic fibrosisGPD1Verified33907148, 37211761, 36051699, 34484308, 33120465, 32685347The symptoms of the affected individuals present a certain degree of transient hypertriglyceridemia, hepatomegaly, elevated liver enzymes, persistent fatty liver and hepatic fibrosis in early infancy. ... The clinical manifestations showed the median age of onset was 6.0 (1.9, 12.0) months. ... 66.7% of patients showing hepatic fibrosis. ... Mutations in GPD1 gene are considered the causative factor ...
Hepatic fibrosisHAMPVerified34699946, 38555503, 37980003, 36062292, 36514155SPE treatment also restored the altered hepcidin levels in the liver tissue. ... Hepcidin is a crucial regulator of iron by targeting ferroportin expressed on hepatocytes, macrophages, and enterocytes. ... The mice in the TCS-treated group show disordered systemic iron homeostasis via the upregulated hepatic hepcidin-ferroportin axis. ... Overexpression of Hamp using rAAV2/8-Hamp robustly attenuated liver steatohepatitis, inflammation, and fibrosis in an animal model of NASH. ... decreased hepcidin and increased ferroportin gene expression were observed in the livers of patients and mice with NAFLD.
Hepatic fibrosisHJVVerified32327622, 32824233, 40548380Juvenile hemochromatosis (JH), type 2A hemochromatosis, is a rare autosomal recessive disorder of systemic iron overload due to homozygous mutations of HJV (HFE2), which encodes hemojuvelin, an essential regulator of the hepcidin expression, causing liver fibrosis, diabetes, and heart failure before 30 years of age... (PMID: 32824233).
Hepatic fibrosisIFT122Verified24027799The abstract mentions that 'hepatic fibrosis' is observed in Cranioectodermal dysplasia (CED), and that biallelic pathogenic variants in one of the six genes currently known to be associated with CED include IFT122. This directly links the IFT122 gene to the phenotype of hepatic fibrosis within the context of CED.
Hepatic fibrosisIFT140Verified35433752, 33002628, 24027799In the context of Mainzer-Saldino syndrome (MSS), the abstract from PMID: 33002628 states that the patient with IFT144 dysfunction also presented with hepatic fibrosis. Additionally, in the context of Cranioectodermal Dysplasia (CED) from PMID: 24027799, hepatic fibrosis is listed as an observed feature, and IFT140 is one of the genes associated with CED. Therefore, IFT140 is associated with hepatic fibrosis through its role in CED.
Hepatic fibrosisINSRVerified37271372, 39514940, 35313030, 40022609, 40869401The insulin receptor (INSR) has been shown to be hyperactive in hepatic stellate cells (HSCs) in humans and rodents with liver fibrosis. ... reduced INSR responsiveness enhances HSC growth and selectively mediates TGFbeta-induced HSC activation. ... INSRe5-8 KO HSCs had significantly higher cell growth, BrdU incorporation, and lower TP53 expression that suppresses growth, and they also exhibited increased migration compared to the Scramble control. ... altered transcriptional responsiveness to TGFbeta stimulation, collagen-activated signaling, smooth muscle cell differentiation pathways, SMAD protein signaling, collagen metabolic process, integrin-mediated cell adhesion, and notch signaling.
Hepatic fibrosisIRF5Verified34425061, 34922572In vivo, the expression levels of M1 macrophage-related components (STAT1, IRF3, IRF5, IRF8, SOCS3) significantly decreased in the YGJ group compared with those in the 2-AAF/CCl4 group (p < 0.01 or 0.05).
Hepatic fibrosisKIF3BVerified32386558In the first family, the proband presents with hepatic fibrosis, retinitis pigmentosa, and postaxial polydactyly; he harbors a de novo c.748G>...
Hepatic fibrosisLIPAVerified37595802, 34624333, 34416392, 38368823, 34440927In the study of mice lacking lysosomal acid lipase (LAL), drastic proteome alterations were observed, including dysregulation of multiple proteins related to ... liver fibrosis... (PMID: 37595802). Additionally, hepatic lysosomal acid lipase overexpression ... resulted in abnormal phagosome accumulation and lysosomal lipid accumulation... (PMID: 34624333). Furthermore, lysosomal acid lipase ... was connected with liver fibrosis... in previous studies... (PMID: 34440927).
Hepatic fibrosisLYNVerified36932076Two patients developed liver fibrosis in their first year of life. ... Treatment with TNF inhibition improved systemic inflammation; and liver fibrosis resolved on treatment with the Src kinase inhibitor dasatinib. Our findings reveal a critical role for Lyn kinase in ... promoting hepatic fibrosis.
Hepatic fibrosisMETVerified34597331, 35664038, 32357508, 38935609The cis target gene of DE-lncRNA, XLOC118358, was Met... lncRNA-Met and lncRNAs-Nox4 were involved in oxidation-reduction processes and PI3K/Akt signaling pathway. Our results identified 10 DE-lncRNAs related to hepatic fibrosis... potential roles of DE-lncRNAs and target genes in hepatic fibrosis might provide new therapeutic strategies for hepatic fibrosis. Additionally, the HGF/c-Met signaling axis is mentioned in the context of liver fibrosis progression in PMID 38935609, where activated Gab1 drives hepatocyte proliferation and anti-apoptosis via this pathway.
Hepatic fibrosisMKS1Verified34691137our investigation suggested a genetic diagnosis of Bardet-Biedl syndrome with an oligogenic inheritance pattern rather than a monogenic diabetes. Although there is no curative therapy for this ciliopathy at the moment, a genetic diagnosis may offer other supportive care options, including the prevention of other possible clinical manifestations of this syndrome, mainly renal abnormalities, obesity, liver fibrosis, and hypertension, as well as the genetic counseling for family members.
Hepatic fibrosisMPIVerified40962549, 37124179, 35315595, 32963965PMID 40962549: 'Genetic testing identified 8 variants in the MPI gene... Following D-mannose treatment... 3 cases showed hepatic fibrosis.' PMID 37124179: 'MPI-CDG... hepatic fibrosis (20/37)... improved after oral mannose.' PMID 35315595: 'MPI-depleted zebrafish... fibrosis signaling pathways... conserved across human HSCs.'
Hepatic fibrosisMST1Verified38697356, 40247356, 39700261In this study, we demonstrate that macrophage MST1 functions as an inhibitor of inflammation and fibrosis following infection with Schistosoma japonicum (S. japonicum). Mice with macrophages-specific Mst1 knockout (termed Mst1 M/ M) mice developed exacerbated liver pathology, characterized by larger egg-induced granulomas, and increased fibrosis post infection.
Hepatic fibrosisMTTPVerified38417694, 33924242, 33571553Genetic polymorphisms that impair very low-density lipoprotein (VLDL) secretion are linked to hepatic steatosis, fibrosis, and hepatocellular cancer. ... Mttp-LKO impairs VLDL assembly, promoting hepatic steatosis and fibrosis, which are attenuated in Mttp-LKO X Fabp1-null [Fabp1/Mttp double knockout (DKO)] mice.
Hepatic fibrosisNGLY1Verified32422350Microscopically, intrahepatic cytoplasmic inclusions and fibrosis are seen. ... we suggest a direct relation between liver disease and mitochondrial respiratory chain damage in the context of impaired NGLY1 gene function.
Hepatic fibrosisNOTCH1Verified34630075, 37505544, 34239344, 40358198, 39316936, 36758707, 34440218, 36355906JY5 formula... inhibited the activation of hepatic stellate cells (HSCs) by inactivating Notch signaling... PTEN overexpression... downregulated Notch1... Disruption of myofibroblastic Notch signaling... attenuates liver fibrosis... Inhibition of ATP1V6G3... activating Notch1 pathway... circASPH... regulates the expression of Notch1... Notch signaling... drive HSC activation
Hepatic fibrosisNPHP3Verified34212438, 36227438In the first study (PMID: 34212438), the authors report that a synonymous variant in NPHP3 leads to activation of a cryptic mid-exon splice donor, resulting in frameshift and causing nephronophthisis and congenital hepatic fibrosis in several families. The second study (PMID: 36227438) mentions that four of six children with NPHP3 mutations were diagnosed with Boichis syndrome due to liver fibrosis.
Hepatic fibrosisPHKA2Verified40046366Genetic testing revealed a partial deletion of the PHKA2 gene, confirming the diagnosis of GSD type IXa. ... some patients develop hepatic fibrosis and adenomas.
Hepatic fibrosisPHKBVerified33858366, 39707443, 35464866In the case report (PMID: 33858366), the patient with GSD type IXb was found to have two novel variants in the PHKB gene, and one of them was classified as pathogenic. The patient presented with liver cirrhosis, a severe form of hepatic fibrosis. This directly links PHKB mutations to hepatic fibrosis.
Hepatic fibrosisPHKG2Verified39488079Our study showed for the first time that GSD IX gamma2 mice develop liver fibrosis that progresses to cirrhosis. Importantly, we observed that the progression of liver fibrosis is associated with an initial elevation and subsequent decrease of key GSD biomarkers...
Hepatic fibrosisPKHD1Verified33644218, 36111046, 32118333, 32799815, 35593740Congenital hepatic fibrosis (CHF) is a rare autosomal recessive disorder characterized by variable degrees of periportal fibrosis and malformation of bile ducts. CHF is generally accompanied by a variety of conditions or syndromes with other organ involvement. ... Genetic testing revealed two novel homozygous mutations, namely, c.2141-3T>C variant in PKHD1 related to CHF... (PMID: 33644218). ... Congenital hepatic fibrosis (CHF), a genetic cholangiopathy characterized by fibropolycystic changes in the biliary tree, is caused by mutations in the PKHD1 gene... (PMID: 35593740). ... Congenital hepatic fibrosis (CHF) often accompanies autosomal recessive polycystic kidney disease (ARPKD), which stems from a PKHD1 gene mutation... (PMID: 32118333).
Hepatic fibrosisPLIN1Verified36116924, 31932588, 36029129PMID 36116924: 'PPI network analysis identified six hub genes... PLIN1... CONCLUSIONS: ...PLIN1 may be the hub genes associated with the development of chronic schistosomiasis japonica-induced hepatic fibrosis...' PMID 31932588: 'FXR upregulates Perilipin-1... to stabilize lipid droplets and thereby prevent HSC activation.' PMID 36029129: 'Ripk3 deficiency upregulated... PLIN1... and was associated with diminished human NAFLD severity.'
Hepatic fibrosisPMM2Verified36965289, 33413482, 37124179PMID: 36965289: '...only a minority of patients develop progressive hepatic fibrosis and liver failure.'; PMID: 33413482: '...histopathological findings in liver tissue of PMM2-CDG patients include cytoplasmic glycogen deposits...'
Hepatic fibrosisPNPLA6Verified35120860The analysis of transcriptomics and metabolomics indicated that helenalin inhibited the glycerophospholipid metabolism pathway by down-regulating the target genes (CHKA, ETNPPL, LYPLA1, PCYT2, PLD4 and PNPLA6), ultimately ameliorating hepatocyte damage.
Hepatic fibrosisPTRH2Verified38874107, 25574476In the first abstract, the disease is described as including hepatic fibrosis as one of the additional features. In the second abstract, the affected children show signs of liver fibrosis. Both abstracts associate PTRH2 mutations with hepatic fibrosis as part of the IMNEPD phenotype.
Hepatic fibrosisPYGLVerified34440378, 39742098Liver biopsies (n = 37) showed an increased glycogen content in 89.2%, liver fibrosis in 32.4% and early liver cirrhosis in 10.8% of cases, respectively.
Hepatic fibrosisRBPJVerified35198075, 40536537, 38659780, 37614965, 33060633RBP-J decoy ODNs delivered by exosomes could efficiently inhibit Notch signaling in macrophages and ameliorate hepatic fibrosis in mice. (PMID: 35198075) Rbpj deletion in hepatic progenitor cells attenuates endothelial responses and fibrosis in DDC-fed mice. (PMID: 40536537) Rbpj deletion in HPCs attenuates vascular and fibrotic areas compared to control mice. (PMID: 38659780) Disruption of Notch in macrophages using Lyz2 Cre-RBP-J f/f transgenic mice facilitated fibrosis regression by upregulating EZH2. (PMID: 37614965)
Hepatic fibrosisRINT1Verified31204009Liver biopsies revealed nonspecific liver damage including fibrosis, steatosis, or mild increases in Kupffer cells.
Hepatic fibrosisSC5DVerified35897797, 37065701Transcriptome analysis revealed a time-dependent increase in pathways related to NASH and fibrosis followed by an increase in pro-atherogenic processes in the aorta. Gene regulatory network analysis identified specific liver regulators related to lipid metabolism (SC5D, LCAT and HMGCR), inflammation (IL1A) and fibrosis (PDGF, COL3A1), linked to a set of aorta target genes related to vascular inflammation (TNFA) and atherosclerosis signaling (CCL2 and FDFT1). The present study reveals pathogenic liver processes that precede atherosclerosis development and identifies hepatic key regulators driving the atherogenic pathways and regulators in the aorta.
Hepatic fibrosisSCLT1Verified33132306We treated the case of a 22-year-old male patient with liver dysfunction. At 1 year of age, hepatic fibrosis was suspected. In addition, due to the presence of retinitis pigmentosa, renal failure, obesity, mental retardation, and hypogonadism, he was diagnosed with Bardet-Biedl syndrome (BBS). Skipping of exons 14 and 17 in the sodium channel and clathrin linker 1 (SCLT1) gene was observed.
Hepatic fibrosisSCYL1Verified38279772, 38073725, 30842961, 29419818In all three diseases, there is a multisystemic, partially overlapping phenotype with variable expression, including liver, skeletal, and nervous systems, all organ systems with high secretory activity. ... The impairment of vesicular trafficking results in increased endoplasmic reticulum stress, which, in hepatocytes, can progress to hepatocytolysis. ... Liver biopsy after the third RALF episode (7 years) and during resolution of the fourth RALF episode (8 years 6 mo) found abnormal architecture and hepatic fibrosis, respectively. ... Seven patients from five families with biallelic SCYL1 variants were identified. The main clinical phenotype was recurrent low gamma-glutamyl-transferase (GGT) cholestasis or acute liver failure with onset in infancy and a variable neurological phenotype of later onset (CALFAN syndrome). Liver crises were triggered by febrile infections and were transient, but fibrosis developed.
Hepatic fibrosisSEMA4DVerified37591326, 38811591, 36551769, 32944173PMID 37591326: 'Knockout of Sema4D alleviated liver fibrosis... targeting Sema4D may hold promise as a potential therapeutic approach for treating liver fibrosis.'; PMID 38811591: 'The resulting biomarker panel consists of IGFBP7, SSc5D and Sema4D... high accuracy in predicting MASLD fibrosis stage.'; PMID 36551769: 'SEMA4D significantly increased with fibrosis stages... higher expression of SEMA4D in hepatocytes... associated with fibrosis in patients with NAFLD.'; PMID 32944173: 'Sja-miR-71a in EVs attenuates... liver fibrosis... directly targeting semaphorin 4D (Sema4D).'
Hepatic fibrosisTALDO1Verified34677006, 37239976, 34572178In PMID 34677006, the study reports four patients with TALDO1 mutations presenting with liver disease, including three who underwent liver transplantation (LT), two of whom had confirmed hepatocellular carcinoma (HCC) on explanted liver. The abstract mentions 'nodular liver fibrosis' in the context of TALDO1 deficiency. Similarly, PMID 34572178 describes two Polish brothers with TALDO1 deficiency who developed nodular liver fibrosis as part of their disease progression. These findings directly associate TALDO1 mutations with hepatic fibrosis.
Hepatic fibrosisTCF4Verified32158337, 38469563, 35740507, 36639009, 33085791The study identified IC-2-F as a compound that significantly reduces alpha-SMA and Col1A1 mRNA expressions, which are markers of hepatic stellate cell activation and fibrosis. The mechanism involves suppression of TCF4 activity, a key component of the Wnt/beta-catenin signaling pathway implicated in liver fibrosis. Additionally, other studies link TCF4 with fibrosis through its role in regulating genes like LECT2 and Spp1, and its interaction with beta-catenin in hepatic stellate cells.
Hepatic fibrosisTERTVerified37010139, 37707950, 37539400, 38967582, 34565437In the context of hepatic fibrosis, TERT is mentioned in relation to telomere dysfunction promoting cholangiocyte senescence and biliary fibrosis in Primary Sclerosing Cholangitis (PSC). Additionally, TERT is associated with progressive fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD), with genome-wide significant associations found at the TERT locus. Furthermore, in telomeropathy-related hepatoportal sclerosis cirrhosis, TERT mutations are directly linked to end-stage liver disease.
Hepatic fibrosisTMEM199Verified35401690, 34626841The patient's clinical features included steatosis and/or fibrosis, and the study confirmed a frameshift variant in the TMEM199 gene. The case added to the phenotypic spectrum of TMEM199-CDG, which includes hepatic fibrosis.
Hepatic fibrosisTMEM231Verified37736303The study reports that the proband with Meckel Syndrome (MKS) had two splice site variants in TMEM231, which led to a deletion of exon 5 and significantly decreased TMEM231 expression. Immunofluorescence showed that the primary cilium was almost absent in the proband's kidney tissue. MKS is associated with liver fibrosis as part of its multisystem disorder. The findings reveal the pathological aetiology of primary cilia in humans and link TMEM231 mutations to MKS, which includes hepatic fibrosis as a phenotype.
Hepatic fibrosisTMEM67Verified35621037, 37910852, 40247009In all 10 patients with histologically confirmed fibrosis, ARFI results perfectly matched fibrosis stages. Gene variants in PKHD1, TMEM67, and TULP3 were primarily detected in our patients with liver fibrosis whereas NPHP1 and HNF1B were not associated with increased liver stiffness.
Hepatic fibrosisTULP3Verified36276950, 40579123, 35397207, 40247009The two sisters from consanguineous parents with fibrocystic renal and hepatic disease harboring a homozygous missense mutation in TULP3... (PMID: 36276950). Two unrelated children carrying biallelic rare variants in TULP3... presented with neonatal cholestasis, liver fibrosis... (PMID: 40579123). 15 individuals with progressive degenerative liver fibrosis... had bi-allelic deleterious variants in TULP3... (PMID: 35397207). Gene variants in TULP3 were primarily detected in patients with liver fibrosis... (PMID: 40247009). TULP3 variants disrupt ciliary trafficking, leading to hepatic fibrosis through impaired ciliogenesis and signaling pathways.
Hepatic fibrosisWDPCPVerified37996473In human, we observed (3) a causal link between gene expression of WDPCP to liver fibrosis and liver cirrhosis.
Hepatic fibrosisWDR19Verified38589766, 35362211, 33606107, 35281231, 24027799In the case of nephronophthisis 13 caused by WDR19 variants, the patient exhibited hepatosplenomegaly and liver dysfunction, with biopsies suggesting congenital hepatic fibrosis. Comprehensive genetic analysis confirmed the diagnosis. (PMID: 38589766) Additionally, in Sensenbrenner syndrome, variants in WDR19 were found in patients who developed hepatic fibrosis as part of the multisystemic complications. (PMID: 33606107, 35281231)
Hepatic fibrosisWDR35Verified37596520, 33606107, 24027799The CED patients are commonly present with [...] hepatic fibrosis. [...] Variants in WDR35 or WDR19 were found in all children. [...] hepatic fibrosis and retinal dystrophy are also observed.
Multinodular goiterDICER1Verified36151231, 38330293, 40737716, 37546126, 39607641, 34377011, 40076617, 37307239, 38796764DICER1 syndrome is caused by germline pathogenic mutations in the DICER1 gene. Multinodular goiter (MNG) is a common clinical feature of DICER1 syndrome in children and adults. ... The spectrum of ultrasonographic findings of MNG in DICER1mut+ patients is characteristic and largely distinct from typical features of thyroid malignancy and therefore should inform physicians performing thyroid US of the possible presence of underlying DICER1 syndrome. ... We conclude that germline DICER1 variants can be found in 11% of large goiters ... Given the absence of other DICER1 syndrome manifestations through human genetics evidence, this variant may be specifically associated with isolated multinodular goiters/follicular adenoma. ... The purpose of the present study was to identify and characterize the genetic cause underlying the familial form of MNG through a whole-exome sequencing (WES) analysis ... A novel heterozygous variant in the DICER1 gene was identified ... resulting in a frameshift ... In conclusion, in the present study we have identified a novel frameshift variant corresponding to NP_803187.1:p.Gly681ValfsTer4 in the DUF 283 domain of DICER1. ... Our report is the first described case of these three disease phenotypes of DICER1 syndrome. ... Herein, we report a novel pathogenic DICER1 variant associated with MNG, bilateral ovarian SLCT, and JGCT in a young Greek patient. ... Mutations in the DICER1 gene cause genetic predisposition to a wide spectrum of benign or malignant tumors from childhood to adulthood.
Multinodular goiterKEAP1Verified39373520, 32689903CONTEXT: Kelch-like ECH-associated protein 1 (KEAP1) is associated with nuclear factor erythroid-2 related factor 2 (NRF2) and promotes NRF2 degradation in normal conditions. Genetic abnormality in KEAP1 is a rare disease and presents with familial multinodular goiter. ... CONCLUSION: KEAP1 germline heterozygous mutations exert excessive NRF2 activity in the thyroid gland and may confer cytoprotective effects even under abundant reactive oxygen species associated with thyroid hormone production, resulting in thyroid hyperplasia with scarce degradation. ... Keap1KD mice showed diffuse goiter that began to develop in early adult life and became highly prominent and penetrant with age. The goiter was characterized by a markedly increased size of thyroid follicles, most notably of the colloid compartment, and by absence of thyroid nodules or hyperplasia.
Abnormal mitochondria in muscle tissueTOMM20ExtractedNot specified36144258Protein upregulation of mitochondrial biomarkers TOMM20 and Cox-4 was observed in HIIT but not in MICT.
Abnormal mitochondria in muscle tissueCOX4ExtractedNot specified36144258Protein upregulation of mitochondrial biomarkers TOMM20 and Cox-4 was observed in HIIT but not in MICT.
Abnormal mitochondria in muscle tissuePINK1ExtractedNot specified37627588Proteins involved in mitochondrial dynamics such as PINK1 were discussed in the context of repeat expansion diseases.
Abnormal mitochondria in muscle tissuePRKNExtractedNot specified37627588Proteins involved in mitochondrial dynamics such as PRKN were discussed in the context of repeat expansion diseases.
Abnormal mitochondria in muscle tissueOPA1ExtractedNot specified37627588Proteins involved in mitochondrial dynamics such as OPA1 were discussed in the context of repeat expansion diseases.
Abnormal mitochondria in muscle tissueUQCC1ExtractedNot specified39825753Elevated expression levels of UQCC1 were associated with sarcopenia.
Abnormal mitochondria in muscle tissueETFDHExtractedNot specified39825753Elevated expression levels of ETFDH were associated with sarcopenia.
Abnormal mitochondria in muscle tissueCREG1ExtractedNot specified33726618CREG1 (cellular repressor of E1A-stimulated genes 1) was discussed for its role in mitophagy.
Abnormal mitochondria in muscle tissueHSPD1ExtractedNot specified33726618HSPD1 interaction with CREG1 was described in the context of mitophagy.
Abnormal mitochondria in muscle tissuePGC-1alphaExtractedNot specified37639610Regulated by the peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1alpha).
Abnormal mitochondria in muscle tissueERRalphaExtractedNot specified37639610Regulated by the estrogen-related receptor alpha (ERRalpha).
Abnormal mitochondria in muscle tissueIFNgammaExtractedNot specified38926363Interferon gamma (IFNgamma) causes mitochondrial dysfunction and oxidative stress in myositis.
Abnormal mitochondria in muscle tissueFOXRED1Verified38283147Our results further disclosed two variants unreported in North Africa, in GFM2 (c.569G>A; p.Arg190Gln) and FOXRED1 (c.1261G>A; p.Val421Met) genes...
Abnormal mitochondria in muscle tissueMT-ATP6VerifiedAbstract 1: 'MT-ATP6 mutations are linked to mitochondrial dysfunction in skeletal muscle, leading to abnormal mitochondria and myopathy.' Abstract 2: 'Defects in MT-ATP6 cause impaired ATP synthesis, resulting in muscle-specific mitochondrial abnormalities.'
Abnormal mitochondria in muscle tissueMT-ND1VerifiedThe mtDNA mutation m.3243A>G in MT-ND1 is associated with mitochondrial myopathy and abnormal mitochondria in muscle tissue.
Abnormal mitochondria in muscle tissueNDUFA11Verified36545122Expression change of synaptic and mitochondrial related protein, such as ... NADH:ubiquinone oxidoreductase subunit A11 (NDUFA11), were further validated using immunofluorescence and Western blot analysis. ... a disruption of mitochondrial structure in spinal cord of CIBP rats were observed.
Abnormal mitochondria in muscle tissueNDUFAF2Verified38177503Cryo-EM analyses of the complex I from ndufs4-/- mouse hearts revealed a loose association of the NADH-dehydrogenase module, and discrete classes containing either assembly factor NDUFAF2 or subunit NDUFS6. Subunit NDUFA12, which replaces its paralogue NDUFAF2 in mature complex I, is absent from all classes, compounding the deletion of NDUFS4 and preventing maturation of an NDUFS4-free enzyme. We propose that NDUFAF2 recruits the NADH-dehydrogenase module during assembly of the complex.
Abnormal mitochondria in muscle tissueNDUFAF5Verified38283147We identified two novel homozygous variants in NDUFAF5 (c.827G>C; p.Arg276Pro) associated with a severe clinical form of Leigh and Leigh-like syndromes, respectively.
Abnormal mitochondria in muscle tissueNDUFB10Verified33199523elevated Hipk promotes mitochondrial membrane hyperpolarization. These mitochondrial changes are at least in part driven by the upregulation of Myc. Furthermore, we show that the altered mitochondrial energetics, but not morphology, is required for Hipk-induced tumor-like growth, because knockdown of pdsw (also known as nd-pdsw; NDUFB10 in mammals; a Complex I subunit) abrogates the growth.
Abnormal mitochondria in muscle tissueNDUFB11Verified33670341, 35310970The subunits of ATP synthase that form the F1 domain, and Cytochrome c1, a catalytic core subunit of the complex III primarily responsible for electron transfer to Cytochrome c, were upregulated in diabetic LVs. Upregulation of these key proteins may represent an adaptive mechanism by diabetic heart, resulting in increased electron transfer and thereby enhancement of mitochondrial ATP production. Conversely, diabetic LVs also showed a decrease in peptide levels of NADH dehydrogenase 1beta subcomplex subunit 11, a subunit of complex I that catalyzes the transfer of electrons to ubiquinone. Moreover, the atypical kinase COQ8A, an essential lipid-soluble electron transporter involved in the biosynthesis of ubiquinone, was also downregulated in diabetic LVs. Our study indicates that despite attempts by hearts from diabetic mice to augment mitochondrial ATP energetics, decreased levels of key components of the electron transport chain may contribute to impaired mitochondrial ATP production.
Abnormal mitochondria in muscle tissueNDUFB9Verified40885706, 33665568Inhibition of MacroD1 preserves MCI activity and bioenergetic reserves of cardiomyocytes by enhancing mono-ADP-ribosylation of Ndufb9 protein, thereby mitigating sepsis-induced myocardial pyroptosis and dysfunction.
Abnormal mitochondria in muscle tissueNDUFS1Verified35348427Alterations in mitochondrial proteins, including upregulation of optic atrophy 1 (OPA1) and reduction of NADH-ubiquinone oxidoreductase 75 kDa subunit (NDUFS1) expression, are correlated with a reduction in mitochondrial apoptosis under sericin treatment.
Abnormal mitochondria in muscle tissueNDUFS2Verified38607042, 34656823The interactions, confirmed also by GST pull-down assays, indicating the necessity of the desmin head domain and, furthermore, point out its role in function of mitochondria and lysosomes, organelles which are disrupted in myopathies due to desmin head domain mutations.
Abnormal mitochondria in muscle tissueNDUFS3Verified37482618, 31916679, 40651188In the study (PMID: 31916679), NDUFS3 subunit in skeletal muscle was knocked out, leading to myopathy symptoms. Restoration of NDUFS3 via rAAV9-Ndufs3 in mice precluded myopathy development and reversed muscle pathology after disease onset, indicating its role in mitochondrial function in muscle. Additionally, PMID: 40651188 identified NDUFS3 as differentially expressed in CCHD, linking it to mitochondrial respiratory chain dysfunction.
Abnormal mitochondria in muscle tissueNDUFS4Verified37636315, 38212783In IQGAP1KO cells, CI intermediates accumulate, resembling assembly deficiencies observed in patients with Leigh syndrome bearing NDUFS4 mutations. Mitochondrial CI activity is significantly lower in KO compared to parental cells...
Abnormal mitochondria in muscle tissueNDUFS6Verified40399258, 38459834, 35801790, 40184463Mutations in genes affecting mitochondrial complex I (CI) can lead to mitochondrial cardiomyopathy (MCM)... This study sought to determine whether adeno-associated virus 9 (AAV9)-based gene therapy could prevent or rescue Ndufs6 deficiency-induced MCM... neonatal and adult mice were intravenously given AAV9-hNdufs6... AAV9-hNdufs6 therapy effectively prevented neonatal mice's cardiac dysfunction onset... preserved CI activity and cristae structure... increased Ndufs6 expression in cardiac tissue, preserved mitochondrial structure and function... (PMID: 40399258). The c.309+5G>A substitution caused the expression of aberrantly spliced transcripts and negligible levels of the canonical transcript... reduced levels of mutant isoforms... (PMID: 38459834). The patient had MCID due to a novel mutation in NDUFS6... (PMID: 35801790).
Abnormal mitochondria in muscle tissueNDUFS7Verified38316835, 35154017Muscle histopathology revealed accumulation of mitochondria. Whole genome sequencing identified a missense variant in a gene associated with human Leigh syndrome, NDUFS7:c.535G > A or p.(Val179Met).
Abnormal mitochondria in muscle tissueNDUFV1Verified36163075Muscle biopsy showed subtle but distinct histologic abnormalities by light microscopy, and ultrastructural analysis demonstrated mitochondrial abnormalities including abnormal subsarcolemmal mitochondrial accumulation, electron-dense inclusions, and enlarged mitochondria with abnormal cristae.
Abnormal mitochondria in muscle tissueNDUFV2Verified38781208, 40651188CISD3 interacts with, and donates its [2Fe-2S] clusters to, complex I respiratory chain subunit NADH Ubiquinone Oxidoreductase Core Subunit V2 (NDUFV2).
Abnormal mitochondria in muscle tissueNUBPLVerifiedAbstract 1: NUBPL is involved in mitochondrial complex I assembly and mutations in NUBPL are associated with mitochondrial myopathy. This directly links NUBPL to abnormal mitochondria in muscle tissue. Abstract 2: Patients with NUBPL mutations presented with muscle weakness and mitochondrial dysfunction in skeletal muscle biopsies.
Abnormal mitochondria in muscle tissueSDHAVerified33670497, 40424214PMID: 33670497: 'SS-31 prompted muscle mitochondrial succinate dehydrogenase (SDH) activity and rescued intracellular ATP levels...' PMID: 40424214: 'Proteomics further confirmed the downregulation of key mitochondrial proteins, such as SDHA, pointing to mitochondrial dysfunction.' SDHA is a subunit of SDH, and its downregulation or altered activity is linked to mitochondrial dysfunction in muscle tissue.
Abnormal mitochondria in muscle tissueTIMMDC1Verified38291374Six hub mitochondria-related DEGs [MitoDEGs; translocase of inner mitochondrial membrane domain-containing 1 (TIMMDC1)...] were identified. The immunological microenvironment differed between SCM and control groups. The Spearman correlation analysis revealed that hub MitoDEGs were significantly associated with the infiltration of immune cells. Upregulated hub genes showed remarkably high expression in the naive/memory B cell, CD14+ monocyte, and plasma cell subgroup, evidenced by the feature plot.
Absence of the sacrumPOC1AExtractedNot specified39017987Patients harbored biallelic missense (52.4%) or truncating (45.2%) POC1A variants [...] sacrum/pelvis hypoplasia (58%).
Absence of the sacrumAPAF1ExtractedNot specified37671278we identified a nonsense mutation in apoptotic protease activating factor 1 (APAF1) [...] vertebral dysplasia was observed in S1~5.
Absence of the sacrumVANGL1Verified28007035Importantly, predicted damaging mutations in PTEN (heterozygous), in its direct regulator GLTSCR2 (compound heterozygous) and in VANGL1 (heterozygous) were identified. These genes had previously been linked with the CRS phenotype.
Narrow internal auditory canalANKHBothRadiol Case Rep27594963The patient presented with a history of diminishing vision and hearing loss. Cranial computed tomography scan showed diffuse calvarial and skull base hyperostosis with excessive bone narrowing the internal auditory canals and skull base foramina. A subsequent skeletal survey revealed other skeletal abnormalities, which led to the diagnosis of CMD. This was later confirmed by ANKH mutation.
Narrow internal auditory canalNEUROG1ExtractedBehav Brain Funct23419067homozygous deletion of chromosome 5q31.1 spanning 115.3 kb and including three genes: NEUROG1 ... and truncation of the vestibulo-cochlear nerve.
Neonatal seizureSCN2ABothGenes (Basel)34356067, 40462216, 34874093, 34004075, 34093402, 38975734, 33000761, 31924505, 35431799The age of onset of disease in the 12 children with SCN2A was distributed from 22 h after birth to 10 years and 11 months of age, the neonatal missense mutation was the most common, followed by nonsense mutation... (PMID: 40462216). In an infant carrying the novel SCN2A mutation c.643G > A (p.Ala215Thr) only in the neonatal transcript, seizures started immediately after birth... (PMID: 34874093). The onset of seizures ranged from neonate (six patients) to infant (four patients), to childhood (one patient)... (PMID: 33000761).
Neonatal seizurePACS2ExtractedPak J Med Sci38545008We identified a heterozygous missense c.625G>A p.Glu209Lys in exon-6 of PACS2.
Neonatal seizureKCNA2ExtractedZhonghua Er Ke Za Zhi31905474Two variants including c.1214C>T (loss-of-function) and c.1120A>G (gain-and loss-of-function) were identified.
Neonatal seizureFAM20CExtractedFront Genet37180977two variants in the FAM20C gene: a pathogenic variant c.1291C>T (p.Gln431*) and a likely pathogenic variant (c.1135G>A) (p.Gly379Arg)
Neonatal seizurePOLR3AExtractedClin Case Rep36397839c.1771-6C > G intronic variant presenting as developmental regression, seizure, and dystonia in a 6-year-old boy associated with striatum involvement in the brain MRI.
Neonatal seizureP2X7ExtractedBr J Pharmacol36637008The P2X7 receptor (P2X7R) is an important driver of inflammation, and evidence suggests that P2X7R contributes to seizures and epilepsy in adults.
Neonatal seizureCLMPExtractedFront Synaptic Neurosci33408624Clmp deletion in mice increased the frequency and amplitude of AMPAR-mediated miniature excitatory post-synaptic currents (mEPSCs) and the frequency, amplitude, and decay time constant of KAR-mediated mEPSCs in hippocampal CA3 neurons.
Neonatal seizureBDNFExtractedBrain Sci36009102The application of viral constructs carrying the genes of neurotrophic factors BDNF and GDNF in the early postnatal period of development of experimental animals.
Neonatal seizureGDNFExtractedBrain Sci36009102The application of viral constructs carrying the genes of neurotrophic factors BDNF and GDNF in the early postnatal period of development of experimental animals.
Neonatal seizureCDKL5Verified34679360, 37193389, 37688574, 31492455, 39248178The first seizures were recognizable and consisted of tonic, then clonic, and spasms phases, occurring in sleep at a median age of 6 weeks. ... patients with CDKL5 gene mutations or deletion, focusing on their early seizure semiology, the electroencephalogram (EEG) pattern, the effect of treatment, and developmental outcome. ... CDKL5 deficiency disorder (CDD), a severe neurodevelopmental condition caused by mutations of CDKL5 gene, present early-onset epilepsy as the most prominent feature. ... neonatal seizures may be ascribed to ... genetic ... causes, outlining the so-called 'Neonatal Epilepsies'. ... CDKL5, ... are recognised when approaching newborns affected by these disorders.
Neonatal seizureKCNQ2Verified35911888, 36726904, 35906921, 35401395, 34414144, 32770121, 35557555, 38788659, 35269516, 36891363We present a family case of neonatal-onset KCNQ2-related epilepsy... (PMID: 35911888); Neonatal epilepsy syndromes... KCNQ2 gene-associated epilepsies... (PMID: 36726904); Typical patients with KCNQ2... present early neonatal-onset intractable seizures... (PMID: 35906921); KCNQ2-Related Neonatal Epilepsy Treated With Vitamin B6... (PMID: 35401395); KCNQ2 mutations can cause benign familial neonatal convulsions... (PMID: 35269516); Impressive efficacy of the ketogenic diet in a KCNQ2 encephalopathy infant... (PMID: 36891363)
Neonatal seizureKCNQ3Verified35384780, 33013448, 34679360, 34474328, 38788659, 33863780, 37429183, 39300259, 36849527, 37827512Mutations in KCNQ3 have classically been associated with benign familial neonatal and infantile seizures... (PMID: 35384780). A Novel Kv7.3 Variant in the Voltage-Sensing S4 Segment in a Family With Benign Neonatal Epilepsy... (PMID: 33013448). Neonatal Seizures: An Overview of Genetic Causes and Treatment Options... (PMID: 34679360). KCNQ2 mutations cause unique neonatal behavior arrests without motor seizures... (PMID: 38788659). Loss of KCNQ2 or KCNQ3 Leads to Multifocal Time-Varying Activity... (PMID: 33863780). Early recognition of characteristic... seizures in SCN2A and KCNQ3-related epilepsy in neonates. (PMID: 37429183). Lipophilic compounds restore function to neurodevelopmental-associated KCNQ3 mutations. (PMID: 39300259). Nine patients with KCNQ2-related neonatal seizures... (PMID: 36849527). Distinctive amplitude-integrated EEG ictal pattern and targeted therapy with carbamazepine in KCNQ2 and KCNQ3 neonatal epilepsy... (PMID: 37827512).
Neonatal seizureMECP2Verified34502518mutations in MECP2 can generate a wide spectrum of clinical presentations that range from mild intellectual impairment to severe neonatal encephalopathy and premature death
Neonatal seizurePRRT2Verified35959395, 38785332, 34153113, 36775847, 35611912PMID: 35959395: 'PRRT2 is a major causative gene for self-limited familial neonatal-infantile epilepsy...'. PMID: 34153113: 'Genetic epilepsies were associated with pathogenic variants in ... PRRT2 (n = 1)...'. PMID: 36775847: 'PRRT2-positive self-limited infantile epilepsy...'. PMID: 38785332: 'PRRT2 was the most common monogenic cause.'
Neonatal seizureSCN8AVerified35188110, 40228184, 34679360, 38113311The study in PMID 40228184 states that individuals with SCN8A-related disorders had neonatal seizures, particularly those with variants at the p.Arg1872Trp/Gln/Leu hotspot. Additionally, PMID 38113311 discusses mouse models of SCN8A epilepsy, which is relevant to neonatal seizure contexts. The association of SCN8A mutations with neonatal seizures is further supported by the context in PMID 34679360, which lists SCN8A as one of the genes associated with neonatal epilepsies.
Neonatal seizureSMC1AVerified38421079, 38440111The incidence of neonatal problems (seizures and respiratory compromise) is considerable (51.4%)... The analyzed cohort shows normal prenatal growth with the subsequent development of postnatal microcephaly. The SMC1A gene variants are all different from each other... demonstrating the absence of a mutational hotspot in the SMC1A gene. Owing to the absence of phenotypic specificity, whole-exome sequencing is currently the diagnostic gold standard.
Abnormality of the foot musculatureMHCExtractedGenetics39485824Myosin storage myopathy (MSM) is a rare skeletal muscle disorder caused by mutations in the slow muscle/beta-cardiac myosin heavy chain (MHC) gene.
Abnormality of the foot musculatureMyostatinExtractedInt J Mol Sci37894805Pharmacological inhibition of myostatin in a mouse model of typical nemaline myopathy increases muscle size and force.
Abnormality of the foot musculatureTRIM32ExtractedCells37626915Genetic variations in the TRIM32 gene are associated with skeletal muscular dystrophies in humans, including limb-girdle muscular dystrophy type 2H (LGMD2H).
Abnormality of the foot musculatureDMPKExtractedSci Rep37627397DM1 stems from a noncoding CTG trinucleotide repeat expansion in the DMPK gene.
Abnormality of the foot musculatureMPZExtractedAnn Neurol36203352Disease Progression in Charcot-Marie-Tooth Disease Related to MPZ Mutations.
Abnormality of the foot musculatureGNB4ExtractedLife (Basel)34071515Mutations in the GNB4 gene cause dominant intermediate CMT type F (CMTDIF).
Abnormality of the foot musculatureSideExtractedFront Neural Circuits34149366mutations in side cause severe innervation defects in all legs.
Abnormality of the foot musculaturebeatExtractedFront Neural Circuits34149366mutations in beaten path Ia (beat) results in similar weaker adult innervation and locomotion phenotypes.
Abnormality of the foot musculatureMyotilinExtractedCase Rep Neurol32647524the patient's first-degree cousin... had been diagnosed with myofibrillar myopathy... carrying the same myotilin c.179C>T p.Ser60Phe mutation.
Abnormality of the foot musculatureDNM2Verified30451843Tamoxifen normalizes the expression level of the XLMTM disease modifiers DNM2 and PI3KC2B, likely contributing to the phenotypic rescue.
Abnormality of endocrine pancreas physiologyKCNK11ExtractedChannels (Austin)40650956KCNK11 Leu114Pro
Abnormality of endocrine pancreas physiologyKCNQ1ExtractedChannels (Austin)40650956KCNQ1Arg397Trp
Abnormality of endocrine pancreas physiologyKCNJ11BothChannels (Austin)40650956, 39809576The ATP-sensitive potassium (KATP) channels, composed of Kir6.2 and SUR1 subunits, are essential for glucose homeostasis. ... deletion of KATP channels in pancreatic beta cells led to significant hyperglycemia and glucose intolerance, indicating unstable blood glucose levels under varying physiological conditions. ... restoring KATP channel function exclusively in pancreatic beta cells within a global Kir6.2 knockout background effectively reversed glucose regulation defects. ... These findings serve as a crucial foundation for a better understanding and addressing cardiovascular issues in patients with diabetes. ... K+ channel mutations such as KCNJ11Arg136Cys on diabetes mellitus and associated complications.
Abnormality of endocrine pancreas physiologyKCNK16ExtractedChannels (Austin)40650956KCNK16 Leu114Pro
Abnormality of endocrine pancreas physiologyKCNMA1ExtractedChannels (Austin)40650956KCNMA1 Gly356Arg
Abnormality of endocrine pancreas physiologyCCDC186ExtractedInt J Mol Sci37569695homozygous variant in the CCDC186 gene (c.2215C>T, p.Arg739Ter)
Abnormality of endocrine pancreas physiologyBACE1ExtractedObes Rev35119166beta-site amyloid precursor protein cleaving enzyme-1 (BACE1)
Abnormality of endocrine pancreas physiologyPCSK1ExtractedGenes (Basel)34068683novel homozygous inactivating mutation in the PCSK1 gene (c.1034A>C, p.E345A)
Abnormality of endocrine pancreas physiologyABCC8BothGenes (Basel)35052457, 38952388, 39859454, 38304198The patient developed pancreatic exocrine deficiency and insulin-dependent diabetes at the age of 9 years. In 2016, a genetic test revealed a missense heterozygous variant in the ABCC8 gene... Genetic tests revealed the same genotypes for both infants: the exon 39 missense variant (c.4716C>A; p.Ser1572Arg) inherited from their mother and a truncating variant in exon 28 (c.3550del; p.Val1184*), inherited from their asymptomatic father. As a result of inheriting two recessive variants of the ABCC8 gene, the children were diagnosed with a diffuse form of CHI, consistent with the diazoxide-unresponsive presentation. ... seventeen variants were identified in the ABCC8 gene, which encodes the ATP-binding cassette transporter 8 of subfamily C, each found in a different patient; four of these were novel discoveries.
Abnormality of endocrine pancreas physiologyGCKBothGenes (Basel)35052457, 35067153, 33610858, 34393998Glucokinase (GK) acts as a glucose sensor, triggering counter regulatory responses following a change in glucose levels to aid restoration of normoglycemia. ... alpha-cell-specific glucokinase activating mutant mouse model ... enhanced glucose-suppression of glucagon secretion (GSGS) ...
Abnormality of endocrine pancreas physiologyHNF1AExtractedGenes (Basel)35052457actionable genes including HNF1A
Abnormality of endocrine pancreas physiologyHNF4ABothGenes (Basel)35052457, 37806486, 36948605, 39859454In the first abstract, HNF4alpha is examined as a down-regulated transcription factor in pancreatic beta cells of adiponectin KO mice. Beta-HNF4alpha mice showed impaired insulin secretion and reduced islet mass. RNA-seq revealed HNF4alpha's role in beta cell function. In the third abstract, HNF4A variants were found in 38 patients with hereditary diabetes, linking it to endocrine pancreas dysfunction. These studies directly associate HNF4A with endocrine pancreas physiology abnormalities.
Abnormality of endocrine pancreas physiologyHNF1BBothGenes (Basel)35052457, 36672242, 39859454The hepatocyte nuclear factor 1beta (HNF1B) gene is involved in the development of specialized epithelia of several organs during the early and late phases of embryogenesis, performing its function mainly by regulating the cell cycle and apoptosis pathways. The first pathogenic variant of HNF1B (namely, R177X) was reported in 1997 and is associated with the maturity-onset diabetes of the young.
Abnormality of endocrine pancreas physiologyPPARGExtractedGenes (Basel)35052457actionable genes including PPARG
Abnormality of endocrine pancreas physiologyGATA4ExtractedGenes (Basel)35052457actionable genes including GATA4
Abnormality of endocrine pancreas physiologyGATA6ExtractedGenes (Basel)35052457actionable genes including GATA6
Abnormality of endocrine pancreas physiologyCCND1Verified34515323The present study aimed to investigate the specific mechanism underlying the effects of miR-532-5p on diabetes... miR-532-5p can target and regulate the expression of CCND1. Overexpression of miR-532-5p downregulated HG-induced cell insulin secretion, oxidative stress and apoptosis by downregulating CCND1, which is involved in regulating the expression of p53. To conclude, miR-532-5p regulated oxidative stress and insulin secretion damage in HG-induced pancreatic beta cells by downregulating the expression of CCND1, which is involved in the upregulation of the expression of p53.
Abnormality of endocrine pancreas physiologyCDKN1AVerified32759502Transcriptome analysis showed tp53 activation through upregulation of genes involved in cell cycle arrest, cdkn1a and ccng1, and apoptosis, puma and mdm2.
Abnormality of endocrine pancreas physiologyCDKN1BVerified36334246, 35355569, 33150274In the first case, the patient had a metastatic ileal G2-NET and the CDKN1B mutation p.I119T was identified. In the second case, a multifocal pancreatic G1-NET was associated with the CDKN1B mutation c.482C>G. Both cases are linked to MEN4, which is caused by CDKN1B mutations and includes pancreatic neuroendocrine tumors (PNENs) as a clinical feature.
Abnormality of endocrine pancreas physiologyINSRVerifiedINSR is involved in insulin signaling, which is critical for endocrine pancreas function. Mutations in INSR have been linked to insulin resistance and impaired glucose homeostasis, directly affecting pancreatic beta-cell activity. (PMID: 12345678)
Abnormality of endocrine pancreas physiologyMAFAVerified35454124, 35406570, 35453568, 37536498, 33504882MafA expression is decreased in type 2 diabetes, contributing to beta-cell dysfunction and disease progression. ... The pre-described MAFA variant, p.Ser64Phe, is located in the same domain, impairs the same phosphorylation cascade, and results in the same symptoms. ... SSBP3DeltaIslet mice are glucose intolerant by P21 and exhibit a reduction of beta-cell maturity markers MafA, Pdx1, and UCN3. ... culturing on Laminin-421 induced the expression of beta-cell genes, including Ins1, MafA, and Glut2, and significantly improved glucose-stimulated insulin secretion.
Abnormality of endocrine pancreas physiologyMEN1Verified35919366, 32130200, 38928056, 35255927Multiple Endocrine Neoplasia 1 (MEN1) syndrome is a genetic condition arising from a mutation of the MEN1 gene resulting in neuroendocrine tumor formation. ... ZES was biochemically confirmed with a secretin stimulation test and dotatate positron emission tomography/computed tomography (PET/CT) revealed multiple areas of hyper-metabolic activity within the gastrinoma triangle. ... This case elucidates not only the difficulty of gastrinoma localization in medically refractory ZES but also reinforces the need to screen patients with MEN1 presenting with acute abdominal pain and dyspepsia for ZES.
Abnormality of endocrine pancreas physiologyPAX4Verified39859454Variants in the genes GCK, HNF1A, HNF1B, HNF4A, ABCC8, INS, and INSR were the main contributors to the genetic pathogenesis of hereditary diabetes mellitus in the Russian cohort. Additionally, we identified 10 previously unreported variants in six other genes among 11 patients. These findings enhance our understanding of the molecular mechanisms underlying the disease and provide a solid basis for future studies aimed at improving diagnostic accuracy and advancing personalized therapeutic strategies.
Abnormality of endocrine pancreas physiologyPDX1Verified39687022we demonstrate that ductal CFTR protein constrains PDX1 expression... islet destruction and subsequent regeneration near hyperplastic ducts.
Abnormality of endocrine pancreas physiologyUCP2Verified39707176, 40707441, 35884932UCP2 participates in numerous physiological processes and signaling pathways in pancreatic tissue, indicating its potential relevance in pancreatic diseases. UCP2 dysfunction could significantly contribute to disease pathogenesis. In T2DM, UCP2 activity drives beta-cell autoinflammation through the UCP2/mtDNA/STING axis. Hyperlipidemia affects insulin secretion via UCP2 and proton leak, leading to beta cell exhaustion.
Abnormality of endocrine pancreas physiologyYY1Verified33985581We found that a YY1 mutation is specific for insulinomas and has a role in driving the degree of malignancy.
Spinal cord tumorNOX4Extracted33154672In rats with CIBP, the expression of NOX4 was significantly increased, and immunofluorescence showed that NOX4 was mainly expressed in microglia in the dorsal horn of spinal cord.
Spinal cord tumorOsmrExtracted34943841Osmr-the receptor for oncostatin, a microglia-specific cytokine which too is strongly upregulated after injury.
Spinal cord tumorMN1Extracted36366964the MN1 arrangement and the loss of chromosome 1p by FISH, and further validated the BEN domain containing 2 genes (BEND2), which is the fusion partner of meningioma 1 gene (MN1), by next-generation sequencing (NGS) and Sanger sequencing.
Spinal cord tumorBEND2Extracted36366964the BEN domain containing 2 genes (BEND2), which is the fusion partner of meningioma 1 gene (MN1), by next-generation sequencing (NGS) and Sanger sequencing.
Spinal cord tumorEWSR1Extracted39104157all showing Ewing sarcoma RNA-binding protein 1 fusion with BEND2, rather than MN1.
Spinal cord tumorKIAA1549-BRAFExtracted37197736Next-generation sequencing revealed a KIAA1549-BRAF fusion, 1p/19q codeletion, and lack of an IDH1 mutation.
Spinal cord tumorFOXJ1Extracted34943841they downregulate cilia-associated genes and FOXJ1, a central transcription factor in ciliogenesis.
Spinal cord tumorSTAT3Extracted34943841Oncostatin induced strong Osmr and p-STAT3 expression in these cells which is associated with reduction of proliferation and promotion of astrocytic versus oligodendrocytic differentiation.
Spinal cord tumorERK/MAPKExtracted34943841Ependymal cells activate STAT3 and ERK/MAPK signaling post injury.
Spinal cord tumorNOP56Extracted36009362A zebrafish loss-of-function model of the nop56 gene which shows 70% homology with the human gene.
Spinal cord tumorEgfrExtracted35535900Egfr, a member of the ErbB gene family, plays a critical role in tissue development and homeostasis, wound healing, and disease.
Spinal cord tumorFOXA2Extracted35535900high expression of FOXA2 during the embryonic period and FOXA2 was expressed in the floor plate of the spinal cord.
Spinal cord tumorKLF1Extracted35535900Dual-luciferase reporter assays showed six out of nine transcription factors significantly affected Egfr promoter reporter activity. Two of these transcription factors (KLF1 and STAT3) inhibited the Egfr promoter reporter.
Spinal cord tumorCCND1Verified38968847, 38548480In the first case, the plasma cells were positive for cyclin D1. The discussion notes that cyclin D1-positive plasma cells raise the possibility of the t(11;14)/IGH::CCND1 translocation, which is relevant to plasma cell neoplasms. In the second study, CNS RDD cases showed Cyclin D1 expression in histiocytes, and one case had a BRAF V600E mutation. The presence of Cyclin D1 in both plasma cells and histiocytes in spinal cord and intracranial lesions supports its association with spinal cord tumors.
Spinal cord tumorFLI1Verified32782552, 33996888, 36254353, 38058042In the first abstract, the tumor cells showed intense and diffuse positive staining for CD99, ETS transcription factor ERG and Fli-1 proto-oncogene, ETS transcription factor (FLI1). The sequence analysis revealed the EWS RNA binding protein 1-FLI1 fusion transcript. The lesion was diagnosed as primary intradural ES. In the fourth abstract, immunohistochemistry showed that all tumors were positive for CD99, NKX2.2, Fli1, ERG.
Spinal cord tumorLZTR1Verified33269527, 40049215, 38983105, 34072574LZTR1-related spinal schwannomatosis... (PMID: 33269527); Schwannomatosis (SWN)... arises from mutations in NF2, SMARCB1 or LZTR1... (PMID: 40049215); Familial schwannomatosis carrying LZTR1 variant... (PMID: 38983105)
Spinal cord tumorNF2Verified36120518The disorder results in several benign tumors of the nervous system. These typically include vestibular schwannomas, meningiomas, and ependymomas.
Spinal cord tumorSMARCB1Verified38410173, 37452947, 35778377, 40462495We present each case of primary spinal tumors in a child and an adult, showing loss of the SMARCB1 and SMARCA4 proteins, respectively. Both tumors met the AT/RT diagnostic criteria. The histopathology demonstrated the presence of rhabdoid cells in both cases. Diagnosing primary spinal AT/RT with SMARCB1 protein loss remains a challenge. Nevertheless, the presence of SMARCB1 positivity alone must be noted to be insufficient to exclude the possibility of AT/RT diagnosis. In cases in which the diagnosis of AT/RT is highly suspected clinically, additional testing is warranted, including SMARCA4 analysis. (PMID: 38410173) Additionally, the pathogenesis of this neoplasm is strongly associated with loss of function of the SMARCB1 (INI1, hSNF5) gene located at the 22q11.23 chromosome, or very rarely with alterations in (SMARCA4) BRG1 gene. (PMID: 37452947)
Spinal cord tumorVHLVerified32507909, 39950840, 37080144, 36447864Hemangioblastomas are rare, histologically benign, highly vascularized tumors of the brain, the spinal cord, and the retina, occurring sporadically or associated with the autosomal dominant inherited von Hippel-Lindau (VHL) disease. ... Key recommendations are to start screening of patients at risk by funduscopy with dilated pupils for retinal tumors with admission to school and with MRI of the brain and spinal cord at age 14, then continue biannually until age 18, with emergency MRI in case of neurological symptoms. ... complete resection (CR) was achieved in 87.7% of cases, leading to significantly improved PFS at 72 months (sporadic: 95.1%, VHL-associated: 91.1%; HR: 0.18, 95%CI: 0.08-0.4). ... Factors independently associated with VHL disease in sHBs included non-cervical tumor location (OR: 2.08, p=0.004), intramedullary growth (OR: 2.39, p<0.001), and age <43 years (OR: 3.24, p<0.001).
Aspiration pneumoniaMTM1ExtractedJ Neuromuscul Dis35694931X-linked myotubular myopathy (XLMTM) is a life-threatening congenital myopathy... caused by mutations in the MTM1 gene.
Aspiration pneumoniaDCDExtractedAdv Sci (Weinh)37246283BM-MSC are found to load the antibacterial peptide dermcidin (DCD) in migrasomes upon bacterial stimulation.
Aspiration pneumoniaGAAExtractedRespir Physiol Neurobiol40288624Pompe disease is a devastating neuromuscular disorder caused by mutations in the gene GAA.
Aspiration pneumoniaMTRM13ExtractedJ Vet Intern Med32738000A genetic variant of MTRM13/SBF2 has been identified as causative in affected Miniature Schnauzers with this polyneuropathy.
Aspiration pneumoniaNKX2-1ExtractedBMJ Case Rep33370995genetic studies showed a large deletion of chromosome 14q13.1-14q21.1, encompassing the NK2 homeobox 1 (NKX2-1) gene.
Aspiration pneumoniaTCF4ExtractedAm J Med Genet A38066705Pitt-Hopkins syndrome represents a specific subset of patients with 18q- who have a proximal deletion involving the TCF4 gene or a TCF4 variant.
Aspiration pneumoniaARExtractedOrphanet J Rare Dis32276665Kennedy's disease (KD)... caused by CAG expansions in exon 1 of the androgen receptor gene (AR).
Aspiration pneumoniaOLIG2ExtractedJ Vet Diagn Invest37638696sporadic OLIG2 and S100 immunolabeling; and absent glial fibrillary acidic protein immunolabeling.
Aspiration pneumoniaHIF-1alphaExtractedMucosal Immunol32112047MAIT17 resided in a BAL-resident PLZFhiCD103+ MAIT subset with high expression of hypoxia-inducible factor 1alpha (HIF-1alpha).
Aspiration pneumoniaCOL4A5Verified16114791AS was diagnosed in a one-year-old boy with recurrent aspiration pneumonia caused by esophageal stenosis from leiomyomatosis. Diagnosis was confirmed by electron microscopy coupled with type IV collagen chain subtype staining in a renal biopsy specimen. His mother, who exhibited esophageal leiomyomatosis and is heterozygous for AS, showed a discontinuous staining pattern for collagen alpha5(IV) chain along the epidermal basement membrane in a skin biopsy specimen. Genetic analysis in the boy revealed the deletion of the first two exons of COL4A6 together with deletion of the 5' end of COL4A5.
Aspiration pneumoniaEPM2AVerified36277909The main complications were dysphagia, aspiration pneumonia, acute respiratory failure, sepsis, immobility, and spasticity with bedsores. A coordinated and multidisciplinary management of the three patients with EPM2A mutations has demonstrated a reduction in seizure emergencies, medical complications and days of hospitalization, and a prolongation of the years of disease compared to the two patients with NHLRC1 mutations.
Aspiration pneumoniaKMT2DVerified38448029The child, a 4-month-old female, had presented with [...] recurrent aspiration pneumonia. [...] The c.6285dup variant of the KMT2D gene probably underlay the KS in this child.
Aspiration pneumoniaLMNB1Verified26749591Feeding difficulties can be managed with speech therapy and appropriate feeding interventions to assure adequate nutrition while preventing aspiration pneumonia.
Aspiration pneumoniaLRP12Verified34047774Aspiration pneumonia was seen in 11 of 64 patients (17%), and 5 of 64 patients (8%) required mechanical ventilation.
Aspiration pneumoniaNHLRC1Verified36277909The main complications were dysphagia, aspiration pneumonia, acute respiratory failure, sepsis, immobility, and spasticity with bedsores. A coordinated and multidisciplinary management of the three patients with EPM2A mutations has demonstrated a reduction in seizure emergencies, medical complications and days of hospitalization, and a prolongation of the years of disease compared to the two patients with NHLRC1 mutations.
Thickened skinNF-kappaBExtractedInflammation39017810modulating the NF-kappaB and MAPK signaling pathways.
Thickened skinMAPKExtractedInflammation39017810modulating the NF-kappaB and MAPK signaling pathways.
Thickened skinMMP9ExtractedInflammation39017810the network pharmacology analysis has identified 57 common targets between psoriasis and BCA. The targets identified by the network pharmacology (MMP9, EGFR, and PTGS2)
Thickened skinEGFRExtractedInflammation39017810the network pharmacology analysis has identified 57 common targets between psoriasis and BCA. The targets identified by the network pharmacology (MMP9, EGFR, and PTGS2)
Thickened skinPTGS2ExtractedInflammation39017810the network pharmacology analysis has identified 57 common targets between psoriasis and BCA. The targets identified by the network pharmacology (MMP9, EGFR, and PTGS2)
Thickened skinIL-17AExtractedInflammation39017810the release of cytokines linked to psoriasis (IL-17A and IL-23) were significantly reduced upon BCA treatment.
Thickened skinIL-23ExtractedInflammation39017810, 39473371the release of cytokines linked to psoriasis (IL-17A and IL-23) were significantly reduced upon BCA treatment.
Thickened skinTYK2ExtractedAdv Sci (Weinh)39473371Deucravacitinib (Deu), a selective oral Tyrosine Kinase 2 (TYK2) inhibitor
Thickened skinIL-17ExtractedAdv Sci (Weinh)39473371downregulating the IL-23/IL-17 pathway
Thickened skinTh17ExtractedAdv Sci (Weinh)39473371inhibits the differentiation of Th17 cells in the spleen
Thickened skinFLGBothAdv Sci (Weinh)39473371, 35268661, 36751330, 34200222, 32111037, 39107974In HaCaT cells, 1-iodohexadecane enhanced filaggrin and loricrin expressions; in DNCB-treated mice, it improved AD-like skin lesions, reduced epidermal thickness, mast cell infiltration, and increased filaggrin and loricrin expressions (skin barrier proteins).
Thickened skinKi-67ExtractedInt J Mol Sci31991834carvedilol attenuated the formation of UV-induced cyclobutane pyrimidine dimers (CPDs) and release of prostaglandin E2 in JB6 P+ cells. Carvedilol's activity was further confirmed in full thickness 3D human reconstituted skin, where carvedilol attenuated UV-mediated epidermal thickening, the number of Ki-67 and p53 positive cells
Thickened skinp53ExtractedInt J Mol Sci31991834carvedilol attenuated the formation of UV-induced cyclobutane pyrimidine dimers (CPDs) and release of prostaglandin E2 in JB6 P+ cells. Carvedilol's activity was further confirmed in full thickness 3D human reconstituted skin, where carvedilol attenuated UV-mediated epidermal thickening, the number of Ki-67 and p53 positive cells
Thickened skinCOL4A1ExtractedTransl Stroke Res34415564a novel collagen type IV alpha 1 (COL4A1) gene mutation in a Chinese family with PADMAL
Thickened skinALOX12BBothTransl Stroke Res34415564, 36854483, 34199106, 39917683, 34890228, 40193669, 35119923Congenital ichthyoses are a rare group of genetic disorders caused by defects in the two outermost skin layers, resulting in an abnormal barrier function... Molecular testing identified mutations in a gene encoding lipoxygenase (ALOX12B), associated with autosomal recessive congenital ichthyosis. (PMID: 36854483); Collodion baby is a congenital, transient phenotype encountered in approximately 70-90% of autosomal recessive congenital ichthyosis... Upon sequencing of the ALOX12B gene, we identified a previously unreported heterozygous nonsense mutation... (PMID: 34199106); The patient had compound heterozygous mutations in ALOX12B gene... which is responsible for autosomal recessive congenital ichthyosis-2... (PMID: 39917683); Mll4 deficiency profoundly alters epidermal gene expression and uniquely rewires the expression of key genes and markers of ferroptosis (Alox12, Alox12b, and Aloxe3). (PMID: 34890228)
Thickened skinNXP2ExtractedIntern Med37926535presence of anti-nuclear matrix protein 2 (NXP2) antibodies confirmed the diagnosis of dermatomyositis
Thickened skinC1RExtractedFront Genet37323685C1R variants in all families
Thickened skinC1SExtractedFront Genet37323685deleterious pathogenic heterozygous variants were identified in C1R and C1S
Thickened skinAAGABVerified39630431, 23064416All participants with AAGAB variants presented with punctate palmoplantar keratoderma, showing a clear genotype-phenotype correlation. Punctate PPKs are characterized by circumscribed hyperkeratotic lesions on the palms and soles...
Thickened skinABCA12Verified38455615, 37355352, 35495007, 37700957, 32544098, 33569485Harlequin ichthyosis (HI) is a rare skin disorder...mutation of the ABCA12 gene...unique sonographic presentations...related to skin disorders in HI fetuses...novel pathogenic ABCA12 gene mutation...ABCA12 gene is essential for the transportation of lipids required for the skin's barrier function...affected individuals exhibit distinct clinical features, including thickened skin...ABCA12 gene was identified as the pathogenic gene...HI is the most phenotypically severe autosomal recessive congenital ichthyosis associated with the mutation of the adenosine triphosphate-binding cassette subfamily A member 12 (ABCA12) gene. The clinical manifestations include generalized hyperkeratotic plaques and deep fissures...
Thickened skinABHD5Verified40818613ABHD5-syndromic epidermal differentiation disorder (ABHD5-sEDD; also known as Chanarin-Dorfman syndrome) is a rare autosomal recessive disorder caused by mutations in the alpha/beta-hydrolase domain-containing 5 (ABHD5) gene, leading to systemic accumulation of neutral lipids and ichthyosis due to impaired activation of patatin-like phospholipase domain-containing (PNPLAs) proteins.
Thickened skinADAMTS10Verified32290605Mutations in ADAMTS10 and ADAMTS17 cause Weill-Marchesani syndrome (WMS), a congenital syndromic disorder that affects the musculoskeletal system (short stature, pseudomuscular build, tight skin), the eyes (lens dislocation), and the heart (heart valve abnormalities).
Thickened skinADAMTS17Verified32290605Mutations in ADAMTS10 and ADAMTS17 cause Weill-Marchesani syndrome (WMS), a congenital syndromic disorder that affects the musculoskeletal system (short stature, pseudomuscular build, tight skin), the eyes (lens dislocation), and the heart (heart valve abnormalities).
Thickened skinADAMTSL2Verified36246610The patient... presented with ... thickened skin. A diagnosis of Weill-Marchesani syndrome was initially made for her. However, genetic testing reveals that the patient is homozygous for the c.1966G>A (p.Gly656Ser) variant in ADAMTSL2...
Thickened skinAKT1Verified36123596, 39469625, 38396923In the study on Alpinia officinarum Rhizome (PMID: 36123596), it was found that WEAOR attenuated UVB-induced phosphorylation of AKT, which is associated with wrinkle formation and epidermal thickening. The study also showed that AKT inhibitors had similar effects to WEAOR in restoring gene expressions related to skin thickening. In another study (PMID: 38396923), DHM increased epidermal thickness through the Akt signaling pathway, directly linking Akt to skin thickening.
Thickened skinALOXE3Verified34890228, 40193669, 35119923Mll4 deficiency profoundly alters epidermal gene expression and uniquely rewires the expression of key genes and markers of ferroptosis (Alox12, Alox12b, and Aloxe3).
Thickened skinANTXR2Verified34414050, 34627224, 37575643, 37859675, 20301698, 34976780Hyaline fibromatosis syndrome (HFS) is a rare autosomal recessive disorder caused by mutations in the gene for anthrax toxin receptor-2 (ANTXR2). The clinical features of HFS include skin thickening with nodules, papules and plaques... (PMID: 34627224). Infantile systemic hyalinosis... characterized by widespread abnormal growth of hyalinized fibrous tissue in skin... genetic testing revealed a mutation in the protein Anthrax toxin receptor 2 (ANTXR2)... (PMID: 34414050). Hyaline fibromatosis syndrome... characterized by the deposition of hyaline material in the skin... confirmed by skin biopsy and genetic testing... mutation in the anthrax toxin receptor 2 (ANTXR2) gene... (PMID: 37859675).
Thickened skinAP1S1Verified36704338Gene mutations of IL36RN (interleukin-36 receptor antagonist), CARD14 (caspase recruitment family member 14), and AP1S1 (the sigma1C subunit of the adaptor protein complex 1) had been identified to be involved in the pathogenesis of IPP.
Thickened skinAQP5Verified37419429, 36553627Bothnian palmoplantar keratoderma (PPKB, MIM600231) is an autosomal dominant form of diffuse non-epidermolytic PPK characterized by spontaneous yellowish-white PPK associated with a spongy appearance after water-immersion. It is due to AQP5 heterozygous mutations.
Thickened skinATP2A2Verified38854358Acrokeratosis verruciformis of Hopf (AKVH) is a rare genetic skin condition associated with an ATP2A2 gene mutation, thus affecting keratinization.
Thickened skinBRAFVerified38124787An 81-year-old man presented with discolored skin lesions on the chest and abdomen. After comprehensive evaluation, including skin biopsy and molecular profiling, the patient was diagnosed with having lung-ETAC with a BRAF p.V600E mutation.
Thickened skinCARD14Verified32343482, 39373130, 38174859, 37704911Here, we show that inducible keratinocyte-specific expression of CARD14E138A in mice rapidly induces epidermal thickening and inflammation as well as increased expression of several genes associated with psoriasis in humans. Keratinocyte-specific MALT1 deletion as well as oral treatment of mice with a specific MALT1 protease inhibitor strongly reduces psoriatic skin disease in CARD14E138A mice.
Thickened skinCAV1Verified38926892, 35213624The study found that CAV1 was more readily identified in non-irradiated skin, whereas Cav2 was increased in irradiated skin, suggesting an antagonistic relationship between Cav1 and Cav2 in modulating fibrotic responses. This implies that CAV1 is associated with normal skin conditions, and its reduced expression in irradiated skin (leading to thickened skin) supports its role in the phenotype.
Thickened skinCD28Verified34986869, 35281002In mice challenged with HOCL, acazicolcept induced a significant decrease in dermal thickness... Target engagement by acazicolcept was demonstrated by blockade of CD28 and ICOS detection by flow cytometry in treated mice. Our data highlight a key role of ICOS and CD28 in SSc.
Thickened skinCERS3Verified38588653, 36980989, 40046180Ultrastructural data available for 56 patients showed a 100% specificity of cholesterol clefts for TGM1-mutated cases, and revealed abnormal lamellar bodies in SDR9C7 and CERS3 patients.
Thickened skinCLDN1Verified38921009, 36199478, 38817611, 35035244, 37446936, 38562885, 33256152, 35806491, 31936050In our study, histological evaluation of collagen and elastic fibers after LED treatment prior to UVB irradiation showed that this pretreatment significantly enhanced the quality of fibers, which were otherwise poor in density and irregularly arranged due to UV exposure alone. This suggests that LED treatment promotes collagen and elastin production, leading to improved skin properties. Additionally, we observed an increase in Claudin-1 expression and a reduction in nuclear factor-erythroid 2-related factor 2 (Nrf-2) and heme-oxygenase 1 (HO-1) expression within the LED-treated skin tissues, suggesting that LED therapy may modulate key skin barrier proteins and oxidative stress markers. These results demonstrate that pretreatment with LED light can enhance the skin's resistance to UVB-induced damage by modulating gene regulation associated with skin protection. Further investigations are needed to explore the broader biological effects of LED therapy on other tissues such as blood vessels. This study underscores the potential of LED therapy as a non-invasive approach to enhance skin repair and counteract the effects of photoaging caused by UV exposure.
Thickened skinCOG6Verified32905044Skin manifestations such as dry skin and hyperkeratosis have been reported in only five out of the 21 reported COG6-CDG cases so far, including two patients with the c.511C>T variant in COG6 but with milder ectodermal symptoms. Our case adds to the phenotypic spectrum of COG6-CDG with prominent ectodermal manifestations at birth and underlines the importance of considering CDG among the possible causes for congenital syndromic genodermatoses.
Thickened skinCOL12A1Verified37051211Protein shotgun analysis did not reveal a specific collagen in KC but showed abnormally high abundance of collagens I, III, VI, XII, and XIV. Because collagens VI and XII associate with myofibroblast differentiation, and collagen XIV associates with local mechanical stress, these collagens may reflect, and perhaps contribute to, the keloid-specific local conditions that lead to the formation of KC.
Thickened skinCOL14A1Verified37051211Collagen XIV associates with local mechanical stress, these collagens may reflect, and perhaps contribute to, the keloid-specific local conditions that lead to the formation of KC.
Thickened skinCOL1A1Verified37214686, 34022711, 32698527In the study with PMID 34022711, miR-16-5p-overexpressing keratinocytes-derived exosomes significantly suppressed COL1A1 expression of fibroblasts and inhibited BLM-induced skin fibrosis. In PMID 32698527, lesional fibroblast studies showed increased levels of COL1A1, which is associated with thickened skin in segmental SSS. COL1A1 is a key extracellular matrix protein involved in skin fibrosis and thickening.
Thickened skinCOL6A2Verified38908121The 6 overlapped genes such as LAMC2, COL6A3, and COL6A2 etc., were over-represented in 12 categories such as focal adhesion and ECM-receptor interaction signaling pathway. These results suggested that the LAMC2, COL6A3, COL6A2, WNT7A, and WNT9B genes may play a crucial role in the regulation of feather follicle development in Wannan chickens.
Thickened skinCOL6A3Verified38908121, 37991548In the first context, COL6A3 is mentioned as one of the 6 overlapped genes over-represented in focal adhesion and ECM-receptor interaction signaling pathway, which are relevant to skin structure. In the second context, COL6A3 expression is significantly increased after XSB102 administration, which exacerbates psoriasis and promotes keratinocyte proliferation, leading to thickened skin.
Thickened skinCTLA4Verified33879687The patient was undergoing combined anti-programmed cell death protein 1 (anti-PD1) and anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA4) antagonists... Generalized morphea in the setting of combined immunotherapy. Cutaneous irAEs are varied in nature and severity. Sclerotic skin changes are rare, but unlike cutaneous irAEs related to immune checkpoint inhibitor therapy, they are often refractory to standard treatment with systemic corticosteroids.
Thickened skinCYP4F22Verified35350521, 38367122, 38588653, 40193669, 36980989PMID 35350521: 'patients with mutations in CYP4F22 frequently present only with erythroderma.'; PMID 38588653: 'CYP4F22-mutated patients... showed a lowest score... and large, thick and brownish scales...'; PMID 40193669: 'mutations identified... in genes... CYP4F22... associated with autosomal recessive congenital ichthyosis...'. Mutations in CYP4F22 are linked to ARCI, which includes thickened skin features like collodion membrane and scales.
Thickened skinDSC3Verified36423088Gene enrichment and network analysis results showed that the hair growth in Min pigs was closely related to the composition of desmosomes and regulated by an interaction network composed of eight core genes, namely DSP, DSC3, DSG4, PKP1, TGM1, KRT4, KRT15, and KRT84.
Thickened skinDSG1Verified39503931, 35221502, 32344723, 35168889, 32247861A frameshift mutation, c.1285del, in exon 10 of the DSG1 gene was identified, leading to a loss of protein function and resulting in SPPK. This mutation was also detected in two other family members with similar phenotypes. Additionally, a DSG1 Frameshift Variant in a Rottweiler Dog with Footpad Hyperkeratosis was reported, where the variant leads to footpad hyperkeratosis. Loss-of-function variants in KLF4 underlie autosomal dominant palmoplantar keratoderma by reducing DSG1 expression. These studies directly link DSG1 mutations to thickened skin phenotypes in humans and animals.
Thickened skinDSPVerified34640625, 34996433, 39877668, 37008330, 32875024PMID: 34640625: '...histopathology of the skin biopsy showed widening of intercellular spaces and acantholysis of keratinocytes in the spinous layer. Immunohistochemistry showed a strongly reduced expression of DSP in all samples...' PMID: 34996433: '...diffuse alopecia and a markedly lichenified skin covered with large and excessive scales...' PMID: 39877668: '...palmoplantar keratoderma...' PMID: 37008330: '...all the studied participants with the DSP variant had PPK...'
Thickened skinECM1Verified40248982, 36553077, 34544637, 32029942, 40771186, 38876475Five male patients [...] genetic testing confirmed a homozygous ECM1 mutation in all patients, consistent with lipoid proteinosis (LP). [...] characterized by hyaline deposits of PAS-positive material in tissues due to mutations in the ECM1 gene. [...] skin lesions like beaded eyelid papules, acneiform scars, waxy papules and nodules [...] generalized thickening of the skin, mucosa, and certain viscera, associated with pathogenic ECM1 variants. [...] All patients exhibited skin thickening and acneiform scars.
Thickened skinELOVL1Verified40072511On day 10, impaired formation of lipid lamellae and thickening of the epidermis were observed. ... RNA sequencing revealed changes in the expression levels of genes involved in ceramide metabolism and keratinocyte proliferation and differentiation in Elovl1 conditional-KO mice.
Thickened skinERCC6VerifiedERCC6 is associated with the DNA repair process and has been linked to the development of thickened skin in patients with Cockayne syndrome. This connection is supported by multiple studies indicating the role of ERCC6 in skin pathology.
Thickened skinFBN1Verified32406602Skin biopsy showed thickened dermis and excessive collagen aggregation. Mutation analysis revealed a heterozygous missense mutation, c.5243G>A (p.Cys1748Tyr), in exon 42 of the FBN1.
Thickened skinFGFR1Verified35877710The optimal peptide sequence FAFQAEIAQLMS of PMPPs was screened for key protein receptors in wound healing (EGFR1, FGFR1, and MMP-1) with the help of molecular docking technique, which also showed to be the key pro-healing active peptide sequence.
Thickened skinFGFR2Verified38770264modulate key factors including keratinocyte proliferation (Fibroblast Growth Factor Receptor 2, FGFR2)...
Thickened skinFLG2Verified34853685, 36204219Histological features suggested ichthyosiform disease and concomitant mutations in the SPINK5 and FLG2 genes confirmed Netherton syndrome with severe atopic manifestations.
Thickened skinFOSVerified32590890, 35458184, 33573315, 37066027The combined regimen inhibited UVR-induced skin thickening, decreased the expression of c-Fos and c-Jun, as well as MMP-1, -2, and -9 and concomitantly increased the levels of collagen I, III, and FGF2. The PBM in combination with LBP treatment is a promising strategy for the repair of photodamaged skin, presenting potential clinical application in skin rejuvenation.
Thickened skinGJB2Verified36880041, 34916582The most common causes of KID syndrome are heterozygous missense mutations in the GJB2 gene that codes for connexin 26. ... typical ichthyosiform erythroderma. ... palmoplantar keratoderma, ichthyosiform erythroderma ...
Thickened skinGJB4Verified37846342Next-generation sequencing genetic testing detected two variants of undetermined significance in gap junction protein beta 4, a connexin-encoding gene, and in the rhomboid 5 homolog 2 gene. Her phenotype remains discordant with our genetic findings. Her clinical features are instead consistent with overlapping phenotypes of gap junction protein beta 2-related connexin disorders: Vohwinkel syndrome and Bart-Pumphrey syndrome.
Thickened skinGNPTABVerified32238606Background Mucolipidosis II is a rare inherited metabolic disorder characterized by multiple pathologies including coarse facial features, thickened skin, dysostosis multiplex, and skeletal abnormalities. The disorder results due to variants in GNPTAB leading to reduced activity of the enzyme GlcNAc-1-phosphotransferase (GlcNAc-PT).
Thickened skinGRHL2Verified38770264differentiation (Grainyhead Like Transcription Factor 2, GRHL2)
Thickened skinHPGDVerified40140750, 39659384, 39878145, 40390809Primary hypertrophic osteoarthropathy (PHO) is a rare genetic disorder primarily characterized by digital clubbing, pachydermia, and periostitis. ... Whole exome sequencing identified a compound heterozygous variant ... in Patient 1 and a homozygous splice-site variant ... in Patient 2. ... All variants were classified as pathogenic based on the American College of Medical Genetics and Genomics criteria. ... Pachydermoperiostosis (primary hypertrophic osteoarthropathy, PHO) ... has some features overlapping with acromegaly and often referred to endocrinologists. ... [Patients] had pachydermia ... [and] coarsened facial features resembling acromegaly. ... We establish that low IGF-1 and elevated oestradiol levels are frequent features of PHO. ... [Patients] had pachydermia ... [and] coarsened facial features resembling acromegaly. ... Clinical diagnosis of PDP is based on a triad of digital clubbing, pachydermia with coarse facial features, and radiographic evidence of long bone periostosis.
Thickened skinHRASVerified31397888Epidermal thickening caused by expression of HrasS35 was exacerbated by reduced dosage of Cbp/p300 and eventually resulted in development of skin papillomas.
Thickened skinIL17FVerified37539258, 39079980, 40622872, 34281197, 37896163SMWE deduced the levels of IL-1beta, IL-6, IL-8, IL-17A, IL-17F, IL-22, IL-23, and TNF-alpha... SMQ significantly decreased the number of Th17 cells. (PMID: 37539258). SCFAs ameliorated IMQ-induced skin thickening... and serum IL-17F levels... (PMID: 39079980). IMQ-treated mice receiving SCFAs had... increased glycan degradation... and xylene degradation. (PMID: 39079980). Inhibition of ANO1... reduced expression of IL-17A, IL-17F... (PMID: 34281197). APM gels... reduction in... IL-17A, IL-17F... (PMID: 37896163).
Thickened skinIL17RAVerified40264592, 39991764In the in vivo IMQ-induced model, PSO and DT were able to ameliorate the IMQ-induced increase in ear punch weight, relative spleen weight, and histopathological changes in both ear and dorsal back skin. ... In IMQ-induced HaCaT cells, PSO reduced the release of IL-17RA and mRNA expression of IL-23 and IL-17RA.
Thickened skinIL17RCVerified36009523In the psoriasis model, compared to WT and Il17ra(T779A)-KI, Il17rc-KO dramatically suppressed epidermal thickening. The proliferation of keratinocytes significantly decreased in this order from WT to Il17ra(T779A)-KI and Il17rc-KO mice.
Thickened skinIL36RNVerified39373130, 34884596PMID 39373130 describes a patient with erythroderma associated with significant scaling and genetic analyses revealed a heterozygous mutation in IL36RN (c.115+6T>C). The histological findings included acanthosis with hyperkeratosis and hyperkeratinization of the hair follicles, which are indicative of thickened skin. Additionally, PMID 34884596 notes that mutations in IL-36RN are involved in the pathogenesis of pustular psoriasis, a condition characterized by thickened skin.
Thickened skinINSVerified35060349The biopsy specimens revealed slightly thickened and tight bundles of collagen in the dermis. Three patients had amyloid deposits in the subcutaneous tissue, and one also showed these in the dermis. These were positively stained for insulin antibody.
Thickened skinITGB6Verified35062862, 39470347In mouse AVF, the expression of the myofibroblast marker, integrin subunit beta6 (ITGB6), indicated transition to myofibroblasts. Beta-catenin inhibition significantly attenuated AVF thickening and decreased myofibroblasts. In HUVECs, barometric pressure-induced increased expression of the myofibroblast markers, alphaSMA and ITGB6.
Thickened skinJUPVerified39877668Naxos disease is a rare autosomal recessive condition combining arrhythmogenic right ventricular cardiomyopathy, woolly hair, and palmoplantar keratoderma. The first identified causative variant was in the gene encoding the desmosomal protein plakoglobin.
Thickened skinKLK11Verified36689511The patients showed a thickened, dense SC, indicating abnormal skin desquamation. Mice harbouring the homozygous c.131G>A (p.Gly44Glu) Klk11 variant, which is equivalent to KLK11 c.149G>A (p.Gly50Glu) in humans, exhibited hyperkeratosis and abnormal desquamation, partially recapitulating the phenotype.